The aim of this case report was to describe a potential anti-interleukin (IL)-6 treatment for cryptogenic new-onset refractory status epilepticus (C-NORSE). Background: Although an underlying immune-mediated pathogenesis is considered present in some C-NORSE cases, many cases do not respond to classical immunotherapies. Case report: We describe the case of a 46-year-old woman with C-NORSE who achieved cessation of long-lasting status epilepticus following administration of tocilizumab, an IL-6 receptor-blocking antibody, although the final outcome was poor. Conclusions: Anti-IL-6 treatment may prove effective in stopping status epilepticus in some C-NORSE cases.

Lipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson’s disease (PD). However, it has not been fully determined which lipids are involved in the initiation of αSyn aggregation in PD. Here exploiting genetic understanding associating the loss-of-function mutation in Synaptojanin 1 (SYNJ1), a phosphoinositide phosphatase, with familial PD and analysis of postmortem PD brains, we identified a novel lipid molecule involved in the toxic conversion of αSyn and its relation to PD. We first established a SYNJ1 knockout cell model and found SYNJ1 depletion increases the accumulation of pathological αSyn. Lipidomic analysis revealed SYNJ1 depletion elevates the level of its substrate phosphatidylinositol-3,4,5-trisphosphate (PIP3). We then employed Caenorhabditis elegans model to examine the effect of SYNJ1 defect on the neurotoxicity of αSyn. Mutations in SYNJ1 accelerated the accumulation of αSyn aggregation and induced locomotory defects in the nematodes. These results indicate that functional loss of SYNJ1 promotes the pathological aggregation of αSyn via the dysregulation of its substrate PIP3, leading to the aggravation of αSyn-mediated neurodegeneration. Treatment of cultured cell line and primary neurons with PIP3 itself or with PIP3 phosphatase inhibitor resulted in intracellular formation of αSyn inclusions. Indeed, in vitro protein–lipid overlay assay validated that phosphoinositides, especially PIP3, strongly interact with αSyn. Furthermore, the aggregation assay revealed that PIP3 not only accelerates the fibrillation of αSyn, but also induces the formation of fibrils sharing conformational and biochemical characteristics similar to the fibrils amplified from the brains of PD patients. Notably, the immunohistochemical and lipidomic analyses on postmortem brain of patients with sporadic PD showed increased PIP3 level and its colocalization with αSyn. Taken together, PIP3 dysregulation promotes the pathological aggregation of αSyn and increases the risk of developing PD, and PIP3 represents a potent target for intervention in PD.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by the infiltration of foamy histiocytes into multiple organs. We herein report a case of ECD with central nervous system (CNS) involvement in a 63-year-old man who also presented a positive result for Toxoplasma gondii nested polymerase chain reaction testing of cerebrospinal fluid. Since anti-Toxoplasma treatment proved completely ineffective, we presumed latent infection of the CNS with T. gondii. This case suggests the difficulty of distinguishing ECD with CNS involvement from toxoplasmic encephalitis and the possibility of a relationship between the pathogeneses of ECD and infection with T. gondii.

Background and Purpose: The number of elderly patients with acute cerebrovascular syndrome (ACVS) is increasing. The management of ACVS is difficult especially in very elderly patients such as nonagenarians and centenarians. Therefore, we aimed to clarify the clinical characteristics, treatments, and complications of these patients. Methods: We enrolled 80 patients aged over 90 in a group of 1,420 patients with ACVS who were admitted to our hospital between July 2013 and June 2018. We assessed clinical data and conducted brain MRI/MRA scans, carotid ultrasonograms, echocardiograms, 24hr Holter electrocardiograms and chest-abdominal CT scans to evaluate the severity of atherosclerotic change, stroke subtype, and cardiovascular status in these patients. We categorized them as follows: atherothrombotic brain embolism (ATBE: n=11, 14%), atherothrombotic brain infarction (ATBI: n=9, 11%), cardioembolic infarction (CEI: n=25, n=31%), lacunar infarction (LI: n=15, 19%), transient ischemic attack (TIA: n=6, 8%), and embolic stroke of undetermined source (ESUS: n=14, 18%). Results: Patient age was 92±3 years and 19% were male. Median baseline NIHSS was 9 and median baseline modify Rankin Scale (mRS) was 3. The brain natriuretic peptide (BNP) level was significantly higher in the CEI group (358±206pg/ml) compared to the ATBI group (104±48pg/ml, p<0.001), the ESUS group (130±82pg/ml, p<0.001), the LI group (85±42pg/ml, p<0.001), and the ATBE group (62±49pg/ml, p<0.001). The D-dimer level was correlated to the baseline NIHSS (r=0.44, p<0.01). There were no significant differences of D-dimer level among the stroke subgroups. Anticoagulation for the initial therapy was done in 62 patients (77%) including 2 patients who received thrombolysis. Major complications were aspiration pneumonia (11%), urinary tract infection (10%), bleeding in other organs (6%), and congestive heart failure (5%). The median mRS at discharge was 4 and in-hospital mortality rate was 3.8%. Conclusion: The BNP level was useful to identify the CEI group. Although the ACVS treatment of nonagenarians and centenarians are thought to be high risk for bleeding, the clinical and neurological outcomes were acceptable despite many complications.

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