BMC Neurology
BMC Neurology - Latest Articles
The latest research articles published by BMC Neurology
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Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the primary veins outside the skull that has been reported to be associated with MS. In the blinded Combined Transcranial (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) study, we found that prevalence of CCSVI was significantly higher in multiple sclerosis (MS) vs. healthy controls (HC) (56.1% vs. 22.7%, p < 0.001). The objective was to evaluate the clinical correlates of venous anomalies indicative of CCSVI in patients with MS Methods: The original study enrolled 499 subjects; 163 HC, 289 MS, 21 CIS and 26 subjects with other neurological disorders who underwent a clinical examination and a combined Doppler and TCD scan of the head and neck. This analysis was restricted to adult subjects with MS (RRMS: n = 181, SP-MS: n = 80 and PP-MS: n = 12). Disability status was evaluated by using the Kurtzke Expanded Disability Status Scale (EDSS) and MS severity scale (MSSS). Results: Disability was not associated with the presence ([greater than or equal to]2 venous hemodynamic criteria) or the severity of CCSVI, as measured with venous hemodynamic insufficiency severity score (VHISS). However, the severity of CCSVI was associated with the increased brainstem functional EDSS sub-score (p = 0.002). In logistic regression analysis, progressive MS (SPMS or PP-MS) vs. non-progressive status (including RR-MS) was associated with CCSVIdiagnosis (p = 0.004, OR = 2.34, CI = 1.3-4.2). Conclusions: The presence and severity of CCVSI in multiple sclerosis correlate with disease status but has no or very limited association with clinical disability.
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Incidence of and risk factors for Motor Neurone
Disease in UK women: a prospective study
Background: Motor neuron disease (MND) is a severe neurodegenerative disease with largely unknown etiology. Most epidemiological studies are hampered by small sample sizes and/or the retrospective collection of information on behavioural and lifestyle factors. Methods: 1.3 million women from the UK Million Women Study, aged 56 years on average at recruitment, were followed up for incident and/or fatal MND using NHS hospital admission and mortality data. Adjusted relative risks were calculated using Cox regression models.FindingsDuring follow-up for an average of 9.2 years, 752 women had a new diagnosis of MND. Age-specific rates increased with age, from 1.9 (95% CI 1.3 - 2.7) to 12.5 (95% CI 10.2 - 15.3) per 100,000 women aged 50-54 to 70-74, respectively, giving a cumulative risk of diagnosis with the disease of 1. 74 per 1000 women between the ages of 50 and 75 years. There was no significant variation in risk of MND with region of residence, socio-economic status, education, height, alcohol use, parity, use of oral contraceptives or hormone replacement therapy. Ever-smokers had about a 20% greater risk than never smokers (RR 1.19 95% CI 1.02 to 1.38, p=0.03). There was a statistically significant reduction in risk of MND with increasing body mass index (pfor trend=0.009): obese women (body mass index, 30 kg/m2 or more) had a 20% lower risk than women of normal body mass index (20 to <25 Kg/m2)(RR 0.78 95% CI 0.65-0.94; p=0.03). This effect persisted after exclusion of the first three years of follow-up.Interpretation. MND incidence in UK women rises rapidly with age, and an estimated 1 in 575 women are likely to be affected between the ages of 50 and 75 years. Smoking slightly increases the risk of MND, and adiposity in middle age is associated with a lower risk of the disease.
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An olfactory 'stress test' may detect preclinical Alzheimer's disease
Background: The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer's disease (AD). We speculated that an olfactory 'stress test' (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD. Methods: We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD. Results: In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine ('atropine effect' = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57, p < 0.001) and left hippocampal volume (LHCV) (r = 0.53, p < 0.001). Among non-demented individuals (n = 42), AE correlated with episodic memory (r = 0.52, p < 0.001) and LHCV (r = 0.49, p < 0.001) and hierarchical linear regression models adjusted for age, gender, education, and baseline UPSIT showed that the AE explained more variance in memory performance (24%) than did LHCV (15%). The presence of any APOE epsilon4 allele was associated with a more negative AE (p = 0.014). Conclusions: The OST using atropine as an olfactory probe holds promise as a simple, inexpensive screen for early and preclinical AD and further work, including longitudinal studies, is needed to explore this possibility.
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Early microstructural white matter changes in patients with HIV:
a diffusion tensor imaging study
Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather a reactive origin of depression in HIV-patients.
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Aquaporin-4 expression in distal myopathy with rimmed vacuoles
Background: Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy is clinically characterized by the early involvement of distal leg muscles. The striking pathological features of the myopathy are muscle fibers with rimmed vacuoles. To date, the role of aquaporin-4 water channel in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy has not been studied.Case presentationHere, we studied the expression of aquaporin-4 in muscle fibers of a patient with distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy. Immunohistochemical and immunofluorescence analyses showed that sarcolemmal aquaporin-4 immunoreactivity was reduced in many muscle fibers of the patent. However, the intensity of aquaporin-4 staining was markedly increased at rimmed vacuoles or its surrounding areas and in some muscle fibers. The fast-twitch type 2 fibers were predominantly involved with the strong aquaporin-4-positive rimmed vacuoles and TAR-DNA-binding protein-43 aggregations. Rimmed vacuoles with strong aquaporin-4 expression seen in the distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy patient were not found in control muscles without evidence of neuromuscular disorders and the other disease-controls. Conclusions: Aquaporin-4 might be crucial in determining the survival or degeneration of fast-twitch type 2 fibers in distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy.
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Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review
Background: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. Methods: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. Results: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. Conclusions: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed.
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Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury
Background: The α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury. Methods: Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined. Results: Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059. Conclusion: In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.
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Pilates based core stability training in ambulant individuals with multiple sclerosis: Protocol for a multi-centre randomised controlled trial
Background: People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.This study builds upon the pilot work undertaken in the case series study by implementing a powered randomised controlled study, with the aims of:1 Establishing the effectiveness of core stability training2 Comparing core stability training with standardised physiotherapy exercise3 Exploring underlying mechanisms of change associated with this intervention Methods: This is a multi-centre, double blind, block randomised, controlled trial. Eligible participants will be recruited from 4 UK centres. Participants will be randomly allocated to one of three groups: Pilates based core stability training, standardised physiotherapy exercise or contract-relax relaxation sessions (placebo control). All will receive face to face training sessions over a 12 week period; together with a 15 minute daily home programme. All will be assessed by a blinded assessor before training, at the end of the 12 week programme and at 4 week follow-up. The primary outcome measure is the 10 metre timed walk. Secondary outcome measures are the MS walking Scale (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical Rating Scale to determine "Difficulty in carrying a drink when walking", and the Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound imaging of the abdominal muscles will be performed before and after intervention to assess changes in abdominal musculature at one of the four centres (Plymouth).DiscussionThis pragmatic trial will assess the effect of these exercise programmes on ambulatory people with MS. It may not be possible to extrapolate the conclusions to those who are non-ambulatory.Trial registrationNCT01414725
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How to improve walking, balance and social participation following stroke: a comparison of the long term effects of two walking aids--canes and an orthosis TheraTogs--on the recovery of gait following acute stroke. A study protocol for a multi-centre, single blind, randomised control trial
Background: Annually, some 9000 people in Switzerland suffer a first time stroke. Of these 60% are left with moderate to severe walking disability. Evidence shows that rehabilitation techniques which emphasise activity of the hemiplegic side increase ipsilesional cortical plasticity and improve functional outcomes. Canes are commonly used in gait rehabilitation although they significantly reduce hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset with elasticated strapping) significantly increases hemiplegic muscle activity during gait. The aim of the present study is to investigate the long term effects on the recovery of gait, balance and social participation of gait rehabilitation with TheraTogs compared to gait rehabilitation with a cane following first time acute stroke.Methods/DesignMulti-centre, single blind, randomised trial with 120 patients after first stroke. When subjects have reached Functional Ambulation Category 3 they will be randomly allocated into TheraTogs or cane group. TheraTogs will be applied to support hip extensor and abductor musculature according to a standardised procedure. Cane walking held at the level of the radial styloid of the sound wrist. Subjects will walk throughout the day with only the assigned walking aid. Standard therapy treatments and usual care will remain unchanged and documented. The intervention will continue for five weeks or until patients have reached Functional Ambulation category 5. Outcome measures will be assessed the day before begin of intervention, the day after completion, 3 months, 6 months and 2 years. Primary outcome: Timed "up and go" test, secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius, activation patterns of hemiplegic leg musculature, temporo-spatial gait parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic balance, daily activity measured by accelerometry, Stroke Impact Scale. Significance levels will be 5% with 95% CI's. IntentionToTreat analyses will be performed. Descriptive statistics will be presented.DiscussionThis study could have significant implications for the clinical practice of gait rehabilitation after stroke, particularly the effect and appropriate use of walking aids.The results could be important for the development of clinical guidelines and for the socio-economic costs of post-stroke careTrial registration numberClinicalTrials.gov NCT01366729.
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Carotid endarterectomy and carotid artery stenting utilization trends over time
Background: Carotid endarterectomy (CEA) has been the standard in atherosclerotic stroke prevention for over 2 decades. More recently, carotid artery stenting (CAS) has emerged as a less invasive alternative for revascularization. The purpose of this study was to investigate whether an increase in stenting parallels a decrease in endarterectomy, if there are specific patient factors that influence one intervention over the other, and how these factors may have changed over time. Methods: Using a nationally representative sample of US hospital discharge records, data on CEA and CAS procedures performed from 1998 to 2008 were obtained. In total, 253,651 cases of CEA and CAS were investigated for trends in utilization over time. The specific data elements of age, gender, payer source, and race were analyzed for change over the study period, and their association with type of intervention was examined by multiple logistic regression analysis. Results: Rates of intervention decreased from 1998 to 2008 (P < 0.0001). Throughout the study period, endarterectomy was the much more widely employed procedure. Its use displayed a significant downward trend (P < 0.0001), with the lowest rates of intervention occurring in 2007. In contrast, carotid artery stenting displayed a significant increase in use over the study period (P < 0.0001), with the highest intervention rates occurring in 2006. Among the specific patient factors analyzed that may have altered utilization of CEA and CAS over time, the proportion of white patients who received intervention decreased significantly (P < 0.0001). In multivariate modeling, increased age, male gender, white race, and earlier in the study period were significant positive predictors of CEA use. Conclusions: Rates of carotid revascularization have decreased over time, although this has been the result of a reduction in CEA despite an overall increase in CAS. Among the specific patient factors analyzed, age, gender, race, and time were significantly associated with the utilization of these two interventions.
