Sclerosis Patients Research Articles

Passive Transfer of Sera from ALS Patients with Identified Mutations Evokes an Increased Synaptic Vesicle Number and Elevation of Calcium Levels in Motor Axon Terminals, Similar to Sera from Sporadic Patients.

Previously, we demonstrated increased calcium levels and synaptic vesicle densities in the motor axon terminals (MATs) of sporadic amyotrophic lateral sclerosis (ALS) patients. Such alterations could be conferred to mice with an intraperitoneal injection of sera from these patients or with purified immunoglobulin G. Later, we confirmed the presence of similar alterations in the superoxide dismutase 1 G93A transgenic mouse strain model of familial ALS. These consistent observations suggested that calcium plays a central role in the pathomechanism of ALS. This may be further reinforced by completing a similar analytical study of the MATs of ALS patients with identified mutations. However, due to the low yield of muscle biopsy samples containing MATs, and the low incidence of ALS patients with the identified mutations, these examinations are not technically feasible. Alternatively, a passive transfer of sera from ALS patients with known mutations was used, and the MATs of the inoculated mice were tested for alterations in their calcium homeostasis and synaptic activity. Patients with 11 different ALS-related mutations participated in the study. Intraperitoneal injection of sera from these patients on two consecutive days resulted in elevated intracellular calcium levels and increased vesicle densities in the MATs of mice, which is comparable to the effect of the passive transfer from sporadic patients. Our results support the idea that the pathomechanism underlying the identical manifestation of the disease with or without identified mutations is based on a common final pathway, in which increasing calcium levels play a central role.

Discontinuation of disease-modifying treatments for multiple sclerosis in patients aged over 50 with disease Inactivity.

Treatments may become redundant in older patients with multiple sclerosis (MS). Our aim was to explore whether stopping treatments might be possible in patients aged over 50 with disease inactivity. Patients over 50 were included from the population-based MS Lorraine registry if they had a relapsing-remitting course at onset and had experienced no relapse for ≥ 3years. Patients who stopped treatments were defined as "stoppers", and the others as "stayers". The outcomes were the time to first relapse, to first disability progression, and to the occurrence of EDSS score of 6, assessed by multivariate analysis using a propensity score. 132 stoppers and 366 stayers had a median follow-up of 7years. There was no difference in Log-rank tests for the times to first relapse (p = 0.61) and to first disability progression (p = 0.22). In Cox models, stopping treatments was not associated with an increased risk of relapse (adjusted Hazard ratio (aHR) = 0.92 [0.72-1.16; p = 0.47]) or of an increase in EDSS score (aHR = 0.89 [0.71-1.13; p = 0.34]). However, stopping was associated with a higher risk of occurrence of EDSS score of 6 (aHR = 3.29 [2.22-4.86; p < 0.0001]), with a significant difference for the time to occurrence of EDSS score of 6 (p = 0.003). Our study suggests that stopping injectable disease-modifying treatments, in patients over 50 with disease inactivity, is not associated with an increased risk of relapse or EDSS progression, but there might be a higher risk of reaching EDSS 6. These results have to be confirmed by interventional studies.

Evaluation of the effect of fingolimod (FTY720) on macular perfusion by swept-source optical coherence tomography angiography in patients with multiple sclerosis

Aim To determine changes in retinal microcirculation, caused by fingolimod (FTY720) use, via swept-source optical coherence tomography angiography (SS-OCTA) in relapsing-remitting multiple sclerosis (RR-MS) patients. Materials and methods 80 patients with RR-MS, who were using fingolimod, and 50 healthy control subjects were included in the study. Group 1 consisted of 40 eyes from 40 RR-MS patients, who had been using fingolimod for less than six months, and Group 2 consisted of 40 eyes from 40 RR-MS patients, who had been using fingolimod for longer than six months. All participants underwent SS-OCTA via DRI OCT Triton (Topcon, Tokyo, Japan), analysing their central macular thickness (CMT) (µm), subfoveal choroidal thickness (SFCT) (µm), superficial (VDs) (%) and deep vascular plexuses (VDd) (%), choriocapillaris (VDcc) (%), and superficial and deep foveal avascular zones (FAZs, FAZd, respectively) (%) in mean values. Results The mean follow-up times for patients in Groups 1 and 2 were 2.9 ± 1.5 months and 22.5 ± 11.3 months, respectively. The FAZs value in Group 2 was found to be significantly higher than that in both Group 1 and the control group (p = 0.034, p = 0.042, respectively). The VDs central value in Group 2 did not differ significantly from that in Group 1 or the control group (p > 0.05), while the VDs central value was higher in Group 1 than in the control group (p = 0.008). In Group 1, the VDd central value was significantly higher than in Group 2 and the control group (p = 0.047; p = 0.020, respectively). The CMT measurement for Group 2 was significantly lower than in Group 1 and the control group (p = 0.008, p = 0.003, respectively). Conclusion Fingolimod use seems to remarkably increase VDs and VDd measurements in the early period of administration and decrease CMT over a longer period of administration in patients with RR-MS.

Rare, pathogenic variants in LRP10 are associated with amyotrophic lateral sclerosis in patients from mainland China

Low-density lipoprotein receptor-related protein 10 (LRP10) is associated with a series of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease which share genetic risk factors and pathophysiological processes with amyotrophic lateral sclerosis (ALS). To investigate whether LRP10 variants could cause a predisposition to ALS, we screened rare, pathogenic LRP10 variants among a cohort of 584 patients with ALS from mainland China and performed burden analysis using data from a large external database. A total of 7 rare, pathogenic variants in LRP10, of which one (c.1182A>T, p.R394S) was novel, were identified in 11 unrelated patients. Burden analysis revealed significant associations between ALS and LRP10 at both the gene and single-variant levels (c.1721G>A, p.R574Q; c.1182A>T, p.R394S; and c.1681C>T, p.R561C). Interestingly, patients with sporadic ALS carrying variant c.1721G>A tended to have a bulbar onset, increased phenotype severity, and a worse prognosis. Our findings first provide independent evidence that rare, pathogenic LRP10 variants may be risk factors for ALS and delineate a special phenotype in patients with sporadic ALS carrying variant c.1721G>A.

Phosphorylated TDP-43 localizes to chronic cerebral infarctions in human brains.

The transactivation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein pivotal in RNA processing. Because phosphorylated TDP43 (pTDP-43) has been identified as a component of the ubiquitin-positive and tau-negative inclusions observed in the brains of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients, it is considered to play a major role in neurodegenerative processes. We previously reported that pTDP-43 is located in macrophages of atherosclerotic lesions of human carotid and major cerebral arteries. We hence hypothesized that pTDP-43 might be localized in the macrophages of other human brain lesions. Therefore, we investigated the immunolocalization of pTDP-43 in human brains with chronic cerebral infarction. Furthermore, we investigated the colocalization of pTDP-43 and the 14-3-3 eta isoform and found that pTDP-43 was localized in many macrophages located in chronic cerebral infarctions, in 6 out of the 15 human brains analyzed. pTDP-43 colocalized with the 14-3-3 eta isoform in these lesions. This is the first demonstration of pTDP-43 immunolocalization in chronic cerebral infarctions in human brains. We believe that our findings may be useful towards further understanding the pathophysiological roles of TDP-43 in various neurological disorders.

Treatments and outcomes of encapsulating peritoneal sclerosis in patients undergoing peritoneal dialysis: 295 cases from a nationwide inpatient database in Japan.

The number of patients undergoing renal replacement therapy is increasing. We evaluated the practice patterns and outcomes of encapsulating peritoneal sclerosis (EPS) in patients undergoing peritoneal dialysis. Using a Japanese national inpatient database, we identified 295 patients with EPS who were hospitalized from July 2010 to March 2017. We categorized them into four groups: those who underwent surgery only (n = 39), those who received corticosteroid treatment only (n = 70), those who underwent both (n = 30), and those who underwent neither (n = 156). We investigated their characteristics, treatments, and outcomes. More than half of patients were males and never-smokers and had a normal body mass index. Patients tended to undergo parenteral nutrition for 2 months. The proportions of emergency admission, intensive care unit (ICU) admission, central venous catheterization, catecholamine use, mechanical ventilation, and continuous hemodiafiltration were significantly different among the four groups (61%, 8.1%, 37.0%, 44.0%, 8.8%, and 5.8%, respectively). The both-treatment group had a significantly longer hospital stay (37.0 vs. 37.5 vs. 72.5 vs. 31.0 days, p < 0.001) and higher costs (US$16,554 vs. US$17,029 vs. US$33,757 vs. US$13,983, p < 0.001) than the other groups. In total, 52 patients (18%) died during hospitalization. There was no significant difference in inhospital complications and death, discharge status, 30-day readmission, or length of ICU stay among the four groups. Our findings provide useful information for clinicians and patients hospitalized for treatment of EPS.

Gene expression of semaphorin-3A, semaphorin-7A, neuropilin-1, plexin-C1, and β1 integrin in treated-multiple sclerosis patients

ABSTRACT Objective Recently, members of the semaphorin family have received major attention in various medical fields, especially autoimmunity. In this study, we selected semaphorin-3A (Sema3A), semaphorin-7A (Sema7A), and their receptors to determine the possible relationship between these molecules and multiple sclerosis (MS). Method We measured the gene expression of Sema3A, Sema7A, neuropilin-1 (NP-1), plexin-C1, and β1 integrin in the blood samples of relapsing-remitting multiple sclerosis (RRMS) patients, treated with high-dose interferon-β1a (IFN-β1a), low-dose IFN-β1a, IFN-β1b, and glatiramer acetate (GA) via quantitative real-time polymerase chain reaction (qRT-PCR) assay, and then, compared the results of treatment-naive patients with the healthy controls. Results The gene expression of Sema3A (P = 0.02), NP-1 (P < 0.001), and plexin-C1 (P < 0.01) significantly decreased in the treatment-naive group, compared to the healthy controls. Sema3A significantly increased in all treated patients, compared to the treatment-naive patients (P < 0.001). However, expression of NP-1 (P < 0.001), plexin-C1 (P < 0.001), and β1 integrin (P < 0.05) only increased in patients receiving high-dose IFN-β1a, IFN-β1b, and GA. Expression of Sema7A increased in only two groups of patients treated with IFN-β1b (P < 0.001) and GA (P = 0.018), without any significant decrease in the treatment-naive group, compared to the healthy controls (P > 0.05). Conclusion Our findings confirm that the presence of Sema3A, Sema7A, and their receptors can play critical roles in the treatment of MS patients. Therefore, they can be potential target molecules for MS treatment in the future.

Lipid Mediator Profiles Predict Response to Therapy with an Oral Frankincense Extract in Relapsing-Remitting Multiple Sclerosis

Lipid mediators (LMs) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts. We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis (RR-MS) patients who took a standardised frankincense extract (SFE) daily for eight months in a clinical phase IIa trial (NCT01450124) and in 28 age- and gender-matched healthy controls. Magnetic resonance imaging, immunological outcomes and serum neurofilament light chain levels were correlated to changes in the LM profiles of the RR-MS cohort. Eight out of 44 analysed LMs were significantly reduced during an eight-month treatment period by the SFE and seven of these eight significant LM derive from the 5-lipoxygenase (5-LO) pathway. Baseline levels of 12- and 15-LO products were elevated in patients who exhibited disease activity (EDA) during SFE treatment compared to no-evidence-of-disease-activity (NEDA) patients and could predict treatment response to the SFE in a prediction model at baseline. Oral treatment with an SFE significantly reduces 5-LO-derived LMs in RR-MS patients during an eight-month treatment period. Treatment response to an SFE, however, seems to be related to 12-,15-LO and cyclooxygenase product levels before SFE exposure. Further studies should confirm their biomarker potential in RR-MS and SFE treatment.

Особенности течения рассеянного склероза у больных с коморбидным аутоиммунным субклиническим гипотиреозом и депрессивным расстройством

Особенности течения рассеянного склероза у больных с коморбидным аутоиммунным субклиническим гипотиреозом и депрессивным расстройством

FEATS Score Differences and Comorbid Depression Within in Persons Diagnosed With Multiple Sclerosis

This study investigated the use of the Formal Elements Art Therapy Scale (FEATS) with Multiple Sclerosis (MS) patients. Eighty-eight persons with either relapsing-remitting or progressive type MS drew a Person Picking an Apple from a Tree, and completed a Beck Depression Inventory-Fast Screen (BDI-FS). FEATS scores were compared to BDI-FS scores and across disease type. Statistically significant results were found when comparing FEATS scores in regard to disease type, with overall FEATS scores (p = .014), indicating graphic elements linked to depression present in the drawings of patients with progressive type MS. The relationship between FEATS scores and the BDI-FS was not significant. Further research is needed, as this was the first study of the FEATS with the MS population.

Lack of association between the variant rs10735810 in the VDR gene and the pathogenicity of Multiple Sclerosis in patients of Khuzestan MS Society

Background: Multiple sclerosis (MS) seems to be a multifactorial disease in which the environment and genetics are involved. One of the factors associated with MS disease is the reduction in vitamin D levels and its specialized role in its pathogenicity. In Iran, Khuzestan province has a high relative incidence of the Multiple sclerosis (MS) after the provinces of Isfahan and Markazi, The polymorphism rs10735810 in the VDR gene with change in the initial codon is one of the factors associated with other known diseases, including osteoporosis and diabetes. Methods: In this study, the association of this variant in one hundred and fifty individuals with MS disease was compared with one hundred and fifty healthy individuals. PCR-sequencing was used to determine genotypes. Results: In the patient group, 16 cases had CC genotype, 59 had CT genotype and 75 had TT genotype, which did not show any significant difference in comparison with the control group (P>0.05). Also, there was no significant difference in the alleles distribution in the patient population compared to control (50% vs. 47.55% P=0.47). Additionally, no association was found between age and sex, and the ethnicity of patients (p> 0.05). Conclusion: The polymorphism rs10735810 in the VDR gene showed no association to the etiology of MS.

Advances in oral immunomodulating therapies in relapsing multiple sclerosis.

Oral treatment options for disease-modifying therapy in relapsing multiple sclerosis have substantially increased over the past decade with four approved oral compounds now available: fingolimod, dimethyl fumarate, teriflunomide, and cladribine. Although these immunomodulating therapies are all orally administered, and thus convenient for patients, they have different modes of action. These distinct mechanisms of action allow better adaption of treatments according to individual comorbidities and offer different mechanisms of treatment such as inhibition of immune cell trafficking versus immune cell depletion, thereby substantially expanding the available treatment options. New sphingosine-1-phosphate receptor (S1PR) modulators with more specific S1PR target profiles and potentially better safety profiles compared with fingolimod were tested in patients with relapsing multiple sclerosis. For example, siponimod, which targets S1PR1 and S1PR5, was approved in March, 2019, by the US Food and Drug Administration for the treatment of relapsing multiple sclerosis including active secondary progressive multiple sclerosis. Ozanimod, another S1P receptor modulator in the approval stage that also targets S1PR1 and S1PR5, reduced relapse rates and MRI activity in two phase 3 trials of patients with relapsing multiple sclerosis. Blocking of matrix metalloproteinases or tyrosine kinases are novel modes of action in the treatment of relapsing multiple sclerosis, which are exhibited by minocycline and evobrutinib, respectively. Minocycline reduced conversion to multiple sclerosis in patients with a clinically isolated syndrome. Evobrutinib reduced MRI activity in a phase 2 trial, and a phase 3 trial is underway, in patients with relapsing multiple sclerosis. Diroximel fumarate is metabolised to monomethyl fumarate, the active metabolite of dimethyl fumarate, reduces circulating lymphocytes and modifies the activation profile of monocytes, and is being tested in this disease with the aim to improve gastrointestinal tolerability. The oral immunomodulator laquinimod did not reach the primary endpoint of reduction in confirmed disability progression in a phase 3 trial of patients with relapsing multiple sclerosis. In a phase 2 trial of patients with primary progressive multiple sclerosis, laquinimod also did not reach the primary endpoint of a reduction in brain volume loss, as a consequence the development of this drug will probably not be continued in multiple sclerosis. WHERE NEXT?: Several new oral compounds are in late-stage clinical development. With new modes of action introduced to the treatment of multiple sclerosis, the question of how to select and sequence different treatments in individual patients arises. Balancing risks with the expected efficacy of disease-modifying therapies will still be key for treatment selection. However, risks as well as efficacy can change when moving from the controlled clinical trial setting to clinical practice. Because some oral treatments, such as cladribine, have long-lasting effects on the immune system, the cumulative effects of sequential monotherapies can resemble the effects of a concurrent combination therapy. This treatment scheme might lead to higher efficacy but also to new safety concerns. These sequential treatments were largely excluded in phase 2 and 3 trials; therefore, monitoring both short-term and long-term effects of sequential disease-modifying therapies in phase 4 studies, cohort studies, and registries will be necessary.

Nailfold capillaroscopy: a useful instrument for early diagnosis of systemic sclerosis in patients with primary biliary cholangitis

Introduction: Primary Biliary Cholangitis (PBC) is a cholestatic autoimmune disease affecting small bile ducts. PBC is often associated with Systemic Sclerosis (SSc). SSc prevalence is about 5–12% in PBC patients and diagnosis is often delayed due to lack of specific recommendations. Aim: We assessed the utility of Nailfold Capillaroscopy (NC) in anticipating SSc diagnosis in PBC patients.

Shorter axon initial segments do not cause repetitive firing impairments in the adult presymptomatic G127X SOD-1 Amyotrophic Lateral Sclerosis mouse

Increases in axonal sodium currents in peripheral nerves are some of the earliest excitability changes observed in Amyotrophic Lateral Sclerosis (ALS) patients. Nothing is known, however, about axonal sodium channels more proximally, particularly at the action potential initiating region - the axon initial segment (AIS). Immunohistochemistry for Nav1.6 sodium channels was used to investigate parameters of AISs of spinal motoneurones in the G127X SOD1 mouse model of ALS in adult mice at presymptomatic time points (~190 days old). In vivo intracellular recordings from lumbar spinal motoneurones were used to determine the consequences of any AIS changes. AISs of both alpha and gamma motoneurones were found to be significantly shorter (by 6.6% and 11.8% respectively) in G127X mice as well as being wider by 9.8% (alpha motoneurones). Measurements from 20–23 day old mice confirmed that this represented a change during adulthood. Intracellular recordings from motoneurones in presymptomatic adult mice, however, revealed no differences in individual action potentials or the cells ability to initiate repetitive action potentials. To conclude, despite changes in AIS geometry, no evidence was found for reduced excitability within the functional working range of firing frequencies of motoneurones in this model of ALS.

Cognitive functions in pediatric multiple sclerosis: 2-years follow-up

ABSTRACTObjective: To assess the neuropsychological status of pediatric multiple sclerosis (MS) patients and its relationship with clinical variables in a longitudinal study.Methods: Patients with MS (n = 46) and age- and gender-matched healthy control subjects (HCs, n = 53) were given tests of non-verbal reasoning, attention/concentration, visuospatial judgement and verbal fluency at baseline visit and after 2 years of follow-up. Cognitive impairment was defined as a failure on at least three of the four tests. Patients were grouped according to the age of disease onset (≤12 years as group 1 and > 12 years as group 2).Results: Cognitive impairment was detected in 22 of 46 patients at follow-up (47.8%). Patients with cognitive worsening had higher EDSS scores at follow-up compared to cognitively improved/stable group (0.68 ± 1.16 vs 0.04 ± 0.2, p = 0.01). The most affected domains were attention/concentration and non-verbal reasoning. Comparison between baseline and follow-up tests showed impairment in non-verbal reasoning over time in group 1 patients while other functions improved over time in patient and control groups as expected.Conclusion: Pediatric MS is likely to affect patients’ cognition concurrently with their disability levels. This effect is significant in the non-verbal reasoning area in patients with disease onset before age 12 years. A practical method assessing this function should be part of these patients’ regular follow-up for optimal treatment, prevention and rehabilitation.

Chinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11

BackgroundSpastic paraplegia type 11 (SPG11) mutations are the most frequent cause of autosomal recessive hereditary spastic paraplegia (ARHSP). We are aiming to identify the causative mutations in SPG11 among families referred to our center with ARHSP in a Chinese population.MethodsTargeted next-generation sequencing was performed on the patients to identify disease-causing mutations. Variants were analyzed according to their predicted pathogenicity and their relevance to the clinical phenotypes. The segregation in the family members was validated by Sanger sequencing.ResultsA total of 12 mutations in SPG11 gene from 9 index cases were identified, including 6 frameshift mutations, 3 missense mutations, 1 nonsense mutation, 1 splicing mutation, and 1 intron deletion mutation. In 6 of these patients, the mutations were homozygous, and the other 3 patients carried two compound heterozygous mutations. Six mutations were novel; 2 were classified as pathogenic, 1 were considered as likely pathogenic, and the other 3 were variants of unknown significance. Additionally, 1 missense heterozygous variant we found was also carried by amyotrophic lateral sclerosis (ALS) patient. Clinically and electrophysiologically, some of our ARHSP patients partially shared various features of autosomal-recessive juvenile amyotrophic lateral sclerosis (ARJALS), including combination of both UMN and LMN degeneration.ConclusionsThe results contribute to extending of the SPG11 gene mutation spectrum and emphasizing a putative link between ARHSP and ARJALS.

Developmental Venous Anomalies are More Common in Patients with Multiple Sclerosis and Clinically Isolated Syndrome : Coincidence or Relevant?

Developmental venous anomalies (DVA) are congenital malformations of veins that drain brain parenchyma, with a prevalence up to 9.3% in normal populations and 29.5% in multiple sclerosis (MS) patients. Study purpose was to determine prevalence of DVAs in patients with clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS) and to assess whether DVAs are related to altered clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) laboratory parameters. Routine neurological and MRI examinations took place in asingle center in 93 patients (39 CIS, 54 RRMS). Clinical disability (n = 93), MRI (n ≤ 90), CSF (n ≤ 82) parameters and DVA status were determined and compared statistically. A total of 29DVAs were detected in 25patients (25/93; 26.9%), 10 in 39CIS patients and 15 in 54RRMS patients. Most parameters were not significantly altered in patients with DVAs; no associated higher conversion rates from CIS to MS at 1-year (p = 0.411) or 2‑year follow-up (p = 0.281) were registered. A higher prevalence of DVAs was detected in CIS and early MS patients than reported in non-MS populations, congruent to recent literature. The DVAs were not associated with significantly altered clinical outcomes, brain atrophy rates or disease progression, and no associated higher risk of CIS patients for converting to MS was found.

The Patterns of Clinical Presentation of Multiple Sclerosis in Patients Admitted to the National Center of Neurological Sciences, Khartoum, Sudan 2018

Multiple sclerosis (MS) is an immune- mediated inflammatory disease that attacks myelinated axons in the central nervous system leading to significant disability. This study is a descriptive cross-sectional study conducted at the national center for neurological sciences (NCNS), Khartoum Sudan, over 3 years period from August 2015 to April 2018. The diagnosis was performed based on Poser & Mackdonalds criteria. Data was collected using Questionnaire. The diagnosis was confirmed by brain and cervical spine magnetic resonance imaging (MRI) with sagittal FLAIR, serum and cerebrospinal fluid (CSF) oligoclonal band. Sixty-five patients were enrolled. The majority (90.8%) of them were females. 38.4% were within the age group from 21-30 years and 95.4% had no family history of MS. 18 patients (27.6%) had decreased visual acuity, 13 patients (20%) had ataxia, and 33 patients (50.7%) had a past history of similar condition. 64.6% out of 65 patients had more than two lesions detectable in their brain MRI. Only 18.4% of the patients were examined for CSF analysis. Oligoclonal band was found positive in all of them. Females predominated in 91% of the patients. The most affected age group was ranging between 21-30 years. Relapsing-remitting type was the most common disease course. Oligoclonal band was detected in all of the patients. Azathioprine was found to be very effective.

EEG signal analysis and classification on P300 speller-based BCI performance in ALS patients

Objective: the objective of the presented work is to analyse the electroencephalography signal based on brain computer interface by using P300 speller for amyotrophic lateral sclerosis (ALS) patients and perform classification on extracted features to get accuracy. Analysis/methods: amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that involves the degeneration and death of nerve cell in the brain. It affects the process related to speech and loss of motor function in the patient. BCI technology is a communication solution for all amyotrophic lateral sclerosis (ALS) patients. The P300 speller included in the BNCI Horizon 2020 data is an application allows calculating the accuracy of classifier, which is necessary for the user to spell letters or sentences in a BCI speller paradigm. In this paper, we have extracted wavelet and power spectral density features. Association rule mining and ranking method is used for feature selection. For the classification, we have used multiple techniques and different classifiers and out of those, ten best techniques are selected based on their good performance. Finding: as a result, we get maximum 75% accuracy when we used random committee classifier.

Investigating the Effect of Cinnamon Edible Drop on Balance and Fear of Falling in MS Patients Referred to MS Association in Isfahan Province

Introduction: Imbalance and fear of falling are common symptoms in multiple sclerosis (MS) patients. Drug therapy and complementary and alternative medicine and the use of medicinal plants are considered treatment options in this regard. Accordingly, the present study was conducted to investigate the effect of cinnamon edible drop on balance and fear of falling in MS patients. Materials and Methods: This experimental study was a controlled clinical trial with a parallel design. It was conducted using convenience sampling method. Accordingly, 62 MS patients were randomly divided into control and intervention groups, so that 31 patients were placed in the control group and 31 patients were placed in the intervention group. Data collection tools included the Berg balance scale and Falls Efficiency Scale (international form). The data were analyzed at 5% error level through SPSS version 22 software. Results: The balance scores of the patients in the control and intervention groups at the end of the first and second months were not significantly different than those before the intervention (p >0.05), but the patients' fear of falling score was significantly higher at the end of the third month compared to that before the intervention (p 0.05). Conclusion: Based on the results of the present study, it can be concluded that daily consumption of cinnamon in MS patients can improve their balance status after 3 months, while its effect on fear of falling in these patients was not proven.