Patient headache questionnaires can improve headache diagnosis and treatment in children.

Objective: To examine trends in diagnosis of headache and migraine in a large pediatric neurology cohort, and test whether an electronic health record (EHR)-integrated headache questionnaire can increase specificity of diagnosis and likelihood of prescribing migraine treatment.

Background: Under-diagnosis of migraine contributes to the burden of disease. As we founded our Pediatric Headache Program in 2013, we recognized that the proportion of patients with headache who were given a diagnosis of migraine was much lower than expected.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology.

Nusinersen Treatment in Adults With Spinal Muscular Atrophy.

Objective: To determine changes in motor and respiratory function after treatment with nusinersen in adults with spinal muscular atrophy (SMA) during the first two years of commercial availability in the USA.

Methods: Data were collected prospectively on adult (age >17 years at treatment initiation) SMA participants in the Pediatric Neuromuscular Clinical Research (PNCR) Network. Baseline assessments of SMA outcomes including the Expanded Hammersmith Functional Rating Scale (HFMSE), Revised Upper Limb Module (RULM), and 6-Minute Walk Test (6MWT) occurred <5 months before treatment, and post-treatment assessments were made up to 24 months after nusinersen initation.

Friedreich Ataxia: Multidisciplinary Clinical Care.

Friedreich ataxia (FRDA) is a multisystem disorder affecting 1 in 50,000-100,000 person in the United States. Traditionally viewed as a neurodegenerative disease, FRDA patients also develop cardiomyopathy, scoliosis, diabetes and other manifestation. Although it usually presents in childhood, it continues throughout life, thus requiring expertise from both pediatric and adult subspecialist in order to provide optimal management.

Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disease caused by biallelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterized by motor neuron degeneration, resulting in progressive muscle atrophy and weakness. Before the emergence of disease-modifying therapies, children with the most severe form of SMA would never achieve the ability to sit independently.

Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy.

Background: Onasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019. Here, we look at the safety and efficacy of onasemnogene in seven infants older than seven months who were treated at our center.

Methods: Seven patients were included.

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study.

Objective: To describe the respiratory trajectories and their correlation with motor function in an international pediatric cohort of patients with type 2 and nonambulant type 3 spinal muscular atrophy (SMA).

Methods: This was an 8-year retrospective observational study of patients in the International SMA Consortium (iSMAc) natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC percent predicted (FVC%P), and noninvasive ventilation (NIV) requirement.

Clinical Course in a Patient With Spinal Muscular Atrophy Type 0 Treated With Nusinersen and Onasemnogene Abeparvovec.

Spinal muscular atrophy type 0 is the most severe phenotype of the disease, with patients presenting with contractures, weakness, and respiratory failure at birth, and is typically fatal within weeks. We describe the case of a patient with spinal muscular atrophy type 0 who was treated with both nusinersen and onasemnogene abeparvovec. She has made modest motor improvements since treatment initiation with a 30-point improvement in CHOP-INTEND score, and continues to make motor gains at age 13 months without regression of function, although she remains profoundly weak.

A multidisciplinary approach to dosing nusinersen for spinal muscular atrophy.

Background: In December 2016, nusinersen gained FDA approval as the first pharmacologic treatment for spinal muscular atrophy (SMA), a disorder of motor neurons and the leading genetic cause of infant mortality. Nusinersen's intrathecal delivery requirement, strict dosage protocol, and accelerated FDA approval presented a challenge to health care centers hoping to implement treatment of patients with SMA. Scheduling logistics, combined with the specific ventilatory, anesthetic, and spinal access needs of this patient population, requires extensive coordination of care.

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α-subunit of the voltage-gated Ca2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission.

Pediatric Ataxia: Focus on Chronic Disorders.

Evaluation of a pediatric patient presenting with ataxia can be expensive and time consuming. Acute causes tend to have a clear developmental paradigm, but chronic presentations are more likely to be secondary to a genetic disorder, either one that primarily causes ataxia or that presents ataxia as one of a multitude of symptoms. Evaluation should focus on a quick diagnosis for those that have treatment options and for those that require other systemic monitoring.

Developmental and comparative aspects of posterior medial thalamocortical innervation of the barrel cortex in mice and rats.

The thalamocortical projection to the rodent barrel cortex consists of inputs from the ventral posterior medial (VPM) and posterior medial (POm) nuclei that terminate in largely nonoverlapping territories in and outside of layer IV. This projection in both rats and mice has been used extensively to study development and plasticity of highly organized synaptic circuits. Whereas the VPM pathway has been well characterized in both rats and mice, organization of the POm pathway has only been described in rats, and no studies have focused exclusively on the development of the POm projection.