Lyme Disease and Papilledema: A Retrospective Study on Clinical Characteristics and Outcomes.

Objective: Describe the clinical characteristics, treatment strategies, and outcome data of children with papilledema associated with Lyme disease at a large tertiary care pediatric hospital.

Methods: Retrospective cohort study of children 1-18 years old who received care at our institution between 1995 and 2019 with concurrent diagnoses of papilledema and Lyme disease. Data were abstracted from records and prospective family surveys.

Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures.

Early-life seizures (ELSs) can cause permanent cognitive deficits and network hyperexcitability, but it is unclear whether ELSs induce persistent changes in specific neuronal populations and whether these changes can be targeted to mitigate network dysfunction. We used the targeted recombination of activated populations (TRAP) approach to genetically label neurons activated by kainate-induced ELSs in immature mice. The ELS-TRAPed neurons were mainly found in hippocampal CA1, remained uniquely susceptible to reactivation by later-life seizures, and displayed sustained enhancement in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated (AMPAR-mediated) excitatory synaptic transmission and inward rectification.

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report.

Background: Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders.

Psychometric outcome measures in beta-propeller protein-associated neurodegeneration (BPAN).

Background: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurodegenerative disorder characterized by iron accumulation in the brain with spectrum of neurodevelopmental and movement phenotypes. In anticipation of future clinical trials and to inform clinical care, there is an unmet need to capture the phenotypic diversity of this rare disorder and better define disease subtypes.

Methods: A total of 27 individuals with BPAN were included in our natural history study, from which traditional outcome measures were obtained in 18 subjects.

ERK/MAPK signaling and autism spectrum disorders.

The MAPK pathway is a prominent intracellular signaling pathway regulating various intracellular functions. Components of this pathway are mutated in a related collection of congenital syndromes collectively referred to as neuro-cardio-facio-cutaneous syndromes (NCFC) or Rasopathies. Recently, it has been appreciated that these disorders are associated with autism spectrum disorders (ASD).

Pharmacological Inhibition of ERK Signaling Rescues Pathophysiology and Behavioral Phenotype Associated with 16p11.2 Chromosomal Deletion in Mice.

The human microdeletion is one of the most common gene copy number variations linked to autism, but the pathophysiology associated with this chromosomal abnormality is largely unknown. The 593 kb deletion contains the ERK1 gene and other genes that converge onto the ERK/MAP kinase pathway. Perturbations in ERK signaling are linked to a group of related neurodevelopmental disorders hallmarked by intellectual disability, including autism.

Chronic impairment of ERK signaling in glutamatergic neurons of the forebrain does not affect spatial memory retention and LTP in the same manner as acute blockade of the ERK pathway.

The ERK/MAPK signaling pathway has been extensively studied in the context of learning and memory. Defects in this pathway underlie genetic diseases associated with intellectual disability, including impaired learning and memory. Numerous studies have investigated the impact of acute ERK/MAPK inhibition on long-term potentiation and spatial memory.

Dentate Gyrus Development Requires ERK Activity to Maintain Progenitor Population and MAPK Pathway Feedback Regulation.

The ERK/MAPK pathway is an important developmental signaling pathway. Mutations in upstream elements of this pathway result in neuro-cardio-facial cutaneous (NCFC) syndromes, which are typified by impaired neurocognitive abilities that are reliant upon hippocampal function. The role of ERK signaling during hippocampal development has not been examined and may provide critical insight into the cause of hippocampal dysfunction in NCFC syndromes.

The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway.

Autism spectrum disorders are complex, highly heritable neurodevelopmental disorders affecting ∼1 in 100 children. Copy number variations of human chromosomal region 16p11.2 are genetically linked to 1% of autism-related disorders.

The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations.

Background: Mutations in the glucocerebrosidase gene (GBA) result in Gaucher disease and can be associated with a phenotype characterized by adult-onset progressive neurologic deterioration and parkinsonism.

Objective: To define the clinical and neurologic spectrum of parkinsonian manifestations associated with GBA mutations. Design, Setting, and Patients A prospective case series of 10 patients (7 men and 3 women) with parkinsonism and GBA mutations evaluated at the National Institutes of Health Clinical Center.