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The endogenous cannabinoid anandamide (AEA) plays important roles in modulating pain. Head pain is an almost universal human experience, yet primary headache disorders, such as migraine without aura (MoA) or episodic tension-type headache (ETTH), can represent a serious threat to well-being when frequent and disabling. We assessed the discriminating role of endocannabinoids among patients with ETTH or MoA, and control subjects. We measured the activity of AEA hydrolase and AEA transporter, and the level of cannabinoid receptors in peripheral platelets from MoA, ETTH and healthy controls. Sixty-nine headache patients and 36 controls were selected. Diagnosis of headache type was made according to the International Headache Society criteria. We observed significant sex differences concerning AEA membrane transporter and fatty acid amide hydrolase activity in all groups. An increase in the activity of AEA hydrolase and AEA transporter was found in female but not male migraineurs. Cannabinoid receptors were the same in all groups. Here we show that the endocannabinoid system in human platelets is altered in female but not male migraneurs. Our results suggest that in migraineur women an increased AEA degradation by platelets, and hence a reduced concentration of AEA in blood, might reduce the pain threshold and possibly explain the prevalence of migraine in women. The involvement of the endocannabinoid system in migraine is new and broadens our knowledge of this widespread and multifactorial disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented entitled "Migraine Aura Status and Hypermocysteinaemia," by L. M. Cupini and E. Stipa.

Objective To evaluate seizures as first clinical manifestation of brain arteriovenous malformations (AVMs), in relation to angioarchitectural features of these vascular anomalies. Methods We performed a prospective observational study, collecting records of patients with AVMs consecutively admitted to the Neurological and Neurosurgery Units of Perugia University and to the Neurosurgery Unit of Terni Hospital, during a 10-year period (1 January 2002 to 1 June 2012). Two groups of patients, with or without seizures as AVM first presentation, were analysed to identify differences in demographic and angiographic features. A multivariate logistic regression model was also developed. Results We examined 101 patients with AVMs, 55 male and 46 female. Seizures were the initial clinical manifestation in 31 (30.7%) patients. We found a significant difference (p<0.05) between two groups of patients, with or without seizures as AVM first presentation concerning location, side, topography and venous drainage. A multivariate logistic regression model showed that clinical presentation with seizures was correlated with a location in the temporal and frontal lobes, and with a superficial topography. The strongest association (OR 3.48; 95% CI 1.77 to 6.85) was observed between seizures and AVM location in the temporal lobe. Conclusions Vascular remodelling and haemodynamic changes of AVMs might create conditions for epileptogenesis. However, here we show that malformations with specific angiographic characteristics are more likely to be associated with seizures as first clinical presentation. Location is the most important feature related to epilepsy and in particular the temporal lobe might play a crucial role in the occurrence of seizure. [ABSTRACT FROM AUTHOR]

Background and purpose: Educational intervention has proved to be effective in reducing drug abuse in uncomplicated medication‐overuse headache (MOH). This ancillary of the SAMOHA multicentre study aimed to assess any differences in phenotypic characteristics, type and amount of drugs overused, and comorbidities between patients with MOH who responded to simple advice and those who did not. Methods: Demographic and clinical headache data of the last 3 months before enrollment of patients were collected and patients were then asked to fill out a daily headache diary for 4 weeks. Patients were then divided into two subgroups, i.e. those with confirmed MOH continued in the study [randomized (R) group], whereas those who did not still show any features of MOH dropped out of the study. Results: A total of 88 (67.7%) patients still met the inclusion criteria after the baseline 4 weeks (R group). Conversely, 42 (32.3%) patients dropped out of the study. A detailed analysis of those who dropped out revealed that only 34 were not randomized at visit 2 because they no longer satisfied the inclusion criteria for MOH [screening failures (SF) group]. The SF group was significantly younger and had fewer years of migraine history than the R group. Moreover, the SF group had a significantly shorter history of chronicity compared with the R group. Conclusions: Our findings suggest that in MOH trials, after an educational session, an observational period is needed in order to confirm the diagnosis of MOH and to avoid overestimation of the effect of other treatments used to manage MOH. Future research should focus mainly on those patients with MOH who do not respond to simple advice and with unsuccessful withdrawal. [ABSTRACT FROM AUTHOR]

Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

Background and purpose: In medication-overuse headache (MOH) patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. This multicentre study aimed to assess the occurrence of psychopathological disorders in MOH patients by comparing the incidence of psychopathological disturbances with episodic migraine (EM) patients and healthy controls (HC). Methods: The psychopathological assessment of patients and HC involved the administrations of the Beck Depression Inventory, the Beck Anxiety Inventory, the Modified Mini International Neuropsychiatric Interview (MMINI), the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Leeds Dependence Questionnaire. Results: The MOH, EM and HC groups (88, 129 and 102 subjects, respectively) differed significantly from each other for the presence of moderate/severe anxiety, whereas mood disorder and depression were revealed in similar proportions for both MOH and EM patients. By stratifying the M-MINI questionnaire results according to the number of psychiatric disorders, it was found that MOH patients had a more complex profile of psychiatric comorbidity. Furthermore, clinically relevant obsessive compulsive disturbances for abused drugs assessed by Y-BOCS appeared to be more represented in the MOH group, whilst the prevalence of this trait in the EM group was comparable to that of HC (12.5%, 0.8% and 0%, respectively). Conclusions: Our study indicates the multiple presence of psychopathological comorbidities in patients with MOH. In light of this, it is recommended that the assessment of the psychopathological profile be included in an evaluation of MOH patients, allowing the clinician to more rapidly start an appropriate behavioural treatment, which would greatly improve MOH management. [ABSTRACT FROM AUTHOR]

Cortex and periaqueductal grey (PAG) play a major role in the pathophysiology of migraine. Some antiepileptic drugs (AEDs) influence the activity of these structures by modulating high-voltage-activated (HVA) Ca2+ channels and are effective in migraine prevention. The aim of the present study was to investigate the expression of total HVA Ca2+ channels in cortical and PAG neurons and to study the differential action of AEDs on these channels. Isolated neurons were visually identified based on morphological criteria. HVA currents were recorded by whole-cell patch-clamp technique. The distribution ratio of L-, N-, P-, Q- and R-type HVA Ca2+ channels was different between cortical and PAG neurons. In particular, we found that P- and Q-type HVA Ca2+ channels were more expressed in PAG neurons than in cortical cells, whereas L- and R-type HVA Ca2+ channels showed an opposite distribution. Interestingly, N-type HVA Ca2+ channels were equally distributed in these two neuronal populations. A differential sensitivity to AEDs of HVA Ca2+ channels located on cortical and PAG neurons was observed for topiramate (TPM), but not for lamotrigine (LTG) or levetiracetam (LEV). In fact, whereas both LTG and LEV were equally effective and potent in inhibiting HVA Ca2+ currents in the two neuronal populations, TPM showed a much higher potency and efficacy in blocking these currents in PAG neurons than in cortical pyramidal cells. TPM, in fact, inhibited N-, P- and L-type channels in PAG neurons, whereas in cortical neurons this AED modulated only P- and L-type channels. Unlike the other AEDs investigated, valproic acid did not affect HVA Ca2+ currents in cortical and PAG neurons. The negative modulation of specific subtypes of HVA Ca2+ channels by various AEDs can restore normal electrical activity in target brain areas such as cortex and PAG, providing interesting therapeutic approaches in migraine prevention. [ABSTRACT FROM AUTHOR]

We have investigated the prolactin response to bromocriptine (BRC), a D2 dopamine receptor agonist in migrainous women before and after treatment with flunarizine. We evaluated whether this test was predictive of therapeutic efficacy of flunarizine treatment and whether the therapeutic response to flunarizine treatment was related to its effect on dopaminergic system at tuberoinfundibular level. Ten migrainous women underwent a BRC test in the late follicular phase before and after 1 and 3 months of treatment with flunarizine 10 mg at bedtime. Blood samples of prolactin (PRL), growth hormone, follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were taken at basal condition. PRL was also evaluated 1 and 2 h after BRC (2.5 mg) administration. Each patient kept a daily headache diary for 1 month prior to the test and throughout the study. The level of PRL inhibition after BRC administration, observed before flunarizine treatment, was not predictive of the therapeutic response observed after 1 and 3 months of treatment. The effect of flunarizine on PRL level was not related to the therapeutic efficacy of the drug. These data suggest that flunarizine does not attenuate the activity of dopaminergic neurons in migrainous patients, and that the antimigraine effect of flunarizine does not seem related to its action on dopaminergic system at least at tuberoinfundibular level. [ABSTRACT FROM AUTHOR]