Journal of Central Nervous System Disease最新文献

Background: After standard care, 55%-75% of patients after stroke show a persistent paresis of the upper limb (UL). Assistive devices are developed to increase the patients' level of independence in daily life.

Objectives: To investigate the potential of Functional Electrical Stimulation (FES) to assist object manipulation in activities of daily life.

Design: Seventeen patients after stroke were tested and analyzed in a randomized cross-over design.

Methods: Functional grasping was assessed by means of the Action Research Arm Test (ARAT) and the modified Box and Block Test (mBBT), in one session with and another without FES assistance. The order of sessions was randomized. Patients' motivation was assessed after each session. Task performance and motivation were compared between conditions using the Wilcoxon test and subgroup analyses were performed for impairment severity by distribution-based mixed-factor analyses.

Results: When analyzing the total ARAT, FES did not effectively assist the overall performance (P = .142), but did assist the performance of objects of the Grasp category (P = .020). Impairment severity showed an interaction with the orthotic effect (P = .012), as severely impaired patients profited from FES assistance and mild-moderately impaired did not. When focusing on the more functional items of the ARAT (i.e., excluding scores from thumb-middle and thumb-ring finger combinations), there was a significant orthotic effect of FES on task performance (P = .023). Further, there was an orthotic effect for the number of transported blocks in the mBBT (P = .033), exclusively prominent in the group of severely impaired patients. Functional Electrical Stimulation did not increase the patients' motivation (P = .959), which was high after both conditions.

Conclusion: Functional Electrical Stimulation has the potential to support object manipulation, but is dependent on impairment severity and object type. To observe a consistent orthotic effect, features of the stimulator should be further developed to generate appropriate grasps and forces across subjects and objects.

Trial registration: The trial was registered with the German Clinical Trials Register (DRKS00025889).

Significant advances have been made in the diagnosis and treatment of multiple sclerosis in recent years yet challenges remain. The current classification of MS phenotypes according to disease activity and progression, for example, does not adequately reflect the underlying pathophysiological mechanisms that may be acting in an individual with MS at different time points. Thus, there is a need for clinicians to transition to a management approach based on the underlying pathophysiological mechanisms that drive disability in MS. A Canadian expert panel convened in January 2023 to discuss priorities for clinical discovery and scientific exploration that would help advance the field. Five key areas of focus included: identifying a mechanism-based disease classification system; developing biomarkers (imaging, fluid, digital) to identify pathologic processes; implementing a data-driven approach to integrate genetic/environmental risk factors, clinical findings, imaging and biomarker data, and patient-reported outcomes to better characterize the many factors associated with disability progression; utilizing precision-based treatment strategies to target different disease processes; and potentially preventing disease through Epstein-Barr virus (EBV) vaccination, counselling about environmental risk factors (e.g. obesity, exercise, vitamin D/sun exposure, smoking) and other measures. Many of the tools needed to meet these needs are currently available. Further work is required to validate emerging biomarkers and tailor treatment strategies to the needs of individual patients. The hope is that a more complete view of the individual's pathobiology will enable clinicians to usher in an era of truly personalized medicine, in which more informed treatment decisions throughout the disease course achieve better long-term outcomes.

Introduction: Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA.

Objective: To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA.

Methods: We analyzed 22 pwMS initiated on OFA and 56 sex-, age- and MS course matched pwMS initiated on OCR from 2 prospectively collected observational MS databases (Bern [n: OFA 14, OCR 44] and Vienna [n: OFA 8, OCR 12]) statistically comparing lymphocyte subset counts (Mann Whitney Test).

Results: We found that pwMS treated with OCR showed a stronger reduction of CD20 B-lymphocytes (P = .001), and a trend towards lower counts of CD8⁺ T cells (P = .056) compared to pwMS treated with OFA, whereas reduction of total lymphocyte, CD4⁺ lymphocyte and NK cell count was equally distributed between both treatments.

Conclusion: Different effects on lymphocyte subpopulations appear to be present in pwMS after treatment initiation with different anti-CD20 mAbs. Further studies are needed to determine potential effects on anti-CD20 treatment efficacy as well as treatment associated risks such as failed vaccinations and infections.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending.

Objective: Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting.

Design and methods: This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed.

Results: We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB.

Conclusion: Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members. We report the variant c.877T>C p.(Cys293Arg) found in TYMP gene in all affected siblings showed typical clinical manifestations related to MNGIE. To the best of our knowledge, this is not described in the literature nor in the population databases dbSNP (Single Nucleotide Polymorphism Database) and gnomAD (Genome Aggregation Database). Additionally, it is located in a highly conserved residue and the bioinformatic analysis suggests it is most probably deleterious. Moreover, we estimated 550 number of cases of MNGIE (including 5 cases in this study) after performing an extensive search in the literature across 3 databases from 1983-2023. In addition, we identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.

BACKGROUND: Awake craniotomy has emerged as an advanced surgical technique, characterized by keeping the patient awake during brain surgery. In South America, awake craniotomies have grained traction in neurosurgical practices across various medical centres and hospitals, with notable practitioners contributing to its growth and refinement in the region. PURPOSE: This study aims to explore the integration and impact of awake craniotomies in South American neurosurgical practices. The focus is on understanding the benefits, challenges, and potential transformative effects of the procedure in the region. RESEARCH DESIGN: A comprehensive narrative review and analysis through a thorough examination of the existing literature. RESULTS: The findings indicate that awake craniotomies in South America offer substantial benefits, including cost savings thorugh reduced hospitalization time, quicker recovery and decreased morbidity. Enhanced safety, effective pain management and reduced anaesthesia also contribute to this. CONCLUSION: Whilst the adaptation of awake craniotomies in South America holds great promise in transforming neurosurgical care in the region, significant challenges hinder its widespread adoption. Inadequate infrastructure, limited access to equipment, financial instability, and shortages in trained healthcare providers represent challenges that need to be addressed.

Hypothalamic hamartomas (HHs) are congenital developmental malformations located in the hypothalamus. They are associated with a characteristic clinical manifestation known as gelastic seizures (GS). However, the traditional understanding of HHs has been limited, resulting in insufficient treatment options and high recurrence rates of seizures after surgery. This is consistent with the network hypothesis of focal epilepsy that the epileptogenic zone is not only limited to HH but may also involve the distant cerebral cortex external to the HH mass. The epilepsy network theory, on the other hand, provides a new perspective. In this study, we aim to explore HH-related epilepsy as a network disease, challenging the conventional notion of being a focal lesional disease. We analyze various aspects of HHs, including genes and signaling pathways, local circuits, the whole-brain level, phenotypical expression in terms of seizure semiology, and comorbidities. By examining HHs through the lens of network theory, we can enhance our understanding of the condition and potentially identify novel approaches for more effective management and treatment of epilepsy associated with HHs.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the central nervous system including but not limited to optic neuritis, transverse myelitis and brainstem lesions, including area postrema lesions. These autoimmune attacks can lead to irreversible damage if left untreated, therefore strategies have been developed to prevent relapses. Initial off-label treatments have achieved variable levels of success in relapse prevention, but improved relapse prevention and quality of life remain a goal in the field. A better understanding of the underlying pathophysiology of NMOSD over the last 10 years has led to newer, more specific approaches in treatment, culminating in the first FDA approved treatments in the disease. In this review, we will discuss the seminal trials of PREVENT or Eculizumab in the treatment of aquaporin-4 (AQP4)-IgG positive NMOSD, N-Momentum or Inebilizumab in the study of NMOSD (both AQP4-IgG positive and negative) and SAkura Sky and SAkuraStar which studied satralizumab in AQP4-IgG seropositive and seronegative NMOSD patients. We will also discuss the extension trials of each of these medications and what lead to their approval in AQP4-IgG seropositive NMOSD patients. We will then examine treatments in the pipeline for adult and pediatric NMOSD patients and conclude with discussions on treatment considerations in pregnant patients and how to approach treatment of NMOSD patients during COVID.

Background: In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field.

Objectives: Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS.

Design: A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review.

Data sources and methods: In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale.

Results: We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best.

Conclusion: In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).