What is the most likely diagnosis for a 17-year-old male with recurrent periods of excessive daytime sleepiness, prolonged nighttime sleep of up to 20 hours, increased appetite, and libido, without any pre-existing conditions or medications?

Kleine-Levin Syndrome

The most likely diagnosis is C) Kleine-Levin syndrome (KLS), given the characteristic presentation of recurrent episodes of prolonged hypersomnia (up to 20 hours), increased appetite, and hypersexuality in a 17-year-old male with intervening periods of normal sleep. 1, 2

Clinical Reasoning

Why Kleine-Levin Syndrome is the Answer

KLS is a rare neurological disorder (1-2 cases per million) that primarily affects adolescent males (68-78% male, mean onset at 15 years), making this patient's demographic profile highly consistent with the diagnosis. 2 The syndrome is characterized by:

• Relapsing-remitting episodes of severe hypersomnia (typically 15-21 hours of sleep per day) lasting 1 to several weeks 1, 2
• Cognitive and behavioral disturbances during episodes, including hyperphagia (66% of cases) and hypersexuality (53%, predominantly in males) 2, 3
• Complete return to baseline between episodes, with normal sleep, cognition, and behavior 1, 3
• Episodes typically recur every 3.5 months on average, with patients experiencing 7-19 episodes over a median disease course of 8-14 years 2

Why Not the Other Options

A) Drug or substance use is excluded because the patient explicitly has no medication use and no pre-existing disorders. 4 While substance-related hypersomnia can cause excessive sleepiness, it would not present with the characteristic episodic pattern with complete normalization between episodes. 4

B) Idiopathic hypersomnia presents with daily, chronic excessive daytime sleepiness that persists for years without the relapsing-remitting pattern. 1 Patients with idiopathic hypersomnia have continuous symptoms rather than distinct episodes separated by normal periods. 5, 4 The episodic nature with intervening normal sleep periods definitively rules this out.

D) Narcolepsy typically presents with excessive daytime sleepiness, sleep attacks, cataplexy (in type 1), hypnagogic hallucinations, and sleep paralysis. 4, 6 However, narcolepsy causes persistent daily symptoms rather than episodic hypersomnia with complete resolution between episodes. 5 The increased appetite and libido are not characteristic features of narcolepsy. 4

Diagnostic Confirmation

To confirm KLS diagnosis, the following criteria must be met: 1

• Reliable history of distinct episodes lasting one to several weeks
• Episodes contain severe hypersomnia (>15 hours/day) associated with cognitive impairment (confusion, slowness, amnesia), derealization, apathy, or disinhibited behavior (hypersexuality, megaphagia)
• Complete return to baseline sleep, cognition, behavior, and mood after episodes

Supportive Testing

• EEG may show slow rhythms during episodes (70% of cases) and helps rule out epilepsy 2, 3
• Brain MRI is typically unremarkable but should be performed to exclude structural causes 1
• Functional brain imaging may show hypoperfusion of posterior associative cortex and hippocampus during both symptomatic and asymptomatic periods 1, 3
• Polysomnography and MSLT can rule out narcolepsy and other primary sleep disorders 7

Clinical Pearls

The first episode is triggered by an infection in 72% of patients, so inquire about recent illness. 2 The striking feature of derealization (feeling of unreality or being in a dream-like state) is highly specific for KLS and helps differentiate it from psychiatric mimics. 2, 3 During episodes, patients experience almost complete loss of autoactivation (apathy) where their only spontaneous initiative is to sleep. 3

Management Approach

Lithium carbonate (300 mg twice daily) is the most effective preventive therapy for reducing episode frequency and severity. 3, 7, 8 For long episodes (>30 days), intravenous methylprednisolone can help reduce episode duration. 1, 3 Patients should maintain adequate sleep habits and avoid alcohol and infections, which can trigger episodes. 1

The prognosis shows that episodes tend to become less frequent and disappear with advancing age, particularly when onset occurs during teenage years. 1, 2 However, 15% of patients have no signs of recovery after >20 years, and 20-40% develop long-term mild cognitive impairment or mood disorders, necessitating regular monitoring during asymptomatic periods. 3