BMC Neurology - Latest Articles

Monozygotic twins concordant for Kleine-Levin syndrome

Taro Ueno — 2012-05-30T00:00:00Z

Background: Kleine-Levin syndrome is a rare idiopathic form of episodic hypersomnia that typically occurs during adolescence. The cardinal clinical features are recurrent hypersomnia, accompanied by cognitive disturbances and behavioral abnormalities [1]. The most typical form of classical Kleine-Levin syndrome is associated with hyperphagia [2, 3], although hyperphagia is now optional after change of the criteria. Hypersexuality, behavioral disinhibition, delusions, autonomic alteration and hallucinations have also been described, but the patients show normal cognitive function and behavior between attacks. The pathogenesis of Kleine-Levin syndrome is not yet known. Although most cases of recurrent hypersomnia are sporadic, the occurrence of nine familial cases indicate that there may be a genetic predisposition to the syndrome [4-8] However, no cases of twins affected with Kleine-Levin syndrome have been reported [9]. In this case study we describe monozygotic twins suffering from the syndrome. This is the first case report describing twins affected with Kleine-Levin syndrome thereby supporting the theory that there is an underlying genetic predisposition to the syndrome.

Phenytoin versus Leviteracetam for Seizure Prophylaxis after Brain Injury - A Meta Analysis

Syed Nabeel Zafar — 2012-05-29T00:00:00Z

Background: Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, it is rapidly being replaced by a new drug Levetiracetam (LEV) as the treatment of choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury. Methods: An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures. Results: The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate's Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79) Conclusion: Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.

Towards a definition of refractory neuropathic pain for epidemiological research. An international Delphi survey of experts.

Blair Smith — 2012-05-28T00:00:00Z

Background: Best current estimates of neuropathic pain (NeuP) prevalence come from studies using various screening detecting pain with probable neuropathic features; the proportion experiencing significant, long-term NeuP, and the proportion not responding to standard treatment are unknown. These "refractory" cases are the most clinically important to detect, being the most severe, requiring specialist treatment. Methods: We report an international Delphi survey of experts in NeuP, aiming for consensus on the features required to define, for epidemiological research: (1) neuropathic pain; and (2) when NeuP is "refractory". A web-based questionnaire was developed and data collected from three rounds of questionnaires from nineteen experts. Results: There was good consensus on essential inclusion of six items to identify NeuP ("prickling, tingling, pins & needles", "pain evoked by light touch", "electric shocks or shooting pain", "hot or burning" pain, "brush allodynia on self-examination", and "relevant history") and on some items that were non-essential. Consensus was also reached on components of a "refractory NeuP" definition: minimum duration (one year); number of trials of drugs of known effectiveness (four); adequate duration of these trials (three months / maximum tolerated); outcomes of treatment (pain severity, quality of life). Further work needs to validate these proposed criteria in general population research. Conclusions: This paper presents an international consensus on measuring the epidemiology of refractory neuropathic pain. This will be valuable in reaching an agreed estimate of the prevalence of neuropathic pain, and the first estimate of refractory neuropathic pain prevalence.

Altered Small-world Properties of Gray Matter Networks in Breast Cancer

SM Hadi Hosseini — 2012-05-28T00:00:00Z

Background: Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks. Methods: We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls. Results: Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients. Conclusions: These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy.

Effect of wearing a dorsiflexion assist orthosis on mobility, perceived fatigue and exertion during the six-minute walk test in people with multiple sclerosis: a randomised cross-over protocol

James McLoughlin — 2012-05-25T00:00:00Z

Background: Fatigue in combination with gait and balance impairments can severely limit daily activities in people with multiple sclerosis (PWMS). Generalised fatigue has a major impact onwalking ability, with moderately disabled PWMS experiencing difficulty in walking extended distances. Localised motor fatigue in the ankle dorsiflexors can lead to foot drop, furtherreducing functional ambulation. The aim of this study is to evaluate the effect of a simple dynamic dorsiflexion assist orthosis on walking-induced fatigue, gait, balance and functionalmobility in PWMS. Methods: A randomised cross-over trial will be conducted with 40 community dwelling PWMS with mild to moderate mobility disability. Participants will initially be screened for diseaseseverity, balance, strength, depression and fatigue at the South Australian Motion Analysis Centre. On two non-consecutive occasions, within two weeks, participants will undergoeither the 6-minute walk test (6MWT) or the 6MWT while wearing a dorsiflexion ankle orthosis (with a randomised condition order). Distance walked, perceived exertion, perceivedfatigue and the physiological cost of walking (the primary outcome measures) will be compared between the two walking conditions. Additional pre- and post-6MWT assessmentsfor the two conditions will include tests of strength, reaction time, gait and balance.DiscussionThis study will increase our understanding of motor fatigue on gait and balance control inPWMS and elucidate the effect of a Dynamic Ankle Orthosis on fatigue-related balance andgait in PWMS. It will also examine relationships between mobility and balance performance with perceived fatigue levels in this group.Trial Registration NumberACTRN12612000218897

Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis

Bianca Weinstock-Guttman — 2012-05-15T00:00:00Z

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.

Incidence of and risk factors for Motor Neurone Disease in UK women: a prospective study

Pat Doyle — 2012-05-06T00:00:00Z

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.

An olfactory 'stress test' may detect preclinical Alzheimer's disease

Peter Schofield — 2012-05-02T00:00:00Z

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.

Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study

Bianca Stubbe-Dräger — 2012-05-01T00:00:00Z

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.

Aquaporin-4 expression in distal myopathy with rimmed vacuoles

Akihiko Hoshi — 2012-04-27T00:00:00Z

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.