Kleine–Levin syndrome (KLS) is a rare disorder with periodic hypersomnia, cognitive and behavioural disturbances. The disease was named, “KLS” by Critchley in 1962 after Willi Kleine and Max Levin who studied multiple cases of hypersomnolence and emphasized the association of periodic somnolence with morbid hunger from 1925 to 1936.
International Classification of Sleep Disorders-3 criteria (2013) states following five key points for diagnosis:
- At least two recurrent episodes of excessive sleepiness of 2 days to several weeks
- Episodes recur at least 1 per 18 months
- Normal alertness, cognitive function, behavior and mood between episodes
- At least one of these during an episode:
Symptoms not better explained by other disorders.
- Cognitive dysfunction
- Altered perception, derealization
- Eating disorder (anorexia or hyperphagia)
- Disinhibited behavior (such as hypersexuality)
This disorder because of its sporadic presentation has unknown prevalence. A systematic review of 186 cases showed incidence usually in adolescence with a course lasting for 8 years or more. We describe two cases clinically diagnosed as KLS with atypical presentation and favorable response to armodafinil.
Thirty-year old married Muslim male presented with complaints of excessive sleep episodes of abrupt onset lasting for 14-16 days once a year from last 15 years (onset 15 years age) associated with the irritability, confusion, marked decline in self-care, demonstration of social responsibilities and regularity at work with no hyperphagia or hypersexuality. Interepisodal periods showed complete recovery. There was no positive past or family history of neurological or psychiatric disorder. History of meningitis, head injury and substance abuse were ruled out. All biochemical, endocrine, radiological parameters and electroencephalography (EEG) were found within normal range. A clinical diagnosis of KLS was made, and patient was put on armodafinil 100 mg oral dose for 10 days. He is maintaining well with no recurrence since last 1 year.
Twenty-four year married Muslim female with complaints of episodes of excessive sleep (15-20 days) with anger outburst, irritability with hyperphagia and hypersexuality occurring every month since last 4 years. There was a complicated peripartum and postpartum history in the form of cardiac arrest during emergency caesarean section followed by admission in Intensive Care Unit (ICU) for 15 days. During the stay in ICU and postdischarge there were complaints of auditory hallucinations, confusion, behavioral problems, taking bath 4-5 times a day, disinterest in child care. A diagnosis of postpartum psychosis was made, and she was put on risperidone 4 mg with no response, later on sodium valproate was added, but no major benefits were seen. This presentation continued for 3 months thereafter family noticed remission in complaints of hallucinations but a periodic monthly pattern of excessive sleepiness with feeling of unrealness for surrounding, confusion, irritability, hyperphagia and hypersexuality. There was decreased self-care and childcare during episodes and during interepisodic periods she maintained well. There was no other significant neurological, psychiatric, past and family history, and these episodes did not have any relation with menstrual cycles. Biochemical and endocrine parameters were within normal range. Magnetic resonance imaging and EEG were found to be normal. Technetium 99m-ethyl cysteinate dimer brain perfussion study showed hypo perfusion of bilateral frontal lobes. She was tried on various antipsychotic medications, selective serotonin reuptake inhibitor and valproate combinations over 3 years with no response. Periodicity and poor response to medications raised suspicion on the previous line of treatment initially for postpartum psychosis and eventual diagnosis of mood disorder. A clinical diagnosis of KLS was made and armodafinil 100 mg was started, dose was further raised to 300 mg. Later oxcarbamazepine in dose of 600 mg BD was started. Patient reported decreased in duration and more spaced out frequency of episodes of excessive sleep during first 3 months. She is maintaining well on the same treatment and is a symptom free from last 6 months.
Both the cases fulfilled the criteria for Kleine–Levine syndrome, but due to rarity of the disorder they remained undiagnosed for years. While Case 1 is a presentation with idiopathic etiology with no signs of hyperphagia or hypersexuality, Case 2 had onset with or preceded by postpartum psychosis that is not a very common presentation. Also the fact that case reports of KLS in females are very limited, the possibility of KLS was ignored. As disease mimics and shares psychiatric conditions in many ways, so a first presentation can be in Psychiatry Outpatient Department as in the case of both our patients. Therefore, it is important to have a high index of suspicion in any case presenting with complaints of episodic hypersomnolence and after ruling out differentials like Kluver–Bucey syndrome, atypical depression, substance abuse and other differentials for hypersolomnelence, diagnosis diagnosis of KLS should be made. Lithium, valproate, carbamazepine, amphetamine, L-dopa, modafinil, armodafinil have been tried for symptomatic treatment and for prevention of relapse with variable results in the absence of definitive treatment. In the cases that reported to us the male patient had 1 time treatment and has not got any episode in last 1 year whereas the female patient had a rapid cycling pattern and is continuing medications. Hence, the question arises whether it is advisable to give maintenance treatment to Case 1 or wait for another episode to start a maintenance drug.
Kleine–Levin syndrome is a neurological disorder with a lot of psychiatric coloring, therefore, a case can present to neurologist or psychiatrist depending upon patients understanding of symptoms, so it is important for clinicians to have high index of suspicion mainly for atypical presentations to avoid delay in diagnosis or making erroneous diagnosis. Though most cases develop spontaneously but presence of precipitating events should not stop clinician to suspect KLS. Armodafinil (100-300 mg) and oxcarbamazepine has been found to be effective in preventing relapse in these two cases of KLS. These case reports aim to highlight that KLS though considered a rare disorder may not be that uncommon and lack of enough available research data is likely to be responsible for missed diagnosis; thus we need more systematic studies regarding etiologies and treatment options.
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Conflict of Interest: None declared