Anti-N-methyl-D-aspartate receptor encephalitis associated with intracranial Angiostrongylus cantonensis infection: a case report.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently described paraneoplastic syndrome with prominent neuropsychiatric symptoms. Many of these cases are associated with neoplasma especially teratoma. In addition, a few of cases with anti-NMDAR antibodies triggered by viral infection have been reported, but never by parasitic infection. Here, we report a novel case of NMDA receptor encephalitis in a 51-year-old male related to the development of anti-NMDAR antibodies triggered by Angiostrongylus cantonensis infection.

Glibenclamide Improves Survival and Neurologic Outcome After Cardiac Arrest in Rats.

OBJECTIVES: Glibenclamide confers neuroprotection in animal models as well as in retrospective clinical studies. This study determines whether glibenclamide improves outcome after cardiac arrest in rats. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 126). INTERVENTIONS: Rats successfully resuscitated from 8-minute asphyxial cardiac arrest were randomized to glibenclamide or vehicle group. Rats in the glibenclamide group were intraperitoneally administered glibenclamide with a loading dose of 10 µg/kg at 10 minutes and a maintenance dose of 1.2 µg at 6, 12, 18, and 24 hours after return of spontaneous circulation, whereas rats in the vehicle group received equivalent volume of vehicle solution. MEASUREMENTS AND MAIN RESULTS: Survival was recorded every day, and neurologic deficit scores were assessed at 24, 48, and 72 hours and 7 days after return of spontaneous circulation (n = 22 in each group). Results showed that glibenclamide treatment increased 7-day survival rate, reduced neurologic deficit scores, and prevented neuronal loss in the hippocampal cornu ammonis 1 region. To investigate the neuroprotective effects of glibenclamide in acute phase, we observed neuronal injury at 24 hours after return of spontaneous circulation and found that glibenclamide significantly decreased the rate of neuronal necrosis and apoptosis. In addition, glibenclamide reduced the messenger RNA expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 in the cortex after return of spontaneous circulation. Furthermore, the sulfonylurea receptor 1 and transient receptor potential M4 heteromers, the putative therapeutic targets of glibenclamide, were up-regulated after cardiac arrest and cardiopulmonary resuscitation, indicating that they might be involved in neuroprotective effect of glibenclamide. CONCLUSIONS: Glibenclamide treatment substantially improved survival and neurologic outcome throughout a 7-day period after return of spontaneous circulation. The salutary effects of glibenclamide were associated with suppression of neuronal necrosis and apoptosis, as well as inflammation in the brain.

Is rat hippocampus section immunostaining an indicator for immunotherapy in cryptogenic adult new-onset refractory status epilepticus (NORSE)?

PURPOSE: To evaluate the meaning of immunostaining of rat hippocampus with respect to clinical manifestations, Status epilepticus(SE)severity, treatment, and prognosis of New-Onset Refractory Status Epilepticus(NORSE) patients. METHODS: Consecutive patients with cryptogenic NORSE admitted to the neuro-intensive care unit (NICU) between January 2015 and October 2018 were screened, and those who had serum and cerebrospinal fluid (CSF) immunostaining were included. Subsequently, the patients were classified into positive and negative immunostain groups. Immunotherapy was initiated in patients who progressed to super-RSE (SRSE). The demographic, and clinical, and immunostaining data were collected. The prognosis was evaluated by modified Rankin scale (mRS) at discharge (short-term prognosis) and 6 months (long-term prognosis), with mRS score ≤2 defined as the favorable outcome. The clinical manifestations, treatment response, and prognosis were compared between the patients with positive and negative immunostains. RESULTS: 4/18 patients had positive immunostaining on both CSF and serum, 8 (had positive immunostaining on serum only, while 6 had negative immunostaining on serum and CSF. Twelve (66.7 %) patients progressed to SRSE, with no difference between the positive and negative immunostaining groups (P = 1.000). 7/18 patients had a favorable outcome at discharge and 11/18 after 6 months. No significant difference on the prognosis was detected between patients with positive and negative serum/CSF immunostaining and between the patients with or without immunotherapy at discharge or 6-month follow-up (P = 0.657/P = 0.502, P = 0.445/P = 0.829, P = 0.622, P = 0.567, respectively). CONCLUSIONS: The immunostaining on serum and/or CSF from NORSE patients did not indicate the progression to SRSE and clinical outcomes.

Elevated neuron-specific enolase and S100 calcium-binding protein B concentrations in cerebrospinal fluid of patients with anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND: Anti­N­methyl­d­aspartate receptor (NMDAR) encephalitis is a relatively common autoimmune neurological disease of the central nervous system (CNS). Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) are structural proteins of the central nervous system (CNS). In patients with CNS injury accompanied by nervous tissue and cellular damage, these structural proteins are released from cells; their extracellular concentrations, including those in cerebrospinal fluid (CSF) and blood, subsequently increase. METHODS: Thirty-six patients with anti-NMDAR encephalitis were prospectively recruited. The CSF NSE and S100B concentrations were measured in 19 and 17 patients, respectively. The CSF NSE and S100B concentrations were measured in 21 patients with noninflammatory neurological disease as controls. All measurements were performed using enzyme-linked immunosorbent assays. RESULTS: The CSF NSE and S100B concentrations were remarkably higher in the patients with anti-NMDAR encephalitis than in the controls. The early NSE or S100B concentrations in CSF were associated with the mRS. CONCLUSION: CSF NSE and S100B concentration in patients with anti-NMDAR encephalitis is higher than in patients with non-inflammatory neurological disease. The early NSE or S100B concentrations in CSF were associated with the mRS and we can use it to determine the prognosis of the disease.

Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats.

BACKGROUND: We previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM. METHODS AND RESULTS: Male Sprague-Dawley rats (n=213) subjected to 10-minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7-day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1-TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM. CONCLUSIONS: GBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved.

Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.

In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1ß. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors.

TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons.

The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex.

Identification of a novel nonsense mutation p.Tyr1957Ter of CACNA1A in a Chinese family with episodic ataxia 2.

Type 2 episodic ataxia (EA2) is the most common subtype among a group of rare hereditary syndromes characterized by recurrent attacks of ataxia. More than 60 mutations and several gene rearrangements due to large deletions in CACNA1A gene have been reported so far for the cause of EA2. Because CACNA1A gene is a large gene containing 47 exons and there is no hot spot mutation, direct sequencing will be a challenge in clinical genetic testing. In this study, we used next generation sequencing technology to identify a novel nonsense mutation of CACNA1A (p.Tyr1957Ter, NP_001120693.1) resulting in truncated protein without 305 amino acids in the c-terminus. Sanger sequencing confirmed the heterozygous mutation of CACNA1A in a Chinese family with 11 affected individuals. Affected individuals experienced recurrent attacks with or without nystagmus, dysarthria, seizure, myokymia, dystonia, weakness, blurred vision, visual field defects, diplopia, migraine, dizziness, nausea and vomiting, sweating and abdominal pain. This is the first report of EA2 in a Chinese family that carries a novel mutation in CACNA1A gene and had abdominal pain as a novel phenotype associated with EA2.

[Pathologic changes of the palatopharyngeal muscles in adult patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the pathology of palatopharyngeal muscle obtained from patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The samples from both groups were studied under HE, nicotinamide adenine dinucleotide-tetrazolium reductase (NADH- TR), modified Gomori trichrome (MGT) and adenosine triphosphatase (ATPase) staining. There were 36 cases of OSAHS who received uvulopalatopharyngoplasty in the experimental group (including 6 mild, 6 moderate and 24 severe cases). There were 6 patients with chronic tonsillitis but without OSAHS as matched control group. Both groups were diagnosed by PSG. RESULTS: Centralized located nuclei and obvious variability of the size of fiber types were observed in both groups. The occurrence rate of the former were 1/6 in control group and 52.8% (19/36) in OSAHS, while the rate of the latter were 4/6 and 58.3% (21/36)respectively. A large number of fibers in both groups (control group 5/6, OSAHS group 28/36) presented an irregularly distributed staining for oxidative activity reaction in NADH stain.Endomysium connective tissue proliferation, a lobular or motheaten appearance, target-like fibers, ragged red fiber (RRF) and muscle necrosis were only observed in OSAHS group.While it was more common in serious OSAHS patients. Dominance of type 1 fibers were observed in matched control group in ATPase stain. Clusters of type 2 fibers or clusters of both type fibers were observed in OSAHS, especially more common in serious OSAHS. There was a predominance of the type 2 fibers in some OSAHS patients. CONCLUSIONS: The observation of HE and special muscular stain identified that palatopharyngeal muscle of OSAHS patients had pathological lesion. The pathological changes included muscular lesion and abnormal distribution of different fiber types, the rate of type 1 fiber which maintained the opening of upper air way decreased.