Nerve Transfer Surgery in Acute Flaccid Myelitis: Prognostic Factors, Long-Term Outcomes, Comparison With Natural History.

Background: Nerve transfer surgery is sometimes offered to patients with acute flaccid myelitis (AFM). The objectives of this study were to evaluate surgical efficacy, assess which clinical and neurophysiological data are valuable for preoperative planning, and report long-term outcomes.

Methods: This is a single-center, retrospective case series of patients with AFM who received nerve transfer surgery.

Frequency, facilitators, and barriers for range of motion to prevent shoulder contracture in brachial plexus birth injury: A pilot study.

Purpose: This pilot study investigated the efficacy of passive range of motion (PROM) during the first year of life to prevent development of shoulder contractures in children with brachial plexus birth injury (BPBI) and identified facilitators and barriers to caregiver adherence with daily PROM.

Methods: Five caregivers of children with upper trunk BPBI participated in retrospective interviews about the frequency with which they performed PROM during their child's first year of life including facilitators and barriers to daily adherence. Medical records were reviewed for documentation of caregiver-reported adherence and documented evidence of shoulder contracture by age one.

Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury.

Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage.

Enterovirus D68 molecular and cellular biology and pathogenesis.

In recent years, enterovirus D68 (EV-D68) has advanced from a rarely detected respiratory virus to a widespread pathogen responsible for increasing rates of severe respiratory illness and acute flaccid myelitis (AFM) in children worldwide. In this review, we discuss the accumulating data on the molecular features of EV-D68 and place these into the context of enterovirus biology in general. We highlight similarities and differences with other enteroviruses and genetic divergence from own historical prototype strains of EV-D68.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses.

Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy.

Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs). In this report, we describe 12 individuals from nine unrelated families with 10 different bi-allelic PIGK variants.

Clinical Subpopulations in a Sample of North American Children Diagnosed With Acute Flaccid Myelitis, 2012-2016.

Importance: Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease.

Heat Shock Protein Beta-1 Modifies Anterior to Posterior Purkinje Cell Vulnerability in a Mouse Model of Niemann-Pick Type C Disease.

Selective neuronal vulnerability is characteristic of most degenerative disorders of the CNS, yet mechanisms underlying this phenomenon remain poorly characterized. Many forms of cerebellar degeneration exhibit an anterior-to-posterior gradient of Purkinje cell loss including Niemann-Pick type C1 (NPC) disease, a lysosomal storage disorder characterized by progressive neurological deficits that often begin in childhood. Here, we sought to identify candidate genes underlying vulnerability of Purkinje cells in anterior cerebellar lobules using data freely available in the Allen Brain Atlas.

Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis.

Alterations in macroautophagy (hereafter referred to as "autophagy") are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lipids to the lysosome via autophagy.

Apolipoprotein E genotype and neurological disease onset in Niemann-Pick disease, type C1.

Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder that results in progressive neurological impairment. The NPC1 phenotype is extremely variable and at the individual level is likely influenced by other genetic traits. In addition to residual function of NPC1 protein, we hypothesize that modifier genes, as frequently observed with other autosomal recessive diseases, influence the NPC phenotype.

Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C disease.

Niemann-Pick type C disease (NPC) is a childhood onset neurodegenerative disorder arising from lipid-trafficking defects caused by mutations in the NPC1 or NPC2 gene. Marked accumulation of autophagosomes is a prominent feature of NPC cells, yet a detailed understanding of the disease-associated alterations in autophagy and their role in pathogenesis has been lacking. Prior studies have shown that lipid storage in NPC disease induces autophagy.

Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration.

Pathways regulating neuronal vulnerability are poorly understood, yet are central to identifying therapeutic targets for degenerative neurological diseases. Here, we characterize mechanisms underlying neurodegeneration in Niemann-Pick type C (NPC) disease, a lysosomal storage disorder characterized by impaired cholesterol trafficking. To date, the relative contributions of neuronal and glial defects to neuron loss are poorly defined.

Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis.

Hyperphosphorylation and aggregation of the microtubule-binding protein tau characterize a diverse array of neurodegenerative disorders. Most of these lack mutations in the encoding MAPT gene, and the role of tau in disease pathogenesis remains controversial. Among these tauopathies is Niemann-Pick type C disease (NPC), a lysosomal storage disorder characterized by progressive neurodegeneration and premature death, most often caused by an inherited deficiency in the intracellular lipid trafficking protein NPC1.

Sphingosine, a product of ceramide hydrolysis, influences the formation of ceramide channels.

Ceramides are known to have a regulatory function in apoptosis, including the release of cytochrome c and other proapoptotic factors from the mitochondrial intermembrane space. Ceramides can form large, stable channels in the outer mitochondrial membrane, leading to the proposal that ceramide channels are the pathway through which these proteins are released. Here, we report that sphingosine, a product of ceramide hydrolysis by ceramidase, is capable of destabilizing ceramide channels, leading to their disassembly.