Reliability and validity of the Arabic version of brief international cognitive assessment for multiple sclerosis in Egyptian pediatric multiple sclerosis patients.

BACKGROUND & OBJECTIVES: About one-third of pediatric-onset MS (POMS) patients report cognitive impairment. This case-control study aimed to assess the reliability and validity of the Arabic version of the Brief International Cognitive Assessment for MS (BICAMS) in Egyptian POMS patients. METHODS: A case-control study was conducted on 30 POMS patients aged 9 to 17 years old and 30 healthy controls. Both groups underwent the following tests: neuropsychological testing using the BICAMS-validated Arabic version battery involving the Symbol Digit Modality Test (SDMT), California Verbal Learning Test 2nd edition (CVLT-II) and revised Brief Visuospatial Retention Test (BVRT-R). Test-retest data were obtained from MS patients and controls 2 weeks following the primary evaluation. Mean variances between both groups were evaluated, controlling for age, gender, and educational level. RESULTS: MS patients scored significantly lower on the SDMT, CVLT-II, and BVMT-R tests than healthy controls (P-value <0.001). Test-retest reliability was satisfactory for SDMT, CVLT-II total, and BVRT-R in MS patients and controls with r values of 0.73, 0.83, and 0.80, respectively. CONCLUSION: BICAMS is a feasible approach to cognitive screening in POMS and adults. The Arabic version of BICAMS is a reliable and valid tool for the cognitive assessment of pediatric MS patients in different clinical and research settings.

The risk of secondary progressive multiple sclerosis is geographically determined but modifiable.

Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk.

Long non-coding RNAs BACE1-AS and BC200 in multiple sclerosis and their relation to cognitive function: A gene expression analysis.

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS), and the dysregulation of synaptic plasticity is one of its direct causes. Long non-coding RNAs (lncRNAs) have been shown to play a role in synaptic plasticity, but their role in cognitive impairment in MS has not been fully explored. In this study, using quantitative real-time PCR, we examined the relative expression of two specific lncRNAs, BACE1-AS and BC200, in the serum of two cohorts of MS patients with and without cognitive impairment. Both lncRNAs were overexpressed in both cognitively impaired and non-cognitively impaired MS patients, with consistently higher levels in the cohort with cognitive impairment. We also found a strong positive correlation between the expression levels of these two lncRNAs. Notably, BACE1-AS was consistently higher in the remitting cases of both relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) groups than in the respective relapse cases of the same subtype, with the SPMS-Remitting group of cognitively impaired MS patients showing the highest expression of BACE1-AS among all MS groups. Additionally, we observed that the primary progressive MS (PPMS) group had the highest expression of BC200 in both cohorts of MS. Furthermore, we developed a model called Neuro_Lnc-2, which showed better diagnostic performance than either BACE1-AS or BC200 alone in predicting MS. Our findings suggest that these two lncRNAs may have a significant impact on the pathogenesis of the progressive types of MS and on the cognitive function of the patients. Future research is required to confirm these findings.

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

External validation of a clinical prediction model in multiple sclerosis.

BACKGROUND: Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS). OBJECTIVE: We aimed to validate a previously published predictive model of individual treatment response using a non-overlapping cohort from the Middle East. METHODS: We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously. RESULTS: The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%-96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%-91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%. CONCLUSION: The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.

Comprehensive assessment of facial paralysis based on facial animation units.

Quantitative grading and classification of the severity of facial paralysis (FP) are important for selecting the treatment plan and detecting subtle improvement that cannot be detected clinically. To date, none of the available FP grading systems have gained widespread clinical acceptance. The work presented here describes the development and testing of a system for FP grading and assessment which is part of a comprehensive evaluation system for FP. The system is based on the Kinect v2 hardware and the accompanying software SDK 2.0 in extracting the real time facial landmarks and facial animation units (FAUs). The aim of this paper is to describe the development and testing of the FP assessment phase (first phase) of a larger comprehensive evaluation system of FP. The system includes two phases; FP assessment and FP classification. A dataset of 375 records from 13 unilateral FP patients was compiled for this study. The FP assessment includes three separate modules. One module is the symmetry assessment of both facial sides at rest and while performing five voluntary facial movements. Another module is responsible for recognizing the facial movements. The last module assesses the performance of each facial movement for both sides of the face depending on the involved FAUs. The study validates that the FAUs captured using the Kinect sensor can be processed and used to develop an effective tool for the automatic evaluation of FP. The developed FP grading system provides a detailed quantitative report and has significant advantages over the existing grading scales. It is fast, easy to use, user-independent, low cost, quantitative, and automated and hence it is suitable to be used as a clinical tool.

Classification of facial paralysis based on machine learning techniques.

Facial paralysis (FP) is an inability to move facial muscles voluntarily, affecting daily activities. There is a need for quantitative assessment and severity level classification of FP to evaluate the condition. None of the available tools are widely accepted. A comprehensive FP evaluation system has been developed by the authors. The system extracts real-time facial animation units (FAUs) using the Kinect V2 sensor and includes both FP assessment and classification. This paper describes the development and testing of the FP classification phase. A dataset of 375 records from 13 unilateral FP patients and 1650 records from 50 control subjects was compiled. Artificial Intelligence and Machine Learning methods are used to classify seven FP categories: the normal case and three severity levels: mild, moderate, and severe for the left and right sides. For better prediction results (Accuracy = 96.8%, Sensitivity = 88.9% and Specificity = 99%), an ensemble learning classifier was developed rather than one weak classifier. The ensemble approach based on SVMs was proposed for the high-dimensional data to gather the advantages of stacking and bagging. To address the problem of an imbalanced dataset, a hybrid strategy combining three separate techniques was used. Model robustness and stability was evaluated using fivefold cross-validation. The results showed that the classifier is robust, stable and performs well for different train and test samples. The study demonstrates that FAUs acquired by the Kinect sensor can be used in classifying FP. The developed FP assessment and classification system provides a detailed quantitative report and has significant advantages over existing grading scales.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study.

BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

Impact of Ramadan fasting on disease activity in patients with multiple sclerosis: a multicenter study.

BACKGROUND: The safety of Ramadan fasting for Muslim patients suffering from multiple sclerosis (MS) is still a matter of debate. This work aimed to study the clinical course of MS during Ramadan fasting and to clarify the predictors of relapses and symptoms exacerbation. METHODS: This retrospective study included 153 Muslim patients with MS. Data related to the disease course before Ramadan were obtained from patients' files, whereas data related to the disease activity during Ramadan, were collected from patients over the two months following Ramadan. RESULTS: Patients with MS who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant longer disease duration compared to those who did not experience (P < 0.001, <0.001, 0.01 respectively). Also, patients who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant higher expanded disability status scale (EDSS) compared to those who did not experience (P <0.001, <0.001,0.01, respectively). The occurrence of relapses, exacerbation of symptoms and development of new symptoms during Ramadan, were significantly higher in patients who experienced relapses in the preceding year compared to those who did not (P= 0.002, 0.002, 0.01, respectively). Binary logistic regression revealed that each score elevation of EDSS increased the odds of relapse during Ramadan by 1.02 (P-value = 0.04). Also, each month's increase in disease duration increased the odds of relapse during Ramadan by 1.87 (P-value = 0.046). CONCLUSION: High EDSS and long disease duration are independent predictors of relapse during Ramadan.

Changes in migraine characteristics over 30 days of Ramadan fasting: A prospective study.

OBJECTIVE: To study Ramadan's effect on migraine from the start to the end of the month and the tolerability of patients with migraine to fasting. BACKGROUND: Fasting is a well-known trigger for migraine. Whether this effect on migraine is the same throughout the whole month, or whether it varies from the first to the last days of the month, has not been studied yet. METHODS: A prospective cohort observational study was carried out on persons with migraine who fasted from 24 April to 23 May during Ramadan 2020. Each patient was asked to fill out their headache diary starting from Shaaban (the month before Ramadan) to the end of Ramadan. The Ramadan diary was divided by 10 days each, by which the patient was asked to accurately describe their migraine attacks in terms of frequency, duration, and intensity by using the Visual Analog Scale. Migraine attacks during the first day of fasting were assessed separately. RESULTS: A total of 292 known persons with migraine from Egypt completed the study. Their median age was 33 years; 72/292 (24.7%) were male, and 220/292 (75.3%) were female. About 126/236 (53.4%) of the patients had migraine attacks on Ramadan's first day, most of them during fasting. The frequency of migraine attacks was significantly increased in Ramadan (median 4, interquartile range [IQR] 2-7) compared with Shaaban (median 3, IQR 1-6), p = 0.009. The number of attacks was significantly reduced in both the second (median 1, IQR 0-2.25) and the third 10 days of Ramadan (median 1, IQR 1-3) compared with the first 10 days (median 3, IQR 1-5) (p < 0.001 for each). CONCLUSION: Ramadan's potential exacerbating effect on the frequency of migraine attacks should be discussed with patients with migraine. This effect appears to be limited to the first 10 days of Ramadan and then subsides with successive days of fasting.

The MuSC-19 study: The Egyptian cohort.

OBJECTIVE: This study aimed to report the severity of COVID-19 in a cohort of Egyptian patients with multiple sclerosis (MS) with particular attention on the impact of disease modifying drugs (DMDs). METHODS AND STUDY POPULATION: We included 119 MS patients recruited from two centers, Ain-Shams university and Cairo university with confirmed or suspected COVID-19 during the period from May to September 2020 as a part of the MuSC-19 project. Univariate logistic regression was fitted to assess risk factors for severe COVID-19 (at least one outcome among hospitalization, ICU admission and death). RESULTS: Females were 77%, mean age was 34 years, mean duration of MS was 5.28 years, median EDSS was 3, most of the patients (83%) had RRMS, while 15% and 2% had respectively SPMS and PPMS. Only eleven patients (9% of study population) had a severe outcome and 3 patients (3%) died. Headache was the only symptom significantly associated with the severity of COVID-19 (OR=10.85, P = 0.001). There was no association between any of the DMDs and severe COVID-19 outcome. CONCLUSION: This study showed an acceptable safety profile of DMDs in Egyptian MS patients who developed COVID-19, as 91% of the cohort had a favorable outcome. Headache as a symptom associated with severe outcome in Egyptian patients' needs further validation.

SVM classification of facial functions based on facial landmarks and animation Units.

Quantitative assessment and classification of facial paralysis (FP) are essential for treatment selection and progress evaluation of the condition. As part of a comprehensive framework towards this goal, this study aims to classify five normal facial functions: smiling, eye closure, raising the eyebrows, blowing cheeks, and whistling as well as the rest state. 3D facial landmarks and facial animation units (FAUs) were obtained using the Kinect V2, a fast and cost-effective depth camera. These were used to compute the features used in a Support Vector Machine (SVM) classifier. A dataset of 1650 records from 50 normal subjects was compiled for this study. The performances of different SVM kernel models were tested with different feature groups. The best performance (Accuracy = 96.7%, Sensitivity = 90.2%, and Specificity = 98%) was found when using the RBF kernel model applied on just nine differences in FAUs. This research will be developed and extended to include FP classification.

Efficacy of core stability versus task oriented trainings on balance in ataxic persons with multiple sclerosis. A single blinded randomized controlled trial.

BACKGROUND: Balance and ataxic symptoms are commonly encountered in people with multiple sclerosis (PwMS). Many intervention approaches have been proposed to address balance in PwMS. The purpose of this study was to investigate the efficacy of adding core stability versus task oriented trainings on traditional approaches on balance in ataxic PwMS. METHODS: Forty five ataxic relapsing-remitting PwMS from both sexes were randomly assigned into three identical groups. Control group (CG) treated with conventional balance exercise program; study groups I (GI) and II (GII) received respectively additional training using core stability exercises and task oriented trainings. Outcome measures recorded pre and post study period included stability index (SI), anterior posterior stability index (APSI), and mediolateral stability index (MLSI) using Biodex stability system in addition to the Berg balance scale (BBS). RESULTS: Post treatment, the results indicated significant improvement in (SI) and (APSI) (p<0.05), and non-significant improvement (p>0.05) in (MLSI) and BBS in CG. In GI and GII there was a significant improvement in all balance measures (p<0.05). Comparison of post treatment results between groups indicated a significant improvement of GII compared to CG in all study measures, GI showed non- significant difference in all balance measures compared to the CG(P>0.05). CONCLUSION: In PwMS balance rehabilitation should be multimodal; core stability exercises and task-oriented training in addition to conventional balance training are effective to improve balance and should be considered as an essential part of the training program for balance rehabilitation in ataxic PwMS. Task-oriented training in addition to conventional balance rehabilitation seem to be a favorable approach.

The aquaporin4-IgG status and how it affects the clinical features and treatment response in NMOSD patients in Egypt.

BACKGROUND: In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking. OBJECTIVES: To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients. METHODS: Retrospective analysis of 70 NMOSD patients' records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018. RESULTS: Patients' mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01). CONCLUSION: Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.

Could SARS-CoV-2 herald a surge of multiple sclerosis?

During the current COVID-19 pandemic, many queries are raised regarding its nature, outcome, and sequelae. This letter raises the concern of potential impact on increasing the incidence of multiple sclerosis whose pathology involves a possible viral etiology. Besides, the potential neurotropism of the acute respiratory distress syndrome corona virus-2 (SARS-CoV-2), which is still not established, may raise concerns about the use of certain disease modifying therapies namely natalizumab.

Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

Managing Disease-Modifying Therapies and Breakthrough Activity in Multiple Sclerosis Patients During the COVID-19 Pandemic: Toward an Optimized Approach.

The emergence of the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health challenge of global concern since December 2019, when the virus was recognized in Wuhan, the capital city of Hubei province in China and epicenter of the COVID-19 epidemic. Given the novelty of COVID-19 and the lack of specific anti-virus therapies, the current management is essentially supportive. There is an absence of consensus on guidelines or treatment strategies for complex disorders such as multiple sclerosis (MS), in which the risk of infections is higher than in the general population. This is due to the overall impairment of the immune system typical of autoimmune diseases, in addition to accumulation of disabilities, and the iatrogenic effect generated by corticosteroids and the recommended disease-modifying therapies (DMTs). DMTs have different modes of action, but all modulate and interfere with the patient's immune response, thereby raising concerns about adverse effects, such as an increased susceptibility to infections. In this review, we analyze the evidence for use of DMTs during the current critical period and ratify an algorithmic approach for management to optimize care between keeping DMTs, with their infection hazards, or coming off them, with the risk of disease activation. We also provide an algorithmic approach to the management of breakthrough activity during the COVID-19 pandemic.

Interferon-Beta-Induced Headache in Patients with Multiple Sclerosis: Frequency and Characterization.

BACKGROUND: Studies have shown that interferon-beta (IFN-ß) treatment is associated with headaches in patients with multiple sclerosis (MS). Headaches can affect quality of life and overall function of patients with MS. We examined the frequency, relationships, patterns, and characteristics of headaches in response to IFN-ß in patients with relapsing-remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: This study was a prospective, longitudinal analysis with 1-year follow-up. The study comprised 796 patients with RRMS treated with IFN-ß (mean age 30.84±8.98 years) at 5 tertiary referral center outpatient clinics in Egypt between January 2015 and December 2017. Headaches were diagnosed according to the International Classification of Headache Disorders ICHD-3 (beta version), and data were collected through an interviewer-administered Arabic-language-validated questionnaire with an addendum specifically designed to investigate the temporal relationship between commencement of interferon treatment, and headache onset and characteristics. RESULTS: Two hundred seventy-six patients had pre-existing headaches, and 356 experienced de novo headaches. Of 122 patients who experienced headaches before IFN-ß treatment, 55 reported headaches that worsened following onset of IFN-ß treatment. In patients with post-IFN-ß headaches, 329 had headaches that persisted for >3 months, 51 had chronic headaches, and 278 had episodic headaches, and 216 of these patients required preventive therapies. Univariate analysis showed a >6- and an approximately 5-fold increased risk of headache among those treated with intramuscular (IM) INF-ß-1a (OR 6.51; 95% CI: 3.73-10.01; P-value <0.0001) and 44 µg of SC INF-ß-1a (OR 5.44; 95% CI: 3.15-9.37; P-value <0.0001), respectively, compared with that in patients who received 22 µg of SC INF-ß-1a. CONCLUSION: Interferon-ß therapy aggravated pre-existing headaches and caused primary headaches in patients with MS. Headache risk was greater following treatment with IM INF-ß-1a and 44 µg SC INF-ß-1a.

Micro-RNA-96 and interleukin-10 are independent biomarkers for multiple sclerosis activity.

BACKGROUND: Micro-RNAs (miRNAs) are evolving as biological markers for multiple sclerosis (MS) both in activity and remission. miR-96 is associated with remission, however, the exact mechanism through which it contributes to the anti-inflammatory pathway is not clear. OBJECTIVE: To study the expression of miR-96 and IL-10 (anti-inflammatory mediator) in relapsing remitting (RR) MS. SUBJECTS AND METHODS: A case control study including 32 RRMS patients from Kasr Al-Ainy MS clinic, Cairo University, Egypt, and 26 healthy controls (HC). Assessment of serum IL-10 by ELISA, and miR-96 via real time PCR was done during relapse and remission in patients, and in HC. RESULTS: IL-10 was higher in RRMS patients during remission and in HC compared with relapse (P ˂ 0.001). miR-96 expression was higher in RRMS patients during remission compared with relapse and HC, and was higher in HC than in relapse (P ˂ 0.001). IL-10 level in remission correlated positively with disease duration (r = 0.41; P = 0.02). Otherwise, no correlation was found between IL-10 and relapse number or EDSS (P>0.05). miR-96 in relapse negatively correlated with EDSS in relapse (r=-0.47; P=0.007), but no correlation was found with disease duration or relapse number, whereas, miR-96 in remission did not correlate with any clinical parameters (P>0.05). No correlation was found between IL-10 and miR-96 either in relapse or remission (P>0.05). CONCLUSION: IL-10 and miR-96 are associated with MS quiescence, however, the lack of a significant correlation between them implicates that the influence of miR-96 may be exhibited through some pathway other than IL-10.

Micro-RNA 18b and interleukin 17A profiles in relapsing remitting multiple sclerosis.

BACKGROUND: The involvement of micro RNAs (miRNAs) in multiple sclerosis (MS) has been recently explored. Up-regulated miRNAs may play critical roles in MS pathogenesis and may be used as a signature for MS. Besides, the role of inflammatory cytokines has been long established with recent focus on interleukin-17 (IL-17). OBJECTIVE: To evaluate the level of expression miR-18b in relation to IL-17A in relapsing remitting (RR) MS patients during relapse and remission SUBJECTS AND METHODS: Twenty-eight RRMS patients and 26 age and sex matched control subjects were included. Serum miR-18b was assessed by quantitative real-time PCR, and serum level of IL-17A was measured by ELISA. RESULTS: Serum miR-18b expression was higher in relapse compared with remission and with controls (24.8 ±â€¯21.91 vs 2.49 ±â€¯0.97 vs 1 ±â€¯0.36 respectively; P < 0.001). Serum IL-17Awas higher in MS patients during relapse than during remission and controls (8.49 ±â€¯1.26 vs 5.78 ±â€¯2.27 vs 4.18 ±â€¯2.13, respectively; P < 0.001). No correlations existed between miR-18 and IL-17 in MS patients during relapse (r = 0.35; P = 0.22) or remission (r = 0.340; P = 0.234). CONCLUSION: Upregulation of miR-18 during relapse in patients with RRMS points to a possible contribution to the pathogenesis of the inflammatory process in MS. The lack of a significant correlation between upregulated miR-18 and IL-17A implicates that the influence of miR-18 may be exhibited via another inflammatory pathway.