Myasthenia Gravis Induced by Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors deeply improved the prognosis of metastatic melanoma or other types of cancer, but their related adverse effects (AEs) can be very severe, especially when the neurological system is touched, as in myasthenia gravis (MG). It is a rare immune AE that can be life-threatening and can be revealed by several symptoms. We report a case of our experience and review the current literature of MG exacerbated or occurring during immunotherapy to describe characteristics of this AE, warn the oncologist about this toxicity, and summarize the treatments conducted. Thirty-four cases of MG were reported, mostly with anti-programmed cell death protein 1 checkpoint inhibitor, and with melanoma. Onset was quick after the first or second infusion. Treatment comprised corticosteroids, prostigmine, and more or less plasmapheresis or immunoglobulins. Prognosis is poor, as 13 patients died after MG. MG is a rare immune-related AE that must be rapidly evoked and treated in case of neurological symptoms emerging after immunotherapy.

A Regional Network Organization for Thrombectomy for Acute Ischemic Stroke in the Anterior Circulation; Timing, Safety, and Effectiveness.

BACKGROUND: Mechanical thrombectomy (MT) in association with intravenous thrombolysis is recommended for treatment of acute ischemic stroke (AIS), with large vessel occlusion (LVO) in the anterior circulation. Because MT is only available in comprehensive stroke centers (CSC), the challenge of stroke organization is to ensure equitable access to the fastest endovascular suite. Our aim was to evaluate the feasibility, efficacy, and safety of MT in patients initially managed in 1 CSC (mothership), compared with patients first managed in primary stroke center (PSC), and then transferred to the CSC for MT (drip-and-ship). METHODS: We retrospectively analyzed 179 consecutive patients (93 in the mothership group and 86 in the drip-and-ship group), with AIS secondary to LVO in the anterior cerebral circulation and a clinical-radiological mismatch (NIHSS ≥ 8 and DWI-ASPECT score ≥5), up to 6 hours after symptoms onset. We evaluated 3-month functional modified Rankin scale (mRS), periprocedural time management, mortality, and symptomatic intracranial haemorrhage (sICH). RESULTS: Despite significant longer process time in the drip-and-ship group, mRS ≤ 2 at 3 months (39.8% versus 44.1%, P = .562), Thrombolysis in cerebral infarction 2b-3 (85% versus 78%, P = .256), and sICH (7.0% versus 9.7%, P = .515) were similar in both group regardless of baseline clinical or radiological characteristics. After multivariate logistic regression, the predictive factors for favorable outcome were age (odds ratio [OR] -5years= 1.32, P < .001), initial NIHSS (OR -5points = 1.59, P = .010), absence of diabetes (OR = 3.35, P = .075), and the delay magnetic resonance imagining-puncture (OR -30min = 1.16, P = .048). CONCLUSIONS: Our study showed encouraging results from a regional protocol of MT comparing patients transferred from PSC or brought directly in CSC.

Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.