Benign neonatal sleep myoclonus

Benign neonatal sleep myoclonus is characterized by myoclonic “lightninglike” jerks of the extremities that exclusively occur during sleep; it is not correlated with epilepsy ¹. Benign neonatal sleep myoclonus is a phenomenon typically observed in newborns during the first four weeks of life. The clinical presentation may be varied, the myoclonic jerks being uni- or bilateral, focal, multifocal, generalized or marching ². Benign neonatal sleep myoclonus appear only during sleep and stop when the infant awakens ³. However, because benign neonatal sleep myoclonus so closely mimics seizures during the newborn period, it often prompts hospital admission and extensive diagnostic testing, including neurophysiologic studies, brain imaging, and screening for infection ⁴. A thorough understanding of the phenomenon is crucial to avoid unnecessary testing.

Benign neonatal sleep myoclonus onset is in the neonatal period. In one of the larger studies, a retrospective analysis of 38 children older than 4 years, onset in the first 16 days of life was reported in all children; most children presented in the first 4 days of life ⁵. In this same series, resolution occurred over the next several months, although 22 of the children had resolution by age 2 months.

Benign neonatal sleep myoclonus is not associated with abnormal electroencephalogram (EEG). Laboratory investigations such as glucose, electrolytes (calcium,
magnesium, phosphate) and metabolic investigations are normal. As reported in several studies benign neonatal sleep myoclonus is often not diagnosed or correctly diagnosed only after unsuccessful anticonvulsive therapy ⁶.

Attempts at treatment with anticonvulsants have been reported after movements were mistakenly attributed to epilepsy. Movements appeared to be exacerbated in 2 reports after benzodiazepine administration, perhaps invoking a GABA-mediated substrate ⁷. Apparent GABA-mediated, experimentally induced myoclonus has been reported ⁸. Additionally, a preponderance of neuronal excitatory activity has been demonstrated in newborns, partially due to an excitatory effect of GABA in the immature brain ⁹. This is in contrast with older individuals, in whom GABA activation typically exerts an inhibitory effect. Therefore, an overall excess of excitation occurs in the newborn and may explain the tendency for worsening with touch or sound stimulus in certain infants with benign neonatal sleep myoclonus.

Taking advantage of this reflex component has helped provide diagnostic clues as to the cause of the movements. Provocative maneuvers have been identified in some infants. Rocking infants in a crib at a low frequency (1 Hz) in a head-to-toe direction and repetitive sound stimuli have been used to provoke benign neonatal sleep myoclonus ¹⁰. Several case series report that parents themselves have identified these maneuvers ⁵.

Benign neonatal sleep myoclonus is benign self-limiting non-epileptic condition with excellent outcome. The condition resolves in most by 3 months of age. Parents should be reassured and should also understand the natural history of benign neonatal sleep myoclonus to prevent undue worry and concern. Mild speech delay and mildly abnormal axial tone has been noted in some ¹¹. Development of epilepsy has been reported in only one child on follow up ¹². A study of the natural history of benign neonatal sleep myoclonus has not been performed, and the use of parental reports only may underreport the condition in older children, who often sleep away from their parents.

Benign neonatal sleep myoclonus causes

The cause of benign neonatal sleep myoclonus is unknown. Coulter and Allen ¹³ suggested a benign discharge in the brainstem reticular activating system, the area where the initiation and synchronization of normal sleep is controlled. Resnick ¹⁴ postulated a transient immaturity or imbalance of the serotoninergic system.

The source of the myoclonic stimulus itself is unknown, and the brain cortex appears to be quiet during the movements without a consistent EEG correlate ¹⁵. Although occasional sharp activity in the temporal and central regions has been previously reported, epilepsy or cortical hyperexcitability does not seem to underlie benign neonatal sleep myoclonus ¹⁶. There is, however, a case series report of five US children with excessive myoclonus during sleep in which one third of the events had an EEG epileptiform correlate; the investigators suggested their findings may indicate a variant of benign myoclonic epilepsy of infancty ¹⁷.

As benign neonatal sleep myoclonus ceases spontaneously with age it is most probably related to brain maturation ², although this remains to be demonstrated. A genetic cause is suspected, with reports of occurrence in multiple family members ¹⁸.

A retrospective study (1996-2011) of 15 consecutive Japanese infants with benign neonatal sleep myoclonus, including 3 paired familial cases, suggests there may be an association with migraine ¹⁹. The investigators reported 5 of 12 parents (41.7%) had a history of migraines; 3 of the 15 infants (20%) developed migraine after age 5 years, and one child developed cyclic vomiting syndrome, a precursor of migraine, before age 1 year and remained under follow-up. None of the children developed epilepsy ¹⁹.

Benign neonatal sleep myoclonus symptoms

Although children are sometimes identified with abnormal movements within the first several hours of birth while still in the hospital, parents are often the first to witness the movements in children who were discharged early. These movements are often characterized as jerking of a limb during sleep. This may be repetitive and rhythmic and, thus, may prompt concerns regarding seizure. Unless the movements are previously videotaped or witnessed in the outpatient setting, patients are generally admitted for observation and workup, depending on the clinical concern for seizures.

Caretakers should be aware of the clinical characteristics of benign neonatal sleep myoclonus, which are delineated in the International Classification of Sleep Disorders, revised: Diagnostic and Coding Manual (2nd and 3rd editions), as follows ²⁰, ²¹:

• Repetitive myoclonic jerks that involve the whole body, trunk, or limbs
• Movements that occur in early infancy, typically from birth to age 6 months
• Movements that occur only during sleep
• Movements that stop abruptly and consistently when the child is aroused
• A disorder that is not better explained by another sleep disorder, by a medical or neurologic disorder, or by medication use

An association with sleep is important because clinically evident seizures are often associated with eye opening. Gentle restraint has been reported to possibly worsen the manifestations. Provocative maneuvers include sound stimulus and, in one report, repetitive head-to-toe rocking of the infant ¹⁰. In this report, increased rocking frequency seemed to be associated with increased clinical manifestations. Passive restraint of the child did not ameliorate the signs.

The most important maneuver is waking the child, which should entirely eliminate the symptoms. Movements are often superimposed on normal, purposeless movements of the infant and do not appear to occur in isolation, as is the case in the clonic movements of a seizure. One study reported an infant with benign neonatal sleep myoclonus who developed a pathologic form of myoclonus (ie, myoclonic-astatic epilepsy) ²². This association is likely incidental, and no clear evidence suggests that benign neonatal sleep myoclonus occurs in a continuum with other, more consequential forms of myoclonus.

Benign neonatal sleep myoclonus diagnosis

Physical examination findings of benign neonatal sleep myoclonus are normal, except for the movements themselves. Children are generally otherwise well; however, in one report, neurologic findings were reported ⁵. These were described as mild and included hyperirritability and hypoxia. The authors believed these findings were incidental and not causative; long-term follow-up of these same children indicated only tonal abnormalities. Whether these children had presenting neurologic abnormalities and the degree to which their tone was abnormal is unclear.

Most other reports emphasize the normal aspects of the physical examination findings. Children have normal examination findings and no long-term residua. In fact, a paucity of neurologic findings is, in itself, an aspect of the diagnostic criteria. Additional neurologic findings should prompt more extensive diagnostic testing for possible causes of pathologic myoclonus in infants.

If clinical confusion remains, a pediatric neurologist should be consulted to observe video footage and to perform an extended neurologic examination. Further diagnostic testing could be ordered based on their assessment and based on concern regarding possible seizures or other more ominous causes of myoclonus in children. This would be especially pertinent in patients with late-onset manifestations or with other concerning neurologic findings.

Once benign neonatal sleep myoclonus is identified, no imaging studies are indicated. If epilepsy or seizures remain a concern, MRI is the study of choice in infants.

If seizures remain a consideration, performing EEG is appropriate. Prolonged EEG monitoring, during multiple sleep/wake cycles potentially allows for time-locked data collection during episodes, making this the optimal study for infants in whom diagnostic confusion remains.

Benign neonatal sleep myoclonus treatment

No treatment other than reassurance is required as benign neonatal sleep myoclonus resolves spontaneously over several weeks without longterm neurological deficits ¹¹. Medical care of benign neonatal sleep myoclonus consists of making a correct diagnosis. Delayed recognition often results in extensive diagnostic testing, including screening for infectious causes of seizures (eg, spinal tap, blood cultures, empiric antibiotics) and neurodiagnostics (eg, electroencephalography, brain imaging, brain monitoring). This process almost invariably results in admission to the hospital and a great deal of family distress.

Early recognition can be facilitated by the use of home-video monitoring by parents, especially if the episodes are frequent. If the child is otherwise clinically well, ask the parents to obtain video footage while their child undergoes medical evaluation. Once a provider is experienced in the clinical manifestations, this can be invaluable in the diagnosis of benign neonatal sleep myoclonus. At that point, parents are reassured regarding the benign nature of the condition and educated regarding the prognosis. If clinical concern for possible seizure remains but the child is otherwise clinically stable (eg, without concerning pregnancy-related risk factors or abnormal findings on examination), admission to the hospital for a short stay to facilitate monitoring and observation by trained professionals is prudent.

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