BACKGROUND: Auditory neuropathy (AN) is a hearing disorder that affects neural activity in the VIIIth cranial nerve and central auditory pathways. Progressive forms have been reported in a number of neurodegenerative diseases and may occur as a result of both the deafferentiation and desynchronisation of neuronal processes. The purpose of this study was to describe changes in auditory function over time in a patient with axonal neuropathy and to explore the effect of auditory intervention.
METHODS: We tracked auditory function in a child with progressive AN associated with Charcot-Marie-Tooth (Type 2C) disease, evaluating hearing levels, auditory-evoked potentials, and perceptual abilities over a 3-year period. Furthermore, we explored the effect of auditory intervention on everyday listening and neuroplastic development.
RESULTS: While sound detection thresholds remained constant throughout, both electrophysiologic and behavioural evidence suggested auditory neural degeneration over the course of the study. Auditory brainstem response amplitudes were reduced, and perception of auditory timing cues worsened over time. Functional hearing ability (speech perception in noise) also deteriorated through the first 1.5 years of study until the child was fitted with a \"remote-microphone\" listening device, which subsequently improved binaural processing and restored speech perception ability to normal levels.
CONCLUSIONS: Despite the deterioration of auditory neural function consistent with peripheral axonopathy, sustained experience with the remote-microphone listening system appeared to produce neuroplastic changes, which improved the patient\'s everyday listening ability-even when not wearing the device.

BACKGROUND: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN-INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects.
METHODS: We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics.
RESULTS: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age-normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies.
CONCLUSIONS: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost-efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally.

UNASSIGNED: Patients with Charcot-Marie-Tooth disease (CMT) often suffer from walking-related pain (WRP), muscle weakness, foot deformities, and reduced ankle dorsiflexion (DF), which affects their ability to walk and daily activities. Functional surgery (FS) can restore foot deviations, affecting the loading ability during gait. We assessed the short-term effects of FS in patients with CMT on WRP, foot and ankle structure, and function, along with patients\' perceived improvement.
UNASSIGNED: This is a prospective cohort study on CMT patients who had undergone FS and rehabilitation. We analyzed the changes after 1 month, focusing on WRP, DF, the center of pressure progression (COPP) during walking, and measures of walking ability. The non-parametric Wilcoxon test was used.
UNASSIGNED: Ten patients were included. One month after FS, WRP reduced from 5.5 (IQR = 3.5) to 2 (IQR = 3.5), p = 0.063, with an effect size of 0.615. The highest decrease was found in patients with very high pre-surgical pain levels. DF almost reached 10° for both active and passive movements (p < 0.05), and COPP improved from 44 to 60% (p = 0.009) of foot length. Gait speed, lower limb functioning, and balance did not change. More than half of the sample felt improved or much improved after FS.
UNASSIGNED: FS can be effective in reducing WRP and restoring foot posture in CMT patients in the short-term, which allows them to wear shoes, and leads to a perceived improvement and satisfaction. Lack of improvement in functional skills may be due to muscle weakness typical of CMT. Studies with longer follow-ups may confirm these hypotheses.

Anesthetic management for patients with Charcot-Marie-Tooth disease (CMT) is controversial. Description of the use of regional anesthesia (RA) in patients with CMT is limited. Regional anesthesia has traditionally been avoided because of risk of nerve injury. We retrospectively reviewed patients with CMT who received RA at our institution.
We performed a historical cohort study of all patients with CMT who received RA from 30 April 2010 to 30 April 2020 within our institution. Charts were reviewed for information on demographics, RA procedures, perioperative variables, evidence of neurologic complications, post-RA neurology consults, and perioperative electromyography (EMG) results. Electromyographs were reviewed by a neurologist who was blinded to the surgical and RA details.
Fifty-three patients received a total of 132 regional anesthetics during the study period. Twenty-five patients received RA on more than one occasion. Fifty-five EMGs and 14 postoperative neurology consults were performed. Two patients had neurology consults with peripheral nerve block (PNB) distribution complaints years later. Neither attributed the complaints to the PNB. The other neurology consults were for unrelated complaints. No EMG results suggested injury related to PNB.
This study found no evidence of documented neurologic complications or an increased risk of nerve injury related to RA in CMT patients.
RéSUMé: OBJECTIF: La prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT) est controversée. Les descriptions de l’utilisation de l’anesthésie régionale (AR) chez les patients atteints de CMT sont limitées. L’anesthésie régionale est traditionnellement évitée en raison du risque de lésion nerveuse. Nous avons rétrospectivement passé en revue les dossiers des patients atteints de CMT ayant reçu une AR dans notre établissement. MéTHODE: Nous avons réalisé une étude de cohorte historique de tous les patients atteints de CMT ayant reçu une AR entre le 30 avril 2010 et le 30 avril 2020 au sein de notre établissement. Les dossiers ont été passés en revue pour en tirer des renseignements sur les données démographiques, les interventions d’AR, les variables périopératoires, les signes de complications neurologiques, les consultations en neurologie post-AR et les résultats de l’électromyographie (EMG) périopératoire. Les électromyographes ont été examinés par un neurologue qui n’avait pas accès aux détails concernant la chirurgie et l’AR. RéSULTATS: Cinquante-trois patients ont reçu un total de 132 anesthésies régionales au cours de la période d’étude. Vingt-cinq patients ont reçu une AR à plus d’une occasion. Cinquante-cinq EMG et 14 consultations postopératoires en neurologie ont été effectuées. Deux patients ont consulté en neurologie après s’être plaints de la distribution du bloc nerveux périphérique (BNP) des années plus tard. Ni l’un ni l’autre n’a attribué ces problèmes au BNP. Les autres consultations en neurologie concernaient des plaintes non liées au BNP. Aucun résultat d’EMG n’a suggéré de lésion liée au BNP. CONCLUSION: Cette étude n’a trouvé aucune preuve de complications neurologiques documentées ou d’un risque accru de lésion nerveuse liée à l’AR chez les patients atteints de CMT.

Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy associated with impaired walking capacity. Some patients are too weak in the lower extremity muscles to walk at gravity with sufficient intensity or duration to gain benefit.
The aim was to investigate the effect of aerobic anti-gravity exercise in weak patients with CMT 1A and X.
Five adult patients performed moderate-intensity aerobic anti-gravity exercise 3/week for 10 weeks.
There was a significant positive difference in Berg balance scale and postural stability test between test occasions, and walking distance in the 6-min walk test trended to increase.
The study indicates that the anti-gravity treadmill training of patients with CMT should be pursued in larger CMT cohorts.

UNASSIGNED: Charcot-Marie-Tooth (CMT) disease is clinically and genetically heterogeneous. There are no published series describing clinical, electrophysiological, and genetic information on CMT from the Indian subcontinent. Magnetic resonance imaging (MRI) neurography technique provides useful information about the plexus and roots and can be employed in patients with CMT.
UNASSIGNED: A prospective, observational study carried out at a tertiary care hospital in Western India.
UNASSIGNED: CMT patients fulfilling the UK Genetic Testing Network criteria were included. They underwent clinical, electrophysiological, radiological, and multigene panel testing.
UNASSIGNED: Totally 22 patients (19 males, 3 females; 18 sporadic and 4 familial cases) were studied. Pes cavus (19), hammer toes (16), and scoliosis was seen in 1 patient. Electrophysiology revealed motor predominant neuropathy with 15 demyelinating (10 uniform and 5 multifocal) and 7 axonal patterns. Thickened lumbosacral plexuses on MRI neurography were evident in 6/10 studied patients, all 6 having demyelinating neuropathy. Genetic analysis identified PMP22, GJB1, SH3TC2, HSPB1, SPTLC2, MPZ, AARS, and NEFH gene mutations.
UNASSIGNED: This small series documents the pattern of CMT neuropathies as seen in Western India. Clinico-electrophysiological and genetic diagnosis showed general concordance some overlaps and reiterated advantages of gene panel testing in this heterogeneous group of neuropathies. MRI neurography was useful as an additional investigation to detect nerve enlargement in patients with demyelinating neuropathies.

Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform the duration and outcome measures of any future trials. Clinical and neurophysiological data and lower limb muscle MRI were collected both prospectively and retrospectively from patients with mutations in HSPB1. The natural history was assessed by recording the weighted Charcot-Marie-Tooth Examination Score (CMTES) at annual intervals in a subset of patients. 20 patients from 14 families were recruited into the study. The average age of onset was in the 4th decade. Patients presented with a length dependent neuropathy but with early ankle plantar flexion weakness. Neurophysiology confirmed a motor neuropathy but also showed sensory nerve involvement in most patients. Cross sectional muscle MRI revealed soleus and medial gastrocnemius fat infiltration as an early signature of mutant HSPB1 disease. In this study neither semi quantitative muscle MRI, the CMTES nor neurophysiology were able to detect disease progression in HSPB1 neuropathy over 1 or 2 years. Further studies are therefore required to identify a suitable biomarker before clinical trials in HSPB1 neuropathy can be undertaken.

BACKGROUND: Charcot Marie Tooth disease type 1A (CMT1A) is the most commonly inherited demyelinating polyneuropathy with variable phenotypes, affected by several comorbidities, especially diabetes mellitus (DM). Previous studies showed that DM exacerbates the clinical manifestations of CMT1A.
METHODS: We retrospectively evaluated patients with CMT1A in our hospital, and identified three groups among 12 cases, which comprised four patients with CMT1A, four with CMT1A+DM, and four with DM. We reviewed the CMT neuropathy score (CMTNS), electrophysiological data, and histomorphological parameters of the sural nerve, including fiber density, myelin thickness, axon diameter, g-ratio, regenerative clusters, and regeneration ratio.
RESULTS: The CMTNS was significantly higher in patients with CMT1A+DM (21.5±2.52) than in those with CMT1A only (10.8±4.4; p=0.03). Pathological findings in patients with CMT1A+DM included a significant decrease of myelinated fiber density (p=0.02) and reduction in the regenerative ratio (p=0.01), indicating severe degeneration with impaired regeneration. In non-parametric analyses, DM was found to play a more important role than CMT1A in influencing nerve degeneration and regeneration.
CONCLUSIONS: In patients with CMT1A, DM exacerbated clinical and pathological manifestations including increased loss of myelinated fibers, abnormal axon-myelin interaction, and impaired nerve regeneration.