Epilepsy and Narcolepsy-Cataplexy in a Child

Case Report

This patient was a 5-year-old boy. He was referred to the sleep center in Peking University People’s Hospital because of daytime sleepiness. He was born with no apparent difficulties, and his psychomotor development was normal. The family history was negative for both epilepsy and narcolepsy-cataplexy. At the age of 4 years, his parents noticed that he automatically shook his head to the left for 1 to 2 times each time, and the attack occurred several times a day, which increased during tension or eating. Most of the time, the patient was not aware of the movement of his head, and the attacks did not affect the patient’s daily life. Tourette syndrome was considered in a local hospital, but the patient did not get treated. Six months after this diagnosis, the child began having attacks of limb weakness or sudden falling several times a day during walking, which were easily triggered by emotion, especially laughing. One week later, excessive daytime sleepiness appeared and he often had irresistible naps for about 4 to 5 times per day. Each nap lasted for 30 minutes to 1 hour. At the same time, the parents noticed that the boy often screamed, cried, sleep-talked, and showed fear during night sleep. After waking, he complained of nightmares. The patient did not report hypnagogic hallucinations and sleep paralysis. Other symptoms and behavior changes included bad temper, increased appetite, and weight gain (increase of 12 kg within 6 months). The head shaking remained.

Neurologic examination and head magnetic resonance imaging (MRI) were normal. A short-time EEG showed epileptiform discharges (no attacks were noticed). A diagnosis of epilepsy was made 1 year after the onset of head shaking. The child was given oxcarbazepine, but the frequency of head shaking increased to 20 times per day without any change of other symptoms. Then 24-hour ambulatory electroencephalographic monitoring without video revealed generalized 3- to 4-Hz spike-wave and polyspike-wave discharges during awake and sleep states, but no attacks were mentioned.

The patient was then referred to the Sleep Center in Peking University People’s Hospital. Overnight nocturnal polysomnography was followed by multiple sleep latency tests the next day. Nocturnal polysomnography revealed short sleep latency (4 minutes) and impaired sleep quality, with increased stage 1 sleep and decreased stage 3 sleep. No sleep apneas/hypopneas appeared during polysomnography. Multiple sleep latency tests showed a mean sleep latency of less than 5 minutes and 3 sleep-onset rapid eye movements during 5 naps. Human leukocyte antigens DQB1*0602 was positive. The level of hypocretin-1 in cerebrospinal fluid was 26.9 pg/mL (normal: >110 pg/mL). Narcolepsy with cataplexy was clearly diagnosed. ¹

Because of the severe shaking head attacks, video-EEG monitoring (Nihon Kohden digital Video-EEG-1100 K, Japan) was performed in the Pediatrics Department, Peking University First Hospital. Electromyography (EMG) of the deltoid muscles was simultaneously performed with EEG monitoring. Background EEG was slightly slow, which might be due to the frequent sleep attack of the patient. Interictal generalized 3- to 4-Hz spike-wave and polyspike-wave discharges still existed during both awake and sleep states. The most important fact was that attacks were also recorded. Head shaking to the left side for 2 to 3 times per attack correlated very well with the spike-wave and polyspike-wave discharges. During the 4 hours’ monitoring, several seizures had been recorded in both awake and sleep. Although no obvious upper limb and shoulder jerks had been seen on observation, EMG of deltoid muscles showed short-duration bilateral seizures, confirming limb involvement (Figure 1). A diagnosis of myoclonic seizure was confirmed. Limb weakness or sudden falling triggered by jokes was also noticed during EEG monitoring. There were no discharges in EEG corresponding to the episodes of bilateral deltoid muscles EMG activity decrease or disappearance. Cataplexy was identified by physiological monitoring.

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Figure 1.

Polygraphic recording showing generalized spike and wave discharges associated with myoclonic jerks and EMG outbreak in the bilateral deltoid muscles.

To control his seizures, oxcarbazepine was withdrawn immediately and valproate was administered. After 1½ month, myoclonic seizures were controlled completely. The plasma concentration of valproate was 75.2 µg/mL. At the same time, excessive daytime sleepiness and cataplexy were more and more frequent and had serious impact on his daily life. Repeat multiple sleep latency tests revealed short sleep latency (<5 min) and 5 sleep-onset rapid eye movements in 5 naps. Together with the symptoms, the testing results indicating the aggravation of narcolepsy-cataplexy. Daytime somnolence significantly improved after methylphenidate (10 mg/d) as add-on therapy in combination with valproate. Clomipramine (25 mg/d) was given as add-on therapy for cataplexy. Within 1-year follow-up, he was still seizure free with improvement of daytime somnolence and cataplexy, enabling him to have a normal school life.

Discussion

Epilepsy is a chronic condition of the brain characterized by an enduring propensity to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. ² Epilepsy has specific relationship with the sleep-wake cycle, and the prevalence of sleep disorders in epilepsy patients is high, such as hypersomnia, insomnia, periodic limb movements, or restless leg syndrome. Narcolepsy-cataplexy is a sleep disorder and a chronic disabling disorder that affects the control of wakefulness and sleep. Because both epilepsy and narcolepsy-cataplexy can result in sleep disturbances and episodes of attack events, a differential diagnosis of the 2 disorders has been very well recognized. Here we reported the overlap of epilepsy and narcolepsy-cataplexy in a previously healthy child. To our knowledge, this is the third case of epilepsy coexisting with narcolepsy-cataplexy. The first report was published in 1955. ³ The second case reported by Lagrange et al ⁴ was that of a 40-year-old man. The current case developed epilepsy and narcolepsy-cataplexy symptoms at between 4 and 4.5 years old. Although this is a typical age to develop epilepsy, narcolepsy-cataplexy is considered very rare and typically occurs after puberty and in the second decade of life. This fact makes the clinical diagnosis of narcolepsy-cataplexy in this case much more difficult, although current reports suggest childhood narcolepsy is relatively common in the Chinese population. ^5,6

The onset symptom was myoclonic seizure, which belongs to 1 type of generalized seizures. Myoclonic jerks are shock-like, irregular, and often arrhythmic, clonic-twitching movements that are singular or repetitive. Myoclonic jerks predominantly affect the eyelids, facial and neck muscles, the upper limbs more than the lower limbs, and the body. Generalized polyspike and waves or sometimes spike and waves are the EEG accompaniment of jerks. The jerks can be unilateral or asymmetric, and head/body deviation may be a constant feature in some patients. Nevertheless, in this condition, it is very easy to be misdiagnosed or missed. In our patient, myoclonic seizures had been misdiagnosed as Tourette syndrome. During the course of the disease, although EEG revealed discharges and then epilepsy was diagnosed, a lack of accurate seizure classification led to inappropriate treatment and made seizure attacks more frequent.

In patients with narcolepsy, cataplexy often occurs after excessive daytime sleepiness. In our patient, the onset of cataplexy before sleepiness made it more difficult to judge whether the symptoms of myoclonic seizure and cataplexy were separate events. A typical cataplexy triggered by emotion change and positive multiple sleep latency tests led us to consider the diagnosis of narcolepsy-cataplexy in addition to epilepsy. This is supported by other evidence, including low hypocretin-1 level in the cerebrospinal fluid, positive human leukocyte antigen DQB1*0602 and treatment effect, and the EEG finding of cataplexy attack without epileptiform discharges, but with weakening or resting EMG. Video-EEG and behavior observation confirmed the diagnosis of myoclonic seizures with generalized discharges and EMG activities. Taking into account the rare condition of epilepsy and narcolepsy-cataplexy coexistence, we tried antiepileptic drugs first. Valproate controlled myoclonic seizures completely, but it might induce aggravation of daytime sleepiness of narcolepsy-cataplexy. Methylphenidate and clomipramine were added to improve daytime sleepiness and cataplexy. Although concern was raised initially that the use of a stimulant such as methylphenidate may trigger seizures, no such effect was observed. The improvement of both symptoms in this child by the combination therapy further confirmed the coexistence of the 2 diseases in the patient.

One previous study has indicated that the coexistence of epilepsy and narcolepsy-cataplexy might be due to a common mechanism. The patient reported in the paper by Lagrange et al ⁴ was diagnosed as Rasmussen syndrome. Narcolepsy-cataplexy was the first onset disease, and the interval between narcolepsy-cataplexy and complex partial seizure onset was about 18 months. The authors suggested that an autoimmune basis might be the common pathway, given the autoimmune nature of both disorders. The seizure types and causes in the current case were different from the previous reported case. Based on normal neurologic development and easy-to-control seizures, the diagnosis of epilepsy in our patient might be classified as idiopathic generalized epilepsies, which is considered to be genetically determined, and genetic heterogeneity is also reported to be common. ^{7 –9} Similarly, it is well known that there is a major immunologically related genetic influence on narcolepsy-cataplexy. The disorder is closely associated with the human leukocyte antigen DQA1*01:02/DQB1*06:02 haplotype. ¹⁰ Other genetic associations identified through recent genomewide association studies include the T-cell receptor alpha and the P2RY11 receptor loci. ^11,12 At the present time, more cases with both epilepsy and narcolepsy-cataplexy need to be found before further studies on mechanisms are conducted.