A Guideline for Early Diagnosis of Autoimmune Epilepsy Based on Clinical Manifestations and Common Para-Clinical Tests

No Abstrac

The Role of Immune System Dysfunction in Co-Existence of Neurological Disorders in Psoriasis

No Abstrac

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. RESULTS: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. CONCLUSION: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak

Phenotype and Genotype Heterogeneity of PLA2G6-Associated Neurodegeneration in a Cohort of Pediatric and Adult Patients

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. METHODS: An extensive review of the patients\u27 data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease\u27s underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. RESULTS: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. CONCLUSION: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype

Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology

Antisense oligonucleotides (ASOs) are disease-modifying agents affecting protein-coding and noncoding ribonucleic acids. Depending on the chemical modification and the location of hybridization, ASOs are able to reduce the level of toxic proteins, increase the level of functional protein, or modify the structure of impaired protein to improve function. There are multiple challenges in delivering ASOs to their site of action. Chemical modifications in the phosphodiester bond, nucleotide sugar, and nucleobase can increase structural thermodynamic stability and prevent ASO degradation. Furthermore, different particles, including viral vectors, conjugated peptides, conjugated antibodies, and nanocarriers, may improve ASO delivery. To date, six ASOs have been approved by the US Food and Drug Administration (FDA) in three neurological disorders: spinal muscular atrophy, Duchenne muscular dystrophy, and polyneuropathy caused by hereditary transthyretin amyloidosis. Ongoing preclinical and clinical studies are assessing the safety and efficacy of ASOs in multiple genetic and acquired neurological conditions. The current review provides an update on underlying mechanisms, design, chemical modifications, and delivery of ASOs. The administration of FDA-approved ASOs in neurological disorders is described, and current evidence on the safety and efficacy of ASOs in other neurological conditions, including pediatric neurological disorders, is reviewed

Social anxiety disorder among children and adolescents: A nationwide survey of prevalence, socio-demographic characteristics, risk factors and co-morbidities

Background: Social anxiety disorder is a frequent psychiatric disorder. We aimed to estimate the life-time prevalence, socio-demographic characteristics, risk factors and co-morbidities of this condition among children and adolescents. Methods: This was a cross sectional national survey conducted in Iranian individuals aged 6 to 18 years. Face-to-face household interviews were performed by trained clinical psychologists. The Farsi version of the kiddie schedule for affective disorders and schizophrenia for school-age children/present and lifetime version (K-SADS-PL) was administered to estimate the SAD prevalence. Parental personality traits and their psychopathologies were also obtained using Millon clinical multiaxial inventory, third edition (MCMI-III) to find the possible risk factors. Results: From 29,878 participants, 585 individuals were diagnosed with SAD and weighted lifetime prevalence of 1.8 was observed. The odds of this condition was significantly higher among older adolescents (odds ratio (OR):1.47; 95 confidence interval(CI): 1.11-1.95) and individuals with paternal history of psychiatric hospitalization (OR: 2.96; 95CI: 1.29-6.79). Higher means of persistent depression disorder (OR: 1.009; 95CI: 1.000-1.018) and melancholic personality trait (OR: 1.007; 95CI: 1.001-1.014) in mothers as well as schizophrenia spectrum (OR: 1.014; 95CI: 1.001-1.027) and anxiety (OR: 1.010; 95CI: 1.010-1.021) in fathers were statistically associated with higher odds of SAD in their children. Other anxiety disorders and behavioral disorders were the most prevalent co-morbidities. Limitations: The cross-sectional analysis does not enable analyses of possible causal associations. Lacking control group and follow-up periods were other major limitations that should be resolved in future studies. Conclusion: Clinicians and researchers need to continue studying this condition at all levels and in all developmental periods

In vitro mesenchymal stem cell responses on laser-welded NiTi alloy

The biocompatibility of NiTi after laser welding was studied by examining the in vitro (mesenchymal stem cell) MSC responses at different sets of time varying from early (4 to 12 h) to intermediate phases (1 and 4 days) of cell culture. The effects of physical (surface roughness and topography) and chemical (surface Ti/Ni ratio) changes as a consequence of laser welding in different regions (WZ, HAZ, and BM) on the cell morphology and cell coverage were studied. The results in this research indicated that the morphology of MSCs was affected primarily by the topographical factors in the WZ: the well-defined and directional dendritic pattern and the presence of deeper grooves. The morphology of MSCs was not significantly modulated by surface roughness. Despite the possible initial Ni release in the medium during the cell culture, no toxic effect seemed to cause to MSCs as evidenced by the success of adhesion and spreading of the cells onto different regions in the laser weldment. The good biocompatibility of the NiTi laser weldment has been firstly reported in this study

Laser melting of NiTi and its effects on in-vitro mesenchymal stem cell responses

Control of cell adhesion to synthetic polymers is a key factor in tissue engineering. The bioactivity of NiTi after laser melting was investigated implementing in vitro techniques for studying mesenchymal stem cell (MSC) responses. The effects of physical (surface roughness and topography) and chemical (surface Ti/Ni ratio) modifications as a consequence of laser melting on the cell morphology and cell coverage were studied. The results indicate that MSC morphology was affected primarily by topographical factors. No toxic effect in terms of Ni release affected the MSCs, as evidenced by the adhesion and spreading of the cell