Phenotype-driven preventive strategies for migraine and other headaches.

BACKGROUND: Satisfactory prevention of migraine and other headaches is fraught with difficulties in the real world. Tolerability and safety issues are of concern just as is effectiveness or efficacy and all often seem to be patient-dependent. Maximizing migraine prevention and getting treatment right the first time ought to result in improved patient outcomes. Identifying headache phenotypes recognizes that clinical phenomenology may define or approximate genotypes that may predict specific preventive treatments. REVIEW SUMMARY: The concept of phenotype-driven headache and migraine prevention relies heavily on the indomethacin-responsive headache experience wherein specific treatment is dictated by headache phenotype. Herein are described several additional headache phenotypes: migraine with typical and atypical aura, dopaminergic migraine, new daily-persistent headache, migraine with cluster or sinus features, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing, hypnic headache, thunderclap headache, and imploding headache. Phenotype-driven preventive strategies are described that may offer reasonable first treatment choices, appropriate second choices, or choices when other treatments have failed. CONCLUSIONS: These headache preventive recommendations are based on the best available evidence; however, all reports are observational. Perhaps some of these choices will be tested in prospective, randomized, blinded and controlled trials in the future, but historically clinical medicine has relied on clinical observations. The observations reported herein may help define specific, effective treatments for some patients or simply inspire further discussion and research about patient-specific preventive treatment regimens.

Donepezil treatment of topiramate-related cognitive dysfunction.

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.

Miscellaneous primary headache.

There are many types of miscellaneous primary headache, but two groups have been selected for discussion: trigeminal autonomic cephalalgias (TAC) and cephalalgias without autonomic dysfunction(CWAD). TAC are strictly unilateral and CWAD are usually bilateral. Sudden onset and relatively short duration characterize most,but some are frightening to patient and doctor alike. One, thunderclap headache, is symptomatic until proven otherwise. Although the others are rarely symptomatic, therapy can be difficult until it is recognized that diagnosis often predicts treatment.

Hemicrania continua in African Americans.

OBJECTIVE: The first six cases of hemicrania continua and episodica in African Americans are reported, differences from previous accounts noted, and important diagnostic features described. BACKGROUND: Hemicrania continua is an indomethacin responsive chronic daily headache. Mild to moderate daily headache is strictly unilateral, constant but fluctuating. Superimposed severe headache attacks occur, last seconds to days, and are associated with ipsilateral orbital-nasal autonomic dysfunction. RESULTS: Severe headache attacks are usually pulsatile, occur one to four times daily, and last 40 minutes to three days. Daily unilateral background headache was typically of a pressure, sharp, dull or pulling quality. Ipsilateral orbital-nasal autonomic symptoms were noted in all. Serious concomitant medical illnesses, e.g. coronary artery disease, diabetes, and hypertension, were frequent in this population. CONCLUSIONS: This is the first report of hemicrania continua and episodica in African Americans and the second in persons of African descent in the world's literature. Late age of onset, frequent serious medical illnesses, and family history of migraine differentiate this series from previous reports. The lack of reports in African Americans most likely reflects misdiagnosis rather than true prevalence. Thus, whenever any patient presents with chronic daily unilateral headache, ipsilateral autonomic symptoms should be assessed during severe headache attacks, and an indomethacin trial considered.

Antiepileptic Drug Therapy in Migraine Headache.

Severe migraine affects more than 28 million Americans. It is associated with episodic as well as long-term disability and suffering, yet it is underdiagnosed and undertreated. Acute treatments have advanced considerably, ignited by sumatriptan and the subsequent triptans; unfortunately migraine prevention has lagged far behind. There are no great migraine preventives! No migraine preventive agent studied in good randomized, double blind, placebo-controlled trials proved to be 50% better than placebo. Migraine trials typically focus on episodic migraine, a milder, gentler type of migraine that is selected for low frequency, lack of daily headaches, no preventive need, and previous failure to no more than a few preventive agents. These features are not typical of the usual migraine patient seen in most neurologic practices, thus the results of clinical trials may not carryover to real world situations. Treatment of frequent, chronic, or pervasive migraine is inadequate, and never has been studied in randomized controlled trials. Traditional migraine preventives, eg, beta-blockers, calcium channel blockers, and tricyclic antidepressants, are often ineffective in difficult or complicated populations. The antiepileptic drugs represent a category of pharmaceutics that target the neuronal instability and central hyperexcitability of migraine, and, through these actions, may be more effective than traditional preventives. Episodic migraine attacks are associated with peripheral and central sensitization; however, if attacks are frequent, severe, or long lasting, this sensitization may increase the risk of developing daily headaches. If antiepileptic drugs have an effect on central sensitization, perhaps mediated via glutamate inhibition or gamma-aminobutyric acid potentiation, it is appropriate to use these agents early in migraine treatment, particularly in the highly comorbid patient, possibly in conjunction with agents that antagonize the 5HT2 receptor. This report reviews the best currently available evidence on antiepileptic drugs in the prevention of episodic migraine, and tabulates potential drug-drug and cytochrome P450 interactions. All antiepileptic drugs presented are effective in migraine prevention. However, deciding on the best agent for each individual patient will require recognizing comorbidity and assessing antiepileptic drug pharmacodynamics, tolerability, and safety.

Estudio abierto, multicéntrico de gabapentina para el tratamiento preventivo de migraña / Open, multicentric study of gabapentin as preventive treatment for migraine

El objetivo de este estudio fue describir la respuesta de gabapentina como tratamiento profiláctico para migraña en varios centros de Latinoamérica y Miami. Se estudió un total de 101 pacientes con migraña, que recibieron gabapentina a diferentes dosis, iniciando con 300 mg/día hasta reducción de la frecuencia de migraña o hasta dosis tolerable. Despúes de un mes de tratamiento con dosis de mantenimiento, se determinó la respuesta de cada paciente de acuerdo a la reducción de la frecuencia de las crisis de la migraña (excelente: >75 por ciento, buena: 50-75 por ciento, regular: 25-50 por ciento y pobre: 25 por ciento). La mayoría de los pacientes (84 por ciento) tuvo una respuesta excelente (53 por ciento) o buena (32 por ciento). En estos pacientes, la mayoría recibió una dosis de 600 mg/día. Cincuenta y cinco por ciento de los pacientes no describieron eventos adversos. Los eventos adversos más frecuentes fueron somnolencia y fatiga. Aproximadamente la mitad de estos eventos fueron leves y sólo 9 pacientes (8.9 por ciento) los describieron como severos. Se puede concluir que la gabapentina puede ser útil en el tratamiento preventivo de la migraña, y se amerita un futuro estudio para demostrar la eficacia y seguridad de gabapentina a dosis bajas (600 mg/día) y dosis altas, contra placebo. Palabras claves: gabapentina, migraña, profilaxis de migraña, tratamiento.