Iranian clinical practice guideline for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.

Childhood-Onset Choreo-Dystonia Due to a Recurrent Novel Homozygous Nonsense HPCA Variant: Case Series and Literature Review.

Background: Biallelic variants in HPCA were linked to isolated dystonia (formerly DYT2) in 2015. Since then, the clinical spectrum of HPCA-related disorder has expanded up to including a complex syndrome encompassing neurodevelopmental delay, generalized dystonia with bulbar involvement, and infantile seizures. Cases: We report four individuals with a new phenotype of childhood-onset choreo-dystonia belonging to two unrelated Iranian pedigrees and harboring a novel homozygous nonsense pathogenic variant NM_002143.3:c.49C>T p.(Arg17*) in HPCA. Although the families are both Iranian, haplotype analysis of the exome data did not reveal a founder effect of the variant. Literature Review: A systematic review of articles on HPCA and dystonia published since the disease gene discovery (PubMed; search on July 09, 2022; search strategy "HPCA AND dystonia", "HPCA AND movement disorder", "hippocalcin AND dystonia", and "hippocalcin AND movement disorder"; no language restriction) resulted in 18 references reporting 10 cases from six families. HPCA-related dystonia was isolated or in various combinations with neurodevelopmental delay, intellectual disability, seizures, cognitive decline, and psychiatric comorbidity. Onset of dystonia ranged from infancy to early adulthood. Dystonia started in the limbs or neck and became generalized in most cases. Brain MRI was unremarkable in nearly all cases where performed. There was poor or no response to common antidystonic medications in most cases. Conclusions: Our case series expands the pheno-genotypic spectrum of HPCA-related disorder by describing childhood-onset choreo-dystonia as a new phenotype, reporting on a recurrent novel pathogenic nonsense variant in HPCA, and suggesting that exon 2 of HPCA might be a mutational hotspot.

Clinical and Neuroimaging Characteristics of Ischemic Stroke in Rhino-Orbito-Cerebral Mucormycosis Associated with COVID-19.

PURPOSE: The aim of this study was to compare clinical, neuroimaging, and laboratory features of rhino-orbito-cerebral mucormycosis (ROCM) in COVID-19 patients with and without ischemic stroke complications. METHODS: This observational study was conducted between August and December 2021 and 48 patients who had confirmed ROCM due to COVID-19, according to neuroimaging and histopathology/mycology evidence were included. Brain, orbit and paranasal sinus imaging was performed in all included patients. Data pertaining to clinical, neuroimaging, and laboratory characteristics and risk factors were collected and compared between patients with and without ischemic stroke complications. RESULTS: Of the patients 17 were diagnosed with ischemic stroke. Watershed infarction was the most common pattern (N = 13, 76.4%). Prevalence of conventional risk factors of stroke showed no significant differences between groups (patients with stroke vs. without stroke). Cavernous sinus (p = 0.001, odds ratio, OR = 12.8, 95% confidence interval, CI: 2.3-72) and ICA (p < 0.001, OR = 16.31, 95%CI: 2.91-91.14) involvement was more common in patients with stroke. Internal carotid artery (ICA) size (on the affected side) in patients with ischemic stroke was significantly smaller than in patients without stroke (median = 2.4 mm, interquartile range, IQR: 1.3-4 vs. 3.8 mm, IQR: 3.2-4.3, p = 0.004). Superior ophthalmic vein (SOV) size (on the affected side) in patients with stroke was significantly larger than patients without stroke (2.2 mm, IQR: 1.5-2.5 vs. 1.45 mm IQR: 1.1-1.8, p = 0.019). Involvement of the ethmoid and frontal sinuses were higher in patients with stroke (p = 0.007, OR = 1.85, 95% CI: 1.37-2.49 and p = 0.011, OR = 5, 95% CI: 1.4-18.2, respectively). Patients with stroke had higher D­dimer levels, WBC counts, neutrophil/lymphocyte ratios, and BUN/Cr ratio (all p < 0.05). CONCLUSION: Stroke-related ROCM was not associated with conventional ischemic stroke risk factors. Neuroimaging investigations including qualitative and quantitative parameters of cavernous sinus, ICA and SOV are useful to better understand the mechanism of stroke-related ROCM in COVID-19 patients.

Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a non-syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next-generation sequencing (NGS) a necessary approach for the proper diagnosis of LGMD. METHODS: In this article, 26 Iranian patients with LGMD criteria were diagnosed with disease variants in the genes encoding calpain3, dysferlin, sarcoglycans and Laminin α-2. Patients were referred to the hospital with variable distribution of muscle wasting and progressive weakness in the body. The symptoms along with biochemical and EMG tests were suggestive of LGMD; thus the genomic DNA of patients were investigated by whole-exome sequencing including flanking intronic regions. The target genes were explored for the disease-causing variants. Moreover, the consequence of the amino acid alterations on proteins' secondary structure and function was investigated for a better understanding of the pathogenicity of variants. Variants were sorted based on the genomic region, type and clinical significance. RESULTS: In a comprehensive investigation of previous clinical records, 6 variations were determined as novel, including c.1354-2 A > T and c.3169_3172dupCGGC in DYSF, c.568 G > T in SGCD, c.7243 C > T, c.8662_8663 insT and c. 4397G > C in LAMA2. Some of the detected variants were located in functional domains and/or near to the post-translational modification sites, altering or removing highly conserved regions of amino acid sequence.

On genotype-phenotype relationship of dystrophinopathies among Iranian population.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are inherited X-linked disorders resulting from alterations in the dystrophin gene. Genotype-phenotype matching studies have revealed a link between disease severity, the amount of muscle dystrophin, and the extent of mutation/deletion on the dystrophin gene. This study aimed to assess the relationship between genetic alterations in the dystrophin gene and the clinical status of patients with dystrophinopathies among the Iranian population. Methods: This cross-sectional study examined 54 patients with muscle weakness caused by abnormalities in the dystrophin gene at a hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, in 2021. The participants' demographic information, including age, family history of muscle dystrophies, and family history of other medical diseases as well as the type of muscular dystrophy were recorded. Furthermore, the number and region of deleted exons based on dystrophy types were also evaluated using multiplex ligation-dependent probe amplification (MLPA). The patients' gaits were also assessed as using a wheelchair, the presence of waddling gaits, or toe gaits. The patients' clinical status and the coexistence of pulmonary, bulbar, and mental conditions were also examined and compared between the two groups of dystrophinopathies. Results: In this study, 54 patients with dystrophinopathy with the mean age of 16.63 ± 12.10 years were evaluated, of whom 22 (40.7%) and 30 (55.6%) patients were classified as BMD and DMD, respectively. The most affected regions with deleted exons were exons 45-47 (n = 5) and 45-48 (n = 4) in patients with BMD, while exons 45, 48-52, 51-55, and 53 (2 cases per exon) were the most common affected exons in patients with DMD. Further analyses revealed that deletions in exons 45-47 and 51-55 were significantly associated with older and younger ages at the onset of becoming wheelchair-bound in patients with dystrophy, respectively. The hotspot range in both BMD and DMD was within exons 45-55 (n = 15 for each group); 63% of the patients had alterations on the dystrophin gene within this range [30 patients (68.18%) in the BMD group, 15 patients (53.57%) in the DMD group]. Conclusion: Exon deletion was the most common genetic alteration in patients with dystrophinopathies. No significant difference was observed between DMD and BMD regarding the number of deleted exons. Deletions in exons 45-47 and 51-55 were linked to later and earlier onset of becoming wheelchair-bound, respectively.

Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations.

Infantile neuroaxonal dystrophy (INAD) is a rare recessive neurodegenerative disorder manifested by symptoms like hypotonia, extrapyramidal signs, spastic tetraplegia, vision problems, cerebellar ataxia, cognitive complications, and dementia before the age of three. Various reports evaluated the relationship between the incidence of INAD and different mutations in the PLA2G6 gene. We described cases of two children with INAD whose diagnoses were challenging due to misleading findings and a mutation in the C.2370 T>G (p. Y790X) in the PLA2G6 gene based on NM_001349864, which has been reported previously.

Parsonage-Turner Syndrome following COVID-19 Infection: A Rare and Unique Case.

Parsonage-Turner syndrome (PTS) is a rare syndrome of unknown etiology; however, it is believed that an abnormality of immune response after a previous infection may be the cause of the disease. We report neuralgic amyotrophy in a patient with a history of kidney transplantation with severe acute respiratory distress syndrome coronavirus 2 infection. This literature is reviewed regarding clinical presentation, etiology, treatment, and prognosis of PTS after COVID-19 infection. We should consider PTS as another complication of COVID-19 infection.

Iranian Consensus Recommendations for Treatment of Myasthenia Gravis.

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran's local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG.

Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus.

Background: Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing. Objective: This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities. Methods: A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members. Conclusion: Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease.

Gabapentin versus Pregabalin for management of chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic autoimmune demyelinating peripheral neuropathy that leads to symmetrical muscular weakness, sensory deficit, hyporeflexia, chronic fatigue, and impaired quality of life (QoL). The current study aims to investigate the effects of gabapentin versus pregabalin on pain, sleep disturbances, and QoL in CIDP patients. METHODS: This clinical trial was conducted on 40 patients diagnosed with CIDP randomly allocated to treatment with 100-500 mg gabapentin (n=20) or 50-300 mg pregabalin (n=20) both co-medicated with 37.5 mg venlafaxine. The dose of gabapentin/pregabalin was adjusted based on the patient's tolerability/response to the treatment. Visual analogue scale (VAS), Pittsburg Sleep Quality Questionnaire and Short Form Health Survey (SF-36) were filled at baseline, within three, six, nine and 12 months after the interventions to assess pain severity, sleep quality and QoL, respectively. The Iranian Registry of Clinical Trials (IRCT) code: IRCT20200217046523N16, https://fa.irct.ir/search/result?query=IRCT20200217046523N16. RESULTS: Gabapentin revealed a dose-dependent efficacy in pain severity (P-value =0.004, r=0.287), sleep quality (P-value <0.001, r=0.387) and QoL (P-value =0.001, r=-0.378), but pregabalin (P-value >0.05). Co-medication of gabapentin plus venlafaxine could significantly improve sleep quality (P-value =0.009) and QoL (P-value =0.004), but pain severity (P-value =0.796). Pregabalin plus venlafaxine showed statistically significant improvement in pain (P-value =0.046), sleep quality (P-value <0.001) and QoL (P-value <0.001). The comparison of the two medications revealed the superiority of pregabalin in pain relief (P-value >0.001) and QoL (P-value =0.03) to pregabalin. CONCLUSION: Based on this study, the co-medication of pregabalin and venlafaxine led to remarkable superior outcomes compared to venlafaxine plus gabapentin in the management of pain, sleep quality, and QoL due to CIDP.

Peculiar Presentation of COVID-19: A Case Report of Concurrent Stroke and Guillain-Barré Syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has turned into a pandemic. There are few studies reporting Guillain-Barré syndrome (GBS) and stroke separately associated with COVID-19. In this study, we report an unusual case of COVID-19 with stroke and GBS concurrently. Case Report. A 59-year-old woman presented with left-sided weakness of two weeks' duration followed by right-sided weakness and foot paresthesia. She also complained of cough, myalgia, and respiratory distress of three weeks' duration. On examination, the patient had respiratory distress. The limb examination revealed asymmetric weakness. All limb reflexes were absent. Pinprick sensation was impaired. The chest CT scan and PCR of nasopharyngeal swab confirmed the diagnosis of COVID-19. Further evaluation revealed acute cerebral infarction and GBS. Consequently, the patient was treated by plasmapheresis, and her symptoms partially improved. CONCLUSION: According to reports, 36.4% of COVID-19 cases display neurological complications. The neurological manifestations of the disease can involve both the central and peripheral nervous systems. Previously, a few cases of GBS and cerebrovascular disease have been reported in association with COVID-19 separately, while in the present case, CNS and PNS involvement occurred concurrently. It is hypothesized that this concurrence is related to the imbalance of the systemic inflammatory responses and blood vessel autonomous dysfunction.

An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.

Prevalence and Risk Factors of Posterior Reversible Encephalopathy Syndrome in Isfahan, Iran.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiological syndrome characterized by such symptoms as headaches, altered consciousness, blurred vision, seizure, and focal neurological deficits. We herein present well-documented PRES cases and discuss the risk factors and characteristic imaging patterns of this syndrome. MATERIALS AND METHODS: We prospectively examined 31 patients with PRES in Alzahra Hospital, Isfahan, Iran, and compared the underlying diseases of PRES in terms of their clinical features and cranial magnetic resonance imaging (MRI) findings. RESULTS: The most common underlying disease was hypertension (90.3%), followed by systemic lupus erythematosus (32.3%), preeclampsia (25.8%), chronic renal failure (22.6%), and rheumatoid arthritis (22.6%). Interestingly, we also reported heroin abuse as a possible risk factor for PRES (9.7%). The most frequent clinical signs were headaches (54.8%), seizure (54.8%), and blurred vision (35.5%). The most frequent lesions on cranial MRI were in the parieto-occipital area (87.1%), followed by the cerebellum (19.4%) and the frontal lobe (12.9%). Other abnormalities on MRI were less common. In addition, 16.1% of the study population had vasospasm on magnetic resonance arteriography (MRA). Clinical recovery was followed by radiological resolution in all the patients. CONCLUSIONS: The clinical presentation is nonspecific, most patients present with a combination of symptoms, particularly headaches and seizure. MRI is crucial for the diagnosis of PRES, and MRA is useful in that it can identify associated vasospasm. Timely diagnosis and treatment are required to avoid a devastating outcome.

Guillain-Barre Syndrome and COVID-19 Vaccine: A Report of Nine Patients.

INTRODUCTION: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine. METHODS: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis. RESULTS: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements. CONCLUSION: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.

Quantitative muscle MRI study of patients with sporadic inclusion body myositis.

BACKGROUND: Fat infiltration in individual muscles of sporadic inclusion body myositis (sIBM) patients has rarely been assessed. METHODS: Sixteen sIBM patients were assessed using MRI of the thighs and lower legs (LL). The severity of fat infiltration, proximal-to-distal and side asymmetries, and the correlations with clinical and functional parameters were investigated. RESULTS: All the patients had fat-infiltrated muscles, and thighs were more severely affected than LL. A proximal-to-distal gradient of fat infiltration was mainly observed for adductors, quadriceps, sartorius, and medial gastrocnemius muscles. A strong negative correlation was observed between the whole muscle fat fraction in the thighs and LL and the Inclusion Body Myositis Functional Rating Scale and Medical Research Council scores for the lower limbs. CONCLUSIONS: Fat infiltration in individual muscles of sIBM patients is heterogeneous in terms of proximal-to-distal gradient and severity was correlated with clinical scores. These results should be considered for both natural history investigation and clinical trials.

Rhabdomyolysis and Muscle Necrosis Induced By Lead Poisoning.

A case is presented on a 40-year-old male with chronic lead poisoning with loss of consciousness, rhabdomyolysis, and acute renal failure after occupational exposure. Physical examination revealed generalized atrophy, tenderness, and swelling in the right limb and a decreased proximal muscle strength in the lower limb. A severe acute polyradiculoneuropathy in lower limbs documented by electromyography. All paraclinical tests were normal except increased blood lead level (75 µg/dl) and blue line in gum of the teeth. The patient was treated with penicillamine (500 mg q8 h) and pyridoxine (50 mg daily) for 8 months, only accessible drug in Iran. Force of patient's muscles in the proximal part of the lower limb was improved, and also the blood lead level reached to normal range. This is the first patient with rhabdomyolysis and muscle necrosis induced by lead poisoning.

Guillain-Barre syndrome in patients with coronavirus disease-2019: Report of six cases and review of literature.

Background: Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19. Methods: This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria. Results: Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode. Conclusion: Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship.

Association of helicobacter pylori with multiple sclerosis: Protective or risk factor?

Background: Multiple sclerosis (MS) is a common autoimmune inflammatory disease in the central nervous system (CNS) without exact pathology. Environmental factors such as infections have a causal or protective role in MS. Helicobacter pylori (HP) is one of the infections in digestive diseases and previous studies reported controversial findings of this infection role in MS. So, we conducted this study to assess the frequency of HP infection in patients with MS in comparison to the healthy population. Methods: This cross-sectional study was undertaken between 2015 and 2019. 191 participants including 58 patients with clinically isolated syndrome (CIS), 57 patients with relapsing-remitting MS (RRMS), 39 patients with secondary progressive MS (SPMS), and 39 age- and sex-matched healthy controls (HCs) were tested for the presence of HP immunoglobulin G (IgG) and IgM antibodies (Abs) in their serum sample. Results: The frequency of HP IgG seropositivity in patients with SPMS was significantly higher than patients with CIS [Odds ratio (OR): 6.333, 95% confidence interval (CI): 2.522-15.906, P < 0.001], patients with RRMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001), and HCs (OR: 8.485, 95% CI: 3.058-23.540, P < 0.001). We did not find a significant difference among other study groups regarding IgG seropositivity. No significant difference among groups regarding HP IgM seropositivity was evident. On univariate model, Expanded Disability Status Scale (EDSS) score (OR: 1.038, 95% CI: 1.038-1.460, P = 0.017) and SPMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001) were predictor for HP IgG seropositivity. On multivariate model, only SPMS had higher risk for HP IgG seropositivity compared to RRMS (OR: 5.554, 95% CI: 1.327-23.253, P = 0.019). We did not find a significant association between clinical and demographic variables with HP IgM seropositivity. Conclusion: Based on our findings, progressive MS and HP infection may have association. Further longitudinal studies with large sample size are needed to determine the role of HP infection in MS.

Motor neuron diseases caused by a novel VRK1 variant - A genotype/phenotype study.

BACKGROUND: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia-related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly. RESULTS: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsense-mediated decay machinery and results in a premature termination codon. CONCLUSIONS: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases.

Neuronal autoantibodies in focal epilepsy with or without mesial temporal sclerosis.

Background: This study was designed to investigate the difference in the prevalence of neuronal autoantibodies in patients diagnosed with established temporal lobe epilepsy (TLE) of unknown cause with mesial temporal sclerosis (MTS) and patients with TLE without MTS. Methods: In an observational cohort study design, we included thirty-three consecutive adult patients and divided them into two groups with and without MTS. We evaluated anti-neuronal and nuclear antibodies with immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: From the thirty-three consecutive patients with epilepsy 17 (51.1%) had MTS of which 12 had unilateral and 5 had bilateral MTS. No significant difference was detected between seropositive and seronegative patients in MTS versus non-MTS groups. The studied autoantibodies were present in 16 patients, including gamma-aminobutyric acid receptor (GABA-R) antibodies being the most common in 11 (33.3%), followed by N-methyl-D-aspartate receptor (NMDA-R) in 2 (6.1%), glutamic acid decarboxylase receptor (GAD-R) in 1 (3.0%), anti-phospholipid (APL) antibody in 1 (3.0%), CV2 in 1 (3.0%), Tr in 1 (3.0%), recoverin in 1 (3.0%), and double-stranded deoxyribonucleic acid (dsDNA) antibody in 1 (3.0%) of our patients with focal epilepsy. In both MTS and non-MTS groups, eight patients were positive for antibodies; four patients were positive for GABA in the MTS group and seven for GABA in the non-MTS group. Conclusion: Neuronal antibodies were presented in half of patients with focal epilepsy, GABA antibody being the leading one. No specific magnetic resonance imaging (MRI) findings were found in the seropositive group. Our results suggest that screening for relevant antibodies may enable us to offer a possible treatment to this group of patients.