关键词： comparative study   fluoroquinolones   neurologic manifestations   pharmacoepidemiology   propensity score   survival analysis  

摘要： Background Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones. Purpose To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction. Methods We conducted a propensity score-matched inception cohort study using claims data from a commercially insured population. Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use. Results Our cohort contained 976 568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference <0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05-1.11) for CNS dysfunction, and 1.09 (95% CI 1.07-1.11) for the most commonly occurring PNS dysfunction outcome. Conclusions Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population.

关键词： cerebral small vessel disease   perineuronal extracellular matrix   perivascular extracellular matrix   stroke  

摘要： Vascular damage, central nervous system (CNS) injury, seizure or even psychological stress may trigger activation of microglia and infiltration of other immune cells, accompanied by high levels of expression and activity of extracellular proteases, such as matrix metalloproteinases (MMPs), and degradation/remodelling of the perivascular and perineuronal extracellular matrix (ECM). This acute response is followed by the recovery/chronic phase, during which the activation of astrocytes leads to the upregulated synthesis of ECM molecules, which, in combination with elevated expression of tissue inhibitor of metalloproteinases (TIMP) proteins, increases the aggregation of ECM molecules. This biphasic dysregulation of local balance between extracellular proteases and the ECM activates multiple temporally overlapping signalling cascades, involving receptor-type protein tyrosine phosphatases, integrins, Toll-like receptors, cell adhesion molecules, and ion channels, resulting in impaired synaptic plasticity and cognition. An additional level of complexity is related to the leakage of blood plasma proteins, such as fibrinogen, and the diffusion of perivascularly overproduced MMPs, TIMPs and ECM molecules into the CNS parenchyma, leading to diverse effects on neurons and incorporation of these molecules into the interstitial neural ECM. This review aims to outline these complex common mechanisms in stroke, CNS injury, depression, epilepsy, multiple sclerosis and cerebral small vessel disease and to discuss translational strategies to advance the development of new therapies for these neurological and psychiatric diseases.

关键词： Cardiac arrest   Neural stem cells (NSCs)   Intracerebroventricular (ICV)   Subventricular zone (SVZ)   Functional outcomes  

摘要： Irreversible brain injury and neurological dysfunction induced by cardiac arrest (CA) have long been a clinical challenge due to lack of effective therapeutic interventions to reverse neuronal loss and prevent secondary reperfusion injury. The neuronal regenerative potential of neural stem cells (NSCs) provides a possible solution to this clinical deficit. We investigated the neuronal recovery potential of human neural stem cells (hNSCs) via intracerebroventricular (ICV) xenotransplantation after CA in rats and the effects of transplanted NSCs on the proliferation and migration of endogenous NSCs. Outcome measures included neurological functional recovery measured by neurological deficit score (NDS), electrophysiologic analysis of EEG, and assessment of proliferation and migration at the cellular level and the Wnt/beta-catenin pathway at the molecular level. Neurological functional assessment based on aggregate neurological deficit score (NDS) showed better recovery of function after hNSCs therapy (P < 0.05). Tracking of stem cells' proliferation with Ki67 antibody suggested that the NSCs group had more prominent proliferation compared to control group (number of Ki67+ cells, Control VS. NSC: 89.0 +/- 31.6 VS. 352.7 +/- 97.3, P < 0.05). In addition, cell migration tracked by Dcx antibody showed more Dcx + cells migrated to the far distance zone from SVZ in the treatment group (P < 0.05). Further immunofluorescence staining confirmed that the expression of the Wnt signaling pathway protein (beta-catenin) was upregulated in the NSC group (P < 0.05). ICV delivery of hNSCs promotes endogenous NSC proliferation and migration and ultimately enhances neuronal survival and neurological functional recovery. Wnt/beta-catenin pathway may be involved in the initiation and maintenance of this enhancement.

摘要： Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. It is required for the conversion of oxidised glutathione to the reduced form and for the mitochondrial respiratory chain as complexes I and II contain flavoprotein reductases and electron transferring flavoproteins. Riboflavin deficiency has been demonstrated to impair the oxidative state of the body, especially in relation to lipid peroxidation status, in both animal and human studies. In the nervous system, riboflavin is essential for the synthesis of myelin and its deficiency can determine the disruption of myelin lamellae. The inherited condition of restricted riboflavin absorption and utilisation, reported in about 10-15% of world population, warrants further investigation in relation to its association with the main neurodegenerative diseases. Several successful trials testing riboflavin for migraine prevention were performed, and this drug is currently classified as a Level B medication for migraine according to the American Academy of Neurology evidence-based rating, with evidence supporting its efficacy. Brown-Vialetto-Van Laere syndrome and Fazio-Londe diseases are now renamed as "riboflavin transporter deficiency" because these are autosomal recessive diseases caused by mutations of SLC52A2 and SLC52A3 genes that encode riboflavin transporters. High doses of riboflavin represent the mainstay of the therapy of these diseases and high doses of riboflavin should be rapidly started as soon as the diagnosis is suspected and continued lifelong. Remarkably, some mitochondrial diseases respond to supplementation with riboflavin. These include multiple acyl-CoA-dehydrogenase deficiency (which is caused by ETFDH gene mutations in the major

关键词： Viral encephalitis   Polymerase chain reaction   Herpesvirus   Epstein–   –   Barr virus   Varicella zoster virus  

摘要： The frequency of central nervous system infections due to herpesvirus have been studied in various populations;however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis;polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502;in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

关键词： Post-acute COVID-19 syndrome   COVID-19   Nervous system diseases   Neurologic manifestations   Neurological rehabilitation  

摘要： Study design Literature review. Objectives: Describe the implications of post-COVID syndrome due to neurological sequelae including treatment and the differences that may exist between this group of patients and those who present these events not associated with COVID-19. Methods: A non-systematic review of the literature was carried out in PubMed and Science Direct databases, using the keywords "Post-acute COVID-19 syndrome";"Neurological complications";"Neurologic Manifestations" "COVID-1900 and "Rehabilitation", as well as synonyms, which were combined with the operators "AND"and "OR". Results: The COVID-19 viral caustive agent, SARS-CoV-2, has a high affinity for human angiotensinconverting enzyme 2 receptor on type II pneumocytes. This receptor is also expressed in neurons and glial cells. Based on the foregoing and other not so clear mechanisms, it is stated that SARS-CoV-2 has tropism for the nervous system, being evident through the neurological manifestations observed in patients with mild, moderate and severe phenotype of the disease such as anosmia, ageusia, headache, cerebrovascular accidents, Guillain-Barre syndrome, seizures, and encephalopathy. This can generate severe sequelae and even fatal outcomes in those affected. Conclusions: Neurological complications caused by COVID-19 are frequent and represent a risk that compromises the functional capacity and the life of patients. The suspicion of these conditions, the strict control of metabolic alterations and cardiovascular risk factors, the effective and safe treatment of these entities, are a current challenge throughout the pandemic. The rehabilitation process in these patients is a challenge. This is due to the limitations generated by multi-organ damage, as well as risk of brain death. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： conversion   conversion symptoms   functional neurological   psychosocial trauma  

摘要： Objective: Psychosocial trauma was associated with developing conversion disorder (also known as functional neurological disorder) before Freud, though why a particular symptom should arise is unknown. We aimed to determine if there was a relationship between trauma type and symptom. Methods: We retrospectively reviewed the medical records of patients attending Australia's first functional neurology clinic, including referral, clinic letters and a clinic questionnaire. Results: There were 106 females, 43 males and five transgender patients. Sensory (51%), motor (47%) and seizures (39%) were the commonest functional symptoms. Most patients (92%) reported stressors associated with symptom onset. Multiple trauma/symptom type associations were found: patients with in-law problems experienced more cognitive symptoms (p = .036), for example, while expressive speech problems more commonly followed relationship difficulties (p = .021). Conclusion: Associations were found between type of traumatic events and type of symptoms in conversion disorder. This will require verification in a larger sample.

关键词： Periodic discharges   Death-related factors   EEG   Scoring system   Nervous system diseases  

摘要： Objective: To investigate death-related factors in patients with electroencephalographic (EEG) periodic discharges (PDs) and to construct a model for death prediction. Methods: This case-control study enrolled a total of 80 severe neurological disease patients with EEG PDs within 72 h of admission to the neuroscience intensive care unit (NICU). According to modified Rankin scale (mRS) scores half a year after discharge, patients were divided into a survival group (<6 points) and a death group (6 points). Their relevant clinical and biochemical indicators as well as EEG characteristics were retrospectively analyzed. Logistic regression analysis was used to identify the risk factors associated with the death of patients with EEG PDs. A death risk prediction model and an individualized nomogram prediction model were constructed, and the prediction performance and concordance of the models were evaluated. Results: Multivariate logistic regression analysis showed that the involvement of both gray and white matter in imaging, disappearance of EEG reactivity, occurrence of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and an interval time of 0.5-4 s were independent risk factors for death. A regression model was established according to the multivariate logistic regression analysis, and the area under the curve of this model was 0.9135. The accuracy of the model was 87.01%, the sensitivity was 87.17%, and the specificity was 89.17%. A nomogram model was constructed, and a concordance index of 0.914 was obtained after internal validation. Conclusion: The regression model based on risk factors has high accuracy in predicting the risk of death of patients with EEG PDs. Significance: This model can help clinicians in the early assessment of the prognosis of severe neurological disease patients with EEG PDs. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

关键词： atrial fibrillation   atrial high‐   rate episodes   dual chamber pacemakers   neurological events  

摘要： Background Patients with atrial high-rate episode (AHRE) are at higher risk of neurological events. This study aimed to identify the optimal cutoff threshold for AHRE duration in patients with dual chamber permanent pacemakers (PPM) without prior atrial fibrillation. Methods We included 355 consecutive patients receiving dual chamber pacemaker implantation. Primary outcome was composite endpoint of subsequent neurological events after various AHRE durations. AHRE was defined as >175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) for longer than 30 s. Cox regression analysis with time-dependent covariates was conducted. Results The mean age of included patients was 75.6 +/- 11.3 years. Among 355 included patients, some had multiple AHREs;125 patients (35.2%) developed AHRE >= 2 min, 107 (30.1%) had >= 5 min, 55 (15.5%) had >= 6 h, and 37 (10.4%) had >= 24 h. The mean follow-up was 42.1 +/- 31.2 months. During follow-up, 19 neurological events occurred. After adjustment for CHA(2)DS(2)-VASc score and device type, multivariate Cox regression analysis indicated AHRE >= 2 min (HR 13.605, 95% CI 3.010-61.498), and AHRE >= 5 min (HR 5.819, 95% CI 2.056-16.470) were significantly associated with neurological events. Hence, the optimal AHRE cutoff value was 2 min with the highest Youden index (sensitivity, 89.5%;specificity, 67.8%;AUC, 0.823, 95% CI, 0.763-0.884;p < 0.001). Conclusions Patients with dual chamber PPM who develop AHRE have increased risk of neurological events. Comprehensive assessment of the risks and benefits of prescribing anticoagulants should be considered in PPM patients with AHRE >= 2 min.