Frequency of Dimethyl Fumarate-Induced Lymphopenia among Omani Patients with Multiple Sclerosis.

Objectives: Dimethyl fumarate (DMF) is known to cause lymphopenia when used to treat patients with multiple sclerosis (MS). However, research on DMF therapy in the Arab world, especially in Oman, is scarce. This study aimed to analyse the prevalence of lymphopenia among Omani patients with MS and their reasons for discontinuing DMF therapy. Methods: In this retrospective study, the medical records of Omani patients with MS who were treated using DMF at two tertiary hospitals in Muscat, Oman, from February 2017 to February 2023 were reviewed. Their demographic, clinical and laboratory data were retrieved and analysed. Absolute lymphocyte count values at baseline and at the last follow-up, as well as the reasons for discontinuing DMF therapy, were collected. Descriptive and inferential statistical techniques were used for data analysis. Binary-logistic regression analysis was used to identify the risk factors for DMF-induced lymphopenia. Results: A total of 64 Omani patients with MS were included in this study. The majority of the study participants (n = 40; 63%) were female. All included patients started DMF therapy at the mean age of 33 ± 7.7 years. After administration of DMF, 14 (21.9%) patients developed grades 1-3 of lymphopenia. The DMF therapy was discontinued for 23 (36.0%) patients, mainly in response to adverse events or confirmed pregnancy. Female gender was the only significant predictor of DMF-induced lymphopenia (P = 0.037). Conclusions: Most Omani patients with MS had mild lymphopenia (grades 1-2). Early adverse events and pregnancy were the main reasons provided for discontinuing DMF therapy.

Absence of Meckel's Cave with Trigeminal Neuralgia: A Case Report.

Trigeminal neuralgia (TN) is a disabling painful condition along the course of the sensory distribution of the trigeminal nerve that most commonly occurs due to vascular compression or conflict at the root entry zone of the trigeminal nerve. We report a 27-year-old female patient who presented with pain and an electric shock-like sensation on the right side of her face that started three years ago. Magnetic resonance imaging of the brain was done and revealed no neurovascular conflict along the course of the trigeminal nerve. The absence of Meckel's cave with atrophy of the cisternal segment of the trigeminal nerve on the affected side was reported. The absence of Meckel's cave is an exceedingly rare cause of TN, and only a handful of reported cases in the literature suggest the association between them.

Health outcomes after acute ischemic stroke:retrospective and survival analysis from Oman.

BACKGROUND: Stroke mortality and related functional disability have been declining over the last two decades, but stroke continues to represent the second leading cause of cardiovascular death worldwide and the number one cause for acquired long-term disability. OBJECTIVES: Assess short- and long-term health outcomes after acute ischemic stroke and analyze factors associated with poor survival and functional outcomes. DESIGN: Retrospective and survival analysis SETTING: Inpatient unit at a tertiary care referral hospital. PATIENTS AND METHODS: All patients admitted with acute ischemic stroke from 1 January 2017 to 31 August 2018 were included in the study. Functional status was assessed using the modified Rankin Scale (mRS). Other demographic and clinical variables were obtained from medical records. Data were analyzed by multivariable logistic regression, Cox proportional hazards, and the Kaplan-Meier method. Long-term follow-up data, including mortality and mRS was collected by follow-up phone call. MAIN OUTCOME MEASURES: Functional dependency and factors associated with mortality. SAMPLE SIZE AND CHARACTERISTICS: 110 with mean age of 67.0 (14.7) years; 59 patients (53.6%) were males. RESULTS: Hypertension (75.5%), diabetes mellitus (54.6%), and dyslipidemia (29.1%) were common. Sixty-five patients (59.1%) had mRS >2 upon discharge including 18 patients (16.4%) who died during the hospital stay. The cumulative mortality rate was 25.4% (28/110) at 12 months and 30.0% (33/110) at 24 months. Twenty-nine stroke survivors (29/70, 41.4%) remained physically dependent (mRS >2) at the end of follow-up. Old age, atrial fibrillation, history of prior stroke, chronic kidney disease, and peripheral arterial disease were associated with increased mortality and functional dependence. CONCLUSIONS: Patients in Oman with acute ischemic stroke tend to have a high comorbidity burden, and their functional dependency and mortality are higher compared to patients from developed countries. Therefore, evidence-based measures such as establishing stroke units are essential to improve the health outcomes of patients with acute ischemic stroke. LIMITATIONS: Retrospective at single center. CONFLICT OF INTEREST: None.

Biallelic PTRHD1 Frameshift Variants Associated with Intellectual Disability, Spasticity, and Parkinsonism.

BACKGROUND: PTRHD1 was proposed as a disease-causing gene of intellectual disability, spasticity, and parkinsonism. OBJECTIVES: To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family. METHODS: Clinical evaluation, whole-exome sequencing, Sanger sequencing, reverse transcription polymerase chain reaction (PCR), real-time PCR, immunoblot, and isoelectric focusing. RESULTS: A homozygous 28-nucleotide frameshift deletion introducing a premature stop codon in the PTRHD1 exon 1 was identified in the four affected members. We further confirmed the apparent transcript escape of the nonsense-mediated messenger RNA (mRNA) decay pathway. Real-time PCR showed that mRNA expression of the mutant PTRHD1 is higher compared to the wild-type. Western blotting and isoelectric focusing identified a truncated, but stable mutant PTRHD1 protein expressed in the patient's primary cells. CONCLUSIONS: We provide further evidence that PTRHD1 mutations are associated with autosomal-recessive childhood-onset intellectual disability associated with spasticity and parkinsonism.

Orthostatic intolerance after bariatric surgery: A systematic review and meta-analysis.

There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well described. Therefore, we sought to summarize evidence of orthostatic intolerance after bariatric surgery. We conducted a systematic review using PubMed, Scopus, CINAHL, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant articles from the date of inception until 1st April 2020. Study selection, data extraction and quality assessment of the included studies were performed independently by two reviewers. The findings of the included studies were narratively reported. When feasible, a meta-analysis was done to summarize the relevant results. We included 20 studies (n = 19 843 participants) reporting findings of 12 prospective cohort studies, 5 retrospective cohort studies, 2 cross-sectional studies and one randomized controlled trial. The 5-year cumulative incidence of orthostatic intolerance was 4.2% (one study). Common clinical presentations of orthostatic intolerance were lightheadedness, dizziness, syncope and palpitation. The pooled data suggested improvement in overall cardiac autonomic function (sympathetic and parasympathetic) post-bariatric surgery. In addition, a significant systolic blood pressure drop may reflect a reset of the balance between the sympathetic and parasympathetic nervous systems after weight loss in the pooled analysis. Existing literature on orthostatic intolerance post-bariatric surgeries was limited or of low quality, and larger studies are needed to know the true incidence of orthostatic intolerance post-bariatric surgeries and the pathophysiology. We found one study reporting the 5-years cumulative incidence of orthostatic intolerance post-bariatric surgeries as only 4.2%. This could challenge the idea of increased orthostatic intolerance prevalence post-bariatric surgeries. Registration The review protocol was registered at the International Prospective Register of Systemic Reviews PROSPERO (CRD42020170877).

Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism.

BACKGROUND: Recent studies reported abnormal alpha-synuclein deposition in biopsy-accessible sites of the peripheral nervous system in Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if deposition occurs early, it may enable tissue diagnosis of prodromal PD. OBJECTIVE: The aim of this study was to develop and test an automated bright-field immunohistochemical assay of cutaneous pathological alpha-synuclein deposition in patients with idiopathic rapid eye movement sleep behavior disorder, PD, and atypical parkinsonism and in control subjects. METHODS: For assay development, postmortem skin biopsies were taken from 28 patients with autopsy-confirmed Lewy body disease and 23 control subjects. Biopsies were stained for pathological alpha-synuclein in automated stainers using a novel dual-immunohistochemical assay for serine 129-phosphorylated alpha-synuclein and pan-neuronal marker protein gene product 9.5. After validation, single 3-mm punch skin biopsies were taken from the cervical 8 paravertebral area from 79 subjects (28 idiopathic rapid eye movement sleep behavior disorder, 20 PD, 10 atypical parkinsonism, and 21 control subjects). Raters blinded to clinical diagnosis assessed the biopsies. RESULTS: The immunohistochemistry assay differentiated alpha-synuclein pathology from nonpathological-appearing alpha-synuclein using combined phosphatase and protease treatments. Among autopsy samples, 26 of 28 Lewy body samples and none of the 23 controls were positive. Among living subjects, punch biopsies were positive in 23 (82%) subjects with idiopathic rapid eye movement sleep behavior disorder, 14 (70%) subjects with PD, 2 (20%) subjects with atypical parkinsonism, and none (0%) of the control subjects. After a 3-year follow-up, eight idiopathic rapid eye movement sleep behavior disorder subjects phenoconverted to defined neurodegenerative syndromes, in accordance with baseline biopsy results. CONCLUSION: Even with a single 3-mm punch biopsy, there is considerable promise for using pathological alpha-synuclein deposition in skin to diagnose both clinical and prodromal PD. © 2020 International Parkinson and Movement Disorder Society.

Autonomic Sweat Responses in REM Sleep Behavior Disorder and Parkinsonism.

BACKGROUND: Autonomic dysfunctions including sudomotor abnormalities commonly occur in early Parkinson's disease (PD), but little is known about potential sudomotor abnormalities in idiopathic REM Sleep Behavior Disorder (iRBD), a strong prodromal marker of PD. OBJECTIVE: Our aim was to assess sudomotor dysfunction by galvanic skin response using SudoScan, as well as other autonomic markers in 49 iRBD, 40 PD (21 with RBD, 19 without), 20 atypical parkinsonisms, and 41 age-matched controls. METHODS: All subjects underwent SudoScan of their hands and feet, a 30-second electrocardiogram with assessment of beat-to-beat variability, assessment of orthostatic blood pressure changes and autonomic symptom questionnaires. RESULTS: The galvanic skin response in the hands of PD patients with RBD was significantly smaller than controls (hand mean difference = -7.877, 95% CI (-13.283, -2.470), p-value = 0.004) and PD patients without RBD (hand mean difference = -9.578, 95% CI (-17.215, -1.941), p-value = 0.014). iRBD and atypical parkinsonism did not have different SudoScan profiles than controls. CONCLUSIONS: Galvanic skin responses, as measured by SudoScan did not demonstrate significant sudomotor dysfunction in iRBD, but decreases were seen in the PD subtype associated with RBD.

Sleep Disturbances in the Prodromal Stage of Parkinson Disease.

OPINION STATEMENT: Decades of research on neurodegenerative diseases such as Parkinson's disease (PD) have shifted our focus from clinical symptomatic stages to one step earlier, the prodromal stage. There is convincing evidence showing that sleep disorders such as excessive daytime somnolence, insomnia, obstructive sleep apnea, and particularly REM sleep behavior disorder (RBD) are potential prodromal features starting years and decades before conversion to PD. This review aims to provide an overview on various sleep disorders as prodromal features of PD. We start with a discussion of how neuroanatomy of sleep might link to PD pathology. Afterwards, specific sleep disorders that are either known or suspected to be a prodromal symptom for PD, namely insomnia, sleep apnea, somnolence, and RBD, are discussed. Disturbances in serotonergic, cholinergic, dopaminergic, and glutamatergic neurotransmitter systems have made sleep disorders potential candidates for prodromal PD. Nevertheless, the strength of such linkage varies considerably for different entities. While RBD is by far the strongest prodromal manifestation for PD with a high likelihood of phenoconversion and there is reasonable evidence that somnolence can predict PD, data on the prodromal role of sleep apnea and insomnia is limited. Treatment options are available for symptomatic relief of prodromal sleep disorders; however, there is a dearth of knowledge on neuroprotective agents to be used on people with prodromal sleep disorders to either prevent or postpone conversion to PD.

Acute drug overdose: clinical profile, etiologic spectrum and determinants of duration of intensive medical treatment.

OBJECTIVES: Acute drug overdosing is an important cause of organ dysfunction and metabolic derangements and the patients often require intensive care. This study aims to determine the clinical pattern of severe drug overdose as well as the factors influencing the duration of intensive care METHODS: The clinical characteristics and course of consecutive adult patients admitted with a diagnosis of acute drug poisoning in the ICU of a tertiary hospital in Oman from January 2007 to December 2008 were reviewed retrospectively from the electronic case records. RESULTS: Acute drug poisoning (n=29) constituted 3.9% of admissions to the ICU. Mean age was 29.38±7.9 years. They were brought in by their relatives (72%) or the state services (24%). Accidental poisoning was noted in 21 patients (72%) and suicidal overdosing in 6 (21%). The commonest drug was an opioid (65.5%). Glasgow Coma Scale score of ≤8 was recorded in 18 (62.1%). Sixty two percent of patients required mechanical ventilation. The prominent complications were hypotension in 9 (31%), pulmonary in 19 (65.5%), hepatic in 18 (62.1%) and renal in 12 (41.4%) patients. The major electrolytes abnormalities were low bicarbonate in 11 (37.9%), hyponatremia in 5 (17.2%) and hypokalemia in 4 (13.8%). Patients stayed in the ICU for 1 to 20 days (median-2 days). Factors associated with a longer ICU stay included hypotension upon arrival (p=0.048) and the need for mechanical ventilation on the first (p=0.001) and second (p=0.001) days of hospitalization. There was no mortality. CONCLUSION: Early and prompt intensive medical therapy in acute drug poisoning can favorably influence the outcome. In addition, the presence of hypotension and requirement of mechanical ventilation on the first two days of hospitalization were responsible for prolonged ICU stay.