Anti-disialosyl-immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study.

BACKGROUND AND PURPOSE: In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti-disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA). RESULTS: Fifty-five patients with a polyneuropathy evolving for more than 2 months and with at least one anti-disialosyl ganglioside IgM antibody, that is, anti-GD1b, -GT1b, -GQ1b, -GT1a, -GD2 and -GD3, were identified. Seventy-eight percent of patients were male, mean age at disease onset was 55 years (30-76) and disease onset was progressive (82%) or acute (18%). Patients presented with limb sensory symptoms (94% of cases), sensory ataxia (85%), oculomotor weakness (36%), limb motor symptoms (31%) and bulbar muscle weakness (18%). Sixty-five percent of patients had a demyelinating polyradiculoneuropathy electrodiagnostic profile and 24% a sensory neuronopathy profile. Anti-GD1b antibodies were found in 78% of cases, whilst other anti-disialosyl antibodies were each observed in less than 51% of patients. Other features included nerve biopsy demyelination (100% of cases), increased cerebrospinal fluid protein content (75%), IgM paraprotein (50%) and malignant hemopathy (8%). Eighty-six percent of CNDA patients were intravenous immunoglobulins-responsive, and rituximab was successfully used as second-line treatment in 50% of cases. Fifteen percent of patients had mild symptoms and were not treated. CNDA course was progressive (55%) or relapsing (45%), and 93% of patients still walked after a mean disease duration of 11 years. CONCLUSION: Chronic neuropathies with anti-disialosyl ganglioside IgM antibodies have a recognizable phenotype, are mostly intravenous immunoglobulins-responsive and present with a good outcome in a majority of cases.

Generalization of ocular myasthenia gravis 10 years after onset.

BACKGROUND: Generalization of ocular myasthenia gravis (OMG) represents a pejorative evolution, and no validated generalization-prevention strategy exists. The study aimed to determine the percentage of patients with OMG generalization and identify factors predictive of it to establish a prediction score. METHODS: This retrospective, observational study included 151 patients diagnosed with OMG after an initial work-up in our institution. The outcome measure was time to MG generalization. The explanatory variables were age at onset (> 55 years), sex, first-year anti-acetylcholine-receptor antibody-positivity, repetitive nerve stimulation showing electromyogram decrement and corticosteroid use. Kaplan-Meier estimations of the probability of risk of generalization, and descriptive and multivariate Cox model analyses were computed. A nomogram combining explanatory variables was used to establish a score to predict the probability of OMG generalization. RESULTS: Among 183 patients' charts identified, 151 had confirmed OMG. Their median follow-up was 5.7 years. Estimations (95% CI) of OMG-generalization risk at 1, 3 and 10 years post-symptom onset, respectively, were: 13.0% (7.3-18.2), 25.1% (17.5-32.0) and 37.8% (27.2-45.2). The p-value-based multivariate analysis associated generalization with female sex, electromyogram decrement and first-year anti-acetylcholine-receptor antibody positivity, and Akaike information criterion-based analysis retained those three parameters and corticosteroid use. A nomogram was built and validated with an optimism-corrected C-statistic of 0.68, and calibration plots showed good fit. CONCLUSIONS: Our population's percentage of OMG generalization is in line with recent publications. Using the identified prognostic factors, the nomogram provided a score to predict the probable risk of generalization in our cohort.

Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial.

Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated. Objective: To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen. Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility. Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants. Main Outcomes and Measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted. Results: Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, -3121 to -461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15). Conclusions and Relevance: In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT00987116.

[Indications and follow-up for autologous hematopoietic stem cell transplantation in multiple sclerosis: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) in association with the Francophone Society of Multiple Sclerosis]. / Indications de l'autogreffe dans la sclérose en plaques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC) en lien avec la Société francophone de la sclérose en plaques.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 8th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France. In this article we give the indications of autologous stem cell transplantation in multiple sclerosis as well as recommendations regarding post-transplant follow-up of patients under the hospice of the SFGM-TC and the Francophone Society of Multiple Sclerosis.

Remote brain microhaemorrhages may predict haematoma in glioma patients treated with radiation therapy.

OBJECTIVES: To evaluate the prevalence of cerebral remote microhaemorrhages (RMH) and remote haematomas (RH) using magnetic resonance susceptibility-weighted imaging (SWI) among patients treated for gliomas during follow-up. METHODS: We conducted a retrospective single centre longitudinal study on 58 consecutive patients treated for gliomas from January 2009 through December 2010. Our institutional review board approved this study. We evaluated the presence and number of RMH and RH found outside the brain tumour on follow-up MR imaging. We performed univariate and bivariate analyses to identify predictors for RMH and RH and Kaplan-Meier survival analysis techniques. RESULTS: Twenty-five (43%) and four patients (7%) developed at least one RMH or RH, respectively, during follow-up. The risk was significantly higher for patients who received radiation therapy (49% and 8% versus 0%) (p = 0.02). The risk of developing RH was significantly higher in patients with at least one RMH and a high burden of RMH. The mean age of those presenting with at least one RMH or RH was significantly lower. CONCLUSIONS: RMH were common in adult survivors of gliomas who received radiation therapy and may predict the onset of RH during follow-up, mainly in younger patients. KEY POINTS: • Brain RMH and RH are significantly more likely to occur after RT. • RMH occur in almost half of the patients treated with RT. • RMH and RH are significantly more frequent in younger patients. • RH occur only in patients with RMH.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency.

Encephalitis and CSF increased level of interferon-α in Kikuchi-Fujimoto disease.

Neurological manifestations have been reported in Kikuchi-Fujimoto disease (KFD). Characteristics of brain lesions are not defined. In addition, no biological indexes are known to help clinicians along the diagnosis process. The authors describe encephalitis associated with KFD. Brain MRI, positron emission tomography (PET) scan and a large biological assessment including interferon α (INF-α) level measurement in cerebrospinal fluid (CSF) were performed. A 39-year-old man with chronic headaches developed diplopia, slow ideation and behavioural disturbances. MRI showed brain lesions particularly in the pontine region and internal temporal lobes with enhancement of the perivacular space and the walls of the lateral ventricle. The IFN-α level was increased in the CSF without viral infection. Cervical and mediastinal adenitis were evident as a hypermetabolic focus on a PET scan, and biopsy confirmed the diagnosis of KFD. The encephalitis spontaneously remitted. The authors characterised brain lesions especially related to KFD in association with increased of IFN-α level in the CSF.

[Gliomatosis cerebri: a biopsy and autopsy case report]. / Gliomatose cérébrale diffuse: étude biopsique et autopsique d'un cas.

Gliomatosis cerebri is a rare glial neoplasm, characterized by diffuse brain infiltration with relative preservation of the underlying cytoarchitecture. Its clinical and radiologic features are not specific and its antemortem diagnosis is difficult. We report a case of gliomatosis cerebri in a 68-year-old woman presenting with gait disturbances and episodic seizures. MRI showed bilateral white matter hypersignal intensities on Flair sequences and brain biopsy revealed a poorly cellular proliferation of neoplasic glial cells strongly expressing OLIG-2, Ki-67 and occasionally GFAP, without alpha-internexin expression. The patient status worsened rapidly and she died 2 months after the initial symptoms. Postmortem brain examination confirmed gliomatosis cerebri and revealed a focal glioblastoma in the frontal cortex, with nuclear p53 expression in the highest malignant areas. Gliomatosis cerebri should be included in the differential diagnostic of diffuse brain lesions. Antemortem diagnosis, although difficult, can be assessed by IRM and careful biopsy examination. Progression to glioblastoma has been seldom reported, enhancing the controversy about the etiopathogenesis of this rare tumour.