Background: There is little reliable population-based information about the distribution of risk factors among the various ischemic stroke subtypes, even though determining risk factor profiles is of major importance to develop targeted preventive strategies.

Methods: We established the distribution of first-ever ischemic stroke subtypes in a prospective population-based study conducted in Dijon, France (152,606 inhabitants). Cases were collected between January 2005 and December 2006, and were classified using TOAST classification. Vascular risk factors were recorded to determine a risk factor profile for each subtype.

Results: 332 patients with first-ever ischemic stroke (150 men and 182 women) were recorded. Adjusted-incidence to World population was 54/100,000/year. The distribution of ischemic stroke subtypes was as follows: 119 (35.8%) cases of large artery atherosclerosis, 89 (26.8%) small artery occlusions, 81 (24.4%) cardioembolisms, 43 (13%) other and undetermined causes. The most frequent vascular risk factor was hypertension, whatever the ischemic stroke subtype, with a total prevalence of 62%. Using multivariate regression we demonstrated a positive association between cardioembolism and age (OR, 1.051; 95% CI, 1.026-1.076; P<0.001) and between small artery occlusion and either high blood pressure (OR, 1.86; 95% CI, 1.06-3.27; P=0.03) or hypercholesterolemia (OR, 2.23; 95% CI, 1.33-3.76; P=0.02).

Conclusion: We demonstrate, in a comprehensive prospective population-based study, that vascular risk factors exhibit a particular distribution according to the ischemic stroke subtypes. These findings, as well as the great frequency of hypertension among stroke patients, have implications for prevention strategies, the design of clinical trials, and the organization of health care services.

Background: Risk stratification can contribute to individualized, optimal secondary prevention in patients with cerebrovascular disease.

Objective: To prospectively investigate the prediction of the Essen Stroke Risk Score (ESRS) and a pathlogical ankle brachial index (ABI) in consecutive patients hospitalized with acute ischemic stroke or TIA in 85 neurological stroke units throughout Germany.

Methods: 852 patients were prospectively documented on standardized 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. <3) had a significantly higher risk of recurrent stroke or cardiovascular death (9.7% vs. 5.1%, odds ratio [OR] 2.00, 95% confidence interval [CI] 1.08-3.70) and a higher recurrent stroke risk (6.9% vs. 3.7%, OR 1.93; 95% CI 0.95-3.94). Patients with an ABI ≤0.9 (vs. >0.9) had a significantly higher risk of recurrent stroke or cardiovascular death (10.4% vs. 5.5%, OR 2.00, 95% CI 1.12-3.56) and a higher recurrent stroke risk (6.6% vs. 4.6%, OR 1.47, 95% CI 0.76-2.83).

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.

Background: Postural instability gait difficulty (PIGD) motor phenotype in Parkinson’s disease (PD) is associated with a faster rate of cognitive decline than in tremor dominant cases and may be a risk factor for incident dementia. People with PD display attentional deficits; however it is not clear whether attentional deficits in non-demented PD patients are associated with (i) PIGD phenotype and/or (ii) subsequent cognitive decline.

Aims: (i) To examine rates of cognitive decline (MMSE and CAMCOG) over three years in non-demented PD subjects aged over 65, (ii) using Cognitive Drug Research computerised assessment test battery determine rate of change in power of attention (PoA) scores over time (sum of mean choice reaction time, simple reaction time and digit vigilance reaction time scores), (iii) determine whether PIGD phenotype is associated with changes in PoA and (iv) establish whether baseline PoA is associated with subsequent cognitive decline.

Results: 14 subjects (38%) were classified as PIGD motor phenotype at baseline. Cognitive decline was greater in PIGD compared to non-PIGD subjects (p<0.02). PIGD phenotype was not associated with baseline PoA score although it was associated with subsequent worsening in PoA (mean PoA increase/year: Non-PIGD subjects, 11.3 ms; PIGD subjects, 244.0 ms; p=0.02). Higher baseline PoA scores were associated with greater cognitive decline (MMSE, p=0.03; CAMCOG, p=0.05) independent of PIGD status.

Conclusion: PIGD phenotype and attention deficits are independently associated with a greater rate of cognitive decline in non-demented PD patients. We propose that subtle attentional deficits in non-demented PD patients predict subsequent cognitive impairment.

Objective: We studied the feasibility of multimodal neuroimaging in mild to moderate Alzheimer’s disease (AD) and estimated the size of possible treatment effects of memantine on potential functional, structural, and metabolic biomarkers of disease progression.

Methods: In this randomized, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total-brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations.

Results: In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total-brain volume by 2.1% (p<0.0001), and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs. 4.0%). No between-group differences were seen for changes in total-brain volume.

Conclusions: Our results support the use of multimodal imaging including MRI and PET to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. Our data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.

Background: Ulnar nerve neuropathy is one of the most common entrapment neuropathies and is often considered to be one entity in clinical and follow-up studies.

Objective: The aim of this study was to determine whether there is a difference in the long-term outcome of patients with a severe motor conduction block (mCB) of ¡Y50% (50% group) in comparison to patients with a mCB of ¡Ü20% (20% group).

Methods: In a prospective cohort of 244 patients with ulnar neuropathy at the elbow (UNE), 16% had a mCB of ¡Y50%. These patients were matched with respect to surgery, age and the severity of muscle weakness with patients with a mCB of ¡Ü20%. Thirty-two patients per group were clinically and electrophysiologically evaluated.

Results:The median follow-up period was 25 months. Based on the patient¡s assessment, 26 (81%) patients in the 50% group and 14 (44%) patients in the 20% group had a good outcome (p=0.005). The clinical examination showed a good outcome in 27 (84%) in the 50% group and 13 (41%) in the 20% group (p=0.0008).

Conclusion: This study showed that the prognosis of patients with focal demyelination of the ulnar nerve presenting with a mCB of ¡Y50% is more favourable than those without a mCB.

Objective: Patients with autosomal recessive myotonia congenita display myotonia and transient paresis that diminish with repetitive muscle contractions (warm-up phenomenon). Here, we present a new approach to quantify this warm-up phenomenon under clinically relevant gait and balance tasks.

Methods: Ten patients with DNA proven autosomal recessive myotonia congenita and 14 age-matched controls participated. Subjects performed six everyday gait and balance tasks. Balance control during these tasks was monitored using two angular velocity transducers that measured trunk movements in anterior-posterior (pitch) and medio-lateral (roll) directions at the level of the lumbar vertebral column. Tasks were performed under two conditions in randomized order: after a 10-minute seated rest period (‘rested’) and after having consecutively repeated the task five times (‘warm-up’). Controls were also tested twice.

Results: ‘Rested’ patients showed greatest abnormalities (increased sway in pitch and roll) for tandem walking and walking stairs. Balance impairment was also evident for all other tasks. After ‘warm-up’ balance was markedly improved in patients, as reflected by decreased trunk sway (especially during tandem walking) and reduced task duration for all tasks. These results were evident not only at the group level, but were also clearly present in individual patients.

Conclusion: Our results show that trunk sway analysis detects postural instability in myotonia congenita patients during everyday gait and balance tasks. Moreover, this technique provides a useful tool to quantify the warm-up phenomenon, suggesting a potential use both as clinical endpoint in future clinical trials.

Background: Central post-stroke pain (CPSP) is often resistant to treatment. We have previously proposed that caloric vestibular stimulation might alleviate it.

Methods: We conducted a single-blind placebo controlled trial of caloric vestibular stimulation (CVS) in 9 CPSP patients. Participants rated their pain levels pre and post-procedure on a 10-point scale.

Results: We found a significant immediate treatment effect of the cold-water caloric stimulation with an average pain reduction of 2.58 points (SEM= 0.52) for the experimental condition compared to 0.54 (SEM= 0.49) for the placebos.

Conclusions: Participants who responded best to CVS had suffered strokes that spared and permitted activation of the dominant parieto-insular vestibular cortex (PIVC), which is known to be located in the non-dominant hemisphere. These findings tie in closely with the thermosensory disinhibition hypothesis for central pain, which leads us to propose that vestibular stimulation may alleviate CPSP either from cross-activation between the PIVC and the thermosensory cortex in the adjacent dorsal posterior insula. Alternatively, if one views vestibular function, and thermoregulation, as part of a larger interoceptive system that exists to maintain homeostasis, then it is possible that they share a common integrative mechanism in the brainstem, which may act to, in effect, reset the balance in central pain.

Background: In elderly persons, chronic dizziness is endemic. However, chronic dizziness of unknown origin is difficult to assess.

Objective: To investigate whether mild, unrecognized benign paroxysmal positional vertigo (BPPV) is a cause of isolated chronic dizziness in the elderly.

Patients and Methods: We evaluated the prevalence of extremely weak, horizontal, direction-changing apogeotropic positional nystagmus (HAPN) that had not been detected by conventional examination in 200 patients with isolated chronic dizziness and 155 age-matched control subjects without dizziness.

Results: We found a high prevalence of weak HAPN in patients with isolated chronic dizziness (98/200 [49.0%]) in comparison to the prevalence in control subjects without dizziness (25/155 [16.1%]; p < 0.0001). Symptoms improved in some patients by daily positional exercise for BPPV.

Conclusion: Because BPPV is the most common cause of dizziness in the elderly, and the HAPN is a characteristic of horizontal canal BPPV, our findings suggest that mild, persistent BPPV is a possible cause of chronic dizziness of otherwise unknown origin in the elderly.

Background: Pain is a common symptom in polyneuropathies (PNP), although it is still not known why some PNP are painful whereas others are painless. Increased pro-inflammatory cytokines were found in conditions resulting in exaggerated pain states in animal studies. Recently, elevated pro-inflammatory cytokine levels have also been found in the cerebrospinal fluid (CSF) of patients suffering from complex regional pain syndrome. Pro-inflammatory cytokines have been shown to induce or increase inflammatory or neuropathic pain.

Methods: Using chemiluminescent enzyme immunometric assays, we investigated cytokine levels in 36 patients with painful and painless non-inflammatory PNP in serum and CSF. Severity of PNP was measured with electroneurography (ENG). In subjects with normal results upon conventional ENG, quantitative thermotesting was performed to investigate small nerve fiber function.

Results: IL-6 and TNF-á in serum or CSF did not differ between patients with (n=18) or without (n=18) painful PNP, whereas patients with mechanical allodynia (n=5) had elevated serum TNF- á levels compared to those without allodynia. TNF- á and IL-6 serum levels were higher in patients with severe (n= 21) compared to those with mild neuropathy (n=15) and showed a positive correlation with severity of neuropathy.

Conclusions: Results suggest that nerve fiber degeneration and presence of mechanical allodynia in peripheral non-inflammatory neuropathy determine cytokine expression in serum.

Background: Anderson-Fabry Disease (AFD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Central nervous system (CNS) manifestations consist mainly of cerebrovascular events. Brain magnetic resonance imaging (MRI) results often abnormal. PURPOSE: The aim of the present study was to describe CNS involvement in a group of Italian AFD patients.

Methods: Clinical and brain MRI data of 43 patients with AFD (25 males, 41.94 ± 10.83 yrs old and 18 females, 52.48 ± 17.50 yrs old) were analyzed retrospectively. 17 male patients and 7 female patients were under treatment with enzyme replacement therapy (ERT).

Results: All 43 patients had signs or symptoms of AFD. 16 males (64%) and 13 females (72%) demonstrated CNS involvement although with varying severity. Overall, 6 males and 5 females had suffered from cerebrovascular accidents with an age at onset of 33.64 ± 13.65 yrs and 53.68 ± 11.71 yrs, respectively. Brain MR images were abnormal in 16/25 males and in 13/16 females. During CNS monitoring some patients receiving ERT (5/17 males and 2/6 females) demonstrated neurological deterioration, especially those who had presented with cerebrovascular disease already before starting ERT.

Conclusions: The present study demonstrated a high frequency of CNS involvement in homozygous and heterozygous AFD patients, often characterized by early age at onset and abnormal brain MRIs. At present ERT is widely-used, however, potential beneficent effects may be disguised by the progression of irreversible pathology in short-term follow-up. Therefore primary and secondary prophylaxes of cerebrovascular disease are extremely important.

Objectives: The aim of this meta-analysis was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D.

Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded.

Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 – 0.90).

Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk.

Background:Two single-case studies suggest that a protein-rich diet may be beneficial for patients with McArdle disease, based on improvements in either endurance, or muscle energetics assessed by phosphorous MR spectroscopy. In healthy subjects, proteins contribute very little to energy metabolism during exercise, which questions the effect of protein in McArdle disease.

Methods:In a crossover, open design, we studied 7 patients with McArdle disease, who were randomised to follow either a carbohydrate- or protein-rich diet for three days before testing. Caloric intake on each diet was identical, and was adjusted to the subject’s weight, age and sex. After each diet, exercise tolerance and maximal work capacity were tested on a bicycle ergometer, using a constant workload for 15 minutes followed by an incremental workload to exhaustion.

Results:During the constant workload, heart rate and perceived exertion were consistently lower (p < 0.0005) on the carbohydrate- vs. protein-rich diet. Patients also had a 25% improvement in maximal oxidative work capacity on carbohydrate vs. protein diet.

Conclusions:This study shows that patients with McArdle disease can improve their maximal work capacity and exercise tolerance to submaximal workloads by maintaining a diet high in carbohydrate instead of protein. The carbohydrate diet not only improves tolerance to every-day activities, but will likely also help to prevent exercise-induced episodes of muscle injury in McArdle disease.

Objectives: To examine the relative relapse-rate patterns over time in a relapsing-MS cohort and to investigate potential predictors of relapse-rates and periods of low-relapse activity.

Methods: This retrospective cohort study followed 2477 RRMS patients from onset to July 1, 2003. Annualized relapse rates were examined according to sex, age at onset, the patient’s current age and disease duration. The relationship between relapse-rates and baseline characteristics (sex, onset age and onset symptoms) were examined using Poisson regression. Time to the first 5-years relapse-free was examined using Kaplan-Meier survival analysis.

Results: The mean follow-up time (from onset of MS symptoms) was 20.6 years, during which 11,722 post-onset relapses were recorded. The relapse rate decreased by 17% every 5 years (between years 5 to 30 post-onset), but this decline increased in magnitude with increasing onset age. Women and those with onset sensory symptoms exhibited a higher relapse-rate (p<=0.001). Over three-quarters of patients (1692/2189) experienced a 5-year relapse-free period during the RR phase.

Conclusion: Relapse rates were age and time-dependent. Our observations have clinical implications: 1) any drug able to modify relapse rates has the greatest potential for a population-impact in patients <40 years old and within the first few demi-decades of disease; 2) continuation of drug beyond these times maybe of limited value; 3) long-term follow-up studies must consider that relapse rates likely decline at different rates overtime according to the patient’s onset age; 4) a relapse-quiescent period in MS is not uncommon.

Objective: Endocannabinoids (eCBs) play a pivotal role in the modulation of neuroinflammation and experimental findings suggest that they may be directly involved in the pathogenesis of multiple sclerosis (MS). The objective of our study was to measure eCBs levels in the cerebrospinal fluid (CSF) of MS patients.

Patients and methods: Arachidonoyl-ethanolamide (anandamide, AEA), palmitylethanolamide (PEA), 2-arachidonoyl-glycerol (2-AG) and oleoylethanolamide (OEA) levels were measured in the CSF of 50 MS patients and 20 control subjects by isotope dilution gas-chromatography/mass-spectrometry. Patients included thirty-five MS patients in the relapsing-remitting (RR) form of the disease, 20 in a stable clinical phase and 15 during a relapse, and 15 MS patients in the secondary progressive form (SP).

Results: Significantly reduced levels of all the tested eCBs were found in the CSF of MS patients compared to control subjects, with lower values detected in the SP MS group. Higher levels of AEA and PEA, although below those of controls, were found in the CSF of RR MS patients during a relapse. Higher levels of AEA 2-AG and OEA were found in patients with MRI gadolinium-enhancing (Gd+) lesions.

Discussion: The present findings suggest the presence of an impaired eCB system in MS. Increased CSF levels of AEA during relapses or in RR patients with Gd+ lesions suggest its potential role in limiting the ongoing inflammatory process with potential neuroprotective implications. These findings provide further support for the development of drugs targeting eCBs as potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.

Objective: A stratified, randomized, waitlist controlled study over 12 months assessed the effectiveness of rehabilitation in persons with Multiple Sclerosis (MS) in an Australian community cohort.

Methods: Patients with definite MS (n=101) recruited from a tertiary hospital database, randomized to a treatment group (n=49) for individualized rehabilitation programme, or a control waitlist group (n=52). Functional Independence Measure (FIM) was used to assess ¡¥activity¡¦, while Multiple Sclerosis Impact Scale (MSIS-29) and General Health Questionnaire (GHQ-28) assessed ¡¥participation¡¦ and quality of life (QoL). Assessments were at baseline and 12 months.

Results: Analysis of data from 98 patients (treatment n=48, control n=50) showed reduced disability in the treatment group, with statistically significant differences in post-treatment FIM Motor scores for the two groups ( p<.001). There was a clinical and statistically significant improvement in FIM (Motor) total scores (p<.001), and the FIM Motor domains of : transfer (p<.001), locomotion (p<.001), self care (p<.001), and the FIM cognitive subscale (p<.016). In the treated group 70.8% improved, compared with 13% of the controls. Significantly more patients in the control group deteriorated over the study period (58.7% versus 16.7%: p<.001). There were no differences between control and treatment group scores on the MSIS-Physical (p=.18), MSIS-Psychological (p=.45) or GHQ subscales.

Conclusion: An individualized rehabilitation programme reduces disability in persons with MS compared to no intervention. The impact of rehabilitation on QoL needs further evaluation. More information on effectiveness of the various components of the multidisciplinary rehabilitation programmes are now needed.

AIM: The aim of this trial was to evaluate the effects of albendazole (ALB) on cyst disappearance, reduction of number of cysts, and seizure recurrence.

METHODS: 178 patients with new onset symptoms due to active or transitional NC were randomly assigned to receive either 800 mg of ALB daily or placebo for 8 days. All patients also received prednisone. Imaging studies were done at baseline and months 1, 6, and 12 of follow-up. This trial is registered at Clinicaltrials.gov number NCT00283699.

RESULTS: Active cysts were identified in 59 of the 88 people randomized to ALB and 57 of the 90 in the placebo arm. By 1 month, 31% were free of active cysts in the treatment group compared to 7% in the placebo group (P=0.001). In addition, the ALB group had greater reduction in the number of active cysts compared to the placebo group (P=0.001). After one month following treatment there was no additional gain by treatment group in disappearance or reduction in the number of active cysts. ALB treatment had little effect on cysts in the transitional or calcification stage. We found no difference between the ALB and placebo group in symptoms during treatment or in seizure recurrence during the 12 months after treatment.

CONCLUSION: Albendazole plus symptomatic treatment leads to the disappearance of active cysts in 31% of the patients, compared to 7% of those with symptomatic treatment alone. This treatment effect occurs within the first 30 days after treatment.

Introduction: Copper deficiency is an increasingly recognized cause of neurological impairment. This retrospective review highlights clinical and electrodiagnostic findings in patients diagnosed at our institution with copper deficiency.

Methods: Clinical, radiographic and electrodiagnostic findings were reviewed in patients with evidence of copper deficiency. Patients with other potential causes of myelopathy or neuropathy were excluded.

Results: The predominant clinical feature in all six patients was a sensory ataxia, resulting in marked gait unsteadiness. Nerve conduction studies and needle EMG were performed in all patients and revealed a mild to moderate distal, axonal, sensorimotor peripheral neuropathy. Median and tibial somatosensory evoked potentials were abnormal in all five patients in which it was done, showing impaired conduction in central or proximal peripheral somatosensory pathways.

Conclusions:This pattern of electrodiagnostic findings suggests that impairment in somatosensory pathways demonstrated by somatosensory evoked potential testing, is the main cause of the sensory ataxia in patients with copper deficiency.

Background: The three nucleotide deletion, DGAG within the gene TOR1A is the only proven cause of childhood-onset dystonia (DYT1). A potentially pathogenic role of additional sequence changes within TOR1A has not been shown beyond doubt.

Methods: DNA sequencing of exon 5 of TOR1A in a patient with childhood-onset dystonia (DYT1).

Results: Detection of sequence change c.863G>A in exon 5 of TOR1A in the patient. The G>A transition results in an exchange of an arginine for glutamine (p.Arg288Gln) in subdomain a5 of TOR1A. Several findings point to a potentially pathogenic role of the sequence change in the patient. 1) The base change is absent in 1000 control chromosomes; 2) an Arg at position 288 of TOR1A has been conserved throughout vertebrate evolution. This indicates an important role of Arg288 in TOR1A function; 3) Functional studies demonstrate enlarged perinuclear space in HEK293 cells overexpressing TOR1A with the p.Arg288Gln mutation. The same morphological changes are observed in cells overexpressing the common DGAG TOR1A mutation but not in cells overexpressing WT TOR1A.

Conclusions: The sequence change described here may be a novel pathogenic mutation of TOR1A in early-onset dystonia (DYT1).

Objectives: To determine the long term outcome of a cohort of 436 MS patients seen in 1985 and long-term predictors of benign MS.

Methods: The initial 1985 group of 436 patients with possible MS, including 53 benign patients were followed for 21 years. Disability was recorded using the EDSS. Survival from disease onset was calculated. The indicators of benign MS in the initial 1985 cohort and in the survivors in 2006 were determined.

Results: Of the original 436 patients, the 21-year follow-up outcome in 397 (91%) was established. The diagnosis of MS was incorrect in 41/397 (10%) of the whole cohort and in 2/53 (4%) of the benign group. Median survival of 356 MS patients was 43.6yrs from disease onset. Of 47/51 (92%) benign MS patients followed in 2006 seven remained benign, 18 had died, and 22 were disabled. Median survival advantage for the 47 benign in 1985 compared to the 88 not benign, when corrected for age was six years (p<0.08). In 2006, 40/356 (11%) patients had a benign outcome at a mean follow up of 26.1 yrs. A benign course was significantly associated with female sex, younger age of onset and absence of motor symptoms at presentation.

Conclusions: Although designating patients as having a benign course after 10 years has a poor predictive value; three factors at presentation indicate a better prognosis.

Background: The underlying factors of reversion from cognitive impairment to normal cognitive functioning in stroke are not well understood. We compare demographic, cognitive and imaging factors in Vascular Cognitive Impairment No Dementia (Vascular CIND) patients who revert to normal cognitive functioning to Vascular CIND patients who do not revert.

Methods: Thirty-one ischemic stroke patients, who met classification criteria for Vascular CIND, were > 49.5 years old, met NINDS stroke criteria, and were free from additional neurological illness, completed baseline and one year examinations. Forty-five percent of the Vascular CIND participants reverted to no cognitive impairment at one-year follow-up examination.

Results: There was greater cognitive impairment in non-reverters on a summary score spanning several neuropsychological domains and on psychomotor and working memory summary scores. There were no differences on demographic factors or in stroke severity between reverters and nonreverters. Structural MRI analyses revealed no baseline differences in number of strokes, stroke volume, or stroke location. However, there was greater frontal white matter hyperintensity load in the non-reverter group.

Conclusions: These results suggest that Vascular CIND reversion may be a function of a combination of baseline neuropsychological function and location of cerebrovascular disease.

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare multi-system disorder associated with plasma cell dyscrasia. Several case series and reports have suggested high dose chemotherapy with autologous peripheral blood stem cell transplant is efficacious treatment, but this transplantation is not indicated for elderly patients and patients with renal failure.

Objective: To investigate the effects of thalidomide treatment for POEMS syndrome.

Methods: Nine patients, who were not indicated for high dose chemotherapy, were treated with thalidomide. Neurological disability scores, nerve conduction studies, and serum levels of vascular endothelial growth factor (VEGF) were prospectively examined. VEGF levels were measured by an enzyme-linked immunosorbent assay.

Results: During follow-up periods of 8 to 23 months (mean, 15 months), all patients showed substantial clinical improvement (n=6) or stabilization of symptoms (n=3). Serum VEGF levels decreased in all, and were normalized in five. Nerve conduction velocities in the median nerve increased in seven. There were no serious adverse effects including thalidomide neuropathy.

Conclusion: Thalidomide treatment should be further studied as a treatment of POEMS syndrome, particularly for patients who are not indicated for transplantation therapy.

Background: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria.

Methods: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patients’ records at baseline and latest yearly follow-up.

Results: Of 82 incident patients, 66 underwent at least one year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a "probable" diagnosis in 71% of parkinsonian patients at follow-up but only 15% at initial assessment.

Discussion: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson’s disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis even after a median of 29 months follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.

Objective: Patients with pure autonomic failure (PAF) have an abnormal fall in blood pressure (BP) with supine exercise and exacerbation of orthostatic hypotension (OH) after exercise. We assessed the pressor effect of water on the cardiovascular responses to supine exercise and on OH after exercise.

Methods: 8 PAF patients underwent a test protocol consisting of standing for 5 min, supine rest for 10 min, supine exercise by pedalling a cycle ergometer at workloads of 25 W, 50 W and 75 W (each for 3 minutes), supine rest for 10 min and standing for 5 min. The test protocol was performed without water ingestion and on a separate occasion after 480ml distilled water immediately after pre-exercise standing. Beat-to-beat cardiovascular indices were measured with the Portapress II device with subsequent Modelflow analysis.

Results: All patients had severe OH pre-exercise (BP fall systolic 65.0±26.1 mmHg, diastolic 22.7±13.5 mmHg), with prompt recovery of BP in the supine position. 5 min after water drinking, there was a significant rise in BP in the supine position. With exercise, there was a clear fall in BP (systolic 42.1±24.4 mmHg, diastolic 25.9±10.0 mmHg) with a modest rise in heart rate; this occurred even after water ingestion (BP fall systolic 49.8 ± 18.9 mmHg, diastolic 26.0±9.1 mmHg). BP remained low after exercise, but was significantly higher after water intake resulting in better tolerance of post-exercise standing.

Conclusions: Water drinking did not change the abnormal cardiovascular responses to supine exercise. However, water drinking improved orthostatic tolerance post-exercise.

Background: Mild traumatic brain injury (MTBI) is a significant public health problem affecting approximately one million people annually in the United States. Ten to fifteen percent are estimated to have persistent post-traumatic symptoms. We wished to determine whether focused, scheduled telephone counseling during the first 3 months after MTBI decreases symptoms and improves functioning at 6 months.

Methods: This was a two-group, parallel, randomized clinical trial with outcome assessed by blinded examiner at 6 months after injury. 366 of 389 eligible subjects age 16 or older with MTBI were enrolled in the emergency department with an 85% follow-up completion rate. Five telephone calls were completed, individualized for patient concerns and scripted to address education, reassurance, and reactivation. Two composites were analyzed, one relating to post-traumatic symptoms that developed or worsened after injury and their impact on functioning; the other related to general health status.

Results: The telephone counseling group had a significantly better outcome for symptoms (6.6 difference in adjusted mean symptom score, 95% confidence interval (CI) 1.2 to 12.0), but no difference in general health outcome (1.5 difference in adjusted mean functional score, 95% CI -2.2 to 5.2). A smaller proportion of the treatment group had each individual symptom (except anxiety) at assessment. Similarly, fewer of the treatment group had daily functioning negatively impacted by symptoms with the largest differences in work, leisure activities, memory and concentration, and financial independence.

Conclusions: Telephone counseling, focusing on symptom management, was successful in reducing chronic symptoms after MTBI. ClinicalTrials.gov, #NCT00483444

Objective: To investigate substantia nigra (SN) echogenicity in members of a family with homozygous and heterozygous PINK1 mutations with or without signs of Parkinson’s disease (PD).

Methods: Transcranial sonography (TCS) was employed to investigate 20 members of a family with PINK1 mutations including four homozygous and eleven heterozygous mutation carriers and five individuals with no mutation. For comparison, a healthy control group of 18 subjects without a positive family history of PD (control group) and a healthy control group of 15 subjects with a positive family history of sporadic PD (relative group) were investigated. For statistical analysis, the larger area of the two SNs echogenicity (aSNmax) of each individual was selected.

Results: A significantly increased aSNmax was found for all subgroups compared to the control group. The group of homozygous carriers of a PINK1 mutation had a significantly increased aSNmax compared to all other subgroups, except the group of heterozygous mutation carriers.

Conclusions: Our findings in carriers of a PINK1 mutation are comparable to findings in carriers of Parkin mutations and nongenetic PD. The increased aSNmax in family members without a mutation suggests an additional contributing factor independent of the PINK1 mutation that may also play a role in relatives of sporadic PD patients.

Objective:To assess the frequency and clinical characteristics of the increasingly recognised complication of cerebrovascular dysplasia in children with Neurofibromatosis type 1 (NF1).

Methods: A series of seven patients with NF1 and cerebrovascular dysplasias that were not secondary to radiotherapy were identified and prospectively assessed. An extensive review of the literature was also performed to identify associated features and the natural history of this potentially severe complication of NF1.

Results:The frequency of cerebrovascular dysplasia in NF1 is 2-5%, and vascular lesions are clearly visible on routine magnetic resonance imaging (MRI) of the brain. The majority of our patients were clinically asymptomatic, despite angiographic progression in some cases. Hypoplastic carotid canals and early appearance on MRI suggest that a proportion of cases of cerebrovascular dysplasia are congenital in origin.

Conclusion:These findings have implications for screening of asymptomatic patients with NF1, and highlight the difficult management decisions in those patients identified with cerebrovascular malformations.

Background: The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of Multiple Sclerosis (CIS) is unclear and whole brain or whole normalized grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability.

Methods: We have used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyze regional atrophy and perform voxel-wise correlations between volume and clinical metrics in forty-one untreated CIS patients at presentation compared to forty-nine healthy controls.

Results: Our results confirmed that there was no significant difference in whole normalized grey matter volume between CIS and controls while VBM showed significant areas of bilateral thalamic, hypothalamic, putamen, and caudate atrophy. Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores, and MSFC, and the MSFC was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of Multiple Sclerosis.

Conclusions: Atrophy is present in CIS patients at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.

Holmes’ tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. We report the case of a 20-year-old female patient who developed right-sided Holmes’ tremor nine months after a left-sided, cavernoma induced midbrain/pontine hemorrhage at the age of 16. Beta-CIT SPECT revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle) demonstrated by diffusion tensor MRI (DTI). Tractography showed reduced fiber connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction of tremor severity. In conclusion, our results support the notion of Holmes’ tremor to be the result of diminished striatal dopaminergic input in our patient.

Background: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. Our aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment.

Patients and Methods: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analyzed. Sural nerve SAP amplitude reduction ¡Y 40% was the criteria for discontinuing therapy.

Results: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction > 50 % and 2 < 50 %). One patient showed no changes in SAP amplitude. Five patients complained paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients . At detection of reduction in sural nerve SAP amplitude the median thalidomide cumulative dose was 21,4 g. The threshold neurotoxic dosage is lower than previously reported.

Conclusions: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of sensory fibres degeneration and recovery. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms.

Objectives: Ischemic stroke is a frequent manifestation in patients with adult moyamoya disease (MMD), but the relationship between the lesion pattern and disease severity has rarely been investigated.

Methods: We collected data on a consecutive series of 65 adult MMD patients who visited our hospital between 1999 and 2006. Among them, 32 patients with first-ever ischemic stroke were included. The ischemic lesions were categorized by location and compared as follows: 1) cortical vs subcortical involvement and 2) anterior (fronto-temporal) vs. posterior (parieto-occipital) involvement. The lesions were also compared by disease severity as determined by the extent of intracranial artery involvement (Suzuki's grading method) and by the perfusion status visualized on single photon emission computed tomography (SPECT).

Result: The disease severity was significantly greater in patients with cortical involvement than in those with subcortical involvement (Suzuki's grade, 4.17±0.72 vs. 2.70±0.73, p<0.001). The disease severity was also significantly greater in patients with posterior involvement than in those with anterior involvement (4.50±0.53 vs. 2.83±0.76, p<0.001). In most of the patients (83.3%) the perfusion defect area shown on SPECT was larger than the ischemic lesion area shown on MRI.

Conclusions: We found that patients with advanced stage adult MMD tended to have ischemic lesions involving the cortex and posterior part of the brain and that the stroke mechanism in these patients was largely associated with hemodynamic compromise. Our results suggest that the lesion pattern of ischemic stroke may change along with the extent of arterial involvement.

Background: Suppressing the antigen-presenting capacity of glial cells could represent a novel way of reducing inflammatory activity in multiple sclerosis (MS).

Aims: To evaluate the effects of fluoxetine on new lesion formation in patients with relapsing MS. Methods: In a double-blind, placebo-controlled exploratory study, 40 non-depressed patients with relapsing remitting or relapsing secondary progressive MS were randomised to oral fluoxetine 20 mg or placebo daily for 24 weeks. New lesion formation was studied by assessing the cumulative number of gadolinium-enhancing lesions on brain MRI performed on weeks 4, 8, 16 and 24.

Results: Nineteen patients in both groups completed the study. The mean (SD) cumulative number of new enhancing lesions during the 24 weeks of treatment was 1.84 (2.9) in the fluoxetine group and 5.16 (8.6) in the placebo group (p=0.15). The number of scans showing new enhancing lesions was 25% in the fluoxetine group versus 41% in the placebo group (p=0.04). Restricting the analysis to the past 16 weeks of treatment showed that the cumulative number of new enhancing lesions was 1.21 (2.6) in the fluoxetine group and 3.16 (5.3) in the placebo group (p=0.05). The number of patients without enhancing lesions was 63% in the fluoxetine group versus 26% in the placebo group (p=0.02).

Conclusions: This proof-of-concept study shows that fluoxetine tends to reduce the formation of new enhancing lesions in patients with MS.

Objective: To examine risk factors for mild cognitive impairment (MCI) and progression to dementia in a prospective community-based study of subjects aged 65 years and over.

Methods: 6892 participants who were over 65 and without dementia were recruited from a population-based cohort in three French cities. Cognitive performance, clinical diagnosis of dementia, and clinical and environmental risk factors were evaluated at baseline and 2-year and 4-year follow-ups.

Results: 42% of the population were classified as having MCI at baseline. After adjustment for confounding with logistic regression models, men and women classified as having MCI were more likely to have depressive symptomatology and to be taking anticholinergic drugs. Men were also more likely to have a higher body mass index, diabetes and stroke, whereas women were more likely to have poor subjective health, to be disabled, to be socially isolated, and to suffer from insomnia. The principal adjusted risk factors for men for progression from MCI to dementia in descending order were ApoE4 allele (OR=3.2, 95% CI 1.7 to 5.7), stroke (OR=2.8, 95% CI 1.2 to 6.9), low level of education (OR=2.3, 95% CI 1.3 to 4.1), loss of Instrumental Activities of Daily Living (IADL) (OR=2.2, 95% CI 1.1 to 4.5) and age (OR=1.2, 95% CI 1.1 to 1.2). In women, progression is best predicted by IADL loss (OR=3.5, 95% CI 2.1 to 5.9), ApoE4 allele (OR=2.3, 95% CI 1.4 to 4.0), low level of education (OR=2.2, 95% CI 1.3 to 3.6), subclinical depression (OR=2.0, 95% CI 1.1 to 3.6), use of anticholinergic drugs (OR=1.8, 95% CI 1.0 to 3.0) and age (OR=1.1, 95% CI 1.1 to 1.2).

Conclusions: Men and women have different risk profiles for both MCI and progression to dementia. Intervention programmes should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women.

Objective: We recently described a family with neurological findings similar to HSAN (Hereditary sensory and autonomic neuropathy) type V having a point mutation in the Nerve growth factor beta (NGFB) gene. The homozygous genotype gives disabling symptoms. The purpose of the present study is to evaluate the symptoms in heterozygous patients.

Methods: 26 patients heterozygous for the NGFB-mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and 6 heterozygous patients underwent a sural nerve biopsy.

Results: The heterozygous phenotype ranged from 8 patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom-free patients. There was no difference in MNSI between the young heterozygous (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Aä) and unmyelinated (C) fibres. We found no apparent correlation of small fibre reduction to symptoms.

Conclusions: The NGFB mutation in its heterozygous form results in a milder disease than in homozygots with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps also life style factors, may influence the development of clinical polyneuropathy.

Objective: The goal of this study was to evaluate the utility of the stroke thrombolytic predictive instrument (s-TPI) in predicting clinical outcome in acute ischaemic stroke patients treated with intravenous tissue plasminogen activator (t-PA).

Methods: We assessed the external validity of the s-TPI in 301 consecutive stroke patients treated with intravenous t-PA. Clinical outcome was measured with the modified Rankin scale (mRs) at 3 months. We used the s-TPI to calculate probabilities of a good outcome (mRs 0-1) and a very poor outcome (mRs 5-6). We compared these probabilities with the observed outcome using receiver-operator characteristics (ROC) curves and calibration curves. Subgroup analyses for different onset to treatment time windows were performed.

Results: According to the s-TPI, the mean predicted probability of a good and a very poor outcome in the validation cohort were 0.45 and 0.17. The area under the ROC curves were 0.80 (4.5 hour time window), 0.82 (3 hour time window) and 0.77 (3-4.5 hours time window) for predicting good outcome, and 0.78 (4.5 hours), 0.80 (3 hours) and 0.74 (3-4.5 hours) for predicting very poor outcome. Calibration curves revealed a slight overestimation of probabilities of a good outcome and underestimation of probabilities of a very poor outcome.

Conclusions: The s-TPI appears to be reasonably valid for predicting outcome after t-PA treatment in daily practice, although a slight overestimation of a good and underestimation of a very poor outcome was observed.

Backgrounds: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and relationship with anti-AQP4 antibody remain unknown.

Methods: We reviewed the past medical records of 35 patients with seropositivity for anti-AQP4 antibody. We also followed the titers of anti-AQP4 antibody in a patient with NMO, who newly developed IHN.

Results: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titers of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case.

Conclusions: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.

Objective: To date, the efficacy and safety of repeat radiosurgery (RS) for trigeminal neuralgia (TN) is mainly based on short-term results.

Methods: Between 1994 and 2006, 93 patients were treated radiosurgically for TN at the Department of Neurosurgery in Graz, Austria. Twenty two patients underwent repeat GKRS mean 18.8 months after the initial treatment. The mean dose for repeat treatment was 74.3 Gy. Pain outcome was rated using the Barrow Neurological Institute (BNI) Pain Intensity Scale and facial numbness according to the BNI Facial Numbness Scale.

Results: Mean follow-up after repeat RS was 5.4 years. Pain relief was noted in 72.7% (16/22), 6 patients had a second pain recurrence after mean 9.3 months and underwent medical, alternative and/or further RS. One patient was lost to follow-up, BNI pain scale evaluation for 21 patients indicated improvement in 76.2% (16/21) without medication (BNI I and II). Facial numbness was recorded in 73.7% (14/19), in only one classified as bothersome.

Conclusions: Long-term observation of repeat GKRS for TN showed in more than two third a good pain relief. Despite a high percentage of facial numbness, most likely attributable to the higher delivered dose, repeat RS can still regarded as safe. However, further studies are needed to determine an optimized treatment protocol.

Objective: To determine whether the Nine-Hole-Peg Test (9-HPT) constitutes valid means to assess hand motion disability in cervical spondylotic myelopathy (CSM) patients.

Methods: Forty CSM patients were tested in a prospective observational study in two teaching hospitals. They were assessed in preoperative and postoperative (at month 1) time with the following tests: 9-HPT, modified Japanese Orthopedic Association scale, Nurick scale and 30 meters walking time. Mean time ± 2 standard deviations of 9-HPT in 20 healthy controls defined the normal range in our population. Scores of functional tests in pre and postoperative periods were compared using the non-parametric Wilcoxon rank test. The validity and the test-retest reliability of the 9-HPT was assessed using the Spearman’s rank correlation coefficient.

Results: In preoperative time, 9-HPT in dominant and non dominant hands were over the normal range limit in 42.5% and 50% whereas 25% of both dominant and non dominant 9-HPT were abnormal in postoperative time. 9-HPT showed a statistically significant improvement between pre and postoperative times (p<0.0001) and was highly correlated with the other validated tests. Intrarater reliabilities were high with coefficient correlations estimated at 0.97 and 0.99 for dominant and non dominant hands. Interrater agreements were also excellent with coefficient correlations of 0.97 and 0.98.

Conclusions: 9-HPT is an easily performed, quantitative, and valid means of assessing hand dexterity in CSM and the effects of surgery. The present study constitutes a step in the development of a composite scale that could include the assessment of gait and hand motion disabilities by the walking time test and the 9-HPT.

Background: Hyperglycaemia has been related to poor outcome and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH).

Objective: We aimed to assess whether in patients with aSAH, levels of mean fasting glucose within the first week predict poor outcome and DCI better than single admission glucose levels alone.

Methods: Data on non-diabetic patients admitted within 48hrs after aSAH with at least two fasting glucose assessments in the first week were retrieved from a prospective database (N=265). The association of admission glucose or mean fasting glucose, dichotomized at the median levels, with outcome was assessed with logistic regression, and with DCI with Cox regression. To explore whether the association between glucose levels and outcome was mediated by DCI, we adjusted for DCI.

Results: The crude and multivariable adjusted odds ratios and 95% confidence intervals for poor outcome were 1.9 (1.1-3.2) and 1.6 (0.9-2.7) for high admission glucose and 3.5 (2.0-6.1) and 2.5 (1.4-4.6) for high mean fasting glucose. The crude and adjusted hazard ratios for DCI were 1.7 (1.1-2.5) and 1.4 (0.9-2.1) for high admission glucose and 2.0 (1.3-3.0) and 1.7 (1.1-2.7) for high mean fasting glucose. After adjusting for DCI, the odds ratios on poor outcome for high mean fasting glucose decreased only marginally.

Conclusions: Compared with high admission glucose, high mean fasting glucose, representing impaired glucose metabolism, is a better and independent predictor of poor outcome and DCI. DCI is not the key determinant in the relationship between high fasting glucose and poor outcome.

A higher-than-expected frequency of suicide has been reported among patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) for advanced Parkinson's disease (PD). We conducted a retrospective survey of 200 patients with PD who underwent STN DBS. Two patients (1%) committed suicide and four (2%) attempted suicide, despite clear motor improvements. Suicidal patients did not differ from non suicidal patients with respect to age, disease duration, or pre-operative depressive and cognitive status. Suicidal behavior was associated with post-operative depression and/or altered impulse regulation. Suicidal behavior is a potential hazard of STN DBS, calling for careful preoperative assessment and close post-operative psychiatric and behavioral follow-up.

Objective: The pathophysiology of syringomyelia in Chiari type 1 malformation has not been clarified. Edema-like spinal cord swelling was recently reported in several pathological conditions including Chiari type 1 malformation as a pre-syrinx state. However, the role of the pre-syrinx state in development of syringomyelia is unknown. The purpose of this study is to investigate the parenchymal changes of the spinal cord in syringomyelia associated with Chiari type 1 malformation.

Methods: Pre- and postoperative magnetic resonance imaging findings in fourteen patients who underwent foramen magnum decompression in our institute were reviewed. The analysis was focused on differences in visualization of the syrinx between T1- and T2-weighted images and abnormal parenchymal signal changes. There were 6 men and 8 women, aged from 6 to 79 years. No patients showed hydrocephalus.

Results: Twelve patients had large and expansive syrinx, while 2 patients showed small syrinx confined to the center of the spinal cord. T2-weighted images displayed significantly larger intramedullary abnormal signal areas. Nine patients showed parenchymal hyperintensity areas around the enlarged central canal or base of the posterior white columns adjacent to the syringomyelic cavity. Such parenchymal hyperintensity areas markedly diminished with reduction of the syrinx after surgery and were considered to be interstitial edema.

Conclusions: From this study, the interstitial edema of the spinal cord commonly accompanies syringomyelia with Chiari type 1 malformation. Accumulation of the extracellular fluid due to disturbed absorption mechanisms may play an important role in the pathophysiology of syringomyelia associated with Chiari type 1 malformation.

Objective: Despite the clinical success of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD), little is known about the electrical spread of the stimulation. The primary goal of this study was to integrate neuroimaging, neurophysiology, and neurostimulation data sets from 10 PD patients, unilaterally implanted with subthalamic nucleus (STN) DBS electrodes, to identify the theoretical volume of tissue activated (VTA) by clinically defined therapeutic stimulation parameters.

Methods: Each patient-specific model was created with a series of five steps: 1) definition of the neurosurgical stereotactic coordinate system within the context of pre-operative imaging data; 2) entry of intra-operative microelectrode recording locations from neurophysiologically defined thalamic, subthalamic, and substantia nigra neurons into the context of the imaging data; 3) fitting a 3D brain atlas to the neuroanatomy and neurophysiology of the patient; 4) positioning the DBS electrode in the documented stereotactic location, verified by post-operative imaging data; and 5) calculation of the VTA using a diffusion tensor based finite element neurostimulation model.

Results: The patient-specific models show that therapeutic benefit was achieved with direct stimulation of a wide range of anatomical structures in the subthalamic region. Interestingly, of the 5 patients exhibiting a greater than 40% improvement in their unified PD rating scale (UPDRS), all but one had the majority of their VTA outside the atlas defined borders of the STN. Further, of the 5 patients with less than 40% UPDRS improvement all but one had the majority of their VTA inside the STN.

Conclusions: Our results are consistent with previous studies suggesting that therapeutic benefit is associated with electrode contacts near the dorsal border of the STN, and provide quantitative estimates of the electrical spread of the stimulation in a clinically relevant context.

Objective: To report clinical characteristics, HLA typing and seasonality of birth of a series of fifty-four Southern Chinese suffering from narcolepsy.

Methods: All subjects underwent detailed medical and psychiatric interviews and a standardized nocturnal PSG followed by a daytime MSLT. Each subject also completed a set of sleep questionnaires. HLA typing was performed in 91% of subjects.

Results: Seventy-eight percent and 22% were diagnosed of suffering from cataplectic and non-cataplectic narcolepsy respectively. Majority (n=47, 87%) of patients were referred to our sleep clinic for EDS. The cataplectic narcolepsy differed from non-cataplectics by having more REM-related clinical (more Sleep Paralysis and Sleep-related Hallucination) and sleep disturbances (shorter REM latency) as well as tighter association with HLA DQB1*0602. A bi-modal peak pattern was observed at 11 years and 39 years old. Similar bi-modal pattern also occurred for EDS and cataplexy. Excess winter birth was observed for this series of patients. Eighty-one percent of cataplectic narcolepsy patients were DQB1*0602 positive. There were no difference between early and late onset cases in the association with positive DQB1*0602 (71.4% vs 60%). Narcolepsy has prominent pernicious effects on various social, academic, family and mental aspects in our patients.

Conclusions: In our Southern Chinese narcolepsy series, bi-modal peak pattern of age of onset, excess winter birth and tight association of HLA DQB1*0602 with cataplectic narcolepsy were found.

Objective: To reveal characteristic clinicopathologic correlates of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS)syndrome.

Methods: The clinical features of 22 patients with POEMS syndrome were investigated and correlated with the histopathologic features of sural nerves and serum cytokine profiles.

Results: More than half of the patients complained of pain in the lower extremities, which is closely related to hyperalgesia. Assessment of the total nerve fiber population using complete transverse sural nerve cross-sections, excluding the marked enlargement of endoneurial areas due to intrafascicular edema, showed that myelinated fibers, especially small myelinated fibers, were reduced, while unmyelinated fibers were preserved. Uncompacted myelin lamellae and segmental demyelination were seen more frequently in the small rather than the large myelinated fibers. The presence of hyperalgesia was electrophysiologically associated with a reduction of sensory nerve action potentials in the sural nerve (p < 0.05) and histopathologically associated with myelinated fiber loss (p < 0.01). Serum levels of proinflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-á), but not their soluble receptors, were significantly elevated in patients with hyperalgesia (p <0.05-0.01).

Conclusions: Hyperalgesia seen in POEMS syndrome patients is closely related to a reduction in the myelinated, but not unmyelinated, fiber population. Elevation of proinflammatory cytokines is also correlated with hyperalgesia. The painful symptoms in POEMS syndrome may be generated by well-preserved unmyelinated C-fibers due to the lack of inhibitory myelinated A-fibers along with cytokine sensitization.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder of homocysteine metabolism. Neurologic symptoms usually appear in early life with developmental delay, microcephaly, hypotonia, seizures, apnea and coma. We report on a 56 year-old woman with a history of depression and psychosis, who exhibited acute paraplegia, coma and leukoencephalopathy. High plasma homocysteine with low methionine levels suggested a defect in homocysteine re-methylation. Severe MTHFR deficiency was found, with a new mutation in the MTHFR coding gene. Under treatment consisting of high doses of folinic acid, betaine monohydrate, beflavin and cobalamin, plasma homocysteine normalized with parallel psychiatric, cognitive and brain MRI improvement. Paraplegia remained unchanged. In conclusion, MTHFR deficiency should be considered at any age in patients with an unexplained neuropsychiatric disorder. A simple screening test, such as plasma homocysteine determination, should be performed in order to start treatment before irreversible spinal cord damage has occurred.

Background: In Parkinson’s disease (PD) patients, motor performance may be dramatically improved in urgent and stressful situations. Objective: The aim of this PET H215O study was to determine the changes of brain activation pattern related to this unconscious motor speed up observed in the context of urgency in PD patients.

Methods: Eight right handed PD patients, off medication for at least 12 hours, without tremor were enrolled. A reaching task with the right hand was performed under three conditions: self-initiated (SI), externally-cued (EC) and externally-cued-urgent (ECu).

Results: (1) Self-initiated movements (SI - EC) revealed activations in the prefrontal cortex bilaterally, the right lateral premotor cortex, anterior cingulate cortex and cerebellum, the left primary motor cortex and thalamus; (2) Externally-driven responses (EC - SI) did not involve any statistically detectable activation; (3) Urgent situations (ECu - EC) engaged the left cerebellum. Compared to a control group previously studied the cerebellar activation was greater in PD patients.

Conclusions: This study demonstrates that the increase of movement speed in urgent situations in PD patients is associated with the recruitment of the left (contralateral) cerebellum. This structure is a key node of the accessory motor circuitry typically recruited by PD patients to compensate for basal ganglia dysfunction and by healthy subjects to increase movement velocity in urgent motor contexts.

Background and purpose: Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET) is able to predict the long-term clinical outcome of aSAH.

Methods: The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and one week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI one year after SAH.

Results: High RD2 (OR 1.96; 95% CI 1.18-3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78-24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1-4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome one year after aSAH.

Conclusions: Perfusion heterogeneity is an independent predictor of the clinical outcome of aSAH and may thus be a valuable measure in the assessment of the disease.

Ross syndrome is characterized by tonic pupil, areflexia and anhidrosis and the underlying lesion affects postganglionic skin sympathetic nerve fibers. We describe a 51 years-old man complaining of anhidrosis since adolescence when this problem was limited to the lower arms. The thermoregulatory sweating test disclosed generalized anhidrosis (GA) except for two small skin areas located in the right palm and left neck. Immunofluorescence analysis disclosed no cholinergic sudomotor fibers around the sweat glands of non sweating skin areas which were evident although sparse and deranged in the sweating site. In our patient GA was induced by a postganglionic sympathetic skin nerve fibers degeneration as found in the Ross syndrome although his clinical picture was incomplete lacking tonic pupil and areflexia. Isolated generalized anhidrosis (GA) induced by a postganglionic sympathetic nerve fibers degeneration directly evaluated by skin biopsy has not been previously described.

Two patients with moderate Huntington’s disease (HD) received bilateral foetal striatal allografts. One patient demonstrated, for the first time, increased striatal D2-receptor binding evident with ¹¹C-raclopride PET and prolonged clinical improvement over five years, suggesting long-term survival and efficacy of the graft. The other patient did not improve clinically or radiologically. Our results indicate that striatal transplantation in HD may be beneficial, but further studies are needed to confirm this.

Marburg’s disease is a variant of multiple sclerosis which produces a monophasic fulminant course with extended edema and brain herniation refractory to intensive medical treatments and with poor outcome or dead. We report a case of a 31 years old female patient previously healthy who presented an hyperacute onset of pseudotumoral Marburg’s type of Multiple Sclerosis with left hemispheric massive brain swelling. On the seventh day of admission, patient’s intracranial pressure became uncontrolled in spite of medical aggressive treatment. Left decompressive hemicraniectomy allowed intracranial pressure control. Patient had an excellent outcome with an Expanded Disability Status Scale of 2.5.

Background: The model of care for patients with mild-to-moderate head injury and CT-detected lesions that do not require an immediate intervention is a matter of debate. We compared the effects on outcome of a model based either on observation in a neurosurgical unit (NSU) or in a peripheral hospital (PH) making use of neurosurgical expertise via a teleradiology system.

Patients and methods: We reviewed the data prospectively collected in 865 cases with mild-to-moderate head injury and positive CT scan, not needing immediate neurosurgical evacuation. Outcome was determined at 6 months. The predictive value of location of observation on outcome was evaluated by logistic regression, after adjustment for the propensity score to the type of observation (calculated on main entry variables).

Findings: 7