Showing papers in "European Journal of Neurology in 2013"

EFNS/MDS‐ES recommendations for the diagnosis of Parkinson's disease

Abstract: Background A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. Methods Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. Results For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [123I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. Conclusions The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease

Abstract: Objective: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. Methods: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. Results and Conclusions:: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence. (Less)

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study

Abstract: BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Impact of blood pressure changes and course on hematoma growth in acute intracerebral hemorrhage.

Abstract: Background and purpose An association between high blood pressure (BP) in acute intracerebral hemorrhage (ICH) and hematoma growth (HG) has not been clearly demonstrated. Therefore, the impact of BP changes and course on HG and clinical outcome in patients with acute ICH was determined. Methods In total, 117 consecutive patients with acute ( 180 and >130 mmHg, respectively. HG (>33% or >6 ml), early neurological deterioration (END) and 3-month mortality were recorded. Results Baseline BP variables were unrelated to either HG or clinical outcome. Conversely, SBP 180-load independently predicted HG (odds ratio 1.05, 95% CI 1.010–1.097, P = 0.016), whilst both SBP 180-load (odds ratio 1.04, 95% CI 1.001–1.076, P = 0.042) and SBP variability (odds ratio 1.2, 95% CI 1.047–1.380, P = 0.009) independently predicted END. Although none of the BP monitoring variables was associated with HG in the spot-sign-positive group, higher maximum BP increases from baseline and higher SBP and MAP loads were significantly related to HG in the spot-sign-negative group. Conclusions In patients with acute supratentorial ICH, SBP 180-load independently predicts HG, whilst both SBP 180-load and SBP variability predict END.

Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients

Abstract: Background and purpose: Transcranial direct current stimulation (TDCS) is a potential tool to improve motor deficits in chronic stroke patients. Safety and efficacy of this procedure in acute stroke patients have not yet been addressed. Methods: We performed in our stroke unit a single-centre randomized, double-blind, sham-controlled study to investigate safety and efficacy of anodal TDCS of the affected hemisphere in acute stroke patients. The second day from stroke onset, 50 acute stroke patients received either five-daily sessions of anodal (n = 25) at 2 mA for 20 min or sham TDCS (n = 25) to the ipsilesional primary motor cortex (M1). Motor deficit was assessed by the short form of the Fugl–Meyer motor scale (FM) and overall neurological deficit by the National Institute of Health Stroke Scale (NIHSS) at onset, at 5 days after stroke and after 3 months. Results: No side effects were detected during either TDCS or sham. In both groups, there was a significant improvement in NIHSS and FM scores, which did not significantly differ when comparing TDCS and sham. Conclusions: Five-daily sessions of anodal TDCS to the ipsilesional M1 appear to be safe in acute stroke patients but do not improve clinical outcome.

Obesity and impaired cognitive functioning in the elderly: a population-based cross-sectional study (NEDICES).

Abstract: BACKGROUND AND PURPOSE Studies of high body mass index (BMI) and cognition in the elderly have shown conflicting results. While some studies have shown a detrimental effect of high BMI on cognitive function, others have observed beneficial effects on cognition. Our aim was to assess cognitive function in a large population-based sample of overweight (BMI 25-29.9 kg/m(2) ) and obese (BMI ≥ 30 kg/m(2) ) community-dwelling elderly participants compared with their counterparts with BMI < 25 kg/m(2) (i.e. controls) living in the same population. METHODS One-thousand nine-hundred and forty-nine population-dwelling participants aged ≥ 65 years in central Spain [the Neurological Diseases in Central Spain study (NEDICES)] underwent a neuropsychological assessment, including tests of global cognitive performance [measured with a 37-item version of the Mini-Mental State Examination (37-MMSE)], psychomotor speed, verbal fluency, memory and pre-morbid intelligence. RESULTS There were 507 with BMI < 25 kg/m(2) , 850 overweight and 592 obese participants. In regression analyses that adjusted for age, gender, educational category, intake of medications that potentially affect cognition function, diabetes mellitus, hypertension, dementia, ever smoker, ever drinker and waist circumference, we found that obese/overweight status was associated with the lowest quartiles of the 37-MMSE, Trail Making Test-A (number of errors; indeed more errors), verbal fluency, delayed free recall, immediate logical memory and pre-morbid intelligence. CONCLUSIONS In this large population sample, overweight and obese participants performed poorer on formal neuropsychological tests than their counterparts with BMI < 25 kg/m(2) . These results support the hypothesis of a detrimental effect of high BMI on impaired cognition in the elderly.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease

Abstract: Background and purpose Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD). Methods The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+). Results After 3 years follow-up 11 subjects had developed PD. In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN+. Conclusion With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost-effective screening strategy which might require longer follow-up intervals and application of additional instruments.

Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy.

Abstract: Background and purpose We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. Methods Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18–80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (−2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40-m-walking test (40-MWT), nine-hole-peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. Results SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (P < 0.05) as compared with a decline of 14.4 ± 20.3% (P < 0.05) in the placebo group; the difference between the two groups being significant (P < 0.01). ODSS, NIS, MRC, grip strength and 40-MWT improved following SCIG versus saline. Conclusions SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG.

Impact of a weight loss program on migraine in obese adolescents.

Abstract: Background and purpose Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. Methods In all, 135 migraineurs, aged 14–18 years, with body mass index (BMI) ≥97th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. Results Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. Conclusions Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

High resolution sonography in the evaluation of the peripheral nervous system in polyneuropathy – a review of the literature

Abstract: Clinical, laboratory and electrodiagnostic studies are the mainstay in the diagnosis of polyneuropathy. An accurate etiological diagnosis is of paramount importance to provide the appropriate treatment, prognosis and genetic counselling. High resolution sonography of the peripheral nervous system allows nerves to be readily visualized and to assess their morphology. Ultrasonography has brought pathophysiological insights and substantially added to diagnostic accuracy and treatment decisions amongst mononeuropathies. In this study the literature on its clinical application in polyneuropathy is reviewed. Several polyneuropathies have been studied by means of ultrasound: Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, multifocal motor neuropathy, paraneoplastic polyneuropathy, leprosy and diabetic neuropathy. The most prominent reported pathological changes were nerve enlargement, increased hypo-echogenicity and increased intraneural vascularization. Sonography revealed intriguingly different patterns of nerve enlargement between inflammatory neuropathies and axonal and inherited polyneuropathies. However, many studies concerned case reports or case series and showed methodological shortcomings. Further prospective studies with standardized protocols for nerve sonography and clinical and electrodiagnostic testing are needed to determine the role of nerve sonography in inherited and acquired polyneuropathies.

Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis.

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Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy

Abstract: Background and purpose The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin (TTR) familial amyloidosis polyneuropathy (FAP) in more advanced cases Methods The study was a prospective, non-randomized controlled trial carried out at the French national reference centre for FAP with follow-up at 1 year Thirty-seven consecutive Met30-TTR-FAP patients were enrolled between December 2009 and July 2011, with NIS-LL (Neuropathy Impairment Score-lower limbs) > 10 and Karnofsky score > 60 Their mean (SD) age was 564 (19) years Seventy-seven per cent of patients had a walking disability Seven patients (19%) were withdrawn for adverse effects The primary study outcome measurements, planned before data collection began, were NIS-LL and NIS-UL (upper limbs) scores and disability scores Results Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months During the first 6 months of treatment, the mean progression of NIS-LL score was 48 and was similar to that during the period before treatment Among the 45% of patients without NIS-LL progression, the NIS-UL score worsened in 55% During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period Two out of nine patients who were initially normotensive developed orthostatic hypotension There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two Conclusion In most patients with advanced Met30 TTR-FAP, Tafamidis is not able to stop disease progression, in respect of both NIS-LL and disability Other anti-amyloid medicines should be assessed in this context

Loss of temporal retinal nerve fibers in Parkinson disease: a mitochondrial pattern?

Abstract: Background and purpose: Optic nerve involvement is frequent in mitochondrial disease, and retinal abnormalities are described in Parkinson’s disease (PD). Methods: We evaluated retinal nerve fiber layer (RNFL) thickness by optical coherence tomography in 43 patients with PD and in 86 age-matched controls. We considered separately the eyes ipsilateral and contralateral to the most affected body side in patients with PD. ancova analysis, Pearson test, and multiple regression analysis were used (P < 0.05). Results: Patients with PD showed significantly thinner temporal RNFL thickness compared to controls (P = 0.004), more evident in the eye contralateral to the most affected body side. Average RNFL thickness significantly correlated with age in both controls and patients with PD (P-values ranging from 0.001 to 0.019), whereas in patients with PD RNFL thickness did not correlate with clinical variables. Conclusions: Our study reveals a loss of retinal nerve fibers in the temporal quadrant in PD, which is typically susceptible in mitochondrial optic neuropathies.

High resolution MRI difference between moyamoya disease and intracranial atherosclerosis

Abstract: Background and purpose Along with intracranial atherosclerotic disease (ICAD), moyamoya disease (MMD) is the most common cause of middle cerebral artery (MCA) occlusion in Asians. Although they have differing vascular wall pathologies, conventional angiographic evaluation methods cannot easily differentiate MMD from ICAD in certain situations, such as in young patients with atherosclerotic risk factors. High resolution magnetic resonance imaging (HR-MRI) findings for the diseased segments of MCAs in MMD and symptomatic ICAD were compared to further elucidate differences in arterial wall changes. Methods Angiographically confirmed patients, 12 MMD and 20 ICAD, who suffered a stroke due to MCA occlusion were recruited and underwent HR-MRI. The size of the outer diameter and other stenotic vessel wall characteristics revealed by HR-MRI, including enhancement, eccentricity and other lesion patterns, were analyzed by two independent reviewers in a blind fashion. Results MMD patients were younger than ICAD patients (32.92 ± 11.08 years vs. 51.85 ± 11.97 years; mean ± SD) and displayed a smaller outer diameter in the stenotic portion (1.61 ± 0.43 mm for MMD vs. 3.03 ± 0.53 mm for ICAD, P < 0.0001). Eccentric lesions (three of 12 in MMD vs. 19 of 20 in ICAD, P < 0.0001) and focal enhancements in diseased areas (two of seven in MMD vs. 13 of 17 in ICAD, P = 0.061) were less common in MMD cases. Conclusions Our HR-MRI findings show that MMD is associated with smaller, concentric occlusive lesions which are rarely enhanced compared with symptomatic ICAD, consistent with the results of previous pathological reports. HR-MRI may therefore have utility in differentiating MMD from ICAD.

Autosomal dominant cerebellar ataxias: A systematic review of clinical features

Abstract: Fil: Rossi, M.. Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia; Argentina

PRRT2 mutations and paroxysmal disorders

Abstract: In the past year, mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on PRRT2 mutation-associated disorders. Our objectives were to describe the wide clinical spectrum associated with PRRT2 mutations, and to present the current hypotheses on the underlying pathophysiology. PRRT2 mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The PRRT2 protein, through its interaction with SNAP-25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by PRRT2 loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age-dependent expression. The clinical spectrum of PRRT2 mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.

Anaemia and cognitive performances in the elderly: a systematic review.

Abstract: Anaemia defined as a haemoglobin level <13 g/dl in men and <12 g/dl in women is common in older people and associated with numerous health consequences. The aim of this study was to systematically review all published data from the past 30 years that studied the association between anaemia and cognitive performance in people aged 65 years and over. An English and French Medline and Cochrane Library search ranging from 1979 to 2011 indexed under the Medical Subject Heading (MeSH) terms 'haemoglobin' or 'anaemia' combined with the terms 'dementia' or 'cognition disorders' or 'memory disorders' or 'orientation' or 'executive functions' or 'attention' or 'brain' or 'neuropsychological tests' was performed. Ninety-eight studies were selected. The following specific conditions were excluded: cancer, chronic kidney diseases, chronic heart disease and post-operative cognitive dysfunction. Five observational studies and six prospective cohort studies were included in the final analysis. According to the studies, the number of participants ranged from 302 to 2250 community-dwelling older people aged 55 years or over. Four studies considered the association between haemoglobin concentration and global cognitive functions, another three examined the association between haemoglobin concentration and the incidence of dementia, and four studies evaluated some specific aspects of cognition. A significant positive association was shown between anaemia and global cognitive decline as well as the incidence of dementia. A significant association was also shown between anaemia and executive functions. This systematic review shows a probable association between anaemia and cognitive performances, particularly with executive functions.

Hospital admission due to infections in multiple sclerosis patients.

Abstract: Background and purpose: Multiple sclerosis (MS) patients are at increased infection risk. Here the influences of susceptibility, severity and surveillance bias on infection-related hospital admission are assessed. Methods: Swedish registers identified 20 276 patients with MS, matched with 203 951 people from the general population without MS. Risk of first hospital admission for infection and mortality over 36 years was estimated by Poisson regression. Results: Multiple sclerosis was associated with an increased hospital admission risk for all infections, with an adjusted relative risk (and 95% confidence interval) of 4.26 (4.13-4.40). A proportion of this raised risk was probably due to surveillance and referral bias, although a raised risk remained when MS was compared with other immune-mediated diseases. The 1-month mortality rate following hospital admission for infection was higher in MS patients than in the comparison cohort, with a relative risk of 4.69 (4.21-5.22). There was no clear temporal trend in the results, and risks were higher in males and varied by MS phenotype. Conclusions: Higher hospital admission rates among MS patients for infection are likely to be due to a combination of surveillance bias, cautious medical management and greater susceptibility to severe infections. MS-related functional limitations may increase infection risk and this should be considered in MS management. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Insular stroke is associated with acute sympathetic hyperactivation and immunodepression

Abstract: Background and purpose Post-stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection. Methods We analyzed clinical, brain imaging, and laboratory data of 384 patients (174 women; mean age 70.8 ± 12.9 years) consecutively admitted to the stroke unit no later than 24 h after onset of acute ischaemic stroke involving the MCA territory. Results Patients with lesion affecting >33% of MCA territory had increased serum metanephrine and normetanephrine levels, elevated neutrophil counts but decreased eosinophil, helper T lymphocyte, and cytotoxic T lymphocyte counts compared to patients with lesion in <33% of MCA territory. Patients with large infarctions had increased frequency of infections within 14 days after stroke, especially chest infections (P < 0.001). Considering only patients with non-lacunar infarction in <33% of MCA territory, those with insular lesion had significantly higher normetanephrine levels, higher neutrophil but lower eosinophil and helper T lymphocyte counts than those with non-insular lesion, despite similar lesion diameters. This coincided with an increased frequency of chest infections (P < 0.01) in patients with insular lesion. Whilst patients with right insular lesion showed decreased heart rate variability, lesion laterality had no impact on laboratory findings or infection frequency. Conclusion These findings suggest a specific role of insular lesion in the pathogenesis of stroke-induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.

Serum 25‐hydroxyvitamin D predicts severity and prognosis in stroke patients

Abstract: Background and purpose We aimed to evaluate the association between 25-hydroxyvitamin D (25(OH)D) levels and both clinical severity at admission and outcome at discharge in stroke patients. Methods From February 2010 to December 2010, consecutive stroke patients admitted to the Department of Neurology of Dijon, France, were identified. Clinical information was collected. Serum concentration of 25(OH)D was measured at baseline. Stroke severity was assessed at admission using the NIHSS score. Functional impairment was evaluated at discharge using the modified Rankin scale (m-Rankin). Multivariate analyses were performed using logistic regression models. Results Of the 386 recorded patients, serum 25(OH)D levels were obtained in 382 (median value = 35.1 nM; IQR = 21–57.8). At admission, 208 patients had a NIHSS ≤5, with a higher mean 25(OH)D level than that observed in patients with moderate-to-high severity (45.9 vs. 38.6 nM, P < 0.001). In multivariate analyses, a 25(OH)D level in the lowest tertile (<25.7 nM) was a predictor of a NIHSS ≥6 (OR = 1.67; 95% CI = 1.05–2.68; P = 0.03). The mean 25(OH)D level was lower in patients with moderate-to-severe handicap at discharge (m-Rankin 3–6) than in patients with no or mild handicap (35.0 vs. 47.5 nM, P < 0.001). In multivariate analyses, the lowest tertile of 25(OH)D level (<25.7 nM) was associated with a higher risk of moderate-to-severe handicap (OR = 2.06; 95% CI = 1.06–3.94; P = 0.03). Conclusion A low serum 25(OH)D level is a predictor of both severity at admission and poor early functional outcome in stroke patients. The underlying mechanisms of these associations remain to be investigated.

Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration.

Abstract: Background and purpose Biomarkers as indicators for the progression of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain still elusive. We performed a cross-sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV-infected patients. Methods We enrolled 94 patients (82 men and 12 women; mean age 45 ± 10 years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho-tau, beta-amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF. Results We found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV-infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho-tau or A-beta-amyloid in CSF analysis. Conclusions Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.

Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis

Abstract: Background and purpose Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive paralysis of striated muscles due to the loss of upper and lower motor neurons. The disease leads to death within 2–5 years, mainly due to respiratory failure. The pathogenesis of ALS is still unexplained for the most part. In this study, we aimed to determine the prevalence of different cardiovascular, metabolic, and neuropsychiatric comorbidities in a large ALS cohort and to evaluate their influence on the disease course. Methods A cohort of 514 patients with ALS of our ALS outpatient clinic was investigated retrospectively with reference to known prognostic factors and comorbidities. The prevalence of concomitant diseases was compared with the data from the German general population. Uni- and multivariate survival analyses were performed using the Cox proportional hazards model and Kaplan–Meier analysis. Results The prevalence of cardiovascular diseases and cardiovascular risk factors was significantly lower in patients with ALS compared to the German general population, whilst the prevalence of dementia, parkinsonism, and depressive symptoms was significantly higher in the ALS cohort. None of the investigated comorbidities had an influence on the disease course or on the survival of patients. Conclusions Persons with cardiovascular diseases or risk factors seem to be at lower risk of ALS. Although these diseases are apparently somehow protective regarding ALS susceptibility, their presence did not modify disease progression and survival in patients with ALS. Our study further confirms the well-known continuum between ALS and dementia. It also suggests a link with other neurodegenerative diseases such as Parkinson's disease.

Neuropsychological course of voltage-gated potassium channel and glutamic acid decarboxylase antibody related limbic encephalitis.

Abstract: Background and purpose Autoantibodies (abs) to glutamic acid decarboxylase (GAD) and to voltage-gated potassium channels (VGKC) induce distinct courses of limbic encephalitis, related to MRI findings, seizure outcome and cognition. Methods A detailed analysis of the cognitive course of the two forms is presented, spanning a median time interval of 28 months, including parameters of attention, learning and memory in 15 VGKC-ab-positive and 16 GAD-ab-positive patients. Results In both groups, the initially significantly impaired attention performance recovered to a putatively premorbid level. In VGKC patients the partially severely impaired learning and memory performance improved under treatment but remained subnormal at last follow-up. By contrast, GAD-ab-positive patients had initially less impaired learning and memory scores but did not show an improvement under treatment. Conclusions The results provide evidence of distinct relations between inductive processes and cognitive outcome in VGKC-ab-positive and GAD-ab-positive subforms of limbic encephalitis, which possibly depend on differences in pathogenic molecular mechanisms and affected cerebral loci.

Long‐term efficacy and safety of safinamide as add‐on therapy in early Parkinson's disease

Abstract: Background and purpose Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). Methods Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to ‘intervention’, defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. Results Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). Conclusions The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD.

Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG the ICE study

Abstract: Background and purpose In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. Methods We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. Results A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%–50.9%) than in the placebo group (21.1%–25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. Conclusions Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.

The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage Huntington's disease: a pilot study.

Abstract: Background and purpose: Despite advances in the understanding of Huntington’s disease (HD), treatment remains symptomatic. Multidisciplinary rehabilitation, however, appears to impact disease progression. Here we show the feasibility, safety and efficacy of a 9-month multidisciplinary rehabilitation programme in a small cohort of patients with early-to-middle-stage HD. Methods: Twenty patients with HD were assigned to two groups, equally matched for cognitive and motor scores. One group received the intervention, whilst the other served as control. The Unified-Huntington’s-Disease-Rating-Scale-TotalMotor-Score was the primary outcome measure. Neurocognitive/psychological tests, body composition, postural stability, strength and quality of life assessments were secondary outcome measures. Results: The intervention reduced motor and postural stability deterioration, with minor improvements in depression, cognition and quality of life. Significant gains were observed for fat-free mass and strength. Conclusion: This pilot study suggests that a prolonged multidisciplinary rehabilitation programme in early-to-middle-stage HD is feasible, well-tolerated and associated with therapeutic benefit. Further explorative, larger studies are warranted.

Replication and meta-analysis of common variants identifies a genome-wide significant locus in migraine.

Abstract: Background and purpose Genetic factors contribute to the aetiology of the prevalent form of migraine without aura (MO) and migraine with typical aura (MTA). Due to the complex inheritance of MO and MTA, the genetic background is still not fully established. In a population-based genome-wide association study by Chasman et al. (Nat Genet 2011: 43: 695–698), three common variants were found to confer risk of migraine at a genome-wide significant level (P < 5 × 10−8). We aimed to evaluate the top association single nucleotide polymorphisms (SNPs) from the discovery set by Chasman et al. in a primarily clinic-based Danish and Icelandic cohort. Methods The top association SNPs were assessed in 2523 cases and 38 170 controls, and a meta-analysis was performed, combining the discovery set with all the follow-up studies. Finally the confirmed SNPs were assessed in a genotype–phenotype analysis. Results Two out of three SNPs that showed genome-wide significant associations in the previous study: rs10166942 (near TRPM8) and rs11172113 (in LRP1) were significantly associated with migraine in the present study. The meta-analysis confirmed the previous three genome-wide significant associated SNPs (rs2651899, rs10166942 and rs11172113) to confer risk of migraine. In addition, the C-allele of rs2078371 (near TSPAN-2) also reached genome-wide significance for association with migraine [OR = 1.14; CI = (1.09–1.20); P = 2.55 × 10−8]. Conclusion TSPAN-2 encodes an integral membrane protein involved in oligodendrogenesis. This new finding supports the plausible implication of neuroglia in the pathophysiology of MO and MTA.

Triggers of migraine and tension‐type headache in China: a clinic‐based survey

Abstract: Background and purpose Identification of the trigger factors of headache could be an important aspect of preventive management, but the characteristics of primary headache triggers in China are unknown. This study was performed to estimate the frequencies of the putative headache triggers, which are endorsed by patients with migraine and tension-type headache (TTH). Methods From July 2011 to December 2011, a cross-sectional survey was conducted in the neurological clinic of a tertiary care hospital in Chongqing. All consecutive patients with the chief complaint of headache were interviewed by a board-certified headache specialist. The diagnoses were made according to International Classification of Headache Disorders – 2nd edition. Patients with migraine and TTH were recruited. Results The number of investigated patients was 1219, of whom 394 were migraine and 344 were TTH; and 80.2% migraineurs and 67.4% TTH patients reported trigger factors. The most common triggers for both migraine and TTH were sleep disturbance, negative affect and sunlight. Menstrual cycle (OR 3.6, 95%CI 1.2, 11.2), change of the weather (OR 3.1, 95%CI 1.9, 4.8), noise (OR 2.2, 95%CI 1.1, 4.4) and alcohol (OR 1.8, 95%CI 0.7, 1.8) were more associated with migraineurs. Negative affect was more associated with TTH (OR 2.0, 95%CI 1.3, 2.9). Conclusions Trigger factors were frequent among both migraine and TTH patients. Avoidance of all headache triggers is impractical. Learning to cope with triggers is important to headache prevention.

Ischaemic stroke at a young age is a serious event--final results of a population-based long-term follow-up in Western Norway.

Abstract: Background and purpose Our population-based long-term follow-up of young ischaemic stroke patients and controls showed 10-fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive–dead survey. Methods Patients (n = 232) ≤ 49 years with an index-stroke between 1988 and 1997 were retrospectively selected and compared with age- and sex-matched controls (n = 453). At follow-up from 2004 to 2005, 144 (77%) of 187 patients were clinically examined. Self-assessment information about memory problems, anxiety, depression, sleeping problems, education and employment was compared with answers from standardized questionnaires from 167 controls. Functional outcome was measured by the modified Rankin Scale (mRS). Results Patients compared with controls had more memory problems (41.0% vs. 5.4%, P < 0.001), anxiety (19.4% vs. 9%, P = 0.009), depression (29.2% vs. 13.2%, P = 0.001) and sleeping problems (36.1% vs. 19.2%, P = 0.001). In the multiple regression analysis male gender (OR 9.3, 95%CI 0.10–0.61, P = 0.002), normal memory (OR 12.7, 95%CI 0.07–0.47, P < 0.001) and mRS 0–1 (OR 15.7, 95%CI 0.002–0.12, P < 0.001) were factors for full-time employment. Blood pressure was < 140/90 mmHg in 39% of patients, 49% stopped smoking and 38.2% used statins. After a mean observation time of 18.3 years, 63 (27.2%) of 232 patients were dead. Conclusions Our data show a heterogeneous prognosis and high mortality even for long-time survivors of ischaemic stroke at a young age. Prospective studies of young stroke patients and controls are necessary for direct comparison.

Endovascular therapy in 201 patients with acute symptomatic occlusion of the internal carotid artery.

Abstract: Background and purpose Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest. Methods From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively. Results There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2–3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2–3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91 = 86% and 64/78 = 82%) compared with pharmacological thrombolysis only (15/32 = 47%; P < 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0–2] in 54/28% patients and moderate (mRS 0–3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (P = 0.001). In multivariate analysis age [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93–0.98], NIHSS on admission (OR = 0.9, 95% CI = 0.83–0.98) and functional ICA-T occlusion (OR = 0.35, 95% CI = 0.16–0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (OR = 9.30, 95% CI = 2.03–42.63). Conclusions The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.