V. Shaygannejad
Isfahan neuroscience research center
Department of Neurology

Author Of 7 Presentations

 On-Demand Program
Biostatistical Methods Poster Presentation

P0018 - Variability of the response to immunotherapy among sub-groups of patients with multiple sclerosis (ID 1239)

Speakers
Authors
Presentation Number
P0018
Presentation Topic
Biostatistical Methods

Abstract

Background

Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited.

Objectives

To assess whether patients’ response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype.

Methods

Using the international MSBase registry, we selected patients with MS followed for ≥1 year, with ≥3 visits, ≥1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity.

Results

Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively].

Conclusions

DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. In general, the effectiveness of DMTs was most pronounced in subgroups with shorter MS duration, lower EDSS, lower relapse rate and relapsing MS phenotype.

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Comorbidities Poster Presentation

P0489 - Relationship between comorbidities and health-related quality of life in patients with multiple sclerosis (ID 915)

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Authors
Presentation Number
P0489
Presentation Topic
Comorbidities

Abstract

Background

Multiple sclerosis (MS) patients have reduced health-related quality of life (HRQoL) compared with those without MS in the same age group. The association between HRQoL and comorbidity has received considerable attention in the recent years, but limited studies have attempted to investigate the effect of comorbidities on HRQoL in MS patients.

Objectives

Our aim was to study the association between comorbidity and health-related quality of life in patients with multple sclerosis.

Methods

This cross-sectional study was conducted from July 10, 2018 to October 25, 2019. A total of 976 MS patients who visited MS clinic of Kashani Hospital were included in the study. Comorbidities were assessed through chart review. The 36-Item Short Form Survey (SF-36) was used to assess quality of life. The SF-36 results are presented in two categories of physical component summary (PCS) and mental component summary (MCS). We firstly evaluated the relation between any physical or mental comrbidity and HRQoL. Then, the association between all physical, psychiatric, or autoimmune comorbidities and HRQoL were investigated. Generalized linear model was applied to evaluate the relation between comorbidities and QOL (dependent variable), which were adjusted for sex, age, first and current EDSS and MS type.

Results

The mean PCS and MCS score were 44.81 (10.71) and 43.09 (11.13), respectively. Patients with epilepsy demonstrated less PCS score (B=-4.390; p=0.003) compared to those without epilepsy. Also, history of coronary heart disease and eye disorders have association with lower PCS, respectively with (B=-9.204; p=0.032) and (B=-11.43; p=0.008). The results showed that the women who were diagnosed with ovarian failure had lower level of MCS (B=-6.148; p=0.047). Furthermore, MCS (B=-7.862; p=0.015) was lower in women with polycystic ovary syndrome (PCO) compared to those without PCO. Regarding psychiatric comorbidities, we observed a significant association between OCD (B=-2.300; p=0.005), MDD (B=-2.373; p=0.013) and BPD (B=-5.398; p=0.001) with PCS, but not for GAD. Finally, OCD (B=-2.783; p=0.009) and MDD (B=-4.450; p<0.001) were associated with lower MCS in patients with MS. All physical comorbidities associated with less PCS (B=-1.592; p=0.005) and MCS (B=-1.943; p=0.009). Also, all psychological comorbidity have association with less PCS (B=-2.713; p<0.001) and MCS (B=-3.829; p<0.001). However, there was no association between the autoimmune comorbidities with PCS or MCS.

Conclusions

Our results show that both physical and psychiatric comorbidities associated with reduced quality of life in MS patients.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0700 - Clinical characteristics of neuromyelitis optica spectrum disorder and multiple sclerosis in Iranian pediatric patients (ID 552)

Speakers
Authors
Presentation Number
P0700
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Patients with Neuromyelitis optica spectrum disorder (NMOSD) and Multiple sclerosis (MS) usually experience first symptoms between 20 to 40 years of age. However, the onset of these disease rarely can occur in pediatrics population. Few data are available for patients with pediatric onset of NMOSD (PO-NMOSD) and MS (POMS).

Objectives

To survive the clinical characteristics, outcome, and predictive factors of disability in PO-NMOSD, and compared to patients with POMS.

Methods

This retrospective follow up study was performed evaluating 18 patients with PO-NMOSD and 144 PMS patients presenting at MS clinic, Kashani Hospital, affiliated to the Isfahan University of Medical Sciences, Isfahan, Iran. All cases were ascertained and diagnosed by a neurologist with subspecialty training in MS and NMOSD.

Results

In PO-NMOSD group, female to male ratio was 8.0:1; the mean age of onset was 14.77±2.23; age at last visit was 21.06±5.42; and median (IQR) follow-up was 6.0 (3.0, 11.0). The mean of first and last EDSS were 2.47±1.16 and 2.11±2.01; twelve (66.6%) patients had relapsing course; the median of first inter-attack was 3.0 (1.0, 4.0); and a total of 38 attacks (2.11 attack per patient) were recorded. Up to now, five (27.8%) patients reach EDSS ≥3. Three patients received azathioprine and other were treated by rituximab. For individuals with POMS, female/male ratio was 3.5:1; the mean age of onset was 14.84±2.35; age at last visit was 24.08±7.29; and median follow-up was 8.0 (4.2, 14.0). The mean of first and last EDSS were 1.68±1.20 and 1.44±1.85; no patient had primary progressive course and 20 (13.8%) patients converted to secondary progressive course; the median of first inter-attack interval was 2.0 (1.0, 4.0); and a total of 317 attacks (2.20 attacks per patient) were recorded. Until now, 34 (23.6%) patients reach EDSS ≥3. Most patients received beta interferon (47), fingolimod (23), and rituximab (23). There was statistically significant difference between the groups in the term of first EDSS score (p=0.019). In both groups, multivariate analysis shows significant association between the age at last visit, firs EDSS, disease duration with higher EDSS score at last appointment. The survival curves showed that PO-NMOSD patients reach to EDSS ≥3 earlier than POMS, though the difference was not statistically significant.

Conclusions

Patients with pediatric onset NMOSD and MS show specific features and prognosis, which should be taken in consideration for the diagnosis and treatment.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0716 - Fall frequency and risk factors in patients with neuromyelitis optica spectrum disorder (ID 547)

Speakers
Authors
Presentation Number
P0716
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune chronic disease in the central nervous system (CNS). Some symptoms of NMOSD such as vision loss, sensory loss, weakness, pain, bladder and bowel incontinence, and spasm are in constant with fall risk factors that have been established in general population and other neurological diseases. So, we hypothesized that the frequency of fall in NMOSD patients could be higher than general population.

Objectives

Evaluation of falls frequency and its risk factors in patients with neuromyelistis optica spectrum disorder, and compared to healthy individuals

Methods

Ninety-five NMOSD patients and 100 healthy controls (HC) participated in this cross-sectional study. Participants self-reported fall history including number of falls, rate and type of injury over the last six months. Individual with two or more falls was considered as faller. Subjects were assessed with questionnaires for severity of pain (brief pain inventory) and fatigue (fatigue severity score), and were examined for severity of disease (Expanded Disability Status Scale [EDSS]), cognition function (mini-mental state examination), and balance (berg balance score). We also obtained demographic and other clinical information including age, sex, education level, body mass index (BMI), disease duration, and brain MRI findings.

Results

A total of 58 (61.1%) NMOSD patients and 35 (35.0%) healthy individuals reported at least one fall, with 33 (34.7%) of NMOSD and 15 (15.0%) of healthy participants had two or more falls. The risk to being a faller in NMOSD was significantly higher than HC (adjusted OR=2.497; 95%CI: 1.218, 5.120; p=0.013). On univariate model, EDSS score, disease duration, fatigue severity, pain score, and berg balance score were risk factors for falling. On multivariate model, EDSS score (OR=14.41; 95%CI: 2.108, 98.56; p=0.007), pain severity score (OR=2.646; 95%CI: 1.224, 5.719; p=0.013), and severity of fatigue (OR=1.170; 95%CI: 1.027, 1.332; p=0.018) had association with fall in NMOSD patients. Model performance was further assessed using analysis of the ROC curve. The area under the curve was 0.975 (95% CI: 0.947, 1.000). Using Youden index, the optimal cut-off value of the model was determined to be 0.3439, with sensitivity and specificity at this point being 0.880 (95% CI: 0.687, 0.974) and 0.951 (95% CI: 0.863, 0.989), respectively.

Conclusions

Our findings suggested that NMOSD is a risk factor for falling. Further longitudinal study is needed to fully understand the implications of fall in NMOSD.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0717 - Frequency of comorbidities in Neuromyelitis Optica spectrum disorder (ID 459)

Speakers
Authors
Presentation Number
P0717
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Comorbidity may influence clinical aspects of neuromyelitis optica spectrum disorder (NMOSD). However, there is little knowledge regarding the interaction between comorbidities and NMOSD.

Objectives

We conducted this study to estimate the prevalence of comorbidities in NMOSD patients and assessed their association with disease outcomes.

Methods

This retrospective study assessed records of patients ( interview and medical report abstraction) from 2008 to 2019, categorizing comorbidities into three groups: somatic, psychiatric and autoimmune. We also evaluated the smoking status and BMI as health factors. Severity of disease was evaluated by the Expanded Disability Status Scale (EDSS), progression index (PI) and annualized relapse rate. The frequency of comorbidities was compared between anti-aquaporin 4 antibody (AQP4-IgG) seropositive and matched seronegative patients. Unadjusted and adjusted regression analysis were performed to assess the association between disease outcomes with comorbidities. To compare the frequency of comorbidities between AQP4-IgG seropostive and seronegative patients, we performed propensity score matching (PSM)

Results

A total of 115 NMOSD patients were enrolled. Fifty-five (47.8%) patients reported at least one comorbidity. In total, 69 comorbidities were found, of which 44 occurred prior to NMOSD onset: 43 somatic, 22 psychiatric and four autoimmune entities. The most common comorbidities were migraine 11/115 (9.6%), anxiety disorders 11/115 (9.6%), major depression disorder n=9 (7.8%), iron deficiency anemia 9/115 (7.8%) and non-autoimmune hypothyroidism 8/115 (7.0%). Two patients reported cancer (breast cancer and pituitary adenoma ) Autoimmune conditions were present in four cases: three patients with SLE (2.6%) and one patient with Sjogren’s syndrome (SS). Thirty-six (31.3%) patients were underweight and 19 (16.5%) were overweight with no obese patients (the mean BMI in the whole group: 20.42±3.64). There were 14 (12.1%) ever smokers in the study cohort with the mean of number of packs-years of 11.58±14.95. Psychiatric comorbidities associated with PI in unadjusted (OR=0.649, 95% CI=0.120, 1.178, P=0.017) and adjusted models (OR=0.506, 95% CI=0.082, 0.930, P=0.020). After stratification for AQP4-IgG no significant difference in frequency of comorbidities and outcomes were observed.

Conclusions

Our results showed that half the patients had comorbidities, suggesting screening for comorbidity as part of NMOSD care.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0750 - Relation between helicobacter pylori infection and double seronegative neuromyelitis optica spectrum disorder (ID 551)

Speakers
Authors
Presentation Number
P0750
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinative disease in central nervous system. Different infectious agents’- bacteria, viruses and parasites, including the common flora- have a causal or protective role in NMOSD. Previous studies showed helicobacter pylori (H. pylori) was more common in optico-spinal multiple sclerosis and seropositive NMOSD patients compared to healthy individuals. However, their finding regarding difference between AQP4-IgG negative NMOSD and controls was different compared to seropositive patients. It has been hypothesized that H. pylori infection isn’t risk factor for developing of AQP4-Ab seronegative NMOSD.

Objectives

We conducted this study to survey association between Helicobacter pylori infection and double seronegative NMOSD patients.

Methods

We studied NMOSD patients were visited outpatient MS/NMOSD clinic of Kashani Hospital, affiliated to Isfahan University of Medical Sciences, Isfahan, Iran from October 2017 to May 2019. NMOSD patients with seronegative antibody against AQP4 and Myelin Oligodendrocyte Glycoprotein (MOG) in cell-based method were included in the study. Also, age and sex healthy control (HC) group comprised from the general population were enrolled. Demographic (age and sex) and clinical characteristics (EDSS score, disease duration, annualized relapse rate [ARR], and disease modifying therapies [DMTs] exposure) were recorded. We determined the seroprevalence of IgG and IgM antibodies against H. pylori. Association of seropositive IgG and IgM Ab against H. pylori with demographic and clinical features were assessed.

Results

A total of 35 NMOSD patients and 37 healthy controls were enrolled in the study. For NMOSD patients, mean age was 36.63±9.34; mean of disease duration was 6.33±3.10; mean of EDSS score was 1.54±1.19; and ARR was 0.54±0.29. The frequency of IgG and IgM Ab H. pylori seropositivity in NMOSD patients was 22.9% and 40.0%, respectively. Among HC, 11 (29.7%) and 20 (54.1%) were positive for IgG and IgM Ab H. pylori. Although the frequency of IgG and IgM Ab H. pylori seropositivity in HC were higher than NMOSD patients, these differences weren’t statistically significant. No clinical variables associated with H. pylori IgG and IgM seropositivity.

Conclusions

These finding show there is no possible relation between H. pylori infection and double seronegative NMOSD. Therefore it may be considered that non-specific inflammatory pathways alone cannot elucidate relation of double seronegative NMOSD with H. pylori infection.

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Observational Studies Poster Presentation

P0862 - Disability accrual in primary-progressive & secondary-progressive multiple sclerosis (ID 1232)

Speakers
Authors
Presentation Number
P0862
Presentation Topic
Observational Studies

Abstract

Background

Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS.

Objectives

We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016).

Methods

Inclusion required adult-onset progressive MS; ≥ 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS ≤ 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if ≥ 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over ≥ 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS ≥ 7 (wheelchair required) was assessed (Kaplan-Meier).

Results

5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 ± 10.2, vs. 41.5 ± 10.7 [mean ± SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78–0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98–0.99); and higher in males (1.18; 1.12–1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71–0.87) but similar for PPMS-A (1.01; 0.93–1.10) and SPMS-N (0.94; 0.85–1.05). Sensitivity analyses corroborated these results. However, patients with SPMS-A reached EDSS ≥ 7 at younger ages (cumulative probability 30% by 57, vs. 64–66 for SPMS-N, PPMS-A, PPMS-N).

Conclusions

Progressive phase onset is later in SPMS than PPMS. Hazard of disability accrual during the progressive phase is lower in SPMS than PPMS. However, patients with SPMS-A reach wheelchair requirement younger than other progressive phenotypes, reflecting earlier progression onset versus SPMS-N, and greater disability at onset versus PPMS

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