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.
The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.
Want more personalised results?Request Access
Principal component analysis of texture features for grading of meningioma: not effective from the peritumoral area but effective from the tumor area.Neuroradiology
To investigate whether texture features from tumor and peritumoral areas based on sequence combinations can differentiate between low- and non-low-grade meningiomas.
Consecutive patients diagnosed with meningioma by surgery (77 low-grade and 28 non-low-grade meningiomas) underwent preoperative magnetic resonance imaging including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1WI (CE-T1WI). Manual segmentation of the tumor area was performed to extract texture features. Segmentation of the peritumoral area was performed for peritumoral high-signal intensity (PHSI) on T2WI. Principal component analysis was performed to fuse the texture features to principal components (PCs), and PCs of each sequence of the tumor and peritumoral areas were compared between low- and non-low-grade meningiomas. Only PCs with statistical significance were used for the model construction using a support vector machine algorithm. k-fold cross-validation with receiver operating characteristic curve analysis was used to evaluate diagnostic performance.
Two, one, and three PCs of T1WI, apparent diffusion coefficient (ADC), and CE-T1WI, respectively, for the tumor area, were significantly different between low- and non-low-grade meningiomas, while PCs of T2WI for the tumor area and PCs for the peritumoral area were not. No significant differences were observed in PHSI. Among models of sequence combination, the model with PCs of ADC and CE-T1WI for the tumor area showed the highest area under the curve (0.84).
The model with PCs of ADC and CE-T1WI for the tumor area showed the highest diagnostic performance for differentiating between low- and non-low-grade meningiomas. Neither PHSI nor PCs in the peritumoral area showed added value.
Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis.Alzheimers & Dementia
Whether the reduction in brain amyloid beta (Aβ) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated.
An instrumental variable meta-analysis was performed to infer the effect of change in positron emission tomography (PET)-measured Aβ standardized uptake value ratio (SUVR) on cognitive and functional decline.
Pooling data from 16 randomized trials demonstrates that each 0.1-unit decrease in PET Aβ SUVR is associated with a reduction (95% confidence interval) by 0.09 (0.034-0.15), 0.33 (0.12-0.55), and 0.13 (0.017-0.24) point in the average change of the Clinical Dementia Rating-Sum of Boxes, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination, respectively.
A widely cited meta-analysis article concluded amyloid beta reduction does not substantially improve cognition. We identified data inconsistencies in the initial publication and found new trial data. We repeated the meta-analysis after correcting data inconsistencies and adding new trial data. Updated results suggested statistically significant clinical benefit of amyloid beta reduction. Amyloid beta is a viable biological target for the treatment and prevention of AD.
Global, regional, and national trends of dementia incidence and risk factors, 1990-2019: A Global Burden of Disease study.Alzheimers & Dementia
An ample literature documents the growing prevalence of dementia and associated costs. Less attention has been paid to decreased dementia incidence in some countries.
We analyzed trends in age-standardized dementia, stroke, and ischemic heart disease (the triple threat) incidence rates and population attributable fraction of death and disability attributable to 12 risk factors in 204 countries and territories and 51 regions using Global Burden of Disease 2019 data.
During 1990 to 2019, dementia incidence declined in 71 countries; 18 showed statistically significant declines, ranging from -12.1% (95% uncertainty intervals -16.9 to -6.8) to -2.4% (-4.6 to -0.5). During 2010 to 2019, 16 countries showed non-significant declines. Globally, the burden of the triple threat attributable to air pollution, dietary risks, non-optimal temperature, lead exposure, and tobacco use decreased from 1990 to 2019.
The declining incidence of dementia in some countries, despite growing prevalence, is encouraging and urges further investigation.
In Vivo Functional Characterization of EGFR Variants Identifies Novel Drivers of Glioblastoma.Neuro-Oncology
Glioblastoma is the most common and aggressive primary brain tumor. Large scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.
We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased lipidomics screen.
Our screen identified A289I as the most potent EGFR variant, which has previously not been characterized. One of the mechanisms through with A289I promotes gliomagenesis is to alter cellular triacylglycerides through MTTP. Knockout of Mttp in mouse gliomas, reduces gliomagenesis in multiple models.
EGFR variants that differ by a single amino acid residue differentially promote gliomagenesis. Among the identified mechanism that drive glioma growth include lipid metabolism through MTTP. Understanding triacylglyceride accumulation may present a prospective therapeutic pathway for this deadly disease.
CSF Biomarkers of Alzheimer Disease in Patients With Concomitant α-Synuclein Pathology.Neurology
Cerebrospinal fluid (CSF) biomarkers amyloid-β42 (Aβ42), phosphorylated tau (p-tau181), total tau (t-tau) and neurogranin (Ng) can diagnose Alzheimer's disease (AD) in life. However, it is unknown if CSF concentrations, and thus their accuracies, are affected by concomitant pathologies common in AD, such as α-synuclein (αSyn). Our primary goal was to test if biomarkers in patients with AD are altered by concomitant αSyn. We compared CSF Aβ42, p-tau181, t-tau and Ng levels across autopsy-confirmed AD and concomitant AD and αSyn (AD+αSyn). Antemortem CSF levels were related to postmortem accumulations of αSyn. Finally, we tested how concommitant AD+αSyn affected diagnostic accuracy of two CSF-based strategies: the ATN framework and the t-tau/Aβ42 ratio.
Inclusion criteria were neuropathologic diagnoses of AD, mixed AD+αSyn, and αSyn. A convenience sample of non-impaired controls were selected with available CSF and a mini mental state exam (MMSE)≥27. αSyn without AD and controls were included as reference groups. Analyses of covariance (ANCOVAs) tested planned comparisons were CSF Aβ42, p-tau181, t-tau, and Ng differences across AD and AD+αSyn. Linear models tested how biomarkers were altered by αSyn accumulation in AD, accounting for pathologic amyloid-β and tau. Receiver operating characteristic and area under the curve (AUC), including 95% confidence intervals (CI), evaluated diagnostic accuracy.
Participants were 61 AD, 39 mixed AD+αSyn, 20 αSyn, and 61 Controls. AD had similar median age (73 [IQR=12]), MMSE (23 [IQR=9]), and sex distribution (Male=49%) compared to AD+αSyn age (70 [IQR=13]; p=0.3), MMSE (25 [IQR=9.5]; p=0.19), and sex distribution (Male=69%; p=0.077). ANCOVAs showed AD+αSyn had lower p-tau181 (F(1,94)=17, p=0), t-tau (F(1,93)=11, p=0.0004), and Ng levels (F(1,50)=12, p=0.0004) than AD; there was no difference in Aβ42 (p=0.44). Models showed increasing αSyn related to lower p-tau181 (β=-0.26, SE=0.092, p=0.0065), t-tau (β=-0.19, SE=0.092, p=0.041), and Ng levels (β=-0.2, SE=0.066, p=0.0046); αSyn was not a significant factor for Aβ42 (p=1). T-tau/Aβ42 had the highest accuracy when detecting AD, including mixed AD+αSyn cases (AUC=0.95; CI=0.92 to 0.98).
Findings demonstrate that concomitant αSyn pathology in AD is associated with lower CSF p-tau181, t-tau, and Ng levels, and can affect diagnositic accuracy in AD patients.
Racial Disparities in Stroke Recurrence: A Population-Based Study.Neurology
There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke.
Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence.
There were 3816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within three years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age- and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p=0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p=0.32). At younger ages, Black race was more strongly associated with recurrence and this effect may not be fully attenuated by traditional stroke risk factors.
Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence.
Pearls & Oy-sters: Tumefactive Demyelinating Lesions With MOG Antibodies Preceding Late-Infantile Metachromatic Leukodystrophy.Neurology
The development of acute neurological dysfunction associated with tumefactive demyelinating lesions (TDL) and mild diffuse involvement of the corpu...
Combined Effects of Synaptic and Axonal Integrity on Longitudinal Gray Matter Atrophy in Cognitively Unimpaired Adults.Neurology
Synaptic dysfunction and degeneration is a predominant feature of brain aging and synaptic preservation buffers against Alzheimer's disease (AD) protein-related brain atrophy. We tested whether cerebrospinal fluid (CSF) synaptic protein concentrations similarly moderate the effects of axonal injury, indexed via CSF neurofilament light [NfL], on brain atrophy in clinically normal adults.
Clinically normal older adults enrolled in the observational Hillblom Aging Network study at the UCSF Memory and Aging Center completed baseline lumbar puncture and longitudinal brain MRI (Mean scan [follow-up]=2.6 [3.7 years]). CSF was assayed for synaptic proteins (synaptotagmin-1, synaptosomal-associated protein 2 [SNAP-25], neurogranin, growth associated protein 43 [GAP-43]), axonal injury (NfL), and core AD biomarkers (ptau181/Aβ42 ratio; reflecting AD proteinopathy). Ten bilateral temporo-parietal gray matter ROIs shown to be sensitive to clinical AD were summed to generate a composite temporo-parietal ROI. Linear mixed-effects models tested statistical moderation of baseline synaptic proteins on baseline NfL-related temporo-parietal trajectories, controlling for ptau181/Aβ42 ratios.
Forty-six clinically normal older adults (Mean age=70; 43% female) were included. Synaptic proteins exhibited small to medium correlations with NfL (r range: .10 to .36). Higher baseline NfL, but not ptau181/Aβ42 ratios, predicted steeper temporo-parietal atrophy (NfL x time: β=-0.08, p<.001; ptau181/Aβ42 x time: β=-0.02, p=.31). SNAP-25, neurogranin, and GAP-43 significantly moderated NfL-related atrophy trajectories (-0.07≤βs≥-0.06, ps<.05) such that NfL was associated with temporo-parietal atrophy at high (more abnormal) but not low (more normal) synaptic protein concentrations. At high NfL concentrations, atrophy trajectories were 1.5 to 4.5 times weaker when synaptic protein concentrations were low (β range: -0.21 to -0.07) than high (β range: -0.33 to -0.30).
The association between baseline CSF NfL and longitudinal temporo-parietal atrophy is accelerated by synaptic dysfunction and buffered by synaptic integrity. Beyond AD proteins, concurrent examination of in vivo axonal and synaptic biomarkers may improve detection of neural alterations that precede overt structural changes in AD-sensitive brain regions.
Association of Contrast Enhancement After Reperfusion With Outcomes According to Blood Pressure Lowering in Acute Ischemic Stroke Patients.Neurology
Observational studies described associations between higher systolic blood pressure (SBP) values and intracranial hemorrhages (ICH) and worse outcomes after successful reperfusion by endovascular therapy (EVT). However, the BP-TARGET trial [BP-Target in Acute Ischemic Stroke to Reduce Hemorrhage after EVT] found that an intensive SBP target did not reduce ICH rates after successful EVT. The presence of contrast enhancement (CE) immediately after reperfusion is also associated with higher odds of ICH and worse outcomes. Our research question was to investigate the effect of two SBP strategies after reperfusion on ICH rates and functional outcomes according to the presence of CE in the BP-TARGET trial. We hypothesized that patients with CE could benefit from an intensive SBP control.
This study provides class IV evidence that for adults with contrast-enhancing lesions after successful EVT of an AIS, intensive blood pressure management did not significantly increase the risk of ICH.
Among the 324 patients randomized in BP-TARGET, 164 were included in this analysis, of whom 113 (68.9%) presented CE after reperfusion. The 24-hour mean SBP was significantly lower in the intensive SBP group compared with the standard group (129.7 versus 138.3 mmHg, p<0.001). Patients with CE and randomized in the intensive and standard SBP group had increased ICH rates: aOR=11.26, 95%CI 4.59-27.63 and aOR=4.08, 95%CI 1.75-9.50, respectively. However, the test of heterogeneity did not reach the significant level (aOR=2.76, 95%CI 0.80 to 9.48, p=0.11). Patients with CE and randomized in the intensive SBP group had also higher odds of unfavorable outcomes (aOR=2.91, 95%CI 1.24-6.82) but this association was not significant in the standard SBP group (aOR=1.89, 95%CI 0.85-4.23). No significant of heterogeneity was found between the two groups (aOR, 1.54, 95%CI 0.48 to 4.97, p=0.47).
Altogether, patients with CE and randomized in the intensive SBP group did not have lower rates of ICH or improved outcomes compared to the standard SBP group, as CE was associated with higher odds of ICH in both groups, without significant heterogeneity.
Risk Factors for Term-Born Periventricular White Matter Injury in Children With Cerebral Palsy: A Case-Control Study.Neurology
The aim of this study was to identify possible risk factors associated with term born children with cerebral palsy (CP) and periventricular white matter injury (PVWMI) on imaging.
This is a case-controlled study restricted to term born children with CP with the cases extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls from Alberta Pregnancy Outcomes and Nutrition (APrON) Study. A diagnosis of PVWMI was made based on expert categorization of MRI reports. Risk factor variables were selected a priori; these included pregnancy complications, antenatal toxin exposure, perinatal infection, sex, small for gestational age, and perinatal adversity (i.e. neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia). We used multivariable analyses to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).
A total of 160 cases (7.06% of the registry sample) were compared to 1950 controls. Of the term born PVWMI participants, 59.4% were males and 13.5 % were born to mothers of extreme maternal age. Multivariable analysis of each risk factor controlled for weight showed PVWMI is associated with pregnancy complications (OR=3.35; 95% CI=2.23-4.94), antenatal toxin exposure (OR=2.45; 95% CI=1.67-3.55), perinatal infection (OR=3.61; 95% CI=1.96-6.29) and perinatal adversity (OR=2.03; 95% CI=1.42-2.94). Term born males were not more likely to have PVWMI compared to females (OR=1.37; 95% CI=0.98-1.93). Multiple regression analyses suggested independent associations between PVWMI and pregnancy complications (OR=3.75; 95% CI 2.46-5.62), antenatal toxin exposure (OR=2.80; 95% CI 1.88-4.12), perinatal infection (OR=4.62; 95% CI 2.46-8.42) and perinatal adversity (OR=2.49; 95% CI= 1.71-3.69).
Risk factors such as pregnancy complications, antenatal toxin exposure, perinatal infection as well as perinatal adversity are associated with PVWMI in term born children, suggesting perhaps variable interactions between antenatal and perinatal factors to yield this under-recognized CP phenotype.
Auditory processing in rodent models of autism: a systematic review.Journal of Neurodevelopmental Disorders
Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficult...
Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy.Epilepsia
Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity.
Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected.
The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml).
Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.