Nitrous-oxide-induced polyneuropathy and subacute combined degeneration of the spine: clinical and diagnostic characteristics in 70 patients, with focus on electrodiagnostic studies.

BACKGROUND AND PURPOSE: Nitrous oxide (N2 O) induced neurological symptoms are increasingly encountered. Our aim is to provide clinical and diagnostic characteristics with a focus on electrodiagnostic studies. METHODS: Patients with neurological sequelae due to N2 O presenting in our hospital between November 2018 and December 2021 reporting clinical and diagnostic data were retrospectively reviewed. RESULTS: Seventy patients (median 22 years) were included. Median N2 O usage was 4 kg/week during 12 months. Patients' history revealed a higher rate of sensory symptoms compared to motor (97% vs. 57%) and 77% walking difficulties. Clinical diagnosis was polyneuropathy (PNP) in 44%, subacute combined degeneration (SCD) of the spine in 19%, both in 37%. Median vitamin B12 level was low (159 pmol/L), normal in 16%. The median methylmalonic acid was increased (2.66 µmol/L). Electrodiagnostic abnormalities were observed in 91%, with 72% fulfilling axonal PNP criteria, 20% showing mild to intermediate slowing. One patient fulfilled demyelinating PNP criteria not related to N2 O abuse (Charcot-Marie-Tooth type 1a). More prominent motor nerve conduction abnormalities were found; lower limbs were more affected. In 64% with normal conduction, myography showed signs of axonal loss. Magnetic resonance imaging showed cervical myelopathy in 58% involving generally five to six segments. CONCLUSIONS: Nitrous oxide (N2 O) leads to neurological symptoms by causing PNP and/or SCD primarily involving the legs. Distinguishing PNP and SCD clinically was shown to be insufficient. Electrodiagnostic studies showed axonal PNP. Demyelinating PNP due to N2 O abuse was not present in our cohort. Therefore, further diagnostic work-up is warranted if demyelinating features are present.

Mutations in alpha-B-crystallin cause autosomal dominant axonal Charcot-Marie-Tooth disease with congenital cataracts.

BACKGROUND AND PURPOSE: Mutations in the alpha-B-crystallin (CRYAB) gene have initially been associated with myofibrillar myopathy, dilated cardiomyopathy and cataracts. For the first time, peripheral neuropathy is reported here as a novel phenotype associated with CRYAB. METHODS: Whole-exome sequencing was performed in two unrelated families with genetically unsolved axonal Charcot-Marie-Tooth disease (CMT2), assessing clinical, neurophysiological and radiological features. RESULTS: The pathogenic CRYAB variant c.358A>G;p.Arg120Gly was segregated in all affected patients from two unrelated families. The disease presented as late onset CMT2 (onset over 40 years) with distal sensory and motor impairment and congenital cataracts. Muscle involvement was probably associated in cases showing mild axial and diaphragmatic weakness. In all cases, nerve conduction studies demonstrated the presence of an axonal sensorimotor neuropathy along with chronic neurogenic changes on needle examination. DISCUSSION: In cases with late onset autosomal dominant CMT2 and congenital cataracts, it is recommended that CRYAB is considered for genetic testing. The identification of CRYAB mutations causing CMT2 further supports a continuous spectrum of expressivity, from myopathic to neuropathic and mixed forms, of a growing number of genes involved in protein degradation and chaperone-assisted autophagy.

Cochlear implantation in patients with Charcot-Marie-Tooth disease: two cases with a review of the literature.

PURPOSE: To report two cases of bilateral cochlear implantation (CI) in Charcot-Marie-Tooth disease (CMT) patients with novel mutations. Furthermore, we conducted a detailed literature review on the profile and outcomes of CI in this uncommon clinical circumstance. CASE PRESENTATION: Case 1 involved a 25-year-old woman who was referred for sudden hearing loss (HL) in her left ear and had a 7-year history of HL in her right ear. She was diagnosed with CMT type 1 with a thymidine phosphorylase gene mutation. CI was performed on her left side because her hearing gradually worsened to deafness in both ears. At 3 months post-operation, her speech discrimination score without lip-reading improved from 0 to 100%. She underwent a second CI on her right ear 6 months after her first CI. Two years from her first operation, the speech discrimination score was 100%. Case 2 received her first CI on her right ear at the age of nine for her bilateral HL. She was diagnosed with CMT type 2 with a Twinkle mitochondrial DNA helicase gene mutation. Preoperatively, the speech discrimination score in both ear-aided conditions was 70%. At the 7-year post-operation follow-up, the speech discrimination score was 76%. A second CI was performed due to decreasing hearing ability in her left ear. The speech discrimination score showed 100% at 7 months after the second CI. CONCLUSIONS: CI is an effective hearing rehabilitation option for CMT patients with severe-to-profound SNHL. Neuro-otologists should consider CI as a treatment option, even though hearing loss in CMT is associated with auditory neuropathy spectrum disease (ANSD).

Foot surgery for adults with Charcot-Marie-Tooth disease.

People with Charcot-Marie-Tooth (CMT) disease often undergo foot and ankle surgery, as foot deformities are common and cause a degree of functional limitations impairing quality of life. Surgical approaches are variable and there are no evidence-based guidelines. A multidisciplinary approach involving neurology, physical therapy and orthopaedic surgery is ideal to provide guidance on when to refer for surgical opinion and when to intervene. This review outlines the range of foot deformities associated with CMT, their clinical assessment, and their conservative and surgical and postoperative management.

Frequency, entity and determinants of fatigue in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Fatigue, a disabling symptom in many neuromuscular disorders, has been reported also in Charcot-Marie-Tooth disease (CMT). The presence of fatigue and its correlations in CMT was investigated. METHODS: The Modified Fatigue Impact Scale (MFIS) was administered to CMT patients from the Italian Registry and a control group. An MFIS score >38 indicated abnormal fatigue. The correlation with disease severity and clinical characteristics, the Hospital Anxiety and Depression Scale and Epworth Sleepiness Scale scores, and drug use was analysed. RESULTS: Data were collected from 251 CMT patients (136 women) and 57 controls. MFIS total (mean ± standard deviation 32 ± 18.3, median 33), physical (18.9 ± 9.7, 20) and psychosocial (2.9 ± 2.4, 3) scores in CMT patients were significantly higher than controls. Abnormal fatigue occurred in 36% of the patients who, compared to patients with normal scores, had more severe disease (median CMT Examination Score 9 vs. 7), more frequent use of foot orthotics (22% vs. 11%), need of support for walking (21% vs. 8%), hand disability (70% vs. 52%) and positive sensory symptoms (56% vs. 36%). Patients with abnormal fatigue had significantly increased frequency of anxiety/depression/general distress (Hospital Anxiety and Depression Scale), somnolence (Epworth Sleepiness Scale), obesity (body mass index ≥ 30) and use of anxiolytic/antidepressant or anti-inflammatory/analgesic drugs. CONCLUSIONS: Fatigue is a relevant symptom in CMT as 36% of our series had scores indicating abnormal fatigue. It correlated with disease severity but also with anxiety, depression, sleepiness and obesity, indicating different components in the generation of fatigue. CMT patients' management must include treatment of fatigue and of its different generators, including general distress, sleepiness and obesity.

INF2 mutations in patients with a broad phenotypic spectrum of Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis.

Mutations in INF2 are associated with the complex symptoms of Charcot-Marie-Tooth disease (CMT) and focal segmental glomerulosclerosis (FSGS). To date, more than 100 and 30 genes have been reported to cause these disorders, respectively. This study aimed to identify INF2 mutations in Korean patients with CMT. This study was conducted with 743 Korean families with CMT who were negative for PMP22 duplication. In addition, a family with FSGS was included in this study. INF2 mutations were screened using whole exome sequencing (WES) and filtering processes. As the results, four pathogenic INF2 mutations were identified in families with different clinical phenotypes: p.L78P and p.L132P in families with symptoms of both CMT and FSGS; p.C104Y in a family with CMT; and p.R218Q in a family with FSGS. Moreover, different CMT types were observed in families with CMT symptoms: CMT1 in two families and Int-CMT in another family. Hearing loss was observed in two families with CMT1. Pathogenicity was predicted by in silico analyses, and considerable conformational changes were predicted in the mutant proteins. Two mutations (p.L78P and p.C104Y) were unreported, and three families showed de novo mutations that were putatively occurred from fathers. This study suggests that patients with INF2 mutations show a broad phenotypic spectrum: CMT1, CMT1 + FSGS, CMTDIE + FSGS, and FSGS. Therefore, the genotype-phenotype correlation may be more complex than previously recognized. We believe that this study expands the clinical spectrum of patients with INF2 mutations and will be helpful in the molecular diagnosis of CMT and FSGS.

Assessing the coronal plane deformity in Charcot Marie Tooth Cavovarus feet using automated 3D measurements.

BACKGROUND: This study assesses the coronal-plane deformities in cavovarus feet secondary to Charcot-Marie-Tooth disease (CMT) using Weightbearing-CT (WBCT) and semi-automated 3D-segmentation software. METHODS: WBCTs from 30 CMT-cavovarus feet were matched to 30 controls and analysed using semi-automatic 3D-segmentation (Bonelogic, DISIOR). The software used automated cross-section sampling with subsequent straight-line representation of weighted centre points to calculate 3D axes of bones in the hindfoot, midfoot and forefoot. Coronal relationships of these axes were analysed. Supination/pronation of the bones in relation to the ground and within each joint were measured and reported. RESULTS: The most significant deformity in CMT-cavovarus feet occurred at the talonavicular joint (TNJ) with 23 degrees more supination than normal feet (6.4 ± 14.5 versus 29.4 ± 7.0 degrees, p < 0.001). This was countered by relative pronation at the naviculo-cuneiform joints (NCJ) of 7.0 degrees (-36.0 ± 6.6 versus -43.0 ± 5.3 degrees, p < 0.001). Combined hindfoot varus and TNJ supination resulted in an additive supination effect not compensated by NCJ pronation. The cuneiforms in CMT-cavovarus feet were therefore supinated by 19.8 degrees to the ground relative to normal feet (36.0 ± 12.1 versus 16.2 ± 6.8 degrees, p < 0.001). The forefoot-arch and 1st metatarsal-ground angles demonstrated similar supination to the cuneiforms suggesting no further significant rotation occurred distally. CONCLUSION: Our results demonstrate coronal plane deformity occurs at multiple levels in CMT-cavovarus feet. Majority of the supination arises at the TNJ, and this is partially countered by pronation distally, mainly at the NCJ. An understanding of the location of coronal deformities may help when planning surgical correction. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Evidence of nerve hypertrophy in patients with inclusion body myositis on lower limb MRI.

INTRODUCTION/AIMS: Inclusion body myositis (IBM) is a myopathic condition but in some patients has been associated with an axonal length-dependent polyneuropathy. In this study, we quantified the cross-sectional area of the sciatic and tibial nerves in patients with IBM comparing with Charcot-Marie-Tooth disease type 1A (CMT1A) and healthy controls using magnetic resonance neurography (MRN). METHODS: MRN of the sciatic and tibial nerves was performed at 3T using MPRAGE and Dixon acquisitions. Nerve cross-sectional area (CSA) was measured at the mid-thigh and upper third calf regions by an observer blinded to the diagnosis. Correlations were performed between these measurements and clinical data. RESULTS: A total of 20 patients with IBM, 20 CMT1A and 29 healthy controls (age- and sex-matched) were studied. Sciatic nerve CSA was significantly enlarged in patients with IBM and CMT1A compared to controls (sciatic nerve mean CSA 62.3 ± 22.9 mm2 (IBM) vs. 35.5 ± 9.9 mm2 (controls), p < 0.001; and 96.9 ± 35.5 mm2 (CMT1A) vs. 35.5 ± 9.9 mm2 (controls); p < 0.001). Tibial nerve CSA was also enlarged in IBM and CMT1 patients compared to controls. DISCUSSION: MRN reveals significant hypertrophy of the sciatic and tibial nerves in patients with IBM and CMT1A compared to controls. Further studies are needed to correlate with neurophysiological measures and assess whether this finding is useful diagnostically.

Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary neuropathy, and CMT1A is the most common form; it is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Mutations in the transient sodium channel Nav1.4 alpha subunit (SCN4A) gene underlie a diverse group of dominantly inherited nondystrophic myotonias that run the spectrum from subclinical myopathy to severe muscle stiffness, disabling weakness, or frank episodes of paralysis. CASE PRESENTATION: We describe a Chinese family affected by both CMT1A and myotonia with concomitant alterations in both the PMP22 and SCN4A genes. In this family, the affected proband inherited the disease from his father in an autosomal dominant manner. Genetic analysis confirmed duplication of the PMP22 gene and a missense c.3917G > C (p. Gly1306Ala) mutation in SCN4A in both the proband and his father. The clinical phenotype in the proband showed the combined involvement of skeletal muscle and peripheral nerves. Electromyography showed myopathic changes, including myotonic discharges. MRI revealed the concurrence of neurogenic and myogenic changes in the lower leg muscles. Sural nerve biopsies revealed a chronic demyelinating and remyelinating process with onion bulb formations in the proband. The proband's father presented with confirmed subclinical myopathy, very mild distal atrophy and proximal hypertrophy of the lower leg muscles, pes cavus, and areflexia. CONCLUSION: This study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations.

Charcot-Marie-Tooth disease type 4C associated with myasthenia gravis: coincidental or a foreseeable association?

We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG.

Charcot-Marie-Tooth neuropathy score and ambulation index are both predictors of orthotic need for patients with CMT.

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy with an estimated prevalence of 1 person affected on 2500. Frequent symptoms include distal weakness and muscle wasting, sensory loss, reduced deep tendon reflexes, and skeletal deformities, such as hammer toes and pes cavus. CMT is a progressive disease and patients' needs change over their lifetime. In particular, ambulation aids are increasingly needed to maintain ambulation and reduce the risk of falls. We performed a retrospective analysis of medical records from 149 patients with confirmed CMT to evaluate patients ambulation needs related to the severity of their CMT as measured by the CMT Neuropathy Score (CMTNS) and Ambulation Index (AI). Most patients required some form of orthotics (86.6%). The CMTNS and AI scores both differed significantly between patients with no orthotics compared to those who wore insoles/inserts. The CMTNS and AI also differed significantly between patients wearing insoles and those with ankle foot orthotics (AFOs). CMTNS and the AI were valid predictors of the type and choice of the orthotics. Both the CMTNS and AI can be effective tools to aid in the correct choice of orthotics in patients affected by CMT.

Whole-exome sequencing identifies a novel de novo variant in DYNC1H in a patient with intractable epilepsy.

DYNC1H1 variants are associated with broad phenotypes including Charcot-Marie-Tooth disease, spinal muscular atrophy, and mental retardation. However, DYNC1H1 variants related intractable epilepsy have not yet been described in detail so far. Herein, we describe the detailed clinical manifestations of a female patient, carrying a novel de novo variant in DYNC1H1 (p.H311Y), who presented with malformation of cortical development (MCD), refractory epilepsy, intellectual disability, and lower motor neuron disease. We provide a review of previously reported patients who presented with epilepsy associated with DYNC1H1 variants. Of the patients with epilepsy, the DYNC1H1 variants were distributed, on average, in the tail, linker, and motor domains, rather than being mainly distributed in the tail domain as previously reported.

Regional anesthesia in patients with Charcot-Marie-Tooth disease: a historical cohort study of 53 patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Rocuronium-induced respiratory paralysis refractory to sugammadex in Charcot-Marie-Tooth disease.

PURPOSE: Prolonged postoperative neuromuscular respiratory paralysis after administration of a nondepolarizing neuromuscular blocking agent is a serious concern during anesthetic management of patients with Charcot-Marie-Tooth disease (CMTD). Some recent reports have described rocuronium use without respiratory paralysis in CMTD patients when sugammadex was used for its reversal. We report a case in which an induction dose of rocuronium caused a prolonged respiratory paralysis in a patient with undiagnosed type 1A CMTD (CMT1A). CLINICAL FEATURES: A 63-yr-old-male with an American Society of Anesthesiologists Physical Status score of III underwent a left hip arthroplasty under general anesthesia for osteoarthritis. Preoperative pulmonary function testing indicated a restrictive impairment. Anesthesia was induced with fentanyl, remifentanil, propofol, and 0.73 mg·kg-1 of rocuronium. The train-of-four (TOF) count was 0 for the 273-min duration of surgery. After repeated doses of sugammadex failed to recover the TOF count and spontaneous respirations, a total of 1,200 mg (17.3 mg·kg-1) of sugammadex, which was assumed to be a sufficient amount for capturing the residual rocuronium, was administered. Although the patient expressed that he was awake via eye blinking, he could not breathe. Thus, he was placed on mechanical ventilation for 18 hr after surgery. A postoperative neurology consultation revealed a delayed nerve conduction velocity of 20 m·sec-1 and a mutated duplication of the PMP22 gene; a diagnosis of CMT1A was made. CONCLUSIONS: Our case shows that rocuronium can cause a prolonged neuromuscular respiratory paralysis refractory to sugammadex in patients with CMT1A and impaired respiratory function. Our case may also indicate that restrictive pulmonary impairment and low nerve conduction velocity of 20 m·sec-1 are predictive factors that cause prolonged neuromuscular respiratory paralysis refractory to sugammadex in CMT1A.

RéSUMé: OBJECTIF: La paralysie respiratoire neuromusculaire postopératoire prolongée après l'administration d'un bloqueur neuromusculaire non dépolarisant est une préoccupation sérieuse lors de la prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT). Certains comptes rendus récents ont décrit l'utilisation de rocuronium sans paralysie respiratoire chez les patients atteints de CMT lorsque le sugammadex était utilisé pour le neutraliser. Nous rapportons un cas dans lequel une dose d'induction de rocuronium a provoqué une paralysie respiratoire prolongée chez un patient atteint de CMT de type 1A (CMT1A) non diagnostiquée. CARACTéRISTIQUES CLINIQUES: Un homme de 63 ans avec un score de statut physique III selon la classification de l'American Society of Anesthesiologists a bénéficié d'une arthroplastie de la hanche gauche sous anesthésie générale pour son ostéo-arthrite. Les tests préopératoires de la fonction pulmonaire ont indiqué un syndrome restrictif. L'anesthésie a été induite avec du fentanyl, du rémifentanil, du propofol et 0,73 mg·kg-1 de rocuronium. Le décompte du train-de-quatre (TdQ) était de 0 pour toute la durée de la chirurgie, soit 273 minutes. Après l'échec de doses répétées de sugammadex qui n'ont pas réussi à rétablir un TdQ normal ni la respiration spontanée, un total de 1200 mg (17,3 mg·kg-1) de sugammadex (une quantité qu'on a présumé suffisante pour neutraliser le rocuronium résiduel) a été administré. Bien que le patient ait exprimé qu'il était éveillé en clignant des yeux, il ne pouvait pas respirer. Il a donc été placé sous ventilation mécanique pendant 18 heures après l'opération. Une consultation postopératoire en neurologie a révélé une vitesse de conduction nerveuse retardée de 20 m·sec-1 et une duplication mutée du gène PMP22; un diagnostic de CMT1A a été posé. CONCLUSIONS: Notre cas montre que le rocuronium peut provoquer une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex chez les patients atteints de CMT1A et d'une altération de la fonction respiratoire. Notre cas pourrait également indiquer qu'un syndrome restrictif pulmonaire et une faible vitesse de conduction nerveuse de 20 m·sec-1 constituent des facteurs prédictifs provoquant une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex dans les cas de CMT1A.

Charcot-Marie-Tooth disease type 4J with spastic quadriplegia, epilepsy and global developmental delay: a tale of three siblings.

Charcot-Marie-Tooth (CMT) disease is mainly a disease of peripheral nervous system and patients typically present with features of demyelinating neuropathy or axonal neuropathy or both. Rarely patients present with features of central nervous system involvement. Parkinsonism, aphemia and familial epilepsy syndrome have previously come up as case reports in association with CMT type 4 J.We hereby describe a family with 3 siblings affected with CMT4J with homozygous FIG4 mutation who presented with global developmental delay, epilepsy and spastic quadriparesis.

[Clinical case of the cardiovascular system involvement in a patient with Charcot-Marie-Tooth disease].

Hereditary motor and sensory type 1A neuropathy (known as Charcot-Marie-Tooth disease) is a disease of peripheral nerves characterized by symptoms of progressive polyneuropathy with preferential damage of distal extremity muscles. Damage to the cardiovascular system is extremely rare and heterogenous in this pathology. This disease is not included in the list of indications for interventional antiarrhythmic aid. We could not find in available literature a clinical description of the development of sinus node dysfunction associated with this pathology. The present clinical report presents a case of detection and successful treatment of a damage to the cardiovascular system that manifested itself as sinus node dysfunction/sick sinus syndrome in the tachy-brady variant. A combination treatment approach using radiofrequency catheter ablation, implantation of a permanent pacemaker, and antiarrhythmic therapy associated with drug and non-drug treatment of motor sensory neuropathy resulted in recovery and long-term maintenance of sinus rhythm as well as in beneficial changes in the patient's neurological status.

A prospective study on surgical management of foot deformities in Charcot Marie tooth disease.

Foot deformities are frequently observed in patients with Charcot Marie tooth disease (CMT) and orthopaedic surgery is often required. Currently there is no evidence-based guideline on surgical management and only a few studies which have evaluated long-term outcomes of surgical procedures. The aim of the study was to evaluate longitudinally the effect of foot surgery in a cohort of CMT patients. Twenty-five CMT adult patients were assessed using a comprehensive group of validated scales and questionnaires before and after surgery. A wide range of surgical procedures was performed by one team of dedicated foot ankle orthopaedic surgeons. Foot alignment as measured by the foot posture index, pain, quality of life and callosities significantly improved after one year and the improvement was maintained up to 4 years after surgery. There was a trend towards a reduction in the number of falls post-operatively. Surgery had no effect on fatigue, balance and CMT examination score. Our findings showed significant improvement of pain, foot alignment, callosities and quality of life after surgery and suggested that foot deformity correction in adults with CMT performed in a specialised foot and ankle unit is beneficial.

Optic Neuropathy in Charcot-Marie-Tooth Disease.

BACKGROUND: Charcot-Marie-Tooth disease Type 2A (CMT2A) presents with optic atrophy in a subset of patients, but the prevalence and severity of optic nerve involvement in relation to other CMT subtypes has not been explored. METHODS: Patients with genetically confirmed CMT2A (n = 5), CMT1A (n = 9) and CMTX1 (n = 10) underwent high- and low-contrast acuity testing using Sloan letter charts, and circumpapillary retinal nerve fiber layer (RNFL) and macular total retinal, RNFL, and ganglion cell layer/inner plexiform layer thickness was measured using spectral domain optical coherence tomography (OCT). We used age- and gender-adjusted linear regression to compare contrast acuity and retinal thickness between CMT groups. RESULTS: One of 5 patients with CMT2A had optic nerve atrophy (binocular high-contrast acuity equivalent 20/160, mean circumpapillary RNFL 47.5 µm). The other patients with CMT2A had normal high- and low-contrast acuity and retinal thickness, and there were no significant differences between patients with CMT2A, CMT1A, and CMTX1. CONCLUSIONS: Optic atrophy occurs in some patients with CMT2A, but in others, there is no discernible optic nerve involvement. This suggests that optic neuropathy is specific to certain MFN2 mutations in CMT2A and that low-contrast acuity or OCT is of limited value as a disease-wide biomarker.

Charcot neuroarthropathy in patients with Charcot Marie Tooth Disease.

Charcot Marie Tooth disease (CMT) is the most common inherited neuropathy and is also called Hereditary Motor Sensory Neuropathy (HMSN). Whilst both motor and sensory deficits are present, motor deficits tend to predominate over sensory deficits. Charcot neuroarthropathic joints occur in conditions, most commonly diabetes nowadays, where joints are destroyed in association with reduced protective sensation, pain in particular. Three cases of development of Charcot joint disorders in patients with CMT are discussed and the literature is reviewed. Orthopaedic surgeons should be aware that Charcot joints can occur in CMT and surgery can be complicated by Charcot joints.

Pes cavovarus in Charcot-Marie-Tooth compared to the idiopathic cavovarus foot: A preliminary weightbearing CT analysis.

BACKGROUND: Pes cavovarus is a foot deformity that can be idiopathic (I-PC) or acquired secondary to other pathology. Charcot-Marie-Tooth disease (CMT) is the most common adult cause for acquired pes cavovarus deformity (CMT-PC). The foot morphology of these distinct patient groups has not been previously investigated. The aim of this study was to assess if morphological differences exist between CMT-PC, I-PC and normal feet (controls) using weightbearing computed tomography (WBCT). METHODS: A retrospective analysis of WBCT scans performed between May 2013 and June 2017 was undertaken. WBCT scans from 17 CMT-PC, 17 I-PC and 17 healthy normally-aligned control feet (age-, side-, sex- and body mass index-matched) identified from a prospectively collected database, were analysed. Eight 2-dimensional (2D) and three 3-dimensional (3D) measurements were undertaken for each foot and mean values in the three groups were compared using one-way ANOVA with the Bonferroni correction. RESULTS: Significant differences were observed between CMT-PC or I-PC and controls (p<0.05). Two-dimensional measurements were similar in CMT-PC and I-PC, except for forefoot arch angle (p=0.04). 3D measurements (foot and ankle offset, calcaneal offset and hindfoot alignment angle) demonstrated that CMT-PC exhibited more severe hindfoot varus malalignment than I-PC (p=0.03, 0.04 and 0.02 respectively). CONCLUSIONS: CMT-related cavovarus and idiopathic cavovarus feet are morphologically different from healthy feet, and CMT feet exhibit increased forefoot supination and hindfoot malalignment compared to idiopathic forms. The use of novel three-dimensional analysis may help highlight subtle structural differences in patients with similar foot morphology but aetiologically different pathology. LEVEL OF EVIDENCE: Level III, retrospective comparative study.