Spotlight on Neurostimulation in sleep medicine

Sleep ventilatory disorders are prevalent and include, commonly, both obstructive and central sleep apnea. Positive airway pressure therapy, although widely used, has inherent drawbacks, clinically. Alternative treatment modalities have been approved and hold interest within certain spheres.

Dr. Richard Knudsen of the Pacific Sleep Tech in Aiea, Hawaii reviews the first-in-class, novel “electroceuticals” in this article. These “electroceuticals” rely on the pathway of neural signal modulation via products that regulate the firing of neural circuits, in contradistinction to prescription drugs or pharmaceuticals that harbor untoward, systemic, and generalized side effects.

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Spotlight on Narcolepsy

In this article, Dr. Antonio Culebras of SUNY Upstate Medical University at Syracuse reviews the current information on narcolepsy, a disease that has progressed in only 50 years from a quasi-psychiatric condition to a true neurologic disorder. New knowledge of the etiology and mechanism of the disease relative to the hypocretins has opened a major pathway to understanding excessive sleepiness not only in narcolepsy but also in other sleep disorders. Most cases of narcolepsy with cataplexy are associated with the loss of approximately 50,000 to 100,000 hypothalamic neurons containing hypocretin. Pharmacologic treatment remains symptomatic but increasingly effective. In the United States, the annual direct medical costs are 2-fold higher in patients with narcolepsy than in matched controls without narcolepsy.

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Spotlight on Sleep terror

Sleep terrors consist of abrupt arousals out of sleep stage 3 NREM, primarily in the first third of the night, with disordered motor agitation, screaming, fear, and autonomic activation. Sleep terrors affect between 1% to 6% of prepubertal children with a peak incidence between 5 and 7 years of age and a strong familial clustering. Sleep terrors are usually benign and tend to spontaneously decrease in frequency or cease during adolescence.

In this update, Dr. Federica Provini of the University of Bologna and IRCCS Institute of Neurological Sciences of Bologna addresses the latest clinical and polygraphic criteria for the differential diagnosis between sleep terrors and other motor phenomena occurring during sleep, focusing on sleep-related hypermotor epilepsy in which the differential diagnosis poses particular problems.

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Spotlight on Advanced sleep-wake phase disorder

In this article, Dr. Hrayr Attarian and Dr. Tresa Zacharias of Northwestern University discuss the pathophysiology and treatment of this circadian rhythm sleep disorder. Hallmarks of this disorder include an advance in the habitual bedtime and wake time by several hours. The early morning awakening seen in this disorder may be mistaken for insomnia or depression. This is the first circadian rhythm sleep disorder for which a genetic cause was demonstrated. Current treatment primarily depends on the use of evening light therapy; however, timed melatonin may theoretically be efficacious, but further trials are needed.

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Spotlight on Anti-IgLON5 disease

In this article, Dr. Carles Gaig of Hospital Clínic of Barcelona discusses anti-IgLON5 disease, a newly identified neurologic disorder associated with antibodies in serum and CSF against IgLON5, a neuronal surface protein of unknown function. The disease is characterized by a distinctive sleep disorder associated with symptoms of brainstem dysfunction, gait instability, and a variety of other neurologic symptoms (eg, chorea, cognitive impairment). Anti-IgLON5 disease is associated with specific HLA haplotypes, but neuropathological examinations show a novel neuronal tauopathy predominantly involving the tegmentum of the brainstem and hypothalamus. At present, the exact pathogenesis is unclear, but these findings put anti-IgLON5 disease at the confluence of neurodegenerative and autoimmune mechanisms.

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Spotlight on Fatal familial insomnia

Fatal familial insomnia is a prion disease characterized by loss of sleep, oneiric stupors with dream enactment, autonomic activation, and somatomotor abnormalities. The latter may include diplopia, pyramidal signs, myoclonus, dysarthria or dysphagia, and ataxia. PET shows marked thalamic hypometabolism, and neuropathology invariably reveals a moderate to severe neuronal loss and gliosis in the anteromedial thalamic and inferior olivary nuclei. The disease is usually linked to the D178N mutation in the PRNP gene co-segregating with methionine at the polymorphic codon 129. However, sporadic cases of fatal insomnia, lacking the PRNP mutation, may also occur. Fatal familial insomnia represents a model disease for the study of sleep, emphasizing the role of the thalamo-limbic circuits in sleep regulation.

In this article, Dr. Piero Parchi, Dr. Samir Abu-Rumeileh, and Dr. Pietro Cortelli of the University of Bologna discusses the manifestations and diagnosis of fatal familial insomnia.

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Spotlight on Sleep-related movement disorders

Movement disorders are classically thought to resolve during sleep. Sleep-related movement disorders, however, are a subset that are characterized by their presence in sleep.

In this article, Dr. Lauren Talman and Dr. Stephanie Bissonnette of Boston Medical Center discuss these sleep-related movement disorders based on the International Classification of Sleep Disorders-3rd Edition (ICSD-3). These disorders include restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism, sleep-related rhythmic movement disorder, benign sleep myoclonus of infancy, propriospinal myoclonus at sleep onset, sleep-related movement disorders due to medical disorders, and sleep-related movement disorders due to medication or other substance.

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Spotlight on Psychophysiological insomnia

The essence of psychophysiological insomnia is the focused attention on inability to sleep. Psychophysiological insomnia usually begins as a somaticized response to a stressful event and then, depending on genetic and other environmental variables, becomes a more chronic condition because of negative conditioning. This form of insomnia occurs in 1% to 2% of the general population and 12% to 15% of patients presenting to a sleep disorders center.

Three types of factors play a role in the development of psychophysiological insomnia: (1) predisposing or constitutional factors, eg, the tendency to worry excessively and the tendency to be hyperaroused; (2) precipitating factors, eg, a transient stressor; and (3) perpetuating factors, eg, the individual’s expectation of a poor night’s sleep that becomes a self-fulfilling prophecy.

In this article, Dr. Deirdre Conroy of the University of Michigan discusses diagnosis, complications, and treatment of psychophysiological insomnia. Updates include new information regarding the pathophysiology and unique electroencephalogram characteristic of psychophysiological insomnia. Dr. Conroy also discusses additional data to support cognitive behavioral therapy for insomnia as first-line treatment for psychophysiological insomnia.

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Spotlight on Sleep, trauma, and anxiety

Psychiatric disorders associated with anxiety and autonomic arousal, such as trauma-based disorders and anxiety disorders, are well known to be associated with a variety of sleep complaints, most commonly insomnia and nightmares. A review of trauma-based disorders such as posttraumatic stress disorder and anxiety disorders, including generalized anxiety disorder, panic disorder, and specific and social phobia are provided, along with typical subjective and objective sleep profiles.

In this article, Dr. Rebekah Jakel of Duke University discusses the bidirectional relationship between anxiety symptoms and sleep and highlights studies examining the role of sleep disturbances in the development and exacerbation of such disorders, particularly posttraumatic stress disorder.

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Spotlight on Sleep and depression

Sleep disturbances are common in psychiatric disorders. The relationship between poor sleep and depression is well established. Epidemiologic data suggest that people with psychiatric disorders account for 30% to 40% of those in a community reporting symptoms of insomnia and that depression is the most common psychiatric cause of insomnia. Depression is associated with longer sleep latency, frequent and long awakenings, and early morning awakening associated with poor sleep satisfaction. Sleep disturbance associated with depression sometimes responds to treatment of the underlying depression. Some antidepressants, such as mirtazapine, directly improve sleep quality. Unfortunately, most antidepressants, including the selective serotonin reuptake inhibitors and duloxetine, have the side effect of insomnia. Adjunctive medication is often necessary to treat depression- or antidepressant-associated insomnia.

In this article, Dr. Federica Provini of the University of Bologna and IRCCS Institute of Neurological Sciences of Bologna discusses the evaluation and treatment of sleep disorders associated with depression.

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