Neurological Disability In Patients Research Articles

Analysis of the Association between Telomere Length and Neurological Disability in Stroke Types.

Background and Objectives: The association between neurological disability, prognosis, and telomere length (TL) in patients with stroke has been investigated in various ways. However, analysis of the type of stroke and ischemic stroke subgroups is limited. In this study, we aimed to determine the association between TL and neurological disability according to stroke type. Materials and Methods: This prospective study included patients with stroke who visited a single-center emergency department (ED) between January 2022 and December 2023. The association between TL and neurological disabilities, using the Modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS), was evaluated according to the patient's stroke type and subgroup of ischemic stroke. Multivariate analysis was performed to determine the association between neurological disabilities in patients with ischemic stroke and the subgroups. Results: A total of 271 patients with stroke were enrolled. The NIHSS score was found to be higher at the time of ED visit (adjusted odds ratio [OR], 5.23; 95% confidence interval [CI], 1.59-17.2, p < 0.01) and 1 day later (adjusted OR, 7.78; 95% CI, 1.97-30.70, p < 0.01) in the ischemic stroke group with a short TL. In the other determined etiology (OD) or undetermined etiology (UD) group, the NIHSS was higher in the short TL group at the ED visit (adjusted OR, 7.89; 95% CI, 1.32-47.25, p = 0.02) and 1 day after (adjusted OR, 7.02; 95% CI, 1.14-43.47, p = 0.04). Conclusions: TL is associated with neurological disability in early ischemic stroke and is prominent in the UD and OD subgroups.

Serum Vitamin D3 as a Potential Biomarker for Neuronal Damage in Smoldering Multiple Sclerosis

Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS.

Can Selected Parameters of Brain Injury Reflect Neuronal Damage in Smoldering Multiple Sclerosis?

Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. A single-center prospective observational study was performed. The median age of the patients was 40 (31-52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Neutrophil-to-lymphocyte ratio is an independent predictor for neurological disability in patients with idiopathic transverse myelitis

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort.MethodsWe retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated.ResultsA total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220–14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249–2.734, p = 0.002) were independent predictive factors of the worst neurological disability.ConclusionNLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.

Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury

BackgroundCerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI.MethodsSH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett’s T3 test (for unequal homogeneity) were used for statistical tests.ResultsERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed.ConclusionInhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model.9RDMMKPHSZ2No4hHf87VtDVideo

GABAB receptor agonist baclofen promotes central nervous system remyelination.

Promoting remyelination is considered as a potential neurorepair strategy to prevent/limit the development of permanent neurological disability in patients with multiple sclerosis (MS). To this end, a number of clinical trials are investigating the potential of existing drugs to enhance oligodendrocyte progenitor cell (OPC) differentiation, a process that fails in chronic MS lesions. We previously reported that oligodendroglia express GABAB receptors (GABAB Rs) both in vitro and in vivo, and that GABAB R-mediated signaling enhances OPC differentiation and myelin protein expression in vitro. Our goal here was to evaluate the pro-remyelinating potential of GABAB R agonist baclofen (Bac), a clinically approved drug to treat spasticity in patients with MS. We first demonstrated that Bac increases myelin protein production in lysolecithin (LPC)-treated cerebellar slices. Importantly, Bac administration to adult mice following induction of demyelination by LPC injection in the spinal cord resulted in enhanced OPC differentiation and remyelination. Thus, our results suggest that Bac repurposing should be considered as a potential therapeutic strategy to stimulate remyelination in patients with MS.

Optical coherence tomography and visual evoked potential and its relationship with neurological disability in patients with relapsing-remitting multiple sclerosis

IntroductionTo evaluate the relationship between retinal nerve fiber layer involvement and visual evoked potential with the neurological disability scale in relapsing remitting multiple sclerosis. MethodsFifty-two patients diagnosed with relapsing-remitting multiple sclerosis were evaluated for the study. Optical coherence tomography (retinal nerve fiber layer or RNFL and macular volume or MV), pattern visual evoked potential or VEP (latency and P100 wave amplitude), and neurological disability scale (EDSS) were performed. A baseline evaluation was carried out and it was repeated after one year and two years. ResultsThe baseline values ​​in the retinal nerve fiber layer were 82.5 (75–93.5), the latency and amplitude of the VEP of 116 (108–125.5) and 9 (7–11), respectively, while the EDSS was 2 (1.5–3). A correlation was found between higher EDSS with prolonged latency and decreased amplitude of the P100 wave. There was an association between a higher EDSS with the prolongation of the latency of the P100 wave and a longer time of evolution of MS. No relationship was found between EDSS and macular volume. A higher EDSS was associated with a significant decrease in RNFL. When the discriminative performance of disability was evaluated, the latency of the VEP presented an area under the curve of 0.79 (CI95% 0.67- 0.92), the amplitude of the VEP an area under the curve of 0.71 (CI95% 0.56 - 0.87) and RNFL a area under the curve of 0.76 (95% CI 0.62 - 0.90. When comparing RNFL, MV and PEV in eyes without and with previous optic neuritis with RNFL values ​​of 88 (81–97) and 76 (71–81) (p 0.0007), MV of 246 (232–261) and 241 (229–251) (p 0.2541), PEV latency of 109 (105–117) and 125 (118–129) (p 0.0001), VEP amplitude of 9 (7–10) and 9 (7–11) (p 0.9391), respectively, which shows a statistically significant correlation between decrease in RNFL and prolongation of VEP latency in eyes with previous optic neuritis. In the 2-year follow-up there were no significant differences between the values ​​of RNFL, VEP and EDSS. DiscussionIn our study, a relationship was evidenced between retinal nerve fiber thickness, PEV and the degree of disability measured by EDSS in patients with relapsing MS - remissions in their baseline values. A lower RNFL thickness was correlated with prolonged latency and decreased amplitude in the PEV and was associated with a higher EDSS. This relationship was more significant in eyes with previous optic neuritis in terms of decreased RNFL thickness and prolongation of PEV latency. No significant differences were found in the 2-year follow-up in the measurements made.

An Evaluation of Right-Sided Symptom Onset as a Predictor of Poor Parkinson's Disease Prognosis.

ObjectiveThe current study aimed to measure and compare neurological disability in Parkinson’s disease (PD) patients with right-sided symptom onset with that in PD patients with left-sided symptom onset, using the measurements taken at their first and last visits, to determine if right-sided symptom onset was predictive of a poor PD prognosis.MethodsOne hundred and forty-three PD patients were included in the study. The Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr Scale were used to measure neurological disability in patients at the first and last visits. The scores for the neurological disability of patients at the first and last visits were compared retrospectively relative to disease onset.ResultsSeventy-six PD patients had right-sided symptom onset (53%), and 67 patients had left-sided symptom onset (47%) (p = < 0.001). The differences between the scores at the first and last visits, measured using the UPDRS and the Hoehn and Yahr Scale, were higher for PD patients with right-sided symptom onset than patients with left-sided symptom onset (p = < 0.001, p = < 0.002, respectively). Similarly, the UPDRS Part II and Part III values, used to evaluate motor function, were higher in PD patients with right-sided symptom onset as compared to those with left-sided symptom onset at the first and last visits (p = < 0.001).ConclusionRight-sided symptom onset was predictive of a poor prognosis in PD patients at follow-up.

Resveratrol nanoparticles are neuroprotective in a model of multiple sclerosis

AbstractPurposeOptic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE.MethodsResveratrol nanoparticles (RNs) were formulated using a thin rehydration technique and assessed for stability with spectrophotometric techniques. C57/BL6 mice were immunized with the myelin oligodendroglial glycoprotein peptide. From EAE induction, mice were treated daily for 30 days by oral gavage of RNs (n = 6), vehicle (n = 5) or unconjugated resveratrol (UnRSV); n = 6). Mice were assessed for EAE signs daily and for visual function weekly by optokinetic responses (OKR). Optic nerve and spinal cord inflammation were assessed by hematoxylin and eosin (H&amp;E). Retinal ganglion cells were immunostained with Brn3a.ResultsResveratrol nanoparticles (RNs) containing &gt;10 mg/ml resveratrol were stable over 3 months with an encapsulation efficiency &gt;70%. 16.9 mg/kg RNs reduced the EAE clinical score at day 30 compared to 16.9 mg/kg vehicle (1.4 ± 0.4 versus 3.0 ± 0.4, p &lt; 0.05) whereas up to 100 mg/kg UnRSV did not lead to reduction of EAE scores. OKR, optic nerve inflammation and spinal cord inflammation were not significantly modified by oral administration of RNs. 16.9 mg/kg RNs reduced RGC loss compared to 16.9 mg/kg vehicle (347 ± 12 versus 172 ± 12 cells/standardized field, p &lt; 0.0001). Importantly, to get a similar reduction, at least 100 mg/kg of UnRSV were needed suggesting that RNs increase resveratrol bioavailability.ConclusionsResveratrol nanoparticles (RNs) increase resveratrol solubility and bioavailability. They show neuroprotection by reducing RGC loss. However, as previously reported for resveratrol, these nanoparticles do not have any anti‐inflammatory effect.

Dietary habits in a group of patients with multiple sclerosis are similar to those of healthy control subjects.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Over time, patients with MS accumulate neurological disabilities. MS typically affects young adults and is associated with an inflammatory profile of cytokines and lymphocytes. If a patient were to consume a potentially inflammatory diet, it is possible that the evolution of MS in that individual would be more aggressive. To investigate whether patients with MS living in and around the city of Santos, São Paulo, Brazil, had a profile of inflammatory diet. Patients with MS and healthy control subjects were individually interviewed, and the 24-hour Diet Recall and the Bristol Stool Form Scale were applied. Salt intake was calculated using the WebDiet 2.0 software. There were no remarkable differences in dietary habits between healthy control subjects (n=34) and patients with MS (n=66), except for higher consumption of carbohydrates by patients. Both patients with MS and control subjects had higher protein and lower carbohydrate intake than the World Health Organization's recommended daily amounts. There was no correlation between food intake and neurological disability in patients with MS. The dietary patterns of patients with MS and healthy controls were similar in the city of Santos, São Paulo, Brazil, and surrounding towns, except for higher intake of carbohydrates by patients. No profile of pro-inflammatory diets was identified among the patients with MS enrolled in this study.

Impact of intrathecal IgG synthesis on neurological disability in patients with multiple sclerosis

BackgroundThe association between routine laboratory findings, including cerebrospinal fluid biomarkers, and neurological outcomes in patients with multiple sclerosis (MS) has not been fully elucidated. In this study, we evaluated blood and cerebrospinal fluid (CSF) analysis results at diagnosis and before treatment in patients with MS and assessed their correlations with neurological outcomes. Materials and methodsIn this study, 38 consecutive patients with MS (36 with relapsing-remitting MS and 2 with primary progressive MS) were recruited. Before treatment, all patients underwent routine CSF analysis at the time of diagnosis, including evaluation of albumin and immunoglobulin G (IgG) levels. The association between laboratory data and neurological outcomes was comprehensively evaluated. Subsequent neurological outcome was assessed by using the Expanded Disability Status Scale (EDSS) score at 1 year and 5 years after diagnosis and relapse frequency in the first year and in the first 5 years. ResultsThe IgG level in the CSF (rho = 0.46, p = 0.004), oligoclonal band count (rho = 0.61, p = 0.006), ratio of IgG and total protein in CSF (rho = 0.59, p < 0.0001), and ratio of IgG and albumin in CSF (rho = 0.67, p < 0.0001) showed moderate to strong correlations with the subsequent EDSS score 1 year after diagnosis. These variables still showed significant correlations with EDSS 5 years later. Albumin and lactate dehydrogenase levels in CSF did not correlate with the subsequent EDSS score. Relapse frequency did not correlate with any of the studied serum and CSF biomarkers. ConclusionIgG levels in CSF at MS diagnosis are significantly correlated with the level of neurological disability independent of the relapse frequency. Markers of intrathecal IgG synthesis, such as the IgG index, are useful in estimating the present and subsequent clinical severity in patients with MS.

CSF chitinase 3-like-1 association with disability of primary progressive MS

ObjectiveTo assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS).MethodsWe analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up.ResultsIncreasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118–0.742, p = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063–0.725, p = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999–1.017, p = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = −0.366, 95% CI -0.676–0.054, p = 0.086). There was no correlation with regard to NfL levels.ConclusionsThis analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved.Classification of evidenceThis study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.

Association between electrocardiographic and echocardiographic atrial abnormalities and prognosis in cryptogenic stroke

Background and PurposeThe role of atrial fibrillation in cryptogenic stroke (CS) is well known. However, the usefulness of left atrial (LA) electrical and morphological abnormalities to identify more disabling strokes in sinus rhythm patients is less studied. We evaluated the association between electrocardiographic P-wave abnormalities and echocardiographic LA measures with neurological disability in patients with cryptogenic stroke. MethodsIn a retrospective cohort, we included all consecutive hospitalized patients with cryptogenic stroke. Patients were classified according to modified Rankin scale at hospital discharge and at 3 months. LA abnormalities were identified by electrocardiographic (ECG) P-wave, axis and LA enlargement criteria, and by bidimensional echocardiograph through left atrial diameter and volume index. ResultsAmong the 143 patients with CS (63.4 ± 14.2 years, 53% women), 70 patients were classified as non-disabling stroke (Rankin score < 2) and 73 patients as disabling stroke (Rankin score ≥ 2) at hospital discharge. On echocardiogram, more patients with disabling stroke presented with enlarged LA volume index (48% vs. 25%; p = 0.01). This difference remained significant after adjustment for age, gender, CHA2DS2-VASc and NIHSS scores (p = 0.02) and even when the LA volume index was analyzed as a continuous variable (p = 0.055). Also, enlarged LA volume index was more prevalent (52% vs. 25%; p = 0.03) among those with disabling stroke at 3 months after hospital discharge. Among ECG criteria, only the LA enlargement assessed by downward deflection was more prevalent in disabling stroke. ConclusionOur study demonstrated an association between left atrial enlargement, assessed by downward deflection from ECG and volume index from echocardiogram, and more disabling cryptogenic strokes. This information could help to identify patients with poorer prognosis, or a subgroup where atrial cardiopathy may play a role in cardioembolic pathway.

Stem Cell-Based Therapies for Multiple Sclerosis: Current Perspectives

Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune disease of the central nervous system (CNS). Disease-modifying therapies (DMT) targeting inflammation have been shown to reduce disease activity in patients with relapsing–remitting MS (RRMS). The current therapeutic challenge is to find an effective treatment to halt disease progression and reverse established neural damage. Stem cell-based therapies have emerged to address this dilemma. Several types of stem cells have been considered for clinical use, such as autologous hematopoietic (aHSC), mesenchymal (MSC), neuronal (NSC), human embryonic (hESC), and induced pluripotent (iPSC) stem cells. There is convincing evidence that immunoablation followed by hematopoietic therapy (aHSCT) has a high efficacy for suppressing inflammatory MS activity and improving neurological disability in patients with RRMS. In addition, MSC therapy may be a safe and tolerable treatment, but its clinical value is still under evaluation. Various studies have shown early promising results with other cellular therapies for CNS repair and decreasing inflammation. In this review, we discuss the current knowledge and limitations of different stem cell-based therapies for the treatment of patients with MS.

Evaluation of the efficacy of recombinant tissue plasminogen activators in improving clinical status of acute ischemic stroke: A randomized clinical trial in Iran

Background: Acute ischemic stroke is caused by blockage of a cerebral artery and is also known as cerebrovascular accident (CVA). Recombinant tissue plasminogen activator (rt-PA) therapy is effective in reducing early and long-term neurologic disabilities if it is started quickly. Therefore, the aim of this study was to determine the efficacy of treatment with recombinant tissue plasminogen activators in improving the clinical status of acute ischemic stroke.&#x0D; Methods: The current study was performed as a clinical trial of two groups- treatment and control (n=20 per group). The treatment group consisted of patients who received rt-PA, while the control group consisted of patients who did not receive rt-PA. For each group, evaluation of neurological disabilities following ischemic stroke was based off the National Institutes of Health Stroke Scale (NIHSS), for early assessment of disability on the third day of treatment), and off the modified Rankin Scale (MRS) at 90 days after stroke. The drug effect criterion was used to reduce the neurological disability or the difference in NIHSS on day 3 after treatment. Also, the duration of onset of symptoms until the arrival of the patients to the emergency room (ER), as well as the risk factors, complications and number of deaths in both groups, were recorded. Data obtained were analyzed by SPSS software.&#x0D; Results: The results of the study showed that the mean of ER arrival time, NIHSS before treatment, and NIHSS on day 3 of treatment in the control group was higher than that of the treatment group; the difference was statistically significant (P&lt;0.05). The results also indicated that the probability of improvement of neurological disabilities in the experimental group was greater than that of the control group (relative risk (RR) =1.25). Additionally, the odds ratio (OR) for receiving rt-PA in the NIHSS positive treatment group compared to the control group was equal to 1/5 (OR=1.5). The results showed that 30% of the patients in the treatment group were treated with a complication. The mean of MRS was higher in the control group at 90 days after the stroke, compared with the treatment group.&#x0D; Conclusion: Treatment with rt-PA reduces the neurological disability in patients with ischemic stroke, since the mean of MRS is lower in the treatment group, compared with the control group, after 90 days of treatment.

Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies characterized by predominant involvement of the optic nerves and spinal cord. In most patients, an IgG autoantibody binding to astrocytic aquaporin 4, the principal water channel of the central nervous system, is detected. Rituximab, a chimeric monoclonal antibody specific for the CD20 B-lymphocyte surface antigen, has been increasingly adopted as a first-line off-label treatment for patients with NMOSDs. To perform a systematic review and a meta-analysis of the efficacy and safety of rituximab use in NMOSDs, considering the potential predictive factors related to patient response to rituximab in this disease. English-language studies published between January 1, 2000, and July 31, 2015, were searched in the MEDLINE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov databases. Patient characteristics, outcome measures, treatment regimens, and recorded adverse effects were extracted. Forty-six studies were included in the systematic review. Twenty-five studies that included 2 or more patients with NMOSDs treated with rituximab were included in the meta-analysis. Differences in the annualized relapse rate ratio and Expanded Disability Status Scale score before and after rituximab therapy were the main efficacy measures. Safety outcomes included the proportion of deaths, withdrawals because of toxic effects, and adverse effects. Among 46 studies involving 438 patients (381 female and 56 male [sex was not specified in 1 patient]; mean age at the outset of treatment, 32 years [age range, 2-77 years]), rituximab therapy resulted in a mean (SE) 0.79 (0.15) (95% CI, -1.08 to -0.49) reduction in the mean annualized relapse rate ratio and a mean (SE) 0.64 (0.27) (95% CI, -1.18 to -0.10) reduction in the mean Expanded Disability Status Scale score. A significant correlation was observed between disease duration and the Expanded Disability Status Scale score. Adverse effects were recorded in 114 of 438 (26%) patients treated with rituximab. Specifically, 45 patients (10.3%) experienced infusion-related adverse effects, 40 patients (9.1%) had an infection, 20 patients (4.6%) developed persistent leukopenia, 2 patients (0.5%) were diagnosed as having posterior reversible encephalopathy, and 7 patients (1.6%) died. This systematic review and meta-analysis provides evidence that rituximab therapy reduces the frequency of NMOSD relapses and neurological disability in patients with NMOSDs. However, the safety profile suggests caution in prescribing rituximab as a first-line therapy.

Managing Disability in Progressive Multiple Sclerosis.

Patients with progressive forms of multiple sclerosis have various symptoms which affect their quality of life significantly including depression, cognitive decline, sleep changes, bladder dysfunction, sexual dysfunction, and spasticity. Despite recent promising results on the effects of ocrelizumab on neurological disability in patients with PPMS, currently none of the immunomodulatory therapies are approved for progressive forms of multiple sclerosis. Therefore, clinicians currently mostly focus on management of well-recognized comorbidities of this disease phenotype in order to improve patients' quality of life. There are very few studies evaluating strategies of symptomatic management on progressive forms of multiple sclerosis and most of the data is derived from studies on relapsing forms of multiple sclerosis. Understanding of the risks, benefits, and limitations of these therapies can significantly affect patient care. In this article, we review common comorbidities associated with progressive forms of multiple sclerosis and outline important strategies for their symptomatic management.

Tau protein levels in the cerebrospinal fluid of the patients with multiple sclerosis in an attack period: Low levels of tau protein may have significance, too

ObjectivesAxonal loss is the cause of permanent neurologic disability in patients with MS. There are a lot of candidates to be a surrogate biological marker of the axonal loss in MS including tau protein. In the present study, we aimed to assess the levels of the tau protein in patients with MS, and in neurologically healthy controls. Patients and methodsWe included 41 patients with MS (32 RRMS, 9 SPMS) in this study. All the patients with MS were in an attack period. Control group was consist of 18 neurologically healty patients who underwent spinal anesthesia for orthopedic operations. The CSF tau protein level was measured by double antibody sandwich ELİSA. ResultsThe patients with RRMS had a higher tau protein level than the patients with SPMS and the control group. The patients with SPMS had a lower tau protein level than the control group. ConclusionHigh levels of tau protein in the CSF of RRMS patients in an attack period may indicate ongoing axonal transection owing to inflammation. Due to the brain atrophy, the patients with SPMS have less neurons to produce tau protein. The low levels of tau protein in the CSF of SPMS patients may denote axonal degeneration.

Friedreich ataxia: failure of GABA-ergic and glycinergic synaptic transmission in the dentate nucleus.

Atrophy of large neurons in the dentate nucleus (DN) is an important pathologic correlate of neurologic disability in patients with Friedreich ataxia (FA). Thinning of the DN was quantified in 29 autopsy cases of FA and 2 carriers by measuring the thickness of the gray matter ribbon on stains with anti-glutamic acid decarboxylase, the rate-limiting enzyme in the biosynthesis of γ-amino-butyric acid (GABA). The DN was thinner than normal in all cases of FA, and atrophy correlated inversely with disease duration but not with age at onset or length of the homozygous guanine-adenine-adenine trinucleotide expansions. In 13 of the FA cases, frozen DN tissue was available for assay of frataxin. Dentate nucleus atrophy was more severe when frataxin was very low. Immunohistochemical staining for glutamic acid decarboxylase revealed grumose reaction and preservation of small GABA-ergic neurons in the DN of FA patients. Residual small DN neurons and varicose axons also contained the glycine transporter 2, identifying them as glycinergic. Immunohistochemistry also confirmed severe loss of GABA-A and glycine receptors in the DN with comparable depletion of the receptor-anchoring protein gephyrin. Thus, loss of gephyrin and failure to position GABA-A and glycine receptors correctly may reduce trophic support of large DN neurons and contribute to their atrophy. By contrast, Purkinje cells may escape retrograde atrophy in FA by issuing new axonal sprouts to small surviving DN neurons where they form reparative grumose clusters.

Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis.

No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability. To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS. Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014. Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan. Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128). Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.