A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]. CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Air Pollution and Its Adverse Effects on the Central Nervous System.

Air pollution is recognized as a significant public health problem and is associated with illnesses of the central nervous system (CNS) as well as neuroinflammation and neuropathology. Air pollution may cause chronic brain inflammation, white matter abnormalities, and microglia activation, which increases the risk of autism spectrum disorders, neurodegenerative disorders, stroke, and multiple sclerosis (MS). Methods: A literature review was done on "PubMed, EMBASE and Web of Science" on the relationship of air pollution with MS and stroke, using the keywords "air pollution" OR "pollution"; "ambient air pollution," "particulate matter, ozone, black carbon" AND "stroke" OR "cerebrovascular diseases," "multiple sclerosis," "neuroinflammation," or "neurodegeneration." Results: We first identified 128 articles and their related websites, of which 44 articles were further selected for analysis mainly based on study relevance, study quality and reliability, and date of publication. Further studies on air pollution and its adverse effects on the CNS are needed. The findings of such studies will support the development of appropriate preventive measures in the future.

Neurobiology of Amphetamine use in Stroke Recovery Combined with Rehabilitative Training and Brain Stimulation.

Stroke is a physiological disorder involving a prolonged local interruption of cerebral blood flow. It leads to massive neuronal death and causes short-term or long-lasting functional impairment. Most stroke victims regain some neural function weeks or months following a stroke, but this recovery can plateau six months or more after the injury. The goal of stroke therapy is the rehabilitation of functional capabilities, especially those affecting the patient's autonomy and quality of life. Recent clinical and animal studies combining acute dextro-amphetamine (d-AMPH) administration with rehabilitative training (RT) have revealed that this treatment has significant remedial effects. The review aims to examine the synergistic therapeutic effects of d-amphetamine coupled with RT, administered during the early or late subacute period, on neuronal activation, anatomic plasticity, and skilled motor function in a middle-aged rodent stroke model. The treatment will also include magnetic field stimulation. This review will help increase understanding of the mechanism of d-amphetamine coupled with RT and magnetic field stimulation and their converging therapeutic effects for stroke recovery.

External validation of a clinical prediction model in multiple sclerosis.

BACKGROUND: Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS). OBJECTIVE: We aimed to validate a previously published predictive model of individual treatment response using a non-overlapping cohort from the Middle East. METHODS: We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously. RESULTS: The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%-96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%-91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%. CONCLUSION: The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.

Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis.

The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 109/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.

Rare neurological manifestations in a Saudi Arabian patient with Ehlers-Danlos syndrome and a novel homozygous variant in the TNXB gene.

We report a 38-year-old Saudi male with Ehlers-Danlos Syndrome (EDS). The patient presented with rare and unusual neurological manifestations, including but not limited to ophthalmoplegia and myopathic pattern on his electromyography. In addition to hand weakness, there was skin hyperextensibility, joint hyperflexibility, and frontal baldness. Next-generation sequencing was performed on target exon sequences, using whole exome sequencing and Burrows-Wheeler Aligner for alignment/base calling. Genome Analysis Toolkit and reference genome Homo sapiens (UCSC hg19) were used for sequence processing and analysis. Variant classification was done according to standard international recommendations. A novel homozygous variant, NM_019105.6: c.8488C>T p.(Gln2830*), was detected in the TNXB gene. This variant is not reported in the literature nor dbSNP or gnomAD databases. Additionally, this variant is predicted to create a premature stop codon and produce a truncated protein or nonsense-mediated mRNA decay. Hence, it is classified as a likely pathogenic variant. The same point variant was found in a heterozygous state in the patient's father and sister. Both presented with milder symptoms associated with Ehlers-Danlos syndromes and heritable connective tissue disorders. Therefore, the patient was diagnosed as a tenascin-X (TNX) deficient type of EDS known as classical-like Ehlers-Danlos syndrome. TNX deficient patients may present with clinical and electrophysiological manifestations that are unusual in EDS like frontal baldness, ophthalmoplegia, and myotonia, which mimic myotonic dystrophy type I. Clinicians should be aware of the potential overlap of symptoms among these two diseases to ensure correct diagnosis is made.

Perioperative control of paroxysmal hypertension using esmolol with alpha-blockade in a child with a germline mutated paraganglioma.

SUMMARY: The use of antihypertensive medications in patients with pheochromocytomas and paragangliomas (PCC/PG) is usually a challenge. We report a case of familial paraganglioma that was successfully treated by esmolol and other antihypertensive medications without associated perioperative complications. Our patient was an 11-year-old girl who presented with classic symptoms and signs of PCC/PG and a CT scan of the abdomen that showed a right-sided paravertebral mass. Her father was diagnosed with paraganglioma a few years ago. Prazosin had been started but she continued to experience uncontrolled paroxysms of blood pressure (BP). She was known to have asthma; hence, she developed serious bronchospasm with atenolol. She was, therefore, switched to esmolol that successfully controlled her BP in addition to prazosin and intermittent doses of hydralazine prior to laparoscopic surgery with no side effects of medications or postoperative complications. Esmolol could be a good alternative to routinely used beta-blockers in children with PCC/PG with labile hypertension and related symptoms in the pre and intra-operative periods. It is titrable, effective, and can be weaned rapidly helping to avoid postoperative complications. Further larger studies on the use of esmolol in children with PCC/PG are needed to confirm our observation. LEARNING POINTS: In addition to alpha-blockers, esmolol could be a good alternative for routinely used beta-blockers to control paroxysmal hypertension and tachycardia in the pre- and intra-operative periods. Esmolol is titrable and an effective beta-blocker. It can be weaned rapidly helping to avoid postoperative complications in children with PCC/PG. Children with PCC/PG and other comorbidity like asthma may particularly benefit from the use of esmolol due to no or less side effects on airway resistance and the advantage of rapid titration of the medication compared to other beta-blockers.

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.

Fulminant Guillain-Barré Syndrome Post Hemorrhagic Stroke: Two Case Reports.

Guillain-Barré syndrome (GBS) is an acute, immune-mediated inflammatory peripheral polyneuropathy characterized by ascending paralysis. Most GBS cases follow gastrointestinal or chest infections. Some patients have been reported either following or concomitant with head trauma, neurosurgical procedures, and rarely hemorrhagic stroke. The exact pathogenesis is not entirely understood. However, blood-brain barrier damage may play an essential role in triggering the autoimmune activation that leads to post-stroke GBS. Here, we present two cases of fulminant GBS following hemorrhagic stroke to remind clinicians to be aware of this rare treatable complication if a stroke patient develops unexplainable flaccid paralysis with or without respiratory distress.

Utilization of Multiple Sclerosis Therapies in the Middle East Over a Decade: 2009-2018.

BACKGROUND: The multiple sclerosis (MS) landscape has changed over the past two decades across the world and in the Middle East. The Middle East is an ethnically diverse region located between 12° and 42° of latitude and 35° and 54° of longitude and varying altitudes. The magnitude of the shifts observed in the epidemiology and management of MS differ in each region and from country to country. OBJECTIVES: The aim of this study was to provide a clinicodemographic overview of the cohorts of patients contributed to MSBase, a large international MS registry, in the Middle East and describe disease-modifying treatment (DMT) utilization in the different countries within the region. Understanding the differences between these cohorts is integral to interpretation of the studies conducted using registry data and provides insight into clinical practice in these cohorts. METHODS: The MSBase registry was searched for patients with MS or clinically isolated syndrome from the Middle Eastern countries with data captured between 2009 and 2018. In 2-year epochs, and with special focus on the most recent epoch (2017-2018), we explored the demographic, clinical characteristics and treatment exposures of the studied cohorts and reported the results using standard descriptive statistics. RESULTS: Over the 10-year study period, 13,356 patients from 17 centers in 8 Middle Eastern countries fulfilled the inclusion criteria. The represented countries were Egypt, Iran, Kuwait, Lebanon, Oman, Saudi Arabia, Turkey and the United Arab Emirates. Overall, the represented cohort was young (median 36 years, quartiles 29-45) and captured relatively early after the onset of MS (median disease duration < 10 years, quartiles 3-12). The relapsing-remitting phenotype was the most prevalent phenotype in all countries (73-97%) and the highest proportion of progressive MS was reported in Saudi Arabia (12%). Median Expanded Disability Status Scale (EDSS) ranged from 0 to 3, depicting a mildly disabled cohort, with the exception of Saudi Arabia where the median EDSS was 4 (quartiles 1.5-6.5). The median relapse frequency was highest in Lebanon (median 1.03, 95% CI 0.94-1.16) followed by Egypt (median 1.02, 95% CI 0.89-1.24) and lowest in Saudi Arabia (median 0.70, 95% CI 0.58-0.95) and Kuwait (median 0.75, 95% CI 0.71-0.80). The treatment landscape greatly varied between different countries. Platform injectable therapies were mostly utilized in Egypt, Iran and Turkey (86%, 79% and 53%, respectively), while oral therapies and monoclonal antibodies were more commonly used in Kuwait, Lebanon and the United Arab Emirates (87.2%, 67.3% and 58.7%, respectively). CONCLUSION: Patients in the Middle East enrolled in a large multinational registry are representative of the general MS population. The spectrum of therapies used in the individual countries, however, is highly variable. Further studies that include rural and non-academic practices are needed to enhance our understanding of the MS cohorts in the Middle East.

Clinical course of myeloproliferative leukaemia virus oncogene (MPL) mutation-associated familial thrombocytosis: a review of 64 paediatric and adult patients.

Familial thrombocytosis (FT) is a rare hereditary haematological disorder characterised by increased platelet count, usually caused by germ-line mutations in thrombopoietin (THPO), myeloproliferative leukaemia virus oncogene (MPL) or Janus kinase 2 (JAK2) genes, and can be associated with increased risk of thrombosis. We aimed to determine the yield of diagnostic tests, assess treatment received and describe the clinical course of MPL-associated FT. We retrospectively reviewed all paediatric and adult haematology patients diagnosed with MPL-related FT, who were seen in our clinics from March 2013 to February 2021. Of 64 eligible patients, 26 (41%) were aged <14 years, while the remaining 38 (59%) patients were adults. The median (interquartile range) age at diagnosis was 20 (33·5) years. In all, 26 tribes were represented in this cohort of 64 patients, out of which 31 (48%) patients belonged to two tribes. A total of 60 patients (94%) had thrombocytosis on blood count. Additional genetic tests, including myelodysplastic syndrome (MDS) gene panel, Philadelphia gene breakpoint cluster region-Abelson (BCR-ABL) and JAK2, were carried out for 52 patients and only one patient was positive for JAK2 mutation. In all, 21 (33%) patients were prescribed aspirin and seven (11%) were prescribed hydroxyurea. Overall, 63 (98%) patients did not develop any thrombotic or haemorrhagic event. There was no significant association of MPL-mutated FT with thrombosis or haemorrhage.

A Prospective Multicenter Study for Assessing MusiQoL Validity among Arabic-Speaking MS Patients Treated with Subcutaneous Interferon ß-1a.

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN ß-1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients' clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months (65.67 ± 0.8 at baseline vs. 67.21 ± 0.79 at 6 months and 65.75 ± 0.8 at 12 months; p = 0.0015). Several aspects of patients' HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time (p = 0.215). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN ß-1a in Arabic-speaking patients with MS.

Colchicine-Induced Acute Myopathy: Case Study From Saudi Arabia.

Colchicine-induced myopathy has been described in patients with chronic renal failure and patients who are using a concomitant drug like a statin. However, pure myopathy caused by colchicine has never been reported in Saudi Arabia. A 64-year-old patient received colchicine for his gout arthritis disease and developed upper and lower limb weakness. He had a proximal weakness, and his muscle enzymes were very high. Furthermore, the needle electromyography (EMG) examination showed abundant fibrillations, myotonic discharges, and myopathic motor units. Two weeks after colchicine cessation, his weakness improved dramatically with normalization of creatine kinase (CK) and disappearance of myotonic discharges in the repeated EMG. This is the first case in Saudi Arabia that showed colchicine-induced myositis. The local clinicians' community needs to be aware of this rare side effect, as clinical suspicion is the most important diagnostic clue and the only effective treatment is the termination of colchicine.

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD. METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (ß = 0.45 (per decade), p<0.001) and disease duration (ß = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (ß = -0.48, p<0.001), mycophenolate mofetil (ß = -0.69, p = 0.04) and rituximab (ß = -0.35, p = 0.024). INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.

Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

BACKGROUND: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. OBJECTIVE: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. METHODS: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis. RESULTS: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. CONCLUSION: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Novel MFN2 Missense Mutation Induces Hereditary Axonal Motor and Sensory Neuropathy in a Saudi Arabian Family.

Hereditary axonal motor and sensory neuropathy or Charcot-Marie-Tooth type 2 (CMT2) is a common inherited peripheral neuropathy. Major symptomatologic signs vary from minimal to significant weakness and loss of sensation, feet usually affected more than hands. It may also cause visual acuity impairment, hearing loss, and skeletal deformity. CMT2 classification is based on the clinical, electrophysiological, and genetic inheritance pattern. Dominant CMT2 is classified from CMT2A to CMT2N and recessive CMT2 into CMT2B1 and CMT2B2. CMT2A is the most frequent subtype of CMT2 and caused by mutations in the mitofusin 2 (MFN2) gene. We hereby report a Saudi Arabian CMT2A patient with a variant c.58C>T of the MFN2 gene mutation.

Novel Homozygous Missense Mutation in CAPN3 Gene Detected in a Saudi Arabian Family With Limb-Girdle Muscular Dystrophy Type 2A.

More than 300 mutations were identified in Calpainopathy (CAPN3) gene in limb-girdle muscular dystrophy type 2A (LGMD2A) patients. LGMD2A type is also known as Calpainopathy, which is characterized by selective atrophy and weakness of proximal limb muscles. We report a Saudi Arabian family with weakness in limb-girdle distribution: waddling gait, positive Gowers' sign, and marked muscle atrophy in the shoulder and pelvic girdle muscles. We sequenced all exonic and intronic regions of the CAPN3 gene and identified c.1699 G>A variant as a novel variant not previously described in other patients. In silico predictions indicate that this is probably a disease-causing mutation. Here, for the first time, we report this c.1699 G>A new variant in the CAPN3 gene that can be considered as a robust genetics factor causing LGMD2A disease.

Monomelic amyotrophy with proximal upper limb involvement: a case report.

BACKGROUND: Monomelic amyotrophy is an uncommon, benign, unilateral disorder of the lower motor neurons, affecting predominantly the hand and forearm muscles. Proximal involvement of the arm and shoulder muscles is an unusual presentation that has been rarely reported in the literature. CASE PRESENTATION: A 28-year-old white man presented with insidious-onset, slowly progressive, unilateral weakness and atrophy of his left shoulder girdle and deltoid muscles. A neurological examination revealed weakness and atrophy in his left deltoid, infraspinatus and supraspinatus muscles. Electromyography demonstrated an active and chronic neurogenic pattern affecting his left C5 and C6 myotomes; magnetic resonance imaging of his cervical spine was normal. He did well with conservative treatment. CONCLUSIONS: Upper limb proximal form of monomelic amyotrophy is a rare clinical entity with a wide differential diagnosis. Physicians, especially neurologists, should be familiar with this benign condition to avoid inappropriately labeling patients as having amyotrophic lateral sclerosis and other disorders with less favorable outcomes.

Brain abscess following rituximab infusion in a patient with pemphigus vulgaris.

BACKGROUND: Immunocompromised patients are at increased risk for developing meningitis or, rarely, brain abscess with opportunistic organisms like Listeria monocytogenes. CASE REPORT: A 52 year-old Saudi Arabian woman who was diagnosed with pemphigus vulgaris and diabetes and had been on prednisolone and azathioprine for about 4 years. She presented with headache, low-grade fever, and left-sided weakness 2 weeks after receiving the second dose of rituximab infusion. Magnetic resonance imaging revealed an enhanced space-occupying lesion with multiple small cyst-like structures and vasogenic edema in the right temporoparietal area. Her blood culture was positive for Listeria monocytogenes, and a brain biopsy showed necrotic tissues with pus and inflammatory cells. She recovered after a 6-week course of antibiotics with ampicillin and gentamycin. CONCLUSIONS: Brain abscess due to Listeria monocytogenes is a risk that should be considered when adding rituximab to the regimen of a patient who is already Immunocompromised.