Novas opções para o tratamento preventivo da migrânea: revisão com considerações fisiopatológicas

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.INTRODUÇÃO: O tratamento farmacológico da migrânea pode ser dividido em agudo e preventivo. Crises de migrânea severas, de longa duração e incapacitante requerem profilaxia. Múltiplas linhas de pesquisa ao longo dos últimos 15 anos sedimentaram o conceito de que a migrânea é gerada a partir de um cérebro hiperexcitável. Variadas causas para essa hiperexcitabilidade têm sido sugeridas e incluem baixo nível de magnésio cerebral, anormalidades mitocondriais, disfunções relacionadas ao óxido nítrico e a existência de distúrbios nos canais de cálcio do tipo P/Q. O melhor conhecimento sobre a fisiopatologia da migrânea nos permite discutir novas opções terapêuticas. OBJETIVOS: O objetivo do presente estudo é apresentar revisão baseada em evidências de novos agentes e outros que, embora disponíveis há mais tempo, não são freqüentemente utilizados, com considerações fisiopatológicas. MÉTODOS/RESULTADOS: Serão revistos anticonvulsivantes com vários mecanismos de ação, como gabapentina, lamotrigina, topiramato, tiagabina, levetiracetam e zonisamida. Serão revistos também produtos naturais, como riboflavina e magnésio, toxina botulínica do tipo A, um antagonista CGRP específico e uma nova opção para o tratamento da asma, o montelukast. CONCLUSÕES: Objetivamos apresentar artigo de atualização em opções novas ou não freqüentemente utilizadas no tratamento preventivo da migrânea, drogas que podem reduzir o fardo e os custos de uma doença que deve ser considerada um problema de saúde pública em todo o mundo

Normal-pressure hydrocephalus: evaluation of five-year experience and literature review

Hidrocefalia com pressão normal (HPN) é uma síndrome caracterizada por apraxia de marcha, demência e incontinência urinária, sendo uma das causas tratáveis de demência. O presente estudo avaliou os dados clínicos, laboratoriais e o tratamento dos pacientes com HPN,atendidos no período de 1992 a 1997, no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. A hipótese diagnóstica de HPN foi feita em 56 casos, tendo sido confirmada em 30. Distúrbios motores foram verificados em 100% dos casos, alterações cognitivas em 83,3% e distúrbios esfincterianos em 63,3%. A tríade ocorreu em 53,3% dos casos. A tomografia computadorizada mostrou hidrocefalia em 96,7% dos pacientes, sendo que, em 40%, havia evidência ainda de isquemia cerebral. Os pacientes foram submetidos a dois tipos de tratamento: punções liquóricas de repetição e instalação de derivação liquórica. No primeiro caso, observou-se melhora em 53,3%. Já, no caso da instalação de derivação liquórica, observou-se melhora em 63,1%. Conclui-se que HPN é uma síndrome que não pode ser considerada incomum, devendo, sempre, ser lembrada como diagnóstico diferencial de demências e distúrbios de marcha do idoso, por tratar-se de patologia potencialmente tratável.Normal-pressure hydrocephalus (NPH) is characterized by the clinical triad of gait apraxia, dementia and urinary incontinence, being one of the reversible causes of dementia. The present study evaluated clinical and laboratory data and the patients’ treatment with this disease assisted from 1992 to 1997 in the University Hospital of Ribeirão Preto. The hypothesis of NPH was made in 56 cases, having been confirmed in 30. Disturbances of the motor’s function were verified in 100% of the cases, cognitive alterations in 83,3% and sphincter disorders in 63,3%. The triad was seen in 53,3% of the cases. CT scan showed hydrocephalus in 96,7% of the patients, and in 40% there was still evidence of ischaemic disorders. Patients were submitted to two kinds of treatment: sucessive spinal fluid drainage or ventricular shunts. In the first case improvement was observed in 53,3%, against 63,1% in shunting cases. In conclusion, NPH is a syndrome that is not uncommon, and should always be reminded as a differential diagnosis of dementia and gait disturbances, being a potentially treatable disease

Procedures for acute headache treatment in an emergency room

Importância do problema: cefaléia é dos sintomas mais comuns na prática clínica, responsável por cerca de 9% dos atendimentos em unidades primárias de saúde e por 1% a 3% dos atendimentos em unidades de emergência, acarretando, portanto, considerável impacto econômico sobre o serviço público de saúde.Comentários: a maioria das unidades de emergência, em nosso meio, não dispõem de drogas utilizadas em outros países para tratamento agudo da cefaléia, como os compostos ergotamínicosou triptanos. Os autores revisam aspectos diagnósticos e terapêuticos das cefaléias primárias agudas, propondo protocolos para seu tratamento em uma unidade de emergência.Headache is one of the most common symptoms in the clinical practice and it is responsible for about 9% of the appointments in primary care units and for 1% to 3% in the emergency rooms, leading to a considerable economic impact in the public health care system. Most of the emergency rooms in Brazil does not have drugs, like ergotics compounds and tryptans, used in other countries for the acute treatment of headache. The authors make a review of the diagnostic and therapeutic aspects of the acute primary headaches, suggesting protocols for its treatment in an emergency unit

Migraine and cardiovascular disease: systematic review and meta-analysis

Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease

Fremanezumab for the Preventive Treatment of Chronic Migraine.

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with fremanezumab monthly, and 2.5±0.3 with placebo (P CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .)

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review

Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy