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1.  A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes 
Neurotherapeutics  2012;9(4):739-752.
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.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-012-0150-9) contains supplementary material, which is available to authorized users.
PMCID: PMC3480574  PMID: 23065655
Narcolepsy; Hypocretin; Orexin; Sodium oxybate; Modafinil; Venlafaxine
2.  Sleeping Beauty: Kleine–Levin Syndrome 
Indian Journal of Psychiatry  2014;56(3):298-300.
Kleine–Levin syndrome (KLS) alias sleeping beauty syndrome, is a rare sleep disorder. Clinically presenting as episodes of hypersomnolence, behavioral and cognitive disturbances, hyperphagia and hypersexuality. KLS may have an idiopathic onset or may be precipitated by neurological event or infection. Until date, no definite underlying cause is established and neither there are any definitive management guidelines. It remains a diagnosis of exclusion after other psychiatric and neurological causes have been ruled out. Coloring of presentation with behavioral and mood elements makes it important for a psychiatrist to be well-informed about the condition to avoid the erroneous diagnosis. KLS is a devastating illness, which robs the patient of time, experiences, and relationships. An early diagnosis and effective management can help patient escape from the morbidity caused by this disorder. Armodafinil and oxcarbamazepine have found to be effective in two of the case. The emphasis of this report is to add to the existing clinical knowledge of neurologists, psychiatrists and physicians. In the future, research is needed on genetic etiology and management of this disorder.
PMCID: PMC4181188  PMID: 25316944
Armodafinil; oxcarbamazepine; postpartum Kleine–Levin syndrome; rapid cycling Kleine–Levin syndrome
3.  Apathy and hypersomnia are common features of myotonic dystrophy 
OBJECTIVES—Myotonic dystrophy is a disease characterised by myotonia and muscle weakness. Psychiatric disorder and sleep problems have also been considered important features of the illness. This study investigated the extent to which apathy, major depression, and hypersomnolence were present. The objective was to clarify if the apathy reported anecdotally was a feature of CNS involvement or if this was attributable to major depression, hypersomnolence, or a consequence of chronic muscle weakness.
METHODS—These features were studied in 36 adults with non-congenital myotonic dystrophy and 13 patients with Charcot-Marie-Tooth disease. By using patients with Charcot-Marie-Tooth disease as a comparison group the aim was to control for the disabling effects of having an inherited chronic neurological disease causing muscle weakness. Standardised assessment instruments were used wherever possible to facilitate comparison with other groups reported in the medical literature.
RESULTS—There was no excess of major depression on cross sectional analysis in these patients with mild myotonic dystrophy. However, apathy was a prominent feature of myotonic dystrophy in comparison with a similarly disabled group of patients with Charcot-Marie-Tooth disease (clinician rated score; Mann Whitney U test, p=0.0005). Rates of hypersomnolence were greater in the myotonic dystrophy group, occurring in 39% of myotonic dystrophy patients, but there was no correlation with apathy.
CONCLUSION—These data suggest that apathy and hypersomnia are independent and common features of myotonic dystrophy. Apathy cannot be accounted for by clinical depression or peripheral muscle weakness and is therefore likely to reflect CNS involvement. These features of the disease impair quality of life and may be treatable.

PMCID: PMC2170039  PMID: 9576545
4.  Recurrent encephalopathy? No I’m a sleeping beauty! 
To describe the clinical presentation of ‘Kleine-Levin (sleeping beauty) syndrome’ in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological examination including fundoscopy and other systemic examination was completely unremarkable. All his initial investigations including electrolytes, LFTs, CSF, virology screen and MRI brain scan were normal. Detailed autoimmune screening was also negative. EEG showed non-specific diffuse slowing consistent with encephalopathy. His excessive sleepiness gradually improved together with his altered behaviour in about two weeks after presentation. Hyper sexuality became more overt during this phase. All these symptoms completely disappeared three weeks after his presentation and he attended school as before. He was readmitted six weeks later with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. His recovery was also similar and he was completely back to his normal self in three weeks time. His recurrent symptoms were consistent with ‘Kleine-Levin syndrome (KLS)’ or ‘sleeping beauty syndrome’. KLS is a rare disorder which mainly affects adolescent males. Common symptoms include hypersomnia (100%), cognitive changes (96%), eating disturbances (80%), hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8 years, with on an average seven episode of 10 days each recurring every 3.5 months. It is most frequently precipitated by infections and somnolence decreases using stimulants in nearly 40% of cases.
PMCID: PMC4040046  PMID: 24891916
Hyperphagia; hypersomnia; hypersomnolence; Kleine-Levine syndrome; sleeping beauty syndrome
5.  CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions 
Objective: To determine the role of CSF hypocretin-1 in narcolepsy with and without cataplexy, Kleine-Levin syndrome (KLS), idiopathic and other hypersomnias, and several neurological conditions.
Patients: 26 narcoleptic patients with cataplexy, 9 narcoleptic patients without cataplexy, 2 patients with abnormal REM-sleep-associated hypersomnia, 7 patients with idiopathic hypersomnia, 2 patients with post-traumatic hypersomnia, 4 patients with KLS, and 88 patients with other neurological disorders.
Results: 23 patients with narcolepsy-cataplexy had low CSF hypocretin-1 levels, while one patient had a normal hypocretin level (HLA-DQB1*0602 negative) and the other two had intermediate levels (familial forms). One narcoleptic patient without cataplexy had a low hypocretin level. One patient affected with post-traumatic hypersomnia had intermediate hypocretin levels. The KLS patients had normal hypocretin levels while asymptomatic, but one KLS patient (also affected with Prader-Willi syndrome) showed a twofold decrease in hypocretin levels during a symptomatic episode. Among the patients without hypersomnia, two patients with normal pressure hydrocephalus and one with unclear central vertigo had intermediate levels.
Conclusion: Low CSF hypocretin-1 is highly specific (99.1%) and sensitive (88.5%) for narcolepsy with cataplexy. Hypocretin ligand deficiency appears not to be the major cause for other hypersomnias, with a possible continuum in the pathophysiology of narcolepsy without cataplexy and idiopathic hypersomnia. However, partial hypocretin lesions without low CSF hypocretin-1 consequences cannot be definitely excluded in those disorders. The existence of normal hypocretin levels in narcoleptic patients and intermediate levels in other rare aetiologies needs further investigation, especially for KLS, to establish the functional significance of hypocretin neurotransmission alterations.
PMCID: PMC1757412  PMID: 14638887
6.  Kleine–Levin syndrome: Etiology, diagnosis, and treatment 
Kleine–Levin syndrome (KLS) is a rare sleep disorder mainly affecting teenage boys in which the main features are intermittent hypersomnolence, behavioral and cognitive disturbances, hyperphagia, and in some cases hypersexuality. Each episode is of brief duration varying from a week to 1–2 months and affected people are entirely asymptomatic between episodes. No definite cause has been identified, and no effective treatments are available even though illness is having well-defined clinical features. Multiple relapses occur every few weeks or months, and the condition may last for a decade or more before spontaneous resolution. In this study, PubMed was searched and appropriate articles were reviewed to highlight etiology, clinical features, and management of KLS. On the basis of this knowledge, practical information is offered to help clinicians about how to investigate a case of KLS, and what are the possible treatment modalities available currently for the treatment during an episode and interepisodic period for prophylaxis. Comprehensive research into the etiology, pathophysiology, investigation, and treatments are required to aid the development of disease-specific targeted therapies.
PMCID: PMC3021925  PMID: 21264130
Hypersomnia; hypersexuality; Kleine–Levin syndrome; megaphagia; periodic
7.  Kleine-Levin syndrome: a review 
Kleine-Levin syndrome is a recurrent hypersomnia associated with symptoms of hyperphagia, hypersexuality, and cognitive impairment. This article reviews the current available research and describes common clinical symptoms, differential diagnosis, and acceptable workup and treatment. Although deficits have traditionally been thought to resolve between episodes, functional imaging studies and long-term neuropsychological testing in select patients have recently challenged this notion. This may suggest that Kleine-Levin syndrome is not as benign as previously considered.
PMCID: PMC3901778  PMID: 24470783
Kleine-Levin syndrome; hypersomnia; adolescent sleep disorder; hypersexuality
8.  SPECT in the Kleine–Levin Syndrome, a Possible Diagnostic and Prognostic Aid? 
Introduction: Kleine–Levin syndrome (KLS) is a rare syndrome of periodic hypersomnia and behavioral and cognitive symptoms based on clinical criteria. In the setting of differential diagnosis of hypersomnia disorders, an objective diagnostic aid is desirable. A promising modality is single photon emission computed tomography (SPECT). As intraepisodal investigations are difficult to perform, an interepisodal investigation would be very helpful. Another aim of the study was to correlate SPECT findings to prognosis.
Methods and Materials: Twenty-four KLS-patients were categorized as severe or non-severe based on clinical characteristics. The clinical characteristics were analyzed in relation to SPECT-examinations performed between hypersomnia periods (interepisodal) or after remission, as a clinical routine investigation.
Results: Forty-eight percent of the KLS-patients have hypoperfusion in the temporal or fronto-temporal regions. In patients that have undergone remission, 56% show that pattern. There were no specific findings related to prognosis.
Discussion/Conclusion: SPECT might be a diagnostic aid, in a setting of hypersomnia experience. With a sensitivity of 48%, interepisodal SPECT alone cannot be used for diagnosing KLS.
PMCID: PMC4172011  PMID: 25295028
single photon emission tomography; sleep disorders; brain perfusion; Kleine–Levin syndrome; sleep
9.  Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle 
Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders.
PMCID: PMC4160996  PMID: 25309500
hypersomnia; cognitive fluctuations; sleep; review; brain networks
10.  Hypersomnia 
Hypersomnia, a complaint of excessive daytime sleep or sleepiness, affects 4% to 6% of the population, with an impact on the everyday life of the patient Methodological tools to explore sleep and wakefulness (interview, questionnaires, sleep diary, polysomnography Multiple Sleep Latency Test, Maintenance of Wakefulness Test) and psy-chomotor tests (for example, psychomotor vigilance task and Oxford Sleep Resistance or Osier Test) help distinguish between the causes of hypersomnia. In this article, the causes of hypersomnia are detailed following the conventional classification of hypersomnic syndromes: narcolepsy, idiopathic hypersomnia, recurrent hypersomnia, insufficient sleep syndrome, medication- and toxin-dependent sleepiness, hypersomnia associated with psychiatric disorders, hypersomnia associated with neurological disorders, posttraumatic hypersomnia, infection (with a special emphasis on the differences between bacterial and viral diseases compared with parasitic diseases, such as sleeping sickness) and hypersomnia, hypersomnia associated with metabolic or endocrine diseases, breathing-related sleep disorders and sleep apnea syndromes, and periodic limb movements in sleep.
PMCID: PMC3181743  PMID: 16416710
narcolepsy; idiopathic hypersomnia; recurrent hypersomnia; insufficient sleep syndrome; periodic limb movements in sleep; sleep apnea syndrome; human African trypanosomiasis; infectious disease
11.  From wakefulness to excessive sleepiness: what we know and still need to know 
Sleep medicine reviews  2008;12(2):129-141.
The epidemiological study of hypersomnia symptoms is still in its infancy; most epidemiological surveys on this topic were published in the last decade. More than two dozen representative community studies can be found. These studies assessed two aspects of hypersomnia: excessive quantity of sleep and sleep propensity during wakefulness (excessive daytime sleepiness). The prevalence of excessive quantity of sleep when referring to the subjective evaluation of sleep duration is around 4% of the population. Excessive daytime sleepiness (EDS) has been mostly investigated in terms of frequency or severity; duration of the symptom has rarely been investigated. EDS occurring at least 3 days per week has been reported in between 4% and 20.6% of the population, while severe EDS was reported at 5%. In most studies men and women are equally affected. In the International Classification of Sleep Disorders, hypersomnia symptoms are the essential feature of 3 disorders: insufficient sleep syndrome, hypersomnia (idiopathic, recurrent or posttraumatic) and narcolepsy. Insufficient sleep syndrome and hypersomnia diagnoses are poorly documented. The co-occurrence of insufficient sleep and EDS has been explored in some studies and prevalence has been found in around 8% of the general population. However, these subjects often have other conditions such as insomnia, depression or sleep apnea. Therefore, the prevalence of insufficient sleep syndrome is more likely to be between 1% and 4% of the population. Idiopathic hypersomnia would be rare in the general population with prevalence, around 0.3%. Narcolepsy has been more extensively studied, with a prevalence around 0.045% in the general population. Genetic epidemiological studies of narcolepsy have shown that between 1.5% and 20.8% of narcoleptic individuals have at least one family member with the disease. The large variation is mostly due to the method used to collect the information on the family members; systematic investigation of all family members provided higher results. There is still a lot to be done in the epidemiological field of hypersomnia. Inconsistencies in its definition and measurement limit the generalization of the results. The use of a single question fails to capture the complexity of the symptom. The natural evolution of hypersomnia remains to be documented.
PMCID: PMC2362500  PMID: 18342261
epidemiology; excessive sleepiness; hypersomnia; narcolepsy; genetic epidemiology
12.  Monozygotic twins concordant for Kleine-Levin syndrome 
BMC Neurology  2012;12:31.
Kleine-Levin syndrome is a rare sleep disorder of unknown etiology. It is characterized by intermittent periods of excessive sleepiness, cognitive disturbances and behavioral abnormalities. Nine cases of familial Kleine-Levin syndrome have been identified, but there are no reported cases describing twins that are affected by the syndrome.
Case presentation
We report the cases of 16-year-old monozygotic twin boys who both suffered from Kleine-Levin syndrome. In both cases, the onset of the first episode was preceded by an influenza infection. During symptomatic periods they slept for the entire day except for meals and bathroom visits. Actimetry recordings revealed that during symptomatic periods, daily activity was lower than that of asymptomatic periods, on the other hand, activity during the night was significantly higher in symptomatic periods than asymptomatic periods. Polysomnography (PSG) data during symptomatic periods revealed a decrease in sleep efficiency. Human leukocyte antigen (HLA) typing revealed no DQB1*02 loci. They were administered lithium carbonate but the beneficial effect was limited.
Our observations suggest that Kleine-Levin syndrome may be due to genetic and autoimmune processes, although etiologic relationship to specific HLA type remains controversial.
PMCID: PMC3502424  PMID: 22646233
Recurrent hypersomnia; Kleine-Levin syndrome; Monozygotic twins; HLA typing; Polysomnography; Actimetry
13.  Kleine-Levine syndrome in an adolescent female and response to modafinil 
Kleine-Levine Syndrome (KLS) is a disorder characterized by a triad of periodic hypersomnia, hyperphagia, and hypersexuality. KLS, although more common in young males, it has also been seen in females. Treatment options available for its management include mood stabilisers like lithium, stimulants like amphetamines, antidepressants and other options including electroconvulsive therapy. Modafinil is one of the new stimulant medications approved for narcolepsy. Herein, we report a young female with KLS and showing favorable response to modafinil. More data is required to establish the effectiveness of modafinil in this syndrome.
PMCID: PMC3108080  PMID: 21655207
Females; Kleine-Levin syndrome; Modafinil
14.  Hypersomnia in Inter-Episode Bipolar Disorder: Does it Have Prognostic Significance? 
Journal of affective disorders  2011;132(3):438-444.
Hypersomnia in inter-episode bipolar disorder has been minimally researched. The current study sought to document the prevalence of hypersomnia in a sample of inter-episode patients with bipolar disorder and to examine the relationship between hypersomnia and future bipolar depressive symptoms.
A total of 56 individuals with bipolar disorder (51 Type 1 + 5 Type II) who were currently inter-episode, along with 55 non-psychiatric controls, completed a baseline assessment, including semi-structured interviews for psychiatric diagnoses, sleep disorders, and a battery of indices that included assessment of hypersomnia. Approximately six months later, participants were recontacted by telephone and mood was re-evaluated.
Three of six indices suggested that approximately 25% of participants with bipolar disorder endorsed symptoms of hypersomnia in the inter-episode period. Within the bipolar group, hypersomnia in the inter-episode period was associated with future depressive symptoms. This finding was independent of baseline depressive symptoms and medication use.
Small sample size and concurrent psychopharmacology in the bipolar sample.
Though no gold standard measure for hypersomnia currently exists, this research takes a step towards identifying a clinically and empirically useful hypersomnia assessment. This study demonstrates that hypersomnia in the inter-episode period of bipolar disorder relates to future depressive symptoms, and adds to the growing body of evidence on the importance of inter-episode symptoms predicting bipolar relapse.
PMCID: PMC3139494  PMID: 21489637
hypersomnia; sleep disturbance; bipolar disorder; long sleep
15.  Reduced Thalamic and Pontine Connectivity in Kleine–Levin Syndrome 
The Kleine–Levin syndrome (KLS) is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in KLS during sleep episodes. One patient with KLS and congenital nystagmus was investigated by resting state functional magnetic resonance imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications, and results could be of interest to researchers and clinicians in the whole field of sleep medicine.
PMCID: PMC3980089  PMID: 24765085
periodic idiopathic hypersomnia; nystagmus; sleep; functional magnetic resonance imaging; brain stem; pons; thalamus; cerebellum
16.  Functional Magnetic Resonance Imaging in Narcolepsy and the Kleine–Levin Syndrome 
This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine–Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine–Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine–Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine–Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.
PMCID: PMC4069720  PMID: 25009530
functional magnetic resonance imaging; narcolepsy; hypersomnia; Kleine–Levin syndrome; sleep; ascending arousal system; hypothalamus; thalamus
17.  A Striking Response to Lithium in Kleine–Levin Syndrome 
Kleine–Levin syndrome (KLS) is an episodic hypersomnia with cognitive disturbances such as confusion, apathy, and derealization. Hyperphagia and hypersexuality occur in around 50% of cases. No evidence-based treatments have been established for KLS. Many drugs have been tried, most often with little success. Here, a case with a striking response to lithium is presented.
PMCID: PMC3968761  PMID: 24711803
Kleine–Levin syndrome; lithium; hypersomnia; cognitive disorders; hypothalamus
Indian Journal of Psychiatry  2001;43(3):276-278.
Two cases of Kleine-Levin Syndrome with illness duration of three and four months respectively are presented. Both cases in their adolescence presented with typical features of the syndrome-onset after high grade fever episodic course and spontaneous remission of each episode and normalcy in between the episodes Characteristic features of each episode in both cases were hypersomnia, eating excessively, disinhibited behaviour, affective features like irritability social withdrawal and lack of personal care and cognitive disturbance. The second case had sexual disinhibition which is another important feature seen in Kleine-Levin Syndrome. Both patients responded well to lithium therapy.
PMCID: PMC2956156  PMID: 21407869
Kleine-Levin syndrome
19.  Diagnosis and management of central hypersomnias 
Central hypersomnias are diseases manifested in excessive daytime sleepiness (EDS) not caused by disturbed nocturnal sleep or misaligned circadian rhythms. Central hypersomnias includes narcolepsy with and without cataplexy, recurrent hypersomnia, idiopathic hypersomnia, with and without long sleep time, behaviorally induced insufficient sleep syndrome, hypersomnia and narcolepsy due to medical conditions, and finally hypersomnia induced by substance intake. The Epworth Sleepiness Scale is a subjective tool mostly used for EDS assessment, while the Multiple Sleep Latency Test serves as an objective diagnostic method for narcolepsy and idiopathic hypersomnias. As for symptomatic therapy of EDS, the central nervous system stimulants modafinil and methylphenidate seem to work well in most cases and in narcolepsy and Parkinson’s disease; sodium oxybate also has notable therapeutic value.
PMCID: PMC3437530  PMID: 22973425
Excessive daytime sleepiness; hypersomnia; methylphenidate; modafinil; narcolepsy; sodium oxybate
20.  Psychiatric aspects of organic sleep disorders 
In recent years, a number of studies have attempted to characterize psychological disturbances related to various sleep disorders. The objective of this type of research is to investigate the possibility that psychopathology may represent an etiological factor, a complication, and/or a target for treatment. In addition, disordered sleep can present itself in a complex and atypical fashion in which the primary sleep-related component may not be immediately apparent. This article reviews the evidence for a relationship between organic sleep disorders and psychiatric morbidity. Generally, it can be concluded that organic sleep disorders have a profound negative impact on most domains of health-related quality of life. Results for the sleep disorders that have been studied (narcolepsy, idiopathic hypersomnia, sleep apnea/hypopnea syndrome, restless legs syndrome, periodic limb movement disorder, and circadian sleep disorders) show strong evidence for an association with mood disorders. After treatment, depression scores may or may not improve to the level of population norms, suggesting that this relationship is more complex than one of mere cause and effect.
PMCID: PMC3181746  PMID: 16416709
sleep; mood disorder; narcolepsy; idiopathic hypersomnia; sleep apnea syndrome; restless legs syndrome; periodic limb movement disorder; circadian sleep disorder; quality of life
21.  Hypersomnia and depressive symptoms: methodological and clinical aspects 
BMC Medicine  2013;11:78.
The associations between depressive symptoms and hypersomnia are complex and often bidirectional. Of the many disorders associated with excessive sleepiness in the general population, the most frequent are mental health disorders, particularly depression. However, most mood disorder studies addressing hypersomnia have assessed daytime sleepiness using a single response, neglecting critical and clinically relevant information about symptom severity, duration and nighttime sleep quality. Only a few studies have used objective tools such as polysomnography to directly measure both daytime and nighttime sleep propensity in depression with normal mean sleep latency and sleep duration. Hypersomnia in mood disorders, rather than a medical condition per se, is more a subjective sleep complaint than an objective finding. Mood symptoms have also been frequently reported in hypersomnia disorders of central origin, especially in narcolepsy. Hypocretin deficiency could be a contributing factor in this condition. Further interventional studies are needed to explore whether management of sleep complaints improves mood symptoms in hypersomnia disorders and, conversely, whether management of mood complaints improves sleep symptoms in mood disorders.
PMCID: PMC3621400  PMID: 23514569
Depression; Mood; Sleep; Hypersomnia; Excessive daytime sleepiness; Narcolepsy
22.  Primary sleep disorders seen at a Neurology service-based sleep clinic in India: Patterns over an 8-year period 
There is an increasing awareness for recognition of sleep disorders in India; however, there is still a huge gap in the number of people suffering from various sleep disorders, in the community versus those visiting hospital clinics for the same. Ours is a neurology services-based sleep disorders clinic, which has evolved successfully over the last decade. In this study, we aimed to evaluate the changes in referral patterns and distribution of various sleep disorders in the patients presenting to the clinic.
Materials and Methods:
This is a retrospective chart review-based study on all patients seen over an 8-year period, divided into 2 groups comprising of patients seen during the first 4 years versus those seen over the next 4 years. Only those patients who had the sleep disorder as their presenting manifestation and those who had been formally interviewed with a pre-structured questionnaire detailing about the main features of the common sleep disorders according to the ICSD-R were included. Patients, in whom the sleep disorder could be clearly attributable to another neurological or systemic disorder, were excluded. Statistical analysis was carried out to identify the differences between the two groups as regards the distribution of various sleep disorders and other clinical data.
Among 710 patients registered in the clinic, 469 were included for analysis and 222 patients formed group 1 while 247 formed group 2. The main differences observed were in the form of a clear increase in the percentage of patients with sleep-related breathing disorders, sleep-related movement disorder, and the hypersomnias on comparison of distribution over the first 4 years versus the last 4 years; while a clear decline was seen in the number of patients with insomnia and parasomnias. A 3-fold increase was observed in the number of patients in whom polysomnography was obtained.
The distribution of various sleep disorders as seen in a neurology service-based sleep clinic is demonstrated in this study. Increasing referrals for sleep-disordered breathing, restless legs syndrome, and fewer referrals for insomnia and parasomnias might reflect on changing physician and patient awareness in our community.
PMCID: PMC3724062  PMID: 23956552
Clinic; neurology; referral patterns; sleep disorder
23.  An Investigation into the Use of Stimulant Therapy during Pregnancy 
Sleep Disorders  2012;2012:308952.
Introduction. A lack of documentation of stimulant use during pregnancy means that doctors have difficulty advising narcoleptic and hypersomnolent patients. Objectives. To investigate the use of stimulant therapy in narcoleptic and hypersomnolent patients during pregnancy. Method. A search of clinic letters at a tertiary sleep clinic identified women who became pregnant whilst receiving stimulant therapy between 01/09/1999 and 18/11/2010. Fifteen patients were included in a telephone survey. Results. There were 20 pregnancies. The reported advice received with regards to stimulant use was variable. In 7 pregnancies, medication was stopped preconceptually: 1 had a cleft palate and an extra digit 6 had good foetal outcomes. In 8 pregnancies, medication was stopped postconceptually: 1 had autism and attention-deficit hyperactivity disorder; 7 had good foetal outcomes. In 5 pregnancies, medication was continued throughout pregnancy: 2 ended in miscarriage; 1 was ectopic; 2 had good foetal outcomes. The most common symptom experienced was debilitating hypersomnolence. Conclusion. There are no standardised guidelines for use of stimulants during pregnancy. Women have significant symptoms during pregnancy for which there is an unmet clinical need. More research is needed into whether medication can be safely continued during pregnancy, and if not, when it should be discontinued. Better standardized advice should be made available.
PMCID: PMC3581134  PMID: 23470841
24.  Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study 
Psychiatry Research  2012;201(3):240-244.
Hypersomnolence in major depressive disorder (MDD) plays an important role in the natural history of the disorder, but the basis of hypersomnia in MDD is poorly understood. Slow wave activity (SWA) has been associated with sleep homeostasis, as well as sleep restoration and maintenance, and may be altered in MDD. Therefore, we conducted a post-hoc study that utilized high density electroencephalography (hdEEG) to test the hypothesis that MDD subjects with hypersomnia (HYS+) would have decreased SWA relative to age and sex-matched MDD subjects without hypersomnia (HYS−) and healthy controls (n=7 for each group). After correcting for multiple comparisons using statistical non-parametric mapping, HYS+ subjects demonstrated significantly reduced parieto-occipital all-night SWA relative to HYS− subjects. Our results suggest hypersomnolence may be associated with topographic reductions in SWA in MDD. Further research using adequately powered prospective design is indicated to confirm these findings.
PMCID: PMC3361575  PMID: 22512951
sleep; depression; spectral analysis
25.  Psychosis in a Case of Kleine-Levin Syndrome: A Diagnostic Challenge 
Kleine-Levin syndrome (KLS) is a rare disorder of sleep diagnosed mainly on clinical grounds. It presents a unique diagnostic dilemma for neurologists and psychiatrists; especially due to a high risk of being diagnosed as a psychiatric condition like a mood disorder. However, there is literature available documenting the cooccurrence of psychiatric illnesses in patients diagnosed with KLS. The following case highlights the above points.
PMCID: PMC4031591  PMID: 24860224
Bipolar disorder; diagnosis; Kleine-Levin syndrome; psychosis

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