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.

Introduction

Kleine-Levine syndrome is a rare syndrome, possibly affecting one in a million and is characterized by recurrent episodes of hypersomnia, hyperphagia, behavioral and cognitive disturbances.[1] The literature search done by Arnulf et al. between 1962 and 2004 found only 186 cases in literature. It mainly affects adolescent males between ages of 10 and 25 years but cases have also been reported in females and tends to be of longer duration. The patient sometimes sleeps up to 20 hours in a day. Each episode can last from days to weeks and the individuals are asymptomatic in between the episodes.[2] Recurrent episodes of hypersomnia were first described by Willi Kleine in 1925 and later on Max Levine described the association between hypersomnia and hyperphagia in 1929 and 1936. According to American Academy of Sleep medicine, symptoms may be related to malfunction of the hypothalamus. The pathophysiology remains unclear but many etiological factors have been described. In approximately 50% of cases, the syndrome occurs following a specific factor such as viral upper respiratory tract infection,[3] Epstein Barr virus, herpes zoster infection,[4] encephalitis, head trauma and ingestion of drugs. Recurrent episodes occur every few weeks to months and the condition can last for a decade or even more before spontaneous recovery.

Case Report

A previously well 14-year-old boy presented acutely 10 days following a viral throat infection with excessive sleepiness, tiredness, abnormal behavior and hypersexuality. He was sleeping for almost 22 hours per day and only waking up for eating/drinking and toilet needs. On examination he was sleepy but easily arousable and oriented to time, place and person. His Glasgow Coma Scale (15/15) and rest of the neurological examination including fundoscopy and other systemic examination were completely unremarkable. Detailed investigations including electrolytes, liver function tests, copper, ceruloplasmin, CSF (cerebro spinal fluid), lactates (blood and CSF), ammonia, virology screen (blood and CSF) and autoimmune screening including anti-N-methyl-D-aspartate receptor, antivoltage-gated potassium channel (VGKC) and anti-glutamic acid decarboxylase antibodies were negative. MRI brain scan with and without contrast was normal. EEG showed non-specific diffuse slowing consistent with encephalopathy with no epileptic discharges. His excessive sleepiness gradually improved together with his altered behavior in about 2 weeks after presentation. Hypersexuality became more overt during this phase manifesting as fiddling with his genitalia, putting his pant down in front of parents and even inappropriate behavior towards female staff. All these symptoms completely disappeared 3 weeks after his presentation and he started attending, initially part-time and later full time as before. Parents reported that he is back to his usual self and didn’t have any decline in academic performance.

However, 6 weeks later he was readmitted with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. Rest of investigations including CSF, virology screen and autoimmune antibody screen were again normal. Repeat MRI brain was again normal. Interestingly his recovery was also similar and he was completely back to his normal self in about 3 weeks time.

On second admission after ruling out infectious, metabolic and auto-immune causes it became apparent that his symptoms were consistent with KLS. Parents were reassured and he was managed supportively.

We gave him a trial of Modafinil (CNS stimulant), however due to gastrointestinal side effects he could not tolerate that. At his 6-month follow up, he hasn’t reported any further episodes and is completely normal neurologically. His behavior at school and home is reported to be normal and he is doing very well at school academically.

Discussion

KLS has a benign course of action with spontaneous resolution of symptoms though patient can have recurrent symptoms over period of a decade. The median duration of disease is 8 years and the attacks tend to be of less intensity toward the end of the disease course.[5]

Diagnosis of KLS can be very difficult as there is no single symptom that can positively make the diagnosis. Rather KLS is a diagnosis of exclusion and the patient needs a long list of investigations to eliminate other conditions that mimics the symptoms of KLS. To diagnose KLS, the only essential criterion is recurrent hypersomnia. A patient can experience other symptoms like: (1) hypersexual behavior; (2) hyperphagia with compulsive eating behavior; (3) cognitive and behavior disturbances including confusion, irritability, aggressiveness, hallucination and delusion.

Most of the patients are misdiagnosed as having encephalitis, narcolepsy, epilepsy, psychosis and mood disorders.

In a systemic review of 186 cases in the literature nearly half of the patients experienced hypersexual behavior and only few of the patients had decline in academic performance secondary to school absences.[5]

Our patient had hyperphagia and hypersexuality but didn’t have any decline in school performance.

Various treatment strategies including stimulants like methylphenidate, modafinil, D-amphetamine, ephedrine, methamphetamine, amphetamine, etc., have been used to treat sleepiness in the literature.[6]

KLS should also be differentiated from Narcolepsy[7] which is a chronic sleep disorder characterized by excessive sleepiness and sleep attacks at inappropriate times and has certain symptoms which can help physician in the diagnosis. The other differential which is worth considering is Kluver Bucy syndrome which mainly presents with hyperphagia and hypersexuality but hypersomnia is not its characterized feature.

Early diagnosis helps in starting medical treatment and patient education that helps in alleviating the anxiety of family members, school teachers and work colleagues.

KLS is a clinical diagnosis and should be considered in a patient with episodes of hypersomnia.