Lesson of the week: Narcolepsy mistaken for epilepsy

Abstract

Case reports Case 1—A 26 year old woman was found in the bath “unable to move, speak, or get out.” Her husband reported flickering of the eyelids and muscle twitching. Her speech was slurred as she recovered, over minutes. The referral letter noted a history of short periods of apparent daytime sleep, sometimes at inappropriate moments—for example, during meals—and a tendency to “go weak and limp … if she is having a carry-on or laughing heartily.” The diagnosis at referral was of complex partial seizures; sodium valproate had been prescribed. It emerged that she had clear recall of her period of immobility in the bath: it resembled her episodes of weakness on laughing. On direct questioning she described sleep paralysis and hypnagogic hallucinations. She tended to sleep poorly at night. The combination of daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations suggested narcolepsy. Her HLA type, determined by the microlymphocytotoxicity technique using commercially obtained antisera, was DR152, DQ61, consistent with narcolepsy. Overnight polysomnography gave normal results, but a multiple sleep latency test gave a mean sleep onset time of 4 minutes (normally more than 10), with rapid eye movement sleep in the first 15 minutes of two of her five recorded naps (normally none). These results confirmed the diagnosis. Sodium valproate was withdrawn. Clomipramine controlled her cataplexy; her daytime sleepiness has improved on treatment with stimulants. Case 2—A 23 year old builder complained of excessive sleepiness over two years causing difficulties at work. His general practitioner was concerned by the possibility of epilepsy. Assessment in a general medical clinic elicited a story of “tonic-clonic seizures which occur during sleep,” based on a description from his girlfriend. He was a loud snorer. An electroencephalogram gave a normal recording, but he became drowsy repeatedly during the procedure. We subsequently obtained a history of disabling episodes of cataplexy: he had learnt to keep a straight face to avoid laughter and the resulting weakness. He also reported sleep paralysis and hypnagogic hallucinations. The true nature of the tonic-clonic seizures during sleep eventually became clear: these were episodes of cataplexy with distal muscle twitching, occurring towards the climax of sexual intercourse. His HLA type, determined by the microlymphocytotoxicity technique, was DR152, Drw53, DQ1,3, consistent with narcolepsy. Overnight polysomnography suggested mild obstructive sleep apnoea, but a multiple sleep latency test was indicative of narcolepsy, with a mean sleep latency of 15 seconds and sleep onset rapid eye movement in all four naps. Fluoxetine has controlled his cataplexy; stimulants for his daytime sleepiness and continuous positive airways pressure at night for his sleep apnoea have made a modest impact. Polysomnography Polysomnography involves the measurement of several physiological variables during sleep and aids the diagnosis of sleep disorders. The variables most commonly assessed are brain activity and sleep stage, using electroencephalography, muscle activity at several sites including eye movements, using surface electromyography, chest and abdominal movements related to breathing, oral or nasal airflow, heart rate using electrocardiography, and tissue oxygenation using pulse oximetry. The main use of polysomnography in the diagnosis of narcolepsy is to exclude disorders of nocturnal sleep, such as obstructive sleep apnoea, which might explain daytime sleepiness. Case 3—A 41 year old retired social worker was referred from an epilepsy clinic. Fifteen years before she had begun to experience episodes resembling “a waking dream:” something familiar would come into her mind, but she would be unable to recall its content afterwards. Six years before these episodes had become more sustained. She developed the sense that there “was a film running in my head,” comprising intrusive mental contents, both images and thoughts. She also experienced occasional feelings of déjà vu. Temporal lobe epilepsy was suspected. Computed tomography of the brain and an electroencephalogram gave normal results; treatment with carbamazepine was ineffective. Two years before we saw her the “film running in the head” had resolved itself into individual pictures that entered her mind for a second or so at a time. She sometimes recognised these from recent dreams, and they tended to have a strong emotional content. They appeared three or four times a day; she had similar experiences on dropping off to sleep, when she felt that “a dream comes straight into my mind.” Seven episodes of “waking hallucination” occurred during a 24 hour electroencephalogram recording: during several of these the record showed light sleep with superimposed rapid eye movements. Rapid eye movement also occurred at the onset of overnight sleep. On direct questioning she admitted to daytime sleepiness, with naps at least once a day, but not to cataplexy or sleep paralysis. We believed that her “waking hallucinations” represented a variety of hypnagogic hallucinations, and that these, in combination with daytime sleepiness and sleep onset rapid eye movement, were suggestive of narcolepsy (perhaps not conclusive, however, as some authors require the presence of cataplexy for a definite diagnosis4). Her HLA type, determined by polymerase chain reaction amplification with sequence specific primers, was DRB1*15, DRB5*51, DQB1*6, consistent with narcolepsy. A multiple sleep latency test showed a mean sleep latency of 11 minutes, a minimum latency of seven minutes, and two episodes of sleep onset rapid eye movement.