Recommendations for prophylactic treatment of migraine: Consensus of the Sociedade Brasileira de Cefaléia

The Brazilian Headache Society assigned an Ad Hoc Committee with the purpose of establishing a consensus about prophylactic treatment for migraine and of elaborating recommendations for professionals. The recommendations of the Committee are based in evidences of the world medical literature and on the personal experience of the members, respecting the reality of the existing medication resources in our country.     

Ophthalmoplegic migraine: inflammatory neuropathy with secondary migraine?

BACKGROUND: This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant. METHOD: We review 3 new and 37 reported pediatric OM cases. RESULTS: Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode. Patients demonstrated: 1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache. CONCLUSION: A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition.     

Is migraine a genetic illness? The various forms of migraine share a common genetic cause

Is migraine a genetic illness? This question was previously controversial, but today the answer yes is generally accepted. The scientific evidence is the significantly increased familial risk of migraine, and the significantly higher concordance rate of migraine in monozygotic than dizygotic twin pairs. Finally, the three identified ion-channel genes that can cause familial hemiplegic migraine provide very strong evidence of genetics. Mutations in these genes can also cause sporadic hemiplegic migraine. The next question is whether the different types of migraine, i.e. migraine without aura, migraine with aura, sporadic hemiplegic migraine and familial hemiplegic migraine share a common genetic cause. This question is at present controversial. However, the fact that all types of migraine are paroxystic in nature suggest that a common genetic cause could be mutations in ion channels, although a common mutation has not yet been identified in the more common types of migraine: migraine without aura and migraine with aura.

     

Adverse effects of antipsychotic drugs: survey of doctors’ versus patients’ perspective

Aims  

Almost no data are available on whether patients and doctors have similar or dissimilar opinions on the presence and level of distress due to antipsychotic adverse effects. The aim of this survey is to compare doctors’ versus patients’ perspective on the presence and level of distress due to antipsychotic adverse effects in a sample of patients under the care of the South-Verona mental health services.     

Interleukin-12 plasma levels in drug-naïve patients with a first episode of psychosis: effects of antipsychotic drugs

An overactivation of the Th1 activity in schizophrenia had been described. Interleukin-12 (IL-12), a proinflammatory cytokine, plays a key role in the regulation of the Th1 response. The aims of this study were to investigate the effect of first and second generation antipsychotic drugs on IL-12 production during the acute phase of the illness and its association with clinical features. Participants comprised 56 drug-na?ve first episode psychotic patients and 28 healthy volunteers. Patients were initially randomly assigned to risperidone (n=16), olanzapine (n=20) or haloperidol (n=20); subject were maintained on the same medication throughout the study. Clinical assessments were conducted at baseline and at 6 weeks. IL-12 plasma levels were assessed at baseline and after 6 weeks of antipsychotic treatment. IL-12 haplotypes were also analysed. Patients showed higher IL-12 plasma levels at baseline compared with controls, and had a significant increase in IL-12 plasma level after 6 weeks of antipsychotic treatment. No significant differences in IL-12 level increase were found among the three antipsychotic treatments. IL-12 plasma levels at week 6 were not significantly associated with the severity of psychopathology at week 6. Thus, patients with a first episode of psychosis have inflammatory-like immunological function during early phases of the illness that it is independent of the antipsychotic treatment used.     

Does neurotensin mediate the effects of antipsychotic drugs?

The possibility that the neuropeptide neurotensin (NT) may function as an endogenous antipsychotic compound was first hypothesized almost two decades ago. Since that time, considerable effort has been directed towards determining whether NT neurons mediate the effects of antipsychotic drugs (APDs). The anatomic, biochemical, behavioral, and clinical relevance of this hypothesis is reviewed. Although the majority of the available evidence is indirect, the availability of several NT receptor (NTR) antagonists have now made possible the direct examination of the involvement of the NT system in the mechanism of action of APDs. Preliminary studies in our laboratory demonstrate the ability of a selective NTR antagonist to block the effects of APDs in two models of sensory motor gating deficits characteristic of schizophrenia. These data, taken together with a compelling series of studies demonstrating that increases of NT/neuromedin N mRNA expression and NT content in the nucleus accumbens and striatum after chronic administration of APDs are predictive of clinical efficacy and extrapyramidal side effects, respectively, provide direct preclinical evidence for a role of the NT system in the clinical efficacy of APDs. Although effects of selective NTR antagonists in normal volunteers or schizophrenic patients have not been studied, and nonpeptidergic NTR agonists have not yet been identified, these cumulative results provide the groundwork for the use of NT-ergic compounds in the treatment of schizophrenia.     

Treatment of chronic migraine with medication overuse: is drug withdrawal crucial?

Chronic headaches have increasingly become a focus within the field of head pain. For the most part patients with frequent headaches eventually overuse their medications, and if it happens (the percentage is approximately 4%), the diagnosis of chronic migraine with medication overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse with adequate strategies is an essential component for helping these patients to improve and for preventing relapses. The necessity of withdrawal performed by different treatment schedules, outcomes, and the long-term durability of treatment are discussed.     

Random dominance and childhood migraine: a new marker? A controlled study of laterality in children with migraine

We assessed various aspects of laterality by direct observation in children with migraine and peer controls, with special reference to the frequency of random dominance. This frequency varied with the test battery used, being lower on the Edinburgh and Oldfield inventories which measure hand-use preference, and higher on the Handedness index and Spontaneous gestural index, which explore "genetic laterality". Random dominance would seem to be a new marker of migraine in childhood, for use alongside the hyperreactivity marker found in a previous study.     

Cerebral β amyloid deposition in patients with malignant neoplasms: its prevalence with aging and effects of radiation therapy on vascular amyloid

We examined immunohistochemically 123 autopsy brains from patients aged between 30 to 59, who died as a result of malignant neoplasms. Using antiserum to amyloid protein (A), we found that cerebral A deposits began in the subjects' fifth decade; its prevalence was 0%, 9.8% and 21.5% in the fourth, fifth and sixth decades, respectively. The major form of A deposition was diffuse-type plaques, although one third of the brains with A deposition showed amyloid angiopathy. Subpial A deposition is frequently associated with amyloid angiopathy. The prevalence of cerebral A deposits was about two times higher in the patients who had received brain radiation therapy (27.8%) compared to non-radiated patients (14.8%). Amyloid angiopathy was much more prominent (P<0.05) with radiation therapy (22.2%) than without (8.0%). We found that cerebral A deposition is dependent on aging, even in patients with malignant tumors and at beginning in their forties, and that brain radiation therapy is a possible risk factor of A deposition, especially in the form of amyloid angiopathy.     

Refractory chronic migraine: is drug withdrawal necessary before starting a therapy with onabotulinum toxin type A?

Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient’s needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously.     

SMART: stroke-like migraine attacks after radiation therapy or seizures with migraine-like attacks after radiation therapy? Terms do matter in clinical practice

Neurological Sciences -     

Genetics of migraine and migraine accompagneé: a study of eighty-one children and their families

Eighty-one patients suffering from childhood onset migraine and their families were investigated for familial prevalences of epileptic seizures and migraine. The incidence of epileptic seizures was not increased above the epidemiological risk. - In all, migraine is largely inherited from maternal ascendents, irrespective of the sex of the index case. Clinical subtypes of migraine ("non-focal migraine" and migraine accompagnée) are not accompanied by respectively increased familial prevalences. - Onset of migraine is earlier in patients with a higher familial impact. These findings are discussed in context with a proposed multifactorial pathogenesis of migraine.     

Specific adverse effects of antiepileptic drugs — A true-to-life monotherapy study

BackgroundIn patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.MethodsAll patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.ResultsOut of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.ConclusionIndividual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.     

What future for treatment of chronic migraine with medication overuse?

Chronic headaches have increasingly become a focus within the field of head pain. Most of the patients with frequent headache eventually overuse their medications, and if it happens [the percentage is approximately 4%], the diagnosis of chronic migraine with medication-overuse headache is clinically important, because patients rarely respond to preventive medications while overusing acute medications. This kind of headache is recognized as a biobehavioral disorder, a complex condition wherein emotion and pain are intermingled. Properly treating medication overuse with adequate strategies by different and specific steps are essential components for helping these patients to improve and for preventing relapses. The clinical experience performed at our Headache Unit, the necessity of withdrawal, different treatment schedules, and different treatment strategies of our center were discussed.