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.

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.

Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients.

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

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%.

ٍSome biologically active microorganisms have the potential to suppress mosquito larvae (Culex pipiens, Diptera: Culicidae).

Malaria is a disease caused by protozoan species of the genus Plasmodium. It is widespread and becoming a challenge in several African countries in the tropical and subtropical regions. In 2010, a report was published showing that over 1.2 million death cases were occurred globally due to malaria in just one year. The transmission of the disease from one person to another occurs via the bite of the Anopheles female. It is known that Plasmodium ovale, P. vivax, P. malariae, P. falciparum, and P. knowlesi are the highly infective malaria species. The problem of this disease is the absence of any effective medical treatment or vaccine, making the mosquito control is the only feasible way for disease prevention. Pesticides are currently the most widely used method for mosquito control, despite its well-known negative effects, including health hazards on human, the increasing insecticidal resistance, and the negative impact on the environment and beneficial organisms. Biological control (also called: biocontrol) of insects has been a promising method to overcome the negative effects of using chemical insecticides, as it depends on just using the natural enemies of pests to either minimize their populations or eradicate them. This article provides an overview of the recent and effective biological means to control malaria, such as bacteria, fungi, viruses, larvivorous fish, toxorhynchites larva and nematodes. In addition, the importance, advantages, and disadvantages of the biocontrol methods will be discussed in comparison with the traditionally used chemical methods of malaria control with special reference to nanotechnology as a novel method for insects' control.

Predictive value of magnetoencephalography in guiding the intracranial implant strategy for intractable epilepsy.

OBJECTIVE: Magnetoencephalography (MEG) is a useful component of the presurgical evaluation of patients with epilepsy. Due to its high spatiotemporal resolution, MEG often provides additional information to the clinician when forming hypotheses about the epileptogenic zone (EZ). Because of the increasing utilization of stereo-electroencephalography (sEEG), MEG clusters are used to guide sEEG electrode targeting with increasing frequency. However, there are no predefined features of an MEG cluster that predict ictal activity. This study aims to determine which MEG cluster characteristics are predictive of the EZ. METHODS: The authors retrospectively analyzed all patients who had an MEG study (2017-2021) and underwent subsequent sEEG evaluation. MEG dipoles and sEEG electrodes were reconstructed in the same coordinate space to calculate overlap among individual contacts on electrodes and MEG clusters. MEG cluster features-including number of dipoles, proximity, angle, density, magnitude, confidence parameters, and brain region-were used to predict ictal activity in sEEG. Logistic regression was used to identify important cluster features and to train a binary classifier to predict ictal activity. RESULTS: Across 40 included patients, 196 electrodes (42.2%) sampled MEG clusters. Electrodes that sampled MEG clusters had higher rates of ictal and interictal activity than those that did not sample MEG clusters (ictal 68.4% vs 39.8%, p < 0.001; interictal 71.9% vs 44.6%, p < 0.001). Logistic regression revealed that the number of dipoles (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, t = 3.43) and confidence volume (OR 0.02, 95% CI 0.00-0.86, t = -2.032) were predictive of ictal activity. This model was predictive of ictal activity with 77.3% accuracy (sensitivity = 80%, specificity = 74%, C-statistic = 0.81). Using only the number of dipoles had a predictive accuracy of 75%, whereas a threshold between 14 and 17 dipoles in a cluster detected ictal activity with 75.9%-85.2% sensitivity. CONCLUSIONS: MEG clusters with approximately 14 or more dipoles are strong predictors of ictal activity and may be useful in the preoperative planning of sEEG implantation.

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.

Rainwater-driven microbial fuel cells for power generation in remote areas.

The possibility of using rainwater as a sustainable anolyte in an air-cathode microbial fuel cell (MFC) is investigated in this study. The results indicate that the proposed MFC can work within a wide temperature range (from 0 to 30°C) and under aerobic or anaerobic conditions. However, the rainwater season has a distinct impact. Under anaerobic conditions, the summer rainwater achieves a promised open circuit potential (OCP) of 553 ± 2 mV without addition of nutrients at the ambient temperature, while addition of nutrients leads to an increase in the cell voltage to 763 ± 3 and 588 ± 2 mV at 30°C and ambient temperature, respectively. The maximum OCP for the winter rainwater (492 ± 1.5 mV) is obtained when the reactor is exposed to the air (aerobic conditions) at ambient temperature. Furthermore, the winter rainwater MFC generates a maximum power output of 7 ± 0.1 mWm-2 at a corresponding current density value of 44 ± 0.7 mAm-2 at 30°C. While, at the ambient temperature, the maximum output power is obtained with the summer rainwater (7.2 ± 0.1 mWm-2 at 26 ± 0.5 mAm-2). Moreover, investigation of the bacterial diversity indicates that Lactobacillus spp. is the dominant electroactive genus in the summer rainwater, while in the winter rainwater, Staphylococcus spp. is the main electroactive bacteria. The cyclic voltammetry analysis confirms that the electrons are delivered directly from the bacterial biofilm to the anode surface and without mediators. Overall, this study opens a new avenue for using a novel sustainable type of MFC derived from rainwater.

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.

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.

The combined effect of IL-17F and CCL20 gene polymorphism in susceptibility to multiple sclerosis in Egypt.

BACKGROUND: Levels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the recruitment of T helper (Th17) cells to site of inflammation. OBJECTIVES: Determine the value of single nucleotide polymorphism of CCL20 (rs6749704) and IL-17F (rs763780) genes and their concomitant effect on the serum CCL20 level and susceptibility to MS in Egyptian patients. SUBJECTS AND METHODS: Blood samples were collected from 83 patients and 95 healthy subjects. Serum levels of CCL20 were measured by ELISA. The DNA was analyzed for rs6749704 and rs763780 using Genotyping Taqman assay. RESULTS: The mean serum levels of CCL20 in the MS group were significantly higher than healthy group (P < 0.001). Frequencies of CT genotype of rs6749704 in CCL20 gene and C allele in MS patients were significantly higher compared to controls. Also significant increase of rs763780 in IL-17F gene was detected in MS patients. Concomitant polymorphism in both genes in MS patients showed an increase risk to MS rather than individual locus. CONCLUSION: CCL20 may play an important role in the pathogenesis of MS. Both allelic variation of (rs6749704) within CCL20 gene and (rs763780) within IL-17F gene can be considered risk factor for development of MS in Egyptian patients.

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.

Prediction of Functional Outcome in Ischemic Stroke Patients: An Observational Study on Egyptian Population.

Introduction Determining the prognosis of ischemic stroke is important for neurologists and patients. The aim is to study the predictors of three months clinical outcome in ischemic stroke patients. Materials and methods A total of 397 patients were classified according to three months modified Rankin Scale score (mRS score) into two groups, favorable and unfavorable outcome. Favorable outcome was assumed if the score was zero or one, or unchanged if the score was ≥ 1 before the onset of the most recent event. Results The variables associated with unfavorable outcome were old age (P <0.001), presence of cardiac disease (P <0.001), low ejection fraction (P=0.008), low levels of total cholesterol and low-density lipoproteins (P <0.001), large artery atherosclerosis stroke (P <0.001), early confluent (P=0.005), high National Institute of Health stroke scale (NIHSS) score on admission (P <0.001), mRS score before admission (P <0.001), mRS score on discharge (P <0.001). Lacunar stroke was associated with favorable outcome (P <0.001). The regression analysis showed mRS score on discharge (P <0.001) and the presence of cardiac diseases (P=0.077) as independent predictors of unfavorable outcome. Conclusion High mRS score on discharge and presence of the cardiac disease independently could predict the unfavorable outcome and mRS score on discharge had a high sensitivity and negative predictive value in predicting the unfavorable outcome. Abbreviations MRS: score modified Rankin scale score, NIHSS: National Institutes of Health Stroke Scale, MRI: Magnetic resonance imaging, LDL: Low-density lipoprotein, MRA: Magnetic resonance of arteries.

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.