There are numerous disorders of known or presumed neurologic origin that result in excessive daytime sleepiness, collectively known as the central disorders of hypersomnolence. These include narcolepsy types 1 and 2, idiopathic hypersomnia, Kleine-Levin syndrome, and hypersomnia due to or associated with medical disease, neurologic disease, psychiatric disease, medications or substances, and insufficient sleep durations. This chapter focuses on the treatment of nonnarcoleptic hypersomnia syndromes, from those that are commonly encountered in neurologic practice, such as hypersomnia due to Parkinson's disease, to those that are exceedingly rare but present with dramatic manifestations, such as Kleine-Levin syndrome. The level of evidence for the treatment of sleepiness in these disorders is generally lower than in the well-characterized syndrome of narcolepsy, but available clinical and randomized, controlled trial data can provide guidance for the management of each of these disorders. Treatments vary by diagnosis but may include modafinil/armodafinil, traditional psychostimulants, solriamfetol, pitolisant, clarithromycin, flumazenil, sodium oxybate, melatonin, methylprednisolone, and lithium.

Central disorders of hypersomnolence (CDH) are characterized by excessive daytime sleepiness not related to comorbid sleep or medical disturbances. We systematically examined scientific literature on cognitive functions in patients suffering from CDH. Forty-eight studies proved eligible and were analyzed separately for Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), Idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS). Results were grouped into the cognitive domains of attention, memory, executive functions and higher order cognition. Consistent attention impairments emerged in NT1, NT2 and IH patients, with NT1 patients showing the most compromised profile. Memory functions are largely unimpaired in CDH patients except for KLS patients who display memory deficit. Executive functions and higher-order cognition have been assessed in NT1 while they received little-to-no attention in the other CDH. NT1 patients display high performance in executive functions but exhibit a complex pattern of impairment in higher-order cognition, showing poor decision-making and impaired emotional processing. Moreover, NT1 patients show increased creative abilities. Assessing and monitoring cognitive impairments experienced by CDH patients will allow the design of personalized interventions, parallel to pharmacological treatment, aimed at improving daytime functioning and quality of life of these patients.

Abstract Idiopathic hypersomnia (IH) is a rare neurological sleep disorder, characterized by excessive daytime sleepiness despite normal sleep duration, that can significantly impact patient’s lives. The burden of IH goes beyond excessive daytime sleepiness, pervading all aspects of everyday life. Characteristic and burdensome symptoms of IH include sleep inertia/drunkenness, long sleep duration, and daytime cognitive dysfunction. This systematic review assessed current knowledge regarding IH diagnostic challenges and burden of illness. Literature searches for original epidemiological, clinical, humanistic, or economic research relevant to IH published between 2012 and 2022 in MEDLINE, Embase, Cochrane, gray literature (diagnostic criteria and treatment guidelines), conferences (2019–2022), and clinical trial databases yielded 97 articles. Findings indicate that IH remains a poorly defined diagnosis of exclusion that is difficult to distinguish from narcolepsy type 2 because of symptom overlap and inadequacies of objective testing. Consequently, individuals with IH endure diagnostic delays of up to 9 years. The economic burden of IH has not been characterized to any appreciable extent. Pharmacological treatment options can improve symptoms and functional status, but rarely restores normal levels of functioning. These findings highlight the need to reclassify central disorders of hypersomnolence. Further collaboration is now required between research groups to identify and validate objective markers to help redefine diagnostic criteria for IH. This would move IH into a position that could benefit from future targeted therapeutic interventions. The study was funded by Takeda Development Center Americas, Inc.

Brain fog is an undefined term describing a cluster of symptoms related to fatigue and impaired memory, attention, and concentration. Brain fog or brain fog-like symptoms have been reported in central disorders of hypersomnolence and in a range of seemingly unrelated disorders, including coronavirus disease 2019, major depressive disorder, multiple sclerosis, lupus, and celiac disease. This narrative review summarizes current evidence and proposes a consensus definition for brain fog. Brain fog is prevalent in narcolepsy and idiopathic hypersomnia, with more than three-quarters of patients with either disorder reporting this symptom in a registry study; it has also been reported as particularly difficult to treat in idiopathic hypersomnia. Studies directly evaluating brain fog are rare; tools for evaluating this symptom cluster typically are patient reports, with few objective measures validated in any disorder. Evaluating brain fog is further complicated by confounding symptoms, such as excessive daytime sleepiness, which is a hallmark of hypersomnolence disorders. No treatments specifically address brain fog. The paucity of literature, assessment tools, and medications for brain fog highlights the need for research leading to better disambiguation and treatment. Until a clear consensus definition is established, we propose brain fog in hypersomnia disorders be defined as a cognitive dysfunction that may or may not be linked with excessive sleepiness, related to an underlying neuronal dysfunction, which reduces concentration and impairs information processing, leading to a complaint of lack of clarity of mental thinking and awareness.<h4>Citation</h4>Rosenberg R, Thorpy MJ, Doghramji K, Morse AM. Brain fog in central disorders of hypersomnolence: a review. <i>J Clin Sleep Med</i>. 2024;20(4):643-651.

Little attention has been paid to the long‐term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow‐up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

Purpose of review Idiopathic hypersomnia is a chronic and often disabling sleep disorder characterized by excessive daytime sleepiness despite adequate or prolonged nighttime sleep. With recent advances in diagnosis and treatment, this review is timely in addressing evolving approaches to understanding and managing idiopathic hypersomnia, a condition that remains underrecognized and frequently misdiagnosed. Recent findings Idiopathic hypersomnia is clinically distinct from narcolepsy, lacking REM-related features such as cataplexy and hypnagogic hallucinations. Until recently, treatment options for idiopathic hypersomnia were limited and often off-label. The 2021 FDA approval of low-sodium oxybate (LXB) marked the first medication specifically indicated for idiopathic hypersomnia. Additional agents such as modafinil, pitolisant, and traditional stimulants are used off-label with varying efficacy. Ongoing research is exploring promising treatments, including orexin-2 receptor agonists (e.g. ALKS 2680, ORX-750), serdexmethylphenidate, and flumazenil, which offer new hope for personalized management. Summary Growing insights into the pathophysiology and clinical features of idiopathic hypersomnia have led to improved diagnostic clarity and therapeutic innovation. These developments carry significant implications for clinical practice, offering hope for better symptom control and quality of life in affected individuals. Ongoing research is crucial for refining treatment strategies and deepening our understanding of this complex condition.

Idiopathic hypersomnia (IH) is a poorly understood sleep disorder characterized by excessive daytime sleepiness despite normal nighttime sleep. Combining human genomics with behavioral and mechanistic studies in fish and flies, we uncover a role for beat-Ia/CADM2, synaptic adhesion molecules of the immunoglobulin superfamily, in excessive sleepiness. Neuronal knockdown of Drosophila beat-Ia results in sleepy flies and loss of the vertebrate ortholog of beat-Ia, CADM2, results in sleepy fish. We delineate a developmental function for beat-Ia in synaptic elaboration of neuropeptide F (NPF) neurites projecting to the suboesophageal zone (SEZ) of the fly brain. Brain connectome and experimental evidence demonstrate these NPF outputs synapse onto a subpopulation of SEZ GABAergic neurons to stabilize arousal. NPF is the Drosophila homolog of vertebrate neuropeptide Y (NPY), and an NPY receptor agonist restores sleep to normal levels in zebrafish lacking CADM2. These findings point towards NPY modulation as a treatment target for human hypersomnia.

nstitutes of Health. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. StatPearls [Internet]. Show details Treasure Island (FL): StatPearls Publishing ; 2026 Jan-. Search term Idiopathic Hypersomnia Kunwardeep Dhillon ; Abdulghani Sankari . Author Information and Affiliations Authors Kunwardeep Dhillon 1 ; Abdulghani Sankari 2 . Affiliations 1 Detroit Medical Center/Wayne State University 2 Wayne State University Last Update: July 31, 2023 . Continuing Education Activity Idiopathic hypersomnia (IH) is a central disorder of hypersomnolence, with the primary complaint being the irresistible need to sleep and waking up non-refreshed despite the prolonged duration of sleep. The subtypes and diagnostic criteria for the diseases have been debated in the past. Current subtypes are based on the length of total sleep time- Idiopathic Hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time. Although IH is a diagnosis of exclusion, electrophysiological testing, including polysomnography and mean sleep latency test remain crucial to establish the diagnosis. This activity highlights the role of the interprofessional team in evaluating and managing patients with idiopathic hypersomnia. Objectives: Describe signs and symptoms of idiopathic hypersomnia. Outline differential diagnoses of hypersomnolence. Summarize the diagnostic criteria. Review treatment options for idiopathic hypersomnia. Access free multiple choice questions on this topic. Introduction Idiopathic hypersomnia (IH) is a rare chronic sleep disorder introduced by Bedrich Roth in Prague in 1956. [1] Idiopathic hypersomnia is characterized by excessive daytime sleepiness, uncontrollable need to sleep with long unrefreshing naps, and difficulty waking up from sleep in most instances despite average or longer amounts of nocturnal sleep for at least three months. [2] Idiopathic hypersomnia is considered&#x000a0;a disorder of neurological origin, classified as a cent

Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), hypersomnolence, of which there are several subtypes, appears under sleep-wake disorder Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), hypersomnolence, of which there are several subtypes, appears under sleep-wake disorders. Hypersomnia is a pathological state characterized by a lack of alertness during the waking episodes of the day. It is not to be confused with fatigue, which is a normal physiological state. Daytime sleepiness appears most commonly during situations where little interaction is needed. Since hypersomnia impairs patients' attention levels (wakefulness), quality of life may be impacted as well.…

Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic hypersomnia was first described by Bedrich Roth in 1956, and it can be divided into two forms: polysymptomatic and monosymptomatic. The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had t Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic hypersomnia was first described by Bedrich Roth in 1956, and it can be divided into two forms: polysymptomatic and monosymptomatic. The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had the disorder for many years prior to their diagnosis. As of August 2021, an FDA-approved medication exists for IH called Xywav, which is an oral solution of calcium, magnesium, potassium, and sodium oxybates; in addition to several off-label treatments (primarily FDA-approved narcolepsy medications). Idiopathic hypersomnia may also be referred to as IH, IHS, or primary hypersomnia, and belongs to a group of sleep disorders known as central hypersomnias, central disorders of hypersomnolence, or hypersomnia of brain origin. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defines idiopathic hypersomnia as EDS without narcolepsy or the associated features of other sleep disorders. It occurs in the absence of medical problems or sleep disruptions, such as sleep apnea, that can cause secondary hypersomnia. It is relatively common for mood disorders (depression or bipolar disorder) to occur at the same time as IH, with a small increase in anxiety disorder diagnoses.