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Frontiers in Neurology 2020Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated...
Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease. However, the prevalence of AQP4-IgG seropositivity and MOG-IgG seropositivity in isolated ON is unclear, and studies comparing visual outcomes and optical coherence tomography (OCT)-derived structural retinal measures between MS-ON, AQP4-ON, and MOG-ON eyes are limited by small sample sizes. (1) To assess the prevalence of AQP4-IgG and MOG-IgG seropositivity among patients presenting with isolated ON; (2) to compare visual outcomes and OCT measures between AQP4-ON, MOG-ON, and MS-ON eyes. In this systematic review and meta-analysis, a total of 65 eligible studies were identified by PubMed search. Statistical analyses were performed with random effects models. In adults with isolated ON, AQP4-IgG seroprevalence was 4% in non-Asian and 27% in Asian populations, whereas MOG-IgG seroprevalence was 8 and 20%, respectively. In children, AQP4-IgG seroprevalence was 0.4% in non-Asian and 15% in Asian populations, whereas MOG-IgG seroprevalence was 47 and 31%, respectively. AQP4-ON eyes had lower peri-papillary retinal nerve fiber layer (pRNFL; -11.7 μm, 95% CI: -15.2 to -8.3 μm) and macular ganglion cell + inner plexiform layer (GCIPL; -9.0 μm, 95% CI: -12.5 to -5.4 μm) thicknesses compared with MS-ON eyes. Similarly, pRNFL (-11.2 μm, 95% CI: -21.5 to -0.9 μm) and GCIPL (-6.1 μm, 95% CI: -10.8 to -1.3 μm) thicknesses were lower in MOG-ON compared to MS-ON eyes, but did not differ between AQP4-ON and MOG-ON eyes (pRNFL: -1.9 μm, 95% CI: -9.1 to 5.4 μm; GCIPL: -2.6 μm, 95% CI: -8.9 to 3.8 μm). Visual outcomes were worse in AQP4-ON compared to both MOG-ON (mean logMAR difference: 0.60, 95% CI: 0.39 to 0.81) and MS-ON eyes (mean logMAR difference: 0.68, 95% CI: 0.40 to 0.96) but were similar in MOG-ON and MS-ON eyes (mean logMAR difference: 0.04, 95% CI: -0.05 to 0.14). AQP4-IgG- and MOG-IgG-associated disease are important diagnostic considerations in adults presenting with isolated ON, especially in Asian populations. Furthermore, MOG-IgG seroprevalence is especially high in pediatric isolated ON, in both non-Asian and Asian populations. Despite a similar severity of GCIPL and pRNFL thinning in AQP4-ON and MOG-ON, AQP4-ON is associated with markedly worse visual outcomes.
PubMed: 33132999
DOI: 10.3389/fneur.2020.540156 -
Frontiers in Psychiatry 2020Smartphone technology has enabled the creation of many working memory training (WMT) Apps, with those peer-reviewed described in a recent review. WMT claims to improve...
BACKGROUND
Smartphone technology has enabled the creation of many working memory training (WMT) Apps, with those peer-reviewed described in a recent review. WMT claims to improve working memory, attention deficits, hyperactivity and fluid intelligence, in line with plasticity brain changes. Critics argue that WMT is unable to achieve "far-transfer"-the attainment of benefits to cognition from one taught context to another dissimilar context-associated with improved quality of life. However, brain changes after a course of WMT in frontoparietal and striatal circuits-that often occur prior to behavioral changes-may be a better indicator of far-transfer efficacy, especially to improve impulse control commonly dysregulated in those with addictive disorders, yet not commonly examined in WMT studies.
METHOD
In contrast to previous reviews, the aim here is to focus on the findings of brain imaging WMT training studies across various imaging modalities that use various paradigms, published PubMed, Scopus, Medline, and Google Scholar.
RESULTS
35 brain imaging studies utilized fMRI, structural imaging (MRI, DTI), functional connectivity, EEG, transcranial direct current stimulation (tDCS), cerebral perfusion, and neurogenetic analyses with tasks based on visuospatial and auditory working memory, dual and standard n-back.
DISCUSSION
Evidence suggests that repeated WMT reduces brain activation in frontoparietal and striatal networks reflective of increased neural circuitry efficiency myelination and functional connectivity changes. Neural effects of WMT may persist months after training has ended, lead to non-trained task transfer, be strengthened by auxiliary methods such as tDCS and be related to COMT polymorphisms. WMT could be utilized as an effective, non-invasive intervention for working memory deficits to treat impulse and affective control problems in people with addictive disorders.
PubMed: 33132926
DOI: 10.3389/fpsyt.2020.512761 -
ELife Oct 2020Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these... (Meta-Analysis)
Meta-Analysis
Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.
Topics: Animals; Biomarkers; Humans; Magnetic Resonance Imaging; Mice; Myelin Sheath; Rats
PubMed: 33084576
DOI: 10.7554/eLife.61523 -
PloS One 2020Iron is involved in many processes in the brain including, myelin generation, mitochondrial function, synthesis of ATP and DNA and the cycling of neurotransmitters....
Iron is involved in many processes in the brain including, myelin generation, mitochondrial function, synthesis of ATP and DNA and the cycling of neurotransmitters. Disruption of normal iron homeostasis can result in iron accumulation in the brain, which in turn can partake in interactions which amplify oxidative damage. The development of MRI techniques for quantifying brain iron has allowed for the characterisation of the impact that brain iron has on cognition and neurodegeneration. This review uses a systematic approach to collate and evaluate the current literature which explores the relationship between brain iron and cognition. The following databases were searched in keeping with a predetermined inclusion criterion: Embase Ovid, PubMed and PsychInfo (from inception to 31st March 2020). The included studies were assessed for study characteristics and quality and their results were extracted and summarised. This review identified 41 human studies of varying design, which statistically assessed the relationship between brain iron and cognition. The most consistently reported interactions were in the Caudate nuclei, where increasing iron correlated poorer memory and general cognitive performance in adulthood. There were also consistent reports of a correlation between increased Hippocampal and Thalamic iron and poorer memory performance, as well as, between iron in the Putamen and Globus Pallidus and general cognition. We conclude that there is consistent evidence that brain iron is detrimental to cognitive health, however, more longitudinal studies will be required to fully understand this relationship and to determine whether iron occurs as a primary cause or secondary effect of cognitive decline.
Topics: Adult; Aged; Aged, 80 and over; Brain; Child; Cognition; Female; Humans; Iron; Male; Middle Aged
PubMed: 33057378
DOI: 10.1371/journal.pone.0240697 -
Nutrients Jul 2020Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain...
Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).
Topics: Clinical Trials as Topic; Humans; Neuralgia; Observational Studies as Topic; Peripheral Nervous System Diseases; Treatment Outcome; Vitamin B 12
PubMed: 32722436
DOI: 10.3390/nu12082221 -
Stroke Aug 2020Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.
METHODS
A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742).
RESULTS
We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57-0.81]; <0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29-0.64]; =0.0001), deaths (OR=0.64 [95% CI, 0.49-0.83], <0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54-0.99]; =0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.
CONCLUSIONS
Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.
Topics: Cilostazol; Cognitive Dysfunction; Fibrinolytic Agents; Humans; Phosphodiesterase 3 Inhibitors; Secondary Prevention; Stroke
PubMed: 32646330
DOI: 10.1161/STROKEAHA.120.029454 -
Cells Jun 2020Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs)...
Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC-OL crosstalk is essential in understanding cSVD development.
Topics: Cerebral Small Vessel Diseases; Endothelial Cells; Humans; Oligodendroglia; Wnt Signaling Pathway
PubMed: 32630426
DOI: 10.3390/cells9061545 -
Frontiers in Neurology 2020Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be...
Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be impacted early in Parkinson disease (PD). Diffusion magnetic resonance imaging (dMRI) has been used extensively to understand such pathological WM changes, and the focus of this systematic review is to understand both the methods utilized and their corresponding results in the context of early-stage PD. Diffusion tensor imaging (DTI) is the most commonly utilized method to probe WM pathological changes. Previous studies have suggested that DTI metrics are sensitive in capturing early disease-associated WM changes in preclinical symptomatic regions such as olfactory regions and the substantia nigra, which is considered to be a hallmark of PD pathology and progression. Postprocessing analytic approaches include region of interest-based analysis, voxel-based analysis, skeletonized approaches, and connectome analysis, each with unique advantages and challenges. While DTI has been used extensively to study WM disorganization in early-stage PD, it has several limitations, including an inability to resolve multiple fiber orientations within each voxel and sensitivity to partial volume effects. Given the subtle changes associated with early-stage PD, these limitations result in inaccuracies that severely impact the reliability of DTI-based metrics as potential biomarkers. To overcome these limitations, advanced dMRI acquisition and analysis methods have been employed, including diffusion kurtosis imaging and q-space diffeomorphic reconstruction. The combination of improved acquisition and analysis in DTI may yield novel and accurate information related to WM-associated changes in early-stage PD. In the current article, we present a systematic and critical review of dMRI studies in early-stage PD, with a focus on recent advances in DTI methodology. Yielding novel metrics, these advanced methods have been shown to detect diffuse WM changes in early-stage PD. These findings support the notion of early axonal damage in PD and suggest that WM pathology may go unrecognized until symptoms appear. Finally, the advantages and disadvantages of different dMRI techniques, analysis methods, and software employed are discussed in the context of PD-related pathology.
PubMed: 32477235
DOI: 10.3389/fneur.2020.00314 -
Frontiers in Neuroscience 2020Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of...
Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of treatment is surgical decompression, which leads to partial recovery of symptoms, however, long term prognosis of the condition remains poor. Despite advances in treatment methods, the underlying pathobiology is not well-known. A better understanding of the disease is therefore required for the development of treatments to improve outcomes following surgery. To systematically evaluate the pathophysiology of DCM and the mechanism underlying recovery following decompression. A total of 13,808 published articles were identified in our systematic search of electronic databases (PUBMED, WEB OF SCIENCE). A total of 51 studies investigating the secondary injury mechanisms of DCM or physiology of recovery in animal models of disease underwent comprehensive review. Forty-seven studies addressed the pathophysiology of DCM. Majority of the studies demonstrated evidence of neuronal loss following spinal cord compression. A number of studies provided further details of structural changes in neurons such as myelin damage and axon degeneration. The mechanisms of injury to cells included direct apoptosis and increased inflammation. Only four papers investigated the pathobiological changes that occur in spinal cords following decompression. One study demonstrated evidence of axonal plasticity following decompressive surgery. Another study demonstrated ischaemic-reperfusion injury following decompression, however this phenomenon was worse when decompression was delayed. In preclinical studies, the pathophysiology of DCM has been poorly studied and a number of questions remain unanswered. The physiological changes seen in the decompressed spinal cord has not been widely investigated and it is paramount that researchers investigate the decompressed spinal cord further to enable the development of therapeutic tools, to enhance recovery following surgery.
PubMed: 32425740
DOI: 10.3389/fnins.2020.00138 -
Case Reports in Medicine 2020Lethal congenital contracture syndrome type 7 (LCCS7) and congenital hypomyelinating neuropathy type 3 (CHN3) are rare autosomal recessive diseases, characterized by...
Lethal congenital contracture syndrome type 7 (LCCS7) and congenital hypomyelinating neuropathy type 3 (CHN3) are rare autosomal recessive diseases, characterized by severe neonatal hypotonia, polyhydramnios, arthrogryposis, facial diplegia, and severe motor paralysis, leading to death in early infancy. They are related to mutations in the (contactin associated protein 1) gene, playing an important role in myelination. Recent studies have shown that both diseases could present with a wide phenotypic spectrum, with promising survival up to early childhood. We report on a 7-year-old boy from a nonconsanguineous Lebanese family presenting with neonatal hypotonia, respiratory distress, and arthrogryposis. Molecular analysis revealed the presence of a pathogenic variant in the gene leading to a premature stop codon: NM_003632.2:c.3361C>T p.(Arg1121 ). A review of the literature is discussed.
PubMed: 32328110
DOI: 10.1155/2020/8795607