Case Analysis and Literature Review of Thirteen Patients with Autoimmune Encephalitis.

OBJECTIVE: To investigate the clinical manifestations, laboratory and imaging examinations, and the treatment outcomes of autoimmune encephalitis (AE). METHODS: The clinical data of 13 patients with autoimmune encephalitis who were hospitalized in the department of neurology, Liaocheng People's Hospital from July 2016 to August 2018 were retrospectively analyzed. RESULTS: The average age of onset of the 13 patients was 45 years, including 6 cases (46%) of anti-NMDAR encephalitis, 3 cases (23%) of anti-GABAB receptor encephalitis, and 4 cases (30%) of anti-LG11 encephalitis, and 4 of them showed abnormal signals of brain MRI (30%). 13 patients (100%) had cognitive impairment and psychiatric symptoms; seizures occurred in 12 patients (92%); lung cancer was found in 1 patient (7%). One case was given up because of the treatment of lung cancer, the other was controlled obviously in epilepsy, and cognitive impairment and abnormal mental behavior were also significantly improved. CONCLUSION: Patients with AE still need to be diagnosed early to avoid missed diagnosis and receive early immunosuppressive therapy, which could effectively reduce mortality and morbidity. A detailed history, clinical manifestations, and positive results for specific NSAbs tests can confirm the diagnosis, and the treatment is mainly done by immunosuppressive therapy.

Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: This [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined. METHODS: FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses. RESULTS: P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up. DISCUSSION: Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.

A case of bilateral limbic and recurrent unilateral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein antibody positivity.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody can be detected not only in acute disseminated encephalomyelitis or optic neuritis but also in limbic or cortical encephalitis. However, no previous reports have demonstrated a relapsing case of these two types of encephalitis. CASE REPORT: An 11-year-old girl presented with fever, headache, abnormal behavior, focal impaired awareness seizures (FIAS) on the left side, and MRI hyperintensities in the bilateral amygdala, hippocampus, and right posterior temporal cortex. The symptoms were alleviated with two courses of intravenous methylprednisolone (IVMP) and one course of immunoglobulin. At 16 years of age, the patient returned with left-sided headache and MRI hyperintensities in the left temporal, parietal, and insular cortices, which improved after 3 courses of IVMP. Oral prednisolone (PSL) was tapered over 6 months, when FIAS reappeared on the right side of the body. MRI showed recurrence in the same regions as in the second episode. She received 3 courses of IVMP, followed by gradually tapered PSL without relapse for 1.5 year. Anti-MOG antibodies were positive in both serum and the cerebrospinal fluid prior to treatment in all three episodes. CONCLUSION: Our results revealed that anti-MOG antibody-related bilateral limbic and unilateral cortical encephalitis can manifest with a variety of phenotypes over time in the same patient.

Risk Factors and Brain Metabolic Mechanism of Sleep Disorders in Autoimmune Encephalitis.

Background: Sleep disorders (SDs) in autoimmune encephalitis (AE) have received little attention and are poorly understood. We investigated the clinical characteristics, risk factors, and cerebral metabolic mechanism of SD in AE. Methods: Clinical, laboratory, and imaging data were retrospectively reviewed in 121 consecutively patients with definite AE. The risk factors for SD in AE were estimated by logistic regression analysis. Group comparisons based on 18F-fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) data were made between patients with and without SD, to further analyze potential brain metabolic mechanism of SD in AE. Results: A total of 52.9% patients (64/121) with SD were identified. The multivariate logistic model analysis showed that smoking [odds ratio (OR), 6.774 (95% CI, 1.238-37.082); p = 0.027], increased Hamilton Depression scale (HAMD) score [OR, 1.074 (95% CI, 1.002-1.152); p = 0.045], hyperhomocysteinemia [OR, 2.815 (95% CI, 1.057-7.496); p = 0.038], elevated neuron-specific enolase (NSE) level [OR, 1.069 (95% CI, 1.007-1.135); p = 0.03] were independently correlated with higher risk of SD in AE patients. Contrastingly, high MoCA score [OR, 0.821 (95% CI, 0.752-0.896); p < 0.001] was associated with lower risk of SD in AE subjects. Compared to controls, AE patients had less total sleep time, less sleep efficiency, longer sleep latency, more wake, higher percent of stage N1, lower percent of stage N3 and rapid eye movement, and more arousal index in non-rapid eye movement sleep (p < 0.05 for all). Voxel-based group comparison analysis showed that, compared to patients without SD, patients with SD had increased metabolism in the basal ganglia, cerebellum, brainstem, median temporal lobe, thalamus, and hypothalamus [p < 0.05, false discovery rate (FDR) corrected]; decreased metabolism in superior frontal gyrus, medial frontal gyrus, and posterior cingulate cortex (p < 0.001, uncorrected). These results were confirmed by region of interest-based analysis between PET and sleep quality. Conclusion: Smoking, increased HAMD score, hyperhomocysteinemia, and elevated NSE level were correlated with higher risk of SD. High MoCA score was associated with lower risk of SD in AE subjects. Moreover, a widespread metabolic network dysfunction may be involved in the pathological mechanism of SD in AE.

COVID-19-associated immune-mediated encephalitis mimicking acute-onset Creutzfeldt-Jakob disease.

We report a subtype of immune-mediated encephalitis associated with COVID-19, which closely mimics acute-onset sporadic Creutzfeldt-Jakob disease. A 64-year-old man presented with confusion, aphasia, myoclonus, and a silent interstitial pneumonia. He tested positive for SARS-CoV-2. Cognition and myoclonus rapidly deteriorated, EEG evolved to generalized periodic discharges and brain MRI showed multiple cortical DWI hyperintensities. CSF analysis was normal, except for a positive 14-3-3 protein. RT-QuIC analysis was negative. High levels of pro-inflammatory cytokines were present in the CSF and serum. Treatment with steroids and intravenous immunoglobulins produced EEG and clinical improvement, with a good neurological outcome at a 6-month follow-up.

Study on the effects of quercetin on brain cell apoptosis and HMGB-1 and TLR-4 level in rats with encephalitis.

OBJECTIVE: To explore the therapeutic effects of quercetin on rats with encephalitis, especially on cell apoptosis, and the levels of HMGB-1 and TLR-4. MATERIALS AND METHODS: 32 healthy rats were equally assigned into ZC group (healthy group), NY group (encephalitis group), DJ group (60 ml quercetin group), and GJ group (240 ml quercetin group) followed by analysis of cell apoptosis, brain tissue water content, neurons, HMGB-1, TLR-4 and other inflammatory factors. RESULTS: The ZC group showed normal neuron volume and equitable staining; compared with ZC group, NY group showed neuron volume shrinkage and chromatin condensation; the neuron and color in DJ group were slightly better than NY group; the neuron volume in GJ group increased significantly and chromatin is distributed evenly. TLR-4, IL-4, IL-6, HMGB-1 in ZC and DJ group were significantly lower than those in NY group (p<0.05); IL-4, IL-6, HMGB-1 in GJ group significantly decreased compared with DJ group (p<0.05); MMP-9 enzyme activity in ZC and DJ group was significantly lower than NY group (p<0.05) with lower level in GJ group than DJ group (p<0.05). The water content was higher in brain tissue of NY group than ZC group (p<0.05) and lower in DJ group than NY group (p<0.05) with lower level in GJ group than DJ and NY group (all p<0.05). The hippocampal neurons and cortical neurons in ZC and DJ group were higher than those in NY group (p<0.05) and elevated in GJ group compared with DJ group and NY group (p<0.05). CONCLUSIONS: Quercetin is effective in treating encephalitis rats possibly through inhibition of neuronal cell apoptosis and level of HMGB-1 and TLR-4.

On clinical findings of Bickerstaff's brainstem encephalitis in childhood.

A short review on the clinical presentation of pediatrics cases of Bickerstaff brain encephalitis emphasizing the broad clinical spectrum of the disease. Cases of pediatric Bickerstaff's brainstem encephalitis collected on three electronic medical databases (PubMed, Cochrane Library and Scopus Web of Science) are reviewed. The inclusion criteria of the cases were based on the clinical characteristics of the disorder in the pediatric age. We reviewed 20 articles on Bickerstaff's brainstem encephalitis, identifying 40 pediatric cases focused on the clinical symptoms. We saw that the prevalence was higher in male subjects, and the median age at diagnosis was 8 years. The phenotype of pediatrics patients was similar to previously published literature. We identify three cases of overlapping forms between Bickerstaff brain encephalitis and Guillain-Barré Syndrome in patients with lower limbs weakness and typical signs of Bickerstaff brain encephalitis, suggesting a combined involvement of the central and peripheral nervous system. Although there is no defined data on incidence and prevalence in the literature, Bickerstaff's brainstem encephalitis appears to be a rare disorder, especially in children. The incidence of Bickerstaff brain encephalitis and Guillain-Barré Syndrome, and Miller Fisher Syndrome has been underrated in the past, primarily due to an underestimation of the forms with a Peripheral Nervous System involvement. Bickerstaff brain encephalitis usually has a rapid and acute onset within 2-4 weeks, characterized by a typical picture of ophthalmoplegia, hyperreflexia, cerebellar symptoms as ataxia. The subsequent manifestations of hyperreflexia or consciousness disturbances as drowsiness, sleepiness, or coma, indicative of central involvement, suggest a Bickerstaff brain encephalitis clinical diagnosis.

Clinical Course and Features of Seizures Associated With LGI1-Antibody Encephalitis.

BACKGROUND AND OBJECTIVES: To determine risk factors associated with clinical relapses and development of chronic epilepsy in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) immunoglobulin G encephalitis. METHODS: Patients with seizures related to LGI1-antibody encephalitis with ≥24 months of follow-up from disease onset were identified in the Mayo Clinic electronic medical record and neuroimmunology laboratory records. Charts were reviewed to determine clinical factors, seizure types, imaging, treatment, occurrence of relapse, and outcome. Binary logistic regression analysis was performed to identify predictors of the development of chronic epilepsy. Univariate Cox proportional hazards regression was used to examine the influence of baseline characteristics on relapse risk. RESULTS: Forty-nine patients with LGI1-antibody encephalitis and acute symptomatic seizures were identified. Almost all patients (n = 48, 98%) were treated with immunotherapy. Eight had definite and 2 had possible chronic epilepsy at the last follow-up (10 of 49, 20.4%). Female sex (p = 0.048) and younger age at disease onset (p = 0.02) were associated with development of chronic epilepsy. Relapses occurred in 20 (40.8%), with a median time to first relapse of 7.5 months (range 3-94 months). Initial treatment with long-term steroid-sparing immunotherapy was associated with reduced risk of relapse (hazard ratio 0.28, 95% confidence interval 0.11-0.73, p = 0.009). DISCUSSION: Chronic epilepsy occurred in 20.4% of our patients with LGI1-antibody encephalitis despite aggressive immunotherapy. Risk factors for chronic epilepsy were female sex and earlier age at onset. Relapses occurred in 40.8% of patients with prolonged follow-up, and long-term steroid-sparing immunotherapy was associated with a lower relapse rate.

Reduction of oxidative stress and inflammatory signaling in the commissural nucleus of the solitary tract (commNTS) and rostral ventrolateral medulla (RVLM) in treadmill trained rats.

Inflammation has been associated with cardiovascular diseases and the key point is the generation of reactive oxygen species (ROS). Exercise modulates medullary neurons involved in cardiovascular control. We investigated the effect of chronic exercise training (Tr) in treadmill running on gene expression (GE) of ROS and inflammation in commNTS and RVLM neurons. Male Wistar rats (N = 7/group) were submitted to training in a treadmill running (1 h/day, 5 days/wk/10 wks) or maintained sedentary (Sed). Superoxide dismutase (SOD), catalase (CAT), neuroglobin (Ngb), Cytoglobin (Ctb), NADPH oxidase (Nox), cicloxigenase-2 (Cox-2), and neuronal nitric oxide synthase (NOS1) gene expression were evaluated in commNTS and RVLM neurons by qPCR. In RVLM, Tr rats increased Ngb (1.285 ± 0.03 vs. 0.995 ± 0.06), Cygb (1.18 ± 0.02 vs.0.99 ± 0.06), SOD (1.426 ± 0.108 vs. 1.00 ± 0.08), CAT (1.34 ± 0.09 vs. 1.00 ± 0.08); and decreased Nox (0.55 ± 0.146 vs. 1.001 ± 0.08), Cox-2 (0.335 ± 0.05 vs. 1.245 ± 0.02), NOS1 (0.51 ± 0.08 vs. 1.08 ± 0.209) GE compared to Sed. In commNTS, Tr rats increased SOD (1.384 ± 0.13 vs. 0.897 ± 0.101), CAT GE (1.312 ± 0.126 vs. 0.891 ± 0.106) and decreased Cox-2 (0.052 ± 0.011 vs. 1.06 ± 0.207) and NOS1 (0.1550 ± 0.03559 vs. 1.122 ± 0.26) GE compared to Sed. Therefore, GE of proteins of the inflammatory process reduced while GE of antioxidant proteins increased in the commNTS and RVLM after training, suggesting a decrease in oxidative stress of downstream pathways mediated by nitric oxide.

Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

OBJECTIVE: To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings. METHODS: We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry. RESULTS: Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity. CONCLUSION: AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.

Autoantibodies in neurological disease.

The realization that autoantibodies can contribute to dysfunction of the brain has brought about a paradigm shift in neurological diseases over the past decade, offering up important novel diagnostic and therapeutic opportunities. Detection of specific autoantibodies to neuronal or glial targets has resulted in a better understanding of central nervous system autoimmunity and in the reclassification of some diseases previously thought to result from infectious, 'idiopathic' or psychogenic causes. The most prominent examples, such as aquaporin 4 autoantibodies in neuromyelitis optica or NMDAR autoantibodies in encephalitis, have stimulated an entire field of clinical and experimental studies on disease mechanisms and immunological abnormalities. Also, these findings inspired the search for additional autoantibodies, which has been very successful to date and has not yet reached its peak. This Review summarizes this rapid development at a point in time where preclinical studies have started delivering fundamental new data for mechanistic understanding, where new technologies are being introduced into this field, and - most importantly - where the first specifically tailored immunotherapeutic approaches are emerging.

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti-GABABR encephalitis.

OBJECTIVE: To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. METHODS: We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. RESULTS: Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p > .05). The value between SCLC and non-SCLC subgroup was significantly different (p < .05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p < .05). The average survival time after onset was 27.7 months. CONCLUSIONS: Epilepsy is the most common clinical manifestation of Anti-GABABR encephalitis. The prognosis of anti-GABABR encephalitis is poor. Section of anti-GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti-GABABR encephalitis.

Recurrent Miller-Fisher syndrome overlapping Guillain-Barrè syndrome and Bickerstaff brainstem encephalitis: A case report.

Miller-Fisher syndrome (MFS) together with Guillan-Barré syndrome (GBS) and Bickerstaff brainstem encephalitis (BBE) are considered to form a continuous clinical spectrum of the same disease, possibly affecting the peripheral and/or central nervous systems, with monophasic symptoms. The frequency of overlapping clinical signs and the risk of recurrence are independent and very low, but no cases of GQ1b-seropositive recurrent MFS overlapping with GBS and BBE have been described so far. Here, we describe for the first time an atypical case of recurrent GQ1b-seropositive MFS overlapping GBS and BBE, 12 years after a previous GQ1b-seronegative typical MFS episode. Our case expands the clinical spectrum of recurrent MFS, and it should prompt clinicians to investigate the presence of anti-ganglioside antibodies in recurrent MFS even when these were negative in the previous episode, especially in those presenting with overlapping spectrum symptoms and a critically ill picture during the second episode.

The 'Great Imitator': A Case of COVID-19 Presenting with Encephalitis and Acute Coronary Syndrome.

Although typically patients with coronavirus disease-19 (COVID-19) have pulmonary symptoms atypical cases can occasionally present with extra-pulmonary symptoms. We report an interesting case of COVID-19 female patient presenting with combination of central nervous system disorder and acute myocardial infarct as initial manifestation. Multiorgan involvement in COVID-19 might lead to multiple atypical presentation which could be overlooked by the physician.

Cardiac and Brainstem Neuroinflammatory Pathways Account for Androgenic Incitement of Cardiovascular and Autonomic Manifestations in Endotoxic Male Rats.

ABSTRACT: Inconsistent reports are available on the role of testosterone in end-organ damage caused by endotoxemia. Here, pharmacologic, surgical, and molecular studies were employed to assess the testosterone modulation of cardiovascular, autonomic, and peripheral and central inflammatory derangements caused by endotoxemia. Studies were performed in conscious male rats preinstrumented with femoral indwelling catheters for the measurement of blood pressure and subjected to castration or pharmacologic interventions that interrupt the biosynthetic cascade of testosterone. Compared with the effects of lipopolysaccharide (10 mg/kg intravenously) in sham operated rats, 2-week castration reduced the lipopolysaccharide-evoked (1) falls in blood pressure, (2) decreases in time- and frequency-domain indices of heart rate variability, (3) shifts in spectral measures of cardiac sympathovagal balance toward parasympathetic dominance, and (4) increases in protein expressions of toll-like receptor-4 and monocyte chemoattractant protein-1 in heart and medullary neurons of the nucleus tractus solitarius and rostral ventrolateral medulla. While the ameliorating actions of castration on endotoxic cardiovascular manifestations were maintained after testosterone replacement, the concomitant inflammatory signals were restored to near-sham levels. The favorable influences of castration on inflammatory and cardiovascular abnormalities of endotoxemia were replicated in intact rats pretreated with degarelix (gonadotropin-releasing hormone receptor blocker) or finasteride (5α-reductase inhibitor) but not formestane (aromatase inhibitor). The data signifies the importance of androgens and its biosynthetic enzymes in cardiovascular and autonomic insults induced by the endotoxic inflammatory response. Clinically, the interruption of testosterone biosynthesis could offer a potential strategy for endotoxemia management.

4R-cembranoid confers neuroprotection against LPS-induced hippocampal inflammation in mice.

BACKGROUND: Chronic brain inflammation has been implicated in the pathogenesis of various neurodegenerative diseases and disorders. For example, overexpression of pro-inflammatory cytokines has been associated with impairments in hippocampal-dependent memory. Lipopolysaccharide (LPS) injection is a widely used model to explore the pathobiology of inflammation. LPS injection into mice causes systemic inflammation, neuronal damage, and poor memory outcomes if the inflammation is not controlled. Activation of the alpha-7 nicotinic receptor (α7) plays an anti-inflammatory role in the brain through vagal efferent nerve signaling. 4R-cembranoid (4R) is a natural compound that crosses the blood-brain barrier, induces neuronal survival, and has been shown to modulate the activity of nicotinic receptors. The purpose of this study is to determine whether 4R reduces the deleterious effects of LPS-induced neuroinflammation and whether the α7 receptor plays a role in mediating these beneficial effects. METHODS: Ex vivo population spike recordings were performed in C57BL/6J wild-type (WT) and alpha-7-knockout (α7KO) mouse hippocampal slices in the presence of 4R and nicotinic receptor inhibitors. For in vivo studies, WT and α7KO mice were injected with LPS for 2 h, followed by 4R or vehicle for 22 h. Analyses of IL-1ß, TNF-α, STAT3, CREB, Akt1, and the long-term novel object recognition test (NORT) were performed for both genotypes. In addition, RNA sequencing and RT-qPCR analyses were carried out for 12 mRNAs related to neuroinflammation and their modification by 4R. RESULTS: 4R confers neuroprotection after NMDA-induced neurotoxicity in both WT and α7KO mice. Moreover, hippocampal TNF-α and IL-1ß levels were decreased with 4R treatment following LPS exposure in both strains of mice. 4R restored LPS-induced cognitive decline in NORT. There was a significant increase in the phosphorylation of STAT3, CREB, and Akt1 with 4R treatment in the WT mouse hippocampus following LPS exposure. In α7KO mice, only pAkt levels were significantly elevated in the cortex. 4R significantly upregulated mRNA levels of ORM2, GDNF, and C3 following LPS exposure. These proteins are known to play a role in modulating microglial activation, neuronal survival, and memory. CONCLUSION: Our results indicate that 4R decreases the levels of pro-inflammatory cytokines; improves memory function; activates STAT3, Akt1, and CREB phosphorylation; and upregulates the mRNA levels of ORM2, GDNF, and C3. These effects are independent of the α7 nicotinic receptor.

Reversible splenial lesions during febrile illness with or without white matter lesions.

OBJECTIVE: Reversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological features in RESLEF. METHODS: Fifty-two episodes of CC-only or CC (+) lesions accompanied by neurological symptoms, e.g., seizures, delirious behavior (DB), and disturbance of consciousness (DC), from January 2008 to October 2019 were included. We analyzed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography findings, therapy, and prognosis. RESULTS: The rate of DC in the CC (+) was significantly higher than that in the CC-only group (5/6 [83%] vs 7/46 [15%]; p = 0.0016). The median number of seizures in the CC (+) was also significantly higher than that in the CC-only group (4 [0-7] vs 0 [0-7]; p = 0.034). Further, in RESLEF, the median onset age (months) in the seizure was significantly lower than that in the no-seizure group (39 [12-74] vs 83 [28-174]; p = 0.0007). The median onset age (months) in the DB was significantly higher than that in the no-DB group (74.5 [26-174] vs 28 [12-139]; p = 0.003). CONCLUSIONS: In RESLEF, CC (+) is a more severe neurological symptom than CC-only. Furthermore, the onset age is related to the type of neurological symptoms that appear.

Mine-site derived particulate matter exposure exacerbates neurological and pulmonary inflammatory outcomes in an autoimmune mouse model.

The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.