Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Background: Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. Objectives: This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. Design: This prospective observational study was designed in a tertiary center during one year. Methods: All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Results: Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). Conclusion: The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

Plasmapheresis and IVIG for Treatment of Non-Tumor Anti-Tr/DNER Antibody-Associated Ataxia: A Case Report.

Autoimmune cerebellar ataxia (ACA) is a condition characterized by progressive ataxia resulting from an immune-mediated attack on cerebellar structures. The presence of anti-Tr/DNER antibodies, strongly associated with Hodgkin lymphoma, has been identified in ACA. However, cases with no underlying malignancy are rare. We report the case of a 49-year-old woman presenting with progressive ataxia, slurred speech, and dizziness over three months. The patient exhibited significant cerebellar symptoms, including dysarthria and limb ataxia, without signs of other systemic illnesses. Comprehensive investigations, including imaging, lumbar puncture, and autoantibody testing, were performed. The cerebrospinal fluid (CSF) sample revealed positivity for Tr/DNER antibodies, leading to a diagnosis of autoimmune cerebellar ataxia. The patient underwent nine sessions of plasmapheresis, followed by six doses of intravenous immunoglobulin (IVIG), resulting in significant clinical improvement. Despite extensive cancer screening, no underlying malignancy was detected, suggesting a non-tumor origin of anti-Tr/DNER antibodies. The patient's gait improved, ataxia resolved, and cerebellar tests normalized following treatment. The patient was further managed with rituximab treatment every six months. This case represents a presentation of anti-Tr/DNER-associated autoimmune cerebellar ataxia without malignancy. The successful treatment with plasmapheresis and IVIG suggests that these interventions may be effective in managing autoimmune cerebellar ataxia associated with anti-Tr/DNER antibodies. Further research is needed to understand the underlying mechanisms of this condition and to determine the optimal treatment strategies.

Small fiber neuropathy in irritable bowel syndrome.

Aim: In this study, we intend to evaluate the occurrence of small fiber neuropathy in patients with irritable bowel syndrome (IBS). Background: Small fiber neuropathy (SFN) is a sensory neuropathy that results from the degeneration of small Aδ and unmyelinated C fibers. SFN manifests positive symptoms, such as tingling, burning, prickling, and aching, and negative symptoms, including numbness, tightness, and coldness. The SFN coexistence with other comorbidities (e.g., fibromyalgia, inflammatory bowel disease, celiac disease) has been reported in previous studies. Methods: We conducted a cross-sectional study to assess the coexistence of SFN and IBS. Forty-two IBS patients and forty-three healthy individuals were asked to complete the Michigan Neuropathy Screening Instrument (MNSI) questionnaire. Results greater than three (>3) were considered positive. Participants with positive MNSI questionnaire results were examined for any neuropathy signs according to the Utah Early Neuropathy Scale (UENS) examination. The participants with positive results for the questionnaire and examination were checked for the sural and the superficial peroneal nerve conduction study (NCS). Normal NCS represented intact large fibers and the diagnosis of SFN. Results: Ten participants, 7 (16.7 %) in the IBS group and 3 (6.9 %) in the healthy group, had positive results for the questionnaire. Four participants were positive for the examination, with normal NCS, and were classified as SFN-positive. All four SFN diagnoses were from the IBS group. No one in the healthy group was diagnosed with SFN. We could find a significant statistical difference (p<0.05) between the IBS and healthy groups regarding the prevalence of SFN diagnosis. Conclusion: The co-occurrence of SFN and IBS suggests the possibility of a generalized neuropathy syndrome characterized by widespread neuronal impairment. Thus, any peripheral neuropathy symptom in IBS patients (and potentially other chronic pain disorders) should be evaluated for SFN since timely diagnosis and proper treatment result in a better quality of life for the patients.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran.

OBJECTIVE: The relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. METHODS: In a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. RESULTS: A total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. CONCLUSION: We found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Prevalence and incidence of multiple sclerosis in Isfahan, Iran between 1996 and 2021: A population-based study.

BACKGROUND: There has been no recent comprehensive epidemiological study on a large and stable population of multiple sclerosis (MS) in Isfahan. Therefore, we conducted this study to estimate the incidence and prevalence of MS in Isfahan province from 1996 to 2021. METHOD: In this population-based study, we utilized the dataset from the Vice-Chancellor's Office of Isfahan University of Medical Sciences, which registers all people diagnosed with MS (PDWM) in Isfahan province, excluding those residing in Kashan city. We measured crude incidence and prevalence of MS, separated by sex, and based on age of MS onset, as well as changes in age of MS onset during observation. RESULTS: A total of 9,909 PDWM were included in our study. The incidence during the time period of 1996-2000 was 5.4/100,000 (1.1/100,000 per year), which subsequently increased to 14.1 (2.8/100,000 per years) and 31.1 per 100,000 (6.2/100,000 per year) during 2001-2005 and 2006-2010, respectively. There was a further increase to 70.9/100,000 (14.2/100,000 per year) in 2011-2015, but it remained stable at 71.8/100,000 (12/100,000 per year) during the period of 2016-2021. In 2016, the age-standardized incidence rates of pediatric-onset, adult-onset, and late-onset MS were 1.8/100,000, 31.4/100,000, and 17.5/100,000, respectively. The prevalence of MS in 2021 was 183.9/100,000. The female/male new case ratio was 4.5 during 1996-2000, decreasing to 4.0, 3.9, 3.9, and 2.9 in the subsequent four five-year periods. The mean age of RRMS onset was 26.3 ± 8.1 between 1990 and 1999, 28.5 ± 8.3 during 2000-2009, and increased to 32.8 ± 9.6 in 2010-2019. CONCLUSION: This study shows that Isfahan has one of the highest incidence rate and prevalence ratio of MS in the region. We observed an increase in the incidence rate during the first decade, followed by stability in the last two five- and six-year periods. Further studies are needed to identify the reasons behind the change in incidence of MS in Iran.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids triggered by Hodgkin's lymphoma: A case report and brief literature review.

Key Clinical Message: We presented a patient, diagnosed with lymphoma-associated CLIPPERS, 11 years after lymphoma treatment. Therefore, CLIPPERS may be paraneoplastic neurological syndrome of lymphoma, which needs to be considered in the follow-up of lymphoma cases. Abstract: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system disorder with a recent increase in incidence. There are few reports of lymphoma-associated CLIPPERS, although the relationship between these two diseases and the pathophysiology of CLIPPERS in general need further investigation. Here, we present a patient with a history of Hodgkin's lymphoma (HL) more than 10 years before the onset of CLIPPERS, in contrast to the majority of previously reported lymphoma-associated cases, and discuss the possibility that CLIPPERS is the paraneoplastic neurological syndrome of HL. This highlights the need to consider CLIPPERS as a differential diagnosis during follow-up of patients with a history of lymphoma.

Feasibility and efficacy of an early sensory-motor rehabilitation program on hand function in patients with stroke: a pilot, single-subject experimental design.

OBJECTIVE: Hand and upper limb functional impairments following stroke lead to limitations in performing activities of daily living. We aimed to investigate feasibility and efficacy of an early sensory-motor rehabilitation program on hand and upper limb function in patients with acute stroke. DESIGN: A pilot, single-subject experimental, A-B-A study. SETTING: Stroke unit of an educational hospital and an outpatient occupational therapy clinic. PARTICIPANTS: A convenience sample including five people with acute stroke. PROCEDURES: Participants received 3 h of an intensive hand and upper limb sensory and motor rehabilitation program, 5 days per week for 3 months (15-min mental imagery, 15-min action observation, 30-min mirror therapy, 1.5-h constraint-induced movement therapy, and 30-min bilateral arm training). Activities were chosen based on the task-oriented occupational therapy approach. OUTCOME MEASURES: An assessor blinded to intervention program measured sensory and motor functions using action research arm test, box and block test, Semmes-Weinstein monofilaments, and upper extremity section of Fugl-Meyer assessment. RESULTS: Assessment data points in intervention and follow-up phases compared to baseline were in higher levels, sloped upwardly, and increased significantly for all participants in all outcome measures. CONCLUSIONS: The present pilot study showed that a package of nowadays evidence-based rehabilitation methods including mental imagery, action observation, mirror therapy, modified constraint-induced movement therapy, bilateral arm training, and task-oriented occupational therapy approach is able to improve sensory and motor functions of the hand and upper limb in patients with acute stroke.

Investigating the feasibility of differentiating MS active lesions from inactive ones using texture analysis and machine learning methods in DWI images.

BACKGROUND: Magnetic resonance imaging (MRI) is commonly used in conjunction with a gadolinium-based contrast agent (GBCA) to distinguish active multiple sclerosis (MS) lesions. However, recent studies have raised concerns regarding the long-term effects of the accumulation of GBCA in the body. Thus, the purpose of this study is to investigate the possibility of using texture analysis in diffusion-weighted imaging (DWI) and machine learning algorithms to discriminate active from inactive MS lesions without the use of GBCA. METHODS: To achieve this purpose, we introduce an image processing pipeline. In the proposed pipeline, following registration and alignment of slices, MS lesions from DWI images are segmented and quantized. Next, different texture analysis methods are employed to extract texture features from the lesions. Then, a two-stage feature reduction method is applied, in which the first stage involves a statistical t-test and the second stage relies on principal component analysis (PCA), sequential forward selection (SFS), sequential backward selection (SBS), and ReliefF algorithms. Finally, we use five classifiers logistic regression (LR), support vector machine (SVM), decision tree (DT), K nearest neighbor (KNN), and linear discriminant analysis (LDA) in a 5-fold cross-validation procedure to determine active and inactive MS lesions. RESULTS: In this study, we collected and prepared 255 active/inactive MS lesions from MRI scans of 34 patients diagnosed with MS, with a mean age of 35.56±10.89. Among 89 texture features extracted, 63 features showed statistically significant differences between the means of active and inactive lesions (P<0.05). The SVM classifier with the PCA feature reduction algorithm demonstrated the best performance with an average accuracy of 0.960 (±0.024), specificity and precision of 1.0, sensitivity of 0.913 (±0.053), and AUC of 0.957 (±0.027). CONCLUSION: Our study indicates that DWI changes detected using texture analysis-based machine learning models can precisely differentiate active from inactive MS lesions. This finding provides valuable clinical information for the early diagnosis and effective monitoring of MS disease.

A mechanistic insight into sources of error of visual working memory in multiple sclerosis.

Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, MGL were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM deficit in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) was responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.

Working memory is a system that temporarily stores and manipulates information used in tasks like decision-making and reasoning. Patients with multiple sclerosis ­ a condition that can affect the brain and spinal cord ­ often have impaired working memory, which can negatively affect their quality of life. Traditionally, working memory has been evaluated using tests that determine whether a patient can recall an item or not. In this approach, an incorrect response implies a complete absence of information regarding the specific item, resulting in a binary evaluation. More recently, researchers have shown that the precision of the memories people recall degrades gradually as they are asked to remember more things and that focusing on an item negatively affects recall precision for other items. This implies that working memory is reorganised flexibly between memorised items, a so-called 'resource model'. Unlike previous research, which favoured a binary model, Motahharynia et al. used a resource model to study visual working memory impairment in multiple sclerosis. The study participants consisted of healthy volunteers and patients with two subtypes of multiple sclerosis. Each participant completed one of two different types of test. In one, they were shown targets for short periods of time and then asked to pinpoint their position after they disappeared. In the other, participants were asked to memorise the orientation and colour of consecutively presented bars. The findings confirmed that multiple sclerosis patients had worse memory recall than people without the disease. However, computer modelling provided insights into the sources of error in working memory dysfunction, showing that the memory deficiency was due to imprecision in recalling information and 'swap errors', the phenomenon of mistakenly reporting the property of other memorised items. This rise in swap errors is likely due to an increase in unwanted signals, or noise, in the brains of multiple sclerosis patients. Motahharynia et al. have presented a sensitive way of measuring working memory deficiency. Importantly, the measurements were able to distinguish between different stages of multiple sclerosis. This could help doctors detect disease progression earlier, allowing for more timely and effective treatment interventions. This method could also be useful in the development and testing of drugs for therapy.

Iranian specialists' approach to treatment escalation in multiple sclerosis patients with cognitive impairment.

Background: People with multiple sclerosis (MS) and their physicians recognize cognitive retention as an important desired outcome of disease-modifying therapies (DMTs). In this study, we attempted to gather the opinions of Iranian MS experts regarding the treatment approach toward clinical cases with different physical and cognitive conditions. Methods: Opinions of 20 MS specialists regarding the best approach to 6 case scenarios (with different clinical, cognitive, and imaging characteristics) were gathered via a form. Results: The estimated kappa of 0.16 [95% confidence interval (CI): 0.159-0.163; P < 0.001] suggested a poor degree of agreement on the treatment choice among the professionals. Conclusion: Although most specialists agreed with treatment escalation in cases with cognitive impairment, there was no general agreement. Furthermore, there was not enough clinical evidence in the literature to develop consensus guidelines on the matter.

Iranian specialists' approach to surgery in patients with multiple sclerosis.

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research.

The benefit of intravenous immune globulin in the treatment of delayed radiation myelopathy.

Delayed radiation myelopathy (DRM) is a rare yet severe complication of radiotherapy. This condition has a progressive pattern that is often irreversible. Several therapeutic strategies have been introduced to alleviate disease complications, including corticosteroids, hyperbaric oxygen, anticoagulants, and antivascular endothelial growth factor (VEGF) agents. However, despite their beneficial effect, they have not been the definitive treatments for DRM. Here we present the case of a 55-year-old woman with a history of multiple myeloma who developed neurological complications 11 months after radiation therapy. As her radiologic findings demonstrated transverse myelitis, based on the DRM diagnostic criteria, the diagnosis of delayed radiation myelitis was reached. Therefore, methylprednisolone pulse therapy was initiated, resulting in the complete resolution of her neurological symptoms. However, on her follow-up examination, although she did not have new neurological complications, magnetic resonance imaging (MRI) demonstrated a residual enhancement in the thoracic spinal cord area. Hence, due to the possibility of myelitis progression and spinal cord atrophy, intravenous immune globulin (IVIG) was administered, resulting in the resolution of lesion enhancement. Considering this outcome and the immunomodulatory properties of IVIG, it could be regarded as a potential therapeutic option in the case of DRM activity.

Patterns of attention deficit in relapsing and progressive phenotypes of multiple sclerosis.

Behavioral aspects and underlying pathology of attention deficit in multiple sclerosis (MS) remain unknown. This study aimed to clarify impairment of attention and its relationship with MS-related fatigue. Thirty-four relapse-remitting MS (RRMS), 35 secondary-progressive MS (SPMS) and 45 healthy controls (HC) were included. Results of psychophysics tasks (attention network test (ANT) and Posner spatial cueing test) and fatigue assessments (visual analogue scale and modified fatigue impact scale (MFIS)) were compared between groups. In ANT, attentional network effects were not different between MS phenotypes and HC. In Posner task, RRMS or SPMS patients did not benefit from valid cues unlike HC. RRMS and SPMS patients had less gain in exogenous trials with 62.5 ms cue-target interval time (CTIT) and endogenous trials with 250 ms CTIT, respectively. Total MFIS was the predictor of gain in 250 ms endogenous blocks and cognitive MFIS predicted orienting attentional effect. Executive attentional effect in RRMS patients with shorter disease duration and orienting attentional effect in longer diagnosed SPMS were correlated with MFIS scores. The pattern of attention deficit in MS differs between phenotypes. Exogenous attention is impaired in RRMS patients while SPMS patients have deficit in endogenous attention. Fatigue trait predicts impairment of endogenous and orienting attention in MS.

Thalamic asymmetry in Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. METHODS: This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamic asymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. RESULTS: We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p = 0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p = 0.037). CONCLUSIONS: In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

Familial Mediterranean Fever and Transverse Myelitis: A Causal Relation?

Familial Mediterranean fever (FMF) is a rare autoinflammatory disorder characterized mainly by recurrent self-limited episodes of fever and polyserositis. FMF-related neurologic complication is an old debate, and the correlation between FMF and demyelinating disorders has been a matter of dispute for a long time. Few reports demonstrated a relationship between FMF and multiple sclerosis; however, the existence of a causal relationship between FMF and demyelinating disorders is still a puzzle. This report presents the first case of transverse myelitis following FMF attacks in which neurologic manifestations were resolved using colchicine treatment. Due to relapses of FMF, which were accompanied by transverse myelitis, rituximab was administered, which resulted in stabilizing disease activity. Accordingly, in the case of colchicine-resistant FMF and FMF-related demyelinating conditions, rituximab could be considered as a potential therapeutic option to alleviate both polyserositis and demyelinating manifestations.

Effect of deep gray matter atrophy on information processing speed in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cognitive dysfunction, including reduced Information processing speed (IPS), is relatively common in multiple sclerosis(MS). IPS deficits have profound effects on several aspects of patients' life. Previous studies showed that deep gray matter atrophy is highly correlated with overall cognitive impairment in MS. However, the effect of deep gray matter atrophy on IPS deficits is not well understood. In this study, we evaluated the effects of deep gray matter volume changes on IPS in people with early relapse-remitting MS (RRMS) compared to healthy control. METHODS: In this case-control study, we enrolled 63 case with RRMS and 36 healthy controls. All patients were diagnosed within 6 years. IPS was evaluated using the Integrated Cognitive Assessment (ICA) test. We also performed a 1.5T MRI to evaluate deep gray matter structures. RESULTS: People with RRMS had lower accuracy in the ICA test (p = .01). However, the reaction time did not significantly differ between RRMS and control groups (p = .6). Thalamus volume was significantly lower in the RRMS group with impaired IPS compared to the RRMS with normal IPS and control groups (p < 10-4). Other deep gray matter structures were not significantly different between the RRMS with impaired IPS group and the RRMS with normal IPS group. CONCLUSION: Some people with MS are impaired in IPS even in the early stages of the disease. Thalamic atrophy affected IPS in these patients, however atrophy in other deep gray matter structures, including caudate, putamen, globus pallidus, hippocampus, amygdala, accumbens, and cerebellum, were not significantly correlated with IPS impairment in early RRMS.

Assessment of intelligence quotient in patients with neuromyelitis optica spectrum disease and multiple sclerosis.

BACKGROUND: Cognitive impairment is common in people living with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS). However, there is little published data on intelligence quotient (IQ) in NMOSD patients. Therefore, we performed the present study to compare IQ scores across NMOSD, MS, and control groups. METHOD: In this cross-sectional study, 49 NMOSD (30 with positive aquaporin4 antibody), 41 MS, and 20 control individuals were recruited. The IQ score for each person was measured using Wechsler Adult Intelligence Scale-Revised (WAIS-R). Participants were reported on eleven scores of subsets, verbal IQ (VIQ), performance IQ (PIQ), and full score IQ (FSIQ). RESULT: The scores of FSIQ, VIQ, PIQ, vocabulary, similarities, and digit-symbol in NMOSD and MS individuals were lower than the control group. Relative to control, NMOSD patients reported a lower score of information. We found no difference between NMOSD and MS groups, except in vocabulary and similarities. No significant difference between seropositive and seronegative NMOSD groups was observed except for the information and block design. In NMOSD group, a greater EDSS score was associated with decreased scores of FSIQ, VIQ, and PIQ. Being employed and being married were associated with greater scores of VIQ and PIQ, respectively. In both NMOSD and MS groups, advanced education was associated with increased scores of FSIQ and VIQ. CONCLUSION: Our study showed decreased IQ scores in NMOSD and MS. Further studies are required to examine intellectual quotient in people with NMOSD and MS.

Working memory dysfunction differs between secondary progressive and relapsing multiple sclerosis: Effects of clinical phenotype, age, disease duration, and disability.

BACKGROUND: Cognitive dysfunction is relatively common in patients with multiple sclerosis (MS). Although it occurs in all stages and all phenotypes of MS, it is more prevalent in secondary progressive MS (SPMS) compared to relapsing MS (RMS). It is unclear whether the higher frequency of cognitive impairment in SPMS is linked to the progressive phenotype or other clinical factors. In this study, we compared working memory in patients with RMS, SPMS, and healthy subjects. We also investigated the effects of age, disease duration, and disability on working memory performance. METHODS: This case-control study enrolled 134 MS patients, 69 patients were diagnosed with RMS and 65 patients with SPMS, and 77 healthy control subjects. We designed two working memory tasks with different sets of stimuli (face vs. checkerboard) and different instructions (same or different vs. which one is the same). RESULTS: Accuracy was significantly more impaired in SPMS patients than in RMS patients and both groups were worse than healthy subjects. This finding was similar between both tasks. Age and overall cognitive functions (measured with MoCA) also affected accuracy, but disease duration and disability only affected accuracy in working memory task with checkerboard stimuli. CONCLUSION: MS patients are impaired in keeping the information in the visual working memory for a few seconds. Progressive phenotype significantly affected working memory accuracy, and this effect did not explain out with other demographic or clinical factors. Future studies are needed to reveal underlying mechanisms of working memory dysfunction in SPMS and working memory dysfunction as a biomarker of disease progression.

Ontology for Symptomatic Treatment of Multiple Sclerosis.

OBJECTIVES: Symptomatic treatment is an essential component in the overall treatment of multiple sclerosis (MS). However, knowledge in this regard is confusing and scattered. Physicians also have challenges in choosing symptomatic treatment based on the patient's condition. To share, update, and reuse this knowledge, the aim of this study was to provide an ontology for MS symptomatic treatment. METHODS: The Symptomatic Treatment of Multiple Sclerosis Ontology (STMSO) was developed according to Ontology Development 101 and a guideline for developing good ontologies in the biomedical domain. We obtained knowledge and rules through a systematic review and entered this knowledge in the form of classes and subclasses in the ontology. We then mapped the ontology using the Basic Formal Ontology (BFO) and Ontology for General Medical Sciences (OGMS) as reference ontologies. The ontology was built using Protégé Editor in the Web Ontology Language format. Finally, an evaluation was done by experts using criterion-based approaches in terms of accuracy, clarity, consistency, and completeness. RESULTS: The knowledge extraction phase identified 110 articles related to the ontology in the form of 626 classes, 40 object properties, and 139 rules. Five general classes included "patient," "symptoms," "pharmacological treatment," "treatment plan," and "measurement index." The evaluation in terms of standards for biomedical ontology showed that STMSO was accurate, clear, consistent, and complete. CONCLUSIONS: STMSO is the first comprehensive semantic representation of the symptomatic treatment of MS and provides a major step toward the development of intelligent clinical decision support systems for symptomatic MS treatment.