The latest medical research on Neurology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about neurology gathered by our medical AI research bot.

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Electrical stimulation for seizure induction during SEEG exploration: a useful predictor of postoperative seizure recurrence?

Journal Neurol Neurosurg Psychiatry

Direct electrical stimulations of cerebral cortex are a traditional part of stereoelectroencephalography (SEEG) practice, but their value as a predictive factor for seizure outcome has never been carefully investigated.

We retrospectively analysed a cohort of 346 patients operated on for drug-resistant focal epilepsy after SEEG exploration. As potential predictors we included: aetiology, MRI data, age of onset, duration of epilepsy, age at surgery, topography of surgery and whether a seizure was induced by either low frequency electrical stimulation (LFS) or high frequency electrical stimulation.

Of 346 patients, 63.6% had good outcome (no seizure recurrence, Engel I). Univariate analysis demonstrated significant correlation with favourable outcome (Engel I) for: aetiology, positive MRI and seizure induced by stimulation. At multivariate analysis, informative MRI, type II focal cortical dysplasia and tumour reduced the risk of seizure recurrence (SR) by 47%, 58% and 81%, respectively. Compared with the absence of induced seizures, the occurrence of ictal events after LFS significantly predicts a favourable outcome on seizures, with only 44% chance of disabling SR at last follow-up.

Among the already known predictors outcome, seizure induction by LFS therefore represents a positive predictive factor for seizure outcome after surgery.

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis.

Journal Neurol Neurosurg Psychiatry

To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.

Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre-post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined.

We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%-11.1%). HFrTMS (1.08, 9, 0.35-1.80) and atDCS (0.56, 0.03-1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (-0.79, -2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77-2.54) and ctDCS (2.57, 0.20-4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.

HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

3D fast low-angle shot (FLASH) technique for 3T contrast-enhanced brain MRI in the inpatient and emergency setting: comparison with 3D magnetization-prepared rapid gradient echo (MPRAGE) technique.

Neuroradiology

To retrospectively evaluate the diagnostic performance of a 1-min contrast-enhanced 3D-FLASH pulse sequence for detecting intracranial enhancing lesions compared to standard contrast-enhanced 3D-MPRAGE pulse sequence.

Contrast-enhanced 3D-FLASH (acquisition time 49 s) and contrast-enhanced 3D-MPRAGE (4 min 35 s) pulse sequences were performed consecutively in 110 inpatient/emergency department 3T MRI brain examinations and analyzed by two independent neuroradiologist readers. For each sequence, the readers recorded (1) number of enhancing intracranial lesions; (2) intracranial susceptibility artifact (presence or absence; mm depth of intracranial signal loss); and (3) motion artifact (none, mild, moderate, severe). Inter and intra-reader agreement and reader accuracy relative to a reference standard were determined, and sequence comparison with respect to susceptibility and motion artifacts was performed.

There was substantial intra-reader, inter-sequence agreement [reader 1, κ = 0.70 (95% CI: [0.60, 0.81]); reader 2, κ = 0.70 (95% CI: [0.59, 0.82])] and substantial intra-sequence, inter-reader agreement [3D-MPRAGE assessment, κ = 0.76 (95% CI: [0.66, 0.86]); 3D-FLASH assessment, κ = 0.86 (95% CI: [0.77, 0.94]) for detection of intracranial enhancing lesions. For both readers, the diagnostic accuracy of 3D-FLASH and 3D-MPRAGE was similar (3D-MPRAGE: 86.4 and 88.1%; 3D-FLASH: 88.2 and 84.5%), with no inter-sequence diagnostic accuracy discordancy between the sequences for either reader. 3D-FLASH was associated with less susceptibility artifact (p < 0.001 both readers) and less motion artifact (p < 0.001 both readers).

On 3T brain MRI in the inpatient and emergency department setting, 1-min 3D-FLASH pulse sequence achieved comparable diagnostic performance to 4.5 min 3D-MPRAGE pulse sequence for detecting enhancing intracranial lesions, with reduced susceptibility and motion artifacts.

Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice.

Molecular Neurodegeneration

Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in the brain exclusively on microglia and genetic variants are linked to neurodegenerative diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD) and Nasu Hakola Disease (NHD). The Trem2 variant R47H, confers substantially elevated risk of developing late onset Alzheimer's disease, while NHD-linked Trem2 variants like Y38C, are associated with development of early onset dementia with white matter pathology. However, it is not known how these Trem2 species, predisposes individuals to presenile dementia.

To investigate if Trem2 Y38C or loss of Trem2 alters neuronal function we generated a novel mouse model to introduce the NHD Trem2 Y38C variant in murine Trem2 using CRISPR/Cas9 technology. Trem2Y38C/Y38C and Trem2-/- mice were assessed for Trem2 expression, differentially expressed genes, synaptic protein levels and synaptic plasticity using biochemical, electrophysiological and transcriptomic approaches.

While mice harboring the Trem2 Y38C exhibited normal expression levels of TREM2, the pathological outcomes phenocopied Trem2-/- mice at 6 months. Transcriptomic analysis revealed altered expression of neuronal and oligodendrocytes/myelin genes. We observed regional decreases in synaptic protein levels, with the most affected synapses in the hippocampus. These alterations were associated with reduced synaptic plasticity.

Our findings provide in vivo evidence that Trem2 Y38C disrupts normal TREM2 functions. Trem2Y38C/Y38C and Trem2-/- mice demonstrated altered gene expression, changes in microglia morphology, loss of synaptic proteins and reduced hippocampal synaptic plasticity at 6 months in absence of any pathological triggers like amyloid. This suggests TREM2 impacts neuronal functions providing molecular insights on the predisposition of individuals with TREM2 variants resulting in presenile dementia.

Leisure activity participation and risk of dementia: 18 year follow-up of the Whitehall II Study.

Neurology

To test the hypothesis that leisure activity participation is associated with lower dementia risk, we examined the association between participation in leisure activities and incident dementia in a large longitudinal study with average 18-year follow-up.

We used data from 8,280 participants of the Whitehall II prospective cohort study. A 13-item scale assessed leisure activity participation in 1997-99, 2002-04, and 2007-09 and incidence of dementia (n cases = 360, mean age at diagnosis 76.2 years, incidence rate = 2.4 per 1,000 person-years) was ascertained from 3 comprehensive national registers with follow-up until March 2017. Primary analyses were based on complete cases (n = 6,050, n cases = 247) and sensitivity analyses used multiple imputation for missing data.

Participation in leisure activities at mean age 55.8 (1997-99 assessment), with 18.0-year follow-up, was not associated with dementia (hazard ratio [HR] 0.92, 95% CI 0.79-1.06) but those with higher participation at mean age 65.7 (2007-09 assessment) were less likely to develop dementia with 8.3-year follow-up (HR 0.82 [0.69-0.98]). No specific type of leisure activity was consistently associated with dementia risk. Decline in participation between 1997-99 and 2007-09 was associated with subsequent dementia risk.

Our findings suggest that participation in leisure activities declines in the preclinical phase of dementia; there was no robust evidence for a protective association between leisure activity participation and dementia. Future research should investigate the socio-behavioural, cognitive, and neurobiological drivers of decline in leisure activity participation to determine potential approaches to improving social participation of those developing dementia.

Anti-seizure medication use during pregnancy and risk of ASD and ADHD in children.

Neurology

To determine whether children born to women who use anti-seizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors.

We used Swedish-register data (n = 14,614 children born 1996-2011 and followed through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%); and the 3 most commonly reported individual drugs (valproic acid, 4.8%; lamotrigine, 6.8%; and carbamazepine, 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.

Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (Hazard Ratio = 2.30, 95% CI = 1.53-3.47) and ADHD (HR = 1.74, 95% CI = 1.28-2.38). Whereas a small, non-statistically significant association with ASD (HR = 1.25, 95% CI = 0.88-1.79) and ADHD (HR = 1.18, 95% CI = 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD = 0.86, 95% CI = 0.67-1.53; HRADHD = 1.01, 95% CI = 0.67-1.53).

We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggest that certain ASMs may be safer than others in pregnancy.

Utility of Apical Lung Assessment on Computed Tomography Angiography as a COVID-19 Screen in Acute Stroke.

Stroke

Evaluation of the lung apices using computed tomography angiography of the head and neck during acute ischemic stroke (AIS) can provide the first objective opportunity to screen for coronavirus disease 2019 (COVID-19).

We performed an analysis assessing the utility of apical lung exam on computed tomography angiography for COVID-19-specific lung findings in 57 patients presenting with AIS. We measured the diagnostic accuracy of apical lung assessment alone and in combination with patient-reported symptoms and incorporate both to propose a COVID-19 era AIS algorithm.

Apical lung assessment when used in isolation, yielded a sensitivity of 0.67, specificity of 0.93, positive predictive value of 0.19, negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19, in patients presenting to the hospital for AIS. When combined with self-reported clinical symptoms of cough or shortness of breath, sensitivity of apical lung assessment improved to 0.83.

Apical lung assessment on computed tomography angiography is an accurate screening tool for COVID-19 and can serve as part of a combined screening approach in AIS.

Differences in network controllability and regional gene expression underlie hallucinations in Parkinson's disease.

Brain

Visual hallucinations are common in Parkinson's disease and are associated with poorer prognosis. Imaging studies show white matter loss and functi...

Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.

Journal Neurol Neurosurg Psychiatry

This was a post hoc analysis of the Edaravone Phase III Study MCI186-19 ('Study 19') to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised item scores from Study 19 were retrospectively mapped to King's stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King's and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King's stage.

During double-blind treatment, the percentage of patients who experienced a progression in King's stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo-edaravone arm than among those in the edaravone-edaravone arm (log-rank test, p<0.001).

The King's and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.

Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia.

Journal Alzheimers Research Therapy

In cognitively normal individuals, subjective cognitive decline (SCD) has been reported to predict MCI and dementia (MCI/dementia). However, prior studies mostly captured SCD at single time-points without considering the longitudinal course of SCD. This study examined whether the trajectories of SCD provide any added information-beyond one-time assessments of SCD-on the risk of MCI/dementia.

This cohort study included 5661 participants from the Alzheimer's Disease Centers across the USA, who were ≥ 50 years and had normal cognition in the first-four annual visits (year 1 to year 4). The participants were evaluated for SCD in the first-four annual visits (year 1 to year 4), and followed-up almost annually (year 4 up to year 14) for incident MCI/dementia. SCD trajectories (as identified from latent-class-growth-curve-analysis) were included in Cox regression to estimate their risks of MCI/dementia, with analyses further stratified by age (< 75 years versus ≥ 75 years; based on median-split).

Compared to those without SCD (in the first-four annual visits), Intermittent SCD (i.e., reported in 1-2 of the first-four annual visits) predicted a higher risk (HR 1.4) and Persistent SCD (i.e., reported in 3-4 of the first-four annual visits) predicted the highest risk (HR 2.2), with the results remaining significant even after adjusting for baseline SCD. Age-stratified analysis revealed that the risk associated with Intermittent SCD was only present in older individuals, while risk related to Persistent SCD was consistently present across the younger and older age groups. Age compounded the effects of the trajectories, whereby older individuals with Persistent SCD had > 75% probability of developing MCI/dementia by 10 years, in contrast to < 25% probability by 10 years in younger individuals with No SCD.

The findings demonstrate the utility of SCD trajectories-especially when used in combination with age strata-in identifying high-risk populations for preventive interventions and trials. They also suggest a potential modification in the current SCD criteria, with the inclusion of "persistent SCD over several years" as a feature of SCD plus.

Correction to: Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

Acta Neuorpathica

In the original publication, corresponding author information missed indicating that Dr. Zadeh.

Socioeconomic Status Mediates Racial Differences Seen Using the AT(N) Framework.

Annals Neurology

African Americans are at greater risk for developing Alzheimer disease (AD) dementia than non-Hispanic Whites. In addition to biological considerations (e.g., genetic influences; comorbid disorders), social and environmental factors may increase the risk of AD dementia. This paper (1) Assesses neuroimaging biomarkers of amyloid (A), tau (T), and neurodegeneration (N) for potential racial differences. (2) Considers mediating effects of socioeconomic status (SES) and measures of small vessel and cardiovascular disease on observed race differences.

Imaging measures of AT(N) (amyloid and tau positron emission tomography [PET] structural magnetic resonance imaging (MRI), and resting state functional connectivity (rs-fc) were collected from African American (n=131) and White (n=685) cognitively normal participants age 45 years and older. Measures of small vessel and cardiovascular disease (white matter hyperintensities [WMH] on MRI, blood pressure, body mass index [BMI]) and area-based socioeconomic status (SES) were included in mediation analyses.

Compared to White participants, African American participants had greater neurodegeneration, as measured by decreased cortical volumes (Cohen's f2 = 0.05, p < 0.001). SES mediated the relationship between race and cortical volumes. There were no significant race effects for amyloid, tau, or rs-fc signature.

Modifiable factors such as differences in social contexts and resources, particularly area-level SES, may contribute to observed racial differences in AD. Future studies should emphasize collection of relevant psychosocial factors in addition to the development of intentional diversity and inclusion efforts to improve the racial/ethnic and socioeconomic representativeness of AD studies. This article is protected by copyright. All rights reserved.