ResearchPad - Clinical Neurology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MRI evaluation of the relationship between carotid artery endothelial shear stress and brain white matter lesions in migraine]]> https://www.researchpad.co/product?articleinfo=N33e3509c-592a-4277-a3ee-c1a653188a41

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (n = 29 females, 75 years [SD 3]) and 219 controls (n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group (P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (β-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume.

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<![CDATA[A Community Perspective on Bowel Management and Quality of Life after Spinal Cord Injury: The Influence of Autonomic Dysreflexia]]> https://www.researchpad.co/product?articleinfo=5b591524463d7e552e096273

Abstract

Autonomic dysfunction is common in individuals with spinal cord injury (SCI) and leads to numerous abnormalities, including profound cardiovascular and bowel dysfunction. In those with high-level lesions, bowel management is a common trigger for autonomic dysreflexia (AD; hypertension provoked by sensory stimuli below the injury level). Improving bowel care is integral for enhancing quality of life (QoL). We aimed to describe the relationships between bowel care, AD, and QoL in individuals with SCI. We performed an online community survey of individuals with SCI. Those with injury at or above T7 were considered at risk for AD. Responses were received from 287 individuals with SCI (injury levels C1-sacral and average duration of injury 17.1 ± 12.9 [standard deviation] years). Survey completion rate was 73% (n = 210). Bowel management was a problem for 78%: it interfered with personal relationships (60%) and prevented staying (62%) and working (41%) away from home. The normal bowel care duration was >60 min in 24% and most used digital rectal stimulation (59%); 33% reported bowel incontinence at least monthly. Of those at risk for AD (n = 163), 74% had AD symptoms during bowel care; 32% described palpitations. AD interfered with activities of daily living in 51%. Longer durations of bowel care (p < 0.001) and more severe AD (p = 0.04) were associated with lower QoL. Bowel management is a key concern for individuals with SCI and is commonly associated with symptoms of AD. Further studies should explore ways to manage bowel dysfunction, increase self-efficacy, and ameliorate the impact of AD to improve QoL.

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<![CDATA[Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes]]> https://www.researchpad.co/product?articleinfo=5bfde5d7d5eed0c4846e1e7a

Supplemental Digital Content is available in the text.

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<![CDATA[ACUDIN – ACUpuncture and laser acupuncture for treatment of DIabetic peripheral Neuropathy: a randomized, placebo-controlled, partially double-blinded trial]]> https://www.researchpad.co/product?articleinfo=5b58b238463d7e4e45688638

Background

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus with significant clinical sequelae that can affect a patient’s quality of life. Metabolic and microvascular factors are responsible for nerve damage, causing loss of nerve function, numbness, painful sensory symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti-depressant drugs for neuropathic pain and paresthesia. However, reduced sensation, balance and gait problems are insufficiently covered by this treatment. Previous data suggests that acupuncture, which has been in use in Traditional Chinese Medicine for many years, may potentially complement the treatment options for peripheral neuropathy. Nevertheless, more objective data on clinical outcome is necessary to generally recommend acupuncture to the public.

Methods

We developed a study design for a prospective, randomized (RCT), placebo-controlled, partially double-blinded trial for investigating the effect of acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural sensory nerve action potential amplitude as the primary outcome. The sural sensory nerve conduction velocity, tibial motor nerve action potential amplitude, tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy symptom score, and numeric rating scale questionnaires are defined as secondary outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be randomized into three groups (needle acupuncture, verum laser acupuncture, and placebo laser acupuncture). We hypothesize that needle and laser acupuncture have beneficial effects on electrophysiological parameters and clinical and subjective symptoms in relation to DPN in comparison with placebo.

Discussion

The ACUDIN trial aims at investigating whether classical needle acupuncture and/or laser acupuncture are efficacious in the treatment of DPN. For the purpose of an objective parameter, NCS were chosen as outcome measures. Acupuncture treatment may potentially improve patients’ quality of life and reduce the socio-economic burden caused by DPN.

Trial registration

German Clinical Trial Register (DRKS), No. DRKS00008562, trial search portal of the WHO (http://apps.who.int/trialsearch/).

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<![CDATA[Challenges Across the HIV Care Continuum for Patients With HIV/TB Co-infection in Atlanta, GA]]> https://www.researchpad.co/product?articleinfo=5b5882a9463d7e4a48649414

Abstract

Background

Antiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States.

Methods

Retrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital.

Results

Among 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post–TB treatment; none of these patients had retention or VS after TB treatment.

Conclusions

Among persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post–TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.

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<![CDATA[Aging Decreases the Density of Colonic Interstitial Cells of Cajal Associated With Constipation in Rats]]> https://www.researchpad.co/product?articleinfo=5b4cfd0d463d7e12d26b019f ]]> <![CDATA[Depression and anxiety as determinants of health-related quality of life in patients with multiple sclerosis - United Arab Emirates]]> https://www.researchpad.co/product?articleinfo=5b4ce7e8463d7e11b2f0758e

To study the impact of depression and anxiety on health-related quality of life (HRQOL) in patients with multiple sclerosis (pwMS) in the UAE. All consecutive patients attending the MS clinic over a fourmonth period, October 2014 through February 2015, at Sheikh Khalifa Medical city (SKMC) were asked to complete The World Health Organization quality of life abbreviated scale (WHOQOL-BREF), the Patient Health Questionnaire nine-item (PHQ-9) depression scale, and Generalized Anxiety Disorder seven-item (GAD-7) scale. These last two scales were used to screen for depression and anxiety disorders respectively. The study looked at significant variables associated with HRQOL, using multivariate analysis. Eighty patients were enrolled in the study. Both anxiety and depression had a strong positive correlation with HRQOL in univariate analysis. However, depression was the strongest predictor of HRQOL in the patients using linear multi-regression analysis. Screening and timely treatment of both anxiety and depression in MS patients should be a recommended policy when managing pwMS to improve their optimal care and ensure better quality of life.

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<![CDATA[Neuropsychiatric symptoms as risk factors of dementia in a Mexican population: A 10/66 Dementia Research Group study]]> https://www.researchpad.co/product?articleinfo=5b4c5d50463d7e09f8ec4a8c

Introduction

Cognitive and/or memory impairment are the main clinical markers currently used to identify subjects at risk of developing dementia. This study aimed to explore the relationship between the presence of neuropsychiatric symptoms and dementia incidence.

Methods

We analyzed the association between neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older adults from the general population over 3 years of follow-up, modeling cumulative incidence ratios using Poisson models.

Results

Five neuropsychiatric symptoms were associated with incident dementia: delusions, hallucinations, anxiety, aberrant motor behavior, and depression. The simultaneous presence of two symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes, indicators of cognitive function, and sociodemographic factors, of 1.9 (95% confidence interval, 1.2–2.9), whereas the presence of three to five, similarly adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9–4.8).

Discussion

Neuropsychiatric symptoms are common in predementia states and may independently contribute as risk factors for developing dementia.

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<![CDATA[Altered network hub connectivity after acute LSD administration]]> https://www.researchpad.co/product?articleinfo=5b4c14f3463d7e0329bcc43a

LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within-network and between-network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between-network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum) and cortical (precuneus, anterior cingulate cortex) hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model.

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<![CDATA[Anxiety After Stroke]]> https://www.researchpad.co/product?articleinfo=5bfaa651d5eed0c48473a5a1

Supplemental Digital Content is available in the text.

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<![CDATA[Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate]]> https://www.researchpad.co/product?articleinfo=5b4bfc96463d7e022037ff80

Background

SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404.

Objective

The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Methods

Participants aged 6–17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant.

Results

All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, − 6.6%; SWM total between-search errors, − 22.8%; SST stop signal reaction time, –18.9%), and at the last on-treatment assessment (DMS median reaction time, − 6.5%; SWM total between-search errors, − 32.6%; SST stop signal reaction time, − 25.7%).

Conclusions

Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required.

ClinicalTrials.gov identifier

NCT01328756.

Electronic supplementary material

The online version of this article (10.1007/s40263-017-0487-z) contains supplementary material, which is available to authorized users.

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<![CDATA[De novo mutations in GRIN1 cause extensive bilateral polymicrogyria]]> https://www.researchpad.co/product?articleinfo=5bf9c8e7d5eed0c48441342e

NMDA receptor agonists have been used for many years to generate animal models of polymicrogyria, a malformation of cortical development. Fry et al. identify de novo GRIN1 mutations in eleven patients with severe bilateral polymicrogyria. Polymicrogyria-associated GRIN1 mutations cluster in specific protein domains and significantly alter NMDA receptor function.

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<![CDATA[Dysfunctional frontal lobe activity during inhibitory tasks in individuals with childhood trauma: An event-related potential study]]> https://www.researchpad.co/product?articleinfo=5b4bb899463d7e7b755cb5b6

Background

Individuals who experience childhood trauma are vulnerable to various psychological and behavioral problems throughout their lifetime. This study aimed to investigate whether individuals with childhood trauma show altered frontal lobe activity during response inhibition tasks.

Methods

In total, 157 healthy individuals were recruited and instructed to perform a Go/Nogo task during electroencephalography recording. Source activities of N2 and P3 of Nogo event-related potentials (ERP) were analyzed. The Childhood Trauma Questionnaire (CTQ) and Barratt Impulsivity Scale (BIS) were applied. Individuals were divided into three groups based on their total CTQ score: low CTQ, middle CTQ, and high CTQ groups.

Results

The high CTQ group exhibited significantly higher BIS scores than the low CTQ group. P3 amplitudes of the differences between Nogo and Go ERP waves exhibited higher mean values in the low CTQ than the high CTQ group, with trending effects. In Nogo-P3, the source activities of the right anterior cingulate cortex, bilateral medial frontal cortex (MFC), bilateral superior frontal gyrus (SFG), and right precentral gyrus were significantly lower in the high CTQ than the low CTQ group. Motor impulsivity showed a significant negative correlation with activities of the bilateral MFC and SFG in Nogo-P3 conditions.

Conclusions

Our study revealed that individuals with childhood trauma have inhibitory failure and frontal lobe dysfunction in regions related to Nogo-P3.

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<![CDATA[Surgical management of C-type subaxial cervical fractures using cervical traction followed by anterior cervical discectomy and fusion within 12 h after the trauma]]> https://www.researchpad.co/product?articleinfo=5b4a60dd463d7e5eed3750fc

Study Design:

This was a retrospective cohort study.

Objective:

To report our 10-year experience of closed reduction using Crutchfield traction followed by anterior cervical discectomy and fusion within 12 h from injury for C-type subaxial cervical fractures (according to the AOSpine classification system).

Methods:

Clinical records and neuroimaging were retrospectively reviewed. Surgical details were provided.

Results:

A total of 22 patients were included in the study. The cervical fracture was diagnosed after whole-body computed tomography scan on admission in all cases. Crutchfield traction was applied within 1–5 h from the diagnosis. Surgery consisting of anterior microdiscectomy and fusion with interbody cage and plating was performed 6–12 h after traction positioning. Most patients (19, 86%) had spinal cord injury: 7 were Frankel A (31%), 3 Frankel B (14%), 6 Frankel C (27%), 3 Frankel D (14%), and 3 Frankel E (14%). No neurologic deterioration was observed after the treatment. In 10 cases (45%), neurological symptoms improved 1 year after the trauma. Two patients (10%) died for complication related to spinal cord transition or other organ damage.

Conclusions:

Early reduction gives the best chance of recovery for patients affected by C-type subaxial cervical fracture. Rapid traction is more often successful and safer than manipulation under anesthesia. After close reduction achieving, anterior microdiscectomy, cage, and plating implant seem to be safe and effective with a low rate of complications.

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<![CDATA[Headache following head injury: a population-based longitudinal cohort study (HUNT)]]> https://www.researchpad.co/product?articleinfo=5b4a49e6463d7e44fe5eb45b

Background

Headache is the most frequent symptom following head injury, but long-term follow-up of headache after head injury entails methodological challenges. In a population-based cohort study, we explored whether subjects hospitalized due to a head injury more often developed a new headache or experienced exacerbation of previously reported headache compared to the surrounding population.

Methods

This population-based historical cohort study included headache data from two large epidemiological surveys performed with an 11-year interval. This was linked with data from hospital records on exposure to head injury occurring between the health surveys. Participants in the surveys who had not been hospitalized because of a head injury comprised the control group. The head injuries were classified according to the Head Injury Severity Scale (HISS). Multinomial logistic regression was performed to investigate the association between head injury and new headache or exacerbation of pre-existing headache in a population with known pre-injury headache status, controlling for potential confounders.

Results

The exposed group consisted of 294 individuals and the control group of 25,662 individuals. In multivariate analyses, adjusting for age, sex, anxiety, depression, education level, smoking and alcohol use, mild head injury increased the risk of new onset headache suffering (OR 1.74, 95% CI 1.05–2.87), stable headache suffering (OR 1.70, 95% CI 1.15–2.50) and exacerbation of previously reported headache (OR 1.93, 95% CI 1.24–3.02). The reference category was participants without headache in both surveys.

Conclusion

Individuals hospitalized due to a head injury were more likely to have new onset and worsening of pre-existing headache and persistent headache, compared to the surrounding general population. The results support the entity of the ICHD-3 beta diagnosis “persistent headache attributed to traumatic injury to the head”.

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<![CDATA[Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)]]> https://www.researchpad.co/product?articleinfo=5bf49228d5eed0c484763afb

Supplemental Digital Content is Available in the Text.

Neublastin showed some evidence of pain relief among patients with painful lumbosacral radiculopathy; however, there was no clear dose–response relationship.

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<![CDATA[miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels]]> https://www.researchpad.co/product?articleinfo=5bf4922ad5eed0c484763b2a

Supplemental Digital Content is Available in the Text.

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<![CDATA[Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial]]> https://www.researchpad.co/product?articleinfo=5bf4922bd5eed0c484763b7f

Supplemental Digital Content is Available in the Text.

Cebranopadol, a novel first-in-class combination of nociceptin/orphanin FQ and opioid peptide receptor agonism, as a potential treatment for moderate to severe chronic low back pain.

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<![CDATA[New model of vincristine-induced neuropathic pain in children: a first step towards prediction and prevention]]> https://www.researchpad.co/product?articleinfo=5bf49226d5eed0c484763ad0 ]]> <![CDATA[PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in rat spinal cord]]> https://www.researchpad.co/product?articleinfo=5b4a0487463d7e3e66f5dd72

Background

Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated.

Methods

Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis. Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2 was achieved by intrathecal injection of specific small interfering RNA (siRNA). Von Frey filaments and radiant heat tests were performed to determine mechanical allodynia and thermal hyperalgesia respectively. Lactate and adenosine triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were detected by ELISA kits.

Results

CCI markedly increased PKM2 level in rat spinal cord. Double immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte, and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI-induced ERK and STAT3 activation, but also attenuated mechanical allodynia and thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the activation of AKT. In addition, PKM2 siRNA significantly suppressed the production of lactate and pro-inflammatory mediators.

Conclusion

Our findings demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced neuropathic pain and inflammatory responses in rats, possibly through regulating ERK and STAT3 signaling pathway.

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