Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse.

Ultrasonographic manifestations of Charcot-Marie-Tooth disease due to a mutation in the PMP22 gene: A case image.

In this case, the bilateral brachial plexus, median nerve, ulnar nerve, radial nerve, sciatic nerve, tibial nerve, and common peroneal nerve of the patient all showed diffuse and uniform edema and thickening, with no segmental thickening changes in noncompression areas, consistent with the neuroultrasound findings of CMT1.

Characterizing human KIF1Bβ motor activity by single-molecule motility assays and Caenorhabditis elegans genetics.

The axonal transport of synaptic vesicle precursors relies on KIF1A and UNC-104 ortholog motors. In mammals, KIF1Bβ is also responsible for the axonal transport of synaptic vesicle precursors. Mutations in KIF1A and KIF1Bβ lead to a wide range of neuropathies.

The effect of ankle-foot orthoses on gait characteristics in people with Charcot-Marie-Tooth disease: A systematic review and meta-analysis.

Introduction: Ankle-foot orthoses (AFOs) are commonly prescribed for people with Charcot-Marie-Tooth disease (CMT) to improve gait efficiency and reduce the occurrence of tripping and falls. The aim of this study was to systematically review evidence on the effects of AFOs on gait kinematics and kinetics and postural stability/balance in people with CMT.

Methods: Studies were identified from electronic databases and screened for inclusion online using Rayyan.

Jean-Martin Charcot: Pioneer of Neurology.

Jean-Martin Charcot, born on November 29, 1825, in Paris, France, is known as the father of neurology. During a time when neurology was not yet a recognized medical specialty, Charcot's pioneering contributions significantly advanced the field. Charcot's use of the anatomo-clinical method, which correlates clinical symptoms with anatomical findings, led to the discovery and characterization of numerous neurological conditions, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Charcot's joint, and Charcot-Marie-Tooth (CMT) disease.

Long-term outcomes in children with riboflavin transporter deficiency and surveillance recommendations.

The aim of this longitudinal case series was to describe long-term functional outcome in a group of individuals with riboflavin transporter deficiency (RTD) treated with high-dose oral riboflavin. Data were collected between 2012 to 2022. Eleven individuals with RTD were assessed at 12-month intervals for monitoring of disease progression.

A Novel m.1636A > G Variant in Mitochondrial TV Gene Might Cause New Phenotype of Mitochondrial Disease in a 2-Year Old Chinese Boy.

Pathogenic variants of mitochondrial DNA (mtDNA) are associated with a large number of heterogeneous diseases involving multiple systems with which patients may present with a wide range of clinical phenotypes. Clinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that was performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis.

Efficient data labeling strategies for automated muscle segmentation in lower leg MRIs of Charcot-Marie-Tooth disease patients.

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies.

Hereditary spastic paraplegia and extensive leukoencephalopathy: a case report of a unique phenotype associated with a GJB1/Cx32 p.Pro174Ser variant.

Background: Pathogenic variants in Gap junction protein beta 1 (GJB1), which encodes Connexin 32, are known to cause X-linked Charcot-Marie-Tooth disease (CMTX), the second most common form of CMT. CMTX presents with the following five central nervous systems (CNS) phenotypes: subclinical electrophysiological abnormalities, mild fixed abnormalities on neurological examination and/or imaging, transient CNS dysfunction, cognitive impairment, and persistent CNS manifestations.

Case Presentation: A 40-year-old Japanese male showed CNS symptoms, including nystagmus, prominent spastic paraplegia, and mild cerebellar ataxia, accompanied by subclinical peripheral neuropathy.

Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Background And Aims: Charcot-Marie-Tooth (CMT) is a heterogeneous group of genetic neuropathies and is typically characterized by distal muscle weakness, sensory loss, pes cavus and areflexia. Herein we describe a case of CMT2CC presenting with proximal muscle weakness and equivocal electrophysiological features, that was misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP).

Case Report: A 30-year-old woman complained of proximal muscle weakness with difficulty climbing stairs.

Nerve ultrasound in CANVAS-spectrum disease: Reduced nerve size distinguishes genetically confirmed CANVAS from other axonal polyneuropathies.

Background And Aims: Ultrasound nerve cross-sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions.

Methods: We compared nerve CSA from CANVAS patients (tested positive for biallelic RFC1 gene repeat expansions) with the CSA from a group of patients with chronic idiopathic axonal polyneuropathy (CIAP) who tested negative for RFC1 gene repeat expansions, hereditary axonal neuropathy (Charcot-Marie-Tooth type 2, CMT2), and Friedreich ataxia (FRDA).

Identification and Characterization of Novel Founder Mutations in : Refining the Genetic Landscape of Charcot-Marie-Tooth Disease Type 4D in Bulgaria.

Charcot-Marie-Tooth neuropathy type 4D (CMT4D) is a rare genetic disorder of the peripheral nervous system caused by biallelic mutations in the N-Myc Downstream Regulated 1 gene (). Patients present with an early onset demyelinating peripheral neuropathy causing severe distal muscle weakness and sensory loss, leading to loss of ambulation and progressive sensorineural hearing loss. The disorder was initially described in the Roma community due to a common founder mutation, and only a handful of disease-causing variants have been described in this gene so far.

Pediatric Chronic Inflammatory Demyelinating Polyneuropathy: Challenges in Diagnosis and Therapeutic Strategies.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neurological disorder seen in both pediatric and adult populations. CIDP typically presents with progressive and persistent weakness over at least 4 weeks in addition to sensory symptoms in the extremities. Although CIDP shares common clinical features between children and adults, it sometimes presents as a distinct clinical entity in children that requires close attention and recognition.

Corrigendum: Case report: Chronic inflammatory demyelinating polyneuropathy superimposed on Charcot-Marie-tooth type 1A disease after SARS-CoV-2 vaccination and COVID-19 infection.

[This corrects the article DOI: 10.3389/fneur.2024.

Neurofilaments in neurologic disease.

Neurofilaments (NFs), major cytoskeletal constituents of neurons, have emerged as universal biomarkers of neuronal injury. Neuroaxonal damage underlies permanent disability in various neurological conditions. It is crucial to accurately quantify and longitudinally monitor this damage to evaluate disease progression, evaluate treatment effectiveness, contribute to novel treatment development, and offer prognostic insights.

Hidden hearing loss in a Charcot-Marie-Tooth type 1A mouse model.

Hidden hearing loss (HHL), a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked cochlear compound action potentials, has been proposed to contribute to hearing difficulty in noisy environments in people with normal hearing thresholds and has become a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, we recently showed that transient auditory nerve (AN) demyelination also causes HHL in mice. To test the effect of myelinopathy on hearing in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans.

Méary's angle decoded: 3D analysis of first ray plantarflexion deformity in Charcot-marie-tooth disease.

Background: The typical cavovarus deformity seen in patients with Charcot-Marie-Tooth (CMT) involves plantarflexion of the first ray. The exact apex of the deformity has never been proven, although it is presumed to be within the medial cuneiform. The aim of this study was to utilize weight-bearing computed tomography (WBCT) to localize and quantify first ray plantarflexion deformity in CMT patients.