Migraine

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-24T07:00:00.000-08:00

J Pharmacol Exp Ther. 2010 Jan 11; Salvatore CA, Moore EL, Calamari A, Cook JJ, Michener MS, O'Malley S, Miller PJ, Sur C, Williams DL, Zeng Z, Danziger A, Lynch JJ, Regan CP, Fay JF, Tang YS, Li CC, Pudvah NT, White RB, Bell IM, Gallicchio SN, Graham SL, Selnick HG, Vacca JP, Kane SACalcitonin gene-related peptide (CGRP) has long been hypothesized to play a key role in migraine pathophysiology and the advent of small molecule antagonists have clearly demonstrated a clinical link between blocking the CGRP receptor and migraine efficacy. MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide] represents the third CGRP receptor antagonist to display clinical efficacy in migraine trials. Here we report the pharmacological characterization of MK-3207, a potent and orally bioavailable CGRP receptor antagonist. In vitro, MK-3207 is a potent antagonist of the human and rhesus CGRP receptors (K(i) = 0.024 nM). In common with other CGRP receptor antagonists MK-3207 displays lower affinity for CGRP receptors from other species including canine and rodent. As a consequence of species selectivity the in vivo potency was assessed in a rhesus pharmacodynamic assay measuring capsaicin-induced changes in forearm dermal blood flow via laser Doppler imaging. MK-3207 produced a concentration-dependent inhibition of dermal vasodilation with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. A tritiated analog, [(3)H]MK-3207, was used to study the binding characteristics on the human CGRP receptor. [(3)H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM) and the off-rate was determined to be 0.012 min(-1) with a t(1/2) of 59 min. In vitro autoradiography studies on rhesus brain slices identified the highest level of binding in the cerebellum, brainstem, and meninges. Finally, as an index of CNS penetrability, the in vivo CSF/plasma ratio was determined to be 2-3% in cisterna magna-ported rhesus monkeys.

Inhibition of capsaicin-induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK-0974).

2010-01-19T18:22:00.000-08:00

Br J Clin Pharmacol. 2010 Jan; 69(1): 15-22Sinclair SR, Kane SA, Van der Schueren BJ, Xiao A, Willson KJ, Boyle J, de Lepeleire I, Xu Y, Hickey L, Denney WS, Li CC, Palcza J, Vanmolkot FH, DeprÃ© M, Van Hecken A, Murphy MG, Ho TW, de Hoon JNWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Calcitonin gene-related peptide (CGRP) was first described as a potent vasodilator. * CGRP is also increasingly recognized as a key player in the pathophysiology of migraine, and CGRP receptor antagonists potentially offer a new approach for treating migraine. * A novel pharmacodynamic assay to measure CGRP receptor antagonist activity non-invasively in humans has been developed, which involves measuring the increase in dermal blood flow induced by topical application of capsaicin on the forearm. WHAT THIS STUDY ADDS * This study shows that the novel oral CGRP receptor antagonist, telcagepant, inhibits the increases in dermal blood flow induced by the topical application of capsaicin on the human forearm. * This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists. AIMS To evaluate inhibition of capsaicin-induced increase in dermal blood flow (DBF) following telcagepant (MK-0974), a potent and selective orally bioavailable calcitonin gene-related peptide (CGRP) receptor antagonist being developed for the acute treatment of migraine. METHODS A three-period crossover study in 12 healthy adult men. Each subject received a single oral dose of telcagepant 300 mg, telcagepant 800 mg or placebo at 0 h, followed 0.5 and 3.5 h later by two topical doses of 300 and 1000 microg capsaicin per 20 microl water-ethanol mixture. Capsaicin was applied at two sites on the volar surface of the subjects' left and right forearms. DBF was assessed by laser Doppler perfusion imaging immediately before ('baseline'), and 0.5 h after each capsaicin application at 1 and 4 h. Plasma samples to determine telcagepant concentrations were collected immediately after laser Doppler perfusion imaging. A pharmacodynamic model was developed to explore the relationship between plasma concentration and inhibition of capsaicin-induced increase in DBF. RESULTS Geometric mean plasma concentrations after dosing with 300 mg and 800 mg telcagepant were 720 and 1146 nm, respectively, at 1 h, vs. 582 and 2548 nm, respectively, at 4 h. The pharmacodynamic model suggested that the EC(90) for telcagepant inhibition of capsaicin-induced increases in DBF was 909 nm. CONCLUSIONS Telcagepant inhibits the increases in DBF induced by the topical application of capsaicin on the human forearm. This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists.

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-19T01:44:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-18T17:25:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-18T01:26:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-17T22:11:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-16T23:12:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-15T17:21:00.000-08:00

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-14T17:09:00.000-08:00

Long-term effects of a sensitisation campaign on migraine: the Casilino study.

2010-01-14T01:36:00.000-08:00

J Headache Pain. 2010 Jan 8; Petolicchio B, Di Clemente L, Altieri M, Vicenzini E, Lenzi GL, Di Piero VIn 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs' waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 +/- 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (-13.9%; p < 0.0001) and mean HIT-6 score (-6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (-51.7%; p < 0.0001), pain intensity (-21.8%; p < 0.0001), headache duration (-18.1%; p = 0.0008) and HIT-6 score (-11.7%; p < 0.0001). Our data suggest that the effects of a "single shot" campaign are beneficial not only in a short-term perspective, but even in the long term. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency, severity or duration of headache worsen should be promptly referred to the headache clinic.

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-13T21:18:00.000-08:00

A migraine variant with abdominal colic and Alice in wonderland syndrome: a case report and review.

2010-01-13T06:15:00.000-08:00

BMC Neurol. 2010 Jan 6; 10(1): 2Hamed SAABSTRACT: : Abdominal migraine is a commonly described migraine variant in children and young adults, but associations with Alice in Wonderland syndrome and lilliputian hallucinations are exceptional. CASE PRESENTATION: A 20 years-old male experienced frequent and prolonged attacks of abdominal colic associated with autonomic manifestations started at the age of ten. At the age of 17, he additionally described prolonged attacks ([greater than or equal to] 7 days) of distortions of shape, size or position of objects or subjects. He said: Quite suddenly, objects appear small and distant (teliopsia) or large and close (peliopsia). I feel as I am getting shorter and smaller (shrinking) and also the size of persons are not longer than my index finger (a lilliputian proportion). Sometimes I see the blind in the window or the television getting up and down, or my leg or arm is swinging. I may hear the voices of people quite loud and close or faint and far. Occasionally, I experience attacks of migrainous headache associated with eye redness, flashes of lights and a feeling of giddiness. I am always conscious to the intangible changes in myself and my environment. There is a strong family history of common migraine. Clinical examination, brain-MRI and EEG were normal. Transcranial magnetic stimulation and evoked potentials revealed enhanced cortical excitability in multiple brain regions. Treatment with valproate resulted in marked improvement of all clinical and neurophysiological abnormalities. Conclusions The association between the two migraine variants (abdominal migraine and Alice in Wonderland Syndrome) might have clinical, pathophysiological and management implications. I think this is the first description in the literature.

Pharmacological Properties of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a

2010-01-13T04:30:00.000-08:00

Migraine in junior high-school students: A prospective 3-academic-year cohort study.

2010-01-12T06:45:00.000-08:00

Brain Dev. 2010 Jan 6; Visudtibhan A, Thampratankul L, Khongkhatithum C, Okascharoen C, Siripornpanich V, Chiemchanya S, Visudhiphan PMigraine is a common childhood illness with expected favorable outcome. A study of the long-term clinical course of childhood migraine will provide information of evolution of migraine. A cohort study for 3-academic-year was conducted in Thai junior high-school children from July 2005 to February 2008 to determine the clinical course of migraine. Two hundred and forty-eight students in four junior high schools diagnosed with migraine according to ICHD-II in July 2005 were recruited. Each student was serially evaluated twice yearly from 7th grade during each semester of the academic year until the second semester of 9th grade. Determination of the characteristics, severity, frequency, and treatment of headache were obtained by questionnaire and direct interview. At the final evaluation, clinical course of headache was categorized into seven patterns. Among enrolled students, 209 (84.3%) completed the study. Twenty-eight (13.5%) students had no recurrent headache while that of 153 (73.5%) improved. No improvement of migraine and worsened migraine were observed in four students (1.8%) and 24 students (11.2%), respectively. Spontaneous remission and avoidance of precipitating causes contributed to relief of migraine in the majority of the students. Stress-related daily school activities and inadequate rest were reported as common precipitating factors among students with non-improving or worsening outcome. Chronic daily headache and tension-type headache was observed in 6 and 30 students, respectively. This study confirms that clinical course of migraine in schoolchildren is benign. Frequency and intensity of headache can be reduced with reassurance and appropriate guidance. Early recognition and appropriate prevention of migraine attack will decrease the risk of chronic migraine and disease burden.

A systematic review of adverse events in placebo groups of anti-migraine clinical trials.

2010-01-11T07:58:00.000-08:00

Pain. 2009 Sep 23; Amanzio M, Corazzini LL, Vase L, Benedetti FIn analgesic clinical trials, adverse events are reported for the painkiller under evaluation and compared with adverse events in the placebo group. Interestingly, patients who receive the placebo often report a high frequency of adverse events, but little is understood about the nature of these negative effects. In the present study, we compared the rates of adverse events reported in the placebo arms of clinical trials for three classes of anti-migraine drugs: NSAIDs, triptans and anticonvulsants. We identified 73 clinical trials in 69 studies describing adverse events in placebo groups: 8 were clinical trials with NSAIDs, 56 were trials with triptans, and 9 were trials with anticonvulsants. Studies were selected of all Medline/PubMed or CENTRAL referenced trials published until 2007. Adverse event profiles of the three classes were compared using a systematic review approach. We found that the rate of adverse events in the placebo arms of trials with anti-migraine drugs was high. In addition, and most interestingly, the adverse events in the placebo arms corresponded to those of the anti-migraine medication against which the placebo was compared. For example, anorexia and memory difficulties, which are typical adverse events of anticonvulsants, were present only in the placebo arm of these trials. These results suggest that the adverse events in placebo arms of clinical trials of anti-migraine medications depend on the adverse events of the active medication against which the placebo is compared. These findings are in accordance with the expectation theory of placebo and nocebo effects.

Drug dependence associated with triptans and ergot derivatives: a case/non-case study.

2010-01-10T03:00:00.000-08:00

Eur J Clin Pharmacol. 2009 Dec 19; Beau-Salinas F, Jonville-BÃ©ra AP, Cissoko H, Bensouda-Grimaldi L, Autret-Leca EINTRODUCTION: The aim of this case/non-case study was to assess and compare the risk of drug dependence associated with different migraine-specific drugs, i.e., ergot derivatives and triptans, using the French pharmacovigilance database. METHODS: Reports on drug side effects recorded in this database between January 1985 and June 2007 were analyzed, and triptans (almotriptan, eletriptan, naratriptan, sumatriptan, and zolmitriptan) as well as ergot derivatives used in acute migraine were examined. For all reports, cases were defined as those reports corresponding to "drug abuse," "physical or mental drug dependence," and "pharmacodependence," whereas "non-cases" were defined as all the remaining SED reports. The method's reliability was assessed by calculating the risk associated with a negative (amoxicillin) and a positive (benzodiazepines) control. The risk of dependence associated with each drug and control was evaluated by calculating the odds ratio (OR) with a confidence interval of 95%. RESULTS: Among the 309,178 reports recorded in the database, drug dependence accounted for 0.8% (2,489) of the reports, with 10.9% (449) involving a triptan, and 9.33% (332) an ergot derivative. The risk of dependence was similar for triptans and ergot derivatives and did not differ from that of benzodiazepines. In the triptan group, the risk (odds ratio [95% CI]) ranged from 10.3 [4.8-22.3] for sumatriptan to 21.5 for eletriptan [10.1-45.6], while in the ergot derivative group, it ranged from 12 [8-17.9] for ergotamine to 20.6 [8-53] for dihydroergotamine. CONCLUSIONS: These findings confirm the hypothesis that triptans and ergot derivatives are associated with an increased risk of drug dependence.

Triptan Use as a Function of Cardiovascular Risk. A Population-Based Study.

2010-01-08T07:44:00.000-08:00

Headache. 2009 Dec 21; Bigal ME, Golden W, Buse D, Chen YT, Lipton RB(Headache 2009;**:**-**) Aim.- To estimate the proportion of individuals with migraine using triptan therapy as a function of their cardiovascular (CV) profile and disease severity. Methods.- As a part of the American Migraine Prevalence and Prevention study, we identified migraineurs representative of the U.S. adult population. Triptan use was estimated as a function of presence of CV disease (CVD), of CV risk factors, and by level of migraine-related disability. Results.- Our sample consists of 6102 individuals with migraine. Compared with migraineurs without risk factors for CVD, triptans were significantly less likely to be used in individuals with diabetes (11.5% vs 18.3%, OR = 0.6, 95% CI = 0.5-0.7), hypertension (14.8%, OR = 0.8, 0.7-0.9) and by smokers (12.9%, OR = 0.7, 0.6-0.8). Similar findings were seen for individuals with established CVD. As contrasted to individuals without CVD, those with myocardial infarct (8.5% vs 18.5%, OR = 0.4, 0.3-0.7), stroke (7%, OR = 0.6, 0.3-0.9) and heart surgery (9.3%, OR = 0.5, 0.4-0.7) were less likely to use triptans. Use of triptan increased as a function of disability regardless of CVD status or presence of CV risk factors. Conclusion.- Triptan use is lower in those with vs without CV risk, suggesting that doctors and/or patients fear using triptans in individuals at risk to CVD. Furthermore, triptan use in those with established CVD increases with headache-related disability, suggesting that patients and providers balance risks and benefits. Additional and analytical data are needed on the safety of triptans in the setting of CVD risk. This study has not assessed adequacy of care.

Vestibular dysfunction in migraine: effects of associated vertigo and motion sickness.

2010-01-07T13:39:00.000-08:00

J Neurol. 2009 Dec 30; Jeong SH, Oh SY, Kim HJ, Koo JW, Kim JSThe mechanisms of vestibular migraine and motion sickness remain unknown. The aims of this study were to determine interictal vestibular dysfunction in migraineurs according to associated dizziness/vertigo and motion sickness, and to find out whether impaired uvulonodular inhibition over the vestibular system underlies the vestibular symptoms and signs by measuring tilt suppression of the vestibulo-ocular reflex (VOR). One hundred and thirty-one patients with migraine [65 with vestibular migraine (MV), 41 with migrainous dizziness (MD), and 25 with migraine only (MO)] and 50 normal controls underwent evaluation of vestibular function. Motion sickness was assessed using the motion sickness susceptibility questionnaire (MSSQ) and subjective scale. Compared with normal controls and MO group, patients with MV/MD showed increased VOR time constant (TC) and greater suppression of the post-rotatory nystagmus with forward head tilt. The mean MSSQ score and subjective scale were highest in MV group, followed by MD, MO, and controls (p = 0.002, p < 0.001). Multiple linear regression model analyses revealed that motion sickness is an independent factor of TC prolongation (p = 0.024). Twenty-eight (21.4%) patients with migraine also showed perverted head shaking nystagmus and 12 (9.2%) had positional nystagmus. In view of the increased tilt suppression of the VOR, we speculate that dysfunction of the nodulus/uvula may not account for the prolonged TCs in MD/MV. Instead, innate hypersensitivity of the vestibular system may be an underlying mechanism of motion sickness and increased TC in MD/MV. The increased tilt suppression may be an adaptive cerebellar mechanism to suppress the hyperactive vestibular system in migraineurs.

The "Repeater" Phenomenon in Migraine Patients: A Clinical and Psychometric study.

2010-01-06T08:09:00.000-08:00

Headache. 2009 Dec 21; Villani V, Di Stani F, Vanacore N, Scattoni L, Cerbo R, Bruti G(Headache 2009;**:**-**) Background.- Headache is one of the most common symptoms in an emergency department (ED), while migraine is the most frequently observed headache in this setting. The aim of our study was to evaluate the influence of clinical and psychometric variables on the repeater phenomenon, ie, patients who make at least 3 visits to the ED at least 1 week apart during a 6-month period. Methods.- According to the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, we consecutively recruited Italian-speaking migraine subjects who came to the ED or outpatient service. All the patients underwent the Migraine Disability Assessment Scale for the evaluation of migraine disability. We also administered the Beck Depression Inventory, State and Trait Anxiety Inventory, and Toronto Alexithymia Scale-20 for the evaluation of depressive, anxiety, and alexithymic symptoms, respectively. A personality profile was also obtained by means of the Tridimensional Personality Questionnaire (TPQ). Results.- We consecutively enrolled 465 migraine patients, diagnosed according to the ICHD-II criteria. Seventy (15%) of these patients met the repeater definition. The repeater group had more severe disability and was affected to a greater degree by chronic migraine, regardless of symptomatic drug overuse, than the non-repeater group. As regards the psychometric variables, repeaters were more alexithymic, anxious, and depressed than non-repeaters. The personality profile, as measured by the TPQ, revealed that the repeater patients scored higher on the harm avoidance scale and their subscales than the non-repeater patients. Conclusions.- According to the findings of our study, the repeater migraineur is typically triptan-naÃ¯ve, more alexithymic, and more depressed than the non-repeater migraineur. A clinical and psychometric evaluation of repeater patients who go to the ED because of migraine attacks may help to understand this epidemiological and clinical phenomenon. From a clinical point of view, these psychometric findings may not only shed light on the epidemiology of migraine in the ED, but may also help to design a specific therapeutic protocol for this subgroup of migraine patients.

Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients.

2010-01-05T04:05:00.000-08:00

Neurology. 2010 Jan 5; 74(1): 57-63Pantoni L, Pescini F, Nannucci S, Sarti C, Bianchi S, Dotti MT, Federico A, Inzitari DOBJECTIVE: To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS: Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. CONCLUSIONS: Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.

[Migraine or headache management: a pharmacy survey.]

2010-01-04T07:37:00.000-08:00

Therapie. 2009 Nov-Dec; 64(6): 395-403Desamericq G, Revol A, Laforest L, Chamba G, Bauguil G, Ritleng C, Van Ganse EAim. To describe the characteristics and the management of migraine. Method. Data on headaches, drug consumption and life habits of 762 patients were collected using questionnaires and pharmacy records. Results. The migraine attack was characterized by a severe pain for more than 80% of the patients. The frequency was more than 2 attacks a week in 16% of the cases. Eighty four per cent of the patients had triptans and 45% had a long-term migraine treatment. Nonspecific analgesics were prescribed for 55%. The frequency of over-consumption of treatments of migraine attacks was 46%. Conclusion. The management of migraine still remains inadequate. The pharmacist could contribute to its improvement. Objectif. DÃ©crire les caractÃ©ristiques et la prise en charge de patients migraineux suivis mÃ©dicalement en officines. MÃ©thodes. Des questionnaires et des historiques mÃ©dicamenteux ont permis de rassembler des informations sur les migraines, la consommation mÃ©dicamenteuse et les habitudes de vie de patients traitÃ©s pour migraines. RÃ©sultats. Sept cent soixante deux patients ont participÃ© Ã cette Ã©tude. Les crises se caractÃ©risaient par une douleur intense chez plus de 80 % des patients. La frÃ©quence Ã©tait supÃ©rieure Ã 2 crises par semaine dans 16 % des cas. Quatre vingt quatre pour cent des patients avaient une prescription de triptan et 45 % suivaient un traitement de fond. Les antalgiques non spÃ©cifiques Ã©taient prescrits pour 55 % des patients. Une consommation excessive des traitements de la crise Ã©tait supposÃ©e dans 46 % des cas. Conclusion. Le recours aux antalgiques non spÃ©cifiques est encore Ã©levÃ©. Le pharmacien pourrait contribuer Ã l'amÃ©lioration de la prise en charge.

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine.

2010-01-03T07:52:00.000-08:00

J Neurol. 2009 Dec 25; Ghosh J, Joshi G, Pradhan S, Mittal BWe aimed to look for the association of tumor necrosis factor (TNF) gene polymorphisms (TNFA 308G > A, and TNFB 252G > A) in genetic susceptibility to migraine. The pathogenesis of migraine involves many immune-mediated mechanisms in the vascular endothelium. TNF, being a potent immunomodulator and pro-inflammatory cytokine, is suggested to be involved in inflammatory reactions leading to migraine attacks. A total of 216 normotensive migraine patients, 160 tension type headache (TTH) patients and 216 healthy controls (HC) were recruited in the study. The genetic polymorphisms were investigated through SNP association analysis using a matched case control migraine population. Genotyping of TNFA 308G > A polymorphism and TNFB 252G > A was done using ARMS PCR and PCR-RFLP, respectively. A borderline association was observed in TNFA 308GA genotype in migraine patients versus HC (p = 0.043; OR = 1.763; 95% CI = 1.019-3.051). After sub-grouping migraine into migraine with aura (MA) or without aura, significant difference at genotypic (p = 0.015; OR = 2.293; 95% CI = 1.172-4.487) as well as allelic (p = 0.035; OR = 1.955; 95% CI = 1.047-3.651) level was evident. The difference was even more significant in female MA at genotypic (p = 0.006; OR = 2.901; 95% CI = 1.361-6.181) and allelic level (p = 0.017; OR = 2.318; 95% CI = 1.159-4.635) as well as for A allele carriers in MA [p value = 0.020; OR = 2.205 (1.132-4.295)] and female MA (p value = 0.008; OR = 2.741; CI = 1.297-5.792). No association of TNFB252G > A was observed in migraine patients or any subgroups. We did not find any association of TNFA or TNFB gene polymorphisms with TTH. In conclusion, the TNFA 308G > A polymorphism was found to be associated with MA, particularly in females, whereas we could not find any association of TNFB 252G > A polymorphism in genetic susceptibility to migraine on comparing the migraine patients with HC or TTH patients.

Medication-Overuse Headache and Personality: A Controlled Study by Means of the MMPI-2.

2010-01-01T06:16:00.000-08:00

Headache. 2009 Dec 21; Sances G, Galli F, Anastasi S, Ghiotto N, De Giorgio G, Guidetti V, Firenze C, Pazzi S, Quartesan R, Gallucci M, Nappi G(Headache 2009;**:**-**) Objective.- The main aim of this study involves comparing the personality profiles of patients with medication-overuse headache (MOH) and episodic headaches, in order to elucidate the role of personality characteristics, according to one of the most widely used and validated personality assessment tool: Minnesota Multiphasic Personality Inventory (MMPI-2). Background.- Many studies have assessed the personality of headache patients by means of MMPI-2 only using clinical and content scales. In this study the supplementary scales were also used as they evaluate different aspects of personality, particularly broad personality characteristics, generalized emotional distress and behavioral dyscontrol. Methods.- We recruited 219 subjects (151 women and 68 men) who were grouped in the following categories: MOH group (n = 82); episodic headache group (n = 82; 58 migraine aura; 6 migraine with aura; 6 frequent episodic tension-type headache; 12 migraine+infrequent episodic tension-type headache) and 1 group of 55 healthy controls. MMPI-2 was employed. Data were computed with one-way anova and post hoc analyses. Results.- Medication-overuse headache and episodic headache patients (EH) showed a very similar pattern, differentiating each other only in the Hypochondriasis (Hs) (P = .007; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD 5.88] and Health Concerns [HEA]) (P = .005; MOH: mean 14.06 [SD 5.38]; EH: mean 11.81 [SD 5.59]) scales. Surprisingly, no differences were found between the 3 groups in the scales measuring dependence-related behavior such as Addiction Potential Scale (Aps) and Addiction Admission Scale (Aas). MOH and episodic headache patients scored significantly higher in the so-called neurotic scales Hs (P < .0001; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD 5.88]; Controls: mean 5.91 [SD 3.57]), Depression (D) (P < .0001; MOH: mean 26.44 [SD 7.01]; EH: mean 26.09 [SD 5.85]; Controls: mean 21.47 [SD 4.90]), and Hysteria (Hy) (P < .0001; MOH: mean 27.33 [SD 5.51]; EH: mean 26.81 [SD 5.68]; Controls: mean 21.95 [3.85]) and in many other scales such as Paranoia (Pa), Psychasthenia (Pt), Schizophrenia (Sc) while they scored significantly lower on Ego Strength (Es) and Dominance (Do) scales when compared with controls. Conclusions.- Patients with MOH and episodic headache showed very similar patterns, differentiating only in the Hypochondriasis and Health Concerns scales. Surprisingly, there were no significant differences in the scores of the scales measuring dependence-related behavior. The clinical role of MMPI-2 in discriminating MOH patients with dependency from drugs is discussed, in order to implement a complete tests' battery for headache patients' assessment.

[Migraine]

2009-12-30T14:25:00.000-08:00

Acta Med Port. 2009 Sep-Oct; 22(5): 589-98Martins IPMigraine is one of the most common neurological disorders, with a significant social and economic impact. It is characterized by a constellation of symptoms including headache, nausea or vomiting, intolerance to sensory stimuli and, in 20% of patients, transient neurological signs (the aura). In this article we review new advances on its pathogenesis, based on clinical and experimental data. Recent evidence has shown that, contrary to previous beliefs, migraine is primary a neurogenic disorder. Genetic studies have associated some rare forms of migraine to the mutations of genes that code ionic channels, suggesting that trans-membrane ionic imbalance is a possible pathogenic mechanism for the attacks. Genetic factors may modulate the vulnerability to suffer the attacks in response to environmental/internal triggers. Direct stimulation of the arterial wall is not a provocative factor for the attacks, contrary to stimuli that act primary on the nervous system. It has also been shown that individuals with migraine have an enhanced cortical excitability and lack of habituation. Functional neuroimaging studies have provided evidence that during the attacks there is an abnormal metabolic activity in the cortex and the brainstem. As waves of metabolic depression travel slowly across the cerebral cortex (cortical spreading depression), trigeminal nerve terminals surrounding meningeal arteries are stimulated eliciting a trigemino vascular reflex that explains subsequent vascular changes and headache. Drugs that stabilize nerve membranes and decrease neuronal excitability are effective in migraine prophylaxis. This recent evidence can be used in experimental models to test drugs aimed to new targets, developed to inhibit the cascade of events associated to migraine at different points, based on more fine grain knowledge of migraine pathogenesis.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

2009-12-30T00:27:00.001-08:00

J Neurol Neurosurg Psychiatry. 2010 Jan; 81(1): 90-3Dermaut B, Seneca S, Dom L, Smets K, Ceulemans L, Smet J, De Paepe B, Tousseyn S, Weckhuysen S, Gewillig M, Pals P, Parizel P, De Bleecker JL, Boon P, De Meirleir L, De Jonghe P, Van Coster R, Van Paesschen W, Santens PBACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Pregabalin in the Treatment of Chronic Migraine: An Open-Label Study.

2009-12-04T00:05:00.001-08:00

Clin Neuropharmacol. 2009 Nov 21; Calandre EP, Garcia-Leiva JM, Rico-Villademoros F, Vilchez JS, Rodriguez-Lopez CMOBJECTIVES:: Studies concerning the prophylactic treatment of chronic migraine are scarce, with topiramate being the most thoroughly studied drug at this respect. The aim of our study was to assess if pregabalin could be useful in the preventive management of chronic migraine. METHODS:: Thirty consecutive chronic migraine patients, 24 women and 6 men, aged 24 to 75 years and not receiving any other prophylactic medication, were treated with pregabalin for 12 weeks. The initial daily dosage was 75 mg, subsequently adjusted according to the drug's efficacy and the individual patients' tolerability at 2-week intervals. Patients kept a headache diary from 4 weeks before drug administration until the study ended, and headache impact test (HIT-6) was administered at baseline and at 4-week intervals. The main outcome variable was the change from baseline to end point in headache frequency. The secondary outcome variables included changes in headache severity, rescue medication intake, HIT-6 scores, and adverse reactions to pregabalin. RESULTS:: Pregabalin treatment was associated to significant decreases in headache frequency (P < 0.0001) and severity (P = 0.0005), rescue medication intake (P < 0.0001), and HIT-6 scores (P < 0.0001). Patients with daily headache performed worse than those with nondaily headache, showing no change in headache frequency and less relevant reduction of HIT-6 scores. The most frequent adverse reactions were dizziness (40%), somnolence (29%), abnormal thinking (16.7%), constipation and fatigue (13.3%). CONCLUSIONS:: Despite the limitations of an open-label design, our data suggest that pregabalin may be a useful alternative prophylaxis for chronic migraine. These promising results should be confirmed in randomized clinical trials.

MTHFR 677C>T and ACE D/I Polymorphisms in Migraine: A Systematic Review and Meta-Analysis.

2009-11-30T22:58:00.001-08:00

Headache. 2009 Nov 17; SchÃ¼rks M, Rist PM, Kurth T(Headache 2009;**:**-**) Background.- Data on the association between the MTHFR 677C>T and ACE D/I polymorphisms and migraine including aura status are conflicting. Objective.- The objective of this study is to perform a systematic review and meta-analysis on this topic. Methods.- We searched for studies published until March 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies and reviews on the topic. Assessment for eligibility of studies and extraction of data was performed by 2 independent investigators. For each study we calculated the odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Results.- Thirteen studies investigated the association between the MTHFR 677C>T polymorphism and migraine. The TT genotype was associated with an increased risk for any migraine, which only appeared for migraine with aura (pooled OR = 1.48, 95% CI 1.02-2.13), but not for migraine without aura. Nine studies investigated the association of the ACE D/I polymorphism with migraine. The II genotype was associated with a reduced risk for migraine with aura (pooled OR = 0.71, 95% CI 0.55-0.93) and migraine without aura (pooled OR = 0.84, 95% CI 0.70-0.99). Results for both variants were driven by studies in non-Caucasian populations. Results among Caucasians did not suggest an association. Extractable data did not allow investigation of gene-gene interactions. Conslusions.- The MTHFR 677TT genotype is associated with an increased risk for migraine with aura, while the ACE II genotype is protective against both migraine with and without aura. Results for both variants appeared only among non-Caucasian populations. There was no association among Caucasians.

Altered Cardiovascular Reactivity to Mental Stress But Not to Cold Pressure Test in Migraine.

2009-11-29T22:59:00.001-08:00

Headache. 2009 Nov 17; Domingues RB, Fonseca KB, Ziviane LF, Domingues SA, Vassalo D(Headache 2009;**:**-**) Objectives.- This study assessed cardiovascular reactivity to mental stress and cold pressure test in migraineurs and controls. It compared the cardiovascular reactivity between patients with migraine with aura and patients with migraine without aura. Background.- Several studies have assessed the autonomic nervous system functioning and cardiovascular responses to stressor stimuli in migraine. Cold pressure test and sustained attention tasks are distinct forms of induced stress. It is still unknown if patients with migraine have distinct patterns of response to sustained attention tasks and cold pressure test, since no previous studies have evaluated the cardiovascular responses to these 2 distinct types of stress in the same population of migraine patients. Methods.- Two distinct protocols were used to induce cardiovascular reactivity. Mental stress was induced by using a Stroop test card, a procedure involving the maintenance of the attention control. The other protocol was the cold pressure test. The blood pressure and heart rate were digitally recorded in rest and test phases. The mean elevation and the variance of blood pressure and heart rate were compared between groups. Results.- Patients with migraine had higher rest systolic blood pressure and lower heart rate induced by mental stress than controls. There were no differences between migraineurs and controls with cold pressure test. There were no differences between migraineurs with and without aura. Conclusion.- There was a significantly different pattern of cardiovascular reactivity between migraineurs and controls with mental stress but not with cold pressure test. Distinct central nervous system structures are involved in these 2 types of stress. A distinct pattern of activation of the prefrontal cortex-periaqueductal gray matter circuit in migraine may explain a singular autonomic reactivity to mental stress in this disease.

Efficacy of Biofeedback in the Treatment of Migraine and Tension Type Headaches.

2009-11-28T05:42:00.001-08:00

Pain Physician. 2009 November/December; 12(6): 1005-1011Mullally WJ, Hall K, Goldstein RBACKGROUND: Biofeedback is an established non-pharmacologic technique commonly used in the treatment of migraine and tension type headaches. Multiple published studies have suggested that biofeedback is effective in reducing the frequency and severity of headaches, often allowing patients to decrease their dependence on medication. Studies have also suggested that biofeedback may effect a decrease in medical utilization. OBJECTIVE: Assess the efficacy of biofeedback in reducing the frequency and severity of migraine and tension type headaches. DESIGN: Randomized, prospective, single blind, single center controlled trial. METHODS: Sixty-four patients with migraine with or without aura and/or tension type headaches, by ICHD-1 criteria, age 18 to 55, who had suffered from headaches for more than one year, were entered into the study. Patients were randomly assigned to receive biofeedback in addition to the basic relaxation instruction or relaxation techniques alone. All patients received instruction in pain theory. Biofeedback training consisted of 10 50-minute sessions utilizing standard EMG feedback from the frontalis and trapezius muscles and temperature from the third finger of the dominant hand. Visual and auditory feedback was provided. Thirty-three patients were assigned to receive biofeedback plus the relaxation techniques and 31, the relaxation techniques alone. All patients were asked to respond to periodic questionnaires for 36 months. The primary analysis was an intention-to-treat (ITT) analysis. The subsidiary analyses were not and the 11 subjects (7 in the relaxation alone and 4 in the biofeedback group) who received no treatment at all were analyzed and the results were qualitatively the same. RESULTS: Patients who completed the program with education in pain theory and relaxation techniques showed a statistically significant decrease in the frequency and severity of the headaches in the first 12 months that continued to 36 months. Biofeedback provided no additional benefit, specifically no change in the frequency or severity of the headaches. After 3 months 48% of those in the relaxation group reported fewer severe headaches, while 35% of those in the biofeedback group reported fewer severe headaches; after 6 months, 52% of those in the relaxation group reported fewer severe headaches as compared with 57% reporting fewer severe headaches in the biofeedback group. The number of medications used by the patients and the utilization of medical care decreased in both groups over 36 months suggesting a regression to the mean. LIMITATIONS: Compliance was an issue throughout the study. Patients dropped out from the outset and that increased over time. Recovery of questionnaires was difficult and fewer were completed at each 3-month interval. Lack of a large control group who did not receive biofeedback or instruction in relaxation techniques. CONCLUSION: Biofeedback is an extremely costly and time-consuming treatment modality that, in our study, provided no additional benefit when compared to simple relaxation techniques alone, in the treatment of migraine and tension type headaches in adults.

Headache and cognitive profile in children: a cross-sectional controlled study.

2009-11-27T20:18:00.001-08:00

J Headache Pain. 2009 Oct 20; Parisi P, Verrotti A, Paolino MC, Urbano A, Bernabucci M, Castaldo R, Villa MPWe investigated whether children affected by tension-type headache and migraine without aura, compared with a healthy control group that was matched by age, culturally and socioeconomically display a diverse intellectual functioning and have a separate "cognitive profile". A cross-sectional study was conducted from January 2006 to November 2008 at "Sapienza University" in Rome. A total of 134 children were diagnosed as being affected by either migraine without aura (93) or tension-type headache (41). On the basis of our exclusion/inclusion criteria, we enrolled 82 of these 134 children, 63 of whom were affected by migraine without aura and 19 by tension-type headache. On entry, cognitive functions were assessed in both the affected subjects and the control group by the Wechsler Intelligence Scale for Children-revised. Significant differences were found between the headache and control groups in the mean total intelligence quotient and verbal intelligence quotient scores (p < 0.001). Significant negative correlations were found between the total intelligence quotient, verbal intelligence quotient, performance intelligence quotient and the frequency of attacks (r = -0.55 and p < 0.001, r = -0.61 and p < 0.001, r = -0.29 and p < 0.01, respectively), as well as between the total intelligence quotient score and the age at headache onset (r = 0.234, p < 0.05). Our results suggest that the cognitive profile of children affected by headache should be assessed at the first child neurology outpatient observation. From a therapeutic point of view, although within a normal range, the abilities most likely to be less brilliant in such children are verbal skills.

Non-Peptidic Antagonists Of The Cgrp Receptor, Bibn4096bs And Mk-0974, Interact With The Calcitonin Receptor-Like Receptor Via Methionine-42 And Ramp1 Via Tryptophan-74.

2009-11-24T20:18:00.001-08:00

Biochem Biophys Res Commun. 2009 Nov 12; Miller P, Barwell J, Poyner DR, Wigglesworth MJ, Garland SL, Donnelly DThe receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-olomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1.

Increased vestibular contribution to posture control in individuals with chronic headache.

2009-11-23T20:26:00.001-08:00

J Vestib Res. 2009; 19(1-2): 49-58So CW, Bent LROBJECTIVE: Numerous studies have identified an association between headache disorders and vestibular symptoms, such as dizziness, vertigo, and motion sensitivity. Using bipolar, binaural galvanic vestibular stimulation (GVS), our objectives were to (1) determine the degree of vestibular sensitivity in borderline headache sufferers, and (2) characterize the postural response to vestibular perturbation in these individuals. METHODS: Fourteen volunteers participated in this study: 8 individuals with chronic headache (6 with migraine and 2 with tension type headache (TTH)), and 6 healthy control subjects. Thirty trials of 15-second duration were conducted across 6 conditions (GVS left (L) or right (R), or no stimulation (No GVS) with either eyes open (EO) or eyes closed (EC)). Peak medial-lateral (M-L) centre of pressure (CoP) was calculated during quiet stance. RESULTS: Headache subjects demonstrated significantly higher peak displacement of the M-L CoP than control subjects (p=0.0461). Although peak M-L CoP in both the EO (p = 0.0753) and EC (p=0.09623) visual conditions were not significantly different between headache sufferers compared to healthy controls, there is some suggestion that people with chronic headache may use vestibular information to a greater extent and that the presence of vision may not sufficiently compensate for vestibular induced instability. The initial push M-L CoP was not significantly different between groups, suggesting different sensory contributions for the initial and latter response to GVS. CONCLUSIONS: People with chronic headache exhibit increased postural sway, which may reflect the re-weighting of sensory information with an increased vestibular and a reduced visual contribution to postural control. Significance: These results support existing research on vestibular abnormalities in chronic headache sufferers that may provide a basis for future treatment therapies.

What happens to new-onset headache in children that present to primary care? A case-cohort study using electronic primary care records.

2009-11-19T00:32:00.001-08:00

Cephalalgia. 2009 Dec; 29(12): 1311-6Kernick D, Stapley S, Campbell J, Hamilton WThe aim was to describe the consulting behaviour and clinical outcomes of children presenting with headache in primary care. This was a historical cohort study using data from the UK General Practitioner Research Database. Cases were children aged 5-17 years who presented to primary care with primary headache (migraine, tension-type headache, cluster headache) or undifferentiated headache (no further descriptor). Controls were age, sex and practice matched. Their records were examined for consultations, referrals, relevant treatments and specific diseases in the subsequent year. Children with headache (n = 48 575) were identified and matched to controls. At presentation, 9321 (19.2%) of headaches were labelled primary, 549 (1.1%) secondary and 38 705 (79.7%) received no formal diagnosis. Of the latter group, 2084 (5.4%) received a primary headache diagnosis in the subsequent year. Following a diagnosis of migraine, 258 (3.5%) had received a triptan and 1598 (21%) were using propranolol or pizotifen. Total consultations were higher in cases than in controls in the year before the headache: cases ages 5-8 years, mean (s.d.) 5.0 (4.0) consultations; controls 4.0 (3.5) consultations. In 1 year controls had 43 430 consultations, of which 256 (0.6%) were for headache, of whom 64 (25%) were referred to secondary care. Headache was a risk factor for benign and malignant tumours, cerebrovascular disease, primary disorders of raised intracranial pressure and depression. This risk was reduced if a diagnosis of a primary headache disorder could be made. Although there is an increased likelihood of a serious pathology with headache presentations, the risk is small particularly if a diagnosis of a primary headache is made. General practitioners are likely to be underdiagnosing migraine. This study can inform management guidelines for new presentations of headache in primary care, particularly when a secondary pathology is suspected.

A double-blind comparison of onabotulinumtoxina (BOTOX) and topiramate (TOPAMAX) for the prophylactic treatment of chronic migraine: a pilot study.

2009-11-18T01:20:00.001-08:00

Headache. 2009 Nov-Dec; 49(10): 1466-78Mathew NT, Jaffri SFBACKGROUND: There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. OBJECTIVE: To compare the efficacy and safety of onabotulinumtoxinA (BOTOX), Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX), Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. METHODS: In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and -4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. RESULTS: Of 60 patients randomized to treatment (mean age, 36.8 +/- 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported > or =50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. CONCLUSIONS: OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations.

Outcome reporting in industry-sponsored trials of gabapentin for off-label use.

2009-11-16T20:40:00.001-08:00

N Engl J Med. 2009 Nov 12; 361(20): 1963-71Vedula SS, Bero L, Scherer RW, Dickersin KBACKGROUND: There is good evidence of selective outcome reporting in published reports of randomized trials. METHODS: We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports. RESULTS: We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced. CONCLUSIONS: We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.

[Headache in BehÃ§et's disease: case reports and literature review.]

2009-11-13T14:29:00.001-08:00

Reumatismo. 2009 Jul-Sep; 61(3): 174-81Volpinari S, Monaldini C, Capone JG, Lo Monaco A, La Corte R, Trotta F, Govoni MOBJECTIVE: To evaluate the prevalence of headache and its different patterns in patients with BehÃ§et's disease (BD) with and without neurological involvement and to investigate clinical correlations. METHODS: Patients fulfilling the International Study Group criteria for BehÃ§et disease (ISGc) were studied. Patients were invited to fill a "headache questionnaire", which consisted of two sections: the first one included demographic and anamnestic data, family history for both headache and BD, disease duration and clinical manifestations of BD; the second section included items about headache, investigated accordingly to International Headache Society diagnostic criteria (IHS, 2004). Clinical history and current comorbidities-medications were collected. Each patient underwent a neurological examination to assess neurological involvement (Neuro-BD) and, if necessary, instrumental investigations. One hundred-fifty healthy subjects matched for age and gender were used as control group for comparison. RESULTS: Of the 55 patients diagnosed as BD (ISG criteria) 41 patients adhered and were enrolled into the study. Headache occurred in 29 of BD patients (70,7%) and in 13 of Neuro-BD patients (92,8%). Migraine without aura did prove the most frequent type of headache in BD patients (with and without neurological involvement) and there were no differences in the frequency of the different pattern of headache between BD patients and controls. CONCLUSIONS: Headache is a frequent manifestation in BD and primary headache like migraine emerged as the most frequent type of headache. A careful search for headache should be included in the diagnostic work-up of BD since this manifestation may be related to the underlying disease.

Factors Affecting Rates of Visual Field Progression in Glaucoma Patients with Optic Disc Hemorrhage.

2009-11-12T20:00:00.001-08:00

Ophthalmology. 2009 Nov 4; Prata TS, De Moraes CG, Teng CC, Tello C, Ritch R, Liebmann JMPURPOSE: Optic disc hemorrhage (DH) is an important risk factor for glaucoma progression. We sought to investigated factors affecting the rate of visual field (VF) progression after DH in glaucomatous eyes. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive glaucoma patients from our Glaucoma Progression Study with >/=5 Swedish interactive threshold algorithm standard 24-2 VFs from 1999 through 2008. METHODS: Disc photographs of all patients were evaluated for the presence of DH. Exclusion criteria were conditions other than glaucoma likely to affect the VF and insufficient number of VFs to create a slope after DH detection. Automated pointwise linear regression was used to determine the rate of VF loss after DH detection. Fast progression was defined as a global VF loss of >/=1.5 dB/year. Factors associated with a fast rate of VF loss after the detection of the DH were evaluated. MAIN OUTCOME MEASURES: Assessed variables included baseline (age, gender, intraocular pressure (IOP), central corneal thickness, VF mean deviation (MD), presence of migraine, Raynaud's phenomenon, low blood pressure, and exfoliation syndrome) and intercurrent data (DH recurrence, fellow eye involvement, glaucoma surgery, and IOP reduction). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for each variable. RESULTS: Seventy-six eyes (76 patients; mean age, 68.3+/-10.9 years) were enrolled. Mean IOP and VF MD at the time of the DH detection were 16.6+/-3.8 mmHg and -5.6+/-5.7 dB, respectively. The mean global progression rate after DH was -1.1+/-1.3 dB/year (mean follow-up, 3.8+/-2.8 years). A rate of progression of >/=1.5 dB/year was found in 20 (26%) eyes. Multivariate logistic regression analysis revealed larger baseline MD (OR, 1.11; 95% CI, 1.01-1.20; P = 0.03) and older age (OR, 1.06; 95% CI, 1.01-1.13; P = 0.04) to be significant risk factors for fast progression after DH. Eyes with a baseline MD worse than -4.0 dB had a 270% increased risk of fast progression compared with those with an MD better than -4.0 dB. CONCLUSIONS: The presence of a DH in older subjects with a worse VF predicted further VF global MD deterioration by more than 5 dB within 4 years. These eyes should undergo careful and frequent disease surveillance and consideration should be given to more aggressive treatment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Pressure pain sensitivity mapping of the temporalis muscle revealed bilateral pressure hyperalgesia in patients with strictly unilateral migraine.

2009-11-08T23:20:00.001-08:00

Cephalalgia. 2009 Jun; 29(6): 670-6FernÃ¡ndez-de-las-PeÃ±as C, Madeleine P, Cuadrado ML, Ge HY, Arendt-Nielsen L, Pareja JAPrevious studies on pressure pain sensitivity in patients with migraine have shown conflicting results. There is emerging evidence suggesting that pain sensitivity is not uniformly distributed over the muscles, indicating the existence of topographical changes in pressure pain sensitivity. The aim of this study was to calculate topographical pressure pain sensitivity maps of the temporalis muscle in a blind design in patients with strictly unilateral migraine compared with controls. For this purpose, an electronic pressure algometer was used to measure pressure pain thresholds (PPT) over nine points of the temporalis muscle: three points in the anterior, medial and posterior parts, respectively. Pressure pain sensitivity maps of both sides (dominant or non-dominant; symptomatic or non-symptomatic) were calculated. The analysis of variance showed significant differences in PPT values between both groups (F = 279.2; P < 0.001) and points (F = 4.033; P < 0.001). Patients showed lower PPT at all nine points than healthy controls (P < 0.001). We also found lower PPT in the centre of the muscle compared with the posterior part of the muscle within both groups (P < 0.01). Interaction between group and points (F = 1.9; P < 0.05) was also found. Within the migraine group, PPT levels were decreased bilaterally from the posterior to the anterior column of the temporalis muscle (Student-Newman- Keuls analysis; P < 0.05), with the most sensitive in the anterior part of the muscle. For controls, PPT did not follow such anatomical distribution, the most sensitive point being the centre of the mid-muscle belly. This study showed bilateral sensitization to pressure in unilateral migraine, suggesting the involvement of central components.

[Metabolic syndrome and prevention of migraine headache]

2009-11-07T16:45:00.001-08:00

Brain Nerve. 2009 Oct; 61(10): 1143-53Takeshima TMetabolic syndrome (MetS) are consist of central obesity, diabetes, dyslipidemia and hypertension. Previous studies have reported possible association of migraine and MetS were reviewed. Migraine is a prevalent disabling disorder and have been regarded as an episodic and functional disorder. However, recent evidence suggests that in some cases, the disease may follow a chronic and progressive course. On the basis of available evidence, obesity is considered to be associated with migraine frequency and progression. The association between diabetes and migraine is unclear. Similarly, association of migraine with hypertension is also unclear. Female migraineurs commonly have an unfavorable cholesterol profile, i.e. one with high total cholesterol and low HDL levels. Obesity can be considered as a proinflammatory state in which increased inflammatory mediators, vascular hyperreactivity, plasma calcitonin gene-related peptide (CGRP) concentrations and decreased adiponectin concentrations are observed. These alterations can cause an increase in the frequency of migraine attacks developed of central sensitization, and thereafter, chronic migraine. Migraine and obesity may share some neurobiological abnormalities. Orexins modulate both pain and metabolism. Dysfunction in the orexin pathways seems to be a risk factor for both conditions. The methylene-tetrahydrofolate reductase (MTHFR) gene and the angiotensin converting enzyme (ACE) gene exhibit polymorphism. C677Tmutation in the MTHFR gene and the D-allele of the ACE gene are the shared risk factors for the development of migraine and cardiovascular disease. Certain beta-blockers, Ca blockers, ACE inhibitors, and angionten II receptor blocker (ARB) have excellent efficacy in migraine prophylaxis. The pharmacological mechanism of these agents do not seem to stand on their antihypertensive effect, but the other mechanism of action. Appropriate meal, sleep, and exercise are important for the management of MetS and migraine headaches.

Efficacy and safety of microfoam sclerotherapy in a patient with klippel-trenaunay syndrome and a patent foramen ovale.

2009-11-04T01:33:00.001-08:00

Arch Dermatol. 2009 Oct; 145(10): 1147-51Redondo P, Bastarrika G, Sierra A, MartÃnez-Cuesta A, Cabrera JBACKGROUND: Sclerotherapy with polidocanol microfoam injection under duplex guidance is a new treatment for venous malformations associated with Klippel-Trenaunay syndrome. Multidetector-row computed tomography (MDCT) venography is extremely helpful in the assessment of disease extension and the planning of therapy. Observation In this particular case, MDCT venography demonstrated the origin, course, and relationship to adjacent anatomical structures of aberrant vessels that configure the superficial venous system with an anatomically normal and patent deep venous system. At the end of the treatment, which consisted of 8 sessions of microfoam sclerotherapy within 12 months, a considerable reduction in the number and size of the percutaneously treated aberrant veins was observed. The obvious clinical improvement was objectively demonstrated with MDCT venography, which showed clear reduction in the number and size of treated veins. Further clinical investigation performed because of isolated migraine episodes related to the sclerotherapy session revealed that the patient had a patent foramen ovale. A transcranial Doppler examination during the procedure showed middle cerebral artery bubbles, which indicated right-to-left shunt. No cerebral damage was observed in a subsequent diffusion-weighted magnetic resonance examination. CONCLUSIONS: Microfoam sclerotherapy is an effective treatment option in patients with Klippel-Trenaunay syndrome. MDCT venography allows diagnosis of the disease, planning of therapy, and assessment of response to treatment. Although foam-induced microembolism is a common phenomenon during sclerotherapy, in this report we demonstrate that polidocanol microfoam prepared with a low-nitrogen gas mixture is safe in a patient with a patent foramen ovale.

Migraine and cardiovascular disease: systematic review and meta-analysis.

2009-10-31T00:45:00.001-07:00

BMJ. 2009; 339: b3914SchÃ¼rks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth TOBJECTIVE: To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION: Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS: Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION: Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

Effectiveness of Nonpharmacologic Treatment for Migraine in Young Children.

2009-10-28T23:31:00.001-07:00

Headache. 2009 Oct 5; Eidlitz-Markus T, Haimi-Cohen Y, Steier D, Zeharia AObjective.- To evaluate the effectiveness of nonpharmacologic treatment for migraine in children younger than age 6 years. Background.- The mean age of onset of migraine in children is 7.2 years for boys and 10.9 years for girls. Treatment consists of individually tailored pharmacologic and nonpharmacologic interventions. However, data on migraine management in preschoolers are very sparse. Methods.- Demographic, clinical, and outcome data were collected from the files of patients with migraine who attended a pediatric headache clinic. Only those treated by nonpharmacologic measures, namely, good sleep hygiene, diet free of food additives, and limited sun exposure, were included. Clinical factors and response to treatment were compared between children younger than 6 years and older children. Results.- Of the 92 children identified, 32 were younger than 6 years and 60 were older. There was no difference between the age groups in most of the demographic and clinical parameters. The younger group was characterized by a significantly lower frequency of migraine attacks and shorter disease duration (in months). Mean age of the patients with no response to treatment (grade 1) was 10.588 +/- 3.254 years; partial response (grade 2), 9.11 +/- 4.6 years; and complete response (grade 3), 8.11 +/- 3.93 years (P = .02). The percentage of patients with complete to partial response as opposed to no response was significantly higher in the younger group (P = .00075). Conclusion.- As the primary option, conservative therapy for migraine appears to be more effective in children younger than 6 years than in older children, perhaps because of their shorter duration of disease until treatment and lower frequency of attacks.

Childhood Maltreatment and Migraine (Part II). Emotional Abuse as a Risk Factor for Headache Chronification.

2009-10-28T21:27:00.001-07:00

Headache. 2009 Oct 21; Tietjen GE, Brandes JL, Peterlin BL, Eloff A, Dafer RM, Stein MR, Drexler E, Martin VT, Hutchinson S, Aurora SK, Recober A, Herial NA, Utley C, White L, Khuder SA(Headache 2009;**:**-**) Objectives.- To assess in a headache clinic population the relationship of childhood abuse and neglect with migraine characteristics, including type, frequency, disability, allodynia, and age of migraine onset. Background.- Childhood maltreatment is highly prevalent and has been associated with recurrent headache. Maltreatment is associated with many of the same risk factors for migraine chronification, including depression and anxiety, female sex, substance abuse, and obesity. Methods.- Electronic surveys were completed by patients seeking treatment in headache clinics at 11 centers across the United States and Canada. Physician-determined data for all participants included the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria, average monthly headache frequency, whether headaches transformed from episodic to chronic, and if headaches were continuous. Analysis includes all persons with migraine with aura, and migraine without aura. Questionnaire collected information on demographics, social history, age at onset of headaches, migraine-associated allodynic symptoms, headache-related disability (The Headache Impact Test-6), current depression (The Patient Health Questionnaire-9), and current anxiety (The Beck Anxiety Inventory). History and severity of childhood (/=15 days/month) was reported by 34%. Transformation from episodic to chronic was reported by 26%. Prevalence of current depression was 28% and anxiety was 56%. Childhood maltreatment was reported as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse and neglect were significantly associated with chronic migraine and transformed migraine. Emotional abuse was also associated with continuous daily headache, severe headache-related disability, and migraine-associated allodynia. After adjusting for sociodemographic factors and current depression and anxiety, there remained an association between emotional abuse in childhood and both chronic (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19-2.62) and transformed migraine (OR = 1.89, 95% CI: 1.25-2.85). Childhood emotional abuse was also associated with younger median age of headache onset (16 years vs 19 years, P = .0002). Conclusion.- Our findings suggest that physical abuse, emotional abuse, and emotional neglect may be risk factors for development of chronic headache, including transformed migraine. The association of maltreatment and headache frequency appears to be independent of depression and anxiety, which are related to both childhood abuse and chronic daily headache. The finding that emotional abuse was associated with an earlier age of migraine onset may have implications for the role of stress responses in migraine pathophysiology.

Endonasal Endoscopic Management of Contact Point Headache and Diagnostic Criteria.

2009-10-25T22:04:00.001-07:00

Headache. 2009 Oct 5; Mohebbi A, Memari F, Mohebbi SBackground.- Some types of headaches with sinonasal origin may be present in the absence of inflammation and infection. The contact points between the lateral nasal wall and the septum could be the cause of triggering and sustained pain via trigeminovascular system. Objective.- The aim of this study was to evaluate the feasibility and effectiveness of endoscopic surgery in the sinonasal region for treatment of headache with special attention paid to specific diagnostic methods and patient selection. Methods.- This was a prospective, non-randomized and semi-quasi experimental research study. Thirty-six patients with chronic headaches who had not previously responded to conventional treatments were evaluated by rhinoscopy and/or endoscopy, local anesthetic tests and computed tomography scans as diagnostic criteria. These patients were divided into 4 groups based on the diagnostic methods utilized. The intensity of headaches pre- and post-operatively were recorded by utilizing the visual analog scale scale and performing analysis with analysis of variance test comparison and Statistical Package for Social Sciences. Average follow-up was 30 months. Results.- Our overall success rate approximated 83% while the complete cure rate was 11%. Patients in group 4 achieved the best results. In this group all diagnostic criteria were positive. In addition, patient responses were statistically significant in groups with more than one positive criteria compared with group 1 who only had positive examination. The positive response of 14 migrainous patients diagnosed with migraine prior to treatment was 64%. Conclusion.- Surgery in specific cases of headaches with more positive evidence of contact point could be successful, particularly if medical therapy has failed.

Peri-ictal changes of cortical excitability in children suffering from migraine without aura.

2009-10-24T01:20:00.001-07:00

Pain. 2009 Sep 29; Siniatchkin M, Reich AL, Shepherd AJ, van Baalen A, Siebner HR, Stephani UIn adult patients with migraine, transcranial magnetic stimulation (TMS) has been used to examine cortical excitability between attacks, but there have been discrepant results. No TMS study has examined cortical excitability in children or adolescents with migraine. Here, we employed TMS to study regional excitability of the occipital (phosphene threshold [PT] and suppression of visual perception) and motor (resting motor threshold and cortical silent period) cortex in ten children suffering from migraine without aura and ten healthy age-matched controls. Patients were studied 1-2days before and after a migraine attack as well as during the inter-migraine interval. The motion aftereffect was also investigated at each time-point as an index of cortical reactivity to moving visual stimuli. Migraineurs had lower PTs compared to healthy participants at each time-point, indicating increased occipital excitability. This increase in occipital excitability was attenuated 1-2days before a migraine attack as indicated by a relative increase in PTs. The increase in PTs before the next attack was associated with a stronger TMS-induced suppression of visual perception and a prolongation of the motion aftereffect. Motor cortex excitability was not altered in patients and did not change during the migraine cycle. These findings show that pediatric migraine without aura is associated with a systematic shift in occipital excitability preceding the migraine attack. Similar systematic fluctuations in cortical excitability might be present in adult migraineurs and may reflect either a protective mechanism or an abnormal decrease in cortical excitability that predisposes an individual to a migraine attack.

A novel method for modeling facial allodynia associated with migraine in awake and freely moving rats.

2009-10-21T21:46:00.001-07:00

J Neurosci Methods. 2009 Oct 15; Wieseler J, Ellis A, Sprunger D, Brown K, McFadden A, Mahoney J, Rezvani N, Maier SF, Watkins LRMigraine is a neurovascular disorder that induces debilitating headaches associated with multiple symptoms including facial allodynia, characterized by heightened responsivity to normally innocuous mechanical stimuli. It is now well accepted that immune activation and immune-derived inflammatory mediators enhance pain responsivity, including in the trigeminal system. Nociceptive ("pain" responsive) trigeminal nerves densely innervate the cranial meninges. We have recently proposed that the meninges may serve as a previously unidentified, key interface between the peripheral immune system and the CNS with potential implications for understanding underlying migraine mechanisms. Our focus here is the development of a model for facial allodynia associated with migraine. We developed a model wherein an indwelling catheter is placed between the skull and dura, allowing immunogenic stimuli to be administered over the dura in awake and freely moving rats. Since the catheter does not contact the brain itself, any proinflammatory cytokines induced following manipulation derive from resident or recruited meningeal immune cells. While surgery alone does not alter immune activation markers, TNF or IL6 mRNA and/or protein, it does decrease gene expression and increase protein expression of IL-1 at 4 days after surgery. Using this model we show the induction of facial allodynia in response to supradural administration of either the HIV glycoprotein gp120 or inflammatory soup (bradykinin, histamine, serotonin, and prostaglandin E2), and the induction of hindpaw allodynia in our model after inflammatory soup. This model allows time and dose dependent assessment of the relationship between changes in meningeal inflammation and corresponding exaggerated pain behaviors.

Headache and Symptoms of Temporomandibular Disorder: An Epidemiological Study.

2009-10-12T18:38:00.001-07:00

Headache. 2009 Sep 14; GonÃ§alves DA, Bigal ME, Jales LC, Camparis CM, Speciali JGObjectives.- A population-based cross-sectional study was conducted to estimate the prevalence of migraine, episodic tension-type headaches (ETTH), and chronic daily headaches (CDH), as well as the presence of symptoms of temporomandibular disorders (TMD) in the adult population. Background.- The potential comorbidity of headache syndromes and TMD has been established mostly based on clinic-based studies. Methods.- A representative sample of 1230 inhabitants (51.5% women) was interviewed by a validated phone survey. TMD symptoms were assessed through 5 questions, as recommended by the American Academy of Orofacial Pain, in an attempt to classify possible TMD. Primary headaches were diagnosed based on the International Classification of Headache Disorders. Results.- When at least 1 TMD symptom was reported, any headache happened in 56.5% vs 31.9% (P < .0001) in those with no symptoms. For 2 symptoms, figures were 65.1% vs 36.3% (P < .0001); for 3 or more symptoms, the difference was even more pronounced: 72.8% vs 37.9%. (P < .0001). Taking individuals without headache as the reference, the prevalence of at least 1 TMD symptom was increased in ETTH (prevalence ratio = 1.48, 95% confidence interval = 1.20-1.79), migraine (2.10, 1.80-2.47) and CDH (2.41, 1.84-3.17). At least 2 TMD symptoms also happened more frequently in migraine (4.4, 3.0-6.3), CDH (3.4; 1.5-7.6), and ETTH (2.1; 1.3-3.2), relative to individuals with no headaches. Finally, 3 or more TMD symptoms were also more common in migraine (6.2; 3.8-10.2) than in no headaches. Differences were significant for ETTH (2.7 1.5-4.8), and were numerically but not significant for CDH (2.3; 0.66-8.04). Conclusion.- Temporomandibular disorder symptoms are more common in migraine, ETTH, and CDH relative to individuals without headache. Magnitude of association is higher for migraine. Future studies should clarify the nature of the relationship.

The central analgesia induced by antimigraine drugs is independent from Gi proteins: superiority of a fixed combination of indomethacin, prochlorperazine and caffeine, compared to sumatriptan, in an i

2009-10-09T02:28:00.001-07:00

J Headache Pain. 2009 Sep 15; Ghelardini C, Galeotti N, Vivoli E, Grazioli I, Uslenghi CA hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1 mg/kg, prochlorperazine 1 mg/kg and caffeine 3 mg/kg, s.c.) and sumatriptan (20 mg/kg, s.c.) exert their central antinociceptive action independently from the Gi proteins. In addition, the antinociceptive efficacy of Indoprocaf in this study was statistically superior to that of sumatriptan. This study also showed that the single active ingredients of Indoprocaf, indomethacin (1 mg/kg, s.c.), prochlorperazine (1 mg/kg, s.c.) and caffeine (3 mg/kg, s.c.), were able to exert their central antinociceptive action independently from the Gi proteins. However, Indoprocaf at analgesic doses was able to abolish almost completely the abdominal constrictions, with a statistically higher efficacy compared to the single active ingredients, showing an important synergic effect of Indoprocaf. This synergic effect was evident not only when Gi proteins activity was abolished by PTX, but also under control condition, when Gi proteins were active. This study suggests that the central antinociceptive action induced by antimigraine drugs is independent from Gi proteins.

Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study.

2009-10-08T18:11:00.001-07:00

Acta Neurol Scand. 2009 Oct 5; Termine C, Trotti R, Ondei P, Gamba G, Montani N, Gamba A, De Simone M, Marni E, Balottin UTermine C, Trotti R, Ondei P, Gamba G, Montani N, Gamba A, De Simone M, Marni E, Balottin U. Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01268.x. (c) 2009 The Authors Journal compilation (c) 2009 Blackwell Munksgaard.Objective - To investigate the prevalence of mitral valve prolapse (MVP) and abnormalities of haemostasis in children and adolescents with migraine with aura (MA) compared with peers affected by other idiopathic headaches. Materials and methods - We recruited 20 MA patients (10 men and 10 women; age range 8-17 years) and 20 sex- and age-matched subjects with other idiopathic headaches. Both groups underwent colour Doppler transthoracic echocardiography to detect MVP and the following laboratory work-up: plasma prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, protein C, protein S, homocysteine, lupus anticoagulant, von Willebrand factor (vWF) ristocetin cofactor activity, immunoglobulins (Ig) G and M anticardiolipin antibodies (aCL). Factor V Leiden, factor II and methylenetetrahydrofolate reductase were investigated (we did not test the entire genes, but screened for specific point mutations). Results - The prevalence of MVP was significantly higher in the MA subjects than in the patients affected by other idiopathic headaches (40% vs 10%; P < 0.05). Moreover, the MA patients showed a higher rate of above-normal IgM aCL titres (45% vs 10%; P < 0.05). Finally, in the group of patients with MVP we found a higher prevalence of aCL in those with MA compared with those affected by other idiopathic headaches. Conclusions - A proportion, at least, of the MA patients showed a more complex phenotype characterized by MVP and/or positive aCL titres. The pathogenetic role of these associations is obscure and larger studies are needed to confirm the usefulness of echocardiographic and laboratory investigations in this area and to identify possible new treatment approaches that might be explored in this group of MA patients.

The Safety of Sumatriptan and Naratriptan in Pregnancy: What Have We Learned?

2009-10-08T02:23:00.001-07:00

Headache. 2009 Oct 5; Cunnington M, Ephross S, Churchill PObjectives.- To monitor for a signal of major teratogenicity by determining the risk of all major defects following in utero exposure to sumatriptan and naratriptan. To monitor for unusual patterns of birth defects that might suggest teratogenicity. Background.- The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to these drugs in pregnancy is likely. The Sumatriptan and Naratriptan Pregnancy Registry captures data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. Methods.- Healthcare professionals from anywhere in the world can enroll, on a voluntary basis, women exposed to sumatriptan or naratriptan during their pregnancies in this primarily prospective, observational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The percentage of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. Results.- Data are available on pregnancy outcomes from 599 exposed women. Among 479 first-trimester exposures to sumatriptan, 20 outcomes with major birth defects were reported (4.6%, 95% confidence interval [CI] 2.9-7.2%). The risk of major birth defects following exposure to sumatriptan during any trimester was 4.7% (95% CI 3.1-7.0%). No distinctive pattern of major birth defects among exposed infants was noted. There were 50 first-trimester exposures to naratriptan with 1 reported birth defect in a fetus with exposure to both sumatriptan and naratriptan. Conclusions.- The risk of all major birth defects following first-trimester exposure to sumatriptan was 4.6% (95% CI 2.9-7.2%). This coupled with a consistent failure of additional epidemiological studies to observe a signal for major teratogenicity gives a level of reassurance concerning the safety of sumatriptan in pregnancy. There are too few data on naratriptan to draw definitive conclusions, and the sample size for sumatriptan remains too small to detect any but very large increases in specific birth defects.

A young man presenting with acute encephalopathy, hemiparesis, and headache.

2009-10-07T02:17:00.001-07:00

J Emerg Med. 2009 Sep 24; Weng TH, Chiu WT, Afilalo M, Choy CS, Tselios C, Yip PK, Lam CBackground: Familial hemiplegic migraine (FHM) is a rare type of migraine. Correct diagnosis is challenging for emergency physicians (EPs) due to its variable clinical picture, as well as its lack of diagnostic biological markers. Objectives: To raise awareness among EPs regarding FHM's diverse clinical picture, and to highlight FHM's diagnostic criteria to facilitate an accurate and timely diagnosis of FHM in patients presenting to the emergency department (ED) with indicative symptomatology. Case Report: A 24-year-old male student presented to the ED complaining of dizziness, general weakness, and blurred vision that had developed the previous night. The initial physical examination revealed drowsiness, slow speech production, and slight weakness with paresthesia in all limbs. Detailed communication with the patient's aunt revealed that he had experienced several similar attacks since the age of 12 years, and that there was also an extensive family history of the same symptoms. In addition, 2 h after arrival, the patient experienced severe throbbing headache, vomiting, severe dysphasia, and the weakness shifted to the right side. A computed tomography scan of the brain showed no anomalies. He was admitted with a tentative diagnosis of FHM. Conclusion: A diagnosis of FHM should be considered if the patient's clinical features include headache and weakness, with a family history of similar symptomatology. However, atypical symptoms of FHM may present as recurrent episodes of unexplained encephalopathy. Crucial elements for making an accurate and timely diagnosis of FHM include a detailed knowledge of weakness-related diseases and an ability to consider FHM in the differential diagnosis, as well as obtaining a thorough family history with repeated neurologic assessments.

Isolated elevation of IgA anti-{beta}2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients.

2009-10-06T22:40:00.001-07:00

Lupus. 2009; 18(11): 1011-4Kumar S, Papalardo E, Sunkureddi P, Najam S, GonzÃ¡lez E, Pierangeli SCurrent diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-beta(2)GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-beta(2)GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-beta(2)GPI antibody titres were 118.5 SAU (normal range: 0-20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-beta(2)GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-beta(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-beta(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-beta(2)GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-beta(2)GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

Postmarketing migraine survey of frovatriptan: effectiveness and tolerability vs previous triptans, NSAIDs or a combination.

2009-10-05T17:48:00.001-07:00

Curr Med Res Opin. 2009 Sep 24; Cady RK, Banks J, Jones BA, Campbell JAbstract Objective: Compare the effectiveness and tolerability of current therapy with frovatriptan 2.5-mg tablets (in 1-3 migraines) in patients with migraine previously using other triptans, analgesics/nonsteroidal anti-inflammatory drugs (NSAIDs), or triptans and NSAIDs (T+NSAIDs). Research design and methods: Subanalysis of a postmarketing survey study in patients with migraine managed at primary care facilities in Germany. Main outcome measures: A total of 5025 patients rated the effectiveness and tolerability of previous therapy (triptans; T+NSAIDs; NSAIDs) and current therapy with frovatriptan; physicians rated only frovatriptan effectiveness and tolerability (1 = Very Good, 2 = Good, 3 = Satisfactory, 4 = Poor). Results: Of 7107 patients initially surveyed, 5025 were identified for this subanalysis as previously using NSAIDs (n = 2890), triptans (n = 1418) or T + NSAIDs (n = 717). The mean (SD) age was 42.3 (11.9) years. At baseline, patients who previously used NSAIDs reported significantly fewer migraines per month, lower migraine severity, shorter migraine duration, and poorer ratings for effectiveness and tolerability versus responses from patients previously using triptans or T + NSAIDs (P < 0. 001 for each). Patient effectiveness ratings of Very Good or Good for previous therapy occurred in 49% (n = 691 of 1411) of patients using triptans, 27% (n = 195 of 716) of patients using T + NSAIDs, and 11% (n = 303 of 2866) of patients using NSAIDs (P < 0.04 between each group). Most patients rated current therapy with frovatriptan as Very Good or Good for effectiveness (86%, triptans; 83%, T + NSAIDs; 94%, NSAIDs) and tolerability (95%; 95%; 97%). Most physicians rated frovatriptan as Very Good or Good for effectiveness (87%; 86%; 95%) and tolerability (96%; 96%; 98%). Within-patient comparisons confirmed that frovatriptan had improved effectiveness (P < 0.001) and tolerability ratings (P < 0.001) in all three groups versus previous therapies. Conclusions: Intrapatient comparisons showed that most patients with migraine reported significantly improved effectiveness and tolerability ratings with frovatriptan versus previous acute therapies.

Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan.

2009-10-05T02:08:00.001-07:00

Headache. 2009 Oct; 49(9): 1258-66Cady RK, Vause CV, Ho TW, Bigal ME, Durham PLOBJECTIVES: (1) To measure calcitonin gene-related peptide (CGRP) levels in the saliva of individuals with migraine during the premonitory period, mild headache, moderate to severe headache, and post-resolution phases as compared with baseline (interictal) CGRP levels. (2) To correlate response to rizatriptan administered during moderate headache with levels of CGRP levels measured in saliva. BACKGROUND: CGRP is implicated in the underlying pathophysiology of migraine. To date no study has measured changes of saliva CGRP through the clinical evolution of a migraine attack and correlated saliva CGRP levels to clinical response to therapy. METHODS: Data were summarized using tables and descriptive statistics. Statistical analysis was performed with the non-parametric signed-rank test using Minitab15 statistical software. Results of statistical analyses were considered significant at P < .05. Responding subjects were defined as those who were symptom free at the time of the last collected saliva sample and did not have to rescue. Non-responding subjects were defined as those who rescued with an additional dose of rizatriptan or another medication or who were not symptom free at the end of the collection period. RESULTS: Statistically significant elevations of CGRP were noted in the premonitory, mild headache, and moderate to severe headache phase of the migraine compared with baseline (interictal) levels. A better therapeutic response to rizatriptan was observed in subjects with elevated saliva CGRP levels. Successful treatment with rizatriptan correlated with saliva CGRP levels returning to near baseline levels. In the rizatriptan non-responder group, no significant change in saliva CGRP levels was found at any phase of the migraine attack. CONCLUSIONS: Elevation of saliva CGRP is predictive of responsiveness to rizatriptan. In the rizatriptan responsive population, CGRP levels are elevated beginning with the premonitory period and throughout mild and moderate/severe headache. Successful response to rizatriptan correlated with return of saliva CGRP levels to near baseline (interictal) values.

PTSD, combat injury, and headache in Veterans Returning from Iraq/Afghanistan.

2009-10-04T23:22:00.001-07:00

Headache. 2009 Oct; 49(9): 1267-76Afari N, Harder LH, Madra NJ, Heppner PS, Moeller-Bertram T, King C, Baker DGOBJECTIVE: To examine the relationship between posttraumatic stress disorder, combat injury, and headache in Operation Iraqi Freedom and Operation Enduring Freedom veterans at the VA San Diego Healthcare System. BACKGROUND: Previous investigations suggest that a relationship between posttraumatic stress disorder and primary headache disorders exists and could be complicated by the contribution of physical injury, especially one that results in loss of consciousness. These associations have not been systematically examined in Operation Iraqi Freedom and Operation Enduring Freedom veterans. METHODS: In this observational cross-sectional study, a battery of self-report, standardized questionnaires was completed by 308 newly registered veterans between March and October 2006. The Davidson Trauma Scale was used to determine the degree of posttraumatic stress disorder symptoms and combat-related physical injury was assessed by self-report. The presence of headache was based on a symptom checklist measure and self-reported doctor diagnoses. Logistic regression analysis was performed to predict presence of headache and determine odds ratios and 95% confidence intervals associated with demographic, military, in-theatre, and mental health characteristics. RESULTS: About 40% of the veterans met the criteria for posttraumatic stress disorder; 40% self-reported current headache, 10% reported a physician diagnosis of migraine, 12% a physician diagnosis of tension-type headache, and 6% reported both types of headache. Results from the logistic regression model indicated that combat-related physical injury (odds ratio: 2.25; 95% confidence interval: 1.17-4.33) and posttraumatic stress disorder (odds ratio: 4.13; 95% confidence interval: 2.44-6.99) were independent predictors of self-reported headache. Additional analyses found that veterans with both tension and migraine headache had higher rates of posttraumatic stress disorder (chi-square [d.f. = 3] = 15.89; P = .001) whereas veterans with migraine headache alone had higher rates of combat-related physical injury (chi-square [d.f. = 9] = 22.00; P = .009). CONCLUSION: Posttraumatic stress disorder and combat-related physical injury were related to higher rates of self-reported headache in newly returning veterans. Our finding that posttraumatic stress disorder and injury during combat are differentially related to migraine and tension-type headache, point to a complex relationship between physical and psychological trauma and headache. These findings have implications for a comprehensive approach to interventions for headache and the physical and psychological sequelae of trauma.

Scheduled Short-Term Prevention With Frovatriptan for Migraine Occurring Exclusively in Association With Menstruation.

2009-10-02T22:02:00.001-07:00

Headache. 2009 Sep 14; Silberstein SD, Berner T, Tobin J, Xiang Q, Campbell JCObjective.- This post hoc subgroup analysis evaluated scheduled short-term preventive frovatriptan therapy for women with migraine occurring exclusively in association with menstruation (occurring day -2 to +3; day 1 = menses start, no migraines outside this window). Background.- A previously published randomized, double-blind, placebo-controlled 3-way crossover trial assessed the efficacy and safety of a scheduled 6-day preventive regimen with frovatriptan for the treatment of menstrual migraine; the study population included women experiencing both menstrual and non-menstrual migraine and women experiencing only menstrual migraine. Methods.- Women received each treatment (placebo, frovatriptan 2.5 mg once daily, and frovatriptan 2.5 mg twice daily) once over 3 perimenstrual periods in randomized sequence. For this subset analysis, screening questions were used to identify women with migraine occurring exclusively in association with menstruation. Efficacy was evaluated by occurrence and severity of migraine, functional impairment, and rescue medication use. Adverse events and tolerability were also assessed. Results.- Among 179 patients, the mean age (SD) was 37.3 (7.7) years and mean menstrual migraine history was 10.6 (8.7) years. Significantly fewer women experienced menstrual migraine during treatment with frovatriptan twice daily (37.7%, P < .001) or once daily (51.3%, P = .002) than during treatment with placebo (67.1%); a significant dose response was noted (P = .01, twice daily vs once daily). Significant treatment differences were also found for several secondary endpoints, but the data from this post hoc analysis must be interpreted with caution. Frovatriptan was well tolerated and most adverse events were mild or moderate and similar to those reported with the acute treatment of migraine with frovatriptan; the most common adverse events were nausea, dizziness, and headache. Conclusions.- Scheduled short-term preventive frovatriptan therapy effectively reduced the occurrence of menstrual migraine in women with attacks occurring exclusively in association with menstruation.

[Current clinical evidence on topiramate pharmacokinetics]

2009-09-30T18:15:00.001-07:00

Srp Arh Celok Lek. 2009 Jul-Aug; 137(7-8): 444-8Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered as early as 1979, during middle 1980's it was approved in many countries for the treatment of epilepsies and migraine prevention. More recently, in the experimental stage, possible new indications have been disclosed: treatment of obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral pseudotumour, bulimia, periventricular leucomalatia in preterm infants and alcohol addiction. Most epileptologists consider it to be the first choice antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus of evidence in paediatric population has been accumulated that confirms its efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut syndrome, partial, absence and combined seizures. Having a unique monosaccharide chemical structure among other anticonvulsant drugs, characterizes it with special pharmacokinetic features. This substance exhibits a low interindividual variability in plasma levels and hence it features predictable pharmacokinetics. A steady state plasma concentration of topiramate increases linearly with higher dosages. Serum protein binding is approximately 15%, and biologic half-life in healthy volunteers is considered to range from 20 to 30 hours. Mean expected distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a low and saturable binding capacity toward erythrocytes. It has not been present at the market for a sufficiently long time that would enable us to speak about a significant accumulation of data on its metabolism based on post-registration 4th stage clinical trials. For this purpose, we have done a literature review in order to summarise so far reported experience on topiramate pharmacokinetics in patients and healthy adults. Deeper understanding of its pharmacokinetic profile could enable a better technological design of the produced drug and the choice of the adequate route of its administration, and accordingly a more rational treatment of severe epilepsies resistant to other drugs.

Nitric Oxide-Induced Changes in Endothelial Expression of Phosphodiesterases 2, 3, and 5.

2009-09-30T02:29:00.001-07:00

Headache. 2009 Sep 14; Schankin CJ, Kruse LS, Reinisch VM, Jungmann S, Kristensen JC, Grau S, Ferrari U, Sinicina I, Goldbrunner R, Straube A, Kruuse CObjective.- To investigate nitric oxide (NO)-mediated changes in expression of cyclic nucleotide degrading phosphodiesterases 2A (PDE2A), PDE3B, and PDE5A in human endothelial cells. Background.- Nitric oxide induces production of cyclic guanosine monophosphate (cGMP), which along with cyclic adenosine monophosphate (cAMP) is degraded by PDEs. NO donors and selective inhibitors of PDE3 and PDE5 induce migraine-like headache and play a role in endothelial dysfunction during stroke. The current study investigates possible NO modulation of cGMP-related PDEs relevant to headache induction in a cell line containing such PDEs. Methods.- Real time polymerase chain reaction and Western blots were used to show expression of PDE2A, PDE3B, and PDE5A in a stable cell line of human brain microvascular endothelial cells. Effects of NO on PDE expression were analyzed at specific time intervals after continued DETA NONOate administration. Results.- This study shows the expression of PDE2A, PDE3B, and PDE5A mRNA and PDE3B and PDE5A protein in human cerebral endothelial cells. Long-term DETA NONOate administration induced an immediate mRNA up-regulation of PDE5A (1.9-fold, 0.5 hour), an early peak of PDE2A (1.4-fold, 1 and 2 hours) and later up-regulation of both PDE3B (1.6-fold, 4 hours) and PDE2A (1.7-fold, 8 hours and 1.2-fold after 24 hours). Such changes were, however, not translated into significant changes in protein expression indicating few, if any, functional effects. Conclusions.- Long-term NO stimulation modulated PDE3 and PDE5 mRNA expression in endothelial cells. However, PDE3 and PDE5 protein levels were unaffected by NO. The presence of PDE3 or PDE5 in endothelial cells indicates that selective inhibitors may have functional effects in such cells. A complex interaction of cGMP and cAMP in response to NO administration may take place if the mRNA translates into active protein. Whether or not this plays a role in the headache mechanisms remains to be investigated.

Reduced Adverse Event Profile of Orally Inhaled DHE (MAP0004) vs IV DHE: Potential Mechanism.

2009-09-29T18:40:00.001-07:00

Headache. 2009 Sep 14; Cook RO, Shrewsbury SB, Ramadan NMBackground.- MAP0004 is a novel orally inhaled formulation of dihydroergotamine mesylate (DHE) currently in development that has been clinically observed to provide rapid ( approximately 10 minutes) therapeutic levels of DHE but with lower rates of adverse effects (dizziness, nausea, and paresthesia) compared with intravenous (IV) dosing. Receptor-based mechanistic studies were conducted to determine if differences between IV DHE and inhaled DHE (MAP0004) binding and functional activity were responsible for the improved adverse event profile. Methods.- Radioligand competitive binding assays were performed at adrenergic (alpha1 [non-specific], alpha2A, alpha2B, alpha2C, beta), dopaminergic (D; D(1), D(2), D(3)), and at serotonergic (5-HT; 5-HT(1A), 5-HT(1B), 5-HT(1D), 5-HT(2A), 5-HT(2C), 5-HT(3), 5-HT(4), 5-HT(5A), 5-HT(6), 5-HT(7)) receptors. Binding assays were also conducted for the major metabolite of DHE, 8'-hydroxy-DHE (8'-OH-DHE). Subsequent functional receptor assays were also performed at 5-HT(1B), 5-HT(1D), 5-HT(2A), 5-HT(2C), 5-HT(3), D(2), alpha1A, alpha2A, alpha2B, beta1, and beta2 and muscarinic receptors to ensure that observed receptor binding translated into potential functional response. Results.- For competitive binding studies, DHE demonstrated extensive activity at IV C(max) for all 5-HT receptors tested, except 5-HT(3 )and 5-HT(4), and alpha1, alpha2A, alpha2B, alpha2C, and D(3) receptors. DHE concentrations used in the studies were equal to the peak plasma concentrations (C(max)) observed in human subjects following IV DHE 1.0 mg (the standard approved dose), and 2 and 4 inhalations MAP0004 which, respectively, produced systemic circulation levels of DHE equivalent to 0.44 mg and 0.88 mg administered IV. MAP0004 binding activity at the C(max) concentrations was lower than IV DHE and no binding was observed for the 8'-OH-DHE metabolite. However, MAP0004 preserved potent agonist action at key anti-migraine 5-HT(1B) and 5-HT(1D) receptors, even at the lower C(max )concentrations. Functional binding studies displayed similar results whereby IV DHE C(max) concentrations invoked strong agonist/antagonist responses, for instance at adrenergic and 5-HT(2C) receptors, which could have been responsible for dizziness. Conversely, at C(max) concentrations of MAP0004, inhaled DHE achieved a significantly lower response or no response at the adrenergic and 5-HT(2C) receptors. Conclusions.- The mechanism by which nausea was experienced with IV DHE - yet not with MAP0004 - was not associated with classic nausea pathways/targets (dopamine, 5-HT(3), or muscarinic receptors) or with peripheral action in the intestine via enterochromaffin cells. Importantly, the maximum DHE concentrations following MAP0004 administration were insufficient to interact with receptors implicated in cardiovascular (5-HT(2B) and beta(1)) and pulmonary effects (beta(2), adenosine, muscarinic, and leukotriene).

Otoneurologic Dysfunctions in Migraine Patients With or Without Vertigo

2009-09-25T00:18:00.000-07:00

To evaluate the neurotologic findings in patient suffering from migraine with and without vestibular symptoms. STUDY DESIGN:: Comparative cross-sectional and observational study.

SETTING::
Tertiary referral center.

BACKGROUND::
Migraine headache is often associated with other symptoms, including dizziness, head motion intolerance, or rotational-type vertigo. The neuro-otologic examination in migrainous patients often gives unremarkable results.

To date, it is not fully understood why some migraine patients complain of vestibular symptoms and some do not, and it is not yet clear whether neuro-otologic abnormalities among migraine patients are more common in patients complaining of vestibular symptoms or whether they can be considered a hallmark of migraine itself.

MATERIALS AND METHODS::
Forty-four migrainous patients were divided into 2 groups regarding the presence (22 patients, Group 1) or absence (22 patients, Group 2) of vestibular symptoms, and the results were compared with those obtained from a control group (22 normal subjects). All the patients underwent a complete neurotologic study to verify the presence of vestibular abnormalities.

RESULTS::
Neurotologic abnormalities were observed in only 34% of the total, and the incidence was very similar in the 2 groups (36.3 versus 31.8%). Central vestibular involvement was observed in 18% of Group 1 and in 18% of Group 2 patients. Peripheral vestibular involvement was demonstrated in 18% of Group 1 patients and in 16% of Group 2 patients.

CONCLUSION::
Our data seem to confirm that migraine itself can affect vestibular pathways even if patients do not complain of vestibular symptoms. Vestibular examination alone does not provide enough information for a diagnosis of migrainous vertigo. A careful clinical history is fundamental for assessing the profile of patients with migrainous vertigo.

"Otoneurologic Dysfunctions in Migraine Patients With or Without Vertigo"
Otol Neurotol. 2009 Aug 19; Casani AP, Sellari-Franceschini S, Napolitano A, Muscatello L, Dallan I

Vertigo as a migraine trigger

2009-09-24T22:17:00.000-07:00

It is reported in some individual patients that vestibular stimuli can trigger migraine attacks. This study used a case-control design to examine systematically the hypothesis that vertigo induced by vestibular stimulation (rotation/caloric testing) can act as a specific migraine trigger.

METHODS:
A total of 123 new patients attending neuro-otology or neurology clinics were studied with questionnaires and physician interview to ascertain migraine history according to International Headache Society criteria. A total of 79 who underwent rotation/caloric vestibular testing (test group) were compared with 44 control patients in whom no such testing was carried out (control group). The principal outcome measure was the occurrence of a migraine attack within 24 hours of exposure to vestibular stimulation.

RESULTS:
Of those participants with a past history of migraines, 19/39 (49%) of the test group experienced a migraine in the study time window, compared with 1/21 (5%) of the control group. Binary logistic regression analysis confirmed that vestibular testing was associated (p < 0.05) with migraine attacks.

CONCLUSIONS:
The results indicate that induced vertigo can act as a migraine trigger, a finding with implications for the diagnosis of patients with episodic vertigo and migraine headache. While such patients may well have basilar migraine or migrainous vertigo, alternatively, another disorder causing episodic vertigo (e.g., benign paroxysmal positional vertigo or MÃ©niÃ¨re disease) may be triggering migraine headaches.

"Vertigo as a migraine trigger"
Neurology. 2009 Aug 25; 73(8): 638-42Murdin L, Davies RA, Bronstein AM

Impact of headache on young people in a school population.

2009-09-23T18:53:00.000-07:00

Headache is the most frequent neurological symptom and the most common manifestation of pain in childhood. Estimates of the prevalence of headache in children and adolescents vary widely (depending on the setting, methodology, and diagnostic criteria applied) and the impact is not well understood.

Aim
To quantify the impact of headache in a school population.Design of studyA questionnaire survey.SettingExeter schools.

Method
A total of 1037 school children between the ages of 12 and 15 years were surveyed, of whom 49% were female. Main outcome measures were headache frequency, disease-specific impact using the Pediatric Migraine Disability Assessment Score (PedMIDAS), and generic quality of life impact using the Pediatric Quality of Life Inventory (PedsQL4).Results Twenty per cent of the study population had headache one or more times a week, with an average PedMIDAS score of over 12.1 (and an impact on over 12 days in a 3-month period).

Ten per cent of the population had a PedMIDAS score of 16.8 and a PedsQL4 generic quality of life score of 70.1, indicating a poorer quality of life than that of children with asthma, diabetes, or cancer. An average of 0.6 days of school was lost in a 3-month period across all school children.

Conclusion
There is a significant impact of headache on the quality of life of children. This impact is both unrecognised and unmet. GPs have an important role in identification and management of this problem.Keywordschildren; headache; quality of life.

"Impact of headache on young people in a school population"
Br J Gen Pract. 2009 Aug 11; Kernick D, Reinhold D, Campbell JL

Self-medication with OTC analgesics among 15-16 year-old teenagers

2009-09-23T16:00:00.000-07:00

OTC analgesics were released for sale outside pharmacies in Norway in 2003. This study assesses indications and frequency of use of these drugs among 15-16 year-old teenagers in Norway after 2003.

MATERIAL AND METHOD:
We developed a questionnaire, which contained 65 questions with one or more response options. This was given to all pupils in the final grade at six junior high schools in a town with 60,000 inhabitants (Drammen).

RESULTS:
367 of 626 (58.6 %) pupils participated. 50 % of the boys and 71 % of the girls had used OTC analgesics during the last four weeks; 26 % of them on a daily or weekly basis. Girls experienced episodes of pain more frequently than boys, but the proportion of episodes treated with analgesics did not differ between the sexes.

Headache and muscle pain were common. Half of those with severe headache/migraine used OTC analgesics on a daily or weekly basis. The teenagers reported several reasons for experiencing pain and discomfort, such as long time spent in front of various screens, tight time schedules with physical exercise and friends, drinking too little and much noise in the classroom.

INTERPRETATION:
Use of OTC analgesics has increased considerably among Norwegian teenagers. Drug-induced headache may occur as an adverse event. If more effort is made to improve life situations that adolescents perceive as painful and a cause of discomfort, the need for OTC analgesics may be reduced.

"Self-medication with OTC analgesics among 15-16 year-old teenagers"
Tidsskr Nor Laegeforen. 2009 Aug 13; 129(15): 1447-50LagerlÃ¸v P, Holager T, Helseth S, Rosvold EO

Pathophysiological Basis of Migraine Prophylaxis

2009-09-22T17:36:00.000-07:00

Several cellular and molecular mechanisms have been implicated in migraine pathophysiology including abnormal neuronal excitability and vascular events. Drugs from different pharmacological classes are used for migraine prophylaxis. These agents may normalize neuronal excitability by modulating distinct ionic channels and various neurotransmitter systems.

They can also block cortical spreading depression, prevent peripheral and/or central pain sensitization, and normalize brainstem function. Most of the drugs recently used in migraine prophylaxis have been identified by serendipidy and they have been originally approved for other indications.

Subsequently, their use has been extended to migraine prevention, according to their putative mechanisms of action. More recently, trials on adequate samples of migraine patients have been conducted for several drugs. In the present review, we will present and discuss the pathophysiological bases for the use of antidepressants, beta-adrenergic blockers, calcium channel blockers and antiepileptic drugs in migraine prevention.

Currently, the major classes of conventional migraine preventive drugs include the antidepressant amitriptyline, the beta-adrenergic blocker propranolol, and the antiepileptic drugs topiramate and valproic acid. Promising results have recently been obtained for angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers.

Some limited clinical findings have also been reported for atypical antipsychotic agents, nutritional supplements and also botulinum toxin. Targets of migraine preventive treatment are to reduce frequency and intensity of attacks and to decrease disability related to chronic headache.

"Pathophysiological Basis of Migraine Prophylaxis"
Prog Neurobiol. 2009 Aug 1; Galletti F, Cupini LM, Corbelli I, Calabresi P, Sarchielli P

Hyperinsulinaemia in migraineurs is associated with nitric oxide stress.

2009-09-21T17:23:00.001-07:00

Cephalalgia. 2009 Sep 9; Gruber HJ, Bernecker C, Pailer S, Fauler G, Horejsi R, MÃ¶ller R, Lechner A, Fazekas F, Truschnig-Wilders MThere is growing evidence that alterations in the insulin and glucose metabolism may be involved in the pathogenesis of migraine. Nitric oxide (NO) stress has been associated with migraine. However, the role of NO on the insulin and glucose metabolism in migraineurs has remained elusive to date. The aim of the present study was to investigate the insulin and glucose metabolism in migraineurs and to determine possible interactions with the NO pathway. One hundred and twenty non-obese probands participated in this study, including 48 migraineurs and 72 healthy volunteers. Various parameters of the NO pathway, glucose metabolism as well as body measurement parameters were determined. We found a highly significantly increased insulin and Homeostasis Model Assessment (HOMA)-index in migraine patients, whereas fasting glucose was decreased. Logistic regression revealed an odds ratio of 5.67 for migraine, when comparing the lowest with the highest quartile of HOMA. Multivariate analysis showed that HOMA, waist-to-length ratio and nitrite as parameters of NO stress were highly significantly correlated. We show here that hyperinsulinaemia is associated with migraine and, furthermore, is correlated with increased NO stress. These findings represent a new pathophysiological mechanism that may be of clinical relevance.

Cortical spreading depression-new insights and persistent questions.

2009-09-14T06:25:00.001-07:00

Cephalalgia. 2009 Oct; 29(10): 1115-24Charles A, Brennan KSince its original extensive description by Leao in 1944, thousands of publications have characterized the phenomenon of cortical spreading depression (CSD). Despite the attention that CSD has received over more than six decades, however, many fundamental questions regarding its initiation, propagation, functional consequences, and relationship to migraine and other human disorders remain unanswered. Advances in genetics and cellular imaging have led to important insights into the basic mechanisms of CSD, with increasing attention focused on specific neuronal ion channels, neurotransmitters and neuromodulators. In addition, there is growing recognition that astrocytes and the vasculature may play an active, rather than simply a passive or reactive role in CSD. Several recent descriptions of CSD in humans in the setting of brain injury provide definitive evidence that this phenomenon can occur and have important functional consequences in the human brain. Although the exact role of CSD in migraine has yet to be conclusively established, there is strong evidence that the investigation of CSD in animal models can provide meaningful information about migraine that can be translated into the clinical setting. This review will briefly address the extensive work that has been done on CSD over more than half a century, but focus primarily on more recent studies with a particular emphasis on relevance to migraine.

Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus.

2009-09-13T17:36:00.001-07:00

Brain. 2009 Sep 8; Sixt ML, Messlinger K, Fischer MJSeveral lines of evidence suggest a major role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine and other primary headaches. Inhibition of CGRP receptors by olcegepant and telcagepant has been successfully used to treat acute migraine and to reduce the activity of spinal trigeminal neurons involved in meningeal nociception in rodents. The site of CGRP receptor inhibition is unclear, however. In adult Wistar rats anaesthetized with isofluorane systemic intravenous infusion (0.9 mg/kg) or unilateral facial injection (1 mM in 100 microl) of capsaicin was used to induce activity in the trigeminal nociceptive system. Animals were pre-treated either by saline or olcegepant. In comparison with vehicle infusion or the non-injected side of the face, capsaicin significantly increased the expression of the activation markers Fos in the spinal trigeminal nucleus and phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion. Pre-treatment with olcegepant (900 microg/kg) inhibited the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion was not changed by olcegepant pre-treatment. CGRP receptor inhibition, which has been shown to decrease spinal trigeminal activity, is likely to occur in the central nervous system rather than in the periphery including the trigeminal ganglion. This may be important for future therapeutic interventions with CGRP receptor antagonists in migraine.

The health and psychosocial functioning of caregivers of children with neurodevelopmental disorders.

2009-09-12T15:57:00.001-07:00

Disabil Rehabil. 2009; 31(9): 741-52Lach LM, Kohen DE, Garner RE, Brehaut JC, Miller AR, Klassen AF, Rosenbaum PLPURPOSE: Children with neurodevelopmental disorders (Neuro) pose complex parenting challenges, particularly if the condition co-occurs with behaviour problems. Such challenges are likely to impact caregiver health and well-being. This study explores the extent to which caregivers of children with both 'Neuro' and behaviour problems differ in their physical and psychosocial outcomes from caregivers of children with either condition or neither condition. METHOD: The first wave of data collected in the National Longitudinal Survey of Children and Youth in Canada (1994) was used to identify four groups of caregivers of 4 to 11-year-old children: caregivers of children with a 'Neuro' disorder and externalising behaviour problems (Both; n=414), caregivers of children with a 'Neuro' disorder only (Neuro Only; n=750), caregivers of children with an externalising behaviour problem only (Ext Only; n=1067), and caregivers of children with neither health condition (Neither; n=7236). RESULTS: Caregivers in the 'Both' group were least likely to report excellent or very good health, and more frequently reported chronic conditions such as asthma, arthritis, back problems, migraine headaches, and limitations in activities as compared to the 'Neither' group. This group also exhibited higher depression scores, experienced more problematic family functioning, and reported lower social support than the 'Neither' group. Scores for caregivers in the 'Ext Only' and 'Neuro Only' groups tended to lie between the 'Both' and 'Neither' group scores and often did not differ from one another. CONCLUSIONS: Caregivers of children with both neurodevelopmental disorders and behaviour problems exhibited a greater number of health and psychosocial problems. While addressing children's behaviour problems, health care professionals should also consider caregiver physical and psychosocial health as this may also have an impact on children's well-being.

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse.

2009-09-11T17:52:00.001-07:00

Cephalalgia. 2009 Oct; 29(10): 1021-7Diener HC, Dodick DW, Goadsby PJ, Bigal ME, Bussone G, Silberstein SD, Mathew N, Ascher S, Morein J, Hulihan JF, Biondi DM, Greenberg SJDiener H-C, Dodick DW, Goadsby PJ, Bigal ME, Bussone G, Silberstein SD, Mathew N, Ascher S, Morein J, Hulihan JF, Biondi DM & Greenberg SJ. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia 2009. London. ISSN 0333-1024Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

The course of migraine-a diary study in unselected patients.

2009-09-10T23:35:00.001-07:00

Cephalalgia. 2009 Oct; 29(10): 1049-58Lieba-Samal D, Bartl S, Salhofer S, Prajsnar A, Massl R, Freydl E, Fathinia P, WÃ¶ber-BingÃ¶l C, WÃ¶ber CLieba-Samal D, Bartl S, Salhofer S, Prajsnar A, Massl R, Freydl E, Fathinia P, WÃ¶ber-BingÃ¶l C & WÃ¶ber C. The course of migraine-a diary study in unselected patients. Cephalalgia 2009. London. ISSN 0333-1024The course of disease and the predictive value of depression and anxiety in patients with migraine were prospectively examined. We recruited 393 migraineurs through articles in newspapers and performed a follow-up examination 30 months later. At baseline and follow-up, patients underwent a semistructured interview, filled out the Headache Impact Test (HIT-6), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) and they kept a headache diary for 30 days. One hundred and fifty-one patients (38.6%) were seen at follow-up. The baseline data of patients with and without follow-up were comparable. At follow-up the number of headache days per month had decreased from 9.6 +/- 5.8 to 8.1 +/- 6.3 (P < 0.001) and the proportion of patients with chronic headache (15.4%) and medication overuse (13%) had remained stable. SDS and SAS scores were associated with a high migraine frequency and high initial SDS scores predicted high migraine frequency at follow-up. This longitudinal study in unselected patients with migraine not excluding subjects with chronic headache, medication overuse, depression or anxiety does not point towards migraine as a progressive disease in the vast majority of patients and confirms the importance of psychiatric comorbidity.

Physicians appeals on the dangers of mobile communication - what is the evidence? Assessment of public health data.

2009-09-10T17:44:00.000-07:00

Int J Hyg Environ Health. 2009 Sep 5; Zur Nieden A, Dietz C, Eikmann T, Kiefer J, Herr CEIn October 2002 German physicians appealed to persons in the field of health care, politicians and the public with "great concern" ("Freiburger Appell", "Appeal of Freiburg") claiming "soaring incidences of symptoms and diseases in the general population" to be causally related to the "commence of radio (wave) burden", i.e. due to mobile radio technology. This first example was followed by several further appeals published nationally and Europe-wide up until today. The aim of the present paper is an evaluation of the scientific literature and databases to check incidence and prevalence of symptoms and diseases stated in the appeals to have "dramatically increased" or to have appeared in "greater frequency" in adults. If the allegations were true a clear time-trend should show up since the start of widely-used mobile communication technology. The following health conditions were considered: Alzheimer's disease, dementia, sleep disturbances, tinnitus, cerebrovascular disease, ischemic heart-diseases, headache, migraine. Data on the incidence of these conditions were assessed from 1993 through at least 2005. For this, a systematic search by keywords was performed in the online-database of the National Library of Medicine (pubmed) and other national and international (European and US) databases. For none of the considered symptoms or diseases a "dramatic increase" was found to have occurred since 1993. Because of the different diagnoses and terms used in the studies, direct comparability is somewhat difficult. Indeed, with the data available no time related increases and surely no "dramatic increase" can be identified, even if the limited comparability is considered. This analysis strongly suggests that the allegations of the quoted appeals are not supported by public health data.

The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid.

2009-09-09T23:26:00.001-07:00

Cerebrospinal Fluid Res. 2009 Sep 7; 6(1): 10Harrington MG, Fonteh AN, Oborina E, Liao P, Cowan RP, McComb G, Chavez JN, Rush J, Biringer RG, Huhmer AFABSTRACT: BACKGROUND: Cerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission. METHOD: Lumbar CSF was collected prospectively from 17 participants: with no neurological or psychiatric disease, with Alzheimer's disease, multiple sclerosis, or migraine; and ventricular CSF from two cognitively healthy participants with long-standing shunts for congenital hydrocephalus. Cell-free CSF was subjected to ultracentrifugation to yield supernatants and pellets that were examined by transmission electron microscopy, shotgun protein sequencing, electrophoresis, western blotting, lipid analysis, enzymatic activity assay, and immuno-electron microscopy. RESULTS: Over 3,600 CSF proteins were identified from repeated shotgun sequencing of cell-free CSF from two individuals with Alzheimer's disease: 25% of these proteins are normally present in membranes. Abundant nanometer-scaled structures were observed in ultracentrifuged pellets of CSF from all 16 participants examined. The most common structures included synaptic vesicle and exosome components in 30-200 nm spheres and irregular blobs. Much less abundant nanostructures were present that derived from cellular debris. Nanostructure fractions had a unique composition compared to CSF supernatant, richer in omega-3 and phosphoinositide lipids, active prostanoid enzymes, and fibronectin. Conclusions Unique morphology and biochemistry features of abundant and discrete membrane-bound CSF nanostructures are described. Prostaglandin H synthase activity, essential for prostanoid production and previously unknown in CSF, is localized to nanospheres. Considering CSF bulk flow and its circulatory dynamics, we propose that these nanostructures provide signaling mechanisms via volume transmission within the nervous system that are for slower, more diffuse, and of longer duration than synaptic transmission.

Migrainous infarction: association with vascular risk factors in a male subject.

2009-09-09T02:37:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S145-6Decima D, Cavallo M, Leotta MR, Gaballo AMigraine with aura (MA) is associated with an increased risk of ischemic stroke, especially in young women with vascular risk factors (smoke, contraceptive pill). Patent foramen ovale (PFO) has also been associated with MA. We describe a 41-year-old man, in good health, with MA since 16, familiar history of diabetes, heavy smoker (30 cigarettes/day). Frequency (1-2 attacks/year) and clinical features of migraine have been unchanged since the onset. A few days before our examination he suffered a typical migraine attack. In the following hours, however, the headache became more and more throbbing and the aura symptoms (regressed as usual in 30 min) reappeared and persisted, so he went to an Emergency Department. The CT-scan (without contrast) was normal. The following days he had visual disturbances and spatial disorientation. We found a normal neurological examination and fundus oculi. He referred persisting visual troubles. We prescribed MR + angioMR which confirmed a migrainous infarction and ruled out others pathological conditions. Further tests found out dyslipidemia, hyperhomocysteinemia, impaired glucose tolerance. Transcranial Doppler showed right to left shunting. We also prescribed the screening tests for vasculitis (normal). In our opinion this case highlights the relevance of vascular risk factors in MA complications also in male subjects.

Is allodynia influenced by psychological profile in headache patients?

2009-09-08T17:28:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S113-5Lovati C, D'Amico D, Bertora P, Morandi E, Mariani C, Bussone GCutaneous allodynia is a frequent complain in headache patients, particularly in those with migraine. A stronger association is present in patients with migraine with aura and with chronic or transformed migraine. The aim of the present study was to investigate if the psychological profile may be related to the presence/absence of allodynia in a sample of headache patients. The psychological profile of patients was assessed by the SCL90R; the presence of allodynia was assessed by a set of semi-structured questions used in previous studies. For the purpose of the study, patients were divided into subgroups according to the headache type (ICDH-II diagnoses), as well as to the temporal pattern (episodic or chronic). A total of 213 consecutive headache patients were studied. Most patients had episodic migraine (116); 37 had tension-type headache. Overall, 156 patients had episodic headache forms, and 57 had chronic forms. As far as allodynia, 93 were non-allodynic; 120 presented allodynic symptoms during their headaches. No significant difference was found between allodynic and non-allodynic patients neither if studied in a whole group (t test, P = 0.10 NS) nor when patients were evaluated comparing different subgroups on the basis of headache type, and of the episodic/chronic pattern. Our results suggest that the presence/absence of allodynia may not be influenced by the psychological profile.

A woman with abdominal pain and headache.

2009-09-08T02:34:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S141-3Vaccaro M, Moschiano FWe describe a case of a 27-year-old woman who came to the Emergency Department presenting severe abdominal pain. She was evaluated by a gynaecologist and submitted to pelvic ecography without finding relevant alterations. In the successive hours, she presented severe headache in occipital region and in the posterior neck, poorly responsive to analgesic drugs. A cerebral CT scan was performed and was normal, and the patient came to our Department of Neurology. The neurological examination on admission was normal. This woman had a 7 years of long-lasting history of headache, diagnosed in another hospital as migraine without aura, and she referred a recent and progressive worsening of both the frequency and the severity of the headache. In the suspect of subarachnoidal haemorrhage, a lumbar puncture was performed, and was negative for bleeding, showing only a mild increase in the number of cells (12 leucocytes). Following the lumbar puncture, the patient presented a dramatic improvement of the headache. In the successive days, she lamented sellar hypoesthesia and, when asked, she referred a recent history of urinary and faecal retention. She was, therefore, submitted to an NMR of the lumbar and sacral medulla with evidence of a voluminous extradural formation in the sacral region suggestive for extradural sacral meningeal cyst. She was finally dispatched to the Department of Neurosurgery for surgical asportation of the cyst.

Spectral changes of near-infrared spectroscopy signals in migraineurs with aura reveal an impaired carbon dioxide-regulatory mechanism.

2009-09-07T17:48:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S105-7Liboni W, Molinari F, Allais G, Mana O, Negri E, Bussone G, D'Andrea G, Benedetto CSubjects suffering from migraine with aura (MwA) present an altered cerebral autoregulation during migraine attacks. It is still unclear whether MwA sufferers present a normal autoregulation during attack-free periods. In this study, we characterized cerebral autoregulation in the frequency domain by analyzing the spontaneous oscillations superimposed on the cerebral hemodynamic signals, as detected by near-infrared spectroscopy (NIRS). Ten healthy women (age: 38.4 +/- 9.5 years) and ten women suffering from MwA (age: 35.2 +/- 10.5 years) underwent NIRS recording in resting conditions and during breath-holding (BH). Being the NIRS signals during BH nonstationary, we used the Choi-Williams time-frequency distribution to perform spectral analysis. We considered 256 s of signals and quantified the variation in the power of the very-low frequencies (VLF: 20-40 mHz) and of the low frequencies (LF: 40-140 mHz) as response to BH. Results showed that BH increases the power in the LF band both in healthy and MwA subjects. Considering the signal of the deoxygenated hemoglobin, the average power increase in the LF band was equal to 20% +/- 15.4% for the healthy group and significantly lower, 4.8% +/- 8.3%, in the MwA group (Student's t test, P < 0.02). No significant difference was observed in the VLF band or in the oxygenated hemoglobin signal power variations of the LF and VLF bands. The resulting data reveal a possible impairment in the carbon dioxide-regulatory mechanism in MwA subjects.

Epidemiology and characteristics of occipital brain infarcts in young adults in southwestern Finland.

2009-09-06T18:13:00.001-07:00

J Neurol. 2009 Sep 3; Martikainen MH, Majamaa KOccipital stroke and occipital epilepsy are possible manifestations of mitochondrial diseases. A previous study in northern Finland suggested a frequency of 10% for mitochondrial disorder in young patients with stroke. Here we studied the epidemiology of occipital brain infarcts in a defined population in southwestern Finland. Patients diagnosed with brain infarct or visual field defect with onset at the ages of 18-45 years were identified from the discharge files at the Turku University Hospital. We further ascertained those patients with an occipital brain infarct in brain imaging or homonymous hemianopia with no signs of other etiology in brain imaging. We reviewed the clinical data for known stroke risk factors and analyzed samples for the m.3243A > G and m.8344A > G mutations in mitochondrial DNA (mtDNA), and determined mtDNA haplogroups and five common mutations in the gene encoding polymerase gamma (POLG1). Migraine was more common in young patients with occipital brain infarct than in the general population, especially among women. None of the patients harboured the m.3243A > G or m.8344A > G mutation in mtDNA or any of the five common mutations in POLG1. Interestingly, 17% of the men and 33% of the women belonged to the mtDNA haplogroup Uk, while its frequency in the general population is 17%. Our results suggest that mtDNA haplogroup Uk is associated with increased risk of occipital stroke in young women. POLG1 mutations have been associated with occipital epilepsy, but we did not find the common mutations in patients with occipital stroke.

Efficacy of Ginkgolide B in the prophylaxis of migraine with aura.

2009-09-06T05:30:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S121-4D'Andrea G, Bussone G, Allais G, Aguggia M, D'Onofrio F, Maggio M, Moschiano F, Saracco MG, Terzi MG, Petretta V, Benedetto CIn a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 +/- 2.2 in the run-in period, to 2.0 +/- 1.9 during TI and to 1.2 +/- 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 +/- 19.4 min during run-in, 28.2 +/- 19.9 during TI, and 17.6 +/- 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.

Chronic migraine and chronic tension-type headache: are they the same or different?

2009-09-05T16:28:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S81-4Manzoni GC, Torelli PThe question in the title of this article arises from ambiguities in the diagnostic criteria for chronic migraine (CM) included in the 2004 International Classification of Headache Disorders, 2nd Edition (ICHD-II), and in the 2006 revision. More broadly speaking, it also arises from the fact that to date the general subject of chronic daily headaches (CDH) has not been approached in a correct and appropriate way. For all its limitations, ICHD-II has unquestionable merits and remains a fundamental tool. However, it is a tool that gets a snapshot picture of headache; so, it is not applicable to a dynamic form that evolves from and is transformed by a chain of events. If these events are ignored, there will be no accurate interpretation of the final clinical picture. Today, we still do not have any classification of headache syndromes to complement ICHD-II. Currently, then, the only way to approach the CDH issue is to put patients at the center and to focus on their life histories. If we reason strictly in terms of diagnostic classification criteria, which for this headache subtype are artificial and ambiguous, we may have trouble finding an answer to the title question. However, if we reason in broader clinical terms, putting at the center of our reasoning not only headache features, but patients with all their histories, the answer can only be that CM and chronic tension-type headache are two different clinical entities.

Migraine prevalence in eating disorders and pathophysiological correlations.

2009-09-04T18:29:00.001-07:00

Neurol Sci. 2009 May; 30 Suppl 1: S55-9D'Andrea G, Ostuzzi R, Francesconi F, Musco F, Bolner A, d'Onofrio F, Colavito DThe eating disorders (ED): anorexia nervosa (AN) and Bulimia nervosa (BN) are severe psychiatric and somatic conditions occurring mainly in young woman. Although the etiology is largely unknown, same evidences suggest that biological and psychological factors play a relevant role in the pathogenesis, along with monoamine, indole and same hypothalamic hormonal dysfunctions. Migraine is characterized by similar metabolic and psychological anomalies suggesting that a possible relationship exists between the two pathological conditions. In order to understand the possible relationship between migraine and ED, we have investigated the prevalence of migraine and the other primary headaches in a large group of AN and BN patients. In addition, we have studied the role of tyrosine metabolism in the same group of AN and BN young woman sufferers. In particular, we measured plasma levels of elusive amines: tyramine (Tyr) and octopamine (Oct) and catecholamines: noradrenalin (NE), dopamine (DA). The results of this study show that the prevalence of migraine in the woman affected be EA is very high (>75%). The levels of Tyr and DA were higher and levels of NE were lower in the ED patients with respect to the control subject. These biochemical findings suggest that abnormalities of limbic and hypothalamic circuitries play a role in the pathogenesis of ED. The very high prevalence of migraine in our group of ED sufferers and the biochemical profile of migraine, similar to that ED patients have shown in this study, suggest that migraine may constitute a risk factor for the occurrence of ED in the young females. This hypothesis is supported by the onset of migraine attacks that initiated, in the majority of the patients, before the occurrence of ED symptoms.

A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine.

2009-09-03T18:43:00.001-07:00

Cephalalgia. 2009 Aug 10; Evans RW, Evans RE, Kell HJEvans RW, Evans RE & Kell HJ. A survey of family doctors on the likeability of migraine and other common diseases and their prevalence of migraine. Cephalalgia 2009. London. ISSN 0333-1024A survey of 148 family doctors attending a continuing medical education migraine update lecture was performed to assess whether family doctors like to treat migraine and other common disorders and the prevalence of migraine. Doctors were asked to respond to the following statement using a five-point Likert scale (from 1, strongly disagree to 5, strongly agree): 'I like to treat patients with this disease or symptom'. The response rate was 53% with a mean age of 51.5 years. Doctors reported liking to treat general medical conditions more (mean = 4.40) than migraine (mean = 3.38) and other neurological diseases (mean = 3.20). Doctors reported a personal history of migraine in the prior 1 year of 22.8% and 45.6% lifetime, with 17% becoming aware for the first time that they personally had migraine after attending the lecture. Respondents with a personal history of migraine liked to treat migraine more than those without a history.

Transcranial Doppler and transesophageal echocardiography: comparison of both techniques and prospective clinical relevance of transcranial Doppler in patent foramen ovale detection.

2009-09-02T18:32:00.001-07:00

J Stroke Cerebrovasc Dis. 2009 Sep-Oct; 18(5): 343-8Caputi L, Carriero MR, Falcone C, Parati E, Piotti P, Materazzo C, Anzola GPBACKGROUND: Patent foramen ovale (PFO) has been investigated in several conditions apart from cryptogenic ischemic stroke. Contrast transesophageal echocardiography (cTEE) is the gold standard for the diagnosis, although it has some known limitations. Contrast transcranial Doppler (cTCD) allows a semiquantitative estimation of right-to-left shunt (RLS) volume. The aims of our study were to confirm the diagnostic accuracy of cTCD in PFO diagnosis and to compare the abilities of cTCD and cTEE to detect a RLS and PFO, respectively, under normal breathing. The latter could represent an important feature for its clinical significance. METHODS: A total of 100 consecutive patients (59 women and 41 men, age 46 +/- 12 years) were evaluated after stabilized ischemic stroke/transient ischemic attack, migraine, and lacunae, and before neurosurgery in sitting position. All patients undertook cTEE and cTCD, at rest and under Valsalva maneuver (VM). cTEE under VM was the reference standard. A categorization of patients and a semiquantitative cTCD classification were proposed. RESULTS: In all, 63 of 100 patients had PFO diagnosed by cTEE. A general concordance of up to 90% between both techniques was found. cTCD sensitivity and specificity were 96.8% and 78.4%, respectively. In 17 of 100 patients with cTEE-proven PFO under VM, cTCD and cTEE detected RLS at rest in 75% (95% confidence interval [CI] 62%-85%) and 48% (95% CI 35%-61%) of cases, respectively (P < .001). cTEE disclosed RLS at rest in about 71% (95% CI 9%-42%) of cTCDs showing a "shower-curtain" pattern and only in about 22% (95% CI 52%-85%) of those cTCDs without that pattern. CONCLUSIONS: In diagnosing PFO, cTCD has a good accuracy compared with cTEE. To detect a RLS at rest, cTCD appears to be more sensitive than cTEE. The latter resulted positive under normal breathing, mostly in cases of significant RLS at cTCD. Our results point out the impact of cTCD in the evaluation of RLS volume, thus aiding, in association with the anatomic details by cTEE, in the prevention of the occurrence or recurrence of paradoxical embolism in individuals with and without cerebrovascular diseases. The combination of cTEE and cTCD could be considered the real gold standard for PFO in the near future.

Impact of osteopathic manipulative treatment on cost of care for patients with migraine headache: a retrospective review of patient records.

2009-09-02T08:09:00.001-07:00

J Am Osteopath Assoc. 2009 Aug; 109(8): 403-7Schabert E, Crow WTCONTEXT: Migraine headache is highly prevalent in the United States, resulting in large healthcare expenditures. OBJECTIVE: To determine whether the use of osteopathic manipulative treatment (OMT) at an osteopathic family practice residency clinic affected the cost of treating patients with migraine headache, compared with non-OMT care at the osteopathic clinic and care at an allopathic family practice residency clinic. METHODS: A retrospective review of electronic medical records from patients treated for migraine at two residency clinics within the Florida Hospital organization from July 1, 2002, to June 30, 2007. One of the clinics was osteopathic and offered OMT services, and the other clinic was allopathic and did not offer OMT. All costs compiled during the office visits and costs of prescribed medications were tabulated for each patient. Patients' pain-severity ratings, as reported in office visits in 2006 and 2007, were also tabulated. Results: Electronic medical records from 631 patients, representing 1427 migraine-related office visits, were analyzed. Average cost per patient visit was approximately 50% less at the osteopathic clinic than at the allopathic clinic ($195.63 vs $363.84, respectively; P

Optical coherence tomography: another useful tool in a neuro-ophthalmologist's armamentarium.

2009-09-01T08:14:00.001-07:00

Curr Opin Ophthalmol. 2009 Aug 18; Subei AM, Eggenberger ERPURPOSE OF REVIEW: Optical coherence tomography (OCT) affords clinicians the ability to quantify the thickness of the retinal nerve fiber layer (RNFL), which is useful in managing diseases of the optic nerve. The purpose of this review is to coalesce the current literature on the use of OCT in neuro-ophthalmology to enhance its use in clinical practice. RECENT FINDINGS: OCT's advancement into spectral domain refined its ability to measure the RNFL by increasing scanner speed. Although OCT was shown to be superior to other instruments in measuring the RNFL in certain conditions, it lacks laser polarimetry's ability to detect microtubule changes. Moreover, OCT's measurements cannot be used interchangeably with other instruments' assessments of the RNFL. OCT has been studied in several neuro-ophthalmic conditions, including anterior ischemic optic neuropathy, optic neuritis/multiple sclerosis, neuromyelitis optica, pseudotumor cerebri, migraine, optic nerve head drusen, compressive optic neuropathy, and Leber's hereditary optic neuropathy. SUMMARY: OCT's wide use in evaluating the optic nerve and the visual system has revolutionized our assessment, management, research, and understanding of neuro-ophthalmic diseases.

MTHFR 677C-->T and ACE D/I polymorphisms and migraine attack frequency in women.

2009-08-31T18:43:00.000-07:00

Cephalalgia. 2009 Aug 10; SchÃ¼rks M, Zee RY, Buring JE, Kurth TSchÃ¼rks M, Zee RYL, Buring JE & Kurth T. MTHFR 677C-->T and ACE D/I polymorphisms and migraine attack frequency in women. Cephalalgia 2009. London. ISSN 0333-1024Data on the association of the MTHFR 677C-->T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >/= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >/= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.

The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe.

2009-08-30T15:51:00.001-07:00

Lupus. 2009; 18(10): 889-93Cervera R, Boffa MC, Khamashta M, Hughes GThe Euro-Phospholipid project started in 1999 with a multicentre, consecutive and prospective design. A total cohort of 1000 patients with antiphospholipid syndrome (APS), derived from 13 countries (Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Israel, Italy, the Netherlands, Portugal, Spain and United Kingdom), has been followed since then. This project allowed the identification of the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of APS and demonstrated that it is possible to recognize more homogeneous subsets of clinical significance. Patients with APS associated with systemic lupus erythematosus (SLE) had more episodes of arthritis, livedo reticularis and more frequently exhibited thrombocytopenia and leucopenia. Female patients had more episodes of arthritis and livedo reticularis - both connected with the higher prevalence of migraine and SLE-related APS in women, while male patients had more myocardial infarction, epilepsy and lower limb arterial thrombosis. Childhood onset patients presented more episodes of chorea and jugular vein thrombosis, whereas older onset patients were more frequently male and had more strokes and angina pectoris, but less frequently livedo reticularis.

Migraine.

2009-08-30T08:13:00.001-07:00

Handb Exp Pharmacol. 2009; 75-89Benemei S, Nicoletti P, Capone JG, Cesaris FD, Geppetti PMigraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. However, various drugs for the symptomatic or prophylactic treatment of the disease are available. Recently, better knowledge of the neurobiological and pharmacological aspects of a subset of trigeminal primary sensory neurons has provided key information for the development of effective molecules that specifically target the activation of the trigeminovascular system and may represent a significant advancement in the treatment of the disease. These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.

Interictal quantitative EEG in migraine: a blinded controlled study.

2009-08-30T03:50:00.001-07:00

J Headache Pain. 2009 Aug 25; BjÃ¸rk MH, Stovner LJ, EngstrÃ¸m M, Stjern M, Hagen K, Sand TAbnormal electroencephalography (EEG) in migraineurs has been reported in several studies. However, few have evaluated EEG findings in migraineurs during a time period when neither the last attack nor the next attack may interact with the results. We, therefore, compared interictal EEG in migraineurs and headache-free subjects with a design controlled for interference by pre-ictal changes. Pre-ictal EEG findings in the painful cranial side during the next attack after registration were also investigated. Correlations between clinical variables and EEG are reported as well. Interictal EEGs from 33 migraineurs (6 with and 27 without aura) and 31 controls were compared. Absolute power, asymmetry and relative power were studied for delta, theta and alpha frequency bands in parieto-occipital, temporal and fronto-central areas. EEG variables were correlated to attack frequency, headache duration, attack duration, pain intensity, photo- and phonophobia. Compared with controls, migraineurs had increased relative theta power in all cortical regions and increased delta activity in the painful fronto-central region. Absolute power and asymmetry were similar among groups. In age-adjusted analyses, headache intensity correlated with increased delta activity. In this blinded controlled study, we found globally increased relative theta activity in migraineurs. A slight interictal brain dysfunction is probably present between attacks.

Effects of affective pictures on pain sensitivity and cortical responses induced by laser stimuli in healthy subjects and migraine patients.

2009-08-29T15:42:00.001-07:00

Int J Psychophysiol. 2009 Aug 24; de Tommaso M, Calabrese R, Vecchio E, De Vito Francesco V, Lancioni G, Livrea PVisually induced analgesia has been correlated with the affective content of pleasant, neutral or unpleasant pictures. The aim of the present study was to assess the effect of affective images vision on laser evoked potentials and pain perception, in a cohort of healthy subjects and migraine patients. Twenty-two healthy subjects and 24 migraine without aura patients (recorded during the inter-critical phase) participated in the study. Eighty-four colour slides, arranged in two blocks, each consisting of 14 pleasant, 14 unpleasant and 14 neutral images, in random presentation, were chosen from the International Affective Picture System. The Co(2) laser stimuli were delivered on the dorsum of the right hand and supra-orbital zone at 7.5-watt intensity and 25-ms duration, in basal condition and during the viewing of affective pictures. Migraine patients expressed higher scores of valence and arousal for pleasant and unpleasant pictures, compared to controls. In both groups, a late positive potential in the 400-700 ms time range was clear for pleasant and unpleasant pictures, but its amplitude was significantly reduced in migraine patients. The pain rating and the N2 component were reduced in both groups during the visual task compared to basal condition. In migraineurs and controls the P2 wave was reduced during the vision of pleasant pictures, compared to basal condition. This indicates that stimulation by images with different affective content reduces subjective pain for a cognitive mechanism of attentive engagement, while a special inhibition of later LEPs is produced by a positive emotional impact. In migraine, affective images are able to modulate pain perception and LEPs, differently from other modalities of distraction, suggesting a possible emotive elaboration of painful stimuli.

EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force.

2009-08-28T16:13:00.001-07:00

Eur J Neurol. 2009 Sep; 16(9): 968-81Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, SÃ¡ndor PSBACKGROUND: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. OBJECTIVES: To give evidence-based or expert recommendations for the different drug treatment procedures in the particular migraine syndromes based on a literature search and the consensus of an expert panel. METHODS: All available medical reference systems were screened for the range of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies (EFNS) resulting in level A, B, or C recommendations and good practice points. RECOMMENDATIONS: For the acute treatment of migraine attacks, oral non-steroidal antiinflammatory drug (NSAID) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAID and triptans, oral metoclopramide or domperidone is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful, or dihydroergotamine. For the prophylaxis of migraine, betablockers (propranolol and metoprolol) flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis include amitriptyline, naproxen, petasites, and bisoprolol.

Electrophysiological and morphological properties of neurons in the substantia gelatinosa of the mouse trigeminal subnucleus caudalis.

2009-08-28T04:41:00.001-07:00

Pain. 2009 Aug 22; Davies AJ, North RAThe excitability of the second order neurons within the trigeminal subnucleus caudalis underlies pain perception and processing in migraine and trigeminal neuralgia. These neurons were studied with whole-cell patch-clamp technique in slices from mouse brain stem. Electrical and morphological characteristics of 56 neurons were determined. Four categories were distinguished from electrophysiological properties: tonic (39%), phasic (34%), delayed (16%) and single spiking (11%). These categories did not show distinct morphological properties. Neurons had tetrodotoxin-sensitive sodium currents that activated and inactivated within milliseconds. They also showed a high voltage-activated, slowly inactivating calcium current: up to half of this current was blocked by omega-conotoxin GVIA (1muM) and omega-agatoxin IVA (100-300 nM), but it was not affected by nifedipine (10muM). Exogenously applied capsaicin (1muM) and alphabetamethylene-5'-adenosine triphosphate (100muM) elicited large amplitude, spontaneous excitatory postsynaptic currents that were blocked by capsazepine (10muM) and 5-[(3-phenoxybenzyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-benzene-1,2,4-tricarboxylic acid (A-317491: 10muM), respectively. Thus, neurons of the mouse trigeminal subnucleus caudalis substantia gelatinosa exhibit N-type and P/Q-type voltage-gated calcium channels, and receive presynaptic afferents that express TRPV1 and P2X(2/3) receptors. These results suggest possible therapeutic interventions, and serve as a basis for the characterization of cellular changes that may underlie trigeminal neuropathic pain.

Depressive symptoms and migraine comorbidity among pregnant Peruvian women.

2009-08-27T02:35:00.001-07:00

J Affect Disord. 2009 Aug 19; Cripe SM, Sanchez S, Lam N, Sanchez E, Ojeda N, Tacuri S, Segura C, Williams MABACKGROUND:: Migraine and depression are known to be comorbid conditions in non-pregnant women and men. However, the migraine-depression comorbidity among pregnant women, particularly women in developing countries has not been evaluated. Therefore, we evaluated the migraine-depressive symptom relationship in a large cohort of pregnant Peruvian women. METHODS:: Women who delivered singleton infants (n=2293) at the Instituto Nacional Materno Perinatal, Lima, Peru were interviewed during the postpartum hospital stay. Women were asked questions related to their lifetime and pregnancy experiences with headaches and migraines. Responses to these questions enabled the classification of "probable" and "strict" migraines according to the International Headache Society diagnostic criteria. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire Depression Subset. Logistic regression procedures were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS:: Approximately 32% of the women reported a history of migraine, while 41% reported experiencing moderate to severe depressive symptoms during pregnancy. Compared with women without a history of migraine, women with strict migraine had AORs of 2.12 (95% CI 1.54-2.93), 1.85 (95% CI 1.16-2.96) and 2.23 (95% CI 1.08-4.62) for moderate, moderately severe and severe depressive symptoms, respectively. CONCLUSION:: This is the first report of a cross-sectional association between migraine and depressive symptoms in pregnant women. If our findings are confirmed, pregnant women with a history of migraine may benefit from increased vigilance for screening and treating depressive symptoms.

Intact neurovascular coupling during executive function in migraine without aura: interictal near-infrared spectroscopy study.

2009-08-26T16:11:00.001-07:00

Cephalalgia. 2009 Aug 11; Schytz HW, CiftÃ§i K, Akin A, Ashina M, Bolay HSchytz HW, CiftÃ§i K, Akin A, Ashina M & Bolay H. Intact neurovascular coupling during executive function in migraine without aura: interictal near-infrared spectroscopy study. Cephalalgia 2009. London. ISSN 0333-1024An altered neurovascular coupling has been proposed in migraine. We aimed to investigate neurovascular coupling during a mental task interictally in patients with migraine without aura (MO) by near-infrared spectroscopy (NIRS). Twelve migraineurs and 12 healthy controls were included. Using NIRS, we recorded the magnitude and latency of cortical changes in oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (Hb) during the colour-word matching Stroop test via 16 channels covering the forehead. We found no differences in the magnitude of responses between migraineurs and healthy subjects in the incongruent Stroop task subtracted by the neutral Stroop task on either side of the frontal cortex for HbO(2) (left, P = 0.984; right, P = 0.406) or Hb (left, P = 0.689; right, P = 0.406) values. No differences in error rate (P = 0.611) or reaction time (P = 0.936) were found between healthy subjects and MO patients for incongruent tasks. The present study suggests that vascular reactivity and oxygen supply during a mental task in patients with MO are intact interictally.

Episodic spontaneous hypothermia potentially triggered by hyperinsulinemia.

2009-08-24T23:02:00.001-07:00

Horm Res. 2009; 72(2): 124-8Capanna R, Marcovecchio ML, Verrotti A, Trotta D, Chiarelli F, Mohn AEpisodic spontaneous hypothermia is an infrequent disorder, the pathogenic mechanisms of which have not been completely clarified, although alterations in the serotoninergic system have been suggested. We report the history of a girl with episodes of dizziness and shivering associated with a body temperature lower than 35 degrees C since the age of 10 months. At the age of 11 years, she was admitted to a local hospital and an oral glucose tolerance test showed high total insulin levels. Hypoglycemia secondary to hyperinsulinemia was suspected, and a low-carbohydrate (simple) diet was proposed without results. Due to the recurrence of the episodes, episodic spontaneous hypothermia triggered by hyperinsulinemia was suspected, and treatment with flunarizine, a drug considered the first line in the treatment of migraine-related disorders, was started with a resulting reduction in the episodes. A new endocrinological evaluation showed decreased insulin secretion. In our patient, the success of the therapy might be due to the well-known effect of calcium antagonists in inhibiting serotonin uptake and thereby regulating serotonin levels after hyperinsulinism. This case suggests hyperinsulinemia as a potential mechanism for episodic spontaneous hypothermia, probably mediated by an interaction between insulin and the serotoninergic system.

Utility and Preliminary Effects of Online Digital Assistance (ODA) for Behavioral Attack Prevention in Migraine.

2009-08-24T16:14:00.001-07:00

Telemed J E Health. 2009 Aug 20; Kleiboer A, Sorbi M, MÃ©relle S, Passchier J, van Doornen LThere were two objectives of this research. First was to establish the utility of online digital assistance (ODA), a generic software-based method designed to support behavioral training (BT) in migraine. The second was to test whether ODA can produce additional effects in BT. Utility (feasibility and acceptability) was based on 44 patients with migraine who received ODA as an adjuvant to BT delivered to small groups by lay trainers with migraine at home. ODA tracking files were used to determine ODA feasibility. Acceptability was assessed by a structured interview. To examine ODA effects, 31 patients with migraine who received ODA during BT and at 6 months' follow-up were compared with a matched group of 31 participants who received BT only. Feasibility was established based on minimal technical problems, good compliance, and successful execution of ODA. Acceptability was confirmed by positive participant responses concerning usefulness, supportiveness, and low burden. Finally, ODA participants did not mark better improvements considering migraine attack frequency, internal control, and migraine-specific quality of life compared to those that underwent BT only. ODA is feasible, well-accepted, and perceived to support self-care in 44 patients with migraine. The method is currently designed for these patients, but it can be easily adapted for other health settings. Whether ODA can induce higher gains remains to be established.

The effect of migraine prophylaxis on migraine-related resource use and productivity.

2009-08-24T08:21:00.001-07:00

CNS Drugs. 2009; 23(9): 727-38LÃ¡inez MJIn the US, it is estimated that up to 10% of men and 25% of women, particularly those aged 25-55 years, experience debilitating migraines, such that the condition presents an enormous economic burden for patients, health systems, employers and society. Migraine headache is a particularly prevalent condition associated with major reductions in patients' quality of life. From a payer perspective, the implementation of relevant programmes of migraine prophylaxis is highly desirable. Consistent evidence exists, from several randomized, controlled studies, of the efficacy of amitriptyline, divalproex sodium, propranolol, timolol and topiramate in migraine prophylaxis. Considering resource utilization, various studies suggest that migraine prophylaxis with antiepileptics, antidepressants, beta-blockers or calcium channel antagonists markedly reduces triptan use and visits to physician offices and emergency departments (EDs), without compromising quality of care or treatment outcomes. Over recent years, the effects of topiramate in reducing resource utilization in patients with migraine have been relatively widely studied. In US claims database analyses involving >4000 patients with migraine, topiramate significantly reduced triptan use by up to 20% in the 12-month period after starting treatment. Reductions were also noted in the numbers of ED visits, diagnostic procedures, hospital admissions and migraine-related hospitalization days. These long-term benefits of topiramate manifested without any increase in overall headache-related costs. Furthermore, in detailed modelling analyses based on UK and US data, topiramate-induced savings in acute medical services were estimated to offset about one-quarter of the monthly per patient cost of the topiramate regimen, which was shown to be a dominant cost-effective intervention relative to no preventive therapy: cost-effectiveness ratios were calculated as pound 5728 per quality-adjusted life-year (QALY) [2005 costings] and $US10 888 per QALY (2002 costings), respectively. Overall, there is a need to improve quality of care in migraine, and prophylactic therapy appears to be an effective option, particularly with respect to decreasing resource use and improving productivity. For both health-plan payers and employers, topiramate appears to be a cost-effective intervention for preventing migraine.

The ergot alkaloid gene cluster: Functional analyses and evolutionary aspects.

2009-08-23T23:31:00.001-07:00

Phytochemistry. 2009 Aug 18; Lorenz N, Haarmann T, PaÅ¾outovÃ¡ S, Jung M, Tudzynski PErgot alkaloids and their derivatives have been traditionally used as therapeutic agents in migraine, blood pressure regulation and help in childbirth and abortion. Their production in submerse culture is a long established biotechnological process. Ergot alkaloids are produced mainly by members of the genus Claviceps, with Claviceps purpurea as best investigated species concerning the biochemistry of ergot alkaloid synthesis (EAS). Genes encoding enzymes involved in EAS have been shown to be clustered; functional analyses of EAS cluster genes have allowed to assign specific functions to several gene products. Various Claviceps species differ with respect to their host specificity and their alkaloid content; comparison of the ergot alkaloid clusters in these species (and of clavine alkaloid clusters in other genera) yields interesting insights into the evolution of cluster structure. This review focuses on recently published and also yet unpublished data on the structure and evolution of the EAS gene cluster and on the function and regulation of cluster genes. These analyses have also significant biotechnological implications: the characterization of non-ribosomal peptide synthetases (NRPS) involved in the synthesis of the peptide moiety of ergopeptines opened interesting perspectives for the synthesis of ergot alkaloids; on the other hand, defined mutants could be generated producing interesting intermediates or only single peptide alkaloids (instead of the alkaloid mixtures usually produced by industrial strains).

Self-medication with OTC analgesics among 15 - 16 year-old teenagers

2009-08-23T07:24:00.001-07:00

OTC analgesics were released for sale outside pharmacies in Norway in 2003. This study assesses indications and frequency of use of these drugs among 15 - 16 year-old teenagers in Norway after 2003.

MATERIAL AND METHOD:
We developed a questionnaire, which contained 65 questions with one or more response options. This was given to all pupils in the finale grade at six junior high schools in a town with 60 000 inhabitants (Drammen).

RESULTS:
367 of 626 (58.6 %) pupils participated. 50 % of the boys and 71 % of the girls had used OTC analgesics during the last four weeks; 26 % of them on a daily or weekly basis. Girls experienced episodes of pain more frequently than boys, but the proportion of episodes treated with analgesics did not differ between the sexes. Headache and muscle pain were common. Half of those with severe headache/migraine used OTC analgesics on a daily or weekly basis. The teenagers reported several reasons for experiencing pain and discomfort, such as long time spent in front of various screens, tight time schedules with physical exercise and friends, drinking too little and much noise in the classroom.

INTERPRETATION:
Use of OTC analgesics has increased considerably among Norwegian teenagers. Drug-induced headache may occur as an adverse event. If more effort is made to improve life situations that adolescents perceive as painful and a cause of discomfort, the need for OTC analgesics may be reduced.

"Self-medication with OTC analgesics among 15 - 16 year-old teenagers"
Tidsskr Nor Laegeforen. 2009 Aug 13; 129(15): 1447-50LagerlÃ¸v P, Holager T, Helseth S, Rosvold EO

The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission.

2009-08-22T21:30:00.001-07:00

Naunyn Schmiedebergs Arch Pharmacol. 2009 Aug 19; Lambert GA, Davis JB, Appleby JM, Chizh BA, Hoskin KL, Zagami ASThis report examines the effect of the transient receptor potential vanilloid 1 receptor antagonist SB-705498 on neurotransmission and inflammation-induced sensitisation in the trigeminovascular sensory system. A single-neuron electrophysiological animal model for neurovascular head pain was used to evaluate dural and facial noxious inputs and the effects of SB-705498 administered by intravenous (i.v.) injection. Electrical and mechanical stimulation of the dura mater and the facial skin activated second-order neurons in the trigeminal nucleus caudalis of cats, with A-delta latencies. Intravenous injection of SB-705498 (2 mg kg(-1)) produced a slowly developing and long-lasting suppression of responses to dural and skin stimulation. Maximum suppression occurred by 1 h and reached 41% for dura and 24% for skin. Intravenous injection of drug vehicle did not produce significant suppression of responses to stimulation of either dura or skin. Intravenous injection of SB-705498 produced a brief and small rise in blood pressure and dural blood flow, which both returned to normal before suppression of the responses to stimulation became manifest. Application of "inflammatory soup" to the dura mater produced a pronounced increase in dural blood flow and induced a slowly developing increase in the responses of neurons to both electrical and mechanical stimulations of their facial and dural receptive fields. This sensitisation reached a maximum in 60-90 min, at which time responses had risen to approximately twice that of control levels seen before the application of inflammatory soup. Intravenous injection of SB-705498 subsequent to the development of sensitisation produced a slowly developing, prolonged and statistically significant reversal of the sensitisation induced by inflammatory soup. Maximum reversal of sensitisation to electrical stimulation occurred by 150-180 min, when responses had fallen to, or below, control levels. At 70-85 min following injection of SB-705498, the responses of previously sensitised neurons to mechanical stimulation of dura mater and facial receptive field had also returned to near control levels. SB-705498 was also able to prevent the development of sensitisation; application of inflammatory soup to the dura mater induced a slowly developing increase in the responses of neurons to electrical stimulation of the skin and dura mater in cats which had received an i.v. injection of vehicle for SB-705498 but not in cats which had received the active drug. Blood levels of SB-705498 were maximal immediately following i.v. injection and declined over the following 2 h. Significant brain levels of SB-705498 were maintained for up to 9 h. These results suggest that SB-705498 may be an effective suppressant and reversal agent of the sensitisation to sensory input which follows inflammation in the trigeminovascular sensory distribution but may not be particularly useful in blocking primary pain processes such as migraine headache. SB-705498 could thus potentially prevent, modify or reverse the cutaneous trigeminal allodynia seen in certain migraine conditions, especially "transformed" migraine.

A pilot study of rizatriptan and visually-induced motion sickness in migraineurs.

2009-08-22T17:49:00.001-07:00

Int J Med Sci. 2009; 6(4): 212-7Furman JM, Marcus DABACKGROUND: Limited evidence suggests that rizatriptan given before vestibular stimulation reduces motion sickness in persons with migraine-related dizziness. The present study was designed to test whether rizatriptan is also effective in protecting against visually-induced motion sickness and to test whether rizatriptan blocks the augmentation of motion sickness by head pain. MATERIAL AND METHODS: Using randomized double-blind, placebo-controlled methodology, 10 females, 6 with migrainous vertigo (V+) and four without vertigo (V-) received 10 mg rizatriptan or placebo two hours prior to being stimulated by optokinetic stripes. Visual stimulation was coupled with three pain conditions: no pain (N), thermally-induced hand pain (H) and temple pain (T). Motion sickness and subjective discomfort were measured. RESULTS: Motion sickness was less after pre-treatment with rizatriptan for 4 of 10 subjects and more for 5 of 10 subjects. Augmentation of motion sickness by head pain was seen in 6 of 10 subjects; this effect was blunted by rizatriptan in 4 of these 6 subjects. Subjective discomfort was significantly more noticeable in V+ subjects as compared with V- subjects. CONCLUSIONS: These pilot data suggest that rizatriptan does not consistently reduce visually-induced motion sickness in migraineurs. Rizatriptan may diminish motion sickness potentiation by cranial pain.