Journal of Central Nervous System Disease最新文献

Background: Rho-kinase inhibition in a rat middle cerebral artery occlusion (MCAO) model is reported to improve neurological functions and decrease infarction size.

Objective: The objective of this study is to investigate the underlying mechanisms of such improvement by evaluating the effects of Rho-kinase inhibition on astrocytes and microglial accumulation and activation in this condition.

Methods: Adult male Sprague-Dawley (SD) rats were used to generate the MCAO model, which received an I.P injection of a chemical Rho-kinase inhibitor (Fasudil- 5 mg/kg/day) or vehicle (PBS) for 2 and 4 days.

Results: Fasudil treatment significantly decreased the stroke volumes and water content in the lesion areas, as revealed by MRI. Immunostaining and Western blotting results demonstrated that Fasudil significantly decreased the levels of Aquaporin-4, a water channel protein. The number of GFAP⁺ astrocytes and Iba-1⁺ macrophage/microglia was decreased in the lesion areas. Proinflammatory transcription factor NF-κB protein levels were decreased in the Fasudil group 2 days after MCAO. Also, proinflammatory mediators including TNF-α, IL-1β, and iNOS levels were decreased. In vitro migration study using a human microglial cell line (HMO6) confirmed the inhibitory effects of Fasudil on the process. Fasudil also decreased combined IL-1β and IFNγ-induced NF-κB nuclear translocation in HMO6. Moreover, Fasudil transiently decreased combined IL-1β and IFNγ-induced iNOS, TNFα, and IL-1β mRNA levels in HMO6.

Conclusion: Our study demonstrates the inhibitory effects of Rho-kinase on NF-κB-mediated glial activation and cerebral edema, which might be a promising therapeutic target in acute cerebral ischemia conditions.

Background: In EXPAND (NCT01665144), a phase 3 randomized clinical trial, siponimod reduced disability progression versus placebo in patients with secondary progressive multiple sclerosis (SPMS).

Aim: To understand how a real-world population with SPMS relates to that in EXPAND, we conducted a retrospective, observational cohort study using the German NeuroTransData (NTD) multiple sclerosis (MS) registry.

Methods: The NTD MS registry is run by a Germany-wide network of physicians. Two cross-sectional analyses were performed using the NTD MS registry. The first included patients with SPMS, as recorded in the registry, and compared their characteristics between 1 January 2018 and 31 December 2018 with patients in EXPAND. The second described the characteristics of patients in the registry at the time of diagnosis of SPMS between 1 January 2010 and 31 December 2018.

Results: The first analysis included 773 patients: patients were older in the NTD MS registry than in EXPAND (mean age, 57.9 vs 48.0 years) and had a longer duration of SPMS (mean, 6.2 vs 3.8 years). In the NTD MS registry, median Expanded Disability Status Scale (EDSS) scores were comparable to EXPAND (6.0 versus 6.0), although fewer patients had relapses in the previous 24 months (16% vs 36% [siponimod] and 37% [placebo]). Data on gadolinium-enhancing lesions were only available for 5.8% of patients in the NTD MS registry. The second analysis included 916 patients: at the time of SPMS diagnosis, the mean age was 53.2 years and the median EDSS score was 5.0.

Conclusion: The population in the NTD MS registry was older to that in EXPAND, but were similar in terms of disability. Differences likely reflect the inclusion criteria of EXPAND but also highlight that real-world populations encompass a wider range of patient characteristics.

Background: Both inflammation and thrombotic/hemostatic mechanisms may play a role in acute ischemic stroke (AIS) pathogenesis, and a biomarker, such as the platelet-to-lymphocyte ratio (PLR), considering both mechanisms may be of clinical utility.

Objectives: This meta-analysis sought to examine the effect of PLR on functional outcomes, early neurological changes, bleeding complications, mortality, and adverse outcomes in AIS patients treated with reperfusion therapy (RT).

Design: Systematic Review and Meta-Analysis.

Data sources and methods: Individual studies were retrieved from the PubMed/Medline, EMBASE and Cochrane databases. References thereof were also consulted. Data were extracted using a standardised data sheet, and systematic reviews and meta-analyses on the association of admission (pre-RT) or delayed (post-RT) PLR with defined clinical and safety outcomes were conducted. In the case of multiple delayed PLR timepoints, the timepoint closest to 24 hours was selected.

Results: Eighteen studies (n=4878) were identified for the systematic review, of which 14 (n=4413) were included in the meta-analyses. PLR collected at admission was significantly negatively associated with 90-day good functional outcomes (SMD=-.32; 95% CI = -.58 to -.05; P=.020; z=-2.328), as was PLR collected at delayed timepoints (SMD=-.43; 95% CI = -.54 to -.32; P<.0001; z=-7.454). PLR at delayed timepoints was also significantly negatively associated with ENI (SMD=-.18; 95% CI = -.29 to -.08; P=.001. Conversely, the study suggested that a higher PLR at delayed timepoints may be associated with radiological bleeding and mortality. The results varied based on the type of RT administered.

Conclusions: A higher PLR is associated with worse outcomes after stroke in terms of morbidity, mortality, and safety outcomes after stroke.

Background: Recent data indicate that the three-month prevalence of severe headaches or migraines in the US general population is close to 25%. Participation of primary care providers will therefore be critical in providing care to affected individuals.

Objective: To determine the number of headache disorder consult requests to a neurology outpatient service in a tertiary medical center, the appropriateness of the consult requests, and the effectiveness of a lecture series on headache diagnosis and management in preventing inappropriate consult requests from non-neurology providers.

Methods: Clinical data on US Veterans is captured and documented in the Veterans Health Information Systems and Technology Architecture (VISTA). The Computerized Patient Record System (CPRS) electronic medical record (EMR) was used for data entry and retrieval. All consult requests for the study period within the VA North Texas Health Care System were identified in VISTA, and the clinical information reviewed in CPRS. Based on a defined algorithm, headache consult request were categorized as appropriate or inappropriate. A board-certified neurologist provided four in-person/virtual lectures to ambulatory care providers, primary care providers, internal medicine residents, and emergency room providers within the VA North Texas Health Care System on the diagnosis and management of headaches. Prior and post the lecture series, the total number of headache consults per day was assessed over 45-day periods.

Results: The number of daily headache consult requests in the 45-day period prior to the lecture series was 3.6 per day (standard deviation 2.7), and 6.0 per day after the lecture series (standard deviation 2.1). The difference was not statistically significant. There were as many inappropriate headache consult requests after the lecture series as appropriate ones (50% each).

Conclusion: We found that a short-term educational initiative that instructed primary care providers on the diagnosis and management of common headache disorders did not reduce the number of consultation requests and, surprisingly, it did not improve the appropriateness of the consults. Given the prevalence of headaches in the general population, better training of all primary care providers in headache management should be pursued.

COVID-19 associated neurological syndromes, including acute ischemic stroke, pose a challenge to treating physicians. The role of MRI in aiding diagnosis and further management is indispensable. The advent of new MRI sequences such as vessel wall imaging (VWI) allows an avenue in which these patients could be better investigated and treated. We describe our experience in managing a patient with COVID-19 associated atherothrombosis and stroke, focusing on the VWI imaging findings.

Background: Drivers of differences in disease presentation and symptom duration in Lyme neuroborreliosis (LNB) are currently unknown.

Objectives: We hypothesized that neurofilament light (NfL) in cerebrospinal fluid (CSF) would predict disease location and sequelae in a historic LNB cohort.

Design: Using a cross-sectional design and archived CSF samples from 185 patients diagnosed with LNB, we evaluated the content of NfL in the total cohort and in a subgroup of 84 patients with available clinical and paraclinical information.

Methods: Individuals were categorized according to disease location: a. Central nervous system (CNS) with stroke (N=3), b. CNS without stroke (N=11), c. Peripheral nervous system (PNS) with cranial nerve palsy (CNP) (N=40) d. PNS without CNP (N=30). Patients with hospital follow-up more than 6 months after completed antibiotic therapy were categorized as having LNB associated sequelae (N=15).

Results: At diagnosis concentration of NfL exceeded the upper reference level in 60% (105/185), especially among individuals above 30 years. Age-adjusted NfL was not found to be associated with symptom duration. Age-adjusted NfL was significantly higher among individuals with CNS involvement. Category a. (stroke) had significantly higher NfL concentrations in CSF compared to all other categories, category b. (CNS involvement without stroke) had significantly higher values compared to the categories of PNS involvement. We found no significant difference between the categories with PNS involvement (with or without CNP). Significantly higher NfL was found among patients with follow-up in hospital setting.

Conclusion: Comparison of NfL concentrations between the 4 groups of LNB disease manifestations based on clinical information revealed a hierarchy of neuron damage according to disease location and suggested evolving mechanisms with accelerated injury especially when disease is complicated by stroke. Higher values of NfL among patients with need of follow-up in hospital setting suggest NfL could be useful to identify rehabilitative needs.

Virtual care is here to stay. The explosive expansion of telehealth caused by the SARS-CoV-2 pandemic is more than a necessary measure of protection. The key drivers of this transition in healthcare delivery to a virtual setting are changes in patient behavior and expectations and societal attitudes, and prevailing technologies that are impossible to ignore. The younger population - Generation Z - is increasingly connected and mobile-first. We are heading to a world where we expect to see healthcare in general and neurology, in particular, delivered virtually. The medical community should prepare for this overhaul; proper implementation of virtual care from the ground up is the need of the hour. In an era of virtualization, it is up to the medical community to ensure a well-informed patient population, overcome cultural differences and build digital infrastructure with enhanced access and equity in care delivery, especially for the aging neurological patient population, which is not technologically savvy. Virtual care is a continuum of care that needs deeper integration at systematic levels. The design principles of a patient's journey need to be incorporated while simultaneously placing physician satisfaction with a better user experience at the center of implementation. In this paper, we discuss common challenges and pitfalls of virtual care implementation in neurology - logistical, technical, medicolegal, and those faced in incorporating health and medical education into virtual care - intending to provide solutions and strategies.

Coronavirus disease 2019 (COVID-19) has raised serious concerns worldwide due to its great impact on human health and forced scientists racing to find effective therapies to control the infection and a vaccine for the virus. To this end, intense research efforts have focused on understanding the viral biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19. The ever-expanding list of cases, reporting clinical neurological complications in COVID-19 patients, strongly suggests the possibility of the virus invading the nervous system. The pathophysiological processes responsible for the neurological impact of COVID-19 are not fully understood. Some neurodegenerative disorders sometimes take more than a decade to manifest, so the long-term pathophysiological outcomes of SARS-CoV-2 neurotropism should be regarded as a challenge for researchers in this field. There is no documentation on the long-term impact of SARS-CoV-2 on the human central nervous system (CNS). Most of the data relating to neurological damage during SARS-CoV-2 infection have yet to be established experimentally. The purpose of this review is to describe the knowledge gained, from experimental models, to date, on the mechanisms of neuronal invasion and the effects produced by infection. The hope is that, once the processes are understood, therapies can be implemented to limit the damage produced. Long-term monitoring and the use of appropriate and effective therapies could reduce the severity of symptoms and improve quality of life of the most severely affected patients, with a special focus on those have required hospital care and assisted respiration.