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Radi Shahien1, Silvia Bianchi2, Abdalla Bowirrat11Department of Neurology, Ziv Medical Center, Safed, Israel; 2Department of Neurological and Behavioral Sciences, University of Siena, Viale Bracci, Siena, ItalyAbstract: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of hereditary cerebral microangiopathy, and is caused by over 170 different mutations in the NOTCH3 gene at locus 19p13.1–13.26. We report the first study of familial CADASIL in a 39-year-old Jewish woman and her mother who had died previously. The patient's investigations revealed a normal hemogram with no vascular risk factors or chronic disease. Lumbar puncture was normal. Cranial computed tomography scan revealed bilateral diffuse hypodensities in the subcortical white matter. Cranial magnetic resonance imaging showed hyperintense lesions in the cerebral white matter on T2-weighted images. On electron microscopy, a characteristic granular osmiophilic material was seen in the basement membrane surrounding the pericytes and smooth muscle cells in small-sized and medium-sized vessels. Molecular analysis of the NOTCH3 gene was performed with automatic sequencing of exon 3 and 4 (and intron-exon boundaries) showing a nucleotide c.268C > T substitution, leading to a pathogenic amino acid substitution of p.Arg90Cys, confirming a diagnosis of CADASIL. This mutation was also found in the patient's mother. Although the exact prevalence of CADASIL is not known, this disorder has been reported worldwide, and now including Jews, with a genotype and clinical phenotype similar to that in other ethnic groups.Keywords: CADASIL, autosomal-dominant inheritance, genetic diagnostics, NOTCH3, arteriopathy

The indirect impact of the COVID-19 pandemic on clinical services in peripheral hospitals has not been fully described. We compared the impact of COVID-19 on Cerebral Vascular Accident (CVA) and ST-elevation myocardial infarction (STEMI) management and outcome in an Israeli peripheral hospital. We included 1029 CVA and 495 STEMI patients. Patients who arrived during (15/3/2020-15/4/2022) and before (1/1/2018-14/3/2020) the pandemic, were demographically comparable. During the pandemic, median time for CVA patients from arrival to imaging was longer (23 vs. 19 min, p = 0.001); timing from arrival to tissue Plasminogen Activator administration was similar (49 vs. 45 min, p = 0.61); transfer to another hospital was more common (20.3% vs. 14.4% p = 0.01) and median length of stay (LOS) was shorter (3 vs. 4 days, p < 0.05). Among STEMI patients, median time from arrival to intervention intra- pandemic was shorter (45 vs. 50 min p = 0.02); Mean LOS shorter (3.86 vs. 4.48 p = 0.01), and unplanned re-admission less frequent (7.8% vs. 14.6% p = 0.01). Mortality did not change significantly. Our data shows no major negative impact of the COVID-19 pandemic on CVA outcomes, and improved care for STEMI patients. Interviews with the neurology and cardiology staff are performed to investigate how quality of care was maintained during the crises., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study received approval and consent from Ziv medical center ethics committee, number ZIV-0014–22. Due to the retrospective nature of the study written informed consent was waived by Ziv medical center ethics committee., (© 2024. The Author(s).)

The Galilee region of Israel boasts a rich ethnic diversity within its Arab population, encompassing distinct Muslim, Christian, Druze, and Bedouin communities. This preliminary exploratory study uniquely examined potential ethnic and gender differences in ischemic stroke characteristics across these Arab subgroups, which are seldom investigated separately in Israel and are typically studied as a homogeneous "Arab" sector, despite significant variations in their ethnicity, culture, customs, and genetics. The current study aimed to comparatively evaluate stroke characteristics, including recurrence rates, severity, and subtypes, within and across these distinct ethnic groups and between genders. When examining the differences in stroke characteristics between ethnic groups, notable findings emerged. The Bedouin population exhibited significantly higher rates of recurrent strokes than Muslims (M = 0.55, SD = 0.85 vs. M = 0.25, SD = 0.56; p < 0.05). Large vessel strokes were significantly more prevalent among Christians (30%) than Druze (9.9%; p < 0.05). Regarding gender differences within each ethnic group, several disparities were observed. Druze women were six times more likely to experience moderate to severe strokes than their male counterparts ( p < 0.05). Interestingly, Druze women also exhibited a higher representation of cardio-embolic stroke (19.8%) compared with Druze men (4.6%; p < 0.001). These findings on the heterogeneity in stroke characteristics across Arab ethnic subgroups and by gender underscore the need to reconsider the approach that views all ethnic groups comprising the Arab sector in Israel as a homogeneous population; instead, they should be investigated as distinct communities with unique stroke profiles, requiring tailored culturally aware community-based prevention programs and personalized therapeutic models. The identified patterns may guide future research to develop refined, individualized, and preventive treatment approaches targeting the distinct risk factors, healthcare contexts, and prevention needs of these diverse Arab populations.

Background: Multiple sclerosis (MS) is a multifactorial disease of uncertain etiology damaging myelin sheaths around axons of the central nervous system. Myelin protects the axon from potentially harmful exogenous factors. The aetiological role of environmental exposure metals and organophosphates is unclear., Objective: Identify whether urinary levels of metals and organophosphates differed in MS patients and controls., Methods: We recruited MS patients from Ziv Medical Centre and healthy controls. MS patients were evaluated according to Expanded Disability Status Scale into mild and moderate-severe conditions. Each participant provided a urine sample and completed epidemiological questionnaires. The levels of six metal (Aluminum, Cadmium, Chromium, Lead, Mercury, Nickel) and one metalloid (Arsenic) and common organophosphates pesticide metabolites (6 dialkylphosphates, DAP) were measured in urine using inductively coupled plasma-mass spectrometry and gas-chromatography mass-spectrometry. We compared cases with controls in terms of urinary levels of these compounds using Mann-Whitney and Kruskall-Wallis tests., Results: Urinary cadmium and mercury levels were higher in the 49 MS patients than the 37 controls (p < 0.01). Cadmium levels were higher in moderate-severe MS patients (n = 24) than mild MS patients (n = 25) (p = 0.003)., Conclusion: Urinary cadmium and mercury levels were higher among MS patients than controls. Cadmium levels correlated with disease severity. Further studies are needed to explore potential causal pathways between these compounds and MS pathogenesis., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: The two cerebral hemispheres influence the immune response differently. While the left hemisphere enhances cellular immunity, the right hemisphere inhibits it., Objectives: To determine whether immune and inflammatory markers correlated with stroke severity and hospitalization duration as a function of stroke side., Methods: The study included 137 patients with unilateral ischemic stroke. The medical records were reviewed for demographic and clinical laboratory data, including C-reactive protein (CRP), white blood cell (WBC) count, its differential stroke side and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), and length of hospital stay (LOS). We examined differences between right side (RS) and left side (LS) stroke on immune and inflammatory markers and compared correlations between these markers and NIHSS and LOS as a function of stroke side., Results: RS stroke patients had higher CRP and monocytes than LS stroke patients. In RS stroke patients, CRP, total WBC, and lymphocyte levels positively correlated with both NIHSS and LOS, whereas levels of neutrophils were positively correlated with NIHSS alone. No correlations were found for LS stroke patients., Conclusions: Immune-inflammatory markers correlated with stroke severity and LOS only in patients with RS stroke. Neuroimmunological processes influence short-term clinical outcomes after stroke, especially considering the differential effects of the hemispheres on immunity. Prospective studies that evaluate long-term clinical outcomes are needed. Testing the effects of anti-inflammatory treatments on prognosis of RS stroke patients should be considered.

There are different diagnostic modalities to investigate atherosclerosis cervical artery disease in suspected stroke patients. We aimed to test the concordance of findings of the two most widely used diagnostic modalities in stroke patients: duplex ultrasound (DUS) and computerized tomographic angiography (CTA). A total of 100 stroke patients were retrospectively included in the study, all of them had DUS followed by CTA. Discrepancies of DUS compared to the CTA results in both the internal carotid and vertebral arteries were found in 44% of the patients. The patients with significant differences in diagnostic results were characterized by older age. Evaluation of the degree of carotid artery stenosis revealed vast differences in patients with 50-69% stenosis found by DUS, in which 45.5% of them had a different percentage of stenosis found by CTA. In studying the degree of stenosis of the vertebral artery, only 47.1% of the patients with more than 50% stenosis found by DUS had the same results with CTA, while the remaining revealed normal or less than 50% stenosis by CTA. The current study emphasizes that CTA is more accurate than DUS in the evaluation of stenosis of the cervical arteries including both the internal carotid and vertebral arteries.

Retrospective study. The purpose of this study was to investigate the clinical symptomatology of discopathies before and 7 days after treatment with one of the following: intravenous dexamethasone, selective nerve root block (SNRB), and systemic treatment with different nonsteroidal antiinflammatory drugs (NSAIDs). Radiculopathy is a clinical condition in which dysfunction of one or more nerves occurs due to mechanical compression and/or chemical irritation of the nerve roots. Most often located in the lumbar spine, radiculopathy remains one of the most common complaints in primary health. Some patients responded well to conservative treatment. However, those who show no improvement may benefit from more invasive treatment options, such as intravenous corticosteroids, spinal injections, and surgical procedures. We conducted a retrospective study of 81 male and female patients aged 18 years and above who had radicular pain and were referred to our facility over a 7-year period. Of the 100 patients assessed for eligibility, 19 patients were not included in the study due to malignancy or surgical intervention, 32 patients received intravenous dexamethasone, 24 patients received SNRB, and 25 received various NSAIDs as the control group. The visual analog scale, straight leg raise test and neurological deficits were assessed to evaluate the patients before and after receiving treatment. All patients underwent spinal computed tomography to confirm the diagnosis of disc herniation. Pearson chi-squared test, Kruskal-Wallis test, and Mann-Whitney test were used to evaluate the results. Visual analog scale scores and the ability to perform straight leg raise test significantly improved after treatment with dexamethasone, SNRB, and NSAIDs. However, clinical improvement was significantly better in both the dexamethasone and SNRB groups than in the control group. Motor deficits improved significantly after dexamethasone treatment alone. Dexamethasone and SNRB are useful and safe treatment options for treating patients with acute radicular pain. Randomized, double-blinded, control studies are warranted., Competing Interests: The study was approved by the Ethics Committee of Ziv Medical Center (0100-16-ZIV). The authors state that the study was performed at the hospital without any external help. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest. The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic HSCT, partially accounting for the variability in OM severity. Using 16S ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- and post-HSCT. Transplantation was associated with a decrease in oral α diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graft-versus-host disease prophylaxis pre-HSCT, Kingella and Atopobium abundance correlated with future development of severe OM. Posttransplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes post-HSCT, compared with patients with no or mild OM. Changes in specific metabolites were well explained by microbial composition, and the common metabolic pathway was the polyamines pathway, which is essential for epithelial homeostasis. Together, our findings suggest that salivary microbial composition and metabolites are associated with the development of OM, offering new insights on pathophysiology and potential avenues of intervention., (© 2020 by The American Society of Hematology.)

Background: Multiple sclerosis (MS) is a multifactorial disease of the central nervous system in young adults. Mitochondrial respiration provides fuel necessary for cellular function and is especially important in cells with large energy demand including neurons. Various studies suggest that the pathogenesis of MS may be associated with mitochondrial dysfunction., Methods: We examined 145 volunteers including 62 MS patients and healthy controls. MS patients were divided into two groups according to their disease severity: those with mild disability (EDSS=0-3.0) and those with moderate-severe MS (EDSS=3.5-8). After signing an informed consent, blood was taken and was separated to platelets and lymphocytes. Mitochondria activity was monitored as mitochondrial transmembrane potential following staining with JC1 dye in platelets and lymphocytes utilizing flow cytometry., Results: We examined mitochondria activity as JC1 values from all separated lymphocyte samples and found significantly higher levels of mitochondrial activity in lymphocytes separated from healthy controls vs. MS patients (mean of 87.9% vs. 75.6%, p = 0.001). Significant differences in mitochondrial activity were also found when comparing means of groups divided according to MS disease severity. Interestingly, there were no significant differences in mitochondrial activity between patients treated with diverse medications or untreated patients. Mitochondrial activity was also examined in platelets, but no significant differences were found between groups., Conclusions: Results obtained here show that mitochondrial activity was significantly lower in MS patients in comparison to healthy controls. In addition, there was a significant difference in mitochondrial activity depending on MS degree of disability. These initial findings in a peripheral examination hold potential for new diagnostic biomarkers to be considered in the future., Competing Interests: Declaration of Conflicting Interests None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is a multifactorial disease with unknown etiology. It is assumed to result from interplay between genetic and environmental factors, including nutrition. We hypothesized that there are differences in nutritional parameters between MS patients and healthy controls., Methods: We examined 63 MS patients and 83 healthy controls. Nutritional status was determined by a dietary questionnaire, blood tests, quantification of cell membrane fatty acids, and serum antioxidant capacity., Results: We found that MS patients consumed a more limited diet compared with the healthy group, indicated by a lower average of 31 nutrients and by consumption levels of zinc and thiamine below the recommended daily intake. Both consumption and measured iron values were significantly lower in MS patients, with the lowest measures in the severe MS group. Long saturated fatty acids (>C16) were significantly lower in MS patients, while palmitic and palmitoleic acids were both higher. Serum total antioxidant capacity was significantly lower in the MS group compared with healthy controls, with the lowest measures in patients with severe MS., Conclusions: This study points to a possible correlation between nutritional status and MS. Understanding the clinical meaning of these findings will potentially allow for the development of future personalized dietary interventions as part of MS treatment.

A previously healthy 35-year-old man suffering from behavioral and mental deterioration for three months was referred to our facility. On admission, the patient was dysphasic and had tonic-clonic seizures. Neurological examination showed mental confusion, euphoric mood, mania, paranoia, and mild motor dysphasia. Magnetic resonance imaging (MRI) was performed twice but no abnormalities were revealed. His acute confusional state, elevated cerebrospinal fluid (CSF) protein, epileptic seizure and electroencephalogram showing intermittent frontal slowness were all suggestive of encephalitis. The patient was treated with acyclovir without significant improvement in his condition. Testing for herpes simplex virus and human immunodeficiency virus was negative. Limbic encephalitis was suspected and the patient was treated with intravenous immunoglobulin (IVIG) for five days. Venereal disease research laboratory and Treponema pallidum hemagglutination assay were both tested positive in serum and CSF. Neurosyphilis was diagnosed, and the patient received a 14-day course of penicillin G with gradual improvement. Anti-N-methyl-D-aspartate-receptor (anti-NMDAR) antibodies were positive in serum, confirming the presence of encephalitis. The atypical clinical presentation of neurosyphilis with symptomatology mimicking encephalitis and no MRI abnormalities made the diagnosis challenging. Coexistence of neurosyphilis with anti-NMDAR encephalitis has been reported only in one recent study. Our case demonstrates the importance of testing for syphilis in patients with unexplained neurologic deficits and suspected encephalitis.

Background: Multiple sclerosis (MS) prevalence and genetic susceptibility varies among the different ethnic groups of Jews and Arabs in Israel., Objective: Characterization of MS disease course in Christian, Muslim and Druze Arabs in Israel., Methods: Historical cohort and three-year follow-up cohort analyses based on interviews and clinical charts of 149 Arab MS patients (78 Muslims, 49 Christians and 22 Druze) from three MS centers in Israel. Significant findings were adjusted for use of disease modifying therapy., Results: Age of onset (means between 30 and 31 years) and incomplete recovery rates after the first relapse (~50%) were similar for Christian, Muslim and Druze patients. Low rates of primary progressive MS (≤1%) were observed. Differences between the ethnicities in the time from onset to the second neurological episode were observed among females, but not males. Druze and Muslim women were more likely to have a second event within two years from the first event compared with Christians (odds ratios =8.8, p= 0.02; odds ratio=6.6, p=0.007 respectively). Trends for higher annual relapse rates, annual disability progression rates and MS Severity Scores were observed among the Druze., Conclusions: Among the Israeli Arab female MS patients, Druze and Muslims exhibit a more rapid disease course in comparison with Christians. Further elucidation of population-specific MS phenotypes may contribute to improved disease management.

We report a complication related to epidural analgesia for delivery in a 24- year-old woman who was admitted with mild pre-eclampsia and for induction of labor. At the first postpartum day she developed a postdural puncture headache, which was unresponsive to conservative measures. On the fifth day an epidural blood patch was done, and her headache subsided. Sixteen hours later she developed paralysis of the right facial nerve, which was treated with prednisone. Seven days later she complained of pain in the left arm and the posterior region of the shoulder. She was later admitted and diagnosed with partial brachial plexopathy.

Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Drug-induced aseptic meningitis (DIAM) is an important entity and has been reported as an uncommon adverse reaction with numerous agents. Thus, DIAM constitutes a diagnostic and patient management challenge. We present a patient with three episodes of aseptic meningitis due to amoxicillin, and then review the literature on this rare idiosyncratic event which may occur after local or systemic drug administration. A 77-year-old man was admitted to our hospital with fever, headache, and neck stiffness. Seven days before admission he had a dental and gingival inflammation. He was treated with two oral doses of 500 mg daily of amoxicillin for one week. The seventh day he awoke with the complaints that prompted hospital admittance. Amoxicillin was stopped 1 day before his admission. From his history we knew of two similar episodes: The first episode was after a dental procedure 3 months before this incident. He had received a 1-week course of postprocedure amoxicillin of 500 mg daily and had similar headache, fever, and chills during the entire course of treatment. He wasn't admitted to the hospital, because he stopped taking amoxicillin and he felt spontaneous pain relief after taking symptomatic pain treatment. The second episodes was 6 months after his first admission, he had been admitted to our hospital with the same symptoms. Amoxicillin was stopped and changed with intravenous (IV) ceftriaxone (CTRX) for 10 days due to suspected partial untreated meningitis. The patient improved rapidly within 2 days and was discharged from the hospital. On the basis of these three confirmed episodes of meningitis after recurrent exposure to amoxicillin, with repetitive negative testing for viral, bacterial, and mycobacterial micro-organisms, we diagnosed aseptic meningitis induced by amoxicillin. To our knowledge, this is the seventh well documented publication of such a severe side effect of a commonly used antibiotic.

Background: Neurologic involvement in Behçet's disease (BD), also known as neuro-Behcet's disease (NBD), is one of the most devastating manifestations of the disease. The etiology of BD remains obscure and speculative. NBD usually occurs 1-10 years after the first symptom of BD has occurred, and its incidence is 18% (range of 4%-49%)., Objective: This study was conducted to describe the clinical and prognostic aspects of neurologic involvement in BD among patients attending a multidisciplinary hospital clinic., Methods: Eighty patients with BD were diagnosed according to the International Study Group Criteria for BD at our hospital. Sixteen patients (20%, including 11 men and five women) had evidence of and fulfilled the diagnostic criteria for NBD. These patients underwent laboratory and imaging investigations, including human leukocyte antigen-typing, lumbar puncture, electroencephalographic studies, and computed tomography scanning., Results: Fourteen of the 16 patients received high-dose steroids, and four of these 14 patients were treated with a combination of steroids and cytotoxic agents. Relief was observed in 14 of 16 patients (87.5%). The remaining two patients were untreated males who suffered severe brainstem lesions, and later died., Conclusion: In contrast with previous reports of a poor prognosis with NBD, our study shows that early aggressive intervention with corticosteroids and cytotoxic agents may ameliorate the prognosis in these patients, and can diminish and stabilize the negative effect of neurologic involvement.