Kleine-Levin Syndrome: A Report of Three Adolescent Female Patients

M. Sadeghi MD

Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

Introduction

Kleine-Levin syndrome (KLS) is a relatively rare sleep disorder characterized by recurrent episodes of hypersomnia, hyperphagia, and mental and behavioral changes.¹ Other features include apathy, irritability, confusion, sexual disinhibition, delusion, hallucination, disorientation memory impairment, incoherent speech and depression or agitation.^2-5 In about 50% of cases, the syndrome has occurred following a specific factor such as thalamic infarction,⁶ Epstein Barr/herpes zoster infection,⁷ encephalitis,^8,9 Asperger syndrome,¹⁰ head trauma,¹¹ multiple cerebral infarcts,¹² and ingestion of drugs like triazolam.¹³ About 100 cases have been reported in the psychiatric literature to date;¹⁴ it is more common in young males, although it may be seen at any age. Reports of an established diagnosis of KLS in a female are relatively sparse.¹⁵ Herein 3 cases of KLS in females are presented underlining the common features, and also pitfalls in the diagnosis.

Case Report

Case 1: F.H., a 10-year-old girl developed excessive crying, apprehension, and dependency upon her mother shortly after recovering from a common cold. This episode lasted for 2 days and she recovered spontaneously. Twenty days later she began to show the same behavior for 8 days, again recovering fully thereafter. These episodes recurred 3 more times with durations of about 3 days and intervals of 9-11 days. During the episodes, she had excessive somnolence and hyperphagia while during the intervals she seemed completely normal. EEG showed a generalized slowing, and her LP and CT scan were normal. She had been diagnosed as having some form of epilepsy and/or affective disorder and was treated with carbamazepine and tricyclic drugs which were generally ineffective. Her growth and development were normal but she had been hospitalized when she was 3 years old because of septicemia, from which she had recovered without any significant sequela. On mental state examination she was confused, drowsy, fearful and clinging to her mother. With the diagnosis of KLS she was put on methylphenidate with a daily dose of 30 mg. With this treatment, the intervals became longer and after 3 subsequent short episodes, the illness ceased to recur.

Case 2: A.Z., a 12-year-old girl developed a high- grade fever and was hospitalized. The diagnosis of viral encephalitis was made and supportive measures ended in recovery and discharge from the hospital. Ten months later she began to sleep excessively during the day and subsequently her appetite increased, and a state of irritability together with a fear of getting lost or separated from her family developed. These features lasted about 3 days and recurred a week later. On mental state examination she was drowsy and yet restless, playing with her fingers and hair, laughing and singing. She seemed somewhat disinhibited and distractible, pointing to imperative auditory hallucinations: "Evil orders me to sing". Her personal and family background were unremarkable except for some degree of separation anxiety toward her mother. EEG showed nonspecific dysrhythmia; CT and laboratory data were normal. She had been treated with carbamazepine and antipsychotics which were not effective. With probable diagnosis of KLS she was given methylphenidate 10 mg daily, and 2 days later all her symptoms disappeared and did not recur until 5 months later when the drug was discontinued, and also following a common cold.

Case 3: The illness of L.M., a 13-year-old girl, began suddenly; she became drowsy and hyperphagic. Meanwhile, she was very restless and showed decreased attention to her environment. These symptoms lasted about 4 days and gradually disappeared without treatment. One week later the symptoms returned and she was referred for medical evaluation. CT imaging and routine laboratory tests were normal, EEG showed a general slowing, and CSF antibody test for measles was negative. She had been born prematurely with congenital bilateral ptosis together with a history of septicemia at 8 months old. She had been completely normal before the illness. A probable diagnosis of encephalitis with behavioral symptoms were made, but she did not respond to Zovirax, antiepileptics and haloperidol. Her symptoms waxed and waned with intervals of about one week. When she was first visited by the author, severe agitation, decreased attention and concentration, irritability, and disinhibition especially in sexual matters were the main symptoms. These features suggested the probability of KLS and treatment with methylphenidate was begun. Her symptoms responded dramatically to the drug and did not return in a 6-month follow-up despite discontinuation of the drug after 3 months.

Discussion

All these 3 patients show common features of KLS, including hypersomnia, hyperplasia, confusion, behavioral and psychotic symptoms such as disinhibition, affective instability, agitation and fear or hallucinatory experiences. All of them had abnormal non-specific EEG's; in 2 patients the illness appeared after a probable viral infection (Cases 1-2). All were misdiagnosed as encephalitis, epilepsy, mood disorder or acute psychosis, but responded well to the stimulant drug methylphenidate. These features may suggest an infective or immunologic process acting on hypothalamic structures through an unknown mechanism. In addition, it is concluded that KLS may go unrecognized or may be misdiagnosed as narcolepsy,¹⁶ addiction, schizophrenia, hysteria, depression and seizure disorder, resulting in frequent delays in diagnosis and the institution of inappropriate treatment. The syndrome is generally self-limited and drugs such as amphetamine or methylphenidate and lithium have been used with variable success.^17,18 It is recommended that this rare disorder should be considered in any child or adolescent (male or female) who shows bizarre and periodic symptomatology.

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