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    ABSTRACT: Narcolepsy and other syndromes associated with excessive daytime sleepiness can be challenging to treat. New classifications now distinguish narcolepsy/hypocretin deficiency (also called type 1 narcolepsy), a lifelong disorder with well-established diagnostic procedures and etiology, from other syndromes with hypersomnolence of unknown causes. Klein-Levin Syndrome, a periodic hypersomnia associated with cognitive and behavioral abnormalities, is also considered a separate entity with separate therapeutic protocols. Non hypocretin-related hypersomnia syndromes are diagnoses of exclusion. These diagnoses are only made after eliminating sleep deprivation, sleep apnea, disturbed nocturnal sleep, and psychiatric comorbidities as the primary cause of daytime sleepiness. The treatment of narcolepsy/hypocretin deficiency is well-codified, and involves pharmacotherapies using sodium oxybate, stimulants, and/or antidepressants, plus behavioral modifications. These therapies are almost always needed, and the risk-to-benefit ratio is clear, notably in children. Detailed knowledge of the pharmacological profile of each compound is needed to optimize use. Treatment for other syndromes with hypersomnolence is more challenging and less codified. Preferably, therapy should be conservative (such as modafinil, atomoxetine, behavioral modifications), but it may have to be more aggressive (high-dose stimulants, sodium oxybate, etc.) on a case-by-case, empirical trial basis. As cause and evolution are unknown in these conditions, it is important to challenge diagnosis and therapy over time, keeping in mind the possibility of tolerance and the development of stimulant addiction. Kleine-Levin Syndrome is usually best left untreated, although lithium can be considered in severe cases with frequent episodes. Guidelines are provided based on the literature and personal experience of the author.
    Journal of the American Society for Experimental NeuroTherapeutics 10/2012; 9(4):739-52. DOI:10.1007/s13311-012-0150-9 · 3.88 Impact Factor
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    ABSTRACT: Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of unknown etiology and characterized by generalized body pain, hyperalgesia, and other functional and emotional comorbidities. Despite extensive research, no treatment modality is effective for all FMS patients. In this paper, we briefly review the history of FMS and diagnostic criteria, and potential pathophysiological mechanisms including central pain modulation, neurotransmitters, sympatho-adrenal and hypothalamic-pituitary-adrenal systems and peripheral muscle issues. The primary focus of the paper is to review treatment options for managing fibromyalgia symptoms. We will discuss FDA-approved medications and other pharmacologic agents, and non-pharmacologic treatments that have shown promising effects.
    12/2013; 2(2):87-104. DOI:10.1007/s40122-013-0016-9
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    ABSTRACT: Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. Occurring spontaneously, cataplexy is typically triggered by strong positive emotions such as laughter and is often underdiagnosed owing to a variable disease course in terms of age of onset, presenting symptoms, triggers, frequency and intensity of attacks. This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin neurons. One pathogenetic mechanism that has been hypothesized for cataplexy is the activation, during wakefulness, of brainstem circuitry that normally induces muscle tone suppression in rapid eye movement sleep. Muscle weakness during cataplexy is caused by decreased excitation of noradrenergic neurons and increased inhibition of skeletal motor neurons by γ-aminobutyric acid-releasing or glycinergic neurons. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and γ-hydroxybutyrate being the most effective treatments. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies.
    Nature Reviews Neurology 06/2014; 10(7). DOI:10.1038/nrneurol.2014.97 · 15.52 Impact Factor

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