Hot Topics on COVID-19 and Its Possible Association with Guillain-Barré Syndrome

As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing. However, despite a high number of case reports and case series on COVID-19 and Guillain-Barré-Syndrome (GBS), a causal association is still highly debated, due to the lack of case-control studies. In this opinion paper, we focus on a few clinically relevant questions regarding the possible link between GBS and SARS-CoV-2 infection or vaccination based on our personal clinical experience and literature review

A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity

RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesion assessment in multiple sclerosis.

In multiple sclerosis (MS), the presence of a paramagnetic rim at the edge of non-gadolinium-enhancing lesions indicates perilesional chronic inflammation. Patients featuring a higher paramagnetic rim lesion burden tend to have more aggressive disease. The objective of this study was to develop and evaluate a convolutional neural network (CNN) architecture (RimNet) for automated detection of paramagnetic rim lesions in MS employing multiple magnetic resonance (MR) imaging contrasts. Imaging data were acquired at 3 Tesla on three different scanners from two different centers, totaling 124 MS patients, and studied retrospectively. Paramagnetic rim lesion detection was independently assessed by two expert raters on T2*-phase images, yielding 462 rim-positive (rim+) and 4857 rim-negative (rim-) lesions. RimNet was designed using 3D patches centered on candidate lesions in 3D-EPI phase and 3D FLAIR as input to two network branches. The interconnection of branches at both the first network blocks and the last fully connected layers favors the extraction of low and high-level multimodal features, respectively. RimNet's performance was quantitatively evaluated against experts' evaluation from both lesion-wise and patient-wise perspectives. For the latter, patients were categorized based on a clinically relevant threshold of 4 rim+ lesions per patient. The individual prediction capabilities of the images were also explored and compared (DeLong test) by testing a CNN trained with one image as input (unimodal). The unimodal exploration showed the superior performance of 3D-EPI phase and 3D-EPI magnitude images in the rim+/- classification task (AUC = 0.913 and 0.901), compared to the 3D FLAIR (AUC = 0.855, Ps < 0.0001). The proposed multimodal RimNet prototype clearly outperformed the best unimodal approach (AUC = 0.943, P < 0.0001). The sensitivity and specificity achieved by RimNet (70.6% and 94.9%, respectively) are comparable to those of experts at the lesion level. In the patient-wise analysis, RimNet performed with an accuracy of 89.5% and a Dice coefficient (or F1 score) of 83.5%. The proposed prototype showed promising performance, supporting the usage of RimNet for speeding up and standardizing the paramagnetic rim lesions analysis in MS

Decompressive hemicraniectomy followed by endovascular thrombosuction in a patient with cerebral venous thrombosis

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Selective inhibition of anti-MAG IgM autoantibody binding to myelin by an antigen-specific glycopolymer.

Anti-myelin-associated glycoprotein (MAG) neuropathy is a disabling autoimmune peripheral neuropathy that is caused by circulating monoclonal IgM autoantibodies directed against the human natural killer-1 (HNK-1) epitope. This carbohydrate epitope is highly expressed on adhesion molecules such as MAG, a glycoprotein present in myelinated nerves. We previously showed the therapeutic potential of the glycopolymer poly(phenyl disodium 3-O-sulfo-β-d-glucopyranuronate)-(1→3)-β-d-galactopyranoside (PPSGG) in selectively neutralizing anti-MAG IgM antibodies in an immunological mouse model and ex vivo with sera from anti-MAG neuropathy patients. PPSGG is composed of a biodegradable backbone that multivalently presents a mimetic of the HNK-1 epitope. In this study, we further explored the pharmacodynamic properties of the glycopolymer and its ability to inhibit the binding of anti-MAG IgM to peripheral nerves. The polymer selectively bound anti-MAG IgM autoantibodies and prevented the binding of patients' anti-MAG IgM antibodies to myelin of non-human primate sciatic nerves. Upon PPSGG treatment, neither activation nor inhibition of human and murine peripheral blood mononuclear cells nor alteration of systemic inflammatory markers was observed in mice or ex vivo in human peripheral blood mononuclear cells. Intravenous injections of PPSGG to mice immunized against the HNK-1 epitope removed anti-MAG IgM antibodies within less than 1 hr, indicating a fast and efficient mechanism of action as compared to a B-cell depletion with anti-CD20. In conclusion, these observations corroborate the therapeutic potential of PPSGG for an antigen-specific treatment of anti-MAG neuropathy. Read the Editorial Highlight for this article on page 465

Cerebral Computed Tomography Scan Demonstrating Ischemic Stroke in a Filly After Intravenous Antibiotic Administration.

Performing a brain computerized tomography scan (CT scan) on a foal requires specific equipment and anesthesia for large animals. However, the information obtained may demonstrate lesions responsible for the neurological deficits. Especially, CT scan findings may help to understand a mechanism of cerebral ischemia. Indeed, categories of cerebral ischemia are divided in three types: territorial infarctions (downstream of the territory of an artery), watershed infarctions (slow-flow at the junction of two arterial territories), and lacunar infarctions (small-vessel occlusions). Hypersensitivity reactions and type I anaphylactic IgE antibody reactions are severe potential adverse effects of sulfonamide administration, which occur in about three percent of cases. In horses, anaphylaxis is often clinically expressed as hypotension and collapse. Cardiovascular collapse may lead to multiorgan slow-flow leading to infarction with multiorgan failure and death. We report the case of a filly that suffered a presumed watershed cerebral infarction after antibiotic injection, indicated on a brain CT scan. This was attributed to a cerebral slow-flow during cardiovascular collapse, at the posterior junction of the right cerebral arteries. No abnormalities were initially identified on the CT scan; however, a review of the imaging by a radiologist specialized in cerebrovascular diseases detected a limited right occipital cortico-subcortical lesion in the visual cortex, interpreted as an ischemic scar in the watershed area related to hemodynamic infarction. This case highlights that detection of brain lesions by CT scan might require specialized knowledge and careful reading for interpretation particularly in the case of limited lesions

First-ever treatment in multiple sclerosis.

The current treated MS population is very different from that of patients in randomized clinical trials. To study the long-term efficacy and tolerance of fingolimod (FTY) and dimethyl fumarate (DMF), both available as first-line treatment in early-treated treatment-naïve MS patients. Retrospective analysis of 75 patients from our prospective MS registry fulfilling the inclusion criteria: FTY or DMF as first-line treatment, treatment initiation within 36months of disease onset and treatment duration>12months. Demographics and MRI characteristics at baseline were similar in both groups (FTY 55 patients, DMF 20), but patients on FTY had higher pretreatment clinical activity (P=0.008). Twenty-two percent of patients in the FTY group and 15% in the DMF group had highly active disease. At last follow-up (mean: 44.2, SD: 17.3months), the majority of the patients were still on treatment while 54.5% of FTY and 65% of DMF patients reached NEDA 3 status (P=0.444). Both treatments significantly decreased relapses and occurrence of new T1 Gd-enhancing lesions (P<0.001). The main reason for discontinuation was disease activity without severe side effects on either treatment. Our findings support efficacy and tolerance of both drugs in early-treated treatment-naive MS patients, arguing in favour of efficient early immunomodulation in MS patients. Both drugs significantly reduced the incidence of new relapses and Gd-enhancing lesions on treatment with FTY being more frequently prescribed than DMF, especially in patients with evidence of higher clinical disease activity

Delayed and recurrent dimethyl fumarate induced-lymphopenia in patients with multiple sclerosis.

Early lymphopenia is a known side effect of dimethyl fumarate, a disease-modifying therapy for MS. However, the long-term effects on immune response and the impact on lymphocyte counts when another disease-modifying treatment is introduced, remain unknown. To better understand these specific aspects, we reviewed cases that develop prolonged grade 2 to 4 lymphopenia under dimethyl fumarate in Lausanne MS clinic. Retrospective analysis of the 12 patients (10.1%) who discontinued dimethyl fumarate because of prolonged lymphopenia amongst the 119 patients treated with dimethyl fumarate. We reviewed their demographics, as well as their clinical, biological and MRI characteristics compared to the non-lymphopenic patients, during dimethyl fumarate therapy, and within a timeframe of up to 18 months after switching to another disease-modifying treatment. We also focused on lymphocyte subsets in a subgroup of patients. Compared to non-lymphopenic patients, lymphopenic patients were older at dimethyl fumarate initiation (51.4 yo vs 39.7, p = 0.0003) and the majority were male (p = 0.037). Three of them (25%) developed delayed lymphopenia, more than one year after treatment onset. Despite persistent lymphopenia, three patients experienced disease activity. Amongst the nine patients (75%) who were switched to another therapy, five (55.6%) presented recurrent lymphopenia, predominantly with a CD8 <sup>+</sup> T cell decrease. Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after dimethyl fumarate