Kleine-Levin syndrome: a review

Figures & data

Table 1 Diagnostic criteria for recurrent hypersomnia and Kleine-Levin syndrome (ICSD-2)

Recurrent hypersomnia

– Recurrent episodes of excessive daytime sleepiness lasting for 2 days to 4 weeks

– Episodes recur at least once per year

– Alertness, cognitive function and behavior are normal between episodes

– Hypersomnia is not explained by another sleep, medical, neurological, or psychiatric disorder, medication use, or substance abuse

Kleine-Levin syndrome

In addition to the recurrent hypersomnia criteria, the patient should also have at least one of the following

– Cognitive abnormalities – ex confusion, derealization, hallucinations

– Abnormal behavior – irritability, aggression

– Hyperphagia

– Hypersexuality

Abbreviation: ISCD-2, International Classification of Sleep Disorders – revison 2.

Table 2 Common symptoms in patients with Kleine-Levin syndrome

– Hypersomnia

– Derealization

– Apathy

– Disinhibition and hypersexuality

– Compulsive hyperphagia

– Altered perception and temperature sensation

Table 3 Kleine-Levin syndrome: key clinical points

– Symptoms of depersonalization and sensory disturbances are more common than disinhibition

– Hypersexuality is much more common in men than women

– Peak symptomatic period occurs within 24 hours and lasts anywhere between 1 and 3 weeks

– Recurrences vary in frequency but typically occur every 2–3 months

– Common triggers include infection, fever, alcohol intake, sleep deprivation, vaccination, menses, and head trauma

– Episodes tend to wane in frequency and severity as the disease progresses

– Depression and anxiety are common

– Most patients are amnestic to the episodes

– Patients may report persistent memory deficit

Table 4 Differential diagnosis

– Medication or substance use

– Primary psychiatric illness (ie, atypical depression, bipolar disorder)

– Sleep disordered breathing

– Narcolepsy

– Menstruation-related hypersomnia

– Complex partial seizures

– Klüver-Bucy syndrome (bilateral temporal lobe lesions)

– Metabolic encephalopathies

– Herpes simplex virus encephalitis

– Lyme disease

– Intermittent porphyria

Table 5 Ancillary testing in Kleine-Levin syndrome

– Electroencephalography (EEG): generalized slowing in up to 70% of cases during episodes.

– Polysomnography (PSG): typically normal. If performed toward the beginning of an episode, a decrease in slow wave sleep may be observed; if performed toward the end of an episode, a decrease in rapid eye movement (REM) sleep may be observed.

– Multiple sleep latency tests (MLST): typically normal.

– Routine blood work, including inflammatory markers: normal.

– Lumbar puncture: normal cell count, protein and glucose. Cerebrospinal fluid hypocretin may be lower during episodes, however still within the normal range.

– Magnetic resonance imaging (MRI): normal.

– Single photon emission computed tomography: hypoperfusion in the thalamus, hypothalamus, temporal lobes, orbitofrontal and parasagittal frontal lobes, and, less commonly, the basal ganglia and occipital regions. Hypoperfusion may persist in the mesial temporal lobe, frontal lobe and basal ganglia during asymptomatic periods.

– Neuropsychological testing: impairment in working memory during episodes. Persistent deficits in immediate and delayed, verbal and visual recall in some individuals.

Table 6 Treatment of Kleine-Levin syndrome

A. Supportive

1. Allow patient to rest at home under supervision in a safe and comfortable environment.

2. Postpone or adjust school and work activities to accommodate long sleep times.

3. Do not allow the patient to wander unattended or to operate a car or heavy machinery.

4. Monitor for symptoms of depression or anxiety.

5. Between episodes, maintain consistent sleep-wake schedules, avoid alcohol and sick contacts.

B. Medication

1. Consider amantadine if patient presents in the early stages of an episode.

2. Consider modafinil for excessive daytime sleepiness in the early symptomatic period.

3. Consider short-term course of an antidepressant, mood stabilizer, anxiolytic or antipsychotic for psychiatric symptoms.

Note: Modafinil, Teva Pharmaceuticals Indsutries Ltd., Frazer, PA, USA.