Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous diseases caused by mutations affecting neuromuscular transmission. Even if the first symptoms mainly occur during childhood, adult neurologists must confront this challenging diagnosis and manage these patients throughout their adulthood. However, long-term follow-up data from large cohorts of CMS patients are lacking and the long-term prognosis of these patients is largely unknown. We report the clinical features, diagnostic difficulties, and long-term prognosis of a French nationwide cohort of 235 adult patients with genetically confirmed CMS followed in 23 specialized neuromuscular centres. Data were retrospectively analysed. Of the 235 patients, 123 were female (52.3%). The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. Mean follow-up time between first symptoms and last visit was 34 years (SD = 15.1). Pathogenic variants were found in 19 disease-related genes. CHRNE-low expressor variants were the most common (23.8%), followed by variants in DOK7 (18.7%) and RAPSN (14%). Genotypes were clustered into four groups according to the initial presentation: ocular group (CHRNE-LE, CHRND, FCCMS), distal group (SCCMS), limb-girdle group (RAPSN, COLQ, DOK7, GMPPB, GFPT1), and a variable-phenotype group (MUSK, AGRN). The phenotypical features of CMS did not change throughout life. Only four genotypes had a proportion of patients requiring intensive care unit (ICU) admission that exceeded 20%: RAPSN (54.8%), MUSK (50%), DOK7 (38.6%) and AGRN (25.0%). In RAPSN and MUSK patients most ICU admissions occurred before age 18 years and in DOK7 and AGRN patients at or after 18 years of age. Different patterns of disease course (stability, improvement and progressive worsening) may succeed one another in the same patient throughout life, particularly in AGRN, DOK7 and COLQ. At the last visit, 55% of SCCMS and 36.3% of DOK7 patients required ventilation; 36.3% of DOK7 patients, 25% of GMPPB patients and 20% of GFPT1 patients were wheelchair-bound; most of the patients who were both wheelchair-bound and ventilated were DOK7 patients. Six patients died in this cohort. The positive impact of therapy was striking, even in severely affected patients. In conclusion, even if motor and/or respiratory deterioration could occur in patients with initially moderate disease, particularly in DOK7, SCCMS and GFPT1 patients, the long-term prognosis for most CMS patients was favourable, with neither ventilation nor wheelchair needed at last visit. CHRNE patients did not worsen during adulthood and RAPSN patients, often severely affected in early childhood, subsequently improved.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

BACKGROUND & PURPOSE: In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. RESULTS: 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. CONCLUSION: 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.

Multiple Sclerosis-Associated Uveitis: A Case Report of Refractory Bilateral Chronic Granulomatous Panuveitis Successfully Treated with Tocilizumab.

PURPOSE: To report a case of uveitis associated with multiple sclerosis (MS) that was refractory to multiple lines of therapy but achieved remission with tocilizumab. METHODS: We conducted a retrospective analysis of the patient's medical record including clinical, biological and imaging data. RESULTS: A 33-year-old female patient with a history of MS inactive for 5 years on teriflunomide, and no significant medical or ophthalmological history, presented with bilateral granulomatous panuveitis. Initial examination revealed a visual acuity of 0.4 logMAR and 1.3 logMAR in the right eye and the left eye, respectively, along with a significant anterior chamber flare in both eyes, posterior synechiae, large granulomatous keratic precipitates, bilateral vitritis, bilateral macular edema with foveolar pigment epithelial detachment, and significant bilateral venous and arterial vasculitis. The patient underwent several lines of treatment, all of which proved unsuccessful, including corticosteroids alone or in combination with azathioprine, methotrexate, and mycophenolate mofetil. As a final therapeutic option, tocilizumab was initiated, leading to the remission of uveitis. One year later, the uveitis remained inactive under a 5 mg/day prednisone regimen. CONCLUSIONS: Tocilizumab appears to be an efficient option for managing uveitis associated with MS and may be a valuable choice for clinicians dealing with such cases.

Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available. METHODS: In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy. RESULTS: 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants (n = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p = .007), significant weight loss (33 vs 11%, p = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p = .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. CONCLUSION: 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.

White matter abnormalities in 15 subjects with SPG76.

BACKGROUND AND OBJECTIVES: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders characterized by progressive pyramidal tract involvement. SPG76 is a recently identified form of HSP, caused by biallelic calpain-1 (CAPN1) variants. The most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy and non-specific white matter abnormalities were reported in only one case. Following the identification of prominent white matter abnormalities in a subject with CAPN1 variants, which delayed the diagnosis, we aimed to verify the presence of MRI patterns of white matter involvement specific to this HSP. METHODS: We performed a retrospective radiological qualitative analysis of 15 subjects with SPG76 (4 previously unreported) initially screened for white matter involvement. Moreover, we performed quantitative analyses in our proband with available longitudinal studies. RESULTS: We observed bilateral, periventricular white matter involvement in 12 subjects (80%), associated with multifocal subcortical abnormalities in 5 of them (33.3%). Three subjects (20%) presented only multifocal subcortical involvement. Longitudinal quantitative analyses of our proband revealed increase in multifocal white matter lesion count and increased area of periventricular white matter involvement over time. DISCUSSION: SPG76 should be added to the list of HSPs with associated white matter abnormalities. We identified periventricular white matter involvement in subjects with SPG76, variably associated with multifocal subcortical white matter abnormalities. These findings, in the presence of progressive spastic paraparesis, can mislead the diagnostic process towards an acquired white matter disorder.

Are Miller Fisher syndrome and CANDA due to a paranodopathy?

OBJECTIVE: To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier. STUDY DESIGN AND SETTING: 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). RESULTS: 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. CONCLUSION: 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.

Untreated patients with multiple sclerosis: A study of French expert centers.

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.

Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.

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.

Multidimensional evaluation is necessary to assess hand function in patients with Charcot-Marie-Tooth disease type 1A.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis.

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.

Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study.

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.

Foot Function Index: A Promising Questionnaire for Individuals With Charcot-Marie-Tooth Disease Type 1A.

OBJECTIVE: To evaluate in a preliminary methodologic study, the Foot Function Index (FFI), a 3-subscale (pain, disability, and activity restriction) foot disability assessment questionnaire, in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). DESIGN: Monocentric exploratory cross-sectional study with 2 identical evaluations by the same physical medicine and rehabilitation physician at 14-day intervals (test-retest) according to international guidelines for validating health-related patient-reported outcomes, the Consensus-based Standards for the Selection of Health Measurement Instruments Criteria. SETTING: Physical medicine and rehabilitation and neurology departments in a French academic hospital. PARTICIPANTS: Patients with CMT1A confirmed by molecular biology (N=26). INTERVENTION: The FFI and a health-related quality-of-life questionnaire (Medical Outcomes Study Short Form 36 [SF-36] with mental and physical composite scores) combined with quantitative walk analysis by instrumental gait analysis and evaluation of isokinetic quadriceps and hamstrings peak torque by isokinetic dynamometer. MAIN OUTCOME MEASURES: FFI score and its dimensions. RESULTS: Acceptability was satisfactory, with less than 5% missing data and good distribution of results. Internal consistency was very satisfactory, with Cronbach α of 0.95. Reproducibility was very satisfactory, with Lin concordance coefficient 0.82. External consistency was satisfactory, with expected correlation coefficients: the FFI was significantly correlated with the SF-36 physical composite score and gait parameters (cadence) (r=-0.58 and r=-0.52; P<.005) but not with peak torque or SF-36 mental composite score. CONCLUSIONS: This study confirms the very good metrologic properties of the FFI in patients with CMT1A. The FFI could be a promising questionnaire to assess foot-related disability in a neurologic disease. Complementary studies are still needed to confirm these promising preliminary results.

Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions.

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.

Walking Speed Is Correlated With the Isokinetic Muscular Strength of the Knee in Patients With Charcot-Marie-Tooth Type 1A.

Charcot-Marie-Tooth disease type 1A is the most common hereditary neuropathy. Affected individuals have a distal motor deficit, initially affecting the lower limbs and impairing walking performance. Isokinetic dynamometry can be used to objectively assess muscle strength of patients with neuromuscular disorders. No studies have evaluated the effect of muscle strength deficits of knee extensors and flexors on walking parameters for patients with Charcot-Marie-Tooth disease type 1A. The purpose of this study was to determine correlations between the isokinetic muscular strength of knee flexors and knee extensors and walk parameters for patients with Charcot-Marie-Tooth disease type 1A. isokinetic muscular strength of the knee was assessed on an isokinetic dynamometer (Cybex) and walking by instrumented walkway analysis (GaitRite). We included 33 patients (23 females, mean ± SD age 46.7 ± 13.3 yrs, mean ± SD body mass index 25.7 ± 4.6 kg/m). We found a correlation between walking speed and isokinetic muscular strength of knee extensors for the entire population and between walking speed and isokinetic muscular strength of knee extensors and knee flexors for patients younger than 50 yrs. Isokinetic dynamometry can provide objective measures of knee muscle strength, which is correlated with walking speed but not cadence or step/stride length of patients with Charcot-Marie-Tooth disease.

Decreased prevalence of cancer in patients with multiple sclerosis: A case-control study.

BACKGROUND: 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. OBJECTIVES: To evaluate lifetime cancer prevalence in a large cohort of MS patients relative to appropriate controls. METHODS: 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. RESULTS: 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. CONCLUSION: MS was associated with a reduced overall cancer risk.

Natalizumab-PML survivors with subsequent MS treatment: Clinico-radiologic outcome.

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.

Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E.

INTRODUCTION: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. CASE REPORT: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding.  A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. CONCLUSION: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has  not yet been determined.

Toxoplasmic pachymeningitis with visual field impairment in a single-eyed patient and a literature review.

To describe the clinical features of a patient with toxoplasmic pachymeningitis and provide a review of the recent cases of pachymeningitis in the literature.Retrospective, observational case report. A one-eyed patient who presented to our institution with blurred vision, floaters, and visual field shrinkage. Review of clinical, laboratory, perimetric, and radiologic records of the patient and description of the efficacy of antibiotic therapy. The signs of ocular impairment, including visual acuity, visual field, and magnetic resonance imaging (MRI) changes. A one-eyed patient who complained of blurred vision and unexplained visual field shrinkage was evaluated. The diagnosis of toxoplasmic pachymeningitis was confirmed by existence of a toxoplasmic seroconversion, cerebrospinal fluid abnormalities, radiological features, absence of other diagnoses, improvement of symptoms, and resolution of pachymeningitis in MRI with oral trimethoprim-sulfamethoxazole combination.Pachymeningitis is a rare disease and toxoplasmic pachymeningitis has never been described. Among the various infectious causes, screening for toxoplasmosis must be performed because it can lead to pachymeningitis and sequelae. Variable features may lead to misdiagnosis and delay in the treatment of this sight-threatening and potentially fatal disease.