Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution.

Perinatal stroke is associated with significant short- and long-term morbidity and has been recognized as the most common cause of cerebral palsy in term infants. The diagnosis of presumed perinatal stroke (PPS) is made in children who present with neurological deficit and/or seizures attributable to focal chronic infarction on neuroimaging and have uneventful neonatal history. The underlying mechanism of presumed perinatal stroke remains unknown and thorough investigation of potential monogenic causes has not been conducted to date. Here, we describe the use of untargeted exome sequencing to investigate a cohort of eight patients from six families with PPS. A likely deleterious variant was identified in four families. These include the well-established risk genes COL4A2 and JAM3. In addition, we report the first independent confirmation of the recently described link between ESAM and perinatal stroke. Our data also highlight NID1 as a candidate gene for the condition. This study suggests that monogenic disorders are important contributors to the pathogenesis of PPS and should be investigated by untargeted sequencing especially when traditional risk factors are excluded.

Serial MRI studies over 12 months using manual and atlas-based region of interest in patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper and lower motor neurons. There is a need for an imaging biomarker to track disease progression. Previously, magnetic resonance imaging (MRI) has shown loss of grey and white matter in the brain of patients with ALS compared to controls. We performed serial diffusion tractography imaging (DTI) study of patients with ALS looking for changes over time. METHODS: On all subjects (n = 15), we performed three MRI studies at 6 month intervals. DTI changes were assessed with tract-based spatial statistics (TBSS) and region of interest (ROI) studies. Cortic-spinal tract (CST) was selected for our ROI at the upper level; the posterior limb of internal capsule (PLIC), and a lower level in the pons. RESULTS: There was no significant change in DTI measures over 12 months of observation. Better correlation of manual and atlas-based ROI methods was found in the posterior limb of the internal capsule than the pons. CONCLUSION: While previous DTI studies showed significant differences between ALS subjects and controls, within individual subjects there is little evidence of progression over 12 months. This suggests that DTI is not a suitable biomarker to assess disease progression in ALS.

Tract integrity in amyotrophic lateral sclerosis: 6-month evaluation using MR diffusion tensor imaging.

BACKGROUND: This study was performed to assess changes in diffusion tensor imaging (DTI) over time in patients with amyotrophic lateral sclerosis (ALS). METHODS: We performed DTI in 23 ALS patients who had two magnetic resonance imaging (MRI) scans at 6 month intervals and to correlate results with clinical features. The revised ALS functional rating scale (ALSFRS-R) was administered at each clinical visit. Data analysis included voxel-based white matter tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analysis of fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: With TBSS, there were no significant changes between the two scans. The average change in FA and MD in the ROIs over 6 months was small and not significant after allowing for multiple comparisons. After allowing for multiple comparisons, there was no significant correlation of FA or MD with ALSFRS-R. CONCLUSION: This study shows that there is little evidence of progressive changes in DTI over time in ALS. This could be because white matter is already substantially damaged by the time of onset of symptoms of ALS.

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications.

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.