Jenny L. Wilson

Krabbe disease (KD) is an autosomal recessive neurodegenerative lysosomal disease typically caused by pathogenic variants in GALC, which encodes for the lysosomal galactosylceramidase enzyme. Age of onset is variable, with earlier symptom onset conferring a more severe, and ultimately fatal, disease course. We present a case of an 18-month-old previously healthy female diagnosed with late-infantile KD following a 3-month period of psychomotor regression and irritability. Clinical features included severe axial hypotonia with lower extremity spasticity and hyperreflexia. Whole genome sequencing disclosed a complex GALC genotype including two likely pathogenic variants, p.(Gly284Ser) and p.(Tyr314del), which had not been observed in compound heterozygosity prior. Magnetic resonance imaging displayed symmetric T2 hyperintensity of the central-parietal white matter. The patient ultimately died 6 months after diagnosis from rapidly progressing neurological deterioration. There was significant atrophy on neuropathologic examination, with diffuse globoid cell infiltrate at the supratentorial and infratentorial white matter with relative sparing of the frontal lobe on light microscopy. This patient’s novel genotype, imaging and pathologic findings expand our understanding of the phenotype-genotype correlation in individuals with KD.

Background: Early‐onset hereditary spastic paraplegias (HSPs) are an underrecognized cause of progressive spasticity, gait impairment, and movement disorders in children and young adults. HSPs frequently mimic cerebral palsy or genetic, metabolic, and acquired disorders, resulting in diagnostic delay. Their broad phenotypic spectrum, encompassing dystonia, parkinsonism, and neurodevelopmental features, makes them highly relevant to movement disorder practitioners across the lifespan. Objectives: This review summarizes the phenotypic spectrum of early‐onset HSP, outlines a practical diagnostic approach for clinicians, and discusses therapeutic strategies. Methods: We conducted a narrative review of PubMed‐indexed literature through February 2026, supplemented by expert consensus. HSPs typically presenting in childhood and adolescence, inclusive of forms presenting across a broader age spectrum, with attention to subtypes presenting with movement disorders, were considered. Results: Early‐onset HSPs encompass both pure and complex forms, with SPG4 ( SPAST ) and SPG11 ( SPG11/KIAA1840 ) among the most prevalent etiologies. Diagnostic challenges include distinction from cerebral palsy and other movement disorders including dopa‐responsive dystonia, and identification of neuroimaging signatures in specific subtypes. A multidisciplinary management approach remains central, with spasticity, movement disorder, and neurological comorbidities each requiring targeted consideration. Disease‐modifying therapies are emerging, including gene replacement strategies and antisense oligonucleotide approaches for select subtypes. Conclusions: Early‐onset HSPs represent a clinically and genetically heterogeneous group with substantial overlap with movement disorder practice. Awareness of characteristic phenotypes, early genetic testing, and an individualized multidisciplinary approach are essential. Recent advances in natural history characterization and mechanism‐targeted therapeutics signal a transition toward disease‐modifying treatment strategies and offer cautious optimism for affected individuals.

Background and ObjectivesCardiac abnormalities are among the most common and complex risk factors of pediatric acute ischemic stroke (AIS). Although endovascular treatment (EVT) is increasingly use...

Background: Recent AHA guidelines recommend the use of IV Tenecteplase (TNK) in adult stroke patients, but there is minimal safety and dosing data on TNK in pediatric patients. We performed a safety surveillance study aiming to evaluate risk of symptomatic intracranial hemorrhage (ICH) in children who received TNK for suspected acute ischemic stroke (AIS). Methods: This was a prospective observational cohort surveillance study analyzing responses from a monthly email survey sent to members of two large international pediatric stroke and neurocritical care research consortia querying recent use of TNK in children. Limited demographic, clinical, and outcome data were collected. A Bayesian beta-binomial model for risk of symptomatic ICH with IV TNK was fit using a prior distribution based on the risk level in adults. Results: Between February 2023-June 2026, 44 children received TNK for suspected AIS. Most patients (n=37, 84.1%) were adolescents; no children under 5 received TNK. Twelve patients (27.3%) were ultimately diagnosed with a stroke mimic. Symptomatic ICH was not reported in any children who received IV TNK; 3 had asymptomatic ICH on follow-up imaging. One patient received intra-arterial TNK and experienced symptomatic ICH. No other major bleeding events were reported. Conclusions: IV TNK is being administered to pediatric patients with suspected stroke in clinical practice, and may be safe in older children with AIS. Rigorous prospective studies are needed to better assess risk and outcomes in this unique population.

Aim: To prospectively characterize the age of developmental milestone attainment and loss, disease milestone acquisition, and associations between a quality of life measure and age in 40 children with infantile PLA2G6 ‐associated neurodegeneration (PLAN). Method: We analysed developmental and disease milestones and health‐related quality of life scores from the 97‐item Infant Toddler Quality of Life Questionnaire (ITQOL‐97) in a prospective, observational, longitudinal natural history study. Developmental and disease milestone attainments were visualized as histograms and Kaplan–Meier curves respectively. We used mixed‐effects linear regression to assess the associations between ITQOL‐97 domains and age and to compare marginal predictions to a US reference population. Results: The study group was comprised of 19 males and 21 females with a mean age at enrollment of 5 years 1 month (SD 3 years; range 1 year 7 months–16 years 8 months). Over the course of the disease, children continued to vocalize, smile, and laugh, while other milestones like walking were rarely met at any time. ITQOL‐97 domains differed significantly from a US reference population in all areas except for ‘general behavior’. The ‘physical abilities’ domain had the greatest change with age (−6.24 per year). Interpretation: In this first prospective natural history study of infantile PLAN, we characterize developmental and disease milestones, and longitudinal associations, with quality of life metrics. These data will provide valuable disease norms for use as clinical references and in the design of interventional trials.

BACKGROUND: Acute respiratory infection transiently increases risk for childhood arterial ischemic stroke (AIS). We hypothesize that this paradox of a common exposure linked to a rare outcome could be explained by either (1) the infection hypothesis: unusual or multiple pathogens or (2) the host response hypothesis: heterogeneity in the inflammatory response to infection. We leverage metagenomic next-generation sequencing (mNGS), a comprehensive microbial detection tool, to test the first hypothesis. METHODS: The VIPS II study (Vascular Effects of Infection in Pediatric Stroke II) prospectively enrolled children with AIS at 22 international sites over 5 years (December 2016 to January 2022). Sites measured prestroke clinical infection via standardized parental interviews and chart abstraction. To assess more broadly the background spectrum of pathogens, a central research laboratory performed mNGS on plasma and oropharyngeal swabs collected within 72 hours of stroke. mNGS was also performed on biological samples from stroke-free children (June 2017 to January 2022), both without (well) and with (ill) documentation of clinical infection. RESULTS: VIPS II enrolled 205 patients with AIS, 95 stroke-free well children, and 47 stroke-free ill children. Clinical infection, most commonly upper respiratory tract infection, was detected in 81 of 205 (40%) of patients. Both plasma and oropharyngeal swab mNGS data were available for 190 of 205 patients with AIS, 91 of 95 stroke-free well children, and 27 of 47 stroke-free ill children. mNGS detected viruses in 27 of 190 (14%) patients with AIS, 9 of 91 stroke-free well children (10%), and 9 of 27 (33%) stroke-free ill children. Most were common upper respiratory viruses. Coinfections were rare. Similar viruses were found in patients with AIS and stroke-free children. CONCLUSIONS: mNGS detected a variety of common childhood viruses in both patients with AIS and stroke-free children, suggesting that the type of infection does not explain AIS susceptibility. Rather, the alternative hypothesis regarding an unusual host immune response to common infections in the pathogenicity of AIS should be further explored.

This clinical guideline provides recommendations for the evaluation and management of individuals with PLA2G6- associated neurodegeneration (PLAN). PLAN, a neurodegeneration with brain iron accumulation disorder, presents with infantile-onset (infantile neuroaxonal dystrophy), juvenile-onset, and adult-onset forms with motor, cognitive, ophthalmologic, and autonomic symptoms. This guideline was developed using a modified Delphi process with input from PLAN experts and family members of individuals with PLAN. A literature search was performed, although in the absence of data, recommendations were based on expert opinion. The guideline contains recommendations on diagnostic approach, disease-specific treatment, and symptom-based management.