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.

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.

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.

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.

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.

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.

Hypogonadism is common in men with myopathies.

BACKGROUND: Hypogonadism has been described in patients with myotonic muscular dystrophy type 1 but has not been evaluated in other myopathies. METHODS: We measured total and free serum testosterone levels in 59 men with myotonic muscular dystrophy type 1 (N = 12), facioscapulohumeral muscular dystrophy (N = 11), dystrophinopathy (N = 12), metabolic myopathy (N = 7), and inclusion body myositis (N = 17) and compared these with the normal reference interval. RESULTS: Thirty-two of the 59 (54%) participants had low total testosterone, 23 (39%) had low total and free values, and 5 (8%) had low free with normal total levels. There were no significant differences in the prevalence of hypogonadism between those with myotonic muscular dystrophy type 1 and the other groups even after considering age as a confounder. CONCLUSIONS: Hypogonadism is common in men with myopathies, and with the importance of testosterone in the maintenance of muscle mass, treatment of hypogonadism should be considered.

Finasteride-induced myalgia and HyperCKemia.

BACKGROUND: Finasteride is an antiandrogen, inhibits type II 5-alpha reductase (enzyme that converts testosterone to more potent form dihydrotestosterone), and is commonly used in the treatment of benign prostatic hyperplasia and male frontal baldness; however, it is not free from side effects, which include sexual dysfunction and, rarely, myopathy. We report a case of finasteride-associated myalgia and hyperCKemia and review similar cases reported in the literature. CASE REPORT: A 30-year-old man who had been taking finasteride 5 mg/d for 10 years to treat frontal baldness developed diffuse muscle aches associated with elevated creatine kinase level to 10,117 IU/L with neither weakness nor pigmenturia. His symptoms resolved and his creatine kinase level dropped down to 256 IU/L 3 weeks after finasteride discontinuation. CONCLUSION: Reversible myalgia associated with significant hyperCKemia is a possible adverse reaction of finasteride therapy.