Comorbidities of migraine: Sleep disorders.

Sleep disorders are commonly found as comorbid problems in patients with migraine. Indeed, there are likely to be numerous levels of interaction between migraine and sleep, including physiological, pathological, and pharmacological. Of note, the presence of sleep disorders may be a modifiable factor in the trajectory of migraine, and therefore active enquiry to elicit their presence, and manage them appropriately, could be an important component in the holistic care of patients with migraine. This review attempts to provide an outline of what is known about these relationships and highlight where relevant which facets could be exploited for therapeutic gain.

Striatal Dopaminergic Deficit and Sleep in Idiopathic Rapid Eye Movement Behaviour Disorder: An Explorative Study.

INTRODUCTION: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucleinopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased phasic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signaling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early caudate dysfunction. Henceforth, we set out to investigate the relationship between early sleep changes and the striatal dopaminergic availability in iRBD. METHODS: Twelve patients with iRBD, who had undergone a video polysomnography and a neuroimaging assessment of striatal dopamine transporter (DaT) uptake tracer signaling, and 22 matched controls who had similarly undergone a video polysomnography were retrospectively identified. Data were statistically analyzed to identify altered sleep parameters and correlate them with striatal dopamine transporter uptake tracer signaling. RESULTS: The iRBD patients exhibited an increased number of periodic limb movements during sleep (P=0.001), compared to 22 age-matched healthy subjects. In addition, several significant links were found between regional DaT-uptakes and sleep architecture. Correlational analyses suggested a strong positive association between sleep fragmentation and dopamine deficiency in left caudate (r=-0.630, P=0.028), whilst an increased uptake in the whole striatum was strongly linked to the sleep efficiency, and to a lesser degree to the length of sleep duration. DISCUSSION: To the best of our knowledge, this is the first demonstration of a close relationship between dopaminergic availability in striatum and the quality of sleep in iRBD. Taken together, our exploratory findings suggest that subtle but functionally significant striatal changes in early stages of iRBD may contribute to the further shaping of sleep architecture.

Delayed sleep-wake phase disorder.

Delayed sleep-wake phase disorder (DSWPD) is the most commonly encountered of the circadian rhythm sleep-wake disorders (CRSDs), and is often confused with sleep initiation insomnia. It typically emerges in teenage years and persists into adulthood. In essence, people with the disorder have an abnormally delayed major sleep episode relative to the dark phase of the solar cycle, and hence great difficulty initiating sleep at an appropriately early time, and, as a knock-on effect, waking at a desirable time in the morning, leading to chronic, and often quite severe sleep restriction trying to conform to a 9 to 5 schedule. As a result, sleep on free days is often extended in compensation. When released from such schedule constraints, sleep duration and quality is normal; it is just delayed. This review highlights elements of our current understanding of the epidemiology, associations and pathophysiology of the disorder, before discussing how some of our knowledge of sleep and circadian physiology can be applied to guide treatment of it.

Migraine with brainstem aura presenting as recurrent hypersomnia (Kleine-Levin syndrome).

Recurrent hypersomnia, or Kleine-Levin syndrome, is rare and frequently causes substantial diagnostic anxiety and delay. Patients often undergo multiple investigations to rule out other causes of encephalopathy. The treatment options are unsatisfactory. Migraine with brainstem aura has not previously been widely considered in the medical literature as a differential diagnosis. We describe two patients referred to a tertiary sleep neurology service with a putative diagnosis of Kleine-Levin syndrome. Each described attacks of hypersomnia with elements of migraine with brainstem aura, in addition to having a history of migraine with aura. Simple acute migraine treatment clearly attenuated further attacks. These cases generate discussion as to the common features and potential mechanisms underlying both disorders. Furthermore, they highlight a hitherto underexplored alternative diagnosis of Kleine-Levin syndrome. This provides scope for offering established and effective migraine treatment options to patients who with a potential misdiagnosis of Kleine-Levin syndrome, providing scope for offering established and effective migraine treatment to some patients originally diagnosed with a rare condition for which there is no current consistently effective therapeutic options.

Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment.

OBJECTIVE: To report our initial experience with a novel device, designed to provide portable, noninvasive, transcutaneous stimulation of the vagus nerve, both acutely and preventively, as a treatment for cluster headache. METHODS: Patients with cluster headache (11 chronic, 8 episodic), from 2 centers, including 7 who were refractory to drug treatment, had sufficient data available for analysis in this open-label observational cohort study. The device, known as the gammaCore, was used acutely to treat individual attacks as well as to provide prevention. Patient-estimated efficacy data were collected by systematic inquiry during follow-up appointments up to a period of 52 weeks of continuous use. RESULTS: Fifteen patients reported an overall improvement in their condition, with 4 reporting no change, providing a mean overall estimated improvement of 48%. Of all attacks treated, 47% were aborted within an average of 11 ± 1 minutes of commencing stimulation. Ten patients reduced their acute use of high-flow oxygen by 55% with 9 reducing triptan use by 48%. Prophylactic use of the device resulted in a substantial reduction in estimated mean attack frequency from 4.5/24 hours to 2.6/24 hours (p < 0.0005) posttreatment. CONCLUSION: These data suggest that noninvasive vagus nerve stimulation may be practical and effective as an acute and preventive treatment in chronic cluster headache. Further evaluation of this treatment using randomized sham-controlled trials is thus warranted. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with cluster headache, transcutaneous stimulation of the vagus nerve aborts acute attacks and reduces the frequency of attacks.

Out of synch with society: an update on delayed sleep phase disorder.

PURPOSE OF REVIEW: Delayed sleep phase disorder is the most common of the circadian rhythm sleep disorders. Its treatment involves exploiting the intrinsic biological properties of the circadian pacemaker to advance biological rhythms, most notably the sleep-wake cycle, to a time which affords the individual an appropriate sleep opportunity compatible with normal societal functioning. This review highlights several new studies published in the last 18 months concerning sleep and circadian physiology relevant to the disorder and its management. RECENT FINDINGS: In addition to new information regarding the epidemiology and associations of the disorder, the pathophysiological importance of light exposure across the entire day, with special relevance to the phase-delaying effects of artificial evening light, is being unravelled. Furthermore, disorder-specific differences in period length and sleep homeostasis are being considered as pathophysiological contributors to delayed sleep phase disorder. The molecular effects of chronic sleep deprivation and circadian misalignment are currently being explored as potential mechanistic markers of the deleterious health consequences associated with these states. SUMMARY: Advances in our understanding of the dynamics of circadian physiology, sleep-wake regulation and the deleterious effects of misalignment and sleep deprivation, are spurring on efforts to find optimal treatment paradigms for patients presenting to sleep clinics with delayed sleep phase disorder.

Headache, drugs and sleep.

BACKGROUND: Headache and sleep mechanisms share multiple levels of physiological interaction. Pharmacological treatment of headache syndromes may be associated with a broad range of sleep disturbances, either as a direct result of the pharmacology of the drug used, or by unmasking physiological alterations in sleep propensity seen as part of the headache symptom complex. PURPOSE: This review summarises known sleep and circadian effects of various drugs commonly used in the management of headache disorders, with particular attention paid to abnormal sleep function emerging as a result of treatment. METHOD: Literature searches were performed using MEDLINE, PubMed, and the Cochrane database using search terms and strings relating to generic drug names of commonly used compounds in the treatment of headache and their effect on sleep in humans with review of additional pre-clinical evidence where theoretically appropriate. CONCLUSIONS: Medications used to treat headache disorders may have a considerable impact on sleep physiology. However, greater attention is needed to characterise the direction of the changes of these effects on sleep, particularly to avoid exacerbating detrimental sleep complaints, but also to potentially capitalise on homeostatically useful properties of sleep which may reduce the individual burden of headache disorders on patients.