Monica E. Lemmon

Efficacy of the ketogenic diet in Lennox–Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature

Aim  To determine the efficacy of the ketogenic diet for children with Lennox–Gastaut syndrome (LGS) at our institution and in the literature.

Risperidone use in autism spectrum disorders: A retrospective review of a clinic-referred patient population

Risperidone is widely used in children with autism spectrum disorders for behavioral modification. In this study, the authors aimed to (1) describe a clinic-referred sample of patients with an autism spectrum disorder on risperidone, (2) identify differences between the success and nonsuccess groups, and (3) describe our experience with young children (< age 5 years) on risperidone. Eighty patients were initiated on risperidone. Indications included aggression (66%), impulsivity (14%), and stereotypies (4%). Sixty-six percent met criteria for success at 6 months and 53% at 1 year. Sixty-seven percent of the nonsuccess group reported side effects, compared to 47% of the success group. Weight gain was the most common side effect in both groups, followed by somnolence. Somnolence was the most robust predictor of nonsuccess. In our clinic-referred sample, the short-term success rate of risperidone was more than 50%, and side effects limited its use. Although weight gain was common, somnolence more significantly influenced treatment discontinuation.

Genotype–Phenotype Correlation of Congenital Anomalies in Multiple Congenital Anomalies Hypotonia Seizures Syndrome (MCAHS1)/ PIGN-Related Epilepsy

Mutations in PIGN, resulting in multiple congenital anomalies‐hypotonia‐seizures syndrome, a glycosylphosphatidylinositol anchor deficiency, have been published in four families to date. We report four patients from three unrelated families with epilepsy and hypotonia in whom whole exome sequencing yielded compound heterozygous variants in PIGN. As with previous reports Patients 1 and 2 (full siblings) have severe global developmental delay, gastroesophageal reflux disease, and minor dysmorphic features, including high palate, bitemporal narrowing, depressed nasal bridge, and micrognathia; Patient 3 had early global developmental delay with later progressive spastic quadriparesis, intellectual disability, and intractable generalized epilepsy; Patient 4 had bilateral narrowing as well but differed by the presence of hypertelorism, markedly narrow palpebral fissures, and long philtrum, had small distal phalanges of fingers 2, 3, and 4, absent distal phalanx of finger 5 and similar toe anomalies, underdeveloped nails, unusual brain anomalies, and a more severe early clinical course. These patients expand the known clinical spectrum of the disease. The severity of the presentations in conjunction with the patients’ mutations suggest a genotype–phenotype correlation in which congenital anomalies are only seen in patients with biallelic loss‐of‐function. In addition, PIGN mutations appear to be panethnic and may be an underappreciated cause of epilepsy.

New Treatment Options for Lennox-Gastaut Syndrome

Opinion statementLennox-Gastaut syndrome (LGS) is one of the most difficult epilepsy syndromes to treat, and many children are refractory to standard treatment regimens. Valproic acid, topiramate, and lamotrigine are considered first-line therapies. Newer agents, including clobazam and rufinamide, are promising additions to the current treatment options. The ketogenic diet and vagus nerve stimulation are important adjuncts, with increasing evidence to support their use. Corpus callosotomy should be considered in refractory cases. Finally, focal resective surgery should be considered in patients with lesional disease, although for most patients with LGS this is unlikely to be the case.

A novel presentation of DYT 16: Acute onset in infancy and association with MRI abnormalities

Department of Neurology, The Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD Department of Neurology, Children’s National Medical Center, George Washington University, District of Columbia McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD

Communication Challenges in Neonatal Encephalopathy

BACKGROUND: Families must process complex information related to neonatal encephalopathy and therapeutic hypothermia. METHODS: In this mixed methods study, semi-structured interviews were performed with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. RESULTS: Thematic saturation was achieved after 20 interviews. Parental experience of communicating with clinicians was characterized by 3 principle themes. Theme 1 highlighted that a fragmented communication process mirrored the chaotic maternal and neonatal course. Parents often received key information about neonatal encephalopathy and therapeutic hypothermia from maternal clinicians. Infant medical information was often given to 1 family member (60%), who felt burdened by the responsibility to relay that information to others. Families universally valued the role of the bedside nurse, who was perceived as the primary source of communication for most (75%) families. Theme 2 encompassed the challenges of discussing the complex therapy of therapeutic hypothermia: families appreciated clinicians who used lay language and provided written material, and they often felt overwhelmed by technical information that made it hard to understand the “big picture” of their infant’s medical course. Theme 3 involved the uncertain prognosis after neonatal encephalopathy. Parents appreciated specific expectations about their infant’s long-term development, and experienced long-term distress about prognostic uncertainty. CONCLUSIONS: Communicating complex and large volumes of information in the midst of perinatal crisis presents inherent challenges for both clinicians and families. We identified an actionable set of communication challenges that can be addressed with targeted interventions.

Clinical and neuroimaging features as diagnostic guides in neonatal neurology diseases with cerebellar involvement

Cerebellar abnormalities are encountered in a high number of neurological diseases that present in the neonatal period. These disorders can be categorized broadly as inherited (e.g. malformations, inborn errors of metabolism) or acquired (e.g. hemorrhages, infections, stroke). In some disorders such as Dandy-Walker malformation or Joubert syndrome, the main abnormalities are located within the cerebellum and brainstem. In other disorders such as Krabbe disease or sulfite oxidase deficiency, the main abnormalities are found within the supratentorial brain, but the cerebellar involvement may be helpful for diagnostic purposes. In In this article, we review neurological disorders with onset in the neonatal period and cerebellar involvement with a focus on how characterization of cerebellar involvement can facilitate accurate diagnosis and improved accuracy of neuro-functional prognosis.

Diffusion Tensor Imaging Detects Occult Cerebellar Injury in Severe Neonatal Hypoxic-Ischemic Encephalopathy

Background: Despite the benefits of whole-body hypothermia therapy, many infants with hypoxic-ischemic encephalopathy (HIE) die or have significant long-term neurodevelopmental impairment. Prospectively identifying neonates at risk of poor outcome is essential but not straightforward. The cerebellum is not classically considered to be a brain region vulnerable to hypoxic-ischemic insults; recent literature suggests, however, that the cerebellum may be involved in neonatal HIE. In this study, we aimed to assess the microstructural integrity of cerebellar and linked supratentorial structures in neonates with HIE compared to neurologically healthy neonatal controls. Methods: In this prospective cohort study, we performed a quantitative diffusion tensor imaging (DTI) analysis of the structural pathways of connectivity, which may be affected in neonatal cerebellar injury by measuring fractional anisotropy (FA) and mean diffusivity (MD) within the superior, middle, and inferior cerebellar peduncles, dentate nuclei, and thalami. All magnetic resonance imaging (MRI) studies were grouped into 4 categories of severity based on a qualitative evaluation of conventional and advanced MRI sequences. Multivariable linear regression analysis of cerebellar scalars of patients and controls was performed, controlling for gestational age, age at the time of MRI, and HIE severity. Spearman rank correlation was performed to correlate DTI scalars of the cerebellum and thalami. Results: Fifty-seven (23 females, 40%) neonates with HIE and 12 (6 females, 50%) neonatal controls were included. There were 8 patients (14%) in HIE severity groups 3 and 4 (injury of the basal ganglia/thalamus and/or cortex). Based on a qualitative analysis of conventional and DTI images, no patients had evidence of cerebellar injury. No significant differences between patients and controls were found in the FA and MD scalars. However, FA values of the middle cerebellar peduncles (0.294 vs. 0.380, p < 0.001) and MD values of the superior cerebellar peduncles (0.920 vs. 1.007 × 10-3 mm/s2, p = 0.001) were significantly lower in patients with evidence of moderate or severe injury on MRI (categories 3 and 4) than in controls. In patients, cerebellar DTI scalars correlated positively with DTI scalars within the thalami. Conclusion: Our results suggest that infants with moderate-to-severe HIE may have occult injury of cerebellar white-matter tracts, which is not detectable by the qualitative analysis of neuroimaging data alone. Cerebellar DTI scalars correlate with thalamic measures, highlighting that cerebellar injury is unlikely to occur in isolation and may reflect the severity of HIE. The impact of concomitant cerebellar injury in HIE on long-term neurodevelopmental outcome warrants further study.

Distinguishing Arterial Ischemic Stroke from Hypoxic-Ischemic Encephalopathy in the Neonate at Birth

OBJECTIVE: To identify perinatal risk factors that can distinguish arterial ischemic stroke from hypoxic–ischemic encephalopathy at birth. METHODS: This is a cohort study of all neonates born at 35 weeks of gestation or greater admitted to our neonatal intensive care unit from January 1, 2010, to December 31, 2015, that compares neonates with stroke with those with hypoxic–ischemic encephalopathy undergoing whole-body hypothermia with abnormal brain magnetic resonance imaging. RESULTS: During this 6-year period, there were 22 neonates with stroke and 47 with hypoxic–ischemic encephalopathy undergoing whole-body hypothermia with abnormal magnetic resonance imaging. Three neonates triaged to hypothermia initially thought to have hypoxic–ischemic encephalopathy were later diagnosed with stroke. All neonates with stroke had a negative thrombophilia workup. Neonates with stroke had a significantly higher incidence of seizures and increased initial platelet counts on univariate analysis. A multivariable model of variables with P<.1 on univariate analysis present within 6 hours of birth found significant increases in nonreassuring fetal heart rate tracings, sentinel events, low Apgar score at 5 minutes, and metabolic acidosis at birth with hypoxic–ischemic encephalopathy. Stroke was associated with a significantly increased initial platelet count. CONCLUSION: Stroke is associated with increased initial platelet counts and is not associated with cesarean delivery for nonreassuring fetal heart rate tracings, sentinel events, or perinatal metabolic acidosis. Stroke is a form of neonatal brain injury not associated with perinatal risk factors that allow early identification.

Palliative care in neonatal neurology: robust support for infants, families and clinicians

Infants with neurological injury and their families face unique challenges in the neonatal intensive care unit. As specialty palliative care support becomes increasingly available, we must consider how to intentionally incorporate palliative care principles into the care of infants with neurological injury. Here, we review data regarding neonatal symptom management, prognostic uncertainty, decision making, communication and parental support for neonatal neurology patients and their families.