OBJECTIVETo quantitatively describe the MRI fat infiltration pattern of muscle degeneration in Charcot-Marie-Tooth (CMT) type 1A (CMT1A) disease and to look for correlations with clinical variables.
...METHODSMRI fat fraction was assessed in lower-limb musculature of patients with CMT1A and healthy controls. More particularly, 14 muscle compartments were selected at leg and thigh levels and for proximal, distal, and medial slices. Muscle fat infiltration profile was determined quantitatively in each muscle compartment and along the entire volume of acquisition to determine a length-dependent gradient of fat infiltration. Clinical impairment was evaluated with muscle strength measurements and CMT Examination Scores (CMTESs).
RESULTSA total of 16 patients with CMT1A were enrolled and compared to 11 healthy controls. Patients with CMT1A showed a larger muscle fat fraction at leg and thigh levels with a proximal-to-distal gradient. At the leg level, the largest fat infiltration was quantified in the anterior and lateral compartments. CMTES was correlated with fat fraction, especially in the anterior compartment of leg muscles. Strength of plantar flexion was also correlated with fat fraction of the posterior compartments of leg muscles.
CONCLUSIONOn the basis of quantitative MRI measurements combined with a dedicated segmentation method, muscle fat infiltration quantified in patients with CMT1A disclosed a length-dependent peroneal-type pattern of fat infiltration and was correlated to main clinical variables. Quantification of fat fraction at different levels of the leg anterior compartment might be of interest in future clinical trials.
Abstract
BACKGROUND AND AIMS
Hereditary transthyretin amyloidosis (ATTR) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has ...been poorly studied and is not well known to nephrologists.
METHOD
We conducted a retrospective study describing kidney phenotype of all prevalent patients with ATTR mutations, with symptomatic amyloidosis or asymptomatic carriers, followed-up in two university hospitals from the South of France, between June 2011 and June 2021.
RESULTS
103 patients were included, among whom 79 were symptomatic and 24 asymptomatic carriers, and 54% carried a V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.7% had a urinary protein/creatinine ratio ≥0.5 g/g. None of the asymptomatic carriers had CKD or proteinuria. Median CKD-free survival in the global cohort was 81.0 years, and the average age of CKD onset was 69.3 ± 13.0 years. In a multivariate analysis, late onset of ATTR symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. In a 38-year-old V30M female, who presented a kidney-predominant phenotype, treatment with Patisiran resulted in remission of the nephrotic syndrome.
CONCLUSION
CKD affects almost one-third of patients with symptomatic ATTR amyloidosis. The role of ATTR amyloidosis per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.
Background
The factors underlying the topography of nitrous oxide (N2O)‐induced neurological complications are unknown.
Methods
We included all consecutive patients admitted to the university ...hospital of Marseille for N2O‐induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission.
Results
In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly N2O consumption (~600 g cylinder per week, odds ratio OR = 1.11, 95% confidence interval CI = 1.001–1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600‐g cylinders consumed weekly (ρ = 0.40, p < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05–1.58). Mean lower‐limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = −0.34, p < 0.05).
Conclusions
The odds of myelopathy increased with the amount of N2O consumption, and the odds of neuropathy increased with the duration of N2O exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications.
CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M IgM paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ...ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.
•This largest study to date of CANOMAD patients revealed that one third harbored an overt hematologic malignancy, consisting mainly in WM.•IVIg and rituximab-based regimens were the most effective therapies with a 50% response rate.
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Introduction
Anti-MAG neuropathies are associated with an IgM monoclonal gammopathy of undetermined significance (MGUS) or with a malignant haemopathy. Our objective was to determine whether the ...presence of a haemopathy or somatic mutations of MYD88 and CXCR4 genes influences disease presentation and response to rituximab (RTX).
Methods
We included 79 patients (mean age 74 years, disease duration 9.68 years) who had a bone marrow aspiration with morphologic and immunophenotypic analysis. MYD88
L265P
and CXCR4 mutations were analysed in peripheral B cells.
Information collected included: inflammatory neuropathy cause and treatment sensory sum score (ISS), MRC testing, overall neuropathy limitation scale (ONLS), Rash-built Overall Disability Score (RODS), ataxia score, anti-MAG titres, peak IgM dosage, neurofilament light chain levels, motor and sensory amplitudes, motor unit index (MUNIX) and motor unit size index (MUSIX) sum scores. Efficacy of RTX was evaluated at 12 months in 26 patients.
Results
Malignant haematological disorders were discovered in 17 patients (22%): 13 Waldenstrom macroglobulinemia, 3 marginal zone lymphoma and one mantle cell lymphoma. MYD88
L265P
mutation was detected in 29/60 (48%) patients and CXCR4 in 1 single patient. Disease severity, biological and electrophysiological data and response to RTX were comparable in patients with MGUS/lymphoma and patients with/without MYD88
L265P
mutation. ISS was lower and MUSIX higher in patients improved by RTX.
Conclusions
MYD88
L265P
mutation and underlying haemopathies are not predictive of a more severe disease. However, in cases of resistant and progressive neuropathy, they provide an opportunity to prescribe newly available drugs such as Bruton tyrosine kinase inhibitors.
•- Triple stimulation technique can be used in routine clinical practice and in multicenter studies in ALS patients.•- Assessment of corticospinal dysfunction at the first visit of the patient was ...improved by the use of triple stimulation technique compared to conventional TMS.•- Triple stimulation technique results are correlated with the clinical upper motor neuron score and ALSFRS-R.
To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study.
Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score.
TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers.
TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients.
This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.
La maladie de Charcot-Marie-Tooth liée à l’X de type 1 (CMTX1) en lien avec une mutation de la connexine 32 est caractérisée par des différences cliniques entre les sexes. Les femmes sont ...généralement moins affectées.
La présentation clinique des femmes atteintes de CMTX semble cependant être hétérogène. Notre objectif est d’étendre la description phénotypique des femmes atteintes de CMTX.
Nous avons évalué rétrospectivement 263 patients atteints de CMT1X provenant de 11 centres de référence français. Des données démographiques, cliniques et de conduction nerveuse motrice ont été recueillies. Le phénotype a été évalué par les scores CMTES et ONLS. Nous avons recherché une force musculaire asymétrique, des VCM hétérogènes et des blocs de conduction moteur.
L’étude a porté sur 137 femmes et 126 hommes. Les femmes présentaient des déficits moteurs et des VCM significativement plus asymétriques que les hommes. Deux groupes de femmes ont été identifiés après 46 ans. Le premier groupe représentait 59 %, avec des femmes évoluant aussi sévèrement que les hommes, mais avec un âge d’apparition des symptômes plus tardif. Le second groupe présentait des symptômes légers. Au total, 41 % des femmes présentaient un bloc de conduction moteur.
Nous avons identifié deux sous-groupes de femmes atteintes de CMTX1 âgées de plus de 46 ans. Nous avons également montré que les femmes atteintes de CMTX peuvent avoir une présentation clinique atypique, ce qui peut conduire à un mauvais diagnostic. Quatre femmes ont reçu de l’immunoglobuline par voie intraveineuse avant d’être diagnostiquées CMTX1.
Chez une femme atteinte de neuropathie chronique, la présence d’une asymétrie clinique, d’une VCM hétérogène et/ou d’un CB moteur doit faire penser à une neuropathie CMTX1.
Define the cutoff thresholds of the Kappa (K) and Lambda (L) free light chains (FLC) indices for the detection of intrathecal immunoglobulin synthesis (IIS) using the new K and L FLC ELISA from ...SEBIA. The reference technique, which is not readily standardized between laboratories, is based on the demonstration of oligoclonal banding (OCB) in cerebrospinal fluid (CSF) which is absent in serum. For the past 6 years, we have also routinely calculated the K FLC index using The Binding Site (TBS) reagents on an Optilite instrument, an approach increasingly used as an alternative and/or a complement to electrophoretic analysis.
We analyzed 391 serum/CSF pairs divided into three groups. The first group were cases without OCB and with normal albumin CSF/serum ratio (n=174). The second group were cases with specific OCB (n=73). The last group included patients with increased albumin CSF/sera ratio without OCB (n=142).
Analysis of the first group determined that the cutoffs for detection of IIS are respectively 2.55 and 1.02 for the K FLC and L FLC indices. Of the 73 cases with IIS, only 2 had a K FLC index below this threshold (sensitivity of 97.26%), while 16 out of 73 cases (78.08%) and 13 out of 72 cases (81.94%) had an IgG and L FLC index below the cutoffs, respectively. Additionally, we illustrate equivalent performances for prediction of the presence of OCB between SEBIA and TBS methods.
Sebia K FLC and L FLC assays are adequate alternative methods for the diagnosis of IIS.
•Patients with antibodies against the node of Ranvier fulfil electrodiagnostic criteria for definite CIDP.•Patients with anti-CNTN1 and anti-NfascC155 antibodies have similar electrophysiological ...patterns.•Electrophysiological abnormalities are more marked in patients with antibodies.
Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics.
The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies.
All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve <24 m/s or motor velocity on ulnar nerve <26 m/s or motor distal latency on ulnar nerve >7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%.
Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier.
Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a “demyelinating” neuropathy.
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