摘要： Plain Language Summary Nerve cell death, oxidative stress, and inflammation of the brain are the most common pathological processes of many neurological diseases. These processes are mediated through changes in glial cells, the supporting cells in the brain, via several molecular pathways. Some of these pathways are potential drug targets for the mitigation of brain pathology. In this review, we focus on pathways involving Src family kinases, inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate oxidase, and their inhibitors, which are promising agents for modifying neurological diseases. Neurological diseases share common neuroinflammatory and oxidative stress pathways. Both phenotypic and molecular changes in microglia, astrocytes, and neurons contribute to the progression of disease and present potential targets for disease modification. Src family kinases (SFKs) are present in both neurons and glial cells and are upregulated following neurological insults in both human and animal models. In neurons, SFKs interact with post-synaptic protein domains to mediate hyperexcitability and neurotoxicity. SFKs are upstream of signaling cascades that lead to the modulation of neurotransmitter receptors and the transcription of pro-inflammatory cytokines as well as producers of free radicals through the activation of glia. Inducible nitric oxide synthase (iNOS/NOS-II) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), the major mediators of reactive nitrogen/oxygen species (RNS/ROS) production in the brain, are also upregulated along with the pro-inflammatory cytokines following neurological insult and contribute to disease progression. Persistent neuronal hyperexcitability, RNS/ROS, and cytokines can exacerbate neurodegeneration, a common pathognomonic feature of the most prevalent neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Using a wide variety of preclinical disease models, inhibit

关键词： Epilepsy   Children   Behavioral problems   Emotional problems   Kenya  

摘要： Introduction: Epilepsy is a common neurological condition, with a lifetime prevalence of 1% in children. Research has shown a high prevalence of emotional and behavioral problems in children with epilepsy. The aim of this study was to determine the prevalence of emotional and behavioral problems in children with epilepsy attending the pediatric neurology clinic in a referral hospital in Kenya and examine associated sociodemographic and clinical variables. Methods: This was a cross-sectional descriptive study. Children with epilepsy aged between 6 and 12 years attending the Kenyatta National Hospital pediatric neurology clinic were recruited. Inclusion criteria for the study were children diagnosed with epilepsy, age between 6 and 12 years, accompanied by a primary caregiver, and the primary caregiver being willing to participate in the study. A sociodemographic questionnaire as well as the Child Behavior Checklist school-age version (CBCL/6-18) was administered to the caregiver accompanying the child. Results: One hundred and seventy-seven children with epilepsy were recruited (66% males) with a mean age of 8.9 (standard deviation (SD): 2) years. The mean age at onset of seizures was 4.5 years;48% of the children had first seizure while aged less than 2 years, 76% reported generalized tonic-clonic seizures, and 58% were on antiepileptic drugs (AEDs). The overall prevalence of emotional and behavioral problems was 46%, and the four leading symptom clusters were attention problems, aggressive behavior, social problems, and withdrawal/depression. The risk of emotional and behavioral problems was increased in children using more than one AED (odds ratio (OR) = 2.21, 95% confidence interval (CI), 1.18-4.14) and those aged ten years and above (OR = 2.7, 95% CI, 1.3-5.64). The risk of emotional and behavioral problems was reduced in children with infrequent seizures (OR = 0.08, 95% CI, 0.01-0.06) and in children reporting no seizure in the past year (OR= 0.08, 95% CI, 0.01

关键词： Autoimmunity   Sleep disorders   Polysomnography   Neurological autoimmunity   Diagnosis   Therapy  

摘要： Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5;leucine-rich, glioma-inactivated protein 1 (LGI1);contactin-associated protein 2 (CASPR2);N-methyl-D-aspartate (NMDA)-receptor;Ma2;dipeptidyl-peptidase-like protein-6 (DPPX);alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R);anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu);anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri);gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R);metabotropic glutamate receptor 5 (mGluR5);and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.

关键词： astrocyte topology   cognitive disfunction   inflammation   reactive gliosis   self-renew   TBI  

摘要： Unlike microglia and NG2 glia, astrocytes are incapable of migrating to sites of injury in the posttraumatic cerebral cortex, instead relying on proliferation to replenish their numbers and distribution in the affected region. However, neither the spectrum of their proliferative repertoire nor their postinjury distribution has been examined in vivo. Using a combination of different thymidine analogs and clonal analysis in a model of repetitive traumatic brain injury, we show for the first time that astrocytes that are quiescent following an initial injury can be coerced to proliferate after a repeated insult in the cerebral cortex grey matter. Interestingly, this process is promoted by invasion of monocytes to the injury site, as their genetic ablation (using CCR2(-/-)mice) increased the number of repetitively dividing astrocytes at the expense of newly proliferating astrocytes in repeatedly injured parenchyma. These differences profoundly affected both the distribution of astrocytes and recovery period for posttraumatic behavior deficits suggesting key roles of astrocyte self-renewal in brain repair after injury.

关键词： Locus coeruleus   Magnetic resonance imaging   Neuromelanin   Noradrenaline   Alzheimer's disease   Parkinson's disease  

摘要： Purpose of Review Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and its degeneration is considered to be key in the pathogenesis of neurodegenerative diseases. In the last 15 years,MRI has been used to assess LC in vivo, both in healthy subjects and in patients suffering from neurological disorders. In this review, we summarize the main findings of LC-MRI studies, interpreting them in light of preclinical and histopathological data, and discussing its potential role as diagnostic and experimental tool. Recent findings LC-MRI findings were largely in agreement with neuropathological evidences;LC signal showed to be not significantly affected during normal aging and to correlate with cognitive performances. On the contrary, a marked reduction of LC signal was observed in patients suffering from neurodegenerative disorders, with specific features. Summary LC-MRI is a promising tool, which may be used in the future to explore LC pathophysiology as well as an early biomarker for degenerative diseases.

摘要： Post-viral anosmia in the setting of upper respiratory tract infections is usually related to mucosal congestion and nasal obstruction, resulting in a conductive olfactory loss; however, few patients with SARS-CoV-2-related anosmia had sinonasal symptoms, suggesting that mucosal congestion is an unlikely aetiology for anosmia in these cases.6 Olfactory epithelium support-cells residing in the olfactory cleft express the angiotensin-converting enzyme 2 receptor, identified as the binding antigen for SARS-CoV-2.6 Imaging of the olfactory cleft showed olfactory cleft opacification in 17 (74%) of cases.6 Moving proximally, olfactory nerve filia clumping, suggestive of inflammation, was observed in eight (35%) of patients, and olfactory bulb signal abnormalities, indicating degeneration or microhaemorrhage, were seen in 21 (91%) *** a case series of five individuals with AIDP and SARS-CoV-2 infection, the latency between respiratory symptom and neurological symptom onset was 14–30 days.7 Most patients presented with the classical findings of AIDP, with ascending paraparesis and hyporeflexia, conduction blocks and increased latency on nerve conduction studies, and albuminocytological dissociation in the CSF.7 However, uniquely to SARS-CoV-2-associated AIDP, patients also showed elevated systemic or CSF levels of IL-6 and IL-8, implicating an overactive inflammatory response in the pathogenesis of AIDP in these ***, vessel wall sequence MRI revealed contrast enhancement of the medium and large arterial vessel walls in these patients.2 This finding, coupled with the absence of CSF inflammatory markers and SARS-CoV-2-specific IgG antibodies, further supports the hypothesis for a systemic rather than CNS-specific inflammatory response contributing to a hypercoagulable state and endothelial cell dysfunction.2 An autopsy of one individual additionally showed systemic endotheliitis.2 Brain autopsy studies8 have described pathological changes that have

关键词： Cerebrovascular disorders   Thrombectomy   Stroke   Neurological improvement  

摘要： The predictive value of and the influencing factors associated with early neurological improvement (ENI) among patients with acute basilar artery occlusion (BAO) have not been well studied. The present study aimed to evaluate whether ENI predicted a better functional outcome and to identify the influencing factors of ENI. We performed a prospective observational analysis among 187 patients with acute BAO who underwent endovascular treatment (EVT) in Beijing Tiantan Hospital from January 2012 to July 2018. ENI was defined as having a drop on the National Institutes of Health Stroke Scale (NIHSS) by 8 or more scores or having a NIHSS of 0-1 within 24 h after EVT. A multivariate logistic regression model with backward selection was used to identify the influencing factors associated with ENI. ENI had a sensitivity of 0.69 and a specificity of 0.68 to predict a favorable outcome at 90 days after EVT. In addition, patients with ENIs had lower modified Rankin Scale score (mRS) (median: 2.0 vs. 5.0, p < 0.001) and were more likely to survive (95.2% vs. 72.0%, p < 0.001) and achieve functional independence (74.2% vs. 36.8%, p < 0.001). NIHSS before EVT, complete recanalization, white blood cell counts and general anesthetics were significant factors associated with ENI. A one-unit higher NIHSS and complete recanalization were associated with 1.04 (95% CI 1.01-1.08) and 2.71 (95% CI 1.14-6.45) times higher odds of achieving ENI, respectively. In conclusion, in patients with acute BAO, ENI within 24 hours after EVT can predict favorable outcomes at 90 day. Patients with higher NIHSS, lower white blood cell counts before surgery, without general anesthetics and patients with complete recanalization were more likely to achieve ENIs.

关键词： glutaric aciduria type 1   glutaric acidemia type 1   newborn screening   outcome   meta-analysis  

摘要： Purpose Glutaric aciduria type 1 (GA1), a rare inherited neurometabolic disorder, results in a complex movement disorder (MD) with predominant dystonia if untreated. Implementation into newborn screening (NBS) programs and adherence to recommended therapy are thought to improve the neurological outcome. Methods Systematic literature search for articles published from 2000 to 2019 was performed using the PRISMA protocol. Studies reporting on more than one individual identified by NBS were included. We investigated effects of interventional and noninterventional variables on neurological outcome. Results Fifteen publications reporting on 647 GA1 patients were included. In the NBS group (n = 261 patients), 195 patients remained asymptomatic (74.7%), while 66 patients (25.3%) developed a MD. Compared with the NBS group, a much higher proportion of patients (349/386;90.4%;p < 0.0001) diagnosed after the manifestation of neurologic symptoms had a MD and an abnormal motor development (285/349;81.7%;p < 0.0001). For NBS patients, deviations from the recommended diet increased the risk of insidious onset MD, while delayed start of emergency treatment increased the risk of acute onset MD. Conclusions This meta-analysis demonstrates that NBS programs for GA1 have an overall positive effect on the neurological outcome of affected individuals but their success critically depends on the quality of therapy.