Stephanie J. Nahas

Chemical Mediators of Migraine: Preclinical and Clinical Observations

Migraine is a neurovascular disorder, and although the pathophysiology of migraine has not been fully delineated, much has been learned in the past 50 years. This knowledge has been accompanied by significant advancements in the way migraine is viewed as a disease process and in the development therapeutic options. In this review, we will focus on 4 mediators (nitric oxide, histamine, serotonin, and calcitonin gene‐related peptide) which have significantly advanced our understanding of migraine as a disease entity. For each mediator we begin by reviewing the preclinical data linking it to migraine pathophysiology, first focusing on the vascular mechanisms, then the neuronal mechanisms. The preclinical data are then followed by a review of the clinical data which support each mediators role in migraine and highlights the pharmacological agents which target these mediators for migraine therapy.

Right-to-left shunt is common in chronic migraine

Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura (P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.

Ketamine Infusions for Treatment Refractory Headache

Management of chronic migraine (CM) or new daily persistent headache (NDPH) in those who require aggressive outpatient and inpatient treatment is challenging. Ketamine has been suggested as a new treatment for this intractable population.

Headache and Temporal Arteritis: When to Suspect and How to Manage

Temporal arteritis, also termed giant cell arteritis, is one of the vasculitides affecting large and medium sized cranial arteries, particularly of the carotid tree. Clinical manifestations may vary from the classic constellation of temporal headache in the elderly accompanied by constitutional signs, jaw claudication, and visual symptoms; therefore, a high index of clinical suspicion may be necessary to identify the disorder. Once suspected, immediate treatment is crucial while exploring any number of diagnostic tools to confirm or refute the diagnosis, since morbidity from untreated temporal arteritis can be devastating. At the same time, achieving a definitive diagnosis is paramount, as treatment can be toxic with significant morbidity of its own. Temporal artery biopsy remains the gold standard, but noninvasive diagnostic approaches are being refined. Corticosteroids remain the cornerstone of treatment, but are ineffective for, not tolerated by, or contraindicated in some individuals, necessitating the exploration of alternatives.

CADASIL: Imaging Characteristics and Clinical Correlation

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene located on chromosome 19p13. CADASIL causes a clinical syndrome of migraines (frequently with aura), progressive strokes, and cognitive decline in adults leading to severe functional impairment by the seventh decade of life. Genetic testing is the gold standard for diagnosing this condition, but the syndrome can be suspected clinically based on history and a characteristic pattern of confluent subcortical white matter disease in the anterior temporal poles and external capsule. Additional abnormalities include cerebral microbleeds and large vessel stenosis, particularly in Asian populations. Familiarity with radiologic findings in CADASIL is essential to the correct diagnosis and subsequent management of this disease.

SUNCT/SUNA: A Review

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting neuralgiform headache attacks with cranial autonomic features (SUNA) are rare headache disorders characterized by severe, short-lasting headaches. These headache disorders are often refractory to treatment and can be secondary phenomena. This article reviews the history, pathophysiology, and treatment of these disorders. Both pharmacotherapy and procedural interventions are discussed in context of historical and more recent reports.

Medication adaptation headache.

The purpose of this editorial is to challenge the choice of the term ‘medication overuse headache’ (MOH). MOH is not a new concept, but the name remains controversial. Although it is an improvement on previous labels such as ‘drug abuse headache’ and ‘rebound headache’, there is still more work to be done. Our criticisms of the portrayal of MOH are scientific and, broadly speaking, moral. We survey possible terms and their implications and make a recommendation. A recent review article states that MOH is ‘an avoidable disorder’ (1). The current diagnostic criteria (International Classification of Headache Disorders, second edition, 2004 [ICHD-2]) are:

Current Treatment Options: Headache Related to Menopause—Diagnosis and Management

Purpose of reviewMenopause is a life-changing event in numerous ways. Many women with migraine hold hope that the transition to the climacteric state will coincide with a cessation or improvement of migraine. This assumption is based mainly on common lay perceptions as well as assertions from many in the healthcare community. Unfortunately, evidence suggests this is far from the rule. Many women turn to a general practitioner or a headache specialist for prognosis and management. A natural instinct is to manipulate the offending agent, but in some cases, this approach backfires, or the concern for adverse events outweighs the desire for a therapeutic trial, and other strategies must be pursued. Our aim was to review the frequency and type of headache syndromes associated with menopause, to review the evidence for specific treatments for headache associated with menopause, and to provide management recommendations and prognostic guidance.Recent findingsWe reviewed both clinic- and population-based studies assessing headache associated with menopause. Headache in menopause is less common than headache at earlier ages but can present a unique challenge. Migraine phenotype predominates, but presentations can vary or be due to secondary causes. Other headache types, such as tension-type headache (TTH) and cluster headache (CH) may also be linked to or altered by hormonal changes. There is a lack of well-defined diagnostic criteria for headache syndromes associated with menopause. Women with surgical menopause often experience a worse course of disease status than those with natural menopause. Hormonal replacement therapy (HRT) often results in worsening of migraine and carries potential for increased cardiovascular and ischemic stroke risk. Estrogen replacement therapy (ERT) in patients with migraine with aura (MA) may increase the risk of ischemic stroke; however, the effect is likely dose-dependent. Some medications used in the prophylaxis of migraine may be useful in ameliorating the vasomotor and mood effects of menopause, including venlafaxine, escitalopram, paroxetine, and gabapentin. Other non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga may also be helpful in reducing headache and/or vasomotor symptoms associated with menopause.SummaryThe frequency and type of headache associated with menopause is variable, though migraine and TTH are most common. Women may experience a worsening, an improvement, or no change in headache during the menopausal transition. Treatment may be limited by vascular risks or other medical and psychiatric factors. We recommend using medications with dual benefit for migraine and vasomotor symptoms including venlafaxine, escitalopram, paroxetine, and gabapentin, as well as non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga.If HRT is pursued, continuous (rather than cyclical) physiological doses should be used, transdermal route of administration is recommended, and the patient should be counseled on the potential for increased risk of adverse events (AEs). Concomitant use of a progestogen decreases the risk of endometrial hyperplasia with ERT. Biological mechanisms are incompletely understood, and there is a lack of consensus on how to define and classify headache in menopause. Further research to focus on pathophysiology and nuanced management is desired.

Supratrochlear and Supraorbital Nerve Stimulation for Chronic Headache: a Review

Chronic daily headache accounts for a significant socioeconomic burden due to decreased productivity, work absenteeism, multiple office and ER visits, and hospital admissions for pain control. Associated comorbidities add to this cost. Current traditional medical therapies may fail to provide adequate relief leading to the search for and use of other therapeutic modalities such as innovative medical devices. It is in this setting of the urgent demand for better pain control and to assimilate chronic headache sufferers back into society that a variety of neuromodulatory approaches have been emerging. This review aims to familiarize the reader with current literature regarding supraorbital and supratrochlear nerve stimulation for chronic headache, point out the advantages of this approach, address unanswered questions about this subject, and highlight future directions.

Diagnosis of Acute Headache

Internists and neurologists often are called to evaluate, or are consulted by, patients during a headache attack. Crucial elements of a systematic evaluation include a thorough history, focused general medical and neurologic examinations, and laboratory testing and neuroimaging when indicated. Most patients with acute headache have a primary headache disorder [1], but the probability of secondary headaches increases in the urgent setting. Certain “red flags” suggest the possibility of secondary headache, and using the SNOOP mnemonic (Table 1) will help identify them. “Comfort signs,” such as a long-standing, stable, or slowly progressive disorder; normal neurologic exam; typical triggers, clinical features, and history; and response to appropriate medication also are important to recognize as indicators of a primary disorder. If secondary headache is excluded, a primary headache diagnosis is assigned according to clinical features.