Clinical and magnetic resonance imaging outcomes in pediatric-onset MS patients on fingolimod and ocrelizumab.

BACKGROUND: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials. OBJECTIVE: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age. METHODS: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18. RESULTS: Eighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 - 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 - 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38-1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04-0.21) and none developed new T2 lesions. CONCLUSION: This study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab.

Short-chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset.

OBJECTIVE: The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric-onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. METHODS: A multicenter case-control study in which 35 pediatric-onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self-reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co-occurrence networks and for predicting functional abundances based on marker gene sequences. RESULTS: Two microbial co-occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short-chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family-level findings from an independent Canadian-US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. INTERPRETATION: Our results suggest that short-chain fatty acid producers may be important contributors to multiple sclerosis onset.

Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors.

BACKGROUND: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk. METHODS: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02). RESULTS: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56-0.78, p < 0.001; OR 0.78, 95 % CI 0.62-0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors. CONCLUSIONS: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.

High serum neurofilament levels are observed close to disease activity events in pediatric-onset MS and MOG antibody-associated diseases.

BACKGROUND: Serum neurofilament light chain (sNfL) is an emerging multiple sclerosis (MS) biomarker which measures neuro-axonal damage. However, understanding its temporal association with disease activity in pediatric-onset MS (POMS) and Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains limited. OBJECTIVE: To investigate the association of sNfL levels and time from disease activity in children with MS and MOGAD. METHODS: POMS and MOGAD cases with onset before 18 years of age were enrolled at the University of California San Francisco (UCSF) Regional Pediatric MS Center. Frequency-matched healthy subjects were recruited from general pediatric clinics. Serum samples were tested for MOG-IgG at Mayo Clinic using a live cell-based fluorescent activated cell sorting assay. sNfL levels were measured using single-molecule array (Simoa) technology measured in pg/mL. Data on demographics, clinical features, MRI, CSF, and treatment data were collected by chart review. RESULTS: We included 201 healthy controls healthy controls, 142 POMS, and 20 confirmed MOGAD cases with available sNfL levels. The median (IQR) age at the time of sampling was 15.6 (3.9), 15.5 (3.1), and 8.8 (4.1) years for controls, POMS, and MOGAD, respectively. Median sNfL levels (pg/ml) were higher in POMS (19.6) and MOGAD (32.7) cases compared to healthy controls (3.9) (p<0.001). sNfL levels ≥100 pg/ml were only detected within four months of a clinical event or MRI activity in both POMS and MOGAD cases. In addition, sNfL levels were higher in POMS patients with new/enlarged T2 and gadolinium-enhanced lesions than those without MRI activity within four months of sampling in POMS cases. CONCLUSION: High sNfL levels were observed close to clinical or MRI events in POMS and MOGAD. Our findings support sNfL as a biomarker of disease activity in pediatric demyelinating disorders.

Gene-environment interactions increase the risk of paediatric-onset multiple sclerosis associated with household chemical exposures.

BACKGROUND: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. METHODS: Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090). RESULTS: 490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes. CONCLUSIONS: The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.

Neuromotor control associates with muscle weakness observed with McArdle sign of multiple sclerosis.

OBJECTIVE: Multiple Sclerosis (MS) is often accompanied by myelopathy, which may be associated with progressive worsening. A specific finding of MS-associated myelopathy is McArdle sign, wherein neck flexion is associated with prominent increased limb weakness relative to that detected with neck extension. In this study, we characterized neuromotor control properties of finger extensors in association with the McArdle sign. METHODS: A custom-built device was utilized to monitor torque production of the wrist extensors with simultaneous recording of surface electromyography of the extensor digitorum. The electromyography was decomposed and analyzed via both linear and nominal regressions. RESULTS: Linear regressions demonstrated a strong difference between groups for MS from healthy controls and other myelopathies for motor unit action potential amplitude and average firing rate (p < 0.001). Further, linear regression demonstrated good correlations of neuromotor variables to mechanical torque output (0.24 ≤ R2 ≤ 0.76). Nominal regression distinguished MS from healthy controls with an AUC of 0.87, specificity of 0.97, and sensitivity of 0.64. Nominal regression of MS from other myelopathies demonstrated an AUC of 0.88, specificity of 0.85, and sensitivity of 0.79. INTERPRETATION: These data demonstrate the neuromotor control factors that largely determine muscle force production change with the observation of McArdle sign; these neuromotor control factors can differentiate MS from both healthy controls and other myelopathy conditions.

Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.

BACKGROUND: The mechanisms by which hypertension accelerates coronary artery disease are poorly understood. Patients with hypertension often have confounding humoral changes, and to date, no experimental models have allowed analysis of the isolated effect of pressure on atherosclerosis in a setting that recapitulates the dimensions and biomechanics of human coronary arteries. OBJECTIVES: This study sought to analyze the effect of pressure on coronary atherosclerosis and explore the underlying mechanisms. METHODS: Using inflatable suprarenal aortic cuffs, we increased mean arterial pressure by >30 mm Hg in the cephalad body part of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)D374Y Yucatan minipigs for >1 year. Caudal pressures remained normal. RESULTS: Under hypercholesterolemic conditions in PCSK9D374Y transgenic minipigs, cephalad hypertension accelerated coronary atherosclerosis to almost 5-fold with consistent development of fibroatheromas that were sufficiently large to cause stenosis on computed tomography angiography. This was caused by local pressure forces, because vascular beds shielded from hypertension, but exposed to the same humoral factors, showed no changes in lesion formation. The same experiment was conducted under normocholesterolemic conditions in wild-type minipigs to examine the underlying mechanisms. Hypertension produced clear changes in the arterial proteome with increased abundance of mechanical strength proteins and reduced levels of infiltrating plasma macromolecules. This was paralleled by increased smooth muscle cells and increased intimal accumulation of low-density lipoproteins in the coronary arteries. CONCLUSIONS: Increased pressure per se facilitates coronary atherosclerosis. Our data indicate that restructuring of the artery to match increased tensile forces in hypertension alters the passage of macromolecules and leads to increased intimal accumulation of low-density lipoproteins.

Biomechanical muscle stiffness measures of extensor digitorum explain potential mechanism of McArdle sign.

BACKGROUND: McArdle sign is a phenomenon of impaired gait and muscle weakness that occurs with neck flexion, immediately reversible with neck extension. A recent report measured the specificity of this sign for multiple sclerosis by measuring differences in peak torque of the extensor digitorum between neck extension and flexion. METHODS: This substudy included 73 participants (29 multiple sclerosis, 20 non-multiple sclerosis myelopathies, 5 peripheral nerve disorders, and 19 healthy controls). The effect of neck position was assessed on muscle stiffness and neuromechanical error of the extensor digitorum. FINDINGS: Patients with multiple sclerosis had greater neuromechanical error (sum of squared error of prediction) compared to controls (P = 0.023) and non-multiple sclerosis myelopathies (P = 0.003). Neuromechanical error also provided improved sensitivity/specificity of McArdle sign. Peak torque, muscle stiffness, and neuromechanical error could distinguish multiple sclerosis from other myelopathies with 80% specificity and 97% sensitivity (AUC = 0.95). INTERPRETATION: A decrease in muscle stiffness and neuromechanical error in neck flexion compared to extension are additional indicators for a diagnosis of multiple sclerosis. Analysis of muscle stiffness may provide insights into the pathophysiology of this specific clinical sign for multiple sclerosis. Furthermore, muscle stiffness may provide an additional accurate, simple assessment to evaluate multiple sclerosis therapeutic interventions and disease progression.

18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis.

BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS: FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.

McArdle Sign: A Specific Sign of Multiple Sclerosis.

OBJECTIVE: To measure McArdle sign (rapidly reversible weakness induced by neck flexion) both qualitatively and quantitatively and to evaluate its specificity and clinical utility for diagnosis of multiple sclerosis (MS). PATIENTS AND METHODS: In this prospective study, McArdle sign was evaluated by a technician blinded to diagnosis by measuring changes in finger extensor strength in successive trials of neck extension and flexion, first clinically and then with a torque measurement device. We studied 25 healthy controls and 81 patients with finger extensor weakness. Patients were not selected for having McArdle sign. Fifty-two patients had MS, 24 had other myelopathies, and 5 had peripheral nerve lesions accounting for their weakness. The study was conducted between February 1, 2016, and June 30, 2017. RESULTS: The median clinical McArdle sign and the 2 quantitative measures of neck flexion-induced strength reduction were greater in patients with MS than in the other groups (P<.001). Baseline strength did not confound the difference. The area under the receiver operating characteristic curve was 0.84 (95% CI, 0.75-0.93) comparing patients with MS vs healthy controls and 0.84 (95% CI, 0.75-0.93) comparing MS vs patients with other myelopathies. The 2 quantitative and 1 clinical measurement of McArdle sign by the technician who performed the quantitative testing were correlated (r=.57 and r=.58; P<.001), and in turn, the technician's and unblinded referring physician's clinical assessments were correlated (r=.58; P<.001). McArdle sign was evident in some patients who had minor disability and who were in early phases of MS. CONCLUSION: McArdle sign, when defined as greater than 10% neck flexion-induced reduction in strength, is entirely specific and 65% sensitive for a diagnosis of MS when compared with other conditions that mimic MS-associated myelopathy. It may facilitate diagnosis in certain clinical situations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03122873.

Diagnosis and Management of Multiple Sclerosis in Children.

Growing evidence indicates the safety and well toleration of treatment by Disease-modifying in children suffering multiple sclerosis (MS). The treatment is not straight forward in a great number of patients, thus patients with pediatric MS must be managed by experienced specialized centers. Common treatments of multiple sclerosis for adults are first-line therapies. These therapies (firstline) are safe for children. Failure in treatment that leads to therapy alteration is almost prevalent in pediatric MS. Toleration against current second-line therapies has been shown in multiple sclerosis children. Oral agents have not been assessed in children MS patients. Although clinical trials in children are insufficient, immunomodulating managed children, experience a side effect similar to the adult MS patients. However, further prospective clinical studies, with large sample size and long follow-up are needed to distinguish the benefits and probable side effects of pediatric MS therapies.

Prevalence of multiple sclerosis in Iranian emigrants: review of the evidence.

Iran has the highest prevalence of multiple sclerosis (MS) in the Middle East and Asia. Rate of emigration has been significantly raised among Iranians and though, multiple studies have been published on prevalence of MS among Iranian emigrants. Here we systematically reviewed these publications. We performed a comprehensive literature search was performed on April 30, 2015 in data bases of MEDLINE, EMBASE, Scopus and Google Scholar for the terms 'multiple sclerosis', 'incidence', 'prevalence', 'epidemiology', 'migration', 'emigrant', 'immigrant', 'Iran', 'Parsis' and 'Persian'. Study location, prevalence day or period, and age of at disease onset were recorded for all the included publications. Nine publications from Sweden, Canada, Norway, UK, and India were included. Only three reported age-adjusted prevalence and six reported age of disease onset. MS prevalence among Iranian emigrants varied from 21 per 100,000 people in Bombay, India in 1985 to 433 per 100,000 people in British Columbia, Canada in 2012. Five studies reported the prevalence in the region of interest, ranging from 1.33 in Bombay, India to 240 in British Columbia, Canada. Five studies also reported the prevalence of MS in the population of the destination country, and in all of them, the prevalence of MS was higher in Iranian immigrants compared to native people. Prevalence studies performed in Iran and also on Iranian emigrants indicate roles for both genetic and environmental factors in MS susceptibility. Data might indicate that living in a high-risk area increases the susceptibility to MS.

Effects of prolonged fasting on fatigue and quality of life in patients with multiple sclerosis.

Fasting is one of the recommended worships of several great religions in the world. During the month of Ramadan, circadian rhythm and pattern of eating changes result in physiological, biochemical and hormonal changes in the body. Many Muslims with medical conditions ask their physicians about the feasibility and safety of fasting during Ramadan. In this study, we aim to assess the effect of Ramadan fasting on the quality of life and fatigue in multiple sclerosis (MS) patients. Relapsing-remitting MS (RRMS) patients according to McDonald's criteria who had mild disability (EDSS score ≤3) were included in this study. Fatigue and quality of life were were assessed using the validated Persian versions of modified fatigue impact scale (MFIS) and multiple sclerosis quality of life-54 (MSQOL-54) questionnaires, respectively. 218 patients (150 females and 68 males) were enrolled in our study. There was no statistically significant difference between the mean total score of MSIF before and after fasting (25.50 ± 13.81 versus 26.94 ± 16.65; p = 0.58). The mean physical health and mental health composites of quality of life increased significantly after fasting (p = 0.008 and p = 0.003 respectively). Despite the observed lack of favorable effects on fatigue, our results showed increased quality of life of MS patients once Ramadan has ended. Whether this is specifically related to Ramadan-related fasting deserves further testing in appropriately designed larger prospective clinical studies.

Epidemiology of neuromyelitis optica in the world: a systematic review and meta-analysis.

Background. Neuromyelitis optica (Devic's disease) is a severe autoimmune inflammatory disorder of the central nervous system. Epidemiological aspects of NMO have not been systemically reviewed. In this study we systematically reviewed and assessed the quality of studies reporting the incidence and/or prevalence of NMO across the world. Methods. A comprehensive literature search using MEDLINE, EMBASE, and Web of Science for the terms "Neuromyelitis optica," "devic disease," "incidence," "prevalence," and "epidemiology" was conducted on January 31, 2015. Study quality was assessed using an assessment tool based on recognized guidelines and designed specifically for this study. Results. A total of 216 studies were initially identified, with only 9 meeting the inclusion criteria. High level of heterogeneity amongst studies precluded a firm conclusion. Incidence data were found in four studies and ranged from 0.053 per 100,000 per year in Cuba to 0.4 in Southern Denmark. Prevalence was reported in all studies and ranged from 0.51 per 100,000 in Cuba to 4.4 in Southern Denmark. Conclusion. This review reveals the gaps that still exist in the epidemiological knowledge of NMO in the world. Published studies have different qualities and methodology precluding a robust conclusion. Future researches focusing on epidemiological features of NMO in different nations and different ethnic groups are needed.

Multiple sclerosis and hyperprolactinemia: a case-control study.

UNLABELLED: Multiple sclerosis (MS) is an autoimmune disease of central nervous system which is characterized with demyelination. Prolactin, synthesized in the anterior pituitary cells, has a role in maturation of immune cells, suggesting its possible implication in autoreactivity. The aim of the current study is to investigate the role of hyperprolactinemia in MS. Twenty-two MS patients with hyperprolactinemia diagnosed with pituitary adenoma and 66 MS patients without hyperprolactinemia were enrolled in our case-control study. They were matched with regard to age, gender, and MS subtypes. Patients with other concomitant autoimmune diseases and pregnancy were excluded. Statistical analyses were carried out using SPSS (SPSS statistic package, version 21.0.0) statistical software. The Pearson Chi-square test and the t test were used to determine whether there were any significant differences. The level of significance was set at p < 0.05. Greater value of relapse rate among hyperprolactinemic MS patients in comparison to non-hyperprolactinemic MS patients was statistically significant (p < 0.001). Statistically significant difference between the two groups in terms of EDSS was observed (case group vs. CONTROL: 1.3 vs. 1.9; p = 0.007). The correlation between MS duration and duration of hyperprolactinemia was significant in the case group (p < 0.05, R = 0.752). No statistically significant difference was found between two groups regarding duration of MS. This study suggested a protective role of prolactin in demyelinating procedure of MS.

Knowledge and attitude assessment of Iranian multiple sclerosis patients receiving interferon beta.

BACKGROUND: Multiple sclerosis (MS) patients permanently confronted with serious challenges from treatment regimen. Developing a new questionnaire in MS management, through evaluation of patients' perspectives and knowledge regarding treatment will help to identify the sources of tension, and to build a therapeutic alliance. We purposed to describe MS patients' understanding of their treatments. METHODS: About 425 completed and returned questionnaire were assessed of a total of 500 recruited MS patients. The knowledge of correct using interferon-beta (IFN-ß) and attitude toward medical care were assessed using self-reported questionnaires consisted of 25 items with validity of multidisciplinary panel and pre-testing on 20 patients. RESULTS: Knowledge about IFN-ß therapy was very low; however, attitude was at a high level. Female patients, self-injection ability, higher educational level, normal functional status, delay from the start of diagnostic workup to definite diagnosis, and being younger were related to a higher level of knowledge. Attitude was associated with functional status, family history of disease and the summary of knowledge variable. CONCLUSION: Developing educational interventions are needed for MS patients regarding to their low levels of knowledge.

Estimated prevalence and incidence of multiple sclerosis in Iran.

BACKGROUND: Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system and its epidemiology has changed in recent years. Previously, Iran was considered to have a low MS prevalence. In this study, we aimed to update the prevalence and incidence of MS in Iran. PATIENTS AND METHODS: This study was conducted based on the data derived from the new report of Iran's Ministry Of Health and Medical Education (MOHME) regarding the patients who have registered to obtain support for treatment in Iran till the end of 2013. RESULTS: Among the 42,200 registered patients, 32,477 were female and 9,723 were male (sex ratio: 3.34: 1), and 4,545 were diagnosed in 2013. This resulted in a prevalence of 54.51 and an incidence of 5.87 per 100,000. CONCLUSION: According to our study results, Iran has a medium-to-high prevalence rate of MS. According to the previous epidemiologic studies from Iran, it seems that the prevalence of MS significantly has increased during recent years. This rate is similar to what is seen in many western countries.

Parkinsonism associated with multiple sclerosis: A report of eight new cases and a review on the literature.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease that affects the central nervous system. Except tremor, other movement disorders such as Parkinsonism are less frequent in MS. However, some investigations have shown inflammatory and autoimmune aspects of Parkinson's disease. In this study, we report eight new cases of MS who present Parkinson's disease. METHODS: This retrospective population-based study was carried out on Isfahan MS society between April 2003 and July 2012. A total of 3792 patients with MS were surveyed for Parkinson's disease. Parkinson's disease was approved according to "UK Parkinson disease Brain Bank" criteria. Eligible cases were invited to have an interview with a neurologist. MRI was carried out according to the baseline. RESULTS: We identified eight patients (three men and five women) who present MS and Parkinson's disease. The mean (±SD) age of onset was 33.3 ± 6.5 (range: 24-42) years for MS and 39.5 ± 8.6 (range: 30-55) years for Parkinson's disease patients. In all patients, MS was preceded Parkinson's disease. Parkinson's disease was developed within mean duration of 6.1 ± 3.4 (range 2-13) years after MS. Focal lesions was shown in six cases, lesions of basal ganglia (BG) in four, lesions of the thalamus in two and lesions of mid-brain in five of cases. In four cases, Parkinsonism occurred before age 40 that is considered as Young-Onset Parkinson's disease. CONCLUSION: We reported eight patients with MS and Parkinson's disease. To the best of our knowledge, 34 cases of Parkinsonism associating with MS are reported so far. Parkinsonism is a movement disorder, defines as deep gray matter disorder which lead to dopamine deficiency in BG. Investigations have shown that MS could affect deep gray matter structures. Demyelinated lesions in MS and consequence axonal loss in BG and/or nigrostriatal pathway may be responsible for Parkinsonism manifestations in such cases.

Fatigue, depression, and physical impairment in multiple sclerosis.

BACKGROUND: Fatigue, depression, and physical impairment are common among multiple sclerosis (MS) patients. The aim of this study was to determine the relationship between depression, physical impairment, and fatigue in an Iranian MS cohort. METHODS: Fifty consecutive relapsing-remitting MS patients and 50 age- and sex-matched healthy controls (HCs) were recruited from Sina Rehabilitation Clinic, Tehran, Iran. The depression substance of Hospital Anxiety and Depression Scale (HADS), Expended Disability Status Scale, and Fatigue Severity Scale questionnaires were used to assess depression, physical impairment, and fatigue, respectively. RESULTS: This study included 38 (76%) females and 12 (24%) males in both patients and HC groups. The depression substance of the HADS in MS and HCs showed a mean value of 1.92 ± 0.80 and 1.17 ± 0.38, respectively (P < 0.001). Pearson's correlation analyses showed that in the MS group depression was associated with fatigue (r = 0.54, P = 0.01), but not with physical impairment (r = 0.16, p = 0.01), while fatigue was associated with both depression (r = 0.54, P = 0.01) and physical impairment (r = 0.36, P = 0.01). Depression in HCs group was also associated with fatigue (r -0.64, P = 0.01). CONCLUSION: Fatigue is associated with both depression and physical impairment, and an intervention in one of these conditions might improve others.