Intravenous (IV) recombinant tissular plasminogen activator (rt-PA) is the only approved pharmacological treatment for acute ischemic stroke. We aimed to analyze potential causes of the variable effect on early course and late outcome.

To investigate brain changes in both basal and cataplectic conditions in awake patients with narcolepsy-cataplexy.

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the brain, caused by reactivation of the polyomavirus JC (JCV). PML has classically been described in individuals with profound cellular immunosuppression such as patients with AIDS, hematological malignancies, organ transplant recipients or those treated with immunosuppressive or immunomodulatory medications for autoimmune diseases.

Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD.

There is some evidence for a therapeutic effect of rTMS on dysphagia in hemispheric stroke.

The pedunculopontine nucleus (PPN) is a brainstem structure with widespread connections to the basal ganglia. Despite the recent introduction of PPN deep brain stimulation (DBS) for the treatment of gait disorders, little is known about its physiology in humans.

Disease-specific quality of life measures have been validated for patients with ischaemic stroke and intracerebral haemorrhage, but not for patients with aneurysmal subarachnoid haemorrhage (SAH). We aimed to validate the Stroke-Specific Quality of Life Scale (SS-QoL) for patients with SAH.

The detrimental impact of dementia upon patient health related quality of life (HRQL) is well established as is the importance of improving HRQL. However, relatively little is known about the natural history of HRQL in dementia and those factors influencing it. This limited knowledge potentially restricts the evaluation of the efficacy of interventions designed to improve HRQL. One such area concerns the relationship between HRQL and patient insight. It remains unclear what impact, if any, impaired insight has upon a patient’s HRQL. The present study aimed to investigate the relationship between insight and HRQL in a sample of patients with Alzheimer’s disease (AD) and their carers.

Whether there is an increased surgical risk in elderly patients who undergo craniotomy for meningioma resection, remains a point of controversy. Utilizing multicenter, prospective data from the National Surgical Quality Improvement Program, the present study sought to address this controversy.

In patients with aneurysmal subarachnoid haemorrhage (SAH), headache typically is severe and often requires treatment with opioids. Magnesium has analgesic effects in several conditions, but whether it reduces headache after SAH is unknown.

Cognition is affected early in Huntington’s disease, and in HD animal models there is evidence that this reflects abnormal synaptic plasticity. We investigated whether there is evidence for abnormal synaptic plasticity using the human motor cortex-rTMS model, and if so, if there is any difference between premanifest HD gene carriers and very early manifest HD patients or any relationship with ratings of the severity of motor signs.

Obvious clinical similarities exist between these disorders but were never investigated. We propose to determine whether there exist any common features in PD between spatiotemporal gait disorders and temporal speech disorders.

Gait and speech were analyzed on eleven PP undergoing deep-brain-stimulation of the sub-thalamic-nucleus (STN-DBS) and eleven control subjects (CS) under 3 conditions of velocity (natural, slow and speed). The patients were tested with and without L-Dopa and stimulator ON or OFF. Locomotor parameters were recorded using an optoelectronic system. Speech parameters were recorded with a headphone while subjects were reading a short paragraph.

The results confirmed that PP walk and read more slowly than controls. Patient’s difficulties in modulating walking and speech velocities seem to be due mainly to an inability to internally control the step length and the interpause-speech duration ISD.

STN-DBS and levodopa increased patients’ walking velocity by increasing the step length. STN-DBS and levodopa had no effect on speech velocity but restored the patients’ ability to modulate the ISD. The walking cadence and speech index of rythmicity (SPIR) tended to be lower in patients and were not significantly improved by STN-DBS or levodopa. Speech and walking velocity as well as ISD and step length were correlated in both groups. Negative correlations between SPIR and walking cadence were observed in both groups

Similar fundamental hypokinetic impairment and probably a similar rhythmic factor affected similarly the patients’ speech and gait. These results suggest a similar physiopathological process in both walking and speaking dysfunction.

Objectives: Asomatognosia is broadly defined as unawareness of ownership of one’s arm, while somatoparaphrenia is a subtype in which patients also display delusional misidentification and confabulation. Studies differ with regard to the underlying neuroanatomy of these syndromes.

Methods: Three groups of patients with right hemisphere strokes and left hemiplegia were analyzed: G1: asomatognosia + neglect, G2: non-asomatognosia + neglect, and G3: hemiplegia only. The asomatognosic group was further subdivided into somatoparaphrenia (G1-SP: asomatognosia + delusions/confabulation) and simple asomatognosia (G1-SA; asomatognosia without delusions/confabulation).

Results: Patients with all forms of asomatognosia (G1) had larger lesions than non-asomatognosic patients in all sectors. While patients with or without asomatognosia had significant temporoparietal involvement, we found that the subset of patients with somatoparaphrenia had the largest lesions overall, and somatoparaphrenia cases had significantly more frontal involvement than patients with simple asomatognosia. All patients with asomotognosia (G1-SP and G1-SA) had significant medial frontal damage suggesting this region may play a role in the development of asomatognosia in general. Somatoparaphrenia cases also had greater orbitofrontal damage than simple asomatognosia cases, suggesting that the orbitofrontal lesion was critical in the development of somatoparaphrenia.

Conclusions: Asomatognosia results from large lesions involving multiple – including temporoparietal- sectors, but the addition of medial frontal involvement appears important. The addition of orbitofrontal dysfunction distinguishes somatoparaphrenia from simple asomatognosia. The data indicate roles for the right medial and orbitofrontal regions in confabulation and self – related systems.

Hyperactive disorders related to neurovascular compression have been described for several cranial nerves of which trigeminal neuralgia and hemifacial spasm are the best known. The present report on four patients, in conjunction with previous reports, suggests that paroxysmal staccato tinnitus might be considered an auditory hyperactivity disorder for N. VIII. The present patients reported attacks, usually lasting 10-20 seconds, of loud monaural tinnitus with a staccato character (for example clattering or sounding like a machine-gun). The attacks occurred very frequently, sometimes every minute. The attacks were spontaneous, however, they were also provoked by certain head positions or by exposure to loud sounds. Most of the patients did not reveal any significant N. VIII sensory loss, and thus it is probably not advisable to rely on any specific test result for this diagnosis. Instead, it is suggested that a diagnosis of paroxysmal staccato tinnitus can be based on the history, since the symptoms are both stereotype and very specific. Further, low doses of carbamazepine, although not effective for the general population of tinnitus patients, relieved the symptoms.

Background: Cognitive decline is common in Parkinson’s disease (PD). Although some of the etiological factors are known, it is not yet known whether drugs with anticholinergic activity (AA) contribute to this cognitive decline. Such knowledge would provide opportunities to prevent acceleration of cognitive decline in PD.

Objective: To study whether the use of agents with anticholinergic properties is an independent risk factor for cognitive decline in patients with PD.

Methods: A community-based cohort of patients with PD (n=235) were included and assessed at baseline. They were re-assessed four and 8 years later. Cognition was assessed using the Mini-Mental State Examination (MMSE). A detailed assessment of the AA of all drugs prescribed was made, and AA was classified according to a standardised scale. Relationships between cognitive decline and AA load and duration of treatment were assessed using bivariate and multivariate statistical analyses.

Results: More than 40% used drugs with AA at baseline. During the 8-year follow-up, the cognitive decline was higher in those who had been taking AA drugs (median decline on MMSE 6.5 points) compared to those who had not taken such drugs (median decline 1 point; p=0.025). In linear regression analyses adjusting for age, baseline cognition and depression, significant associations with decline on MMSE were found for total AA load (standardised Beta=0.229, p=0.04) as well as duration of using AA drugs (standardized beta 0.231, p=0.032).

Conclusion: Our findings suggest that there is an association between the use of drugs with anticholinergic properties and cognitive decline in PD. This may provide an important opportunity for clinicians to avoid increasing progression of cognitive decline by avoiding such drugs if possible. Increased awareness by clinicians is required about the classes of drugs that have anticholinergic properties.

Aim: Many studies have been performed upon the methodological qualities of the (modified) Ashworth Scale, but overall these studies seem insufficiently conclusive. Aim of this study is to investigate the construct validity and inter-rater reliability of the Ashworth Scale (AS) for the assessment of spasticity in upper and lower extremities.

Method: A cross-sectional study on spasticity in the elbow flexors (part 1) and knee extensors (part 2) was carried out. In both parts AS was assessed, while muscle activity and resistance was recorded simultaneously, in patients with upper motor neuron syndrome. Each patient was measured by three raters.

Results: Thirty patients participated, nineteen in each part of the study. For elbow flexor muscles, AS was not significantly associated with electromyographic parameters, except for rater 2 (rho = 0.66, p < 0.01). A moderate significant association was found with resistance (0.54 ≤ rho ≤ 0.61, p < 0.05). For knee extensors, AS scores were moderately associated with muscle activity (0.56 ≤ rho ≤ 0.66, p < 0.05) and also with resistance (0.55 ≤ rho ¡Ü 0.87, p < 0.05).

Intraclass correlation coefficient for absolute agreement was 0.58 for elbow flexors and 0.63 for knee extensors. In linear mixed model analysis the factor Rater appeared to be highly associated with AS.

Conclusion: Validity and reliability of the Ashworth Scale is insufficient to be used as a measure for spasticity.

Objectives: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. We aimed to find out whether an electrophysiological method exploring oro-pharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing.

Methods: We examined patients with different neurologic disorders: Parkinson¡¦s Disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy- Cerebellar variant, stroke, multiple sclerosis, and ataxia-telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of BOTOX, Allergan®). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed : 1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); 2) duration of laryngeal-pharyngeal mechanogram (LPM-D); 3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and 4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngeal-pharyngeal mechanogram (I-SHEMG-LPM).

Results: Two months after treatment, 50 % of patients showed significant improvement. The graphical analysis of the distribution of SHEMG-D and I-SHEMG-LPM at baseline highlighted values for which BTX had no effect (warning values).

Conclusions: Our electrophysiological method can recognize swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Background: Lipid storage myopathy (LSM), defined by triglyceride accumulation in muscle fibers, is a heterogeneous group of lipid metabolic disorders predominantly affecting skeletal muscle. In the past 15 years, more than 200 cases of LSM have been reported in Chinese literature, but the accurate pathogenic mechanisms are still unknown.

Objective: In order to gain more insight into the metabolic and genetic dysfunctions of LSM, we described a group of Chinese patients with LSM who were well responsive to isolated riboflavin treatment (riboflavin responsive LSM, RR-LSM).

Methods: Nineteen consecutive LSM patients collected during 1995-2007 in our Neuromuscular Laboratory who were dramatically responsive to riboflavin and presented with proximal muscle weakness, exercise intolerance and elevated serum CK but without episodic encephalopathy were subjected to pathological, biochemical and molecular analysis.

Results: On the basis of muscle pathology, all 19 patients were diagnosed as LSM. Seventeen patients were suspected to have multiple acyl-CoA dehydrogenase deficiency (MADD) according to blood acylcarnitine profiles and urine organic acid analysis. Genetic analysis identified 19 novel mutations in ETFDH gene in 18 patients, among which one was homozygote, sixteen were compound heterozygotes and one was single heterozygote. No pathogenic mutation was detected in ETFA or ETFB genes. Western blot analysis showed there was no significant decrease in ETF:QO expression except for one patient.

Conclusions: Our research findings suggest that the majority of Chinese patients with RR-LSM are caused by mild type of MADD with unique myopathy which is due to ETFDH gene mutation.

Freezing of gait (FOG) has been long thought of as a motor impairment. However, anecdotal patient reports have implied that these difficulties occur more frequently in confined spaces, and hence it is important to determine how perception of space might contribute to FOG. In an attempt to determine whether FOG may be related to a perceptual impairment, the present study evaluated how doorway size influenced characteristics of gait that might be indicative of freezing. Changes in spatiotemporal aspects of gait were evaluated while walking through three different sized doorways (narrow, normal, and wide) in three separate groups: 15 individuals with PD confirmed to be experiencing FOG at the time of test; 16 non-FOG individuals with PD; and 16 healthy age-matched control participants. Results for step length indicated that the FOG group was most affected by the narrow doorway and was the only group whose step length was dependent on upcoming doorway size. Importantly, the FOG group also displayed increased within-trial variability of step length and step time, which was exaggerated as doorway size decreased. Base of support measures indicated that the non-FOG participants walked similar to the healthy group in the normal and wide doorway conditions, but acted similar to the FOG group in the narrow doorway condition only. These results support the notion that some occurrences of freezing may be the result of an underlying perceptual mechanism that interferes with online movement planning. Neither healthy individuals nor individuals with PD absent of FOG exhibited this same effect.

We report the results of a prospective, multicenter study with open-label, blinded, as well as self-assessed evaluations to investigate the efficacy and safety of bilateral GPi DBS in patients with primary dystonia. Twenty-four patients from ten different hospitals were included and followed for one year. Clinical assessments were done through blinded scoring of video recordings, open-label evaluations, and self-assessment scales. One year after surgery, baseline motor scores were significantly reduced as revealed by both open and blinded assessments. A similar reduction in disability and pain associated with dystonia was also observed. A marked reduction of anti-dystonic medications was observed postoperatively. At six months and one year follow-up, we found correlation between improvement of both motor and functional BFMDRS scores and the age of patients at the moment of surgery. Significant improvement was also seen in quality of life. Despite global improvements in the majority of our dystonic patients, these were not associated with any significant changes in caregiver burden. Six of the 24 patients in this study presented adverse events.

GPi DBS is an effective symptomatic treatment in patients with primary dystonia refractory to medical treatment; younger age at the moment of surgery correlates positively with motor and functional outcome.

Background: Conventional MRI lesion measures modestly predict long term disability in some CIS studies. Brain atrophy suggests neuroaxonal loss in MS with the potential to reflect disease progression to a greater extent than lesion measures.

Objective: To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years).

Methods: Ninety-nine patients presenting with CIS were included in the study. T1 gadolinium-enhanced and T2-weighted brain MRI was acquired at baseline and approximately one year later. Percentage brain atrophy rate between baseline and follow-up scans was analyzed using SIENA.

Results: Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at six years and -0.26% in those who had not. Brain atrophy rate (p=0.005) and baseline T2LL (p<0.001) were independent predictors of CDMS. Whilst brain atrophy rate was a predictor of EDSS score in a univariate analysis, only one-year T2LL change (p=0.007) and baseline gadolinium-enhancing lesion number (p=0.03) were independent predictors of EDSS score at 6-year follow-up. T1 lesion load was the only MRI parameter which predicted MSFC score at the six year follow-up.

Conclusions: The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that one-year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status six years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

Among several etiological factors, PARK2 mutations are the most common cause of Parkinson’s disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, we screened 120,000 patients from 2001 to 2006 for features of PD using UK Parkinson’s disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analyzed. The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analyzed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3, and 12 among sporadic PD patients were found to be higher among younger onset variants (age < 45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.

Background: Upregulation of persistent Na+ conductances has been linked to axonal degeneration in sporadic amyotrophic lateral sclerosis and has also been reported in the transgenic superoxide dismutase-1 (SOD-1) mouse model. The mechanisms of ectopic activity (fasciculations and cramp) and axonal degeneration have yet to be clarified in familial ALS (FALS) in humans, and specifically whether there are differences to the processes identified in sporadic patients. Consequently, novel threshold tracking techniques were used to assess whether upregulation of persistent Na⁺ conductances were a feature linked to axonal degeneration in FALS.

Methods: Axonal excitability studies were undertaken in 6 FALS patients, 13 asymptomatic SOD-1 mutation carriers and 45 SALS patients.

Results: CMAP amplitude was significantly reduced in FALS (6.3±1.3 mV) and SALS (6.0±0.4 mV) compared to controls (10.0±0.4 mV, P<0.05). Mean strength duration time constant (_SD) was significantly increased in FALS (0.55±0.10 ms, P<0.05) and SALS (0.52±0.02 ms, P<0.01) compared to controls (0.41±0.02). There were no differences in _SD between asymptomatic SOD-1 mutation carriers and controls. The increase in _SD correlated with the CMAP amplitude (R= -0.4) and neurophysiological index (R= -0.4). In separate studies that assessed cortical processes, short interval intracortical inhibition (SICI) was significantly reduced (FALS, -2.7±1.3%; controls 13.7±1.3%, P<0.0001) and intracortical facilitation increased (FALS, -5.0±2.2%; controls -0.4±1.1%, P<0.05) in FALS. The reduction in SICI correlated with _SD (R= -0.8).

Conclusions: Taken together, these studies suggest that persistent Na⁺ conductances are upregulated in FALS and that this upregulation is intrinsically associated with axonal degeneration.

Objectives: Infections in stroke patients are common and significantly affect outcome. Various predictors of post-stroke infections were determined, such as degree of neurological impairment and implementation of therapeutic interventions. We investigated whether stroke location and stroke size are independent risk factors for post-stroke infections.

Methods: Five hundred ninety-one patients with acute stroke who were treated on our stroke unit were included in a prospective observational study. Pre-defined endpoints were pneumonia, urinay tract infection (UTI) and other infections. The odds ratio (OR) of infections was calculated for various stroke locations, stroke lateralization and three categories of stroke size. Logistic regression models were used to adjust for factors significantly associated with post-stroke infections in single factor analysis.

Results: In single factor analysis the left anterior cerebral artery territory was associated with pneumonia. After adjustment for relevant covariates this association was no longer statistically significant. Stroke lateralization showed no association with infection frequency. The largest stroke size was positively associated with pneumonia (OR 3.5, P<0.001). The smallest lesion size was significantly less associated with the occurrence of UTI (OR 0.4, P<0.01).

Conclusion: In our study lesion size is an independent risk factor for the development of post-stroke infection. Particular brain regions associated with infections could not be determined.

Background: Hereditary spastic paraplegia (HSP) comprises a group of rare neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the legs. Neurogenic bladder dysfunction is a well-recognized problem in patients with HSP, but it has not yet been described systematically in the literature. The aim of this study was to provide an evidential overview of the ways in which urinary dysfunction presents in HSP.

Methods: Forty-nine patients with HSP were included and underwent evaluation. A history was followed by a semi-structured interview and, in those patients who consented, measurement of residual volume of urine (PVR) and urodynamic evaluation.

Results: Thirty-eight subjects (77.6%) reported some type of urinary symptom. Subjective complaints of bladder problems showed a correlation with verified urinary dysfunction. There were no significant differences in the occurrence of urinary disturbances between the pure and complex forms of HSP (pHSP and cHSP, respectively). The most frequent symptoms were incontinence (69.4%), hesitancy (59.2%), increased frequency of micturition (55.1%), and urgency (51.0%). Incomplete bladder emptying was the rarest (36.7%). The most common combination of symptoms was to have all of them (14.3%). Incomplete bladder emptying as a complaint was associated with an increased risk of PVR. Women had a higher risk of increased voiding frequency.

Conclusions: To our knowledge, this work is the first systematic and disease-oriented overview of neurogenic bladder disturbances in patients with HSP. Our results may be useful to the clinicians who work with HSP patients, allowing them to make appropriate screening and management decisions.

Genetic classification of Parkinson disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown etiology or attributable to distinct genetic forms.

Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine-rich repeat kinase 2 (LRRK2), PTEN-induced kinase 1 (PINK1), and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset, and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis.

In comparison to genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median UPDRS scores ~1.6 times higher, P<0.001), a higher rate of dyskinesia (OR=4.21, P=0.002) and use of dopamine agonists (OR=3.64, P<0.001), and less postural tremor (OR=0.21, P<0.001). PINK1 mutation carriers presented an increased rate of drug-induced dyskinesia (OR=3.81, P=0.007) and a lower rate of postural tremor (OR=0.16, P<0.001) than genetically undefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared to LRRK2 mutation carriers and genetically undefined patients.

Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathologic features will determine diagnosis, preventative medicine and drug intervention strategies.

Objective: To determine whether monitoring facial nerve motor evoked potentials (FNMEPs) elicited by transcranial electrical stimulation during microvascular decompression (MVD) for hemifacial spasm (HFS) is useful for predicting postoperative outcome.

Methods: We analysed FNMEP findings in 25 patients with HFS. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supra-maximal stimuli (152- 450 V). FNMEPs were recorded from the orbicularis oculi, mentalis and oris muscles. Differences in amplitude or response duration between the final (at dural closure) and baseline FNMEP were evaluated. Final-to-baseline FNMEPs ratios (shown as percentages) obtained from the 3 muscles were examined.

Results: In the orbicularis oculi muscles, both duration and amplitude in the final FNMEP were significantly reduced compared to the baseline FNMEP (p < 0.001 and p < 0.0005, respectively). The FNMEP ratio obtained from the orbicularis oculi muscle (44.8 ± 25.4%) was significantly lower than the other 2 muscles (95.8 ± 51.2% for the mentalis muscle and 84.5 ± 34.6% for the orbicularis oris muscle; p < 0.0001). In 1 patient who showed the same degree of symptoms immediately after surgery as in the preoperative state, neither LSRs nor FNMEP from the orbicularis oculi muscle changed.

Conclusions: The FNMEP amplitude from the orbicularis oculi muscle decreased after MVD in HFS patients whose symptoms were resolved postoperatively, thus suggesting normalization of facial nerve excitability. FNMEP monitoring during MVD surgery as well as LSR monitoring could predict postoperative outcome in HFS patients.

Background: Reactivity against terminal NeuNAc(alpha2-3)Gal, common to several gangliosides such as GD1a, GT1b and GM3, have been rarely reported. We recently described a patient with a clinical picture of acute relapsing sensory ataxic neuropathy and bulbar involvement in whom we demonstrated concomitant reactivity against NeuNAc(alpha2-3)Gal and disialosyl epitopes. We suggested a correlation between NeuNAc(alpha2-3)Gal reactivity and bulbar involvement.

Aim: To determine the frequency of reactivity against terminal NeuNAc(alpha2-3)Gal in acute and chronic immune-mediated disorders, and its possible correlation with bulbar involvement.

Methods: We retrospectively reviewed reactivity in the serum of more than 3,000 consecutive patients with acute and chronic disorders in which antiganglioside antibodies were studied. We selected those patients that were simultaneously positive, by ELISA or TLC, for IgG and IgM antibodies anti-GM3, GD1a and GT1b, and we reviewed their clinical features.

Results: Reactivity against NeuNAc(alpha2-3)Gal, shared by GM3, GD1a and GT1b gangliosides, was detected in ten patients: isolated in one patient, and concomitant with reactivity against other gangliosides in the remaining patients. Reactivity against NeuNAc(alpha2-3)Gal was frequently associated (8/10) with symptoms suggestive of bulbar involvement, such as dysphagia, dysarthria or dysphonia. Severe respiratory failure requiring mechanical ventilation was observed in four patients.

Conclusions: Reactivity against the NeuNAc(alpha2-3)Gal epitope is rare and is generally found in association with reactivity against the disialosyl epitope. It can be detected in patients with acute or chronic disorders and could be a serological marker of clinical bulbar involvement and to a lesser extent, associated with the development of severe respiratory failure.

Objective: To determine the risk of cancer before and after the diagnosis of motor neuron disease (MND), multiple sclerosis (MS), and Parkinson’s disease (PD).

Methods: Analysis of statistical database of linked statistical abstracts of hospital and mortality data in an area in southern England.

Results: Only people with PD showed a significant difference in the overall incidence of cancer compared to controls (rate ratio (RR) 0.76, 95 % confidence intervals 0.70-0.82 before PD; RR 0.61, 0.53-0.70, after PD). Rate ratios were close to one for cancer in patients after MND (0.98, 0.75-1.26) and after MS (0.96, 0.83-1.09). There were high rate ratios for malignant brain cancer (RR 7.4, 2.4-17.5) and Hodgkin’s lymphoma (5.3, 1.1-15.6) in patients diagnosed with MND after cancer. In people with MS, malignant brain cancer also showed an increased rate ratio both before hospital admission with a diagnosis of MS (RR 3.2, 1.1-7.6) and after (RR 2.4, 1.2-4.5). In people with PD, several specific cancers showed significantly and substantially reduced rate ratios for cancer, notably smoking-related cancers including lung cancer (RR 0.5, 0.4-0.7, before PD; 0.5, 0.4-0.8, after PD) but also cancers that are not strongly smoking-related including colon cancer (RR 0.7, 0.6-0.9, before PD; 0.5, 0.4-0.8, after PD).

Conclusions: People with MND, or MS, do not have an altered risk of cancer overall. There may sometimes be misdiagnosis between MND or MS and brain tumours. PD carries a reduced risk of cancer overall, of some smoking-related cancers, and of some cancers that are not smoking-related.

The Timed Up and Go (TUG) test has been used to assess balance and mobility in Parkinson’s Disease (PD). However, it is not known if this test is sensitive to subtle abnormalities present in early stages of the disease, when balance and gait problems are not clinically evident but may be detected with instrumented analysis of movement. We hypothesize that postural transitions and arm swing during gait will be the most sensitive characteristics of the TUG for early PD. In the present study, we instrumented the TUG test (iTUG) using portable inertial sensors, and extended the walking distance from 3 meters (traditional TUG) to 7 meters. Twelve subjects with early-to-moderate, untreated PD and 12 healthy individuals participated. Our findings show that although the stopwatch measure of TUG duration did not detect abnormalities in early-to-mid stage PD, the peak arm swing velocity on the more affected side, average turning velocity, cadence and peak trunk rotation velocity were significantly slower. These iTUG parameters were also correlated with the UPDRS Motor Scale. Thus, the iTUG test is sensitive to untreated PD and could potentially detect progression of PD and response to symptomatic and disease-modifying treatments.

Objective: To study mortality and causes of death in an unselected, geographically defined cohort of patients with traumatic spinal cord injury (TSCI) 1952-2001.

Methods: The patients were identified from hospital records. The date of death was obtained from the National Population Register, and causes of death recorded by linkage to the Norwegian Cause of Death Registry. The patient mortality was compared with the mortality in the Norwegian population, using standardized mortality ratios (SMR) adjusted for age and gender.

Results: A total of 401 patients (70 women and 331 men) were identified. By 31 August 2008 173 were dead. The median survival time in deceased patients was 7.4 years; 6.9 years for patients with cervical injuries and 8.2 years for patients with thoracolumbosacral injuries (TLS). TSCI patients had an increased mortality (SMR=1.85) compared to the Norwegian population. SMR did not change during the observation period. SMR was significantly higher for women than for men (2.88 vs. 1.72), and higher in patients with complete TSCI compared to patients with incomplete TSCI (4.23 vs. 1.25). SMR was 6.70 for patients with complete cervical injuries and 3.07 for patients with complete TLS injuries. Cause-specific SMR were 1.96 for respiratory disease, and for suicide including accidental poisoning 3.70 for men and 37.59 for women.

Conclusions: Patients with a TSCI, and especially women, have an increased mortality despite modern treatment and care. Special attention should be paid to respiratory dysfunction and pulmonary infections, and to prevent suicide and accidental poisoning.

Objectives: A serious, catastrophic complications of endoscopic third ventriculostomy (ETV) is basilar artery (BA) damage. Although the BA has been discussed as the cause of hemorrhage and even pseudoaneurysm, variations of the posterior cerebral artery proximal segment (P1) and its protrusion into the third ventricle floor have not been emphasized. The authors report a series of cases in which the P1 segment was located at the stoma during an ETV and was at risk for perforation. Precautionary techniques for complication avoidance are described.

Methods: A retrospective review was performed of all ETVs performed in adults at our institution between 2004 and 2008. Cases were identified in which the P1 segment was noted to herniate into the stoma at the time of third ventricular floor fenestration.

Results: Among 65 cases reviewed, 6 were identified in which the P1 segment significantly herniated into an area of the stoma at the time of third ventricular floor fenestration. In no case was the P1 segment injured by the ETV procedure. Each of the 6 patients had opaque third ventricle floors. A "cookie-cut" technique was used in which the opaque third ventricle floor was abraded to reveal the underlying translucent membrane, offering an improved view of arteries in the basilar cisterns. In 4 of 6 patients, ETV resulted in clinical improvement.

Conclusions: The posterior cerebral artery P1 segment is potentially at risk during ETV in adults as well as children. Awareness and proper precautions may help reduce injuries to either the P1 or the basilar apex during an ETV.

Neuromuscular disorders (NMDs) can lead to specific manual disabilities due to hand muscle weakness and atrophy, myotonia, or loss of sensory function. The aim of this study was to adapt and validate the ABILHAND questionnaire in children and adults with NMDs using the Rasch model. This questionnaire contained specific manual activities for children and for adults, as well as common manual activities. One hundred and twenty-four adult patients and the parents of 124 paediatric patients were asked to provide their perceived difficulty in performing each manual activity on a three-level scale: impossible (0), difficult (1) or easy (2). Items were selected from well-established psychometric criteria (ordered categories, equal item discrimination, adequate fit to the Rasch model, lack of redundancy) using the Rasch Unidimensional Measurement Models (RUMM2020^©) computer programme. The 22 selected items contain 4 children specific items, 4 adult specific items and 14 items commonly applicable to both children and adults. They define a unidimensional and linear measure of manual ability and demonstrate continuous progression in their difficulty. The item hierarchy of difficulty was invariant across six patient-related factors. The scale exhibited good precision (r=0.95) and the 22 items were well targeted to the patients’ locations. The ABILHAND measures were strongly related to the ACTIVLIM measures (r=0.76), and poorly related to grip strength (r=0.36 for the right hand and r=0.40 for the left hand). Moreover, the resulting scale can be used for adults and children, allowing manual ability to be assessed from childhood to adulthood.

Background and purpose: The purpose of this study was to identify the risk factors predisposing to aneurysm rupture and to provide a reliable estimation for likelihood of rupture in unruptured intracranial aneurysms (IAs).

Methods: The authors performed a nested case-control study of 290 aneurysms (123 unruptured aneurysms and 167 ruptured aneurysms) occurring during a prospective cohort study in 1493 consecutive patients who were newly diagnosed with and treated for an IA in a single institute between January 1995 and December 2006. Controls were matched for age, treatment group, number of lesion, sex, region, and study period in which the incidence of ruptured and unruptured IA was equivalently balanced. The authors assessed the predictive risk factors associated with aneurysmal rupture based on the clinical and angiographic findings reported in the patients' medical records.

Results: Between January 1997 and December 2002, 167 patients with ruptured IAs were assigned to group 1, and 123 patients with unruptured IAs during same period were assigned to group 2. Aspect ratio (OR 3.76), maximum diameter of neck (Nmax) ≤ 3 mm (OR 2.56) and family history of cerebrovascular disease (OR 5.63) were strongly correlated with aneurysm rupture (p < 0.05).

Conclusions: There are differences between the clinical and intrinsic characteristics of patients with unruptured and ruptured IA. It will be helpful to make rational decisions regarding the optimal therapeutic strategy for unruptured IA.

Objective: Advanced Parkinson disease (PD) is associated with various motor and nonmotor symptoms which adversely impact health-related quality of life (HRQoL). Subthalamic nucleus (STN) deep brain stimulation (DBS) has been reported to improve some dimensions of HRQoL in appropriately selected candidates. Prior studies of HRQoL following DBS have used instruments comprised of a predetermined list of questions which assess issues that are generally relevant in PD, but that may not be of equal or consistent importance to all individuals. In this study we evaluate the effect of STN DBS on quality of life using the QLS^M, a modular questionnaire in which satisfaction scores for each item are weighted in light of patient-rated importance.

Methods: We prospectively analyzed QLS^M scores in 21 patients with PD (11 men, mean age 61.5 ± 8.6 years) before STN DBS surgery and at a mean 7.4 ± 1.5 and again at a mean 16.6 ± 6.8 months postoperatively.

Results: Following STN DBS, patients experienced an improvement in HRQoL as measured by various items of the movement disorder and health modules of the QLS^M. Specifically, QLS^M items pertaining to energy level/enjoyment of life, independence from help, controllability/fluidity of movement, and steadiness when standing and walking showed significant improvements, although items concerning general life issues (e.g. occupational function, interpersonal relationships, leisure activities) did not improve.

Conclusion: Following STN DBS, symptomatic and functional improvements translate into higher HRQoL, with high satisfaction in domains related to movement disorders and general health.

Gustatory event-related potentials (ERPs) have been developed more than a decade ago. Although first studies were highly promising no clinical routine application has yet been reported. We aimed to use gustatory ERP in a clinical setting and to investigate, gender-related differences, concentration dependency, and their test-retest reliability. We further addressed the question whether investigations in patients with documented taste disorders provide meaningful results.

Seventeen healthy volunteers participated in two sessions. Acetic acid was presented to the left or right portion of the tongue; stimuli were embedded in a constantly flowing air stream. Subjects rated the stimulus intensity using visual analogue scales. Lateralized sour thresholds were established by means of a psychophysical taste test.

ERP amplitude P1 was largest at fronto-central recording sites while amplitude P2 had a parietal maximum. Women had shorter response latencies than men. Concentration-related differences were found for amplitudes P2, and for latencies P1, and N1. Shorter ERP response latencies were seen for stimulation of the right compared to the left side. Test-retest reliability was highest for the higher stimulus concentration, and highest coefficients of correlation were found for latencies of ERP peaks P1 and N1. Preliminary investigations in a patient with hemiageusia indicated the usefulness of gustatory ERPs in the diagnostic process, especially with regard to medico-legal cases.

In conclusion, the present work shows that gustatory ERP provide a relatively unbiased, reliable and easy approach to objective assessment of human taste function.

Objective: To determine the responses to treatment of patients with chronic sensory ataxic neuropathy associated with anti- GD1b IgM antibodies.

Methods: Patients with chronic sensory ataxic neuropathy associated with anti- GD1b IgM antibodies followed in our department for at least 12 months between 2001 and 2008 were identified and studied retrospectively. Patients were tested at regular intervals using the INCAT disability score. Patients whose disability scores improved by at least one point were taken to have responded to the treatment. Intravenous immunoglobulin (IVIg; 2 g/kg) was administered for 3 to 5 days once every 6 weeks or corticosteroids at an initial daily dose of 1 mg/kg.

Results: 13 patients treated during the 8-year period of interest were included in this study. 7 of 13 patients displayed IgM anti-GQ1b, GT1b and GD3 antibodies suggesting reactivity against disialosyl epitope. IgM gammopathy was detected in 4 of 6 of serum with anti-disialosyl antibodies and 2 of the 7 other sera. 9 of the 13 patients improved in response to IVIg. Oral corticosteroid treatment was attempted on 4 patients prior to IVIg treatment, and partial recovery occurred in one, who became steroid-dependent and showed little benefit in the long term.

Conclusions: Screening for anti-GD1b IgM antibodies should be carried out on all patients with chronic ataxic sensory neuropathies. In 69% of the cases studied, the patients’ condition improved in response to IVIg. This study shows the short term efficiency of this treatment. Sustained responses were obtained in the long term by continuing the infusions.

Objective: To investigate the effects of topiramate on Tourette syndrome.

Background: Dopamine receptor blocking drugs have been traditionally used to control tics in patients with TS, but these neuroleptics are associated with potentially limiting side effects.

Methods: This is a randomized, double-blind, placebo-controlled, parallel group study. To be included in the study, subjects required a DSM-IV diagnosis of TS, were 7-65 years of age, had moderate to severe symptoms (Yale Global Tic Severity Scale or YGTSS >19), were markedly impaired as determined by the Clinical Global Impression (CGI) scale severity score of >4, and were taking no more than one drug each for tics or TS co-morbidities.

Results: There were 29 patients (26 males), mean age 16.5 ± 9.89, randomized and 20 (69%) completed the double-blind phase of the study. The primary endpoint was Total Tic Score, which improved by 14.29 ± 10.47 points from baseline to visit 5 (day 70) with topiramate (mean dose 118 mg) compared to 5.00 ± 9.88 point change in the placebo group (p = 0.0259). There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures, including the CGI and premonitory urge CGI. No differences were observed in the frequency of adverse events between the two treatment groups.

Conclusion: This double-blind, placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS.

Objective: To examine rates of decline in individuals at-risk for Huntington disease (HD).

Methods: 106 individuals at-risk for HD completed a battery of neurocognitive, psychomotor, and oculomotor tasks at two visits, approximately 2.5 years apart. Participants were classified as: 1) without the CAG expansion (normal controls, NC; n=68), or 2) with the CAG expansion (CAG+; n=38). The CAG+ were further subdivided into those near to (Near; n=19) or far from (Far; n=19) their estimated age of onset. Longitudinal performance in the CAG+ was evaluated with a repeated measures model with two main effects (time to onset, visit) and their interaction. Analysis of covariance was employed to detect differences in longitudinal performance in the three groups (NC, Near and Far).

Results: In the CAG+, the interaction term was significant (p≤0.02) for 4 measures (movement time, alternate button tapping, variability of latency for a memory guided task and percentage of errors for a more complex memory guided task), suggesting the rate of decline was more rapid as subjects approached onset. Longitudinal progression in the three groups differed for several variables (p<0.05). In most, the Near group had significantly faster progression than NC; however, comparisons of the NC and Far groups were less consistent.

Conclusions: Different patterns of progression were observed during the prediagnostic period. For some measures, CAG+ subjects closer to estimated onset showed a more rapid decline while for other measures CAG+ had a constant rate of decline throughout the prediagnostic period that was more rapid than in CAG- subjects.

Background: Geographical differences in amyotrophic lateral sclerosis (ALS) incidence have been reported in the literature, but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied populations. To address these issues, the authors undertook a pooled-analysis of European population-based ALS registries.

Methods: All new incident ALS cases in subjects 18 years old and older were identified prospectively in six population-based registries in three European countries (Ireland, United Kingdom, Italy) in the two year period 1998-1999 with a reference population of almost 24 million.

Results: Based on 1,028 identified incident cases, the crude annual incidence rate of ALS in the general European population was 2.16 per 100,000 person-years; 95% CI 2.0-2.3), with similar incidence rates across all registries. The incidence was higher among men (3.0 per 100,000 person-years; 95% CI = 2.8 to 3.3) than among women (2.4 per 100,000 person-years; 95% CI=2.2 to 2.6). Spinal onset ALS was more common among men compared to women, particularly in the 70-80 year age group. Disease occurrence decreases rapidly after 80 years of age.

Conclusions: ALS incidence is homogeneous across Europe. Sex differences in incidence may be explained by the higher incidence of spinal onset ALS among males and the age-related disease pattern suggests that ALS occurs within a susceptible group within the population rather than being a disease of aging.

Background and purpose: The pathogenesis of cerebral small vessel disease (SVD) is incompletely understood. Endothelial dysfunction has been implicated and may result in increased blood-brain barrier (BBB) permeability with leakage of blood constituents into the vessel wall and white matter. We used contrast enhanced magnetic resonance imaging (MRI) to determine whether there was evidence for BBB permeability in the white matter of patients with SVD, and whether this was present not only in areas of leukoaraiosis (white matter lesions,WML) but also in normal appearing white matter (NAWM).

Methods: Subjects underwent T1 volumetric MRI before and after bolus injection of contrast. Scanning was continued for 30 minutes post injection to determine the contrast enhancement time course. Mean signal intensity change was plotted against time to calculate area under curve (AUC) values, a parameter related to BBB permeability. Automated brain segmentation and regions of interest analysis were performed to determine "permeability" in different brain compartments.

Results: Compared to controls (n=15), the SVD patient group (n=24) had signal changes consistent with increased BBB permeability in NAWM (P = 0.033). Multivariate regression analyses identified leukoaraiosis grade as an independent predictor of these permeability related signal changes in NAWM after adjustment for age, gender, weight, brain volume, AUC in the internal carotid arteries, and cardiovascular risk factors.

Conclusion: This study provides evidence for increased BBB permeability in SVD, and this is particularly seen in SVD with leukoaraiosis. Its presence in NAWM would be consistent with it playing a causal role in disease pathophysiology.

Objectives: To characterize West Australian cases of longitudinally extensive myelopathy (LEM).

Methods: Twenty six patients with LEM were identified from a cohort of 983 patients with demyelinating disease. Clinical and MRI data and AQP4-IgG results were reviewed.

Results: LEM cases were classified as conventional MS (CMS) 13, neuromyelitis optica (NMO) 7, and isolated LEM 6. LEM was the initial presentation in 13/26 cases. In CMS cases lesions were mainly in the lower cervical cord (C4-C7) whereas in NMO and isolated LEM they were more often thoracic and were longer. The severity of disability was highly variable but was greater in the NMO than the CMS group. Only one of 20 patients tested was seropositive for AQP4-IgG.

Conclusion: LEM occurred as part of CMS or NMO or in isolation. Patients with LEM had highly heterogeneous clinical characteristics and a low rate of AQP4-IgG seropositivity.

Background: The ratio of female to male (F:M) MS cases varies geographically, generally being greater in areas of high prevalence. In many regions, including Canada, rising MS incidence in women has been implied by the marked increase in F:M ratio.

Methods: We examined the F:M ratio over time in MS patients in the Canadian Collaborative Study born outside of Canada, with onset post-migration (n=2531). We compared the (y.o.b.) was a significant predictor of sex ratio in immigrants ( 2 = 21.4, p<0.001 correlation r= 0.61). The rate of change of sex ratio was increasing in all migrant subgroups (by a factor of 1.16 per 10y period, p<0.001), with the steepest increase observed in those from Southern Europe trends to native-born Canadians, by region of origin and age at migration.

Results: Regression analysis showed that year of birth (1.27/10y, p<0.001). The overall immigrant F:M ratio was 2.17, but varied by country of origin. It was significantly lower in migrants from Southern Europe compared to Northern Europe or USA (1.89 vs 2.14 and 2.86, p=0.023 and p=0.0003, respectively). Increasing age at immigration was associated with decreasing sex ratio (p=0.041). The sex ratio of individuals migrating <21 was significantly higher than those migrating ≥21 (2.79 vs 1.96, p=0.004).

Conclusions: MS Sex ratio in immigrants to Canada is increasing but variable by region of origin and influenced by age at migration. The findings highlight the importance of environmental effect(s) in MS risk, which are likely gender-specific.

Background: Diffusion tensor imaging (DTI) is a sensitive method for detecting white matter damage, and in cross-sectional studies DTI measures correlate with age-related cognitive decline. However, there is little data on whether DTI can detect age-related changes over short time periods, and whether such change correlates with cognitive function.

Methods: In a community sample of 84 middle-aged and elderly adults MRI and cognitive testing was performed at baseline and after two-years. Changes in DTI white matter histograms, white matter hyperintensity (WMH) volume and brain volume were determined. Change over time in performance on tests of executive function, working memory and information processing speed were also assessed.

Results: Significant change in all MRI measures was detected. For cognition, change was detected for working memory and this correlated with change in DTI only. In a stepwise regression, with change in working memory as the dependent variable, a DTI histogram measure explained 10.8% of the variance in working memory. Change in WMH or brain volume did not contribute to the model.

Conclusions: DTI is sensitive to age-related change in white matter ultrastructure and appears useful for monitoring age-related white matter change even over short time periods.

Objective: To report our experiences in the treatment of recurrent intracranial aneurysms with re-coiling or covered stents.

Methods: A total of 291 patients with 305 intracranial aneurysms were treated with detachable coils, and 41 (28.9%) of 142 patients with aneurysms in the internal carotid artery (ICA) had a recurrent aneurysm during the follow-up period. For this study, 31 recurrent aneurysms in 31 patients who had angiograms within six months following retreatment with detachable coils (group A, n = 20) or covered stents (group B, n =11) were analyzed. Aneurysms were categorized as complete or incomplete occlusion via angiographic assessment and graded as full recovery, improvement, no change, or deterioration via clinical assessment. Data regarding technical success, initial and final angiographic results, mortality, morbidity, and final clinical outcome were collected and analyzed postoperatively.

Results: Coil embolization and covered stent placement were technically successful in all recurrent aneurysms. The initial angiographic results showed complete occlusion in 11 patients (55%) in group A and 8 (72.7%) in group B (P= 0.452), and the final angiographic results exhibited complete occlusion in 10 patients (50%) in group A and 11 (100 %) in group B (P= 0.005). There were no significant differences in technique success, mortality, culminate morbidity, or final clinical outcome between the two groups.

Conclusions: Recurrent aneurysms after coiling can be successfully treated and occluded with re-coiling or covered stent placement. However, covered stents seem to be more effective than re-coiling with regard to complete occlusion of recurrent aneurysms.

Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Whether this condition involves abnormal cardiac sympathetic innervation or function remains elusive. Metaiodobenzylguanidine (MIBG) resembles guanethidine and is a pharmacologically inactive analogue of norepinephrine, which is similarly metabolized in noradrenergic neurons. MIBG myocardial scintigraphy is clinically used to estimate local myocardial sympathetic nerve damage in some forms of heart disease and autonomic neuropathy. Our objective was to evaluate cardiac sympathetic innervation in POTS-patients.

Methods: We studied twenty patients with POTS using 123I- MIBG-SPECT, standardized autonomic testing, assessment of catecholamine plasma levels and sympathetic skin response.

Results: In four POTS-patients (20.0 %) myocardial MIBG uptake was markedly decreased. The mean heart-to-mediastinum ratio was reduced to 1.22 ± 0.08 compared to the normal range of >1.7. We found no correlation between myocardial MIBG uptake and degree of postural tachycardia, baroreflex sensitivity, catecholamine plasma levels or other autonomic parameters. Sympathetic skin responses were normal in all patients.

Conclusions: These findings suggest that POTS may be, in part, a manifestation of autonomic cardiac neuropathy. MIBG myocardial scintigraphy may be helpful to distinguish patients with neuropathic POTS from patients with orthostatic intolerance of other origin.

Many patients with minor stroke are referred to outpatient clinics and are therefore not scanned immediately. A clinical rule is needed to identify patients who are likely to have intracerebral haemorrhage (ICH) and require urgent brain imaging, and patients who can safely start antiplatelet agents prior to scanning.

Methods: We determined clinical factors associated with ICH in 334 consecutive patients with minor stroke (NIHSS≤3) in the OXVASC Study, and derived a predictive model for ICH which was validated in a cohort of 280 patients presenting to a hospital-stroke clinic. Prognostic value was quantified as the area under the ROC curve (c statistics).

Results: The rate of ICH in minor stroke was 5.1% (95%CI 3.2-8.0%) in OXVASC, and 5.4% (3.3-8.7%) in the clinic cohort. Clinical factors predictive of ICH in OXVASC included BP on initial assessment ≥180/110mmHg (OR=14.5, 95%CI 1.8-114, p=0.001), vomiting (OR=15.7, 5.4-46, p<0.001), confusion (OR=8.2, 2.9-23, p<0.001), and anticoagulation use (OR=7.8, 2.2-28, p=0.006), and at least one predictive factor was identified in all 17 patients with ICH and in 35% overall; c statistic 0.92 (95% CI 0.88-0.97). Therefore, we derived the SCAN rule to identify ICH if ≥1 of the following were present: (S) systolic BP ≥180mmHg or diastolic BP ≥ 110mmHg, (C) confusion, (A) anticoagulation, (N) nausea and vomiting. In the clinic validation cohort, ≥1 predictive factor was identified in 14/15 of patients with ICH and in 24% overall; c statistic 0.87 (0.79-0.95).

Conclusion: The SCAN rule appears to be specific and sensitive at identifying ICH in an independent cohort of patients with minor stroke, although further independent validations are needed.

Background: MR diffusion and perfusion imaging are used to identify ischemic penumbra, but there are few comparisons with neuronal loss and ischaemia in vivo. We compared N-acetyl aspartate (NAA, found in intact neurons) and lactate (anaerobic metabolism) with diffusion/perfusion parameters.

Methods: We prospectively recruited patients with acute ischemic stroke and performed MR diffusion tensor, perfusion (PWI) and proton chemical shift spectroscopic imaging (CSI). We superimposed a 0.5 cm voxel grid on the diffusion-weighted images (DWI) and classified voxels as ‘definitely abnormal’, ‘possibly abnormal’, or normal on DWI appearance, and ‘mismatch’ for voxels in DWI/PWI mismatch areas. We compared metabolite (NAA, lactate), perfusion and ADC values in each voxel type.

Results: NAA differentiated ‘definitely’ from ‘possibly abnormal’, and ‘possibly abnormal’ from ‘mismatch’ (both comparisons p<0.01) voxels, but not ‘mismatch’ from ‘normal’ voxels. Lactate was highest in ‘definitely abnormal’, and progressively lower in ‘possibly abnormal’, ‘mismatch’, then ‘normal’ voxels (all differences p<0.01). There was no correlation between NAA and ADC or PWI values, but high lactate correlated with low ADC (Spearman ñ=-0.41, p=0.02) and prolonged MTT (Spearman ñ=0.42, p=0.02).

Conclusion: ADC and MTT indicate the presence of ischemia (lactate) but not cumulative total neuronal damage (NAA) in acute ischemic stroke, suggesting that caution is required if using ADC and PWI parameters to differentiate salvageable from non-salvageable tissue. Further refinement of the DWI/PWI concept is required prior to more widespread use.

Objective: To assess the ability of potentially neuroprotective compounds to slow the progression of Parkinson’s disease (PD), sensitive rating scales are needed to detect clinically meaningful effects. We evaluated the topographical progression of motor signs in early untreated PD to complement current clinical ratings and enhance the sensitivity to detect disease progression.

Methods: Twelve patients referred for diagnostic evaluation of so far untreated de novo PD underwent detailed clinical assessment of motor parkinsonian signs at baseline, 6, and 12 months’ follow-up using the Unified Parkinson’s Disease Rating Scale, motor part (UPDRS-III), and a newly developed approach of detailed segmental rating taking into account the localization of motor signs in all the major joints and muscle groups in the body. The progression of PD as measured with the UPDRS-III was compared to the segmental ratings.

Results: UPDRS-III scores and segmental ratings for rigidity and rest and postural tremor, but not bradykinesia, progressed significantly during the observation period. Progression of normalized segmental ratings for rigidity and tremor was significantly larger than the UPDRS-III ratings over one year. The segmental ratings for rigidity and tremor as well as their combination with the UPDRS-III bradykinesia rating were more sensitive a measure for progression of PD than the UPDRS-III.

Conclusions: Taking into account the segmental evolution of parkinsonian signs may be a useful adjunct to UPDRS-III evaluations to measure clinical disease progression of PD. If validated in subsequent, larger cohorts, this may be useful in trials of neuroprotective agents.

Reading epilepsy is a rare form of epilepsy, classified among idiopathic, age- and localisation-related (partial) epilepsies as a reflex epilepsy syndrome. Seizures usually consist of myoclonic jerks restricted to the jaw. However, distinct ictal features including visual symptoms and paroxysmal a- or dyslexia are described in some patients. The anatomical substrate of ictogenesis in reading epilepsy remains poorly understood.

We report here the case of a primary reading epilepsy for which ictal semiology was characterized by visual symptoms and dyslexia, investigated by MRI, interictal high-resolution EEG and PET, ictal video-EEG and SPECT. Brain MRI was normal. Interictal high resolution EEG was performed with 64 scalp channels, a realistic head model and different algorithms to solve the inverse problem. Interictal source localizations highlighted the left occipito-temporal junction. Interictal PET demonstrated bilateral occipito-temporal hypometabolism with left-sided predominance. Ictal EEG showed a rhythmic discharge in left temporo-parieto-occipital junction channels, with left occipito-temporal predominance. MRI fusion of the co-registered subtraction between ictal and interictal SPECT individualized relative hyperperfusion affecting (a) the left occipito-parietal junction area (b) the left lateral middle and inferior temporal gyri and (c) the left inferior frontal area.

Besides reading-induced myoclonic jerks of the jaw, a second variant of reading epilepsy exists with clearly partial seizures manifested by visual symptoms and a- or dyslexia. These seizures originate from the occipito-temporal region of the dominant hemisphere, corresponding to the posterior part of the neural network that underlies the function of reading.

Objective: To evaluate clinimetric properties of the Rehabilitation Complexity Scale (RCS) in a neurorehabilitation inpatient sample.

Design: An observational cohort analysis in a tertiary specialist setting.

Subjects: 179 consecutive patients (mean age 44.5(sd15) years, Males:Females 110:69) with complex neurological disabilities, mainly following acquired brain injury.

Methods: Repeat RCS ratings of the level of care, nursing, therapy and medical interventions were examined for dimensionality, repeatability, consistency, and responsiveness; and compared with the Northwick Park Nursing and Therapy Dependency Scales (NPDS and NPTDA), the Functional Independence Measure (FIM) and Barthel Index, recorded at the start and end of treatment.

Results: Test-retest reliability confirmed the RCS to be repeatable (Kappa 0.93-0.96) and moderately responsive to changes in levels of intervention over the course of the programme, suggesting the need for serial evaluation. Coefficient-alpha was 0.76 and item-total correlations all >0.50, with moderate-high loadings on the first principal component. Factor analysis showed two clear factors (‘Nursing/medical care’, and ‘Therapies’). The RCS demonstrated good convergent and discriminant validity with the NPDS and NPTDA, but some ceiling effect. FIM motor and Barthel scores correlated well with basic care and nursing scores (Spearman rho -0.65 to -0.79), but less well with therapy (rho -0.26) and medical (rho -0.28 to -0.33) scores.

Conclusion: In this cohort, the RCS provided a reliable, valid and moderately responsive profile of rehabilitation interventions, separating into two main subscales. It usefully identified medical and therapy inputs not captured by the FIM and BI, which are commonly used to define case complexity in rehabilitation.

Background: Diffusion tensor (DT) MRI enables to quantify the severity of brain and cervical cord pathology in MS.

Objective: To investigate the DT MRI patterns of cervical cord damage in benign MS (BMS) and secondary progressive MS (SPMS) patients, in order to achieve a better understanding of the mechanisms underlying the development of irreversible disability in MS.

Methods: Conventional and DT MRI scans of the cervical cord and brain were acquired from 40 BMS patients, 28 SPMS patients and 18 healthy individuals. Cervical cord and brain mean diffusivity (MD) and fractional anisotropy (FA) maps were created and average MD and FA were calculated. Cross-sectional cord area (CSA) was also computed.

Results: Thirty-seven (92%) BMS patients and all (100%) SPMS patients had macroscopic cervical cord lesions. Compared to healthy individuals, BMS patients had higher average cord MD, while SPMS patients had higher average cord MD, lower average cord FA and lower average CSA. Compared to BMS patients, SPMS patients had lower cord average FA and lower average CSA. In MS patients, expanded disability status scale (EDSS) was correlated with CSA (r=-0.47, p<0.0001), average cord FA (r=-0.37, p=0.002) and brain T2 lesion volume (LV) (r=0.34, p=0.005). A multivariate regression model identified CSA, average cord FA and brain T2 LV as variables influencing independently the EDSS score (r=0.58, p<0.0001).

Conclusions: Cervical cord damage outside focal macroscopic lesions is limited in patients with BMS. The assessment of cord and brain pathology provides complementary information to improve the understanding of disability accumulation in MS.

Mutations in the dysferlin gene lead to limb-girdle muscular dystrophy 2B, Miyoshi Myopathy and distal anterior compartment myopathy. We here describe a cohort of 36 patients affected by dysferlinopathy in the first UK study of clinical, genetic, pathological, and biochemical data. The diagnosis was established by reduction of dysferlin in the muscle biopsy and subsequent mutational analysis of the dysferlin gene. 17 mutations were novel; the majority of mutations were small deletions/insertions, and no mutational hotspots were identified. 61% of patients (22 patients) initially presented with LGMD2B, 31% (11 patients) with a Miyoshi phenotype, one patient with proximodistal mode of onset, one patient with muscle stiffness after exercise, and one patient as a symptomatic carrier. A wider range of age of onset was noted than previously reported with 25% of patients having first symptoms before the age of 13 years. Independent of the initial mode of presentation, in our cohort of patients the gastrocnemius muscle was the most severely affected muscle leading to an inability to stand on tiptoes, and lower limbs were affected more severely than upper limbs.

As previous anecdotal evidence on patients affected by dysferlinopathy suggests good muscle prowess before onset of symptoms, we also investigated pre-symptomatic fitness levels of the patients. 53% of the patients were very active and sporty before onset of symptoms which makes the clinical course of dysferlinopathy unusual within the different forms of muscular dystrophy and provides a challenge to understanding the underlying pathomechanisms in this disease.

Objective: To find predictors of cognitive decline and quality of life one year after bilateral subthalamic nucleus stimulation (STN DBS) in Parkinson’s disease (PD).

Methods: A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery. A control group of 40 PD patients was included to control for effects of repeated testing and disease progression. We determined individual changes in cognition, mood and quality of life using a statistical method that controls for multiple comparisons. We performed logistic regression analyses to assess predictors of cognitive changes and quality of life.

Results: Twelve months after surgery, the improvement in motor function was 41% (UPDRS3 score in off). The STN group showed a large improvement in quality of life compared to the control group (Cohen’s d=0.9). At the individual level, 32 percent (95% CI: 22 – 40) of the STN group showed a substantial improvement in quality of life. Thirty six percent (95% CI: 27 - 46) of the STN patients showed a profile of cognitive decline compared to the control group. Mood improved in 16 STN patients and declined in 16 subjects. Impaired attention, advanced age and a low levodopa response at baseline predicted cognitive decline, whereas a high levodopa response at baseline predicted improvement in quality of life. Postoperative decrease in dopaminergic medication was not related to cognitive decline.

Conclusions: STN DBS improves quality of life. However, a profile of cognitive decline can be found in a significant number of patients. Levodopa response, age and attention at baseline are predictors of cognitive and psychosocial outcome.

Objectives: The possibility of vertical transmission of variant CJD (vCJD) has been raised, because of the widespread distribution of infectivity in vCJD and the demonstration that this condition can be transmitted through blood transfusion. The aim is to search for evidence of this type of transmission of vCJD.

Methods: A national surveillance system for CJD has been established in the UK since 1990. Through this register details were extracted of all children born to vCJD cases up to March 2009. This list was checked against the CJD register and cases identified through the UK study of progressive intellectual and neurological deterioration in children (PIND) to determine whether any of the children of vCJD cases had themselves developed a progressive neurological disorder or vCJD.

Results: 125 children have been born to parents with a diagnosis of vCJD. Nine of these children were born to females with vCJD who were symptomatic at conception, birth or within a year of clinical onset. Only one woman was known to have breast fed her child. None of the children of vCJD cases have been referred to the NCJDSU as suspected vCJD and none have been classified as suffering from a progressive neurodegenerative disorder through the PIND study. One of the children has been investigated by the National Prion Unit (see accompanying case report).

Interpretation: To date there is no evidence of vertical transmission of vCJD. However, the incubation period through this mechanism might be prolonged and it will be many years before observational data can exclude this possibility.

Objective: Paraneoplastic neurological syndromes (PNS) probably result from an immune reaction against antigens shared by the nervous system and tumour cells. To characterize CSF alterations in these syndromes, we studied a large series of paraneoplastic patients.

Methods: Using the PNS European database which includes patients diagnosed with PNS in Europe, we reviewed the clinical data of all patients included between 2000 and 2007 for which information on the CSF was available. Patients were studied if they met the following inclusions criteria: a) definite paraneoplastic disease with anti-Hu, anti-Yo, anti-CV2, anti-Ri anti-Ma/Ta and anti-Tr antibodies; b) clinical information available; c) at least 1 CSF study.

Results: 295 patients met the inclusion criteria. Abnormal CSF (pleiocytosis and/or high protein level and/or oligoclonal bands) was found in 93% of the patients. Pleiocytosis, but not hyperproteinorachia, was more frequently seen in patients in whom the CSF study was done early in the evolution. In 24 patients, OCB were the only abnormality found in the CSF (10%). Elevated numbers of cells were found in 47% of the patients before the 3rd month, vs 28% after the 3rd month (p<0.01). This evolution might suggest a sub-acute inflammation phase within the nervous system, followed by a non-inflammatory phase. The inflammation profile was similar in all antibody types, cancers or neurological syndromes of the PNS. Surprisingly, anti-Hu patients with high pleiocytosis at time of diagnostic had a better survival in this study than those without pleiocytosis, (572 days vs 365 days, p=0.05).

Conclusion: CSF inflammation is a common finding in PNS patient and can be a helpful tool for the diagnosis, especially if this analysis is done within 3 months after neurological onset.

Objective: The striatum, and its projections, are thought to be the earliest sites of Huntington’s disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging.

Method: Diffusion weighted images were acquired in 18 HD patients and 17 healthy controls twice, one year apart. Mean diffusivity (MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures.

Results: MD was significantly higher in caudate and putamen bilaterally for patients, compared to controls, at both time points, although there were no significant MD differences in thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year one. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini Mental State Examination scores and caudate MD and putamen MD at both time points in HD.

Conclusions: We report that microstructural changes influence the cognitive status in HD. Although MD was significantly higher in HD, compared to controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.

Background: Diminished ability to perceive one’s own impairments, whether cognitive or social, is common in dementia, in particular frontotemporal dementia (FTD), where "lack of insight" is listed as a core diagnostic feature. Yet, there is no currently accepted method for measuring insight in dementia. The most commonly used methods, which involve comparing patients’ opinions of their level of impairment with the opinions of caregivers or close family members, are subjective and require the participation of a knowledgeable informant. Here, we introduce a new method that allows objective quantification of an individual’s awareness of their cognitive abilities and relies upon objective bedside testing.

Methods: We administered several tests of everyday, real-world functions to patients with FTD (n=10), Alzheimer’s disease (AD, n=10) and to control subjects (n=10). Prior to the tasks, participants were asked to predict their performance using a percentile-based rating system. They were also asked to estimate their performance after task completion. Differences between their self-rated and actual performances were calculated.

Results: Whereas the control group showed very little discrepancy between pre-test predictions, post-task estimates and actual performance (mean difference of 3.9 percentile points for prediction /3.0 percentile points for post-task estimate), both patient groups over-predicted and overestimated their performance, with a significantly greater discrepancy for FTD (49.0/54.3 percentile points) than AD (27.2/28.3 percentile points).

Discussion: Failures of insight and self-awareness of cognitive dysfunction can be objectively measured in dementia without the assistance of an informant, which will facilitate further study of this key component of higher cognitive functioning.

Neurological involvement in sarcoidosis is serious and often aggressive. Many patients respond to steroids, but some show a progressive course despite treatment with steroids and even more potent immunosuppressive drugs. We aimed to describe our experience in the treatment of refractory neurosarcoidosis with Infliximab; its effect on the course of the disease and side effects. We report a series of four patients with neurosarcoidosis refractory to treatment with steroids combined with various immunosuppressive drugs in whom Infliximab was used. A good response, with improvement or stabilization of the neurological condition was seen in all cases, without significant side effects. Infliximab is a chimeric monoclonal antibody that neutralises the biological activity of TNF-, a cytokine thought to play an important role in the pathophysiology of sarcoidosis. Our experience using infliximab adds to growing evidence that it may fulfil a useful role in cases of refractory neurosarcoidosis.

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.

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.

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Objectives: Gait and mobility problems remain difficult to treat in people with Parkinson’s disease (PD). The RESCUE-trial investigated the effects of a home physiotherapy program based on rhythmical cueing on gait and gait-related activity.

Methods: A single-blind randomized cross-over trial was set up, including 153 patients with PD aged between 41 and 80 years and in Hoehn & Yahr stage II to IV. Subjects allocated to early intervention (N=76) received a three-week home cueing program using a prototype cueing device followed by three weeks without training. Patients allocated to late intervention (N=77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a six week follow-up without training. Posture and Gait scores (PG-scores) measured at 3, 6, and 12 weeks by blind testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain.

Results: Small but significant improvements were found after intervention of 4.2% on the PG-scores (p=0.005). Severity of freezing was reduced by 5.5% as measured in freezers only (p=0.007). Gait speed (p=0.005), step length (p<.0001) and timed balance tests (p=0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p=0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention reduced significantly at 6 week follow-up.

Conclusions: Cueing training in the home has specific effects on gait, freezing and balance. The wearing off of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in PD.

Objectives: Examine the utility of baseline factors to predict disease progression among a clinical cohort of individuals diagnosed with essential tremor (ET).

Measures: Tremor Rating Scale (TRS). Methods. A clinical series of 128 consecutive individuals diagnosed with ET were included for study. A total of 45 (35%) individuals had at least one follow-up exam (mean = 3.6 years). Baseline predictive factors examined included age, age at symptomatic onset, disease duration, sex, handedness, total tremor rating score, asymmetric tremor ratings, location of initial tremor onset, movement disorder medication usage, ETOH responsiveness of tremor, head or neck tremor involvement, depression history, and familial history of essential tremor, Parkinson’s Disease, Alzheimer’s Disease, and other movement disorders. Results. On average, the TRS total score increased by less than one point per year prior to the first clinic visit and about 2 points per year during the observed study period. The 2 points per year increase during the observed study period represented about a 12% annual change from the mean TRS total score at the first clinic visit. Significant (p < .05) predictive factors associated with increased tremor severity at the initial clinic visit included an older age, a longer disease duration, use of movement disorder medication, and the presence of voice tremor (rs = .24, .27, .25, .19). The significant factors associated with an increase in tremor severity from the initial clinic visit to the last follow-up included asymmetrical tremor ratings, unilateral initial tremor onset, and a longer follow-up duration (rs = .32, .31, .30). Multivariable regression analysis accounted for about 17% to 30% of the variance in tremor ratings (p < .05).

Conclusion: ET is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course.

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