Benign Neonatal Sleep Myoclonus

Background
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. A thorough understanding of the phenomenon is crucial to avoid
unnecessary testing.
Pathophysiology
Myoclonus has various potential causes and may arise from a wide array of
sites in the peripheral nervous system and CNS. [3, 4] Although dysfunctional
serotonin neurotransmission is a potential cause, it does not appear to be the
cause in all cases, and data are somewhat contradictory. [5] 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. [6] 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. [7]
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. [6, 8,9, 10] 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. [11, 12] 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. [13]
Myoclonus itself can arise from various locations within the CNS and even the
peripheral nervous system. [3] 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. [14] 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. [14]
Pathologic myoclonus in the newborn is typically associated with
manifestations of encephalopathy, seizures, or both. [15] 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. [11]
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. [11] 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. [16, 17]
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. [8, 18] Apparent GABA-mediated,
experimentally induced myoclonus has been reported. [19] Additionally, a
preponderance of neuronal excitatory activity has been demonstrated in
newborns, partially due to an excitatory effect of GABA in the immature
brain. [20] 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. [21]Several case series report that parents themselves
have identified these maneuvers. [11]
Epidemiology
Frequency
United States
Although the true incidence is unknown, benign neonatal sleep myoclonus is
likely underrecognized. [22] 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.
Mortality/Morbidity
By definition, benign neonatal sleep myoclonus is not due to serious
neurologic injuries or abnormalities; as such, it resolves without residua.
Parents should be reassured and should also understand 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.
Race
No race or sex predilection has been identified, and reports from around the
world appear to support the ubiquitous nature of the condition.
Age
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. [11] 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.

History
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 [23, 24] :
 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. [21] 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). [25] 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.
Physical
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. [11] 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.
Causes
The cause of benign neonatal sleep myoclonus is unknown. However, 2
reports indicate a probable genetic contribution, with several individuals
affected within 2 pedigrees. [16, 17]

Diagnostic Considerations
Important considerations
If benign neonatal sleep myoclonus (BNSM) is misidentified as epilepsy, treatment
could result in a medicolegal challenge, especially because the medication-related side
effects of anticonvulsants have become better recognized. Therefore, careful screening
for epilepsy and consultation with a pediatric neurologist is recommended if treatment is
to be started or continued. Likewise, if benign neonatal sleep myoclonus is considered,
one must ensure that no other risk factors for epilepsy are present and that an
experienced provider makes this diagnosis. A missed diagnosis of epilepsy is a clear
medicolegal risk; therefore, this must be screened for carefully.
Numerous conditions are similar to benign neonatal sleep myoclonus (BNSM), including
nocturnal myoclonus, [26] and the brief, isolated jerks (ie, hypnic jerks) that often occur in
healthy individuals into adulthood upon initiation of sleep. [27] Benign neonatal essential
myoclonus is typically noted in older infants and generally not during sleep, which is an
important distinction.
Differential Diagnoses
 Benign neonatal convulsions
 Electrolyte disturbance
 Epilepsy
 Fifth-day fits
 Hyperekplexia
 Neonatal jitteriness
 Pathologic myoclonus
  Pediatric Aseptic Meningitis
 Pediatric Bacterial Meningitis
Laboratory Studies
If jitteriness or tetany remain in the differential diagnosis, screening
for hypoglycemia and electrolyte disturbances is indicated.
Imaging Studies
Once benign neonatal sleep myoclonus (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
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 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.
Consultations
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.
Medication Summary
No medication is necessary in benign neonatal sleep myoclonus.

Further Outpatient Care

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.
Further Inpatient Care
Further inpatient care is warranted in patients with benign neonatal sleep
myoclonus (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.
Inpatient & Outpatient Medications
No medications are indicated; in fact, treatment with benzodiazepines and
other anticonvulsants may worsen the movements because they may cause
sedation and sleep.
Transfer
If clinical concern remains regarding the diagnosis, transfer the patient to a
location where further neurodiagnostic testing and expertise can support the
evaluation.
Complications
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.
Prognosis
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.