To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier.
We performed the pathological study (nerve biopsy of a sural nerve) of ...two patients, one with an acute form of ataxic peripheral neuropathy called ‘Miller Fisher syndrome’ (MFS), the other one with a chronic form called ‘chronic ataxic neuropathies with disialosyl antibodies’ (CANDA).
A dysimmune process involving peripheral nerves commences in myelin, at the internodal area or/and in the paranodal and nodal regions. Our electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.
Many of the immune-mediated peripheral neuropathies are now classified as nodoparanodopathies. This subtype of auto-immune neuropathy may present various clinical phenotypes such as ‘Acute Motor Axonal Neuropathy’ (AMAN), ‘Acute Motor and Sensory Neuropathy’ (AMSAN) or ‘chronic inflammatory demyelinating polyradiculoneuropathy’ (CIDP), and are associated with anti-disialosyl antibodies. In our two cases, some paranodes seem to be associated with macrophages and we hypothesized that these lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region due to disialosyl antibodies against gangliosides which are mainly located at the level of the axolemma of the paranode.
•Electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.•Some paranodes seem to be associated with macrophages.•These lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region.•This may be due to antibodies against gangliosides which are mainly located at the level of the paranode (axolemma).•Miller Fisher syndrome and CANDA should be classified as paranodopathies.
Studies of cancer prevalence have produced conflicting results concerning the relative risk of overall and specific sub-types of cancer in patients with multiple sclerosis (MS). Contemporary controls ...and information on tobacco use and alcohol consumption are generally missing from previous studies.
To evaluate lifetime cancer prevalence in a large cohort of MS patients relative to appropriate controls.
We conducted a case-control study, using a postal survey of a cohort of MS patients. Of the 1574 questionnaires sent, 1107 could be used for statistical analysis. Data from 1568 controls were prospectively collected using the same self-administered survey among consecutive out-patients in a single neurology department. Propensity scores matched on age, gender, and history of smoking and alcohol consumption were calculated.
Among the MS patients, 7.32% had ever presented with a cancer, whereas 12,63% of the controls had, leading to a bootstrap matched odds ratio (OR) of 0.63; 95% CI 0.57-0.70. Although only exploratory, the use of DMT (immunomodulators or immunosupressants) did not appear to increase this risk (p = 0.42). The disease course also did not affect cancer prevalence.
MS was associated with a reduced overall cancer risk.
In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies.
We identified 166 patients with ...neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified.
This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.
•The severity of axonal loss in Charcot-Marie-Tooth (CMT) disease type 1A may be associated with loss of function and health-related quality of life.•Despite severe impairment in electrophysiological ...parameters and significant distal amyotrophy, we found relative conservation of autonomy for activities of daily living, health-related quality of life and manual function.•Electrophysiological follow-up seems to be of little relevance to follow health-related quality of life in CMT and manual function related to functional objectives for everyday physical medical and rehabilitation.
Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A) is the most common hereditary neuropathy. Several studies have assessed the relation between axonal loss and grip strength; however, the functional impact on dexterity and health-related quality of life (HRQoL) is unknown. We hypothesized that the severity of axonal loss will be correlated with loss of function and HRQoL.
The purpose of this study was to evaluate the relation between severity of electroneuromyography impairment and its impact on function and HRQoL in adults with CMT1A.
Grip and lateral pinch strength were evaluated with specific dynamometers: the Jamar and the Pinch Gauge. Dexterity was explored with the Sollerman, Jebsen, and Nine-hole Peg tests. The CMT impact on well-being was assessed by the validated Medical Outcomes Study Short Form 36 (SF-36), Beck Depression Inventory, and Fatigue Severity Scale, and disease severity by the CMT neuropathy score and Inflammatory Neuropathy Cause and Treatment sensory sum score. Finally, axonal loss and demyelination process was assessed by electroneuromyography.
We included 33 participants with CMT1A (23 females, mean SD age 47.0 4.7 years). We found lack of correlation between severe electroneuromyography impairment (frequency of abnormal results >80%), significant distal amyotrophy (70%) and quality of life (mean SD scores for physical and mental SF-36 36.4 10.0 and 48.4 11.5), autonomy for activities of daily living, and hand function that remains relatively preserved. We found a correlation between lateral pinch and dexterity according to the Sollerman test (r=0.52, p<0.05) but a lack of correlation among the other parameters.
Electrophysiological follow-up seems to be of little relevance to follow HRQoL in individuals with CMT1A and manual function related to functional objectives for everyday physical medicine and rehabilitation practice. The manual function is complex and requires an overall, quantitative, qualitative and multidisciplinary assessment. Each tool (Pinch Gauge, Jamar, Sollerman, Jebsen, Nine-hole Peg) measures a specific element of manual function and is necessary when performing a grip function analysis.
Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from
gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ...ATTRv treatments are available.
In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the
gene in French patients with age >50 years with a progressive idiopathic polyneuropathy.
553 patients (70% males) with a mean age of 70 years were included. A
gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met
variation in 10 cases. In comparison with patients with no
gene pathogenic variants (
= 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%,
= .007), significant weight loss (33 vs 11%,
= .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%,
= .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives.
In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.
Background and purpose
Disease‐modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives ...of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment.
Methods
We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included.
Results
Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval CI 30.7–31.9) were not receiving any DMT. Although patients with a relapsing‐remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2–15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing‐remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio OR 0.52 95% CI 0.44–0.61) and lower EDSS score (OR 0.78 95% CI 0.74–0.82). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT.
Conclusion
A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.
The objectives were to determine the proportion of untreated patients with multiple sclerosis (MS) followed in expert centers in France and to determine the predictive factors of non‐treatment. Among the 21,189 patients with MS, 31.3% were not receiving any disease‐modifying treatment and the most important predictive factor for not being treated was the disease course: 14.8% of patients with a relapsing‐remitting course were untreated, while 50.4% of those with secondary and 64.2% of those with primary progressive MS were untreated. After multivariate analysis among patients with relapsing‐remitting MS, the main factors explaining never having been treated were not having ≥9 lesions on brain magnetic resonance imaging and lower Expanded Disability Status Scale score.
Background
The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and ...multiple sclerosis and NMOSD is not clear.
Objectives
Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions.
Methods
We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed.
Results
Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD.
Discussion
Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
Objectives:
We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin ...oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis.
Material and Methods:
We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0.
Results:
Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0–4.0)) compared to SM patients (2.0, (1.0–3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01–1.95, p = 0.046).
Conclusion:
SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.
Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them,
CAPN1
, when mutated, is responsible for a complex inherited form ...of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new
CAPN1
disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing.
CAPN1
variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.
Objective: To describe the clinico-radiologic outcome of MS patients with natalizumab-related progressive multifocal leukoencephalopathy (Nz-PML) surviving and receiving disease-modifying therapy ...(DMT). Methods: We describe clinical and radiologic evolution of Nz-PML survivors in an observational retrospective multicenter cohort to clarify the effect of different subsequent MS DMT strategies. Twenty-three patients from 11 centers were analyzed. Outcomes were (1) clinical efficacy of post-PML MS DMT, (2) radiologic efficacy of post-PML MS DMT, (3) radiologic evolution of PML lesion, and (4) disability progression. Results: There was no clinical worsening of PML symptoms with a stability of Expanded Disability Status Scale at the last follow-up. No relapse was reported with fingolimod and dimethyl fumarate. No radiologic worsening of Nz-PML lesion was observed at the end of the follow-up. Conclusion: In this large cohort of patients with Nz-PML, MS therapies given after Nz discontinuation were not associated with PML worsening. A larger cohort with longer follow-up will be necessary to confirm this therapeutic strategy.
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