Multiple sclerosis was long considered a relatively rare entity in the Middle East, but research over the past 10 years and the publication of the Middle East North Africa Committee for Treatment and ...Research in Multiple Sclerosis guidelines for multiple sclerosis have allowed diagnosis and treatment to occur more efficiently. Most of the first and second-line disease-modifying therapies approved by the Food and Drug Administration and the European Medicine Agency are available in the Middle East. However, the availability of disease-modifying therapies is quite variable, with some countries having access to all multiple sclerosis disease-modifying therapies, while in others there is only one therapeutic option. Economic limitations remain a challenge for the management of multiple sclerosis, especially in countries of war. Moreover, the burden of multiple sclerosis treatment in Syrian and Palestinian refugees is likely high due to the non-availability of funds to cover the high cost of disease-modifying therapies.
Abstract Background Few published studies addressed real-world clinical experience with fingolimod especially in the Middle East region. Objective To review our clinical experience with fingolimod at ...a specialized academic MS center in Lebanon. Methods All patients treated with fingolimod at the MS Center between October 2011 and January 2015 were retrospectively identified. Results A total of 122 patients were included. The first dose observation was uneventful in 98.8% of patients. Annualized relapse rate decreased from 1.16 pre-treatment to 0.29 post-treatment representing a relative risk reduction of 75% (p < 0.0001). The proportion of patients with no new T2 or enhancing lesions was 66.3%. Seventy-six (62.3%) patients experienced adverse events with lymphopenia, increase liver enzymes, urinary tract infections and fatigue being the most common. Conclusion Our cohort confirms the effectiveness and safety of fingolimod in a real world setting.
BACKGROUND AND PURPOSE—Low ankle-brachial index (ABI) identifies a stroke subgroup with high risk of recurrent stroke, cardiovascular events, and death. However, limited data exist on the ...relationship between low ABI and stroke in low and middle-income countries. Therefore, we evaluated the prevalence of ABI ≤0.90 (which is diagnostic of peripheral artery disease) in nonembolic stroke patients or transient ischemic attack and assessed the correlation of low ABI with stroke risk, factors, and recurrent vascular events and death.
METHODS—Patients ≥45 years with acute transient ischemic attack or minor ischemic strokes were recruited consecutively from over 17 low-income and middle-income countries (Latin America 1543 patients, Middle East 1041 patients, North Africa 834 patients, and South Africa 217 patients). The ABI measurement was performed at a single visit. Stroke recurrence and risk of new vascular events were assessed after 24 months of follow-up.
RESULTS—Among 3487 enrolled patients, abnormal ABI (<0.9) was present in 22.3 %. Patients with an ABI of ≤0.9 were more likely (P<0.05) to be male, older, and have a history of peripheral artery disease, hypertension, and diabetes mellitus. During 2-year follow-up, the rate of major cardiovascular event was higher in patients with ABI <0.9 than those with ABI ≥0.9 (Kaplan-Meier estimates, 22.5%; 95% CI, 19.6–25.8 versus 13.7%; 21.4–15.1; P<0.001), and when ABI was categorized into 4 groups (≤0.6; 95% CI, 0.6–0.9; 0.9–1; 1–1.4), the rate of major cardiovascular event was higher in those with ABI ≤0.6 than the other groups (Kaplan-Meier estimates, 32.6%; 95% CI, 21.0–48.3 for ABI≤0.6 versus 21.7%; 95% CI, 18.8–25.0 for ABI 0.6–0.9 versus 14.3%; 95% CI, 12.4–16.6 for ABI 0.9–1 versus 13.3%; 95% CI, 11.6–15.2 for ABI 1–1.4; P<0.001).
CONCLUSIONS—Among patients with nonembolic ischemic stroke or transient ischemic attack, those with low ABI had a higher rate of vascular events and death in this population. Screening for ABI in stroke patients may help identify patients at high risk of future events.
Background:
Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.
Objective:
The aim of this study was to investigate ...long-term disability outcomes in patients with early cerebellar and brainstem symptoms.
Methods:
This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores.
Results:
The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk.
Conclusion:
Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
We report a case of relapsing remitting multiple sclerosis (RRMS) with severe rebound syndrome 12weeks following discontinuation of teriflunomide therapy. The patient developed severe clinical ...relapses with significant increase in the number of brain and spine magnetic resonance imaging (MRI) lesions. She responded well to intravenous and oral steroids and was later maintained on rituximab.
•Fingolimod is associated with different infections.•Skin wart infections with fingolimod have not been previously reported.•We describe five cases of skin warts in MS patients treated with ...fingolimod.•The overall incidence of warts infection during fingolimod therapy was 2.2%.•No cases of skin warts could be detected in a control group of interferons.
Fingolimod is associated with different infections including lower respiratory tract, herpes virus, cryptococcal meningitis, histoplasmosis, progressive multifocal leukoencephalopathy, atypical mycobacterial infections, kaposi sarcoma and reactivation of hepatitis c.
To describe five cases of skin warts in MS patients treated with fingolimod at the American University of Beirut Medical Center (AUBMC) MS center (MSC).
We reviewed all MS patients treated with fingolimod at our MSC and identified patients who developed skin warts during treatment. We also reviewed a control group of patients treated with different interferons matched for age and sex.
Of 220 patients treated with fingolimod at our MSC, 5 (2.2%) developed skin warts. In 220 patients treated with different interferons and matched for age and sex, no cases of skin warts could be detected.
In conclusion, we report five patients who developed skin warts during fingolimod therapy, especially HPV-related, for an overall incidence of 2.2%. Larger cohorts are needed to confirm this proposed higher susceptibility of fingolimod-treated patients to HPV infections.
•In our study, the relapse rate during pregnancy in MS patients was assessed.•The relapse rate in fingolimod and natalizumab treated patients was high.•Longer washout period of therapies was ...associated with higher relapse risk.•Patients on high efficacy therapies should be counseled on the updated relapse risk.
Relapse rate in women with Multiple Sclerosis (MS) is reduced during pregnancy especially in the third trimester according to the previous studies.
To measure the annual relapse rate (ARR) in women with MS during pregnancy.
A retrospective study was conducted using prospectively collected data from two MS registries in Kuwait and Lebanon. Demographics, clinical characteristics including relapses, disease modifying therapies (DMTs) and their washout periods were extracted. The annual relapse rates pre and post pregnancies were compared and the relationship between relapses and prior use of different DMTs was assessed.
Data of 164 pregnancies (132 MS patients) was reviewed. Mean age and disease duration at the time of pregnancy confirmation were 32.4 ± 5.3 and 7.8 ± 4.7 years respectively. Most patients (91.7%; n = 121) were on DMTs in the year prior to pregnancy. The pre-pregnancy ARR was 0.10 (95% CI: 0.04 – 0.13), which increased to 0.20 (95% CI: 0.13– 0.29) during pregnancy. Most relapses occurred either during the 1st (ARR = 0.24; 95% CI: 0.12 – 0.44) or 3rd (ARR = 0.32; 95%CI: 0.17 – 0.53) trimesters. Fingolimod (31.8%) and natalizumab (22.7%) were the most commonly prescribed DMTs in patients who sustained relapses during pregnancy. The mean washout period was significantly longer among subjects with relapses (9.3 ± 6.6 vs. 2.5 ± 3.9; p < 0.001) than those of without relapses.
Relapse rate during pregnancy was higher than previous studies conducted in patients on platform therapies or untreated. Longer washout period prior to conception was associated with increased relapses especially in fingolimod and natalizumab treated patients.
Purpose
Gadolinium-based contrast agent (GBCA) effect on automated segmentation algorithms of subcortical gray matter (GM) is not fully known. The aim of this study is to determine gadolinium effect ...on the segmentation of the thalamus and whole brain tissue using different automated segmentation techniques.
Methods
Eighty-four multiple sclerosis (MS) patients underwent an MRI acquisition of two 3DT1-weighted sequences with and without gadolinium injection among which 10 were excluded after image quality check. Manual thalamic segmentation considered as gold standard was performed on unenhanced T1 images. volBrain and FSL-Anat were used to automatically segment the thalamus on both enhanced and unenhanced T1 and the degree of similitude (DICE) values were compared between manual and automatic segmentations. Whole brain tissue segmentation (GM, white matter (WM), and lateral ventricles (LV)) was also performed using SIENAX. A paired samples
t
test was applied to test the significance of DICE value differences between the thalamic manual and automatic segmentations of both enhanced and unenhanced T1 images.
Results
Significant differences (FSL-Anat 1.474%
p
< 0.001 and volBrain 1.990%
p
< 0.001) in DICE between thalamic manual and automatic segmentations on both enhanced and unenhanced images were observed. Automatic tissue segmentation showed a mean DICE of 81.5%, with LV having the lowest DICE value (74.2%). When compared to tissue segmentations, automatic thalamic segmentations by FSL-Anat or volBrain demonstrated a higher degree of similitude (FSL-Anat = 91.7% and volBrain = 90.7%).
Conclusion
Gadolinium has a significant effect on subcortical GM segmentation. Although significant, the observed subtle changes could be considered acceptable when used for region-based analysis in perfusion or diffusion imaging.
Abstract Objectives To estimate JCV seroprevalence and risk of seroconversion against JCV among MS patients in the Middle East. Methods This multicenter study was conducted by implementing a ...cross-sectional design to assess JCV seroprevalence, and a longitudinal design to assess the risk of JCV seroconversion. Multivariable logistic and Poisson regression analyses were used to assess the relationship between clinical variables and JCV seropositivity and risk of seroconversion. Results Of 581 MS patients, 64.9% patients were females. Mean age and mean disease duration were 33.9 and 8.4 years respectively. JCV seroprevalence was 48.7%. Male gender ( p = 0.002), age at onset ( p = 0.001) and disease duration of 20 or more years ( p = 0.007) were significantly associated with JCV seropositivity. Among patients (n = 125), followed longitudinally, the risk of JCV seroconversion was 17.6% (95% CI: 11.4%–25.4%) during a median follow-up of 18 months. The proportion of seroreverted and pseudoconverted patients was 4% and 3.2% respectively. Conclusions JCV seroprevalence among MS patients in the Middle East was lower than international figures. Male gender, age at onset and disease duration were significantly associated with JCV seropositivity. Risk of JCV seroconversion was higher than previously reported figures. Observed JCV sero-reversion or pseudo-conversion entail watchful period before embarking on a clinical decision.
The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ...ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.
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