ECG monitoring of post-stroke occurring arrhythmias: an observational study using 7-day Holter ECG

Post-stroke arrhythmias represent a risk factor for complications and worse prognosis after cerebrovascular events. The aims of the study were to detect the rate of atrial fibrillation (AF) and other cardiac arrhythmias after acute ischemic stroke, by using a 7-day Holter ECG which has proved to be superior to the standard 24-h recording, and to evaluate the possible association between brain lesions and arrhythmias. One hundred and twenty patients with cryptogenic ischemic stroke underwent clinical and neuroimaging assessment and were monitored with a 7-day Holter ECG. Analysis of the rhythm recorded over 7 days was compared to analysis limited at the first 24 h of monitoring. 7-day Holter ECG detected AF in 4% of patients, supraventricular extrasystole (SVEB) in 94%, ventricular extrasystole (VEB) in 88%, short supraventricular runs (SVRs) in 54%, supraventricular tachycardia in 20%, and bradycardia in 6%. Compared to the first 24 h of monitoring, 7-Holter ECG showed a significant higher detection for all arrhythmias (AF p = 0.02; bradycardia p = 0.03; tachycardia p = 0.0001; SVEB p = 0.0002; VEB p = 0.0001; SVRs p = 0.0001). Patients with SVRs and bradycardia were older (p = 0.0001; p = 0.035) and had higher CHA2DS2VASc scores (p = 0.004; p = 0.026) respectively, in the comparison with patients without these two arrhythmias. An association was found between SVEB and parietal (p = 0.013) and temporal (p = 0.013) lobe lesions, whereas VEB correlated with insular involvement (p = 0.002). 7-day Holter ECG monitoring proved to be superior as compared to 24-h recording for the detection of all arrhythmias, some of which (SVEB and VEB) were associated with specific brain areas involvement. Therefore, 7-day Holter ECG should be required as an effective first-line approach to improve both diagnosis and therapeutic management after stroke.

Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted.Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8–10.0, Group B mdn = 10, IQR = 6.5–11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity).Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.

A Case of Metastatic CNS Melanoma of Unknown Primary Presenting with Seizures

Seizures are a common occurrence. The goal of evaluating a seizure is to identify the etiology and to determine the likelihood of recurrence as well as guide management. We present a unique presentation of a 47-year-old female that presented with late onset seizures admitted due to status epilepticus. Brain magnetic resonance indicated diffuse supratentorial hemorrhagic lesions. Neurological workup including brain vessel imaging, CT chest, abdomen, and pelvis as well as CSF and serological workup for vasculitis failed to demonstrate the cause of her brain lesions. Ultimately, a brain biopsy showed metastatic melanoma of unknown primary origin.

A phase I study of oral vitamin D3 supplementation in boys with X-linked adrenoleukodystrophy

Objective: Vitamin D status has been linked to risk of inflammatory brain lesions. We sought to assess the safety and pharmacokinetics of oral vitamin D dosing regimens in boys with X-linked adrenoleukodystrophy (ALD). Methods: In this open-label, multi-center, phase I study, we enrolled 21 ALD males without brain lesions, aged 1.5 to 25 years to oral vitamin D supplementation for 12 months. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40-80ng/ml) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in brain and blood. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. Following a mid-study safety assessment, we modified the dosing regimen so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily. Results: Between October 2016 and June 2019, we recruited 21 participants (n=12 fixed dose; n=9 weight-stratified) with a median age and weight of 6.7 years and 20 kilograms. Most participants achieved target plasma vitamin D levels at 6 and 12 months regardless of dosing regimen. In the fixed dose regimen, 6 of 12 participants had asymptomatic elevation in urine calcium:creatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels increased between baseline and 12 months in the brain but not in the blood. Conclusions: Our weight-stratified vitamin D dosing regimen was well-tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels increased over the 12-month trial period. Classification of Evidence: This study provides Class II evidence that a weight-stratified dosing regimen of vitamin D supplementation is safe, well-tolerated, and effective at achieving moderately high vitamin D levels in boys with ALD.

Vitamin D Status & Latitude Predict Brain Lesions in Adrenoleukodystrophy

A subset of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions. Risk factors are largely undefined. We used two independent cohorts to assess whether low vitamin D status predicts lesion development. In our first cohort, we measured 25-hydroxyvitamin D in 53 plasma samples from 20 pre-lesional ALD boys followed at two centers; half subsequently developed lesions. In our second cohort, we measured latitude (using home ZIP code) among 230 ALD boys in a database of 51 US pediatric hospitals; over half developed lesions. In regression models, low plasma vitamin D and northerly latitudes independently predicted ALD brain lesions.

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.

Diverse imaging features of adolescent glioblastoma: a case report

We highlight an unusual case of multifocal glioblastoma in an adolescent patient, manifesting as four discrete brain lesions, each distinct in appearance. Familiarity with the diverse imaging features of glioblastoma can reduce misdiagnosis and avoid treatment delays.