Clinical and genetic evaluation of hereditary myopathies in an adult Saudi cohort.

BACKGROUND: Diagnosis of hereditary myopathy is often challenging owing to overlapping clinical phenotypes and muscle histopathological findings. This retrospective study aimed to identify the phenotypic and genotypic spectra of hereditary myopathies at a tertiary hospital in Riyadh, Saudi Arabia. METHODS: We reviewed the medical records of patients with hereditary myopathy who were evaluated between January 2018 and December 2022. RESULTS: Eighty-seven patients (78 families) were included, two-thirds were men with a mean age of 35 (SD 14.2) years. Limb-girdle muscular dystrophy (LGMD) was the most prevalent clinical diagnosis (25 cases; 29%), of whom, a genetic diagnosis was achieved in 15 of 22 patients tested (68%). In genetically confirmed LGMD, the most prevalent disorders were dysferlinopathy (27%) followed by fukutin-related protein (FKRP) - related limb girdle muscular dystrophy (20%), sarcoglycanopathy (20%), lamin A/C related myopathy (13%), and calpain-3 myopathy (13%). In 26 patients with pathogenic/likely pathogenic variants, the genetic testing method was whole exome sequencing (WES) (42%), Next generation sequencing (NGS) (31%), and targeted single gene analysis (27%). The sensitivity of each genetic testing method was as follows: 100% for targeted single-gene analysis, 100% for targeted analysis of D4Z4 repeat array units, 88% for myotonic dystrophy protein kinase (DMPK) repeat expansion analysis, 42% for NGS-neuromuscular panel, and 46% for WES. CONCLUSION: The prevalent types of hereditary myopathies were consistent with those reported locally and internationally. This study highlights the diagnostic yield of various molecular genetic tests for the diagnosis of hereditary myopathy in an adult cohort and the need for improved access to advanced molecular testing in cases suspected to have facioscapulohumeral muscular dystrophy (FSHD) or mitochondrial myopathies.

Common diagnoses and factors associated with abnormal neuroimaging in headache patients in the emergency department.

OBJECTIVES: To determine causes of headaches in patients who presented to the emergency department (ED) and underwent neuroimaging, and to determine the clinical features associated with abnormal neuroimaging. METHODS: Patients were retrospectively selected from a database between June, 2015 and May, 2019. Patients were included if they had neuroimaging requested from the ED mainly for headache. Associations between clinical characteristics and abnormal neuroimaging were assessed. RESULTS: We included 329 patients (33.4% men, 66.6% women). The mean (SD) age was 39.7 (18.4) years. Neurological signs were reported in 43.8% of the patients, head-computed tomography was requested in 79.6%, magnetic resonance imaging in 77.5%, and both in 57.1%. Abnormal neuroimaging was reported in 31.9%. The most common reported diagnoses were secondary headache disorders (48.9%), followed by primary headache disorders (16.4%). The remainder were nonspecific-headaches (35%). Variables associated with abnormal neuroimaging were headache onset ≤1 month (OR 3.37, CI 1.47-7.70, p=0.004), and presence of an abnormal neurological sign (OR 3.60, CI 1.89-6.83, p<0.001). CONCLUSION: Secondary headache disorders are common in patients who undergo neuroimaging in the ED. Those who have a neurological sign and recent onset of headache are more likely to have abnormal neuroimaging.

Performance of dialysis patients on the standard and basic Arabic versions of the Montreal Cognitive Assessments.

OBJECTIVES: To assess cognitive performance in Saudi patients on dialysis using Arabic versions of the Montreal Cognitive Assessment (MoCA) and assess the reliability of the scales. METHODS: We performed a cross-sectional study at the dialysis unit of King Saud University Medical City, Riyadh from April 2019 to March 2020. Patients ≥ 18 years of age with no history of dementia underwent cognitive assessment with the standard (MoCA-A) and basic (MoCA-B) Arabic versions, with repeat testing in a subset of participants. RESULTS: Recruitment included 83 participants, 56 on hemodialysis (HD) and 27 on peritoneal dialysis (PD). The mean±SD for age was 49.99 (15.48), and for years of education was 10.29 (5.5). The mean score for MoCA-A was 21.03±5.35, and for MoCA-B was 23.45±5.14. Younger age, longer years of education and peritoneal dialysis were significantly associated with higher MoCA scores on both versions (p<0.05). The ICC was 0.81 (95% CI 0.65, 0.91) and 0.77 (95% CI 0.58, 0.89) for MoCA-A and MoCA-B, respectively. The performance on the executive and calculation tasks were higher in the PD group on the MoCA-B. The recall mean score was higher in the PD group on the MoCA-A. CONCLUSION: The HD patients are at higher risk for cognitive impairment compared to PD patients. Age and education are important variables influencing performance. Both Arabic versions of the MoCA are reliable screening tools.

Clinical features and outcome of Guillain-Barre syndrome in Saudi Arabia: a multicenter, retrospective study.

BACKGROUND: Guillain-Barre syndrome (GBS) is an inflammatory polyradiculoneuropathy characterized by rapidly evolving weakness and areflexia, reaching nadir within 4 weeks. Data on the characteristic of GBS in Saudi Arabia are limited. This study aimed to describe the clinical, electrophysiological, and laboratory characteristics and outcome of a multicenter cohort of patients with GBS. METHODS: This is a retrospective multicenter nationwide study. Patients who had GBS, identified through Brighton Criteria, between January 2015 and December 2019 were included. Data collected included demographics, clinical features, cerebrospinal fluid profile, reported electrophysiological patterns, treatment, and outcome. Reported GBS subtypes were compared using chi-square, Fisher's exact, or Mann-Whitney U tests, as appropriate. RESULTS: A total of 156 patients with GBS were included (men, 61.5%), with a median age of 38 (interquartile range, 26.25-53.5) years. The most commonly reported antecedent illnesses were upper respiratory tract infection (39.1%) and diarrhea (27.8%). All but two patients (98.7%) had weakness, 64.1% had sensory symptoms, 43.1% had facial diplegia, 33.8% had oropharyngeal weakness, 12.4% had ophthalmoplegia, and 26.3% needed mechanical ventilation. Cytoalbuminological dissociation was observed in 69.1% of the patients. GBS-specific therapy was administered in 96.8% of the patients, of whom 88.1% had intravenous immunoglobulin, and 11.9% had plasmapheresis. Approximately half of the patients were able to walk independently within 9 months after discharge, and a third regained the ability to walk independently thereafter. Death of one patient was caused by septicemia. Acute inflammatory demyelinating polyradiculoneuropathy was the most commonly reported GBS subtype (37.7%), followed by acute motor axonal neuropathy (29.5%), and acute motor-sensory axonal neuropathy (19.2%). CONCLUSION: The clinical and laboratory characteristics and outcome of GBS in the Arab population of Saudi Arabia are similar to the international cohorts. The overall prognosis is favorable.

Exacerbation Rate in Generalized Myasthenia Gravis and Its Predictors.

OBJECTIVE: The aim of the study was to estimate the exacerbation incidence rate (IR) in acetylcholine receptor antibody (AChR)-positive generalized myasthenia gravis (MG) and its predictors. METHODS: The primary outcome in this retrospective study was to estimate moderate-to-severe (M-S) exacerbations IR in the early course of generalized MG. The secondary outcome was to explore the predictors of MG exacerbations. RESULTS: Between 1999 and 2015, we identified 78 AChR-positive generalized MG patients and 37 M-S exacerbations over the first 6 years following the onset of generalized MG symptoms. The M-S exacerbation IR was 12.2 per 100 person years (95% confidence interval [CI] 8.8-16.8). Any exacerbation (including mild) IR was 24.4 per 100 person years (95% CI 19.4-30.7). After controlling for confounding factors, MG exacerbation IR predictors included gender, disease severity at onset, and prednisone dose reduction with risk ratio of 0.34 (male gender), 2.67, and 20.8, respectively (all p values <0.05). M-S exacerbation occurred in 25 cases (32.1%), while any exacerbation (mild or M-S) was detected in 45 cases (57.7%). CONCLUSION: More than half of newly diagnosed AChR + MG cases experience an exacerbation in the first 6 years. Gender, disease severity at onset and prednisone dose reduction are predictors that could inform clinical practice and future research.

Severity and depression can impact quality of life in patients with myasthenia gravis.

BACKGROUND: The revised 15-item Myasthenia Gravis (MG) Quality of Life Questionnaire (MGQoL15R) is a validated scale of quality of life in patients with MG. We aimed to study the factors causing the variability within the Arabic version of the MGQoL15R (MGQoL15R-A). METHOD: A standardized questionnaire was completed by 118 patients. Correlations and hierarchical regression analyses were used to assess the contribution of sociodemographic variables, clinical factors, Patient Health Questionnaire-9 (PHQ9-A), and Generalized Anxiety Disorder-7 (GAD7-A) to the variability in the MGQoL15R-A. RESULTS: The MGQoL15R-A was highly correlated with PHQ9-A (r = 0.76), and moderately correlated with GAD7-A (r = 0.52). Clinical factors and PHQ9-A independently explained 30.4% and 34.5% of the variability, respectively. Among the clinical factors, uncontrolled MG status, relapse within the past year, and a higher number of current MG therapies were significantly associated with a higher MGQoL15R-A score. CONCLUSIONS: MG severity and depressive symptoms (measured by PHQ9-A) can affect the MGQoL15R-A score.

Electrodiagnostic reference data for sensory nerve conduction studies in Saudi Arabia.

OBJECTIVE: To estimate reference data for the commonly performed sensory nerve conduction studies (NCS) using a cohort of healthy subjects from Saudi Arabia. METHODS: This is a cross-sectional study conducted between May 2015, and June 2019. Sensory nerve action potential (SNAP) amplitude, conduction velocity (CV), and peak latency (PL) were recorded. Associations between these parameters and the covariates (age, sex, height, weight, and body mass index) were tested with Pearson correlations. Reference data were then derived using the lowest percentile that could be reliably determined for SNAP amplitude and CV. Reference data were derived using the highest percentile for PL. RESULTS: Upper and lower limb sensory NCS were performed in 127 and 137 participants, respectively. Age was the only covariate that required adjustment for estimation of SNAP amplitude. Therefore, a prediction model was generated for each nerve. Percentile estimation for PL and CV did not require adjustment for any of the covariates. Hence, it was derived for all the subjects pooled together. CONCLUSION: The sensory NCS reference data were comparable to the data from other countries. However, minimal differences were observed. Further studies are required with a focus on the older age group.

Electrodiagnostic reference data for motor nerve conduction studies in Saudi Arabia.

OBJECTIVE: To determine nerve conduction studies (NCS) reference data for motor nerves and F-waves in the upper and lower limbs of healthy subjects in Saudi Arabia. METHODS: This is a cross-sectional study conducted between May 2015 and June 2019. Healthy subjects without neurological or systemic diseases were recruited. Motor NCS were performed following a standard protocol. Pearson correlations were employed between NCS parameters and age, gender, height, weight, and body mass index. Reference data were generated using the percentile method. RESULTS: A total of 127 subjects were recruited for the upper limb studies and 137 for the lower limb studies. Quantile regression models were generated to estimate compound muscle action potential amplitude (adjusted for age), as well as F-wave minimal latency (adjusted for height). The estimated reference limits of distal motor latency (ms) and conduction velocity (m/s) for the different nerves were, respectively, 3.7 and 50 for the median nerve, 3.3 and 50 for the ulnar nerve, 5.8 and 40 for the tibial nerve, and 5.0 and 40 for the fibular nerve. CONCLUSION: The reference data for motor NCS parameters and F-wave minimal latency are generally comparable with those of Western countries. However, minimal differences were observed. The underrepresentation of the older age group warrants future studies. The reference data for motor NCS parameters and F-wave minimal latency are generally comparable with those of Western countries. However, minimal differences were observed. The underrepresentation of the older age group warrants future studies.

Knowledge of and attitudes toward epilepsy surgery among neurologists in Saudi Arabia.

OBJECTIVE: To investigate the levels of knowledge and attitudes toward epilepsy surgery among neurologists in Saudi Arabia and evaluate the factors that affect the physicians` knowledge and attitudes. METHODS: A quantitative observational cross-sectional study conducted at King Saud University Medical City, Riyadh. The data were collected using a newly developed, self-administered online questionnaire. The questionnaire contained 3 sections: demographic information, knowledge, and attitudes which then sent to neurologist in Saudi Arabia from December 2016 to March 2017. RESULTS: A total of 106 neurologists met our inclusion criteria. Eighty percent of the participants had at least one epilepsy center in their city, and 78% indicated that they had access to adequate expertise and resources to enable the appropriate selection of epilepsy surgical candidates. Only 57.5% of the neurologists had a sufficient level of knowledge regarding epilepsy surgery. Neurologists with higher level of knowledge referred more patients to EMU and discussed epilepsy surgery more often with their patients. Overall, more than half of the neurologists (52.8%) had a positive attitude toward epilepsy surgery. There was a significantly positive correlation between the scores of knowledge and attitude (p less than 0.001). CONCLUSION: Neurologists in Saudi Arabia appear to have moderate knowledge of and positive attitudes toward epilepsy surgery. The place of the last neurology certificate, type of practicing hospital, and access to expertise and resources, affected their knowledge. Adequate knowledge was positively correlated with attitude.

Translation and validation of the arabic version of the myasthenia gravis activities of daily living scale.

INTRODUCTION: We translated the myasthenia gravis (MG)-specific activities of daily living (MG-ADL) scale into Arabic (MG-ADL-A) and assessed its psychometric properties. METHODS: We assessed reliability using Cronbach's α, reproducibility using the intraclass correlation coefficient, and validity using Spearman's correlations with MG composite (MGC) score, MG-specific manual muscle test (MG-MMT), and MG quality-of-life revised Arabic version (MGQOL15R-A). Differences in MG-ADL-A scores among patients with different disease severity were evaluated by using the Kruskal-Wallis test. Sensitivity to change was examined by using the Wilcoxon signed-rank test. RESULTS: We recruited 87 patients. The mean MG-ADL-A score was 3.38 ± 3.38 (α = 0.77, ICC = 0.99). The correlation coefficients between the MG-ADL-A and MGQOL15R-A, MGC, and MG-MMT were 0.63, 0.74, and 0.61, respectively (P < 0.001). The MG-ADL-A discriminated between different severity groups and was responsive to clinical improvement at follow-up. DISCUSSION: The MG-ADL-A has rigorous psychometric properties and can be used with Arabic-speaking patients with MG. Muscle Nerve 59:583-583, 2019.