Neurological Disability Score Research Articles

Using biothesiometer, Neuropathy Symptom Score, and Neuropathy Disability Score for the early detection of peripheral neuropathy: A cross-sectional study.

Patients with peripheral neuropathy could have damaged peripheral nerves, which leads to sensory and motor dysfunction. Diabetes, infections, and trauma are the major causes of peripheral neuropathy. Vibratory perception threshold (VPT) tools are commonly used to detect peripheral neuropathy. This study aims to determine the assessment of peripheral neuropathy through the different diagnostic tools in the community in Malaysia. A total number of 1283 participants were recruited from the seven retail pharmacies located in Selangor, Malaysia. The peripheral neuropathy test was conducted based on VPT tools on both feet using the digital biothesiometer. Following that, Neurological Symptom Score (NSS) and Neurological Disability Score (NDS) were taken from the participants to assess the neurological symptoms. Participants had an average age of 40.6 ± 12.9 years and were mostly of Chinese ethnicity (54.1%). The findings show that increasing age was associated with more severe peripheral neuropathy across the various assessment tools, but gender differences were found with the biothesiometer test and ethnicity has severity in the biothesiometer and disability scores. The sensitivity and specificity of the biothesiometer test were 0.63 and 0.84, respectively. The combined tool NSS and NDS had high specificity and a high positive predictive value, suggesting that it could be a reliable indicator of peripheral neuropathy when both scores are elevated. The findings show that the biothesiometer test, NSS, and NDS are considered screening VPT tools for diagnosing peripheral neuropathy. However, further evaluation and diagnostic testing are necessary in cases of a positive test result.

Resveratrol-loaded copolymer nanoparticles with anti-neurological impairment, antioxidant and anti-inflammatory activities against cerebral ischemia–reperfusion injury

During cerebral ischemia/reperfusion (I/R) injury, oxidative stress and inflammation are major contributors to disability. Finding compounds that reduce oxidative stress, inflammation and strengthen the antioxidant defense system properties is one of the vital areas of research. Therefore, the present research aimed to evaluate the effects of resveratrol loaded in copolymer nanoparticles (RES.CP.NPs) on cerebral I/R injury in rats. After preparing and characterization RES.CP.NPs, these platforms were administered to cerebral I/R injured rats at a dose of 20 mg/kg after 2 h occlusion and the neurological disability scores were measured 24 h later. The content of malondialdehyde (MDA), glutathione (GSH), and catalase (CAT) activity as well as the expression levels of TNF-α, IL-10 and NF-κB-p65 in rat brain homogenates were measured. The RES.CP.NPs synthesized in the present study had a spherical structure with a zeta potential of −38 mV and a stable RES release for 72 h. Administration of RES.CP.NPs to I/R rats resulted in significant improvement in neurological disability score, decreased MDA levels, increased GSH content, increased CAT activity, decreased TNF-α expression, increased IL-10 expression, and decreased NF-κB-p65 expression (P < 0.0001). RES.CP.NPs can have neuroprotective effects in cerebral I/R conditions as a result of their strong antioxidant and anti-inflammatory activities.

Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review.

Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating the effects of oral-administered ALA versus a placebo in patients with DSPN and determining the optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to determine the efficacy of oral ALA for patients with DSPN. The primary outcome was total symptoms' score (TSS), and secondary outcomes were the neurological disability score (NDS), neuropathy impaired score (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, and global satisfaction. A subgroup analysis of the ALA dosage (600, 1200, and 1800 mg/day) was also conducted. Ten RCTs (1242 patients) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS, and the global satisfaction score. For VAS, VPT, NIS-LL, and NCS results, ALA did not produce favorable results. ALA treatment had favorable effects on DSPN by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.

Application of Shouwu Yizhi prescription in decubation of patients with ischemic stroke

ABSTRACT We investigate the application of Shouwu Yizhi prescription (SYP) in decubation of patients with ischemic stroke (IS). The clinical data of 106 patients recovering from IS who came to our hospital from December 2019 to December 2020 were selected for retrospective analysis, and they were separated into experimental group (n = 53, basic treatment + SYP) and control group (n = 53, basic treatment) based on the principle of random grouping. The clinical indexes such as lipid indexes and neurological disability score (NDS) after treatment were compared between both groups to comprehensively evaluate the clinical effects of different treatment regimens. Except for high-density lipoprotein cholesterol value, the lipid indexes in the experimental group after treatment were remarkably lower than those in the control group (P < 0.001). After treatment, the levels of hypersensitive C-reactive protein, homocysteine and lipoprotein-associated phospholipase A2 were remarkably lower in the experimental group than control group (P < 0.05). After treatment, the experimental group had remarkably higher mean scores of Montreal Cognitive Assessment, Fugl-Meyer Assessment in upper and lower limbs and lower NDS than control group (P < 0.001). SYP is an efficient treatment plan in decubation of IS, which can effectively improve the blood lipid indexes and neurological function of patients, and further studies will help establish a better solution for such patients.

Reliability of Isometric Muscle Strength Measurement and Its Accuracy Prediction of Maximal Dynamic Force in People with Multiple Sclerosis.

Background and Objectives: Multiple sclerosis (MS) is a disease that manifests with varied neurological symptoms, including muscle weakness, especially in the lower extremities. Strength exercises play an important role in the rehabilitation and functional maintenance of these patients. The individualized prescription of strength exercises is recommended to be based on the maximum force determined by the one-repetition maximum (1RM), although to save time and because it requires less equipment, it is often determined by the maximum voluntary isometric contraction (MVIC). The purpose of this work was to study, in patients with MS (pwMS), the reliability of MVIC and the correlation between the MVIC and 1RM of the knee extensors and to predict the MVIC-based 1RM. Materials and Methods: A total of 328 pwMS participated. The study of the reliability of MVIC included all pwMS, for which MVIC was determined twice in one session. Their 1RM was also evaluated. The sample was randomized by MS type, sex, and neurological disability score into a training group and a testing group for the analysis of the correlation and prediction of MVIC-based 1RM. Results: MVIC repeatability (ICC, 2.1 = 0.973) was determined, along with a minimum detectable change of 13.2 kg. The correlation between MVIC and 1RM was R2 = 0.804, with a standard error estimate of 12.2 kg. The absolute percentage error of 1RM prediction based on MVIC in the test group was 12.7%, independent of MS type and with no correlation with neurological disability score. Conclusions: In patients with MS, MVIC presents very good intrasubject repeatability, and the difference between two measurements of the same subject must differ by 17% to be considered a true change in MVIC. There is a high correlation between MVIC and 1RM, which allows estimation of 1RM once MVIC is known, with an estimation error of about 12%, regardless of sex or type of MS, and regardless of the degree of neurological disability.

Neuropathy scale score as an independent risk factor for myocardial infarction in patients with type 2 diabetes.

To investigate whether peripheral neuropathy scale scores are associated with myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). In this cross-sectional study, 32,463 T2DM patients were enroled from 103 tertiary hospitals in 25 Chinese provinces. Based on a history of MI, participants were divided into the MI group (n=4170) and the non-MI group (n=28,293). All patients were assessed using four neuropathy scales, namely, Neurological Symptom Score (NSS), Neurological Disability Score (NDS), Toronto Clinical Scoring System (TCSS), and Michigan Neuropathy Screening Instrument (MNSI), and some of the patients underwent evaluation of nerve conduction velocity (NCV) (n=20,288). The relationship between these scores and myocardial infraction was analysed. The neuropathy scale scores in the MI group were higher than those in the non-MI group (p<0.001). After dividing patients into four groups based on the grading criteria, our results showed that, in addition to aggravating the degree of neuropathy signs, the incidence of MI increased (p<0.001). Logistic regression analysis results showed that neuropathy scale scores and NCV were both independent risk factors for MI (p<0.001). Furthermore, among the scales used, MNSI presented a higher odds ratio and area under the curve (AUC; 0.625, p<0.001) than the other three scales (AUCNSS =0.575, AUCNDS =0.606, and AUCTCSS =0.602, p<0.001) for MI. Increased scores on these neuropathy scales (NSS, NDS, TCSS, and MNSI) and NCV were significantly associated with increased risk of MI and were considered independent risk factors.

Long-term anxiety in spontaneous intracerebral hemorrhage survivors.

Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH). In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants. Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1-2, 3-5, and 6-8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models. Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12-23) had anxiety 1-2 years, 38 (27%; 95% CI = 19-34) 3-5 years, and 18 (21%; 95% CI = 12-30) 6-8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1-2 years, 61% 3-5 years, and 56% 6-8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1-2 years after ICH (odds ratio = 2.8; 95% CI = 1.2-6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment. Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event.

Cerebellum and brain stem volume loss in relapsing remission multiple sclerosis by MRI volumetry: relation to neurological disability score and number of relapses

BackgroundMRI is the method of choice in the diagnosis of MS as well as in monitoring the disease activity. MRI volumetry is used to assess whole or regional brain volume loss which reflects neurodegenerative aspect of the disease and plays an important role in all stages of disease. The aim of this work is to study MRI volumetry in the evaluation of cerebellum and brain stem volume loss in RRMS patients and its correlation with neurological disability score and number of relapses.ResultsVolumes of whole brainstem, medulla, and pons showed a significant decrease in RRMS cases compared to controls (p < 0.05). Brainstem volume had a mean volume of 22.17 and 25.09 cm3 in cases and controls, respectively. However, midbrain volume showed no significant difference between cases and controls (p = 0.134). Volume of left cerebellar cortex showed a significant decrease in RRMS cases compared to controls (p < 0.001). It had mean volumes of 81.64 and 92.14 ml in cases and controls, respectively, at left cerebellar hemisphere, while right cerebellar hemisphere cortex volumes were 80.37 and 91.97 ml in cases and controls, respectively. Cerebellar white matter showed no significant volume decrease in cases and controls.ConclusionVolumetric MR imaging is an important tool for quantifying the MS disease, assesses MS activity, progression, and tissue loss. The degree and the pattern of atrophy on MRI images correlate significantly with the neurological disability score and number of relapses.

A real-world cohort analysis of alemtuzumab outcomes in relapsing multiple sclerosis

Multiple sclerosis (MS) is a chronic and progressive neurological disease characterized by recurrent episodes of inflammatory demyelination of the brain and spinal cord. Alemtuzumab has been previously shown in large phase III trials to be an effective therapy in reducing MS clinical flares as well as new radiological activity and atrophy rates. The purpose of this study was to examine real-world effectiveness and safety data from a large cohort of people treated with alemtuzumab at an academic medical center, including those who failed B-cell depletion therapy. Over an average of 2.6 years follow-up, there were small but significant improvements in neurological disability scores, and a 61% rate of the composite “No Evidence of Disease Activity” (NEDA-3) outcome at 2-year follow-up. There were no substantial safety issues encountered in our review; rates of adverse events were similar or below those reported in Phase III trials. We compare and contrast our results to other available real-world data using alemtuzumab in multiple sclerosis.

Oral Alpha Lipoic Acid Treatment for Symptomatic Diabetic Peripheral Neuropathy: A Randomized Double-Blinded Placebo-Controlled Study.

Alpha-lipoic acid (ALA) was used in the treatment of diabetic peripheral neuropathy (DPN) using different routes, doses and treatment durations. The aim of this work is to assess the efficacy of oral 600mg ALA twice daily over 6 months in the treatment of patients with DPN. This is a prospective, single-center, double-blinded, placebo-controlled study conducted at the outpatient clinic of Mansoura Specialized Hospital, Mansoura University. A total of 200 patients with DPN were randomly assigned to add on treatment with either oral 600mg twice daily ALA (n=100) or placebo (n=100) for 6 months. Treatment outcome was assessed using vibration perception threshold (VPT), neurological symptom score (NSS), neurological disability score (NDS), and visual analog scale (VAS) for pain at baseline and at each visit (1, 3 and 6 months) after the start of treatment. Comparison between the study groups regarding the baseline data revealed no statistically significant differences. with respect to the outcome parameters, no significant differences were found between the studied groups at baseline. However, in subsequent visits, ALA-treated patients had significantly better results regarding almost all the outcome parameters (NSS, NDS, VAS, VPT). Mild nausea was reported in 6 patients. None of the studied patients discontinued treatment. Oral 600mg ALA twice-daily treatment for DPN over 6 months is effective, safe and tolerable.

Under-recognized post-stroke acute kidney injury: risk factors and relevance for stroke outcome of a frequent comorbidity.

Acute kidney injury (AKI) is emerging as a predictor of poor stroke outcome, however, it is often not recognized. The aim of our study was to evaluate post-stroke AKI burden, AKI risk factors and their influence in post-stroke outcome. From 2013 to 2016, 440 individuals with stroke diagnosis admitted in Stroke Unit, Foundation IRCCS Policlinico San Matteo (Pavia, Italy), were retrospectively enrolled. AKI cases identified by KDIGO criteria through the electronic database and hospital chart review were compared with the ones reported in discharge letters or in administrative hospital data base. Mortality data were provided by Agenzia Tutela della Salute of Pavia. We included 430 patients in the analysis. Median follow-up was 19.2months. We identified 79 AKI cases (18% of the enrolled patients, 92% classified as AKI stage 1), a fivefold higher number of cases than the ones reported at discharge. 37 patients had AKI at the admission in the hospital, while 42 developed AKI during the hospitalization. Cardioembolic (p = 0.01) and hemorrhagic (p = 0.01) stroke types were associated with higher AKI risk. Admission National Institutes of Health Stroke Scale (NIHSS, p < 0.05) and Charlson Comorbidity Index (p < 0.01) were independently associated with overall AKI, while admission NIHSS (p < 0.05) and eGFR (p < 0.005) were independently associated with AKI developed during the hospitalization. AKI was associated to longer in-hospital stay (p = 0.01), worse Rankin Neurologic Disability Score at discharge (p < 0.0001) and discharge disposition other than home (p = 0.03). AKI was also independently associated to higher in-hospital mortality (OR 3.9 95% CI 1.2-12.9 p = 0.023) but not with long-term survival. Post-stroke AKI diagnosis needs to be improved by strictly monitoring individuals with cardioembolic or hemorrhagic stroke, reduced kidney function, higher Charlson Comorbidity Index and worse NIHSS at presentation.

Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis.

Metabolic disturbances have been implicated in demyelinating diseases including multiple sclerosis (MS). Melatonin, a naturally occurring hormone, has emerged as a potent neuroprotective candidate to reduce myelin loss and improve MS outcomes. In this study, we evaluated the effect of melatonin, at both physiological and pharmacological doses, on oligodendrocytes metabolism in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Results showed that melatonin decreased neurological disability scores and enhanced remyelination, significantly increasing myelin protein levels including MBP, MOG, and MOBP. In addition, melatonin attenuated inflammation by reducing pro-inflammatory cytokines (IL-1β and TNF-α) and increasing anti-inflammatory cytokines (IL-4 and IL-10). Moreover, melatonin significantly increased brain concentrations of lactate, N-acetylaspartate (NAA), and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR). Pyruvate dehydrogenase kinase-4 (PDK-4) mRNA and protein expression levels were also increased in melatonin-treated, compared to untreated EAE mice. However, melatonin significantly inhibited active and total pyruvate dehydrogenase complex (PDC), an enzyme under the control of PDK4. In summary, although PDC activity was reduced by melatonin, it caused a reduction in inflammatory mediators while stimulating oligodendrogenesis, suggesting that oligodendrocytes are forced to use an alternative pathway to synthesize fatty acids for remyelination. We propose that combining melatonin and PDK inhibitors may provide greater benefits for MS patients than the use of melatonin therapy alone.

Improved Outcome in an Animal Model of Prolonged Cardiac Arrest Through Pulsatile High Pressure Controlled Automated Reperfusion of the Whole Body.

The reperfusion period after extracorporeal cardiopulmonary resuscitation has been recognized as a key player in improving the outcome after cardiac arrest (CA). Our aim was to evaluate the effects of high mean arterial pressure (MAP) and pulsatile flow during controlled automated reperfusion of the whole body. Following 20 min of normothermic CA, high MAP, and pulsatile blood flow (pulsatile group, n = 10) or low MAP and nonpulsatile flow (nonpulsatile group, n = 6) controlled automated reperfusion of the whole body was commenced through the femoral vessels of German landrace pigs for 60 min. Afterwards, animals were observed for eight days. Blood samples were analyzed throughout the experiment and a species-specific neurologic disability score (NDS) was used for neurologic evaluation. In the pulsatile group, nine animals finished the study protocol, while no animal survived postoperative day four in the nonpulsatile group. NDS were significantly better at any given time in the pulsatile group and reached overall satisfactory outcome values. In addition, blood analyses revealed lower levels of lactate in the pulsatile group compared to the nonpulsatile group. This study demonstrates superior survival and neurologic outcome when using pulsatile high pressure automated reperfusion following 20 min of normothermic CA compared to nonpulsatile flow and low MAP. This study strongly supports regulating the reperfusion period after prolonged periods of CA.

Effects of omalizumab therapy on peripheral nerve functions: short observational study.

IntroductionPeripheral neuropathy (PN) is a common neurological condition causing symmetrical and diffuse damage in nerves. The etiology of PN includes systemic diseases, toxic exposure, medications, infections, and hereditary diseases. Omalizumab is a humanized monoclonal anti-IgE antibody that exerts its activity by binding to free IgE in circulation.AimTo investigate the relationship between omalizumab and peripheral neuropathy.Material and methodsThe study included 30 patients who underwent omalizumab therapy (Xolair) due to the diagnosis of chronic urticaria. A detailed neurological and physical examination was performed in each patient both before and 3 months after the therapy. Electrophysiological examination was also performed using a Medelec Synergy instrument.ResultsThe 30 patients included 8 (26.7%) men and 22 (73.3%) women with a mean age of 37.5 ±14.14 years. No serious side effect of the medication was detected in any patient although local wound irritation occurred in 3 (10%) patients. Moreover, no change occurred in the pre-treatment Neuropathy Symptom Score (NSS) or Neurological Disability Score (NDS) of the patients and no pathological values that could result in neuropathy were observed during motor/sensory nerve conduction. However, significant changes were detected in the sensory and motor components of the nerves with regards to pre- and post-treatment values.ConclusionsOmalizumab therapy caused no peripheral neuropathy in any of our patients but altered the latency, amplitude, and velocity values of the peripheral nerves.

Nicotine Augments the Beneficial Effects of Mesenchymal Stem Cell-based Therapy in Rat Model of Multiple Sclerosis

ABSTRACTExperimental autoimmune encephalomyelitis (EAE) in rats through immunization with guinea pig spinal cord homogenate (GPSCH) produces a chronic disease with a relapsing pattern such as multiple sclerosis (MS) in humans. In previous studies, the immunomodulatory benefits of mesenchymal stem cells (MSCs) and nicotine have already been determined. Thus, this research was conducted to assess the additional benefits of the combination therapy of MSCs and nicotine in a rat model of MS. EAE was induced by GPSCH and complete Freund’s adjuvant (CFA) in female Wistar rats. The therapies were initiated at day 12 post-immunization (p.i.), when the rats developed a neurological disability score. The symptoms were recorded daily until day 33, when the rats were sacrificed. Finally, the splenocytes were evaluated by Enzyme-linked immunosorbent assay (ELISA) for cytokine production. The therapeutic treatment in the EAE rats with a combination of MSCs and nicotine exhibited a more desirable outcome, causing the regression of the average mean clinical score and neuropathological features to be more favorable than the treatment with either therapy alone. The combination therapy led to a significant reduction in the cumulative disease disability from day 21. For the EAE rats treated with nicotine and MSCs, this period was started from day 22 and 28 p.i., respectively. Besides the increase in the levels of IL-10, the combined therapy significantly reduced the splenocytes production of pro-inflammatory IL-17 as well as TNF-α more profoundly than either of the medications alone. In conclusion, the combination of MSCs and nicotine can be suggested as a promising strategy for further MS therapeutics improvement.

Olfactory Dysfunction Associated With Neuro-Behçet Disease.

Neurologic involvement associated with Behçet disease (BD) is defined as a different entity: Neuro-Behçet disease (NBD). Behçet disease presents with olfactory dysfunction. It is not known whether this is the consequence of mucosal involvement or neurologic involvement. The aim of this study was to investigate whether olfactory dysfunction was further aggravated as the result of neurologic involvement. Sixteen patients diagnosed with NBD and 16 healthy control patients with similar demographic characteristics were recruited as the healthy control group. Expanded Disability Status Scale (EDSS) scoring was used for quantification of neurological disability. All diagnoses were confirmed and categorized with magnetic resonance imaging studies in all patients individually: parenchymal or nonparenchymal. A well-established test of orthonasal olfaction developed at the CCCRC was used. Correlation analysis was carried out. The mean CCCRC score of NBD patients was 4.60 out of 7, and this group was diagnosed to be moderately hyposmic, whereas the average score of the control group was 6.5; the difference was significant (P < 0.0001). CCCRC scores of NBD patients were significantly lower compared both healthy control patients and those of BD patients reported in the literature. Mean EDSS score of NBD patients was 1.75 ± 1.0 out of 10 (0-no neurologic disability and 10-worst neurologic disability). Magnetic resonance imaging of NBD patients revealed 4 nonparenchymal and 12 parenchymal patients. Neuro-Behçet disease patients with parenchymal involvement presented with (worse) EDSS scores. Mean olfactory CCCRC score of this group was 4.38 whereas the average olfactory score of the vascular group was 5.25 out 7. Average EDSS score of vascular group was 0.75, much better compared to higher average neurologic disability score of 2.08 for the parenchymal group. Significant correlation existed between the duration of NBD and both olfactory and neurologic dysfunction scores. Neuro-Behçet disease present with aggravated olfactory dysfunction compared to BD. Neurologic involvement-especially parenchymal involvement-seems to deteriorate the olfactory dysfunction. Duration of disease is correlated with this severity of dysfunction.

Neurobehavioral outcomes in autoimmune encephalitis

This study evaluates long-term neurobehavioral function in patients with clinically diagnosed autoimmune encephalitis (AE) of various etiologies through retrospective chart review and a cross-sectional structured telephone interview. Of 77 patients meeting clinical diagnostic criteria for AE over a ten year period, 39/77 (51%) patients had known AE-associated antibodies, and 38/77 (49%) had no detected antibody. 9/77 (12%) died, and 26/77 (34%) had “poor” neurologic disability score (mRS 3–5) at the last documented follow-up. 44 participants enrolled in the telephone interview, of whom 38/44 (86%) endorsed ongoing difficulties with fatigue, emotional lability, short-term memory, and/or concentration. On standardized assessment of adaptive behavior (ABAS-3), 23/44 (52%) scored “below average” (general adaptive composite: mean 86.95, standard deviation 18.45). Of the participants with “good” neurologic disability outcome (mRS 0–2), 12/30 (40%) scored “below average” in adaptive behavior. In summary, patients with AE frequently have persistent impairments in neurologic disability, neurocognitive symptomatology, and adaptive behavior, which may not be adequately captured by routine neurologic assessments. Comprehensively elucidating these persistent neurobehavioral impairments and predicting which patients are at highest risk will allow for optimal care of patients and their families.

Psoriasis comorbidity affects multiple sclerosis neurological progression: a retrospective case - control analysis.

Multiple sclerosis (MS) and psoriasis are inflammatory disorders, with epidemiological and biological associations. The impact of one disease on the course of the other has not been studied. To characterize patients with psoriasis and MS, and to assess whether psoriasis comorbidity affected the progression of MS. A retrospective case-control study. Patients with psoriasis comorbidity were identified from 3456 patients included in the Sheba Hospital Multiple Sclerosis Center database. Clinical and demographical characteristics and MS progression-related outcomes in patients whose follow-up exceeded 5 years were analysed and compared to those of a matched control cohort of MS-only (MSO) patients. Forty-five (1.3%) MS patients had psoriasis comorbidity. Psoriasis preceded MS in 35 (78%) cases. The psoriasis was defined as mild, moderate and severe in 24 (53%), twelve (27%) and nine (20%) cases respectively. MS progression-related outcomes were evaluated in 35 patients that had follow-up over 5 years. Patients with psoriasis onset preceding relapsing-remitting MS (RRMS) had slower progression of disease compared to MSO patients, as manifested by a longer time to second relapse (P < 0.01) and a longer time to significant neurological disability scores (P < 0.03). Psoriasis comorbidity preceding the onset of MS is associated with slower progression of disability.

Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise from the elevated MeCP2E1 vs. MeCP2E2 ratio in the SC that creates a more hostile environment thereby preventing local BDNF production. At the level of transcript, we demonstrate that EAE-induces the pathological enhanced expression of MeCP2E1 that contributes to enhanced NDS during the entire disease course. Thus, the pathological induction of the MeCP2E1 isoform contributes to the disruption of the normal homeostatic signaling equilibrium network that exists between cytokines, neurotrophins and chemokines that regulate the myelin repair process by repressing BDNF. Our research suggests that the elevated ratio of MeCP2E1 relative to MeCP2E2 may be a useful diagnostic marker that clinicians can utilize to determine the degree of neurological disability with associated myelin damage. The elevated MeCP2E1 vs. MeCP2E2 ratios (E1/E2) in the SC prevent BDNF from reaching optimal levels required for myelin repair. Thus, the lower E1/E2 ratios in the DRG, allow the DRG to serve as a weak secondary compensatory mechanism for enhanced production and delivery of BDNF to the SC to try to assist in myelin repair.

Herding: a new phenomenon affecting medical decision-making in multiple sclerosis care? Lessons learned from DIScUTIR MS.

PurposeHerding is a phenomenon by which individuals follow the behavior of others rather than deciding independently on the basis of their own private information. A herding-like phenomenon can occur in multiple sclerosis (MS) when a neurologist follows a therapeutic recommendation by a colleague even though it is not supported by best practice clinical guidelines. Limited information is currently available on the role of herding in medical care. The objective of this study was to determine the prevalence (and its associated factors) of herding in the management of MS.MethodsWe conducted a study among neurologists with expertise in MS care throughout Spain. Participants answered questions regarding the management of 20 case scenarios commonly encountered in clinical practice and completed 3 surveys and 4 experimental paradigms based on behavioral economics. The herding experiment consisted of a case scenario of a 40-year-old woman who has been stable for 3 years on subcutaneous interferon and developed a self-limited neurological event. There were no new magnetic resonance imaging (MRI) lesions. Her neurological examination and disability scores were unchanged. She was advised by an MS neurologist to switch from interferon to fingolimod against best practice guidelines. Multivariable logistic regression analysis was conducted to evaluate factors associated with herding.ResultsOut of 161 neurologists who were invited to participate, 96 completed the study (response rate: 60%). Herding was present in 75 (78.1%), having a similar prevalence in MS experts and general neurologists (68.8% vs 82.8%; P=0.12). In multivariate analyses, the number of MS patients seen per week was positively associated with herding (odds ratio [OR] 1.08, 95% CI 1.01–1.14). Conversely, physician’s age, gender, years of practice, setting of practice, or risk preferences were not associated with herding.ConclusionHerding was a common phenomenon affecting nearly 8 out of 10 neurologists caring for MS patients. Herding may affect medical decisions and lead to poorer outcomes in the management of MS.