Benign sleep myoclonus in infancy mistaken for epilepsy

Benign sleep myoclonus in infancy is a distinctive but underdiagnosed disorder of quiet sleep, which according to our findings occurs from the first day of life up to age 3 years. Its main features are rhythmic myoclonic jerks when drowsy or asleep, which stop if the child is woken, and normal encephalograms during or after the episodes.¹,² When all these features are present the diagnosis should be clear cut. The diagnosis may be difficult if the association with sleep is not noted and if no attempt is made to stop the “seizures” by waking the child. We report on15 patients in whom benign sleep myoclonus was initially mistaken for epilepsy.

Patients

All the patients were referred during the five year period 1996-2001 for investigation and treatment of prolonged “seizures”; some had been given anticonvulsants, without effect. The table summarises the clinical details of all the patients.

Illustrative case

A 14 day old boy (case 1; see table) was admitted after emergency helicopter transfer. In the previous week he had had several episodes of what was assumed to be status epilepticus but these had failed to respond to rectal and intravenous diazepam. Phenobarbitone and then phenytoin had been added but the seizures had continued. When he reached hospital he had been having generalised myoclonic movements for one hour. He was receiving three anticonvulsants in high doses. After the “seizure” ceased he appeared well but was drowsy. He fed well. Spontaneous movements and newborn and positional reflexes were normal.

Encephalograms during and after the episodes showed excess beta activity with generalised slowing, which was ascribed to his medication. There was no epileptic activity. The results of ultrasound and magnetic resonance imaging of his brain were normal, as were concentrations of plasma calcium, magnesium, glucose, ammonia, and urinary amino acids and organic acids.

Despite triple anticonvulsant therapy the “seizures” recurred and he was given repeated doses of diazepam, resulting in shallow and irregular respiration with periods of apnoea and oxygen desaturation needing intensive care. There the nurses observed that “seizures” occurred only when he was drowsy or asleep, never when he was awake. A severe form of benign sleep myoclonus was then suspected and the anticonvulsants were discontinued. He became less drowsy and both respiration and the frequency of “seizures” improved. Waking the child abolished the myoclonic episodes. He continued to have similar episodes until 3 months of age but developed normally and had no further “seizures” during four years of follow up.

Data on other cases

One child's mother had had benign sleep myoclonus during early infancy. In three other cases there was a history of unusually strong sleep onset myoclonus affecting in one case the mother and in the two other cases a sibling. In all cases pregnancy and delivery had been normal.

All 15 patients had generalised rhythmic myoclonic “seizures” but eight had also had focal clonic episodes affecting various sites. Brief periods of oxygen desaturation were noted in four of the nine patients who were monitored.

“Seizures” lasted longer than 30 minutes in four children, 10 minutes in two, and 2-10 minutes in nine.

Seven children were receiving anticonvulsants when first seen; all were being given phenobarbitone and two children were receiving one and one child two additional drugs (see table). After diagnosis all anticonvulsants could be discontinued.

All patients developed normally during six months and four years of follow up. None has developed epilepsy.

Discussion

The prevalence of benign sleep myoclonus is unknown but our experience in two centres suggests the condition is being under-recognised. Since writing this report one of us (JE) has seen four more infants with the condition during one year at the Kinderspital Meran, which has 1300 births annually. During the same period neonatal epilepsy was diagnosed in three other infants.

Benign sleep myoclonus usually presents within a few days of birth. Rhythmic myoclonic movements appear while the infant is drowsy or asleep but they stop if the child is woken, and this characteristic feature confirms the diagnosis. We have not encountered any cases clinically diagnosed as having sleep myoclonus—stopping on waking—who later turned out to have epilepsy. Sleep myoclonus usually disappears after a period of weeks and has resolved in most cases by 3 months of age. This coincides with the period of rapid maturation in sleep patterns seen during the first 3 months of life, at the end of which the longest nocturnal sleep period occurs and the diurnal-nocturnal pattern is established. During the first 12 weeks of life the initial period of sleep gradually changes from REM to non-REM sleep, and the total REM sleep periods continue decreasing markedly during the first six months of life.³,⁴

Although most patients with sleep myoclonus seem free of “seizures” by the age of 3 months, some may be having prolonged episodes of nocturnal myoclonus beyond that period unobserved because after that age prolonged sleep occurs mainly at night time when parents are asleep. Indeed the condition may persist for months and years, as the table shows—in patient 6 it lasted until age 3 years, and in patients 5, 9, and 11 it resolved at 7, 6, and 5 months respectively.

Benign sleep myoclonus may be mistaken for neonatal epilepsy due to a serious underlying disorder, or for benign neonatal or familial neonatal seizures. When the myoclonic jerks are unilateral, a more serious condition is often suspected and the diagnosis of benign sleep myoclonus may not be considered. All our 15 patients had generalised jerking and eight had unilateral jerks as well. Investigations other than an encephalogram are not helpful. Ultrasound scans of the brains of all of our patients were normal, and so was cranial computed tomography in two and magnetic resonance imaging in one. Ultrasound examination of the brain is justified, especially if there are doubts about the diagnosis and to allay parents' anxiety, but neither the irradiation from tomography nor the risks of anaesthesia for magnetic resonance imaging can be justified in this self limiting condition.

Seven of our patients received anticonvulsants for periods ranging from three months to seven years, without benefit. Anticonvulsants are ineffective in sleep myoclonus, and indeed may be harmful: by causing drowsiness, they may increase the frequency of fits: there is no indication for giving them. The episodes can be effectively managed by waking the child, and parents have become expert in this by simple measures such as changing nappies or gently squeezing extremities. It is important to tell parents not to waken their child by shaking.

Mistaking this benign self limiting condition for epilepsy may result in unnecessary investigations, unnecessary treatment, and unnecessary parental anxiety.

Table.

Clinical details of 15 infants with sleep myoclonus

Case	Sleep myoclonus			Rhythmic myoclonus			Electroencephalography			Neuroimaging		Treatment	Outcome
	Onset (day of life)	Age resolved		General	Focal		Between episodes	During episodes		Ultrasound	CCT/MRI
1	7	3 months		Present	Present		Normal	Normal		Normal	MRI normal	Phenobarbitone, phenytoin, diazepam	Normal
2	2	6 weeks		Present	Absent		Normal	Normal		Normal	ND	Phenobarbitone	Normal
3	4	3 months		Present	Absent		Normal	Normal		Normal	ND	Phenobarbitone	Normal
4	8	2 months		Present	Present		Normal	ND		Normal	ND	None	Normal
5	4	7 months		Present	Present		Normal	ND		Normal	ND	Phenobarbitone, phenytoin	Normal
6	7	3 years		Present	Absent		Normal	Normal		Normal	ND	Phenobarbitone, carbamazepine	Normal
7	7	4 weeks		Present	Absent		Normal	Normal		Normal	ND	None	Normal
8	5	3 months		Present	Present		Normal	ND		Normal	ND	None	Normal
9	7	6 months		Present	Present		Normal	ND		Normal	ND	None	Normal
10	7	4 months		Present	Present		Normal	ND		ND	ND	None	Normal
11	28	5 months		Present	Present		Normal	Normal		ND	ND	None	Normal
12	5	9 weeks		Present	Absent		Normal	ND		Normal	CCT normal	Phenobarbitone	Normal
13	8	4 months		Present	Absent		Normal	ND		Normal	CCT normal	Phenobarbitone	Normal
14	7	3 months		Present	Absent		Normal	ND		Normal	ND	None	Normal
15	2	3 months		Present	Present		Normal	ND		Normal	ND	None	Normal

ND = investigation not done; MRI = magnetic resonance imaging; CCT = cranial computed tomography.