Disorders of the spinal cord and roots

Disorders of the spinal cord and roots, I, Introduction

The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    Epigenetic downregulation of STAT6 increases HIF-1α expression via mTOR/S6K/S6, leading to enhanced hypoxic...

    Epigenetic downregulation of STAT6 increases HIF-1α expression via mTOR/S6K/S6, leading to enhanced hypoxic..., Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastom..., Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastom..., admin,

    White matter DNA methylation profiling reveals deregulation of HIP1 , LMAN2 , MOBP , and other loci in...

    White matter DNA methylation profiling reveals deregulation of HIP1 , LMAN2 , MOBP , and other loci in..., Abstract Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson’s disease are α-synucleinopathies.,

    Abstract


    Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson’s disease are α-synucleinopathies. Pathologically, MSA can be categorized into striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) or mixed subtypes. Despite extensive research, the regional vulnerability of the brain to MSA pathology remains poorly understood. Genetic, epigenetic and environmental factors have been proposed to explain which brain regions are affected by MSA, and to what extent. Here, we explored for the first time epigenetic changes in post-mortem brain tissue from MSA cases. We conducted a case–control study, and profiled DNA methylation in white mater from three brain regions characterized by severe-to-mild GCIs burden in the MSA mixed subtype (cerebellum, frontal lobe and occipital lobe). Our genome-wide approach using Illumina MethylationEPIC arrays and a powerful cross-region analysis identified 157 CpG sites and 79 genomic regions where DNA methylation was significantly altered in the MSA mixed-subtype cases. HIP1, LMAN2 and MOBP were amongst the most differentially methylated loci. We replicated these findings in an independent cohort and further demonstrated that DNA methylation profiles were perturbed in MSA mixed subtype, and also to variable degrees in the other pathological subtypes (OPCA and SND). Finally, our co-methylation network analysis revealed several molecular signatures (modules) significantly associated with MSA (disease status and pathological subtypes), and with neurodegeneration in the cerebellum. Importantly, the co-methylation module having the strongest association with MSA included a CpG in SNCA, the gene encoding α-synuclein. Altogether, our results provide the first evidence for DNA methylation changes contributing to the molecular processes altered in MSA, some of which are shared with other neurodegenerative diseases, and highlight potential novel routes for diagnosis and therapeutic interventions.

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    Disorders of the spinal cord and roots

    Disorders of the spinal cord and roots, I, Introduction

    The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    Causes, Predictors, and Trends of Unplanned Readmissions after Elective Endovascular Embolization of Cerebral...

    Causes, Predictors, and Trends of Unplanned Readmissions after Elective Endovascular Embolization of Cerebral..., Background: 30- and 90-day readmissions (dRA) are being increasingly scrutinized as quality metrics for hospital and provider performances. Little information regarding risk factors for readmission after elective endovascular treatment (EVT) of an unruptured cerebral aneurysm (UCA) is available., Background: 30- and 90-day readmissions (dRA) are being increasingly scrutinized as quality metrics for hospital and provider performances. Little information regarding risk factors for readmission after elective endovascular treatment (EVT) of an unruptured cerebral aneurysm (UCA) is available. Methods: The Nationwide Readmissions Database was used to identify patients who underwent elective endovascular embolization of an unruptured aneurysm between 2010 and 2014. The primary outcomes of interest were unplanned readmissions occurring within 30 or 90 days of discharge., admin,

    Effects of the Interaction among Motor Functions on Self-care in Individuals with Stroke

    Effects of the Interaction among Motor Functions on Self-care in Individuals with Stroke, No study to date has focused on what combinations of motor functions are strongly associated with self-care independence in individuals with stroke. The purpose of this study is to clarify the impact of motor function interactions on self-care independence in individuals with stroke., No study to date has focused on what combinations of motor functions are strongly associated with self-care independence in individuals with stroke. The purpose of this study is to clarify the impact of motor function interactions on self-care independence in individuals with stroke., admin,

    Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with...

    Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with..., Objective: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). Methods: We prospectively analyzed the incidence of stroke recurrence., Objective: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). Methods: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test., admin,

    Water-Based Exercise on Functioning and Quality of Life in Poststroke Persons: A Systematic Review and...

    Water-Based Exercise on Functioning and Quality of Life in Poststroke Persons: A Systematic Review and..., Objective: To investigate the effects of water-based exercise on functioning and quality of life in poststroke persons. Data Sources: We searched the following electronic database: MEDLINE, PeDro, Scielo, and the Cochrane Central Register of Controlled Trials up to September 2018 Study Selection: Only randomized controlled trials were included., Objective: To investigate the effects of water-based exercise on functioning and quality of life in poststroke persons. Data Sources: We searched the following electronic database: MEDLINE, PeDro, Scielo, and the Cochrane Central Register of Controlled Trials up to September 2018 Study Selection: Only randomized controlled trials were included. Two review authors screened the titles and abstracts and selected the trials independently. Data Extraction: Two review authors independently extracted data of the included trials, using standard data-extraction model., admin,

    Psychiatric and neurodevelopmental aspects of Becker muscular dystrophy

    Psychiatric and neurodevelopmental aspects of Becker muscular dystrophy, Becker muscular dystrophy (BMD, OMIM 300376) is an X-linked recessive form of muscular dystrophy caused by mutations in the dystrophin gene (DMD), which is located on chromosome Xp21.2 [1]. The DMD gene is the largest gene identified in humans and contains 79 exons. Mutations in the gene result in a deficient dystrophin protein [2]., Becker muscular dystrophy (BMD, OMIM 300376) is an X-linked recessive form of muscular dystrophy caused by mutations in the dystrophin gene (DMD), which is located on chromosome Xp21.2 [1]. The DMD gene is the largest gene identified in humans and contains 79 exons. Mutations in the gene result in a deficient dystrophin protein [2]. BMD is typically associated with mutations that maintain the open reading frame, producing an internally altered but partially functional dystrophin protein, with an intact C terminal domain [3,4]., admin,

    Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis

    Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis, Frontotemporal dementia (FTD) with tau pathology is associated with aberrant hyperexcitability of neuronal networks. In human iPSC-derived neurons, Sohn et al., Frontotemporal dementia (FTD) with tau pathology is associated with aberrant hyperexcitability of neuronal networks. In human iPSC-derived neurons, Sohn et al. demonstrates that FTD-causing tau mutation abolishes activity-dependent plasticity of the axon initial segment and impairs homeostasis of neuronal activity via impacting AIS cytoskeleton, resulting in dysregulation of neuronal network function., admin,

    Disorders of the spinal cord and roots

    Disorders of the spinal cord and roots, I, Introduction

    The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    Location-Specific Association Between Cerebral Microbleeds and Arterial Pulsatility

    Location-Specific Association Between Cerebral Microbleeds and Arterial Pulsatility, Objective: Increased arterial pulsatility index (API), usually representative of distal vascular resistance, have been linked to cerebral small vessel disease. However, their relationship with cerebral microbleeds (CMBs) is less well-studied. The present study aimed to evaluate the relationship between CMBs and API.,

    Objective: Increased arterial pulsatility index (API), usually representative of distal vascular resistance, have been linked to cerebral small vessel disease. However, their relationship with cerebral microbleeds (CMBs) is less well-studied. The present study aimed to evaluate the relationship between CMBs and API.

    Methods: We cross-sectionally evaluated participants from a non-clinical stroke, non-demented community-based population. APIs of cervical internal carotid and vertebral arteries were measured by ultrasonography. CMBs were assessed by susceptibility-weighted-imaging on 3T magnetic resonance imaging (MRI). Subjects were classified according to CMB locations: deep/infratentorial (DI) or strictly lobar (SL) CMB groups. DI-CMB group also included subjects with simultaneous lobar CMBs.

    Results: Of the 681 subjects [62.2 (8.4) years, 43.5% men] included, CMBs were found in 92 (13.5%) subjects: 57 (8.4%) with DI-CMB and 35 (5.1%) with SL-CMB. The results showed that CMB location influenced their association with API. DI-CMB was significantly associated with elevated API of internal carotid arteries (β = 0.031; 95% confidence interval = 0.002–0.059; P = 0.03), while SL-CMB was significantly associated with elevated API of vertebral arteries (β = 0.050; 95% confidence interval = 0.006–0.094; P = 0.025) in multivariate analyses adjusting for age, sex, cardiovascular risk factors, white matter hyperintensities (WMH), and lacunes.

    Conclusion: Our study again emphasizes (1) the association between API and cerebral small vessel disease and (2) the pathogenic differences between DI- and SL-CMBs. Our results lead to the postulation that in the presence of CMBs without clinical dysfunction yet, insidious small vascular disorders might already occur with corresponding topography.

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    Abnormal Functional Connectivity in Cognitive Control Network, Default Mode Network, and Visual Attention...

    Abnormal Functional Connectivity in Cognitive Control Network, Default Mode Network, and Visual Attention..., Internet addiction (IA) has become a global mental and social problem, which may lead to a series of psychiatric symptoms including uncontrolled use of internet, and lack of concentration. However, the exact pathophysiology of IA remains unclear.,

    Internet addiction (IA) has become a global mental and social problem, which may lead to a series of psychiatric symptoms including uncontrolled use of internet, and lack of concentration. However, the exact pathophysiology of IA remains unclear. Most of functional connectivity studies were based on pre-selected regions of interest (ROI), which could not provide a comprehensive picture of the communication abnormalities in IA, and might lead to limited or bias observations. Using local functional connectivity density (lFCD), this study aimed to explore the whole-brain abnormalities of functional connectivity in IA. We evaluated the whole-brain lFCD resulting from resting-state fMRI data in 28 IA individuals and 30 demographically matched healthy control subjects (HCs). The correlations between clinical characteristics and aberrant lFCD were also assessed. Compared with HCs, subjects with IA exhibited heightened lFCD values in the right dorsolateral prefrontal cortex (DLPFC), left parahippocampal gyrus (PHG), and cerebellum, and the bilateral middle cingulate cortex (MCC) and superior temporal pole (STP), as well as decreased lFCD values in the right inferior parietal lobe (IPL), and bilateral calcarine and lingual gyrus. Voxel-based correlation analysis revealed the significant correlations between the Young's Internet Addiction Test (IAT) score and altered lFCD values in the left PHG and bilateral STP. These findings revealed the hyper-connectivity in cognitive control network and default mode network as well as the hypo-connectivity in visual attention network, verifying the common mechanism in IA and substance addiction, and the underlying association between IA, and attention deficit/hyperactivity disorder in terms of neurobiology.

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    Risk Factors of Transient Cortical Blindness After Cerebral Angiography: A Multicenter Study

    Risk Factors of Transient Cortical Blindness After Cerebral Angiography: A Multicenter Study, Background: Although transient cortical blindness is a rare complication following cerebral angiography, identification of risk factors for the development of transient cortical blindness after cerebral angiography is an important clinical issue.,

    Background: Although transient cortical blindness is a rare complication following cerebral angiography, identification of risk factors for the development of transient cortical blindness after cerebral angiography is an important clinical issue.

    Material and methods: Between January 2008 and April 2018, 5,126 patients at five high-volume medical centers who underwent cerebral angiography procedures were enrolled in this multicenter cohort study. Patient baseline characteristics and surgery-related factors were analyzed. We used multivariate logistic regression to examine factors associated with transient cortical blindness.

    Results: Eighteen patients (0.35%) in the total cohort of 5,126 suffered transient cortical blindness. After univariate statistical analysis, no significant differences were determined between the transient cortical blindness group and the control group regarding gender (p = 0.454), age (p = 0.872), smoking (p = 0.170), diabetes (p = 0.800), and hypertension (p = 0.100). Compared with the control group, the transient cortical blindness group weighed less (p = 0.020), and had a larger dose of contrast agent (p = 0.034) and more instances of contrast agent injected into the posterior circulation (p < 0.001). Logistic regression analysis identified contrast agent dose and contrast agent injected into posterior circulation as independent predictive factors for transient cortical blindness (P < 0.05).

    Conclusion: Larger doses off contrast agent and contrast agent injected into the posterior circulation are potential independent predictive factors for transient cortical blindness following cerebral angiography.

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    Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency

    Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency, Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency.,

    Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency.

    Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB).

    Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers.

    Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN.

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