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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Dysregulated oscillatory connectivity in the visual system in autism spectrum disorder.


Autism spectrum disorder is increasingly associated with atypical perceptual and sensory symptoms. Here we explore the hypothesis that aberrant sen...

Fluctuating cognition in the Lewy body dementias.


Fluctuating cognition is a core diagnostic feature of dementia with Lewy bodies and is also a key clinical feature of Parkinson's disease dementia....

MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis.


Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative disease affecting the brain, spinal cord and optic nerves. Neuro...

Deep brain stimulation induced normalization of the human functional connectome in Parkinson's disease.


Neuroimaging has seen a paradigm shift away from a formal description of local activity patterns towards studying distributed brain networks. The r...

Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2.


Basal ganglia are subcortical grey nuclei that play essential roles in controlling voluntary movements, cognition and emotion. While basal ganglia ...

Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy.


Pathogenic variants of KCNQ2, which encode a potassium channel subunit, cause either benign (familial) neonatal epilepsy-B(F)NE)-or KCNQ2 encephalopathy (KCNQ2 DEE). We examined the characteristics of KCNQ2 variants.

KCNQ2 pathogenic variants were collected from in-house data and two large disease databases with their clinical phenotypes. Nonpathogenic KCNQ2 variants were collected from the Genome Aggregation Database (gnomAD). Pathogenicity of all variants was reevaluated with clinical information to exclude irrelevant variants. The cumulative distribution plots of B(F)NE, KCNQ2 DEE, and gnomAD KCNQ2 variants were compared. Several algorithms predicting genetic variant pathogenicity were evaluated.

A total of 259 individuals or pedigrees with 216 different pathogenic KCNQ2 variants and 2967 individuals with 247 different nonpathogenic variants were deemed eligible for the study. Compared to the distribution of nonpathogenic variants, B(F)NE and KCNQ2 DEE missense variants occurred in five and three specific KCNQ2 regions, respectively. Comparison between B(F)NE and KCNQ2 DEE sets showed that B(F)NE missense variants frequently localized to the intracellular domain between S2 and S3, whereas those of KCNQ2 DEE were more frequent in S6, and its adjacent pore domain, as well as in the intracellular domain between S6 and helix A. The scores of Protein Variation Effect Analyzer (PROVEAN) and Percent Accepted Mutation (PAM) 30 prediction algorithms were associated with phenotypes of the variant loci.

Missense variants in the intracellular domain between S2 and S3 are likely to cause B(F)NE, whereas those in S6 and its adjacent regions are more likely to cause KCNQ2 DEE. With such regional specificities of variants, PAM30 is a helpful tool to examine the possibility that a novel KCNQ2 variant is a B(F)NE or KCNQ2 DEE variant in genetic analysis.

The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS).


To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment.

Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10).

A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P = .037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy.

This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.

A single-nuclei RNA sequencing study of Mendelian and sporadic AD in the human brain.

Journal Alzheimers Research Therapy

Alzheimer's disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. Using bulk RNA-seq from the parietal lobes and deconvolution methods, we previously reported that brains exhibiting different AD genetic architecture exhibit different cellular proportions. Here, we sought to directly investigate AD brain changes in cell proportion and gene expression using single-cell resolution.

We generated unsorted single-nuclei RNA sequencing data from brain tissue. We leveraged the tissue donated from a carrier of a Mendelian genetic mutation, PSEN1 p.A79V, and two family members who suffer from sporadic AD, but do not carry any autosomal mutations. We evaluated alternative alignment approaches to maximize the titer of reads, genes, and cells with high quality. In addition, we employed distinct clustering strategies to determine the best approach to identify cell clusters that reveal neuronal and glial cell types and avoid artifacts such as sample and batch effects. We propose an approach to cluster cells that reduces biases and enable further analyses.

We identified distinct types of neurons, both excitatory and inhibitory, and glial cells, including astrocytes, oligodendrocytes, and microglia, among others. In particular, we identified a reduced proportion of excitatory neurons in the Mendelian mutation carrier, but a similar distribution of inhibitory neurons. Furthermore, we investigated whether single-nuclei RNA-seq from the human brains recapitulate the expression profile of disease-associated microglia (DAM) discovered in mouse models. We also determined that when analyzing human single-nuclei data, it is critical to control for biases introduced by donor-specific expression profiles.

We propose a collection of best practices to generate a highly detailed molecular cell atlas of highly informative frozen tissue stored in brain banks. Importantly, we have developed a new web application to make this unique single-nuclei molecular atlas publicly available.

Depression, subjective cognitive decline, and the risk of neurocognitive disorders.

Journal Alzheimers Research Therapy

Depression and subjective cognitive decline (SCD) both predict neurocognitive disorders (NCD). However, the two correlate strongly with each other. It remains uncertain whether they reflect independent neurobiological underpinnings which deserve separate attention. This study evaluated the independent risks of NCD associated with depression and SCD.

This cohort study included 13,462 participants who were ≥ 50 years and had normal cognition at baseline. The participants were evaluated for depression and SCD and followed up almost annually for incident mild cognitive impairment or dementia (MCI/dementia) (median follow-up = 4.4 years). Depression and SCD were included in Cox-regression to investigate their independent risks of MCI/dementia.

At baseline, 1307 participants (9.7%) had depression and 3582 (26.6%) had SCD. During follow-up, 1490 (11.1%) developed MCI/dementia. Depression and SCD demonstrated independent risks of MCI/dementia (HR 1.4 and 2.0 respectively). The risk was highest when depression and SCD co-occur (HR 2.8), with half of the participants in this group developing MCI/dementia within 7.2 years of follow-up (compared to 12.2 years in participants without depression or SCD).

The findings may change the clinical approach in managing SCD in depression, suggesting the need for greater emphasis on detecting prodromal NCD. They may also have implications to our understanding of NCD, suggesting the need for further research to delineate the commonalities and distinctions in the neurobiological pathways of depression and SCD.

Role of Population Receptive Field Size in Complex Visual Dysfunctions: A Posterior Cortical Atrophy Model.

JAMA Neurology

The neuronal mechanism of visual agnosia and foveal crowding that underlies the behavioral symptoms of several classic neurodegenerative diseases, including impaired holistic perception, navigation, and reading, is still unclear. A better understanding of this mechanism is expected to lead to better treatment and rehabilitation.

To use state-of-the-art neuroimaging protocols to assess a hypothesis that abnormal population receptive fields (pRF) in the visual cortex underlie high-order visual impairments.

Between April 26 and November 21, 2016, patients and controls were recruited from the Hadassah-Hebrew University medical center in a cross-sectional manner. Six patients with posterior cortical atrophy (PCA) were approached and 1 was excluded because of an inability to perform the task. Participants underwent functional magnetic resonance imaging-based cortical visual field mapping and pRF evaluation and performed a masked repetition priming task to evaluate visuospatial perception along the eccentricity axis. The association between pRF sizes and behavioral impairments was assessed to evaluate the role of abnormal pRF sizes in impaired visual perception. Posterior cortical atrophy is a visual variant of Alzheimer disease that is characterized by progressive visual agnosia despite almost 20/20 visual acuity. Patients with PCA are rare but invaluable for studying visual processing abnormalities following neurodegeneration, as atrophy begins in visual cortices but initially spares other brain regions involved in memory and verbal communication.

Participants underwent a magnetic resonance imaging scan.

Population receptive field sizes and their association with visual processing along the fovea-to-periphery gradient.

Five patients with PCA (4 men [80%]; mean [SEM] age, 62.9 [3.5] years) were compared with 8 age-matched controls (1 man [25%]; mean [SEM] age, 63.7 [3.7] years) and demonstrated an atypical pRF mapping that varied along the eccentricity axis, which presented as abnormally small peripheral and large foveal pRFs sizes. Abnormality was seen in V1 (peripheral, 4.4° and 5.5°; foveal, 5.5° and 4.5° in patients and controls, respectively; P < .05) as well as in higher visual regions, but not in intermediate ones. Behaviorally, an atypical fovea-to-periphery gradient in visual processing was found that correlated with their pRF properties (r = 0.8; P < .01 for the correlation between pRF and behavioral fovea-to-periphery slopes).

High-order visuocognitive functions may depend on abnormalities in basic cortical characteristics. These results may fundamentally change approaches to rehabilitation in such conditions, emphasizing the potential of low-level visual interventions.

Association Between Serum Neurofilament Light Chain Levels and Long-term Disease Course Among Patients With Multiple Sclerosis Followed up for 12 Years.

JAMA Neurology

Blood sample-based biomarkers that are associated with clinically meaningful outcomes for patients with multiple sclerosis (MS) have not been developed.

To evaluate the potential of serum neurofilament light chain (sNFL) measurements as a biomarker of disease activity and progression in a longitudinal MS data set.

Single-center, ongoing, prospective observational cohort study of 607 patients with MS from the longitudinal EPIC (Expression, Proteomics, Imaging, Clinical) study at the University of California, San Francisco from July 1, 2004, through August 31, 2017. Clinical evaluations and sample collection were performed annually for 5 years, then at different time points for up to 12 years, with a median follow-up duration of 10 (interquartile range, 7-11) years. Serum NFL levels were measured using a sensitive single molecule array platform and compared with clinical and magnetic resonance imaging variables with the use of univariable and multivariable analyses.

The main outcomes were disability progression defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score and brain fraction atrophy.

Mean (SD) age of the 607 study participants at study entry was 42.5 (9.8) years; 423 (69.7%) were women; and all participants were of non-Hispanic European descent. Of 3911 samples sequentially collected, 3904 passed quality control for quantification of sNFL. Baseline sNFL levels showed significant associations with EDSS score (β, 1.080; 95% CI, 1.047-1.114; P < .001), MS subtype (β, 1.478; 95% CI, 1.279-1.707; P < .001), and treatment status (β, 1.120; 95% CI, 1.007-1.245; P = .04). A significant interaction between EDSS worsening and change in levels of sNFL over time was found (β, 1.015; 95% CI, 1.007-1.023; P < .001). Baseline sNFL levels alone were associated with approximately 11.6% of the variance in brain fraction atrophy at year 10. In a multivariable analysis that considered sex, age, and disease duration, baseline sNFL levels were associated with 18.0% of the variance in brain fraction atrophy at year 10. After 5 years' follow-up, active treatment was associated with lower levels of sNFL, with high-potency treatments associated with the greater decreases in sNFL levels compared with platform therapies (high-potency vs untreated: β, 0.946; 95% CI, 0.915-0.976; P < .001; high-potency vs platform: β, 0.972; 95% CI, 0.948-0.998; P = .04).

This study found that statistically significant associations of sNFL with relevant clinical and neuroimaging outcomes in MS were confirmed and extended, supporting the potential of sNFL as an objective surrogate of ongoing MS disease activity. In this data set of patients with MS who received early treatment, the prognostic power of sNFL for relapse activity and long-term disability progression was limited. Further prospective studies are necessary to assess the assay's utility for decision-making in individual patients.

Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo.

JAMA Neurology

In multiple sclerosis (MS), chronic active lesions, which previously could only be detected at autopsy, can now be identified on susceptibility-based magnetic resonance imaging (MRI) in vivo as non-gadolinium-enhancing lesions with paramagnetic rims. Pathologically, they feature smoldering inflammatory demyelination at the edge, remyelination failure, and axonal degeneration. To our knowledge, the prospect of long-term in vivo monitoring makes it possible for the first time to determine their contribution to disability and value as a treatment target.

To assess whether rim lesions are associated with patient disability and long-term lesion outcomes.

We performed 3 studies at the National Institutes of Health Clinical Center: (1) a prospective clinical/radiological cohort of 209 patients with MS (diagnosis according to the 2010 McDonald revised MS criteria, age ≥18 years, with 7-T or 3-T susceptibility-based brain MRI results) who were enrolled from January 2012 to March 2018 (of 209, 17 patients [8%] were excluded because of uninterpretable MRI scans); (2) a radiological/pathological analysis of expanding lesions featuring rims; and (3) a retrospective longitudinal radiological study assessing long-term lesion evolution in 23 patients with MS with yearly MRI scans for 10 years or more (earliest scan, 1992).

(1) Identification of chronic rim lesions on 7-T or 3-T susceptibility-based brain MRI in 192 patients with MS and the association of rim counts with clinical disability (primary analysis) and brain volume changes (exploratory analysis). (2) Pathological characterization of 10 expanding lesions from an adult with progressive MS who came to autopsy after 7 years of receiving serial in vivo MRI scans. (3) Evaluation of annual lesion volume change (primary analysis) and T1 times (exploratory analysis) in 27 rim lesions vs 27 rimless lesions.

Of 209 participants, 104 (50%) were women and 32 (15%) were African American. One hundred seventeen patients (56%) had at least 1 rim lesion regardless of prior or ongoing treatment. Further, 84 patients (40%) had no rims (mean [SD] age, 47 [14] years), 66 (32%) had 1 to 3 rims (mean [SD] age, 47 [11] years), and 42 (20%) had 4 rims or more (mean [SD] age, 44 [11] years). Individuals with 4 rim lesions or more reached motor and cognitive disability at an earlier age. Normalized volumes of brain, white matter, and basal ganglia were lower in those with rim lesions. Whereas rimless lesions shrank over time (-3.6%/year), rim lesions were stable in size or expanded (2.2%/year; P < .001). Rim lesions had longer T1 times, suggesting more tissue destruction, than rimless lesions. On histopathological analysis, all 10 rim lesions that expanded in vivo had chronic active inflammation.

Chronic active lesions are common, are associated with more aggressive disease, exert ongoing tissue damage, and occur even in individuals treated with effective disease-modifying therapies. These results prompt the planning of MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS.