Showing papers in "European Journal of Neurology in 2009"

Stops walking when talking: a predictor of falls in older adults?

Abstract: The objective of this study was to systematically review all published articles examining the relationship between the occurrence of falls and changes in gait and attention-demanding task performance whilst dual tasking amongst older adults. An English and French Medline and Cochrane library search ranging from 1997 to 2008 indexed under 'accidental falls', 'aged OR aged, 80 and over', 'dual task', 'dual tasking', 'gait', 'walking', 'fall' and 'falling' was performed. Of 121 selected studies, fifteen met the selection criteria and were included in the final analysis. The fall rate ranged from 11.1% to 50.0% in retrospective studies and from 21.3% to 42.3% in prospective ones. Amongst the three retrospective and eight prospective studies, two and six studies, respectively, showed a significant relationship between changes in gait performance under dual task and history of falls. The predictive value for falling was particularly efficient amongst frail older adults compared with healthy subjects. Two prospective studies challenged the usefulness of the dual-task paradigm as a significant predictor compared to single task performance and three studies even reported that gait changes whilst dual tasking did not predict falls. The pooled odds ratio for falling was 5.3 (95% CI, 3.1-9.1) when subjects had changes in gait or attention-demanding task performance whilst dual tasking. Despite conflicting early reports, changes in performance whilst dual tasking were significantly associated with an increased risk for falling amongst older adults and frail older adults in particular. Description of health status, standardization of test methodology, increase of sample size and longer follow-up intervals will certainly improve the predictive value of dual-task-based fall risk assessment tests.

In Two Minds. Dual Processes and Beyond

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Vitamin D and cognitive performance in adults: a systematic review.

Abstract: Chronic low serum 25-hydroxyvitamin D (25OHD) concentrations are common in adults and are associated with numerous non-skeletal diseases Vitamin D receptors (VDR) are located in the human cortex and hippocampus, which are key areas for cognition The objective of this study was to systematically review all published data from the past 30 years which examined the association between serum 25OHD concentrations and cognitive performance in adults An English and French Medline, PsycINFO and Cochrane Library search ranging from 1979 to 2008 indexed under the Medical Subject Heading (MeSH) terms 'Vitamin D' or 'Hydroxycholecalciferols' combined with the terms 'Dementia' or 'Cognition' or 'Cognition Disorders' or 'Delirium' or 'Memory' or 'Memory Disorders' or 'Orientation' or 'Executive Functions' or 'Attention' or 'Brain' or 'Neuropsychological Tests' was performed Of the 99 selected studies, five observational studies met the selection criteria and were included in the final analysis No prospective cohort study was found The number of participants ranged from 32 to 9556 community-dwelling older adults (45-65% women) Three studies showed four significant positive associations between serum 25OHD concentrations and global cognitive functions, whereas three other studies exploring specific aspects of cognition showed 11 non-significant associations This systematic review shows that the association between serum 25OHD concentrations and cognitive performance is not yet clearly established The inconclusive results of the reviewed studies could be due to methodology, types of the cognitive tasks used and/or the cellular mechanisms of vitamin D

Cognitive function in early Parkinson's disease: a population-based study.

Abstract: BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with ...

Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study.

Abstract: Objective To estimate the incidence and lifetime risk of motor neuron disease (MND) in a population-based sample in the United Kingdom.

Cause of death in patients with dementia disorders.

Abstract: Background: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. Methods: The autopsy reports were studied on all patients (n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974-2004. Results: The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. Conclusions: In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders.

Role of 1 and 3 Hz repetitive transcranial magnetic stimulation on motor function recovery after acute ischaemic stroke

Abstract: Background and purpose: The purpose of this study was to compare the long-term effect of five daily sessions of 1 vs. 3 Hz repetitive transcranial magnetic stimulation (rTMS) on motor recovery in acute stroke. Methods: A total of 36 patients with acute ischaemic stroke participated in the study. The patients were randomly assigned into one of three groups; the first and second groups received real rTMS; 1 and 3 Hz and third group received sham stimulation, daily for 5 days. Motor disability was assessed before and after the last session, and then after first, second and third month. Cortical excitability was assessed before and after the second and fifth session. The outcome measure was clinical disability at 3 months post-rTMS. Results: No significant differences were found in basal rating scales between the three groups. At the 3-month time point, both of the real rTMS groups had improved significantly more in different rating scales than the sham group; in addition, the 1 Hz group performed better than the 3 Hz group. Measures of cortical excitability immediately after the last session showed that the 1 Hz group had reduced excitability of the non-stroke hemisphere and increased excitability of the stroke hemisphere, whereas the 3 Hz group only showed increased excitability of the stroke hemisphere. Conclusion: These results confirm that five daily sessions of rTMS over motor cortex using either 1 Hz over the unaffected hemisphere or 3 Hz over the affected hemisphere can enhance recovery. At 3 months, the improvement was more pronounced in 1 Hz group.

Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis

Abstract: BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. METHODS: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. RESULTS: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P > 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075). CONCLUSIONS: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.

Levodopa in the treatment of Parkinson's disease.

Abstract: The predominant motor features of Parkinson's disease (PD) are caused by degeneration of dopaminergic neurones and can be reversed in part or whole by dopamine replacement or augmentation strategies. Physicians have most experience with the use of levodopa, which remains the most potent oral dopaminergic treatment for PD. There are reservations about the long-term use of levodopa, most particularly in the context of its propensity to induce motor fluctuations and dyskinesias. Strategies exist to delay or diminish these complications, but the physician must lay the basis for these in the selection of drugs for early treatment and the sequence of drugs introduced subsequently. Levodopa efficacy and duration of effect may be enhanced by combination with a catechol-O-methyl transferase inhibitor. Maintaining good motor function and quality of life remain the primary goals of therapy and the principle that treatment must be tailored to the individual patient's needs is paramount.

Subthalamic deep brain stimulation and impulse control in Parkinson's disease.

Abstract: Background and purpose: Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson’s disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy. Methods: In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive–compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory. Results: Independent samples t-tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients. Conclusions: Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.

Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options

Abstract: Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature

Abstract: BACKGROUND AND PURPOSE: To investigate the prevalence of subependymal giant cell ependymomas (SEGA) in patients with tuberous sclerosis complex (TSC). METHODS: We performed a retrospective cross-sectional study in a cohort of 285 patients with known TSC. Institutional review board approval was obtained. We included all 214 TSC-patients who had received a contrast-enhanced computed tomography (CT) scan of the brain. The most recent scan was evaluated for SEGA and presence of hydrocephalus. Additionally, a literature search was performed, and pooled estimates of SEGA prevalence in TSC were calculated. We used descriptive statistics, two sample t-test, chi-squared-test, and meta-analysis as appropriate. RESULTS: Computed tomography showed radiological evidence of SEGA in 43 of the 214 TSC-patients (20%); 23 of 105 men (22%) and 20 of 109 women (18%; P = .52). Average maximum tumor size was 11.4 mm (range, 4-29 mm). Patients with SEGA (mean, 31 years; range, 16-58 years) were on average younger than patients without SEGA (mean, 37 years; range, 10-72 years; P = 0.007). No association between tumor size and patient age was detected. Nine patients had bilateral SEGA. Hydrocephalus was present in six of the 43 patients (14%). Meta-analysis of reported prevalence and our current study showed that studies using radiological evidence to diagnose SEGA gave a higher pooled estimate of the prevalence of SEGA in TSC (0.16; 95% CI: 0.12, 0.21) than studies using mainly histopathological evidence of SEGA (0.09; 95% CI: 0.07, 0.12). CONCLUSIONS: In our cohort, CT demonstrated evidence of SEGA in 20% of TSC-patients. Prevalence of SEGA in TSC is higher in studies using radiological evidence to diagnose SEGA than in studies using histopathological evidence.

The effect of onset age on the clinical features of Parkinson's disease.

Abstract: Many clinicians view age at onset as an important determinant of clinical phenotype in Parkinson's disease (PD) and this has been reinforced by the identification of Mendelian genes that account for some cases of younger onset PD. A systematic review of OVID Medline for articles relevant to the relationship between clinical features and age at onset in PD published in English between 1950-2007 was performed. There are very few prospective community based studies which focus on the relationship between age at onset and the features of PD and a variety of case definitions are used in the literature. Most studies of young onset PD are based on specialist clinic referral series. The available evidence suggests that PD patients with a younger age at onset have: (i) a slower disease progression, (ii) an increased rate of dystonia at onset and during treatment, (iii) a lower rate of dementia and (iv) an increased rate of dyskinesias in response to L-DOPA treatment. The majority of the available studies do not report patient genotype data, but it is probably that the clinical heterogeneity of PD will be further refined with detailed clinico-genetic studies.

Anticipatory postural adjustments prior to step initiation are hypometric in untreated Parkinson’s disease: an accelerometer‐based approach

Abstract: Background and purpose: Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson’s disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods: Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results: Our findings show that APAs measured from the peak COP displacement toward the swing leg and the peak trunk acceleration toward the stance leg were smaller in untreated PD compared with control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion: These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes.

A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain.

Abstract: Background: Duloxetine has demonstrated analgesic effect in chronic pain states This study assesses the efficacy of duloxetine in chronic low back pain (CLBP) Methods: Adult patients with non-radicular CLBP entered this 13-week, double-blind, randomized study comparing duloxetine 20, 60 or 120 mg once daily with placebo The primary measure was comparison of duloxetine 60 mg with placebo on weekly mean 24-h average pain Secondary measures included Roland-Morris Disability Questionnaire (RMDQ-24), Patient’s Global Impressions of Improvement (PGI-I), Brief Pain Inventory (BPI), safety and tolerability Results: Four hundred four patients were enrolled, 267 completed No significant differences existed between any dose of duloxetine and placebo on reduction in weekly mean 24-h average pain at end-point Duloxetine 60 mg was superior to placebo from weeks 3–11 in relieving pain, but not at weeks 12–13 Duloxetine 60 mg demonstrated significant improvement on PGI-I, RMDQ-24, BPI-average pain and BPI-average interference Significantly more patients taking duloxetine 120 mg (241%) discontinued because of adverse events, versus placebo (85%) Conclusions: Duloxetine was superior to placebo on the primary objective from weeks 3–11, but superiority was not maintained at end-point Duloxetine was superior to placebo on many secondary measures, and was well-tolerated

Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial.

Abstract: Background and purpose: For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better quality of life. Methods: In a randomized single-blinded cross-over study, nine IVIG responsive patients were allocated to receive either SCIG or IVIG for a period equivalent to three IVIG treatment intervals and, subsequently, crossed over to the other treatment. Primary end-points were (i) dynamometric strength of affected muscles and (ii) the SF-36 quality of life questionnaire. Results: The two treatments were equally effective, the mean change in muscle strength after SCIG being 3.6% (95% CI −3.6% to 10.9%) vs. 4.3% (−1.3% to 10.0%) after IVIG (P = 0.86). One patient had sustained erythema and oedema at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred. Conclusion: In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion. Subcutaneous administration is an alternative option that adds flexibility to the treatment schedule.

Peritumoral edema on MRI at initial diagnosis: an independent prognostic factor for glioblastoma?

Abstract: Background: Peritumoral brain edema in glioblastoma patients is a frequently encountered phenomenon that strongly contributes to neurological signs and symptoms. The role of peritumoral edema as a prognostic factor is controversial. Materials and Methods: This multi-centre clinical retrospective study included 110 patients with histologically proven glioblastoma. The prognostic impact on overall survival of pre-treatment peritumoral edema detected on MRI-scans was evaluated. All patients had preoperative MRI, surgery, histology, and received standard treatment regimens. Edema on MRI-scans was classified as minor ( 1 cm). Results: Our results confirm that peritumoral edema on preoperative MRI is an independent prognostic factor in addition to postoperative Karnofsky performance score (KPS), age, and type of tumor resection. Patients with major edema had significant shorter overall survival compared to patients with minor edema. Conclusion: This easily applicable early radiological characterization may contribute to a more subgroup oriented treatment in glioblastoma patients for future trials, as well as in clinical routine.

Pre‐hospital notification reduced the door‐to‐needle time for iv t‐PA in acute ischaemic stroke

Abstract: Background and purpose: Intrahospital delay is the most serious obstacle in thrombolysis in acute ischaemic stroke (AIS). We implemented the pre-hospital notification system from the emergency medical information system in our metropolitan area to reduce intrahospital delay. Methods: From October 2007, we implemented a 24-h hotline system between our stroke center and the Korean Emergency Medical Information System in Busan. We compared processing times and clinical outcomes amongst patients after using intravenous tissue type plasminogen activator (iv t-PA) with and without the hotline system. Results: After the pre-hospital notification system was implemented, the rate of iv t-PA use increased from 6.5% to 14.3%. Time of onset in patients with pre-hospital notification was much longer than in patients without (121.5 ± 34.8 min vs. 74.7 ± 38.5 min, P < 0.01) notification but door-to-needle time was significantly reduced (28.9 ± 11.4 min vs. 47.7 ± 22.8 min, P < 0.01). However, there were no significant differences in 90-day clinical outcomes between the two groups. Conclusions: The pre-hospital notification system reduced intrahospital processing times which led to increased iv t-PA use after AIS. However, the improvement of clinical outcomes in thrombolysis might require organization of not only intrahospital processes but of outside processes such as the early recognition and rapid dispatch of patients with suspected AIS.

Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis

Abstract: Background: Prevalence rates of headache in multiple sclerosis (MS) patients varied widely in recent studies. This study aimed to investigate the 1 year prevalence of headache in MS compared with the general population. Methods: Population-based case–control study in Germany. Results: We included 491 patients with definite MS (68% female, mean age 45.3 years, 63.7% relapsing remitting MS, mean Expanded Disability Status Scale (EDSS) 3.2, 106 treated with interferon-β, 53 with glatiramer acetate, 271 untreated) and 447 age and gender matched controls. Headache was diagnosed with a validated questionnaire according to the International Headache Society Criteria. Headache prevalence was 56.2% (tension type headache 37.2%, migraine 24.6%). Headache prevalence rates did not differ from controls. Headache was not associated with disability or treatment. Trigeminal neuralgia was found in 6.3% of MS cases. Conclusion: Results suggest that headache in MS patients reflects comorbidity in most conditions.

One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis.

Abstract: BACKGROUND AND PURPOSE: To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing-remitting multiple sclerosis (RR-MS) patients with sustained disability progression during interferon beta (IFNB) treatment. METHODS: All patients receiving treatment with one of the available IFNB formulations for at least 1 year were included in this single-centre, prospective and post-marketing study. Demographic, clinical and MRI data were collected at IFNB start and at 1 year of therapy; patients were followed-up at least yearly. Poor clinical response was defined as the occurrence of a sustained disability progression of > or =1 point in the Expanded Disability Status Scale (EDSS) during the follow-up period. RESULTS: Out of 454 RR-MS patients starting IFNB therapy, data coming from 394 patients with a mean follow-up of 4.8 (2.4) years were analysed. Sixty patients were excluded because of too short follow-up. Less than 1/3 (30.4%) of the patients satisfied the criterion of 'poor responders'. Patients presenting new lesions on T2-weighted MRI scan after 1 year of therapy (compared with baseline) had a higher risk of being poor responder to treatment with IFNB during the follow-up period (HR 16.8, 95% CI 7.6-37.1, P < 0.001). An augmented risk increasing the number of lesions was observed, with a 10-fold increase for each new lesion. CONCLUSIONS: Developing new T2-hyperintense lesions during IFNB treatment was the best predictor of long-term poor response to therapy. MRI scans performed after 1 year of IFNB treatment may be useful in contributing to early identification of poor responders.

Total daily sleep duration and the risk of dementia: a prospective population‐based study

Abstract: Background and purpose: We determined in a population-based study whether sleep duration was associated with an increased risk of incident dementia. Methods: In a population-based study in central Spain, participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded and participants indicated their daily sleep duration as the sum of night-time sleep and daytime napping. The average daily total sleep duration was grouped into five categories: ≤5 (short sleepers), 6, 7 (reference), 8, and ≥9 h (long sleepers). We identified all cases with incident dementia, diagnosed using DSM-IV criteria. Results: Three thousand two hundred eighty six participants with baseline information about sleep duration had a median duration of follow-up of 3.2 years. There were 140 incident cases of dementia. The relative risks (RR) for short sleepers and for long sleepers were 2.36 (95% CI = 1.07–5.21, P = 0.03) and 2.40 (95% CI = 1.20–4.81, P = 0.01), respectively. After adjustment for potential confounders, the RR was only marginally increased for short sleepers (1.87, 95% CI = 0.85–4.15, P = 0.12) but remained increased for long sleepers (2.18; 95% CI = 1.09–4.37, P = 0.03). Conclusions: Prolonged sleep duration (night-time sleep and daytime napping) may be associated with an increased risk of dementia.

The role of nutrition in Alzheimer's disease: epidemiological evidence.

Abstract: The prevalence of Alzheimer’s disease (AD) increases exponentially with age but there is limited knowledge of the modifiable risk factors for AD. However, there is growing evidence for possible dietary risk factors in the development of AD and cognitive decline with age, such as antioxidant nutrients, fish, dietary fats, and B-vitamins. Numerous animal and laboratory studies have shown that antioxidant nutrients can protect the brain from oxidative and inflammatory damage, but there are limited data available from epidemiological studies. There is more substantial epidemiological evidence from a number of recent studies that demonstrate a protective role of omega-3 fatty acids, such as docosahexaenoic acid, in AD and cognitive decline. This review will focus on epidemiological evidence investigating the relationship between nutrition and AD, focusing particularly on the roles of dietary fats and antioxidants.

Cognitive deficits in multiple system atrophy correlate with frontal atrophy and disease duration

Abstract: Background and purpose: Dementia remains an exclusion criterion in diagnosing multiple system atrophy (MSA). This study aimed to determine the cognitive changes and brain atrophy patterns in the Parkinsonian (MSA-P) and cerebellar (MSA-C) variants of MSA. Methods: Voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and neuro-psychological tests were applied to 10 MSA-C and 13 MSA-P patients, and compared to 37 age-matched controls. Correlation analyses were performed between cognitive test results and morphometric data extracted from the VBM data. Results: In neuro-psychological testing, the 23 MSA patients scored lower in the Stroop interference test and took longer in the trail-making test as compared with the controls, whereas MSA-C performed worse than MSA-P in the memory scores, Stroop test, and time to complete the trail-making test. MSA, as a group, showed atrophy in the cerebellum, insular cortex, fusiform gyrus, inferior orbito-frontal gyrus, superior temporal gyrus, and caudate nucleus. Memory scores correlated well with pre-frontal lobe atrophy but not in the insular area. Conclusion: In conclusion, although dementia is not a typical presenting feature of MSA and is regarded as a sub-cortical movement disorder, frontal atrophy, cognitive changes, and dementia are identifiable as MSA progresses.

Successful treatment of refractory generalized myasthenia gravis with rituximab.

Abstract: Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder for which current therapies carry a high risk of side-effects and may be insufficient in stabilizing the clinical status. Many therapeutic options can be ruled, such as thymectomy, corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin (IVIg) or less frequently plasmapheresis must be ruled. Methods: We followed prospectively six patients with MG who presented with a poor response to two or three lines of immunosuppressive conventional drugs associated with oral corticosteroids. All but one were acetylcholine receptor negative and three were anti-MuSK positive. IVIg did not improved the neurological status and all patient required high doses of cholinesterase inhibitors. Results: Rituximab was introduced with a mean follow-up of 1.5 years (375 mg/m2, days 1, 8, 15, 28 during the first month and then one dose every 2 months). After 2 years of follow-up, all patients stopped corticosteroids and tapered off cholinesterase inhibitors from 60 to 180 mg/day without severe infectious events. Conclusion: Rituximab, a chimeric IgG k monoclonal antibody that target CD20 is used for the treatment of relapsing/refractory CD20 positive low-grade non-Hodgkin’s lymphoma and other autoimmune neuromuscular diseases. Four previous short reports have described a good response of MG associated with lymphoma with rituximab. It appears to be a promising and effective drug for the treatment of MG without lymphoma, with a substantial benefit to the clinical status and good tolerability.

TARDBP (TDP-43) sequence analysis in patients with familial and sporadic ALS: identification of two novel mutations.

Abstract: Background and purpose: Increasing evidence suggests a direct role of the TAR DNA-binding protein 43 (TDP-43) in neurodegeneration. Mutations in the TARDBP gene, which codes for TDP-43, have been recently reported in familial and sporadic amyotrophic lateral sclerosis (ALS) cases. Methods: To further define the spectrum and frequency of TARDBP mutations, we present genetic analysis data on TARDBP in 314 ALS mainly Italian patients, including 16 subjects with non-SOD1 familial ALS. Results: We identified four heterozygous missense mutations in five unrelated ALS patients (1.6%). Two of these mutations (p.G348C and p.A382T) were detected in carriers coming from families with an autosomal dominant transmission of different geographic origin (Belgian and Italian, respectively). The Belgian pedigree showed several affected members within five generations and with variable clinical features. Two novel mutations (p.G294V and p.G295S) were identified in two sporadic cases. Conclusion: The identification of five ALS patients carrying TARDBP alterations extends the spectrum of TARDBP mutations and supports the pathological role of TDP-43 in motor neurone disease. Our findings provide evidence that TARDBP mutations are not frequent in Italian sporadic ALS patients (1%); however, combined with the literature, our data further support TARDBP mutations as a relevant cause of familial ALS.

Risk factors for stroke-related pain 1 year after first-ever stroke.

Abstract: Objective: To estimate the prevalence of stroke-related pain and to explore its relation to spasticity. Design: Cross-sectional survey. Patients and methods: One hundred and forty patients were examined at 1 year after first-ever stroke. Pain was assessed by a structured interview and categorized as stroke-related or not, pain intensity by use of the visual analogue scale (VAS), spasticity by use of the modified Ashworth scale, stroke severity and the presence of specific neurological impairments by use of the National Institute of Health Stroke Scale (NIHSS), and depression by

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers

Abstract: Background: Natalizumab affects systemic cytokine expressions and clinical course in relapsing–remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP)-9 and osteopontin (OPN) in CSF, and clinical outcome measures in 22 natalizumab-treated RRMS patients. Methods: mRNA levels of cytokines in cells were detected with real-time RT-PCR. Protein levels of OPN and MMP-9 were measured by ELISA. Results: Natalizumab reduced CSF cell counts (P < 0.0001). Tumor necrosis factor (TNF) and interferon-c (IFN-c) mRNAs were significantly increased in PBMCs. In contrast, expressions of IFN-c and interleukin (IL)-23 were decreased but IL-10 increased in the CSF cells. OPN and MMP-9 were reduced in the CSF. Patients being in remission at baseline showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. Conclusions: Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow increased production of the antiinflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy.

Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review

Abstract: Degenerative cervical radiculopathy: clinical diagnosis and conservative treatment. A review. To provide a state-of-the-art assessment of diagnosis and non-surgical treatment of degenerative cervical radiculopathy a literature search for studies on epidemiology, diagnosis including electrophysiological examination and imaging studies, and different types of conservative treatment was undertaken. The most common causes of cervical root compression are spondylarthrosis and disc herniation. Diagnosis is made mainly on clinical grounds, although there are no well-defined criteria. Provocative tests like the foraminal compression test are widely used but not properly evaluated. The clinical diagnosis of degenerative cervical radiculopathy can be confirmed by magnetic resonance imaging. The role of electromyography is mainly to rule out other conditions. Cervical radiculopathy is initially treated conservatively, although no treatment modality has been evaluated in a randomized controlled trial. Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review.