Benign Neonatal Sleep Myoclonus

Seizures are the most common manifestation of neurologic compromise in the newborn period and often portend serious neurologic injury or dysfunction. Understandably, movements that mimic seizures during this period cause significant concern for parents and physicians alike and often prompt extensive diagnostic evaluation.

Benign neonatal sleep myoclonus (BNSM), first described in 1982 by Coulter and Allen,[1] is a disorder commonly mistaken for seizures during the newborn period. Benign neonatal sleep myoclonus is characterized by myoclonic "lightninglike" jerks of the extremities that exclusively occur during sleep; it is not correlated with epilepsy.[2] However, because this condition so closely mimics seizures, it often prompts hospital admission and extensive diagnostic testing, including neurophysiologic studies, brain imaging, and screening for infection.[3] A thorough understanding of the phenomenon is crucial to avoid unnecessary testing.

Myoclonus has various potential causes and may arise from a wide array of sites in the peripheral nervous system and CNS.[4, 5] Although dysfunctional serotonin neurotransmission is a potential cause, it does not appear to be the cause in all cases, and data are somewhat contradictory.[6] Although some types of myoclonus are relatively well understood from a physiologic basis, the underlying etiology of benign neonatal sleep myoclonus remains unknown.

Although the first report postulated an abnormality of the reticular activating system, this was speculative and was based solely on the clinical association with sleep.[1] The close association with sleep, specifically quiet sleep, may indicate an association with structures or pathways that subserve sleep.[7] This may explain the apparent decrease in frequency and severity throughout infancy because sleep states transition into a mature pattern, with less quiet sleep during the latter portion of infancy.[8]

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.[7, 9, 10, 11] Although occasional sharp activity in the temporal and central regions has been previously reported, epilepsy or cortical hyperexcitability does not seem to underlie the condition.[12, 13, 14] 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 infancy.[15]

Myoclonus itself can arise from various locations within the CNS and even the peripheral nervous system.[4] It is described as brief, rapid, lightninglike movements of truncal, bulbar, or appendicular musculature. It can be further characterized as positive (associated with muscle activation) or negative (brief loss of muscle tone), isolated or repetitive, and rhythmic or nonrhythmic.

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.[16] 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.[16]

Pathologic myoclonus in the newborn is typically associated with manifestations of encephalopathy, seizures, or both.[17] However, benign neonatal sleep myoclonus is generally reported in otherwise healthy newborns without signs of neurologic compromise. The myoclonic activity is positive and semirhythmic and can be stimulus sensitive, with more prominent activity in response to loud sounds, touch, or attempts at passive restraint.[12]

Although initially described by Coulter and Allen as "bilateral, synchronous, and repetitive, located primarily in the distal parts of the upper extremities,"[1] the condition can cause unilateral, isolated, myoclonic limb movements that transition from one limb to another. The defining characteristic of this condition is resolution with waking and occurrence only during sleep. Infants are otherwise normal. Although some reports indicated an "offset" within the neonatal period, other larger retrospective series indicate that benign neonatal sleep myoclonus can extend later into infancy.[12] In fact, some suggest that this condition may persist beyond early infancy; most children sleep through the night during the latter part of the first year away from their parents, who are potentially unaware of the occurrence of this condition.

Indeed, parents often report that their older children jerk during sleep, although these are not typically described as repetitive as is seen in benign neonatal sleep myoclonus. Nocturnal myoclonus may represent a continuum; benign neonatal sleep myoclonus may be the most obvious and readily recognized manifestation, with diminished signs as the CNS matures, although this remains to be demonstrated. A genetic etiology is suspected, with reports of occurrence in multiple family members.[18, 19]

Attempts at treatment with anticonvulsants have been reported after movements were mistakenly attributed to epilepsy. Movements appeared to be exacerbated in two reports after benzodiazepine administration, perhaps invoking a GABA-mediated substrate.[9, 20] Apparent GABA-mediated, experimentally induced myoclonus has been reported.[21] Additionally, a preponderance of neuronal excitatory activity has been demonstrated in newborns, partially due to an excitatory effect of GABA in the immature brain.[22] 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 etiology 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 the condition.[23] Several case series report that parents themselves have identified these maneuvers.[12]

United States data

Although the true incidence is unknown, benign neonatal sleep myoclonus is likely underrecognized.[24] Although the condition is benign by definition, this condition often prompts extensive neurodiagnostic testing. Therefore, a broader understanding of its frequency and benign nature is important to establish among primary care providers to prevent complex, expensive, and largely unnecessary testing.

Race-, sex-, and age-related demographics

No race or sex predilection has been identified, and reports from around the world appear to support the ubiquitous nature of the condition.

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.[12] In this same series, resolution occurred over the next several months, although 22 of the children had resolution by age 2 months. As has been mentioned in the literature, 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.

By definition, benign neonatal sleep myoclonus is not due to serious neurologic injuries or abnormalities; as such, it resolves without residua.[25] Parents should be informed of the natural history of the condition to prevent undue worry and concern. Indeed, if neurologic comorbidity becomes evident in an affected child, a reconsideration of the diagnosis is indicated.

The prognosis is good, and no long-term residual sleep or neurobehavioral difficulties have been identified. Parents should be reassured that their child is normal and that no long-term implications are known. However, studies with follow-up longer than 1 year remain to be completed.

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 (BNSM), which are delineated in the International Classification of Sleep Disorders, revised: Diagnostic and Coding Manual (2nd and 3rd editions) (ICSD-2, ICSD-3), as follows[26, 27] :

• 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.[23] 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 BNSM who developed a pathologic form of myoclonus (ie, myoclonic-astatic epilepsy).[28] This association is likely incidental, and no clear evidence suggests that BNSM occurs in a continuum with other, more consequential forms of myoclonus.

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.[12] 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. In the author's experience, 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.

No long-term complications of benign neonatal sleep myoclonus are known. However, relatively small populations have been reported, and follow-up beyond 1 year has not been reported.

Benign neonatal sleep myoclonus (BNSM) closely mimics seizures, so it often prompts hospital admission and extensive diagnostic testing, including neurophysiologic studies, brain imaging, and screening for infection. A clear understanding of the condition is crucial to avoid unnecessary testing.

Laboratory Studies

If jitteriness or tetany remain in the differential diagnosis, screening for hypoglycemia and electrolyte disturbances is indicated.

Imaging Studies

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

Other Tests

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.

Medical care of benign neonatal sleep myoclonus (BNSM) consists of making a timely 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 of BNSM 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.

Inpatient care is warranted in patients with BNSM only if other risk factors for neurologic disease are evident, such as developmental concerns, deficits or abnormalities upon examination, or signs of metabolic or infectious disease. However, as mentioned above, inpatient care should be strongly considered if the movements have not been clearly identified as benign in nature by a medical provider.

No medication is necessary in benign neonatal sleep myoclonus. In fact, treatment with benzodiazepines and other anticonvulsants may worsen the movements because they may cause sedation and sleep.

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.

If clinical concern remains regarding the diagnosis, transfer the patient to a location where further neurodiagnostic testing and expertise can support the evaluation.

Outpatient care of the child with a clear history of benign neonatal sleep myoclonus is within the purview of a general pediatrician. Monitoring for other neurologic or developmental concerns is included in the standard recommendations for pediatric care in the first year of life.