Clinical perspectives: Treating spinal muscular atrophy.

Spinal muscular atrophy is a rare and progressive neuromuscular disease that, without treatment, leads to progressive weakness and often death. A plethora of studies have led to the approval of three high-cost and effective treatments since 2016. These treatments, nusinersen, onasemnogene abeparvovec, and risdiplam, have not been directly compared and have varying challenges in administration. In this review, we discuss the evidence supporting the use of these medications, the process of treatment selection, monitoring after treatment, the limited data comparing treatments, as well as future directions for investigation and therapy.

Challenging Neuromuscular Disease Cases.

The diagnosis of neuromuscular disorders requires a thorough history including family history and examination, with the next steps broadened now beyond electromyography and neuropathology to include genetic testing. The challenge in diagnosis can often be putting all the information together. With advances in genetic testing, some diagnoses that adult patients may have received as children deserve a second look and may result in diagnoses better defined or alternative diagnoses made. Clearly defining or redefining a diagnosis can result in understanding of potential other systems involved, prognosis, or potential treatments. This article presents several cases and approach to diagnosis as well as potential treatment and prognostic concerns, including seipinopathy, congenital myasthenic syndrome, central core myopathy, and myotonic dystrophy type 2.

Creating a New Set of Milestones for the Clinical Neurophysiology Fellowship.

INTRODUCTION: The Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology first developed milestones for the clinical neurophysiology (CNP) fellowship in 2015. The milestones provide a comprehensive evaluation of the fellow's development based on six domains of competency. Here, we describe the development of a new set of milestones for CNP fellowship with level 1 as the incoming level, level 4 as the goal for graduation, and level 5 as the aspirational level that may not be achieved. METHODS: Committee members were nominated or volunteered to participate in the milestones update. Milestone development began with the creation of a shared mental model of the ideal skills and knowledge a graduating CNP fellow should attain. RESULTS: The CNP committee met virtually 7 times for a total of 14 meeting hours. Nine Patient Care and five Medical Knowledge milestones evolved from the seven Patient Care and six Medical Knowledge milestones that were in the first iteration. The committee incorporated 11 "Harmonized Milestones" into the revision and a supplemental guide was created. CONCLUSIONS: The revised Accreditation Council for Graduate Medical Education milestones for CNP fellowship contain important updates that program directors should review against their curricula to identify any gaps in learning. Program leadership should take note of two new Patient Care milestones for telemedicine and intraoperative monitoring. Clinical neurophysiology fellowships are not designed to provide level 4 competency across all milestones. The revised milestones should be viewed within the context of an individual program's goals.

Early cognitive and behavioral problems in children with nodular heterotopia.

Adults with periventricular nodular heterotopia (PNH) have epilepsy and dyslexia, but most have normal intelligence. It is not known whether PNH-related reading difficulty can be detected earlier in childhood or whether associated behavioral problems are present. We studied 10 children with PNH, 3 of whom did not have seizures, and 10 matched controls with neuropsychological testing and parental rating instruments at two time points separated by about 1 year. Children with PNH performed significantly worse than controls on a task related to reading fluency. In addition, those with PNH showed significantly worse adaptive skills, and a measure of conduct problems significantly worsened over time. Mood and behavioral problems were reported more commonly, though not significantly so, in children with PNH. These findings demonstrate that reading dysfluency can be evident in children with nodular heterotopia, even in the absence of epilepsy, but also highlight difficulties with behavior in this population.

Patients With Extreme Early Onset Juvenile Huntington Disease Can Have Delays in Diagnosis: A Case Report and Literature Review.

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

Guillain-Barré Syndrome in a Child With COVID-19 Infection.

Guillain-Barré syndrome (GBS) is characterized by a monophasic, ascending, and symmetrical paralysis with areflexia that progresses over days to weeks. It is typically a postinfectious autoimmune process that leads to destruction of myelin. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China, in late 2019 and rapidly spread around the world, causing a pandemic of novel coronavirus disease 2019 (COVID-19). There have been scattered reports of adults with possible GBS and concurrent evidence of COVID-19, but no previous reports in children. The patient is an 8-year-old boy who presented to the emergency department with progressive, ascending weakness with areflexia. He was intubated for airway protection because of poor secretion control. MRI of the spine revealed abnormal enhancement of posterior nerve roots. A lumbar puncture revealed albuminocytologic dissociation with 1 nucleated cell per mm3 and a protein level of 620 mg/dL. Electrodiagnostic findings were compatible with sensorimotor demyelinating polyneuropathy. The lumbar puncture, MRI, and electrodiagnostics were all consistent with GBS. Results of SARS-CoV-2 nucleic acid amplification and SARS-CoV-2 immunoglobulin G antibody tests were positive. Treatment was initiated with intravenous immunoglobulin; he received a total of 2 g/kg. His neurologic examination revealed improvement in the subsequent days. He was extubated after 4 days of intubation. This case is the first reported case of a child with GBS in the setting of an acute COVID-19 infection. This case reveals the wide scope of presentations of COVID-19 and postinfectious processes. Clinicians should constantly have a high level of suspicion for COVID-19.

Developing a New Set of ACGME Milestones for Child Neurology Residency.

BACKGROUND: The Educational Milestones developed by the Accreditation Council for Graduate Medical Education (ACGME) are a construct used to evaluate the development of core competencies during residency and fellowship training. The milestones were developed to create a framework for professional development during graduate medical education. The first iteration of milestones for the child neurology residency was implemented in 2015. In the years that followed, the ACGME received and reviewed feedback about the milestones and set out to revise them. METHODS: A committee was assembled to review the original milestones and develop a new set of milestones. The group was also encouraged to not only consider the child neurology residency graduate of today but also the graduate of tomorrow, taking into account growing fields such as genetics and technology. RESULTS: A diverse group of 12 individuals, including 10 child neurologists (all of whom were current or previous program directors or associate program directors), one child neurology resident, and one non-physician program coordinator, were recruited from programs of varying size across the country. CONCLUSIONS: The committee developed a revision to the child neurology milestones. All changes made were with a focus on how the milestones can be useful to trainees, program directors, and clinical competency committee members. Implementation and further feedback should help guide future revisions. These changes should help trainees, clinical competency committee members, and program directors find more meaning from their use.

Failure of a clot retrieval device in an adolescent stroke patient.

A previously healthy 14-year-old boy collapsed after a football game, with aphasia and right hemiparesis. Cranial magnetic resonance imaging and magnetic resonance angiography revealed left middle cerebral artery distribution ischemic infarct with thrombus and possible dissection at the horizontal segment of the middle cerebral artery. The patient was treated 9 hours after collapse with intra-arterial tissue plasminogen activator, but without success. The Merci clot retrieval device was then used, but the device broke in the middle cerebral artery and led to complete occlusion. At follow-up 3 months later, the boy had persistent aphasia, but notable improvement in his right hemiparesis. This is a novel report of a complication of mechanical clot retrieval treatment in a child. Further research is needed to determine the safety and effectiveness of intracranial endovascular clot retrieval devices in children.

Proximal muscle weakness in a 15-year-old boy.

Proximal muscle weakness, often indicative of a myopathy, has a broad differential diagnosis in children. We present a case of an adolescent boy with proximal weakness and a mildly elevated creatine kinase. He was found to have spinal muscular atrophy type III rather than a myopathy.