Prevalence of primary headaches in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system. It is characterized by symptoms such as visual disturbances, paresis with spasticity, paresthesia, numbness, and fatigue. However, several studies have shown a high prevalence of headaches in individuals with MS. Migraine and tension-type headaches are the most frequent types of headaches experienced by those with MS. Additionally, the role of MS disease-modifying agents must be considered. These agents have different modes of action and side effect profiles, and their use may sometimes trigger headaches in patients with MS. OBJECTIVES: This study aimed to explore the prevalence and clinical characteristics of primary headaches in MS patients. The relationship between headache and clinical features of MS (Course of MS, duration, EDSS, brain imaging and DMD) are also investigated. SUBJECTS AND METHODS: Two hundred and eighty-one MS patients diagnosed according to according to the 2017 revisions to the McDonald Criteria were included in the study. Data was collected from the MS unit medical records and from the interview with the patients. Patients with reported headaches are asked to recall their headache characteristics and patterns using an interviewer administered Arabic language-structured validated questionnaire. RESULTS: The median age of patients was 33 years old, with a range of 22-55. Tension-type headache (TTH) was more common in males, patients with more severe disability (EDSS ≥ 3), and those with SPMS and PPMS phenotypes. Additionally, patients on rituximab or cyclophosphamide therapy were more likely to have TTH. On the other hand, females, patients with milder disability (EDSS < 3), and those with RRMS phenotype were more likely to have migraine. This was also true for patients with MRI lesions involving the periaqueductal gray, and those receiving INF or fingolimod (P < 0.05). Periaqueductal gray matter lesions were found in the MRI of 48 patients (40 %) who experienced headaches on more than 10 days per month. Sensorimotor lesions in the brain were found in 55 patients (53.4 %) with severe headaches (p-value < 0.001). Interferons were associated with an increased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 2.84, 3.72; relative risk: 1.63, 2.04; p-value = 0.03, < 0.001, respectively). On the other hand, rituximab was associated with a decreased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 0.04, 0.09; relative risk: 0.11, 0.18; p-value = < 0.001, < 0.001, respectively). CONCLUSION: Primary headaches are a common occurrence in patients with MS. Migraines and tension-type headaches (TTH) are among the most prevalent types. It has been observed that interferon can exacerbate preexisting headaches and even cause new ones. Additionally, the location of MS plaques may play a role in the frequency and severity of headaches.

New algorithmic approach for easier and faster extended disability status scale calculation.

Background: The traditional paper and pencil method for EDSS calculation (pEDSS) is the cornerstone of multiple sclerosis practice; however, it requires an expert for an accurate calculation, and it takes a lot of time to perform the function scores. A new algorithmic approach (aEDSS) has been developed for easier and faster assessment. Objective: To determine if using aEDSS can achieve good inter-rater agreement and save time compared to pEDSS. Subjects and methods: This study was conducted on 200 MS patients; EDSS was performed twice for each patient by two neurologists on the same day; one used the pEDSS, and the other used the aEDSS in a random order to test the inter-rater agreement regarding functional system scores and the final EDSS score and to detect the difference in the time needed for calculation between both methods. Results: The new algorithmic approach achieved excellent agreement with the traditional method (Kappa > 0.81) with a shorter calculation time (16 ± 2.67 min for aEDSS vs 31 ± 4.3 min for pEDSS, P < 0.0001). Conclusion: The new algorithmic approach could represent a suitable alternative to the traditional method, making EDSS calculation easier and faster.

Sensitivity and Specificity of Central Vein Sign as a Diagnostic Biomarker in Egyptian Patients with Multiple Sclerosis.

Purpose: Magnetic resonance imaging (MRI) findings in multiple sclerosis (MS) overlap with numerous MS mimics. The central vein sign (CVS) can help to differentiate MS from other mimics. This study aimed to determine the value of CVS as a diagnostic biomarker for distinguishing MS from its mimics. Patients and Methods: Patients were prospectively recruited into two groups: a typical clinical (TC) MS presentation with an atypical MRI for MS and an atypical clinical (ATC) MS presentation with a typical MRI for MS. Patients underwent a 1.5T MRI brain scan with a T2*-weighted gradient-echo sequence. The presence of the central vein was assessed by a radiologist blinded to patients' clinical presentation. The MS consultant made the final diagnosis without reviewing the T2*-weighted gradient-echo sequence or the CVS analysis results. Results: Forty-two patients were included. Ten (40%) out of 25 TC patients were diagnosed with clinically definite MS (CDMS), with a mean percentage of CV-positive lesions of 65.5% among CDMS patients. Four (23.5%) out of 17 ATC patients were diagnosed with CDMS with a mean CV-positive lesions percentage of 68.25% among CDMS patients. TC patients who were not diagnosed as CDMS had a mean CV-positive lesions percentage of 10.13%, while ATC patients who were not diagnosed as CDMS had a mean CV-positive lesions percentage of 16.38%. The CVS showed 85.7% sensitivity and 100% specificity (95% confidence interval: 0.919-1.018) for diagnosis of MS at a cut off value of 45% (p < 0.001). The percentage of CV-positive lesions was significantly higher in oligoclonal bands (OCBs) positive patients compared to OCBs negative patients (p < 0.001) and those with spinal cord lesions compared to patients with no spinal cord lesions (p = 0.017). Conclusion: The CVS has 85.7% sensitivity and 100% specificity for the diagnosis of MS at a cutoff value of 45%.

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.

Clinical and molecular characterization of Unverricht-Lundborg disease among Egyptian patients.

BACKGROUND AND PURPOSE: Unverricht-Lundborg disease (ULD) is a common type of progressive myoclonic epilepsy (PME). It is caused mostly by biallelic dodecamer repeat expansions in the promoter region of CSTB gene. Despite highly prevalent in the Mediterranean countries, no studies have been reported from Egypt. This article study the presence of CSTB gene mutations among Egyptian patients clinically suspected with ULD, and describes the clinical and genetic characteristics of those with confirmed gene mutation. METHODS: Medical records of patients following up in two specialized epilepsy clinics in Cairo, Egypt were retrospectively reviewed. Twenty patients who belonged to 13 unrelated families were provisionally diagnosed with ULD based on the clinical presentation. Genetic testing was done. Clinical characteristics, demographic data and EEG findings were documented. RESULTS: Genetic studies confirmed the presence of the CSTB dodecamer repeat expansion in 14 patients from 8 families (frequency 70 %). The mean duration of the follow-up was 5 years. Male to female distribution was 1:1 with a mean age of onset 9.7 years. Consanguinity was noted in 4 families. Eight patients had their first seizure between the age of 10 and 20 years. Myoclonic jerks ranged in severity from mild in three unrelated patients to severe in one. Only 3 had cognitive impairment. CONCLUSION: Our study confirms the presence of CSTB mutation among Egyptian patients suspected with ULD. There was no clear phenotype-genotype correlation among the studied group of patients. In addition, we noticed variable inter and intra familial severity among patients from the same family.

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.

Glutamate and Nitric Oxide as biomarkers for disease activity in patients with multiple sclerosis.

BACKGROUND: Despite multiple diagnostic tests, multiple sclerosis (MS) remains a clinical diagnosis with supportive paraclinical evidence. OBJECTIVE: To measure glutamate and nitric oxide serum levels in MS patients during and in between relapses to assess their potential role as biomarkers of disease activity and relapses. SUBJECTS AND METHODS: This cross sectional study was carried out on 70 MS patients and 40 age and sex matched apparently healthy controls. MS patients were divided into 2 groups; group 1 that included thirty MS patients without history of relapse within the last 3 months prior to recruitment and group 2 that included forty MS patients with history of relapse within the last 30 day prior to recruitment. RESULTS: Serum glutamate was significantly higher in group 2 (24.67 ±â€¯9.58 µg/ml) compared to group 1(12.5 ±â€¯4.9 µg/ml) (P value < 0.0001) and apparently healthy controls (3.5 ±â€¯1.3 µg/ml) (P value < 0.0001). Serum nitric oxide was significantly higher in group 2 (84.87 ±â€¯29.6 nmol/µl) than group 1 (41.99 ±â€¯24.2 nmol/µl) (P value < 0.0001) and apparently healthy controls (12.03 ±â€¯3.59 nmol/µl) (P value < 0.0001). Cutoff values of 17.5 µg/ml for glutamate and 75.2 nmol/µl for nitric oxide were found to predict occurrence of a relapse (sensitivity = 70% and 72.5% and specificity= 90% and 93.3% respectively). CONCLUSION: Serum glutamate and nitric oxide can be potential easily-accessible biomarkers of disease activity and relapses in MS patients.

Cognitive and physical disability in Egyptian patients with multiple sclerosis: genetic and optical coherence tomography study.

Objectives: The aim of this study was to explore the relationship between cognitive dysfunction, neurodegeneration, and genetic factors among multiple sclerosis (MS) patients. Methods: Fifty patients of definite MS were included. Physical disability was assessed by expanded disability status scale (EDSS). Cognitive functions were assessed by using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). For each eye, optical coherence tomography (OCT) was used to track thickness of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), respecting the previous history of optic neuritis (ON). All patients were genotyped for glutamate N-methyl-D-aspartate receptors (NMDARs). Results: A statistically significant negative correlation was found between scores of EDSS and each of neuropsychological tests scores and thickness of both RNFL and GCC. The predictor for progressive disability assessed by EDSS was Symbol Digit Modalities Test (SDMT) (P = 0.021), that is dependent on the educational level of the patients (P = 0.016). A statistically significant positive correlation was found between scores of all neuropsychological tests and the thickness of both RNFL and GCC. Eighty-three percent of MS patients with CC genotype reported previous attacks of ON with significant thinning in RNFL and GCC despite their higher cognitive performance in comparison to other genotypes. Discussion: Deficit in information processing speed measured by SDMT is a predictor of early progressive disability in MS patients. Thinning of RNFL and GCC is a potential biomarker for cognitive and physical disability in MS. The CC genotype of glutamate NMDAR gene has a divergent effect on visual and cognitive functions.

Pediatric-onset multiple sclerosis in Egypt: a multi-center registry of 186 patients.

INTRODUCTION: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers. OBJECTIVE: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS. PATIENTS AND METHODS: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt. RESULTS: Multiple sclerosis was diagnosed in 186 patients, 47 (25.27%) patients had disease onset before the age of 12 years; "early-onset pediatric multiple sclerosis (EOPMS)". The mean age of disease onset was (14.13±2.49 years), with a female:male ratio of 1.62:1, none of the enrolled patients had a primary progressive course (PPMS), whereas 10 patients (5.38%) had a secondary progressive form. Approximately two-thirds of the patients had monofocal disease onset, and less than 10% presented with encephalopathy; most of them had EOPMS. Motor weakness was the presenting symptom in half of the patients, whereas cerebellar presentation was detected in 34.95%, mainly in EOPMS. Seizures (not related to encephalopathy) were more frequent in those with EOPMS. Initial brain magnetic resonance images were positive in all patients, with detected atypical lesions in 29.03%, enhanced lesions in 35.48%, black holes in 13.98%, and infratentorial in 34.41%. Cervical cord involvement was found in 68.28%. More than two-thirds of the patients received either immunomodulatory or immunosuppressant (IS) treatment throughout their disease course, and about half of them received their treatment within the first year from symptoms onset, with a more favorable outcome, and patients with highly active disease received natalizumab, fingolimod, or other IS. CONCLUSION: The results from this registry - the largest for MS in the Arab region to date - are comparable to other registries. Immunomodulatory therapies in POMS are well tolerated and efficacious and they can improve the long-term outcome in children.

Characteristics and predictors of progression in an Egyptian multiple sclerosis cohort: a multicenter registry study.

BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease with a heterogeneous presentation and diverse disease course. Recent studies indicate a rising prevalence of MS in the Middle East. OBJECTIVE: To characterize the demographics and disease features of Egyptian patients attending four tertiary referral MS centers in Cairo. MATERIALS AND METHODS: This was a retrospective, observational study on 1,581 patients between 2001 and 2015. Medical records were reviewed and data were identified and extracted in a standardized electronic registry. RESULTS: The mean age of disease onset was 26.6±7.8 years, with the majority being female (2.11:1). Relapsing-remitting MS was the most common type (75.1%). The main presenting symptom was motor weakness (43.9%), which was also the most frequent symptom during the disease course. Family history of MS was found in 2.28%. Higher initial Expanded Disability Status Scale score, black holes, and infratentorial lesions on initial magnetic resonance imaging were independent factors for disease progression by univariate analysis (OR 3.87 [95% CI 1.84-6.51], 4.14 [95% CI 3.08-5.58], 4.07 [95% CI 3.21-4.99], respectively); however, in multivariate analysis, only infratentorial lesions were an independent risk for disease progression (OR 6, 95% CI 2.99-12.02; P=0.0005). CONCLUSION: The results from this registry - the largest for MS in the Arab region to date - are comparable to other registries with slight differences.

Brain aging in normal Egyptians: cognition, education, personality, genetic and immunological study.

Studying the cognitive and immunological changes that occur in old age as well as genetic function have been considered an important subject to differentiate between normal brain aging and early dementia especially Alzheimer's disease. The aim of this study is to stress on age-related neuropsychological and electrophysiological (P(300)) changes in normal Egyptian subjects, to throw light on the value of genetic (Apo-E(4) genotype) and immunological markers [interleukin-6 (IL-6) and intercellular adhesion molecules (ICAM-1) in the serum] as tools used in early detection of cognitive decline in cerebral aging. Ninety-four normal Egyptian subjects (below and above 60 years) were submitted to the following: (1) neuropsychological tests for testing memory, perception, psychomotor performance and attention, (2) Eysenck Personality Questionnaire (EPQ) for personality traits, (3) event-related potential study (P(300), latency and amplitude), (4) genetic test for detection of Apolipoprotein E genotype and (5) immunological studies including detection of the level of IL-6 and ICAM-1 in serum. There was a significant impairment of memory, psychomotor performance and perception in elderly subjects particularly males and subjects with low level of education. Regarding personality, significantly high scores were obtained in neuroticism scale of EPQ in elderly subjects. Apo-E(3)/E(3) was the most common genotype encountered in Egyptian subjects (49.1%). It was found that subjects with Apo-E(4) genotype did significantly worse in scores of intentional memory test (sensory memory) when compared with other genotypes. Statistically significant impairment in attention and sensory memory was found in subjects with high IL-6 level. This could not be detected in subjects with high ICAM-1 level. In conclusion, advancing age and lower levels of education are considered risk factors for cognitive decline in normal brain aging. Neuropsychological tests remain as the highly sensitive tools for detection of early cognitive impairment. Neurotic traits are more encountered in old age. Apo-E(4) genotype is associated with significant sensory (intentional) memory impairment. High IL-6 level in the serum is accompanied by significant impairment in attention and sensory (intentional) memory.