Journal of Central Nervous System Disease最新文献

Purpose: The establishment of early diagnostic methods for Parkinson disease (PD) is one of the key features to clinically control the rate of PD progression. This study aimed to give a first step toward recognizing the efficacy of multiple postural indices of balance control in differentiating medicated PD patients from health participants.

Methods: Nine individuals with PD (Hoehn and Yahr Stage up to 2), 9 staged 2.5 and up, and 9 healthy age-matched Controls performed bipedal stances for 120 seconds with eyes either open or closed on a stable force platform. All participants with PD were under anti-Parkinsonian medication. Non-parametric tests investigated the effects of PD and visual input on postural indices extracted from the center of pressure coordinates.

Results: Independent of the stage of the disease, individuals with PD presented faster and shakier body sway compared with Controls. Advanced stages of PD also revealed increased body sway length and variability. In addition, medio-lateral postural instability was more pronounced in all stages of PD when visual inputs were not allowed.

Conclusion and significance: Body sway velocity, jerkiness, length, and its variability revealed to be potential markers for subclinical signs of adjustments in the neuromechanisms of balance control and postural instability even at early stages of disease and under anti-Parkinsonian medication. Results produced here will direct future studies aiming to investigate the efficacy of these same indices on recognizing subclinical development of PD as well as those individuals susceptible to faster rates of progression.

Background: Carbamazepine and valproate are widely used in the treatment of epileptic seizures. However, these agents exhibit certain adverse effects including hematopoietic disorders (carbamazepine) and severe hepatotoxicity (valproate).

Purpose: To determine the extent of monitoring of the hematologic effects of carbamazepine as well as the extent of monitoring of the hepatic effects of valproate in patients with epilepsy receiving treatment with these agents.

Method: A cross-sectional antiepileptic drug use study using case notes of patients with epilepsy managed at the neurologic clinics of 2 tertiary medical facilities in Nigeria between January and December 2017.

Results: Carbamazepine was the most frequently prescribed antiepileptic drug (48.24%), followed by valproate (29.34%) and levetiracetam (9.24%). Pretreatment monitoring of hematologic effect was carried out in only 61.11% of patients placed on carbamazepine therapy while follow-up monitoring was done in 3.7% of these patients. Also, in patients placed on valproate therapy, pretreatment and follow-up monitoring of the hepatic effect was done in only 33.71% and 19.0% of the patients, respectively.

Conclusions: The extent of monitoring of the hematologic effects of carbamazepine, as well as the hepatic effects of valproate in the cohort studied, is poor.

Background: Health-related quality of life (HRQOL) is an important measure that enables evaluation of rehabilitation outcomes. Stroke and Aphasia Quality of Life Generic Scale-39 (SAQOL-39g) is a disease-specific questionnaire that measures HRQOL of patients with stroke. This study was conducted to adapt the preliminary version of proxy-rated Sinhala version of the SAQOL-39g.

Methods: The study was conducted with the participation of 115 proxies of the patients with stroke. The SAQOL-39g was translated and back translated, and culturally adapted by evaluating the items of the questionnaire. The culturally adapted scale was evaluated for its internal consistency, test-retest reliability, and validity.

Results: The mean age of the patients with stroke was 67.07 (standard deviation [SD] = 11.2) years; males comprising two-thirds of the study sample (67% [n = 77]). The proxy-rated Sinhala version of the SAQOL-39g showed excellent internal consistency (α = 0.98 [overall score]), 0.97, 0.96, and 0.95 for physical, communication, and psychosocial domains, respectively. The intraclass correlation coefficient (ICC) was 0.92 for overall, and 0.93, 0.92, and 0.91 for physical, communication, and psychosocial domains, respectively. Factor analysis extracted 3 factors with 72.4% of the variance.

Conclusions: Proxy-rated Sinhala version of the SAQOL-39g is a psychometrically sound, reliable, and valid tool to assess the post-stroke quality of life of Sinhala-speaking patients with stroke and aphasia.

Background: Alzheimer disease is a progressive neurodegenerative disease, affecting a very high proportion of the aging population. Several studies have demonstrated that one of the main contributors to this disease is oxidative stress (OS), which causes peroxidation of protein, lipids, and DNA resulting in the formation of advanced glycosylated end products (AGE) in the brain tissues. These AGE are usually associated with the amyloid β (Aβ), which could further aggravate its toxicity and its clearance. Antioxidants counteract the deterioration caused by OS.

Objective: We aimed to evaluate the effect of vitamin D3 and curcumin on primary cortical neuronal cultures exposed to Aβ_1-42 toxicity for different time periods.

Methods: Primary cortical neuronal cultures were set up and exposed to Aβ_1-42 for up to 72 hours. Cell viability was studied by 3[4,5-dimethylthiazole-2-yl]-2,5-dipheyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Biochemical assays for OS such as lipid peroxidation, reduced Glutathione(GSH), Glutathione S-transferase (GST), catalase, and superoxide dismutase (SOD) were conducted. Sandwich enzyme-linked immunosorbent assay (ELISA) was used to study the neurotrophic growth factor (NGF) expression.

Results: Treatments with Aβ_1-42 caused an elevation in lipid peroxidation products, which were ameliorated in the presence of vitamin D3 and curcumin. Both enzymatic (GST, catalase, and SOD) and nonenzymatic antioxidants (reduced GSH) were raised significantly in the presence of vitamin D3 and curcumin, which resulted in the better recovery of neuronal cells from Aβ_1-42 treatment. Treatment with vitamin D3 and curcumin also resulted in the upregulation of NGF levels.

Conclusions: This study suggests that vitamin D3 and curcumin can be a promising natural therapy for the treatment of Alzheimer disease.

[This corrects the article DOI: 10.1177/1179573519899471.].

Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a "precision medicine" context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.

Background: In addition to the reduced energy production, characteristic of mitochondrial disorders, nitric oxide (NO) deficiency can occur as well. The NO produced by vascular endothelial cells relaxes vascular smooth muscles, resulting in vasodilation that maintains the patency of small blood vessels and promotes blood flow through microvasculature. Endothelial dysfunction due to inability of vascular endothelium to generate enough NO to maintain adequate vasodilation can result in decreased perfusion in the microvasculature of various tissues, contributing to many complications seen in individuals with mitochondrial diseases. The amino acids arginine and citrulline are NO precursors: increasing their concentrations could potentially restore NO production.

Methods: In this study, we assessed endothelial dysfunction in children and adolescents with mitochondrial diseases. We also investigated the effect of arginine and citrulline supplementation on endothelial dysfunction in these individuals. We used peripheral arterial tonometry to measure the reactive hyperemic index (RHI), which is low when there is endothelial dysfunction.

Results: The results demonstrated low RHI in individuals with mitochondrial diseases, indicating endothelial dysfunction. RHI increased with arginine or citrulline supplementation suggesting that supplementation with NO precursors can improve endothelial dysfunction by enhancing NO production.

Conclusions: This study is the first one to use peripheral arterial tonometry methodology in mitochondrial diseases. The results of this study provide evidence for endothelial dysfunction in mitochondrial diseases and demonstrate that arginine or citrulline supplementation can alleviate the endothelial dysfunction, providing more evidence for the potential therapeutic utility of these amino acids in mitochondrial diseases.

Background and rationale: Stroke is considered the most common cause of adult disability. Intensive rehabilitation protocols outperform nonintensive counterparts. The subacute stroke phase represents a potential window to recovery. Virtual reality (VR) has been shown to provide a more stimulating environment, allowing for increased patient compliance. However, the quality of current literature comparing VR with standard therapies is limited. Our aim is to measure the impact of VR versus standard therapy on the recovery of the upper limb motor function in patients with stroke in the early subacute recovery phase.

Method: This is a randomized, controlled trial that will assign 262 patients to tailor-made standard rehabilitation (TMSR) or TMSR plus immersive VR device. The trial will be conducted in an urban rehabilitation clinic in the United States with expertise in the management of poststroke patients. Patients will be 18 to 70 years of age and in the early subacute period (30-90 days post ischemic stroke). The primary outcome will be the change of Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score, measured at baseline and 13 weeks after randomization. The secondary outcome will be the change in the UK Functional Independence Measure and Functional Assessment Measure (UK FIM-FAM) score at the same time points.

Discussion: If the use of VR in the rehabilitation of patients with stroke proves to have a significant impact on their motor recovery, it will constitute an extremely important step into decreasing the functional impairment associated with stroke and the related health care expense burden.

Multiple sclerosis (MS) is a complex neurological disorder characterized by an aberrant immune system that affects patients' quality of life. Several environmental factors have previously been proposed to associate with MS pathophysiology, including vitamin D deficiency, Epstein-Barr virus (EBV) infection, and cigarette smoking. These factors may influence cellular molecularity, interfering with cellular proliferation, differentiation, and apoptosis. This review argues that small noncoding RNA named microRNA (miRNA) influences these factors' mode of action. Dysregulation in the miRNAs network may deeply impact cellular hemostasis, thereby possibly resulting in MS pathogenicity. This article represents a literature review and an author's theory of how environmental factors may induce dysregulations in the miRNAs network, which could ultimately affect MS pathogenicity.

Background: Cognitive impairment is a very frequent and severe nonmotor symptom of Parkinson's disease (PD). Early intervention in this at-risk group for cognitive decline may be crucial for long-term preservation of cognitive functions. Computerized working memory training (WMT) has been proven beneficial in non-PD patient populations, but such evidence is still needed for patients with PD.

Objective: This study aimed to evaluate the effect of WMT on visuo-spatial working memory (WM) in cognitively unimpaired patients with PD.

Methods: A single-blind randomized controlled trial encompassing 76 patients with PD but no cognitive impairment according to level II diagnostic criteria was conducted. Thirty-seven patients engaged in home-based adaptive WMT 5 times per week for a period of 5 weeks, whereas the remaining patients were in the waiting list arm of the study (control group [CG]). Working memory performance was evaluated using a computerized task before and after intervention and at 14-week follow-up, allowing to quantify the precision of WM on a continuous scale, ie, to test not only if an item was remembered but also how well the location of this item was retained.

Results: Coincidently, the WMT group showed slightly worse WM performance compared with the CG at baseline, which was ameliorated after WMT. This training-induced effect remained stable until follow-up.

Conclusion: Patients showing relatively low WM performance, despite not formally diagnosable as Parkinson's disease with mild cognitive impairment (PD-MCI), seem to benefit from home-based WMT. Thus, WMT could potentially be implemented in future trials as a time- and cost-efficient route to counteract subtle cognitive changes in early disease stages.

Trial registration: German Clinical Trial Register (drks.de, DRKS00009379).