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Objective To compare spiral drawings between essential tremor (ET) and functional tremor (FT); exploring spiral size, axis, density and tremor severity score for parameters to potentially distinguish ET from FT. Method Spiral drawing data of 29 patients with either ET or FT were acquired from ASPH using the NHs patient database and patient notes. Using a ruler spiral size was represented as the horizontal diameter, and it was also measured to 3-loops (3-turn diameter/3TD). Spiral density was determined using total loop number and the horizontal diameter of each spiral. Tremor severity score was determined using a validated tremor scale (Bain). The spirals were also rated for the presence of single or multiple axes. An independent t-test was used to compare tremor severity, 3TD and size and a Mann-Whitney test was used to compare spiral density between both groups. Results Spirals drawn by ET patients had significantly higher tremor severity scores than FT patients (4.18 vs 2.82 p=0.03). Spiralaxis is significantly affected by tremor type (p=0.03); there was a significantly greater proportion of patients in the ET group that demonstrate a single axis on spirography compared to those in the FT group (57% vs 14.3%; p=0.02). In two patients with FT and ET there were variable degrees of change in tremor severity over time, with the change in severity in FT being greater than in ET. Conclusion ET and FT can be distinguished by tremor severity and the presence of a single vs multiple axis on analysis of handwritten spiral drawings.

Turner MR, Kiernan MC, eds. Published by Oxford University Press, (New York, USA) 2015. ISBN 978-0-19-965860-2. “Let us keep looking, in spite of everything. Let us keep searching. It is indeed the best method of finding, and perhaps thanks to our efforts, the verdict we will give such a patient tomorrow will not be the same we must give this man today.”Jean-Martin Charcot (1889) Though written more than 120 years ago, this quote has not lost its validity, and today represents the essence of this book named ‘ Landmark Papers in Neurology ’. The book invites the reader to explore and understand the evolution and development of neurology over the past two centuries, taking us through the stories of critical and meticulous neurologists and investigators, whose perseverance in looking and searching ended with the achievement of the characterisation and comprehension of the key neurological syndromes. Without doubt, Landmark Papers in Neurology fills an empty niche in the neurological literature. The Landmark Papers series …

How to read a paper. The basics of evidence based medicine . Bytrisha greenhalgh. (Pp 222, £16.95). Published by BMJ Books, London, 2001. ISBN 0 7279 1578 9 The title of this slim paperback is somewhat misleading, as it covers considerably more than reading scientific papers (including how to deal with a visit from a drug rep!). There are two chapters which orientate the reader on why and how to keep abreast of the medical literature, including its electronic forms, nine on various aspects of reading papers, and one on implementing evidence based data. All necessary skills for the medical academic, of course, or for someone approaching a little aired but thorny issue. However, the author works in primary care, and much of her guidance seems directed towards drug trials, and particularly to the needs of her colleagues who may be wondering “how shall I treat the patient actually sitting in my surgery today?”. Good as the advice she gives may be, it is difficult to picture the general practitioner, medical registrar, or even less the tyro casualty officer, asking the patient to wait while he or she boots the computer and searches the medical literature, starting with a couple of systematic reviews and delving into an …

Background: The mismatch between perfusion and diffusion lesions on magnetic resonance perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) may help identify patients for thrombolysis. Evidence underlying this hypothesis was assessed. Methods: All papers describing magnetic resonance PWI/DWI findings in patients with acute ischaemic stroke, and their functional and/or radiological outcome at 1 month, with or without thrombolysis were systematically reviewed. Results: 11 papers fulfilled the inclusion criteria. Among these, there were 5 different mismatch definitions and at least 7 different PWI methods. Only 3 papers including 61 patients with and 18 without mismatch provided data on mismatch, outcome and influence of thrombolysis. Mismatch ( v no mismatch) without thrombolysis was associated with a non-significant twofold increase in the odds of infarct expansion (odds ratio (OR) 2.2, 95% confidence interval (CI) 0.34 to 14.1), which did not change with thrombolysis (OR 2.0, 95% CI 0.37 to 10.9). Half of the patients without mismatch also had infarct growth (with or without thrombolysis). No data were available on functional outcome. Conclusions: Standardised definitions of mismatch and perfusion are needed. Infarct growth may occur even in the absence of mismatch. Currently, data available on mismatch are too limited to guide thrombolysis in routine practice. More data are needed from studies including patients with and without mismatch, and randomised treatment allocation, to determine the role of mismatch.

Objectives: The lack of agreement regarding assessment methods is responsible for the variability in the reported rate of occurrence of spatial neglect after stroke. The aim of this study was to assess the sensitivity of different tests of neglect after right hemisphere stroke. Methods: Two hundred and six subacute right hemisphere stroke patients were given a test battery including a preliminary assessment of anosognosia and of visual extinction, a clinical assessment of gaze orientation and of personal neglect, and paper and pencil tests of spatial neglect in the peripersonal space. Patients were compared with a previously reported control group. A subgroup of patients (n=69) received a behavioural assessment of neglect in daily life situations. Results: The most sensitive paper and pencil measure was the starting point in the cancellation task. The whole battery was more sensitive than any single test alone. About 85% of patients Presented some degree of neglect on at least one measure. An important finding was that behavioural assessment of neglect in daily life was more sensitive than any other single measure of neglect. Behavioural neglect was considered as moderate to severe in 36% of cases. A factorial analysis revealed that paper and pencil tests were related to two underlying factors. Dissociations were found between extrapersonal neglect, personal neglect, anosognosia, and extinction. Anatomical analyses showed that neglect was more common and severe when the posterior association cortex was damaged. Conclusions: The automatic rightward orientation bias is the most sensitive clinical measure of neglect. Behavioural assessment is more sensitive than any single paper and pencil test. The results also support the assumption that neglect is a heterogeneous disorder.

Objective: Patients with left neglect on line bisection show normal implicit sensitivity to manipulations of both the stimulus and the visual background. Three experiments were designed to define this sensitivity more exactly. Methods: Normal controls and patients with left neglect performed a series of horizontal line bisection tasks. Independent variables were the configurations of the backgrounds for the line—rectangle, square, circle, left and right pointing isosceles triangles—and whether the background was the shape of the piece of paper or an outline drawn on a standard piece of paper. In a separate experiment different components of the triangle were outlined on a piece of paper. Deviation from true midpoint was calculated. Results: Simply placing the target lines in a symmetric background such as a square or circle did not reliably reduce neglect. A triangle asymmetric in the horizontal plane caused a shift in bisection away from the triangle9s vertex. With right pointing triangles the perceived midpoint shifted to the left of true centre (crossed over). The effects of the triangles were comparable in the patients and the controls when controlled for baseline bisection bias. The critical components of the triangles were the angular legs. This effect of background was not influenced by lesion site or by hemianopia. Conclusions: Patients with left visual neglect remain sensitive to covert manipulations of the visual background that implicitly shift the perceived midpoint of a horizontal line. This effect is strong enough to eliminate neglect on a bisection task. The mechanism of this effect is expressed through preattentive visual capacities.

OBJECTIVE To review the clinical effectiveness and costs of a range of disease modifying drugs in multiple sclerosis. Drugs included are azathioprine, cladribine, cyclophosphamide, intravenous immunoglobulin, methotrexate, and mitoxantrone. METHODS Electronic databases and bibliographies of related papers were searched for randomised controlled trials (RCTs) and systematic reviews, and experts and pharmaceutical companies were contacted for further information. Inclusion and quality criteria were assessed, data extraction undertaken by one reviewer and checked by a second reviewer, with discrepancies being resolved through discussion. Costs were obtained and cost-effectiveness papers sought. RESULTS Seventeen studies met the inclusion criteria for the review. Evidence for the clinical effectiveness of the drugs showed some reductions in relapse rates and/or progression to disability for people with MS, although benefits may be lessened by wide ranging side effects. Annual drug costs/patient are estimated to range from £60 to £10 200. No cost effectiveness studies were found. CONCLUSION Evidence for the effectiveness of these drugs in multiple sclerosis is problematic because there are few good quality trials for each drug. Trials often have methodological limitations and use different treatment regimes, patient groups, and outcome measures. Well conducted trials using outcome measures with clinical significance for groups of patients with different types of multiple sclerosis and long term follow up are needed if the evidence base of treatment for the disease is to be improved.

Objectives: Although epileptic seizures are an infrequent feature of acute attacks of the neuropsychiatric porphyrias, there are no significant reports of porphyria in chronic epilepsy. This paper attempts to redress the balance. Methods: Three case reports, including detailed laboratory and molecular diagnostics. Results: Two patients with variegate porphyria and one with acute intermittent porphyria, referred within 1 year to a specialist porphyria service, with a long history of chronic refractory epileptic seizures, are described. Conclusions: Porphyria may be an aetiological factor in some cases of chronic refractory partial or generalised epilepsy. Porphyria should also be considered if addition of a new anti-epileptic medication causes a major deterioration in the epilepsy.

Background: Spasticity and loss of function in an affected arm are common after stroke. Although botulinum toxin is used to reduce spasticity, its functional benefits are less easily demonstrated. This paper reports an exploratory meta-analysis to investigate the relationship between reduced arm spasticity and improved arm function. Method: Individual data from stroke patients in two randomised controlled trials of intra-muscular botulinum toxin were pooled. The Modified Ashworth Scale (elbow, wrist, fingers) was used to calculate a "Composite Spasticity Index". Data from the arm section of the Barthel Activities of Daily Living Index (dressing, grooming, and feeding) and three subjective measures (putting arm through sleeve, cleaning palm, cutting fingernails) were summed to give a "Composite Functional Index". Change scores and the time of maximum change were also calculated. Results: Maximum changes in both composite measures occurred concurrently in 47 patients. In 26 patients the improvement in spasticity preceded the improvement in function with 18 showing the reverse. There was a definite relationship between the maximum change in spasticity and the maximum change in arm function, independent of treatment (ρ = –0.2822, p = 0.0008, n = 137). There was a clear relationship between the changes in spasticity and in arm function in patients treated with botulinum toxin (Dysport) at 500 or 1000 units (ρ = –0.5679, p = 0.0090, n = 22; ρ = –0.4430, p = 0.0018, n = 47), but not in those treated with placebo or 1500 units. Conclusions: Using a targeted meta-analytic approach, it is possible to demonstrate that reducing spasticity in the arm is associated with a significant improvement in arm function.

Objectives: This paper reports for the first time three cases of infection by HTLV-I via organ transplantation; all the organs coming from the same asymptomatic infected donor. The need is considered for the implementation of compulsory screenings for HTLV antibodies on organ donors and on blood banks. Methods: The determination of antibodies for HTLV-I/II on samples of serum and cerebral spinal fluid from the patients and the donor was performed by enzyme immunoassay and western blot. Analysis of proviral DNA was performed by polymerase chain reaction. To detect changes in the sequence of aminoacids, the tax gene was sequentiated, amplified, and compared with ATK prototype stocks. Spinal cord magnetic resonance imaging, cerebral spinal fluid, and somatosensory evoked potential studies were carried out in all patients. Results: All three transplanted patients developed a myelopathy within a very short period of time. In all three patients and donor the virus belonged to the Cosmopolitan A subtype. The homology of HTLV-I sequences recovered from the patients and donor was 100% in all four cases. Proviral load was high in all three patients. The factors that certainly contributed to the infection in the first place, and the development of the disease later, were on the one hand the high proviral load and their immunosupressed condition, and on the other the virus genotype, which proved to be an aggresive variant. However, the analysis of the histocompatibility antigen showed that two of the patients carried an haplotype that has been associated with a lower risk of developing this disease. Conclusions: It is argued that, although in Spain and other European countries there is not compulsory screening for HTLV antibodies because of the studies that show a low seroprevalence, in view of the cases here reported, and to avoid the serious consequences that such infection has on transplanted patients, compulsory screenings, both on organ donors and on blood banks, should be implemented.

Background and purpose Cognitive and behavioural symptoms represent primary clinical manifestations of anterior thalamic infarcts (ATIs) in the tuberothalamic artery territory. The aim of the study is to understand the pathomechanism of cognitive and behavioural disturbances in left ATI (LATI). Methods 6 patients with isolated LATIs were investigated using neuropsychological assessments, MRI stereotactic lesion localisation and positron emission tomography. Results The patients were characterised clinically by verbal memory impairment, language disturbances dominated by anomia and word-finding difficulty and apathy. The ventral anterior nucleus (VA) proper, magnocellular VA (VAmc), ventral lateral anterior nucleus (VLa), ventral lateral posterior nucleus (VLp) and mammillothalamic tract were involved in all patients. Compared with healthy controls, the regional cerebral blood flow was lower in the thalamus, the dorsolateral, medial and orbital frontal lobes, the anterior temporal lobe, the inferior parietal lobule and the occipital lobe of the left hemisphere. Conclusions The authors propose that the Papez circuit disruption at the mammillothalamic tract and possibly thalamomedial temporal disconnection at the VA region is responsible for memory impairment and that the thalamo-anterior temporal disconnection is associated with language disturbance in LATI, respectively.

Objective To investigate salivary cortisol samples in patients with Parkinson's disease (PD) with and without impulsive compulsive behaviours (ICB) during a risk task. Methods Salivary cortisol levels were measured in 13 PD patients without ICB (PD−ICB) and in 15 PD patients with ICB (PD+ICB) before, after medication and throughout the day, and were compared with results with 14 healthy controls. All participants also performed a gambling task to assess risk taking behaviour. Results Significantly higher diurnal cortisol levels were found in the PD−ICB group compared with healthy controls but no differences were seen between the PD+ICB and the control group. Increased cortisol levels were significantly correlated with increased risk taking in PD+ICB patients but no interaction was found in the PD−ICB group. Conclusions The findings are in keeping with previous studies which have linked low cortisol levels with antisocial behaviour. The higher cortisol levels during the risk task in the PD+ICB group are consistent with reports in pathological gamblers during gambling and addicts during drug abuse. The results support the hypothesis that cortisol plays an important role in risk taking in ICBs.

Background In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, selective neuronal damage can be detected as a decrease in central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex. This study aimed to determine whether a decrease in the BZRs in the non-infarcted cerebral cortex is associated with poor performance on the Wisconsin Card Sorting Test (WCST), which assesses executive functions. Methods The authors measured the BZRs using positron emission tomography and 11C-flumazenil in 60 non-disabled patients with unilateral atherosclerotic ICA or MCA disease and no cortical infarction. Using three-dimensional stereotactic surface projections, the abnormally decreased BZR index (extent (%) of pixels with Z score >2 compared with controls×average Z score in those pixels) in the cerebral cortex of the anterior cerebral artery (ACA) or MCA territory was calculated and found to be correlated with the patient's score on the WCST. Results On the basis of the WCST results, 39 patients were considered abnormal (low categories achieved) for their age. The BZR index of the ACA territory in the hemisphere affected by arterial disease was significantly higher in abnormal patients than in normal patients. The BZR index of the MCA territory differed significantly between the two groups when patients with left arterial disease (n=28) were analysed separately. Conclusions In atherosclerotic ICA or MCA disease, selective neuronal damage that is manifested as a decrease in BZRs in the non-infarcted cerebral cortex may contribute to the development of executive dysfunction.

Background: Risk stratification can contribute to individualised optimal secondary prevention in patients with cerebrovascular disease. Objective: To prospectively investigate the prediction of the Essen Stroke Risk Score (ESRS) and a pathological Ankle Brachial Index (ABI) in consecutive patients hospitalised with acute ischaemic stroke or transient ischaemic attack (TIA) in 85 neurological stroke units throughout Germany. Methods: 852 patients were prospectively documented on standardised case report forms, including assessment of ESRS and ABI. After 17.5 months, recurrent cerebrovascular events, functional outcome or death could be assessed in 729 patients predominantly via central telephone interview. Results: After discharge from the documenting hospital, recurrent stroke occurred in 41 patients (5.6%) and recurrent TIA in 15 patients (2.1%). 52 patients (7.1%) had died, 33 (4.5%) from cardiovascular causes. Patients with an ESRS ⩾3 (vs 0.9) had a significantly higher risk of recurrent stroke or cardiovascular death (10.4% vs 5.5%; OR 2.00, 95% CI 1.12 to 3.56) and a higher recurrent stroke risk (6.6% vs 4.6%; OR 1.47, 95% CI 0.76 to 2.83). Conclusion: Our prospective follow-up study shows a significantly higher rate of recurrent stroke or cardiovascular death and a clear trend for a higher rate of recurrent stroke in patients with acute cerebrovascular events classified as high risk by an ESRS ⩾3 or a pathological ABI.

Objective: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington’s disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis. Methods: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor. Results: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. Conclusions: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.

OBJECTIVES—Quantitative measurement of lesion load on proton density or T2 weighted brain MRI in multiple sclerosis is a widely used marker of disease progression in treatment trials and natural history studies. However, it has proved difficult to obtain highly reproducible measurements. Several factors account for this, one of which is uncertainties in lesion identification, particularly very small white matter abnormalities. This paper aims to ascertain the significance of very small white matter abnormalities in the measurement of lesion load in multiple sclerosis. METHODS—All visible lesion areas identified by an experienced observer on proton density weighted spin echo brain MRI with 5 mm thick slices were measured by using a contouring technique in 15 patients with secondary progressive multiple sclerosis (SPMS) and 13 with relapsing remitting multiple sclerosis (RRMS). The size distribution of these lesions was analysed. RESULTS—80% of the number of the lesions were smaller than 80 mm2. Lesions that were smaller than 10 mm2 (equivalent diameter

Introduction: In complex regional pain syndrome type 1 (CRPS-1), patients may have manifestations of central involvement, including allodynia, hyperalgesia or dystonia. We noted that more severely affected patients may experience hyperacusis, which may also reflect central involvement. The aim of this study was to evaluate the occurrence and characteristics of hyperacusis in patients with CRPS related dystonia. Methods: The presence of hyperacusis, speech reception thresholds (SRT), pure-tone thresholds (PTT) and uncomfortable loudness (UCL) was evaluated in 40 patients with CRPS related dystonia. Results: PTT and SRT were normal for all patients. 15 patients (38%) reported hyperacusis and this was associated with allodynia/hyperalgesia and with more affected extremities. UCLs of patients with hyperacusis were significantly lower than UCLs of patients without hyperacusis. Conclusion: Hyperacusis is common among severely affected patients with CRPS related dystonia and may indicate that the disease spreads beyond those circuits related to sensory–motor processing of extremities.

Objective: To estimate the frequency, mechanisms and predictive factors of sleep apnoea syndrome (SAS) in a large group of children and adults with type I (CMI) and II (CMII) Chiari malformation (CM). Background: The anatomical and functional integrity of both respiratory circuits and lower cranial nerves controlling the upper airway is necessary for breathing control during sleep. These latter structures may be altered in CM, and a few investigations have reported CM related sleep disordered breathing. Methods: Forty-six consecutive unrelated patients with CM (40 CMI, six CMII), of which 20 were children (eight males) and 26 were adults (12 males), underwent physical, neurological and oto-rhino-laryngoscopic examination, MRI and polysomnography. Results: SAS was present in 31 (67.4%) of the patients with CM (70% of CMI, 50% of CMII, including mainly children). Sixty per cent of children with CM exhibited SAS, including 35% with obstructive (OSAS) and 25% with central (CSAS) sleep apnoea syndrome. SAS was observed in 73% of CM adults (57.7% OSAS, 15.4% CSAS). Severe SAS was found in 23% of CM adults. Multiple regression analysis revealed that age, type II Chiari and vocal cord paralysis predicted the central apnoea index. Conclusion: SAS is highly prevalent in all age groups of patients suffering from CM. CSAS, a rare condition in the general population, was common among the patients with CM in our study. Sleep disordered breathing associated with CM may explain the high frequency of respiratory failures observed during curative surgery of CM. Our results suggest that SAS should be systematically screened for in patients with CM, especially before surgery.

To determine the effect of electrode contact location on efficacy of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary generalised dystonia (PGD).A consecutive series of 15 patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent bilateral GPi DBS, were assessed using the Burke-Fahn-Marsden (BFM) dystonia scale before and 6 months after surgery. The position of the stimulated electrode contact(s) was determined from the postoperative stereotactic MRI. Contralateral limb and total axial BFM subscores were compared with the location of the stimulated contact(s) within the GPi.The mean total BFM score decreased from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5% (p0.00001). Cluster analysis of the stimulated contact coordinates identified two groups, distributed along an anterodorsal to posteroventral axis. Clinical improvement was greater for posteroventral than anterodorsal stimulation for the arm (86% vs 52%; p0.05) and trunk (96% vs 65%; p0.05) and inversely correlated with the y coordinate. For the leg, posteroventral and anterodorsal stimulation were of equivalent efficacy. Overall clinical improvement was maximal with posteroventral stimulation (89% vs 67%; p0.05) and inversely correlated with the y (A-P) coordinate (r = -0.62, p0.05).GPi DBS is effective for PGD but outcome is dependent on contact location. Posteroventral GPi stimulation provides the best overall effect and is superior for the arm and trunk. These results may be explained by the functional anatomy of GPi and its outflow tracts.

Objective: To calculate the best possible estimates for age specific life expectancy (LE) and anticipated age at the time of death (AAD) in patients with Parkinson’s disease (PD) compared with the general population in the UK. These may be of greater value to patients than standardised mortality ratios (SMRs), which are usually reported in studies on mortality in PD. Methods: A literature review identified articles with data on age stratified life expectancy or SMRs to calculate estimations of LE using the Gompertz function and data on mortality and LE in the UK from the Office of National Statistics and Actuarial Department for the year 2003. Results: Two UK studies and four from Western Europe were used to estimate LE and AAD for patients with PD from SMRs. The mean LEs of patients with PD compared with the general population were: 38 (SD 5) years for onset between 25 and 39 years compared with 49 (SD 5) years; 21 (SD 5) years for onset between 40 and 64 years compared with 31 (SD 7) years; and 5 (SD 4) years for onset age ⩾65 years compared with 9 (SD 5) years. The average AAD of patients with PD with onset between 25 and 39 years was 71 (SD 3) years and considerably lower than that of the general population (82 (SD 2) years). The difference between average AAD for older individuals with PD (onset ⩾65 years) and the general population was smaller, with an AAD of approximately 88 (SD 7) years compared with 91 (SD 5) years. Conclusions: The calculations showed that LE and AAD in PD are reduced for all onset ages but this reduction is greatest in individuals with a young onset. While the results are average estimates, these can provide useful indications of LE and AAD.

Aim: The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. Subjects and methods: All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d’Aosta (4 334 225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. Results: The crude prevalence rate was 3.58/100 000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting–relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995–2001, the mean annual crude incidence rate was 0.36/100 000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age>60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. Conclusion: Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases.

Background: Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. Methods: 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi-sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. Results: The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). Conclusions: Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease.

Background: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer’s disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. Methods: A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [ 123 I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls. Results: Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%. Conclusion: FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.

Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used. Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the relations with demographic, disease related and clinical variables. Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution. Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity. Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

Background: Clinical assessment of cerebral concussion relies on the presence and duration of post concussive symptoms (PCS). Given that these PCS are subjective reports and not always specific to concussion, their usefulness remains to be validated. Objective: To evaluate the usefulness of self-reported PCS by means of cognitive tests and functional MRI (fMRI). Method: 28 male athletes with and without concussion were grouped according to their PCS score. They were then administered a computerised cognitive test battery and submitted to an fMRI session where cerebral activations associated with verbal and non-verbal working memory tasks were analysed. Results: Behaviourally, response accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population-based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months-58 years), which was younger than in the reference population (difference between means 8 years, 95% confidence interval (CI) 3-13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex and mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13-30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Objective: X linked spinobulbar muscular atrophy (Kennedy disease (KD)), which is clinically characterised mainly by neuromuscular and endocrine symptoms, has to be considered as a multisystem disorder. Based on clinical evidence of central nervous system involvement, potential KD associated cerebral volume alterations were analysed in vivo. Methods: Whole brain based analysis of optimised voxel based morphometry (VBM) was applied to three dimensional MRI data from 18 genetically confirmed KD patients and compared with age matched controls. Results: Subtle decreases in grey matter volume, mainly localised in frontal areas, were found, but extensive white matter atrophy was observed, particularly in frontal areas, but also involving multiple additional subcortical areas, the cerebellar white matter and the dorsal brainstem from the midbrain to the medulla oblongata. Conclusion: The VBM results demonstrated a morphological correlate of central nervous system involvement in KD, in agreement with aspects of the clinical phenotype (behavioural abnormalities, central–peripheral axonopathy) and with pathohistological findings.

Objective: The aims of this study were to develop models of personality change after traumatic brain injury (TBI) based on information provided by the TBI survivor and a significant other (SO), and to compare the models generated from the two different sources of information. Methods: Individuals with and without TBI and an SO were interviewed separately about their current personality. The SOs were also interviewed about the personality of the TBI survivor before the injury. A subset of TBI survivors and their SOs were interviewed twice to assess test-retest reliability. Items which were not associated with personality change after TBI, which could not be measured reliably or which did not contribute to the model, were excluded. Results: Of the 123 original items, 29 items from the interview with the survivor and 31 items from the interview with the SO were retained to form the Brain Injury Personality Scales. Separate factor analyses of ratings from each interview (survivor and SO) resulted in seven first order factors. The second order factor analyses for each interview resulted in four factors. Concordance between the information obtained from the two interviews was low. Conclusions: The information obtained from the interviews with the TBI survivors and the SOs produced two models with a similar structure: three superordinate factors of personality items (affective regulation, behavioural regulation and engagement) and one superordinate factor of items relevant to mental state (restlessness and range of thought). Despite the similarity in structure, the content of the information obtained from the two interviews was different.

Background: Anterior temporal lobe resection (ATLR) benefits many patients with refractory temporal lobe epilepsy (TLE) but may be complicated by material specific memory impairments, typically of verbal memory following left ATLR, and non-verbal memory following right ATLR. Preoperative memory functional MRI (fMRI) may help in the prediction of these deficits. Objective: To assess the value of preoperative fMRI in the prediction of material specific memory deficits following both left- and right-sided ATLR. Methods: We report 15 patients with unilateral TLE undergoing ATLR; eight underwent dominant hemisphere ATLR and seven non-dominant ATLR. Patients performed an fMRI memory paradigm which examined the encoding of words, pictures and faces. Results: Individual patients with relatively greater ipsilateral compared with contralateral medial temporal lobe activation had greater memory decline following ATLR. This was the case for both verbal memory decline following dominant ATLR and for non-verbal memory decline following non-dominant ATLR. For verbal memory decline, activation within the dominant hippocampus was predictive of postoperative memory change whereas activation in the non-dominant hippocampus was not. Conclusion: These findings suggest that preoperative memory fMRI may be a useful non-invasive predictor of postoperative memory change following ATLR and provide support for the functional adequacy theory of hippocampal function. They also suggest that fMRI may provide additional information, over that provided by neuropsychology, for use in the prediction of postoperative memory decline.

Background and purpose: Health related quality of life outcomes are increasingly used to measure the effectiveness of stroke interventions. People with severe aphasia after stroke may be unable to self-report on such measures, necessitating the use of proxy respondents. We explored the level of agreement between people with aphasia (PWA) and their proxies on the Stroke and Aphasia Quality of Life Scale (SAQOL-39) and whether this agreement is influenced by demographic variables and proxy levels of depression and carer strain.\ud \ud Methods: People with chronic aphasia (≥6 months post stroke) were recruited through the UK national charity for PWA. They were interviewed on the SAQOL-39 and their nominated proxies were interviewed on the SAQOL-39, the General Health Questionnaire and the Caregiver Strain Index. Proxy respondents had to be ≥18 years of age, see the person with aphasia at least twice a week and have no known severe mental health problems or cognitive decline.\ud \ud Results: 50 of 55 eligible pairs (91%) took part in the study. Proxies rated PWA as more severely affected than PWA rated themselves. The SDs of the difference scores were large and the difference was significant for three of the four SAQOL-39 domains and the overall mean (p≤0.01). However, the bias as indicated by effect sizes was small to moderate (0.2–0.5). The strength of the agreement was excellent for the overall SAQOL-39 and the physical domain (intra-class correlation coefficient ICC 0.8), good for the psychosocial and communication domains (0.7) and fair for the energy domain (0.5). Demographic variables and proxy’s mood and carer strain did not affect the level of agreement.\ud \ud Conclusions: For group comparisons, proxy respondents who are in frequent contact with people with chronic aphasia can reliably report on their health related quality of life, using the SAQOL-39. Although there are significant differences between PWA and proxy responses, the magnitude of this difference is small to moderate.

Objective: To compare the clinical aspects of peripheral neuropathy associated with Wegener’s granulomatosis (WG), Churg–Strauss syndrome (CSS) and microscopic polyangiitis (MP). Methods: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. Results: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. Conclusions: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Background and aim: As non-randomised studies have suggested that surgical decompression may reduce mortality in patients with space occupying hemispheric infarction, randomisation may be considered unethical in controlled trials testing this treatment strategy. We studied differences in recall of information and in appreciation of the informed consent procedure between representatives included in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) and representatives of patients participating in the randomised trial of Paracetamol (Acetaminophen) In Stroke (PAIS). Methods: 1 year after study inclusion, we contacted 30 consecutive representatives who had given informed consent for participation of their relative in HAMLET, and 30 for PAIS. Recall of trial details and appreciation of the informed consent procedure were investigated using standardised questionnaires and compared between the two groups. Results: All 30 PAIS representatives and 28 HAMLET representatives were interviewed. Participation of their relative in a clinical trial was remembered by 86% of HAMLET and 40% of PAIS representatives (p

Contains fulltext : 51936.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. RESULTS: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p

Contains fulltext : 51546.pdf (Publisher’s version ) (Closed access) BACKGROUND: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGT) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease. METHODS: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT genotype as reference. RESULTS: We found that AGT-235T increased systolic (p for trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1.25-fold (95% CI 1.02-1.52) in AGT-TT carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p = 0.008). A significant interaction was found between AGT and AT1R, further increasing the effect on periventricular and subtotal WML (p for interaction = 0.02). We found a non-significant increased risk of silent brain infarction for AGT-TT carriers and AT1R-CC carriers, but no effect on stroke. CONCLUSION: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and AT1R on the development of WML. These findings raise the question of whether the renin-angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology.

Background: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology. Setting: The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and at the Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Patients and methods: Information was collected retrospectively from 1956 and prospectively from 1975 on clinical data, concomitant diseases, concentration of serum acetylcholine receptor antibodies (AChR-abs), immunosuppressive treatment (IS) and response to it, in 537 patients of whom 326 were thymectomised. Follow-up time was 1.5–50 years. Results: Age at onset of MG increased from a median age of 24 years before 1975 to a median age of 61 years after 2000. Thymoma was found in 65, hyperplasia (HPL) in 185 and a normal thymus in 76 patients. The trans-sternal surgical approach for thymectomy was used in 255 patients (78%). In five patients with thymoma, MG appeared after thymectomy. Of 537 patients, 466 (87%) had circulating AChR-abs. IS was given to 300 (56%) patients, mostly those with thymoma (85%). In total, 441 patients (82%) showed an improvement. One-third of patients with HPL, a quarter of those with thymoma, one-fifth of those with a normal thymus and one-seventh of those not operated on went into remission. Conclusion: The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy.

To determine the accuracy of the bedside head impulse test (bHIT) by direct comparison with results from the quantitative head impulse test (qHIT) in the same subjects, and to investigate whether bHIT sensitivity and specificity changes with neuro-otological training.Video clips of horizontal bHIT to both sides were produced in patients with unilateral and bilateral peripheral vestibular deficits (n = 15) and in healthy subjects (n = 9). For qHIT, eye and head movements were recorded with scleral search coils on the right eye and the forehead. Clinicians (neurologists or otolaryngologists) with at least 6 months of neuro-otological training ("experts": n = 12) or without this training ("non-experts": n = 45) assessed video clips for ocular motor signs of vestibular deficits on either side or of normal vestibular function.On average, bHIT sensitivity was significantly (t test: p0.05) lower for experts than for non-experts (63% vs 72%), while bHIT specificity was significantly higher for experts than non-experts (78% vs 64%). This outcome was a consequence of the experts' tendency to accept bHIT with corresponding borderline qHIT values as still being normal. Fitted curves revealed that at the lower normal limit of qHIT, 20% of bHIT were rated as deficient by the experts and 37% by the non-experts.When qHIT is used as a reference, bHIT sensitivity is adequate and therefore clinically useful in the hands of both neuro-otological experts and non-experts. We advise performing quantitative head impulse testing with search coils or high speed video methods when bHIT is not conclusive.

Background: Neurofibromatosis type 1 (NF1) is a single gene disorder associated with a high frequency of cognitive deficits and a complex cognitive phenotype. These cognitive deficits have been associated with focal areas of high signal intensity on T2 weighted MRI images but the relationship remains controversial. Method: A cohort of 76 children with NF1 and 45 unaffected sibling controls (aged 8–16 years) underwent extensive neuropsychological assessment, with the NF1 children having MRI examinations. Results: The presence or number of T2 hyperintensities (T2H) was not associated with cognitive dysfunction. However, the location of discrete (well circumscribed) T2H in the thalamus was associated with severe and generalised cognitive impairment. More diffuse lesions in the thalamus were also associated with reductions in IQ but the effects were less marked compared with the discrete lesions. Comparing children with NF1 to their unaffected siblings revealed more subtle effects of the lesions on cognitive ability. Conclusions: T2H cannot be used in general as a radiological marker for cognitive deficits in children with NF1; however, lesions in the thalamus are strongly associated with cognitive impairment. It is possible that lesions in the thalamus in conjunction with more general thalamic hypometabolism may compound the level of thalamic dysfunction, resulting in cognitive deficits well beyond those produced by T2H in other regions.

Objective: Although research has implicated the apolipoprotein E (APOE) epsilon-4 genotype as having a negative effect on neuropsychological outcomes following traumatic brain injury (TBI), the potentially negative role of the ϵ4 allele on TBI outcomes has recently been challenged. In light of this debate, the present study served to examine the role of APOE genotype on neuropsychological outcomes approximately 1 month following mild to moderate TBI in a military population. Because of the well documented role of the APOE-ϵ4 allele in increasing the risk of Alzheimer’s disease, we predicted that persons with the APOE-ϵ4 genotype would display relatively greater deficits in cognition than their non-ϵ4 counterparts. Methods: 78 participants were consecutively recruited following a mild to moderate TBI and were divided into two groups based on the presence or absence of an APOE ϵ4 allele. Groups were comparable on demographic characteristics and psychosocial outcomes. Participants were administered a comprehensive neuropsychological battery. Results: Analyses revealed comparable performances on most neuropsychological measures and better performances by ϵ4 carriers on select measures of attention, executive functioning and episodic memory encoding. Furthermore, differences remained after accounting for the effects of TBI severity. Conclusions: Evidence from these analyses supports current literature refuting the notion of relatively poorer neuropsychological functioning associated with the APOE-ϵ4 genotype among young adult participants shortly following mild or moderate brain injury. Neuropsychological performance differences by APOE genotype following TBI are discussed in terms of the importance of considering severity of injury, timing of postinjury assessment and possible neurocognitive compensatory mechanisms.

Objective: Musician’s focal dystonia is usually considered to be task specific but secondary motor disturbances have been reported also. We carried out a detailed evaluation of the incidence of these secondary motor problems in 101 patients. Method: Symptoms were assessed using clinical histories, neurological examinations and observation of instrumental manoeuvres. Results: 53.5% of patients reported secondary motor disturbances in activities other than playing their main instrument, with the onset delayed in some cases by up to 12 years from the awareness of dystonic symptoms. 46.5% suffered from simple, 19.8% from complex and 33.7% from progressive cramps. Plucked string players (guitarists) mainly suffered from simple cramps while keyboardists more frequently displayed the progressive form. In all patients, symptoms were focal, and the type of cramp was unrelated to the severity of the perceived symptoms. Those patients playing a second instrument similar to their main instrument showed symptoms which worsened to a higher degree than those playing either only one instrument or whose second instrument was different. Conclusions: Longer follow-up assessments may reveal secondary motor symptoms that are not visible over shorter examination periods. Therefore, a thorough evaluation of everyday life motor activities should be considered in any clinical and treatment protocol. We speculate that the avoidance of movements that are similar to the main affected task may be of help in limiting symptoms. Consequently, focal dystonia may be considered more movement than task specific.

Introduction: Neurocysticercosis (NC), a parasitic disease caused by Taenia solium , may be either asymptomatic or show a mild to severe clinical picture with intracranial hypertension. The most severe form of the disease is caused when viable cysticerci are localised in the ventricles or in subarachnoidal cisterns at the base of the skull. Detection of the secreted metacestode antigen HP10 in cerebrospinal fluid is a sensitive and specific method for the diagnosis of these severe NC cases. Objective and methods: To evaluate the validity of HP10 antigen detection ELISA when applied to serum, using paired serum and cerebrospinal fluid samples from 116 radiologically and clinically characterised NC patients. Results: The HP10 antigen assay exhibited a similarly high sensitivity in identifying severe NC cases from sera (84.8%) and CSF (91.3%). In contrast, HP10 antigen was rarely detected in asymptomatic or mild NC cases (3 of 57). Importantly, the HP10 antigen assay applied to serum showed high specificity (94%) when used in 126 serum samples of non-NC subjects from an endemic community with a confirmed coproparasitological diagnosis of intestinal parasitic infections. Finally, the HP10 assay also proved to be of value in the follow-up of treated patients. Conclusion: This study confirms that detection of the metacestode HP10 antigen in serum is a useful tool for diagnosis and follow-up of patients with severe forms of NC treated with cysticidal drugs.

Background: Identifying quantitative gait markers of preclinical dementia may lead to new insights into early disease stages, improve diagnostic assessments and identify new preventive strategies. Objective: To examine the relationship of quantitative gait parameters to decline in specific cognitive domains as well as the risk of developing dementia in older adults. Methods: We conducted a prospective cohort study nested within a community based ageing study. Of the 427 subjects aged 70 years and older with quantitative gait assessments, 399 were dementia-free at baseline. Results: Over 5 years of follow-up (median 2 years), 33 subjects developed dementia. Factor analysis was used to reduce eight baseline quantitative gait parameters to three independent factors representing pace, rhythm and variability. In linear models, a 1 point increase on the rhythm factor was associated with further memory decline (by 107%), whereas the pace factor was associated with decline on executive function measured by the digit symbol substitution (by 29%) and letter fluency (by 92%) tests. In Cox models adjusted for age, sex and education, a 1 point increase on baseline rhythm (hazard ratio (HR) 1.48; 95% CI 1.03 to 2.14) and variability factor scores (HR 1.37; 95% CI 1.05 to 1.78) was associated with increased risk of dementia. The pace factor predicted the risk of developing vascular dementia (HR 1.60; 95% CI 1.06 to 2.41). Conclusion: Our findings indicate that quantitative gait measures predict future risk of cognitive decline and dementia in initially non-demented older adults.

Background: Stroke is a leading cause of death and disability in developing countries, afflicting individuals at a young age. The contribution of established vascular risk factors to ischaemic stroke in young adults has not been evaluated systematically in Indians. Methods: We conducted a case control study in 214 South Indian patients with first acute ischaemic stroke that occurred between the ages of 15 and 45 years, 99 age and sex matched hospital controls and 96 community controls. We compared the prevalence of the following risk factors: smoking, elevated blood pressure, high fasting blood glucose and abnormal lipids. Results: Compared with community controls, stroke patients had a higher prevalence of smoking (multivariable adjusted odds ratio (OR) 7.77, 95% CI 1.93 to 31.27), higher systolic blood pressure (OR per SD increment of 1.88, 95% CI 1.01 to 3.49) and fasting blood glucose (OR per SD increment of 4.55, 95% CI 1.63 to 12.67), but lower high density lipoprotein (HDL) cholesterol (OR per SD increment of 0.17, 95% CI 0.09 to 0.30). Compared with hospital controls, stroke patients had a higher prevalence of smoking (OR 3.95, 95% CI 1.61 to 9.71) and lower HDL cholesterol (OR per SD increment 0.27, 95% CI 0.17 to 0.44). The presence of ⩾3 metabolic syndrome components was associated strongly with stroke (OR 4.76, 95% CI 1.93 to 11.76; OR 2.09, 95% CI 1.06 to 4.13) compared with community and hospital controls. Conclusions: Key components of the metabolic syndrome and smoking are associated with ischaemic stroke in young South Indian adults. Our observations underscore the importance of targeting adolescents and young adults for screening and prevention to reduce the burden of ischaemic stroke in young adults.

Background: Psychiatric symptoms are a common feature of Huntington’s disease (HD) and often precede the onset of motor and cognitive impairments. However, it remains unclear whether psychiatric changes in the preclinical period result from structural change, are a reaction to being at risk or simply a coincidental occurrence. Few studies have investigated the temporal course of psychiatric disorder across the preclinical period. Objectives: To compare lifetime and current prevalence of psychiatric disorder in presymptomatic gene carriers and non-carriers and to examine the relationship of psychiatric prevalence in gene carriers to temporal proximity of clinical onset. Methods: Lifetime and current psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non-carriers) were obtained using a structured clinical interview, the Composite International Diagnostic Interview. Psychiatric disorders were classified using both standardised diagnostic criteria and a more subtle symptom based approach. Follow-up of gene carriers (n = 51) enabled analysis of the role of temporal proximity to clinical onset. Results: Gene carriers and non-carriers did not differ in terms of the lifetime frequency of clinical psychiatric disorders or subclinical symptoms. However, gene carriers reported a significantly higher rate of current depressive symptoms. Moreover, the rate of depression increased as a function of proximity to clinical onset. Conclusions: Affective disorder is an important feature of the prodromal stages of HD. The findings indicate that depression cannot be accounted for by natural concerns of being at risk. There is evidence of a window of several years in which preclinical symptoms are apparent.

In patients with posterior inferior cerebellar artery infarction (PICAI) or lateral medullary infarction (LMI), the ipsilateral vertebral artery is often hypoplastic and therefore at an increased risk of ischaemic stroke.To investigate the frequency and clinical relevance of hypoplastic vertebral artery (HVA) in patients with ischaemic stroke with or without vertebral artery territory and in normal healthy people.529 patients with ischaemic stroke, including vertebral artery territory infarction (LMI or PICAI), were classified according to their stroke location (303 anterior circulation strokes (ACS) and 226 posterior circulation strokes (PCS)) by MRI. The frequency of HVA, defined as a diameter ofor = 2 mm by magnetic resonance angiography, was measured in comparison with 306 normal healthy people.185 patients (35.2%) from the cohort had HVA (3.4%, bilaterally). Patients with PCS showed a higher rate of HVA than those with ACS (45.6% vs 27.1%, p0.001). The HVA frequency of those with ACS was similar to that of the normal group (26.5%). Of the 112 patients with vertebral artery territory stroke, 58 (51.8%) had HVA (bilateral HVA in 10), and all of 48 showed ipsilateral HVA territory stroke. In 102 patients with vertebral artery territory stroke, classification of the ipsilateral vertebral artery as hypoplastic (vs dominant or symmetric) tended to predict the involvement of multiple and extensive lesions, and a higher incidence of steno-occlusion (p0.001).HVA is not rare in the normal population, and is frequent in patients with PCS. People with HVA may have a high probability of PCS, with atherosclerotic susceptibility and ipsilateral lesions in the vertebral artery territory.

Background: Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) already at an early stage in FD. Objective: Investigator independent and sensitive quantification of brain structural changes in clinically affected men and women with FD. Methods: The authors performed a voxel-based analysis of diffusion tensor images (DTI) in 25 FD patients and 20 age-matched normal controls. Results: DTI revealed significant increases of cerebral white matter diffusivity (MD) in FD patients that were pronounced in the periventricular white matter. Even the subgroup of patients without significant WMLs-load (n = 18) showed increased diffusivity in the cerebral white matter. In gray matter areas MD elevation could only be detected in the posterior part of the thalamus, independently from visible pulvinar alterations on the T1-weighted images. Voxel-based anisotropy (FA) measurements did not differ significantly between patients and controls. Conclusions: The present study demonstrates the clinical feasibility of voxel-based analysis of DTI as a sensitive tool to quantify brain tissue alterations in FD. The pattern of increased brain tissue diffusivity is probably due to microangiopathic alterations mainly affecting the long perforating arteries.

Background: Measurement of the duration of post-traumatic amnesia (PTA) is common practice, serving as an important index of the severity of traumatic brain injury (TBI) and a predictor of functional outcome. However, controversy exists regarding the nature of PTA; some studies indicate that it is a confusional state with symptoms that extend beyond disorientation and amnesia. Objective: To evaluate the contribution of the severity of acute confusion 1 month after TBI to prediction of employment at 1 year after injury, comparing it with PTA duration. Methods: Prospective study involving 171 participants with complete data, who met the study criteria, from 228 consecutive TBI Model System admissions. Outcome measures included weekly administration of the Delirium Rating Scale-Revised-98 (DelRS-R98) to measure the severity of acute confusion. Evaluations closest to 1 month after injury were used for study purposes. Duration of PTA was defined as the interval from injury until two consecutive Galveston Orientation and Amnesia Test scores of ⩾76 were obtained within a period of 24–72 h. Univariable and multivariable logistic regression were used to predict employment status at 1 year after injury. Results: Age, education and DelRS-R98 were significant predictors accounting for 34% of outcome variance. Individuals with greater confusion severity at 1 month after injury, older age and lower levels of education were less likely to be employed at 1 year after injury. Severity of confusion was more strongly associated with employment outcome (r s = −0.39) than was PTA duration (r s = −0.34). Conclusions: In addition to demographic indices, severity of acute confusion makes a unique contribution to predicting late outcome after TBI.

Background: Chronic tinnitus is a disabling, almost untreatable, condition, usually accompanied by psychiatric distress. In patients with complex neuropsychiatric diseases, such as chronic pain, with which tinnitus shares pathophysiological similarities, placebo effects may be pronounced. Moreover, it may be difficult to distinguish actual repetitive transcranial magnetic stimulation (rTMS) induced clinical benefits beyond placebo effects in neuropsychiatric patients. Methods: 16 patients with chronic tinnitus underwent a randomised, double blind, crossover, placebo controlled trial of 1 Hz rTMS (120% of motor threshold; 1200 stimuli/day for 5 days) of the left temporoparietal region. Patients were screened for psychiatric comorbidity; additionally, anxiety and depression were monitored throughout the study. Moreover, an original placebo rTMS procedure produced the same activation of ipsilateral face muscles (a condition which may per se change the subjective rating of tinnitus) as the real rTMS. Results: There were 8 out of 14 responders. Two patients dropped out for transient worsening of tinnitus. Active rTMS induced an overall significant, but transient, improvement (35% of the basal score) of subjective tinnitus perception that was independent of either tinnitus laterality or mood or anxiety changes. No correlations were found between response to rTMS and tinnitus duration, initial subjective score or patient age. When asked after the study was over, 71.4% of patients failed to identify the temporal sequence of the real or sham rTMS interventions. Conclusion: The beneficial effects of rTMS on tinnitus are independent of mood changes. Moreover, they appear in the context of an original placebo stimulation designed to more closely replicate the somatic sensation of active stimulation. Because of the limited temporal duration of the clinical benefit, these neuromodulatory effects could be mediated by transient functional changes taking place in the neural circuits underlying tinnitus processing.

Objective: This randomised, double blind, placebo controlled, two parallel group study was conducted to assess the beneficial effect of injection of botulinum toxin A (Dysport) into the subscapularis muscle on shoulder pain in stroke patients with spastic hemiplegia. Methods: A single dose of botulinum toxin A (500 Speywood units) or placebo was injected into the subcapularis muscle. Pain was assessed using a 10 point verbal scale. Subscapularis spasticity was assessed by the change in passive shoulder lateral rotation and abduction. Upper limb spasticity was assessed using the Modified Ashworth Scale for shoulder medial rotators, and elbow, wrist and finger flexors. Assessments were carried out at baseline and at weeks 1, 2 and 4. Results: Twenty patients (10 patients per group), 11 with ischaemic stroke and 9 with haemorrhagic stroke, completed the study. Pain improvement with botulinum toxin A was observed from week 1; score difference from baseline at week 4 was 4 points versus 1 point with placebo (p = 0.025). Lateral rotation was also improved, with a statistically significant difference compared with placebo at week 2 (p = 0.05) and week 4 (p = 0.018). A general improvement in upper limb spasticity was observed; it was significant for finger flexors at week 4 (p = 0.025). Conclusions: Subscapularis injection of botulinum toxin A appears to be of value in the management of shoulder pain in spastic hemiplegic patients. The results confirm the role of spasticity in post-stroke shoulder pain.

While some regard the flail arm syndrome as a variant of amyotrophic lateral sclerosis (ALS), others have argued that it is a distinct clinical entity. Consequently, the present study applied novel central and peripheral nerve excitability techniques to further explore disease pathophysiology in flail arm syndrome.Cortical and peripheral nerve excitability studies were undertaken in 11 flail arm patients, defined by muscle weakness limited to the proximal aspects of the upper limbs for at least 24 months.Mean age at disease onset (60.3 years) was similar to other ALS phenotypes (58.3 years), with strong male predominance (male:female distribution: flail arm 10:1; ALS 1.5:1; p0.05) and prolonged disease duration (flail arm 62.5 months; ALS 15.8 months; p0.05). There was evidence of cortical hyperexcitability in flail arm patients, similar to findings in ALS, with reduction in short interval intracortical inhibition (flail arm 0.8 (0.6)%; ALS 4.1 (1.1)%; controls 8.5 (1.0)%; p0.0001) and resting motor threshold (flail arm 53.4 (2.8)%; ALS 56.6 (1.8)%; controls 60.7 (1.5)%; p0.05), along with an increase in motor evoked potential amplitude (flail arm 49.5 (9.0)%; ALS 44.4 (4.9)%; controls 25.8 (2.8)%; p0.05). Peripheral nerve excitability studies demonstrated changes consistent with upregulation in persistent Na+ currents and reduction of slow K+ conductances, similar to findings in ALS.This study has demonstrated the presence of cortical hyperexcitability in flail arm syndrome, along with abnormalities in peripheral nerve excitability, findings consistent with previous studies in other ALS phenotypes. By demonstrating the presence of upper motor neuron dysfunction, the present study suggests that the flail arm syndrome is an unusual variant of ALS.

Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD). Objective: We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD. Methods: Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson’s Disease Rating Scale III score in the off-medication state. Seven patients had 18 F-dopa positron emission tomography scans before and 1 year after transplantation. Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal 18 F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18 F-dopa uptake (r = −0.829; p = 0.042). Conclusions: CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.