Annals of Neurology

"Stem cell tourism," the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the US. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures...

No abstract text is available yet for this article.

OBJECTIVE: The rs12608932 single nucleotide polymorphism in UNC13A is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) susceptibility, and may underlie differences in treatment response. We aimed to characterize the clinical, cognitive, behavioral, and neuroimaging phenotype of UNC13A in ALS patients. METHODS: We included 2,216 ALS patients without a C9orf72 mutation to identify clinical characteristics associated with the UNC13A polymorphism...

No abstract text is available yet for this article.

OBJECTIVE: To compare the diagnostic performance of an artificial intelligence deep learning system with that of expert neuro-ophthalmologists in classifying optic disc appearance. METHODS: The deep learning system was previously trained and validated on 14,341 ocular fundus photographs from 19 international centers. The performance of the system was evaluated on 800 new fundus photographs (400 normal optic discs, 201 papilledema [disc edema from elevated intracranial pressure], 199 other optic disc abnormalities) and compared with that of two expert neuro-ophthalmologists who independently reviewed the same randomly-presented images without clinical information...

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands...

No abstract text is available yet for this article.

Disability in multiple sclerosis (MS) is considered primarily a result of axonal loss. However, correlation with spinal cord cross-sectional area - a predictor of disability - is poor, questioning the unique role of axonal loss. We investigated the degree of synaptic loss in post-mortem spinal cords (18 chronic MS, eight healthy controls) using immunohistochemistry for synaptophysin and synapsin. Substantial (58-96%) loss of synapses throughout the spinal cord was detected, along with moderate (47%) loss of anterior horn neurons, notably in demyelinating MS lesions...

No abstract text is available yet for this article.

OBJECTIVE: Impairment of glycinergic neurotransmission leads to complex movement and behavioral disorders. Patients harboring glycine receptor autoantibodies suffer from stiff-person syndrome or its severe variant progressive encephalomyelitis with rigidity and myoclonus. Enhanced receptor internalization was proposed as the common molecular mechanism upon autoantibody binding. Although functional impairment of glycine receptors following autoantibody binding has recently been investigated, it is still incompletely understood...

OBJECTIVE: Recent studies carried on amyotrophic lateral sclerosis patients suggest that the disease may initiate in the motor cortex and spread to its targets along the corticofugal tracts. In this study, we aimed at experimentally testing the corticofugal hypothesis of amyotrophic lateral sclerosis. METHODS: Sod1G86R and Fezf2 knockout mouse lines were crossed to generate a model that ubiquitously expresses a mutant of the murine Sod1 gene, a condition sufficient to induce progressive motor symptoms and premature death, but genetically lacks corticospinal neurons and other subcerebral projection neurons, one of the main populations of corticofugal neurons...

OBJECTIVE: CGRP pathway inhibitors are emerging treatments for migraine. CGRP-mediated vasodilation is, however, a critical rescue mechanism in ischemia. We, therefore, investigated whether gepants, small molecule CGRP receptor antagonists, worsen cerebral ischemia. METHODS: Middle cerebral artery was occluded for 12-60 minutes in mice. We compared infarct risk and volumes, collateral flow and neurological deficits after pretreatment with olcegepant (single or 10 daily doses of 0...

OBJECTIVE: To demonstrate that antibodies from patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis alter the levels of dopamine 1 receptor (D1R) and dopamine 2 receptor (D2R) and cause psychotic-like features in mice. METHODS: Cultured rat hippocampal neurons were treated with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, and the effects on clusters of D1R and D2R were quantified. In vivo studies included 71 C57BL/6J mice that were chronically infused with patients' or controls' CSF through ventricular catheters connected to subcutaneous osmotic pumps...

No abstract text is available yet for this article.

OBJECTIVE: There are no validated methods for predicting the timing of seizures. Using machine learning, we sought to forecast 24-hour risk of self-reported seizure from e-diaries. METHODS: Data from 5,419 patients of SeizureTracker.com (including seizure count, type and duration) was split into training (3,806 patients/1,665,215 patient-days) and testing (1,613 patients/549,588 patient-days) sets with no overlapping patients. An artificial intelligence (AI) program, consisting recurrent networks followed by a multilayer perceptron ("deep learning" model) was trained to produce risk forecasts...

No abstract text is available yet for this article.

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy...

OBJECTIVE: To examine associations of molecular markers of brain insulin signaling with Alzheimer's disease (AD) and cognition, among older persons with or without diabetes. METHODS: This clinical-pathologic study was derived from a community-based cohort study, the Religious Orders Study. We studied 150 individuals (mean age-at-death =87 years, 48% women): 75 with and 75 without diabetes (matched by sex on age-at-death and education). Using ELISA, immunohistochemistry and ex vivo stimulation of brain tissue with insulin, we assessed insulin signaling in the postmortem middle frontal gyrus cortex...

OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings to Lewy body synucleinopathies. METHODS: In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14) we utilized ELISA to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF...

Facial expressions are important for intentional display of emotions in social interaction. For people with severe paralysis, the ability to intentionally display emotions can be impaired. Current brain-computer interfaces (BCIs) allow for linguistic communication but are cumbersome for expressing emotions. Here, we investigated the feasibility of a BCI to display emotions by decoding facial expressions. We used electrocorticographic recordings from the sensorimotor cortex of people with refractory epilepsy and classified 5 facial expressions, based on neural activity...