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Proceedings of the Association of British Neurologists, Queens University of Belfast, Ireland, 30 March to 1 April 2005

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The abstracts are published as supplied by the Association of British Neurologists; they have been formatted for consistency.Every effort has been made to reproduce the abstracts faithfully; however, no responsibility is assumed by the publishers or editor for any injury and/or damage to persons or property as a matter of product liability, negligence or otherwise, or from any use or operation of any methods, products, instruments, or ideas contained in the material herein. We recommend independent verification of diagnoses and drug dosages.

001 EMAIL TRIAGE FOR NEW NEUROLOGICAL OUTPATIENT REFERRALS: WHAT THE CUSTOMERS THINK

L. A. Loizou, V. Patterson, C. Donaghy, K. Zoniou.Royal Victoria Hospital, Belfast, Ireland; Pinderfields Hospital, Wakefield, UK

The waiting time to see a neurologist in the UK is still unduly long and this delay is problematic for patients, general practitioners (GPs), neurologists, health authorities, and politicians alike. Increasing neurologist numbers is one possible solution but email triage of new referrals is another. This has been shown to prevent 50% of referrals entering the hospital clinic system and is safe, efficient, and sustainable. One of the objections to it is that patients and their GPs will be unhappy with a system in which the patients are not seen. To test this we asked patients waiting to see a neurologist and also GPs which system they would prefer in both Wakefield and Northern Ireland. We made explicit the trade-off between a rapid response and the possibility of not being seen (the email system), and a less rapid response with the guarantee of being seen (the conventional system). 86% of patients and 61% of GPs preferred the email system. Patient preference was similar in Wakefield and Northern Ireland but more GPs in Northern Ireland preferred the email system (80% vs 49%). These results should encourage neurologists who wish to try out an email triage system for new patient referrals.

002 THE ABILITY OF A NURSE SPECIALIST TO DIAGNOSE SIMPLE HEADACHE DISORDERS COMPARED WITH CONSULTANT NEUROLOGISTS

D. J. Nicholl, J. Edwards, A. Sivaguru, P. Davies, C. Wiskin, C. E. Clarke.Department of Neurology, City Hospital, Birmingham, UK; Departments of Clinical Neurosciences, Primary Care and General Practice, Institute of Child Health, University of Birmingham, UK

Objectives: Headache disorders account for 39% of our new neurology outpatient referrals. Can a Headache Nurse Specialist be trained to diagnose migraine and tension headache to relieve pressure on neurologists?

Methods: An experienced neurology ward sister was trained in the differential diagnosis of headache. Over 6 months, patients with non-acute headache disorders were seen by both the nurse and a consultant neurologist. Both reached an independent diagnosis after history and examination. Since serious causes of headache disorder are rare, role players were included who had been trained to present with either benign or sinister headaches.

Results: Consultants diagnosed 239 patients with tension headache (47%), migraine (39%), or other disorders (14%). The nurse agreed with the consultant in 92% of tension headache subjects, 91% of migraineurs, and 61% of other diagnoses. Both the nurse and the consultant misdiagnosed the same 3/13 role players. The investigation rate varied between 18–59% for individual consultants. Only 1/69 head scans (CT/MRI) showed a clinically relevant abnormality, and this was strongly suspected clinically.

Conclusions: A nurse can be trained to diagnose tension headache and migraine. A nationwide nurse-led diagnostic headache service could lead to substantial reduction in neurology waiting times. There needs to be debate about what proportion of patients with headache should undergo neuro-imaging.

003 COULD ANALYSIS OF OCULAR FIXATION IMPROVE THE CLINICAL DIAGNOSIS OF PARKINSONISM?

J. M. Gibson, R. C. McGivern.Royal Hospitals Trust, Belfast, Ireland; N I Regional Medical Physics Agency, Royal Hospitals Trust, Belfast, Ireland

Simple non-invasive quantitative tests are needed in parkinsonism to aid both differential diagnosis and disease monitoring. Although the ocular motor system is well understood and eye movements are easy to measure, existing ocular motor tests either show minimal or no abnormalities in idiopathic Parkinson’s disease (PD) or else are time consuming and difficult to analyse. Other studies in atypical parkinsonism have identified the presence of large saccadic intrusions. However, concentrating on saccadic intrusions only excludes a large amount of the data.

We used infra-red oculography to examine horizontal fixation in 56 normal subjects (age 21–81 years) mean 43 years, (35 male, 21 female) under a variety of viewing conditions. We extracted measurement of fixation periods and amplitudes of all saccadic intrusions. We also examined fixation in 34 patients with idiopathic PD or atypical PD. In normal subjects, we found that fixation period and saccadic intrusion amplitudes were not affected by gender, age, or visual acuity. This allowed us to determine normal ranges.

Parkinsonism patients showed statistically significant (p < 0.001) reduced fixation periods and increased saccadic intrusion amplitudes. Study of ocular fixation by this method could be utilised in the diagnosis and monitoring of parkinsonism.

004 LEVODOPA ACUTELY IMPROVES ALERTNESS IN PARKINSONISM

S. Molloy, I. G. McKeith, J. T. O’Brien, B. K. Saxby, T. Manktelow, K. Wesnes, D. J. Burn.Institute for Ageing & Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK; Cognitive Drug Research, Goring on Thames, UK

Background: Levodopa (Ldopa) is the gold standard treatment for parkinsonism. Ldopa can induce somnolence and decreased reactivity. The effect of Ldopa on attention in parkinsonian syndromes with and without cognitive impairment is unclear.

Aim: To determine the effect of Ldopa on alertness in parkinsonian syndromes with and without cognitive impairment.

Method: Patients with Parkinson’s disease (PD, n  =  23) without and with (PDD, n  =  29) dementia and dementia with Lewy bodies (DLB, n  =  15) underwent acute Ldopa challenges. All patients with dementia were taking cholinesterase inhibitors. Alertness was assessed subjectively via sequential visual analogue scale and objectively using reaction time tests for speed and accuracy every 30 minutes for 2 hours.

Results: Off Ldopa, subjective alertness did not differ between groups but PD patients performed significantly better in speed and accuracy of reaction time tests (p < 0.05 in all tests). After receiving Ldopa acutely, subjective alertness increased in all (p < 0.0001) and speed of simple and choice reaction times increased (p < 0.0001); however, accuracy of choice reaction time testing deteriorated in both groups with dementia (p  =  0.003).

Conclusion: Alertness and speed of reaction in parkinsonism increase with Ldopa but accuracy of reaction deteriorates in patients with known cognitive impairment.

005 WELDING-RELATED PARKINSONISM PLUS

M. R. Cullen, D. T. Erwin, T. E. Harris, W. B. Smith, M. Swash.School of Public Health, Yale University; School of Neuropsychology, Boston University, USA; Oxner Clinic, New Orleans; New Orleans Center for Clinical Trials, USA; Queen Mary School of Medicine, London, UK

We describe a unique neurological syndrome in a convenience sample of 39 Mississippi welders (aged 34–76 years, median 55 years) exposed daily to welding fume during many years in poorly ventilated working environments, taken from a much larger population of welders, of undetermined size. All were considering legal action against their former employers. On the basis of prior screening (DTE), 28 welders were selected for neurological examination. This revealed a syndrome consisting of parkinsonism (in 12), with resting and action tremor (11), axial and limb rigidity (12), bradykinesia (9), and loss of postural reflexes (7), plus prominent nocturnal myoclonus (15) and autonomic disturbances. Autonomic dysfunction includes erectile failure (20), urinary (25) and faecal (24) urgency and incontinence, and copious night sweats (10). Holter monitoring revealed abnormal heart rate regulation as measured by the standard variation of the RR interval and the ratio of low and high frequency variability of the heart rate recorded over 24 hours of ordinary activity. Abnormalities in grooved peg-board and finger tapping tests of manual dexterity were found in both dominant and non-dominant hands. We derived a 3-point categorical exposure metric, the weighted confinement index, based on reported environmental exposure to welding fume and an 11-point clinical score, based on symptoms and abnormal findings on examination and on investigation, to study the relation of this syndrome and its components to the welding environment. Welding fume consists principally of manganese and iron metal and derived compounds. Parkinsonism and myoclonus are recognised features of acute manganese poisoning, but possible neurological toxicity from long-continued low-level exposure to the fume associated with the welding environment, or in other occupational contexts, has not been carefully studied. We are currently evaluating the frequency and specificity of this syndrome in clinical analysis of more than 1000 American welders.

006 CAROTID STENTING TECHNIQUES HAVE EVOLVED SINCE CAVATAS, BUT HAVE THEY HAD AN IMPACT ON PERI-OPERATIVE MORBIDITY. DOES THE SHEFFIELD STENTING REGISTER PROVIDE A CLUE?

M. S. Randall, F. M. McKevitt, T. J. Cleveland, P. A. Gaines, G. S. Venables.Sheffield Teaching Hospital Foundation NHS Trust, Sheffield, UK

Introduction: Carotid artery stenting for symptomatic carotid stenosis (NASCET/ECST criteria) has been performed at the Sheffield Vascular Institute for 9 years. Two radiologists TJC and PAG have over 500 cases experience between them. Procedures are currently performed with dual antiplatelet therapy and protection devices. We assess the impact of these therapies in 391 symptomatic patients.

Methods: Patients in carotid stenting studies were selected by a multidisciplinary team of neurologists, surgeons, and radiologists. Procedures were performed using recommended levels of protection at that time. Pre and post intervention review was performed by a neurologist.

Results: Of 391 stenting procedures, 174 were performed with dual antiplatelet therapy and protection devices. A stroke and death rate of 1.7%(0.58%–4.9%) at 24 hrs and 4%(1.9%–8%) 30 days, compares with 3.7% (1.9%–7.1%) and 7.8%(6%–13.9%) in patients with lower levels of protection. These differences are not statistically significant at 24 hours (p  =  0.197) but reach significance at 30 days (p  =  0.0216). Clopidogrel use had the most significant impact at 24 hrs (p  =  0.0236) and 30 days (p  =  0.0029).

Conclusions: Our small series suggests improved safety of stenting towards a level comparable with carotid endarterectomy. Dual antiplatelet therapy appears to provide greatest benefit.

007 THE THIRD INTERNATIONAL STROKE TRIAL (IST-3). THROMBOLYSIS FOR ACUTE ISCHAEMIC STROKE

I. Kane, P. Sandercock on behalf of the IST-3 collaborative groupUniversity of Edinburgh, Edinburgh, UK

Design: The MRC IST-3 is an international, multicentre, randomised controlled trial of intravenous recombinant tissue plasminogen activator in patients with acute ischaemic stroke. Patients must be assessed and be able to start treatment within 6 hours of symptom onset and brain imaging must have excluded intracerebral haemorrhage. The full protocol is at www.ist3.com. Patients are entered into the trial by telephoning a computerised central randomisation system. Once the baseline data have been successfully recorded and cross-checked, the system generates the treatment allocation with an adaptive algorithm to ensure treatment groups are balanced on key prognostic factors. Repeat brain imaging is required at 24–48 hours and follow up is at 6 months via a postal questionnaire mailed directly to the patient. All scans are reviewed “blind” by a panel of experts. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at 6 months. Progress of current Health Foundation-funded phase: by 15th November 2004, 284 patients had been recruited. The MRC phase will involve 400 centres (at least 50 in the UK) and recruit 6000 patients. Active participation by members of the ABN will be important for the success of the trial in the UK.

008 NEUROMYELITIS OPTICA IN THE UNITED KINGDOM

AnuJacob, KumarDas, RichardNicholas, MikeBoggild.Walton Centre for Neurology & Neurosurgery, Liverpool, UK

Background: Neuromyelitis Optica (NMO) is often a devastating neurological illness, manifesting as severe relapsing optic neuritis and transverse myelitis without additional features suggestive of multiple sclerosis (MS). To characterise this disorder, in a study facilitated by the British Neurological Surveillance Unit (BNSU), we have examined 42 patients from 25 centres across the UK.

Results: The majority are female (28:14), with mean age of onset at 36 years, there is an over representation of patients of Asian and Afro-Caribbean origin. Based on data from Cheshire and Merseyside we estimate the incidence to be 0.4/million/year. Long segment of spinal cord demyelination is common.

Associated autoimmune disorders were present in 21% and other autoantibodies in 42%. Most patients had a relapsing course, with relapse rate in untreated patients approaching 2/year. The majority of patients have been immunosuppressed, most commonly with Azathioprine, with relapse rates on treatment falling to around 0.3/year. Clinical outcomes are often poor, mean of expanded disability status scale (EDSS) 5.5 at 5 years, with disability generally acquired after the first or second clinical event.

Conclusion: This large UK series indicate very poor outcome for patients with relapsing NMO. However, data suggesting the predominantly humoral basis for this condition and response to immunosuppression and plasma exchange argue for early aggressive treatment.

009 LIMB GIRDLE MUSCULAR DYSTROPHY TYPE 21

B. Lecky.Walton Centre for Neurology & Neurosurgery, Liverpool, UK

The limb girdle muscular dystrophies are a heterogeneous group. At present five autosomal dominant (LGMD1 types A–E) and 10 autosomal recessive (LGMD2 types A–J) conditions are described. Most are very rare. In contrast, LGMD2I, caused by a mutation in the fukutin-related protein gene (FKRP), appears to be the commonest cause of LGMD in the UK. FKRP gene mutations also cause congenital muscular dystrophy type 1C (MDC1C).

Five illustrative cases are presented. Clinical onset is between early childhood and the third decade. The dominant clinical features are proximal upper limb weakness, more severe proximal lower limb weakness with milder weakness of ankle dorsiflexion. Although reported to be common the literature, muscle hypertrophy, and cardiac and respiratory muscle involvement was not seen. Serum CK is very elevated in the range of 2000–12 000 and the EMG shows clear myopathic changes. In two patients initial muscle biopsy showed inflammatory change leading to an erroneous diagnosis of idiopathic inflammatory myopathy. The two other initial muscle biopsies showed non-specific myopathic changes. Four patients were homozygous for the C826A mutation of the FKRP gene and the other heterogeneous (presumed to be a compound heterozygote). This condition may be relatively common and is prone to misdiagnosis.

010 FACIAL INVOLVEMENT IN MuSK ANTIBODY POSITIVE MYASTHENIA GRAVIS

M. E. Farrugia, R. P. Kennett, M. D. Robson, P. M. Matthews, D. Hilton-Jones, J. Newsom-Davis, A. Vincent.

Myasthenia gravis (MG) patients with MuSK antibodies (MuSK+ve) have oculobulbar disease and may show tongue atrophy. To study this phenomenon, we performed MRI and quantitative EMG in 15 unselected MuSK+ve patients, comparing with 12 AChR+ve MG patients (selected from 200 AChR+ve MG records for persistent facial weakness and matched for age, sex, and duration of disease), and with healthy subjects.

Tongue atrophy was present in eight MuSK+ve and two AChR+ve patients. On MRI, the facial muscle thickness and tongue areas were significantly reduced in MuSK+ve patients (p < 0.01 for the former and p  =  0.012 for the latter), but not in AChR+ve patients. MuSK+ve patients had greater high signal replacement in the tongue (secondary to fatty change) than AChR+ve patients, and high signal replacement correlated with duration of high dose corticosteroids (p  =  0.02). On single fibre EMG, MuSK+ve patients showed increased jitter in orbicularis oculi but normal jitter in extensor digitorum communis, whereas AChR+ve patients showed increased jitter in both. Motor unit action potential analysis of the facial muscles showed short duration units in 77% MuSK+ve patients compared to 44% AChR+ve patients.

Facial muscle atrophy is more common in MuSK+ve than AChR+ve MG and is probably myopathic in origin. The duration of treatment with high dose corticosteroids may contribute towards this process.

011 TREATING THE UNTREATABLE: EXERCISE INDUCED STEM CELL ACTIVATION AS A NOVEL TREATMENT FOR MITOCHONDRIAL MYOPATHY

A. M. Schaefer, T. Taivassalo, J. L. Gardner, E. L. Blakely, M. J. Barron, R. W. Taylor, R. G. Haller, D. M. Turnbull.Department of Neurology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK; Institute for Exercise and Environmental Medicine, University of Texas Southwestern, Dallas, Texas, USA

The mitochondrial myopathies are an increasingly recognised cause of chronic morbidity and mortality. There is currently no effective treatment for these progressive and debilitating disorders, which are caused by high levels of mutated mitochondrial DNA (mtDNA) within affected tissues. In sporadic mutations, however, despite high levels of mutation in functionally compromised muscle fibres, satellite cells (muscle cell precursors) carry predominantly wild type mtDNA. Studies in healthy individuals demonstrate incorporation of these satellite cells into muscle damaged by eccentric muscle contractions, an observation that we have adopted as a potential treatment strategy.

Twelve mitochondrial myopathy patients, each harbouring a sporadic deletion of the mtDNA, underwent either endurance training to promote mtDNA synthesis, or concentric/eccentric quadriceps exercises to promote low grade myofibre damage and satellite cell incorporation. Biochemical, physiological, and quality of life assessments were undertaken, together with a quadriceps muscle biopsy pre and post training.

To date, we have demonstrated significant improvements in physiological parameters with no deleterious effects on the level of mutated mtDNA or the number of respiratory deficient muscle fibres. Further studies are ongoing to monitor the longer term effects of this intervention.

012 FALLS IN MYOTONIC DYSTROPHY

C. M. Wiles, M. E. Busse, C. M. Sampson, M. T. Rogers, J. M. Fenton-May, R. van Deursen.Dept of Neurology (School of Medicine), Physiotherapy Education (School of Healthcare Studies), Cardiff University and the Institute of Medical Genetics, Cardiff and Vale Trust, Cardiff, UK

Myotonic dystrophy (MyD) patients seem to have frequent falls, some with a major clinical impact. A prospective 13 week study of stumbles and falls was undertaken in 13 (seven female) independently mobile MyD patients aged 46 (8.3) years recruited serially and 12 healthy volunteers (seven female), aged 34 (8.7) years. Falls were classified and related to activity in the community: a range of clinical features were investigated for association.

MyD patients were more inactive than volunteers (80.4 (9.1)% of the time vs 72.1 (4.9)% p<0.01): they walked more slowly, with a shorter stride, and had a lower mean (sd) daily step count of 3445 (1967) compared to volunteers 6324 (1222) (p < 0.001). 11/13 MyD patients (34 falls, 125 stumbles) and 10/12 volunteers (three falls, 26 stumbles) fell or stumbled and four patients had multiple falls (one volunteer had two falls). Patients had 0.21 (0.29) falls/stumbles per 5000 steps compared to 0.02 (0.02) in volunteers (p < 0.007). Volunteers were more likely to stumble or fall because of an extrinsic cause (eg trip, slip): MyD patients did not fall because of vertigo or loss of consciousness but for other intrinsic reasons or falls were unclassifiable. Although self confidence about falling was correlated with a test predicting liability to fall there was no correlation with actual stumbles or falls. Ankle dorsi- and plantar- flexion, knee extension, and hip abduction strength were inversely correlated overall with the rate of falls/stumbles per 5000 steps (Spearman p < 0.01).

The study confirms the clinical impression of increased falls in MyD patients but underlines their multifactorial causation. Impaired central compensatory mechanisms for the multiple impairments may contribute to falls. The relationship with ankle strength also indicates that further exploration of orthosis usage (very low) may also be valuable.

013 MANAGEMENT OF EPILEPSY IN THE COMMUNITY: AN IRISH GENERAL PRACTITIONER’S PERSPECTIVE

A. Neligan, R. Renganathan, B. Sweeney.Department of Neuroscience, Cork University Hospital, Cork, Rep. of Ireland, UK

Background: There are no data on Irish General Practitioners’ (GPs) attitude towards patients with epilepsy and their knowledge of anti-epileptics.

Objective: To determine Irish GPs’ practices towards patients with epilepsy.

Methods: We posted a questionnaire on epilepsy to GPs in Cork and Kerry (population 500 000). The questionnaire consisted of 10 sections.

Results: There was a response rate of 46.7% (175) and revealed that the majority (87%) initially refer patients to a neurologist for further assessment. The majority of GPs gave patients advice about driving, AED side effects, interaction with the OCP, and pregnancy counselling. GP awareness of the newer anti-epileptics is very variable with Gabapentin and Lamotrigine having the highest GP awareness rates. Almost 25% of GPs would initiate treatment following a first time seizure although only 30% would change therapy initiated by a consultant neurologist. Finally the majority of GPs were unhappy with the level of access to neurologists and 95% of GPs felt that the provision of an Epilepsy Clinical Nurse Specialist would help alleviate the problem.

Conclusion: This study highlights the need for greater communication between hospital neurologists and GPs, in particular the need for a management algorithm of patients with epilepsy for GPs.

014 IMAGING THE NEOCORTEX IN EPILEPSY WITH ADVANCED MAGNETIC RESONANCE IMAGING TECHNIQUES

T. M. Salmenpera, M. R. Symms, F. J. Rugg-Gunn, P. A. Boulby, S. L. Free, G. J. Barker, T. A. Yousry, J. S. Duncan.The National Society for Epilepsy and The National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurology, University of Kuopio, Finland; Institute of Psychiatry, London, UK

Our objective was to examine whether new MRI techniques fast FLAIR T2 (FFT2), double inversion recovery (DIR), magnetization transfer ratio (MTR), and voxel-based morphometry (VBM) detect abnormalities in patients with focal epilepsy and normal conventional MRI.

102 MRI-negative focal epilepsy patients who had had ictal videotelemetry were scanned with FFT2, DIR, and MTR using a 1.5T scanner. Statistical parametric mapping was used to compare the images of each patient to a control group.

Temporal lobe (TL) abnormalities were observed in FFT2 in 36%, in DIR in 25%, in MTR in 9%, and in VBM in 7% of the temporal lobe epilepsy patients. The changes were located in ipsilateral TL in 16% (FFT2), in 14% (DIR), in 0% (MTR), in 5% (VBM) of the patients. In frontal lobe epilepsy FFT2 was abnormal in frontal lobe (FL) in 43%, DIR in 48%, MTR in 27%, and VBM in 15% of the patients, and located in ipsilateral FL in 13% (FFT2), in 15% (DIR), in 7% (MTR) and in 14% (VBM) of the patients.

Advanced MRI detects occult structural damage in focal epilepsy patients with normal conventional MRI. These techniques may enable successful presurgical assessment for increasing numbers of intractable epilepsy patients.

015 “CLINICAL” 1.5 TESLA AND “SPECIALIST” 3 TESLA MAGNETIC RESONANCE IMAGING IN PRESURGICAL EPILEPSY

U. C. Wieshmann, S. Keller, N. Roberts.The Walton Centre for Neurology and Neurosurgery, Liverpool, UK; Magnetic Resonance and Image Analysis Research Centre (MARIARC), Liverpool, UK

Aim: High resolution imaging has been greatly improved with the advent of a new generation of ultra high field (3 Tesla) magnetic resonance (MR) scanners. In epilepsy surgery the detection of subtle structural abnormalities with MR imaging is of critical importance. The aim of this study was to compare the yield of 1.5 Tesla MR imaging used clinical NHS routine with the yield of 3 Tesla MR imaging in a specialist unit.

Methods: 14 consecutive patients were included. All patients had clinical 1.5 Tesla MR scans. 3 Tesla scans were performed at MARIARC and included high resolution coronal T1 weighted and FLAIR images and quantitative measurements of hippocampal volumes.

Results: Six 1.5 Tesla MR scans were normal, four showed possible, two definite hippocampal sclerosis, two showed lesions (perinatal infarct and cavernoma). 3Tesla MR imaging identified three additional cases of hippocampal sclerosis in previously normal scans and confirmed 3 of 4 cases of possible hippocampal sclerosis thus increasing the yield of definite abnormalities from 29% to 71%.

Conclusion: The data underline the clinical importance of specialist MR imaging in this patient group.

016 USEFULNESS OF INVESTIGATION IN A FIRST SEIZURE CLINIC

N. Hitiris, J. P. Leach, R. Mohanrav, A. Mallik, J. Greene, R. Duncan.Dept of Neurology, Southern General Hospital, Glasgow, UK; Epilepsy Unit, Western Infirmary, Glasgow, UK

Methods: This presentation looks at the usefulness of ECG, EEG, and MRI in 600 consecutive referrals to the North Glasgow First Seizure Clinic.

Results: Routine ECG revealed few treatable abnormalities: no patient with an ictal presentation had an abnormal ECG requiring further intervention. Of 40 patients with syncope, ECG was normal in 20, but the majority of changes were not of clinical importance. Significant contributory changes requiring investigation were, however, noted in three patients. Among 27 patients with first seizure, cerebral imaging was normal in 89%. Imaging was normal in 50% of patients with partial epilepsy. MRI revealed malignant cerebral lesions in three cases of first seizure. Initial CT had been normal in two of these patients. Imaging carried out by referring clinicians on patients with syncope were uniformly normal. Of 37 patients diagnosed as having had a single seizure, EEG was normal in 70.3%. Prognostic implications will become apparent with long-term follow up. 26 patients diagnosed with epilepsy had an EEG, of whom 57.3% were normal, and 30.7% had generalised discharges.

Conclusions: The future development of relevant guidelines depends on continuing demographic and outcome studies. This will help encourage effective use of resources.

017 NO MORE NEUROPHOBIA: MAKING NEUROLOGY TEACHING ACCESSIBLE TO MEDICAL STUDENTS

L. Ridsdale, M. Massey, L. Darbishire.King’s College, London, UK

Introduction: Following the introduction of a new curriculum of neurology teaching focussed on core problems and skills for the full-time equivalent of five weeks, we aimed to assess medical students’ attitudes to neurology teaching.

Methods: A questionnaire survey of 377 medical students in a one year cohort at Guy’s, King’s, and St Thomas’ School of Medicine.

Results: 247/377 students responded. Students rated their knowledge and skills in neurology as similar to other subjects. They found neurology significantly more interesting (mean difference  = 0.37; CI = 0.22 to 0.52; p < 0.001), and were more likely to endorse it as a subject in which they would like to specialise. Nonetheless, neurology was rated as significantly more difficult than other subjects taught in the same year (mean difference  = 0.73; CI = 0.62 to 0.84; p < 0.001), and students reported significantly less confidence in managing a not-straightforward complaint.

Conclusions: Students do regard neurology as difficult, and have less confidence in managing less straightforward problems. With the introduction of a new curriculum that delivered the equivalent of 5 weeks’ full-time teaching on core neurology problems and skills, students reported similar knowledge and skills levels as in other subjects. They also had high levels of interest and desire to specialise in neurology.

018 OUTSOURCING NEUROLOGY NIGHT-TIME COVER USING INTERCONTINENTAL TELEMEDICINE

V. Patterson, R. Forbes, A. Gowdy, R. Wootton.Royal Victoria Hospital, Belfast, UK; Centre for Online Health, Brisbane, Australia

Outsourcing night-time cover to a different time zone (where it is daytime) is used in radiology in the US. Since realtime telemedicine can be used effectively for acute neurological hospital admissions, we have investigated whether it could be used intercontinentally to provide nighttime neurology cover in the UK from daytime Brisbane. First we analysed demand between 10pm and 8am Sunday to Thursday (equivalent to 8am to 6pm Monday to Friday in eastern Australia) by recording workload of the on-call neurology registrar in Northern Ireland over 92 days; there were only 16 consultations on 14 patients. Second, we performed 12 realtime videoconsultations on neurological patients in Northern Ireland from Brisbane, Australia, recording any technical difficulties; these were encountered in five patients but connection at 384 kb/s was established in all with a mean delay of 2.5 minutes. Third we estimated the cost per patient of telemedicine and conventional care; this was approximately £1200 for conventional care and £370 for telemedicine. Unlike the conventional system the telemedicine system could be scaled up to cover the population of the UK using a single overseas neurologist. Outsourcing neurology cover is therefore possible and would have a number of advantages over the present system.

019 A CANNABIS-BASED MEDICINE (SATIVEX) HAS SUSTAINED EFFICACY IN THE TREATMENT OF SPASTICITY IN MULTIPLE SCLEROSIS

C. Collin, P. Tun, M. G. Serpell, S. Wright.The Royal Berkshire and Battle NHS Trust, Berkshire, UK

Methods: This was a randomised, double-blind, placebo-controlled, parallel group study of a sublingual cannabis-based medicine, Sativex, in 189 multiple sclerosis (MS) patients with spasticity. Patients received either Sativex or placebo for 6 weeks. All patients had failed to obtain adequate symptom relief from existing medication. All participants were given the opportunity to join a monitored extension study using Sativex. First analysis of the data from the extension study included observations up to 30 November 2003.

Results: Sativex was well tolerated and superior to placebo in relieving spasticity (p  =  0.048, ITT population; p = 0.013 per protocol population).

As of 30 November 2003, 77 patients had received Sativex in a long-term safety and tolerability open-label study; their mean baseline spasticity NRS score was 5.62. For the 46 patients who had reached week 28 their mean score was 3.44 (SD = 2.15) with mean change from baseline of 22.38 (SD = 2.33) and mean percent change of 237.8 (SD = 39.27). By 28 weeks eleven (19%) patients had withdrawn. There was no evidence of an increase in daily dose.

Conclusion: These studies demonstrate that Sativex has a positive effect on spasticity that may be sustained, and not associated with dose escalation.

020 AN AUDIT OF THE USE OF MODAFINIL IN CLINICAL PRACTICE FOR THE TREATMENT OF FATIGUE IN MULTIPLE SCLEROSIS PATIENTS

E. T. Littleton, J. Palace.Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK

Background and Aims: Fatigue is one of the commonest and most troublesome symptoms of multiple sclerosis (MS) patients and has been targeted as a research priority by the UK MS Society. None of the previously claimed treatments has proven consistently useful in the clinical setting. In a single-blinded, short-term, placebo-controlled study funded by Cephalon, modafinil was shown to improve three fatigue scales. However the question remains whether these findings can be extended to a clinically useful effect in day-to-day practice and thus we have audited our clinical experience.

Methods: Since 2000, patients seen in the Oxford MS clinic have been offered modafinil for symptoms typical of MS fatigue. They were advised to take a 4 week trial of 200 mg daily, to be continued only if they found a useful improvement in their daily activities. Patients’ response was assessed at follow-up and for this audit a telephone interview was conducted.

Results: 36 patients were included. 53% found the drug beneficial and had continued on it for up to 4 years at the time of interview. All 53% found a useful improvement in daytime sleepiness, with 31% reporting an improvement also in their physical fatigue. Benefit was usually noticed within the first few days. 47% found no overall benefit, 17% citing lack of efficacy as the sole reason for failure, 19% blaming a combination of side effects and lack of efficacy, whilst 11% noticed some improvement in sleepiness or fatigue but found the side effects intolerable.

Conclusions: The positive trial results of modafinil in MS appear to extrapolate to clinical practice where about half the patients found a clinically useful benefit at tolerable doses. Many of the MS patients continued on modafinil for its effect on excessive sleepiness alone, which was not the clinical indication anticipated when the drug was first prescribed.

021 TRENDS IN SURVIVAL AND CAUSE OF DEATH IN PATIENTS WITH MULTIPLE SCLEROSIS IN NORTHERN IRELAND

O. M. Gray, L. T. Lim, S. A. Hawkins.Queens University, Belfast, Ireland; Royal Victoria Hospital, Grosvenor Road, Belfast, Ireland

Objectives: To investigate trends in survival and causes of death in patients with multiple sclerosis, and to investigate the use of death certification in epidemiological research.

Methods: The Northern Ireland Multiple Sclerosis Registry, containing all cases of multiple sclerosis attending neurology outpatients between 1947 and the 1980s, was linked to the Northern Ireland Research and Statistics Agency to identify those who had died and their death certificate documentation.

Results: Of 1931 cases on the registry, 850 had died, with death certificate data available in 809 cases (330 male, 479 female). Median survival time was 30 years (range 63) for men and 33 years (range 61) for females. Median survival increased significantly during the observation period from 25.76 years for deaths in 1951–1960, to 37.0 years for deaths in 1991–2000. Multiple sclerosis was documented as the cause of death (Part I) in 29%, as a contributing factor (Part II) in 38%, and not at all in 33% of death certificates.

Conclusions: Survival improved significantly during the observation period, which may be partly due to earlier establishment of diagnosis and improved case ascertainment. In isolation, death certificates underestimate prevalence rates and mean age at death.

022 MULTI-NODAL MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY IN NORMAL PRESSURE HYDROCEPHALUS

R. Corkill.Greater Manchester Neurosciences Centre, Manchester, UK

Introduction: Magnetic resonance spectroscopy and imaging techniques were used to investigate the haemodynamic and metabolic consequences of idiopathic normal pressure hydrocephalus (iNPH) and its treatment.

Methods & Materials: 11 patients with iNPH were studied pre- and post-operatively and compared with 10 age-matched controls.

Results: Pre-operative periventricular relative cerebral blood volume (rCBV) was reduced in patients (0.76 ± 0.11) compared to control (1.16 ± 0.16, p < 0.01). The periventricular apparent diffusion coefficient (ADC) was elevated in the poor outcome group (1.67 ± 0.3 ×10−3 mm2 s−1) compared to both controls (1.04 ± 0.4 × 10−3 mm2 s−1, p < 0.05) and the good outcome group (0.99 ± 0.3 × 10−3 mm2 s−1, p < 0.05). The white matter (WM) phosphocreatine (PCr)/Adenosine triphosphate (ATP) (1.6 ± 0.3 vs 1.2 ± 0.2, p  =  0.003), inorganic phosphate (Pi)/ATP ratios (0.8 ± 0.4 vs 0.5 ± 0.2, p  =  0.037) and pH (7.15 ± 0.12 vs 7.03 ± 0.03, p  =  0.003) were elevated compared to control and the occipital N-acetyl Aspartate (NAA) concentration was reduced in the patients (11.9 ± 2.4 vs 16.4 ± 0.9, p  =  0.001). These spectroscopy findings were exaggerated in the poor outcome group. No lactate was found. There were no changes following surgery.

Discussion: A higher burden of chronic infarction as characterised by low rCBV and NAA concentration and elevated ADC, WM PCr/ATP and Pi/ATP ratios associated with alkaline WM pH is characteristic of the poor outcome group, and may therefore be useful in selecting patients for surgery.

023 TWO SIMPLE QUESTIONS IN THE IDENTIFICATION OF DEMENTIA

A. J. Larner.Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool, UK

Objective: To examine the utility of two simple questions in identifying patients with dementia: who referred the patient and who accompanied the patient to the clinic.

Methods/Setting: Prospective audit of new referrals to Walton Centre for Neurology and Neurosurgery (WCNN) Cognitive Function Clinic over 2 years (September 2002–August 2004). Dementia was diagnosed using standard criteria based on clinical, neuropsychological, and neuroimaging assessment.

Results: Of 183 referrals seen, 90 (49%) had dementia. Dementia was diagnosed in 40%, 75%, and 58% of referrals from general practitioners, WCNN neurologists, and other hospital practitioners (mostly psychiatrists), respectively. The relative risk of GP referrals having dementia was 0.68 (95% CI: 0.51 to 0.94); of WCNN neurologist referrals 1.79 (95% CI: 1.43 to 2.23). Despite written instructions to bring an informant for collateral history, 33 patients (18%) attended the clinic alone. If attending with a spouse/relative/friend/carer were considered a diagnostic test for dementia, it would have high sensitivity (100%) but low specificity (35%), moderate positive predictive value (60%) and high negative predictive value (100%), unimportant positive likelihood ratio (1.55) but large negative likelihood ratio (0).

Discussion/Conclusions: Frequency of dementia varied markedly with referral source; neurologist referrals had “added value”. Attending the clinic unaccompanied despite written instructions to the contrary was a robust sign of absence of dementia.

024 BRAIN BIOPSY IN DEMENTIA: A REVIEW OF 90 CONSECUTIVE CASES FROM QUEEN SQUARE

J. M. Schott, J. D. Warren, N. C. Fox, M. Thom, T. Revesz, F. Scaravilli, J. Holton, D. G. T. Thomas, G. T. Plant, P. Rudge, M. N. Rossor.Dementia Research Centre, Institute of Neurology, London, UK; Division of Neuropathology, Institute of Neurology; Division of Neurosurgery, Institute of Neurology; National Hospital for Neurology and Neurosurgery, London, UK

Introduction: Brain biopsy has an uncertain role in the diagnosis of dementia.

Methods: We performed a review of brain biopsies undertaken at Queen Square between 1989 and 2003 for the investigation of dementia. We assessed the proportion of diagnostic biopsies; the diagnoses reached; and factors predicting a specific diagnosis.

Results: 59% of biopsies were diagnostic: the most frequent diagnoses were Alzheimer’s disease (18%), Creutzfeldt-Jakob disease (14%), and inflammatory disorders (9%). Other diagnoses included Pick’s disease, corticobasal degeneration, Lewy body dementia, multiple sclerosis, Whipple’s disease, progressive multifocal leukoencephalopathy, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), vasculopathies, and paraneoplastic encephalopathy. The most frequent biopsy finding in the non-diagnostic group and for the series as a whole (37%) was nonspecific gliosis. Complications included seizures and infections; there was no mortality attributable to the procedure. Information obtained at biopsy directly influenced treatment in 11%. A raised CSF cell count was the only predictor of a potentially treatable (inflammatory) process at biopsy. The constellation of behavioural change, raised CSF protein, and positive CSF oligoclonal bands was associated with nonspecific gliosis at biopsy.

Conclusion: Brain biopsy may be useful in the diagnosis of dementia: certain clinical and laboratory features may help guide the decision to proceed to cerebral biopsy.

025 TONSIL BIOPSY IN THE INVESTIGATION OF SUSPECTED VARIANT CREUTZFELDT-JAKOB DISEASE – A COHORT STUDY OF 50 PATIENTS

A. Kennedy, D. Siddique, D. J. Thomas, D. Hill, N. Tolley, J. Collinge.National Prion Clinic, National Hospital for Neurology & Neurosurgery, London, UK

Variant Creutzfeldt-Jakob disease (vCJD) is caused by infection with a bovine spongiform encephalopathy (BSE)-like prion strain designated PrPSc type 4. In contrast to classical (sporadic or iatrogenic) CJD, vCJD prion infection is associated with prominent infection of the lymphoreticular system, which is thought to occur long before neuroinvasion. Early clinical features are nonspecific making early diagnosis difficult. We introduced biopsy of tonsil, which is readily surgically accessible, for firm tissue based diagnosis of vCJD prion infection by demonstration of type 4 PrPSc and characteristic PrP immunostaining of lymphoid follicles.

Fifty patients, referred between 1996–2004 to the National Prion Clinic at St Mary’s Hospital, London, underwent tonsil biopsy. Tissue was analysed by Western blot and PrP immunohistochemistry. Wherever possible, confirmation of diagnosis was obtained at necropsy. Twenty-nine patients (five of whom had a negative pulvinar sign) had a positive tonsil biopsy, which, in the appropriate clinical context, allowed a firm diagnosis of vCJD. Twenty-one patients had a negative tonsil biopsy, and on longitudinal follow-up, confident diagnoses other than vCJD were established. None of these showed pulvinar sign.

100% specificity and sensitivity for antemortem diagnosis was achieved by tonsil biopsy, which may allow earlier diagnosis before extensive neuronal loss. This is increasingly important now that therapeutic trials of anti-prion drugs are underway.

026 DEMENTIA WITH LEWY BODIES IN SINGAPORE

D. Blackburn, E. Ampil, S. Sodagar, A. P. Auchus, C. P. L. H. Chen.Department of Neurology, Singapore General Hospital, Singapore; Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Singapore; Department of Neurology, Case Western Reserve University, Cleveland, OH, USA

Objective: To determine the prevalence of dementia with Lewy bodies (DLB) in a multi-racial Asian population.

Method: The database of 478 patients assessed between 1996–2002 by the Singapore General Hospital Dementia Programme was utilised to identify and review case notes of patients with DLB or Parkinsonism plus dementia (PDD).

Result: Seven cases from 434 eligible patients were diagnosed with DLB. A further 15 patients were diagnosed with PDD. Thus, DLB accounted for only 1.6% of dementias. If PDD is included, then there is a 5% prevalence of dementia associated with Parkinsonism.

Conclusion: The prevalence of DLB is lower than reported in western studies. This confirms previous studies from Asian populations. Ethnic variations in dementia and their subtypes require further research.

027 SPORADIC CREUTZFELDT-JAKOB DISEASE IDENTIFIED ONLY AT AUTOPSY: WHY ARE CASES MISSED IN LIFE?

S. A. Cooper, R. G. Will, R. S. G. Knight.The National CJD Surveillance Unit, Edinburgh, UK

Background: The National CJD Surveillance Unit (NCJDSU) encourages referral of patients with suspect CJD whilst alive. Neuropathologists also refer cases after autopsy, representing those missed in life.

Aim: To examine factors that prevented identification and referral of patients with sporadic CJD (sCJD) in life.

Method: A retrospective review of all pathologically-proven sCJD cases referred to the NCJDSU over a 12 year period. Clinical features and investigation results were assessed in each case notified after autopsy.

Results: 91/485 cases (19%) were referred after autopsy. They were older than those referred in life (p  =  0.005) and had a longer duration of illness (p  =  0.044). In 26/91 CJD was not considered in life (“unsuspected” cases). 38% of unsuspected cases had atypical clinical features (i.e. illness duration of >2 years, age at onset <50 years, a focal onset of disease). In five unsuspected cases the clinical picture was typical for sCJD (i.e. rapidly progressive dementia with myoclonus and death within 6 months). 7/91 (12%) had an EEG characteristic of sCJD. Three had CSF 14-3-3 analysis and all were negative. There were no clear geographical areas that corresponded with cases unreferred in life. Declining autopsy rates are likely to lead to less representative CJD surveillance in the UK.

028 CREUTZFELDT-JAKOB DISEASE ASSOCIATED WITH HUMAN DURA MATER – EXPERIENCE FROM UK SURVEILLANCE

C. A. Heath, K. L. Murray, H. M. Yull, M. Head, R. G. Will, R. S. G. Knight.National CJD Surveillance Unit, Edinburgh, UK

Introduction: Iatrogenic Creutzfeldt-Jakob disease (CJD) results from the inadvertent transmission of CJD during medical and surgical treatment. Human dura mater grafts have been implicated, with over 160 cases identified worldwide.

Aim: To describe the basic clinical and demographic features of dura associated CJD in the UK.

Method: “Suspect” cases of CJD with a surgical history of exposure to a human dura graft were identified from the archives of the National CJD Surveillance Unit (NCJDSU).

Results: Seven cases of human dura mater associated CJD were identified in the UK between 1970–2003.

The time between graft placement and onset of symptoms ranged from 45 to 177 months. The mean age at surgery was 33, and mean age at onset 41. The mean duration of illness was 9.4 months. Lyodura© was implicated in six cases, with all cases exposed prior to May 1987. There is often an association between the site of graft placement, or previous surgical damage, and the presenting clinical features.

Conclusion: In the UK, transmission of CJD via human dura mater is rare and almost exclusively associated with a single graft manufacturer. Presenting symptoms may be related to the site of graft placement, however, diversity in clinical phenotype is recognised.

029 VERTICAL TRANSMISSION OF VARIANT CJD

K. L. Murray.National CJD Surveillance Unit, Edinburgh, UK

Introduction: Variant Creutzfeldt-Jakob disease (vCJD) predominantly affects young adults of reproductive age with a mean age of onset of 28 years. The recent identification of vCJD transmission via blood has raised concerns regarding the possibility of vertical transmission.

Aim: To review the UK data to assess the possibility of vertical transmission of vCJD.

Methods: All children born to vCJD cases were identified from the The National CJD Surveillance Unit (NCJDSU) archives. Obstetric notes were reviewed if the birth was within a year of CJD onset.

Results: 114 children have been born to vCJD cases, with a current age range of 22 months (in utero) to 40 years. In 60% (968/114) the affected parent was the mother and in 40% (46/114) the father. Nine offspring were born within a year of maternal disease onset. In five cases the mother was symptomatic at birth and in two symptomatic at conception. Five of the nine deliveries required surgical instrumentation. Only one baby was breastfed. To date none of the 114 offspring have developed vCJD.

Conclusion: Currently there is no evidence to support vertical transmission of vCJD. However, this possibility cannot yet be firmly excluded due to the limited data and relatively short period of observation.

030 NON CONVULSIVE STATUS EPILEPTICUS IN CREUTZFELDT-JAKOB DISEASE – A SHORT REPORT

J. Vaz, K. Sierazdan, N. Kane.Frenchay Hospital, Bristol, UK

We describe an extremely rare case of a previously fit and well patient who presented with a rapidly progressive change in personality, behaviour, and gait ataxia. She was apathic, withdrawn, and increasingly dependent on her family. Neurologically she had receptive dysphasia, increased tone, and reflexes. MRI scans revealed high signal in the caudate and lentiform nuclei with normal thalami.

Serial EEGs showed widespread almost continuous repetetive1–1.5 Hz triphasic sharp and slow waves at 100–150 uV with an anterior emphasis intermixes with rhythmic 5–7 Hz theta waves in the posterior and central region which did not alter during periods of agitation and eye opening suggestive of non-convulsive status epilepticus that was not responsive to anti epileptic drugs (AED).

Post mortem brain biopsy revealed spongiform changes in the brain, neuronal loss in the cortex, deep grey nuclei, and cerebellum with synaptic pattern of PrP immunopositivity.

Although seizure not responsive to AED can occur in CJD, non-convulsive status epilepticus is extremely rare. A diagnosis of CJD should be considered in patients with rapidly progressive dementia with non-convulsive status epilepticus and patient investigated for CJD markers.

031 MAGNETIZATION TRANSFER SPECTROSCOPY IN PATIENTS WITH EPILEPSY

D. Flügel, M. A. McLean, R. J. Simister, J. S. Duncan.MRI Unit, National Society for Epilepsy, Chalfont St Peter, Gerrard’s Cross, Bucks, UK; Department of Clinical and Experimental Epilepsy, Institute of Neurology and Neurosurgery, University College London, Queen Square, London, UK

Aim: To identify changes in brain metabolites in following seizures using magnetization transfer (MT) spectroscopy.

Methods: 10 healthy controls were scanned twice and 10 patients were studied post- and interictally (seven complex partial, one simple partial, and two secondarily generalised tonic clonic seizures). A modified version of PRESS (TE/TR = 30/3000 ms) with three MT pulses applied at a frequency of either 2.5 kHz (to generate a MT effect) or 30 kHz (not to generate an effect) was used. The percentage MT ratio (MTR) was calculated as MTR = 100×(C30–C2.5)/C30, where C30 and C2.5 were concentrations measured at offset of 30 kHz and 2.5 kHz, respectively.

Results: A significant decrease in the MT ratio of choline was seen following seizures, while the concentrations of N-acetyl aspartate, creatine, choline, myo-inositol lactate, and glutamate+glutamine showed no significant difference between interictal and postictal scans. Interictally, patients had significantly lower N-acetyl aspartate, myo-inositol, and creatine than the healthy controls.

Discussion: Reduced MT ratio of choline indicates a shift from a bound to a more mobile fraction, which may reflect inhibition of the incorporation of choline in membrane phoshatidylcholine and sphingomyelin, as a result of excessive NMDA receptor activation.

032 MR-TRACTOGRAPHY PREDICTS VISUAL FIELD DEFECTS FOLLOWING TEMPORAL LOBE RESECTION

H. W. R. Powell, M. J. Koepp, G. J. M. Parker, D. C. Alexander, M. R. Symms, C. A. M. Wheeler-Kingshott, P. A. Boulby, G. J. Barker, J. S. Duncan.Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London, UK; Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK; Department of Computer Science, University College London; NMR Research Unit, Institute of Neurology, University College London; Centre for Neuroimaging Sciences, Department of Neurology, Institute of Psychiatry, Kings College London, UK

Anterior temporal lobe resections (ATLRs) are increasingly performed in patients with refractory partial epilepsy. A superior homonymous quadrantanopia is a well recognised complication of ATLRs and occurs due to disruption of Meyer’s loop, the anterior loop of the optic radiation.

We studied two patients undergoing unilateral ATLRs with diffusion tensor imaging and MR tractography before and after surgery. Both had good clinical outcomes but one patient developed a visual field defect that precluded driving. We used a tractography algorithm to trace the course of the optic radiations from a seed point in the lateral geniculate body.

In the patient with the quadrantanopia we demonstrated the disruption to the optic radiation that occurred following surgery, with loss of the anterior edge of Meyer’s loop. In the second patient the course of the optic radiation was identified in full on both pre- and post-operative images. On comparison of the two patients’ pre-operative tractography, the anterior boundary of Meyer’s loop extended further anteriorly and inferiorly in the patient who developed a quadrantanopia.

We suggest that this method has the potential to predict visual field defects in patients undergoing temporal lobe surgery, minimising the risks of surgery and allowing improved pre-operative counselling.

033 THE PREVALENCE OF STRUCTURAL ABNORMALITIES IN CLINICALLY SELECTED PATIENTS WITH CHRONIC HEADACHE AND SEIZURE

U. C. Wieshmann.The Walton Centre for Neurology and Neurosurgery, Liverpool, UK

Aim: To determine the prevalence of structural abnormalities in clinically selected patients with chronic headaches and seizures.

Methods: Patients with seizures (including epileptic seizures, non epileptic attacks, and syncope) or headaches attending the out patient department between 2000 and 2004 were included in the study. Patients had x ray computed tomography (CT) and/or magnetic resonance imaging (MRI) scans if a structural abnormality was clinically suspected.

Results: 1443 patients were in the seizure group, 779 patients in the headache group. 650 patients of the seizure group and 194 patients of the headache group were selected for a scan. Structural abnormalities were significantly more frequent in the seizure group. 214 of 650 seizure scans (33%) and 21 of 194 (11%) headache scans were abnormal. Cerebrovascular abnormalities and tumours were the most common pathologies in both groups. 12% of all seizure patients had cerebrovascular abnormalities and 5% tumours. 4% of all headache patients had cerebrovascular abnormalities and 2% tumours.

Conclusion: In clinically selected patients structural abnormalities are less common in chronic headaches than in seizures.

034 TOLERABILITY OF POLYTHERAPY WITH SODIUM VALPROATE, TOPIRAMATE AND LAMOTRIGINE

G. Peters, U. C. Wieshmann.The Walton Centre for Neurology and Neurosurgery, Liverpool, UK

Aim: To determine the frequency of side effects in patients taking Sodium Valproate with Topiramate or Lamotrigine.

Methods: 29 patients were randomly selected. Duration of treatment and side effects were recorded.

Results: 28 patients were treated with Lamotrigine plus Valproate (20 patients subsequently added Topiramate). The mean duration of Lamotrigine plus Valproate treatment was 49 months, 16 continued. The maximum tolerated daily dose was Lamotrigine 400 mg plus Valproate 800 mg. 12 discontinued treatment. Severe side effects (n  =  5) included sedation and rash. The rash occurred on Lamotrigine 25 mg a day, otherwise 250 mg plus Valproate 1500 mg was the minimum dose associated with severe side effects. 21 patients were treated with Topiramate plus Valproate (20 were at some stage exposed to Lamotrigine). The mean duration of Topiramate plus Valproate treatment was 35 months. 15 patients continued. The maximum tolerated daily dose was Topiramate 800 mg plus Valproate 2500 mg. Six patients stopped. Severe side effects (n  =  4) included sedation and weight loss. The minimum dose associated with severe side effects was Topiramate 200 mg plus Valproate 2400 mg. One patient developed Valproate encephalopathy when Valproate was added to Topiramate.

Conclusion: About 20% of all patients treated with polytherapy develop severe side effects.

035 VOLTAGE GATED POTASSIUM CHANNEL ANTIBODY ASSOCIATED LIMBIC ENCEPHALITIS: A CASE OF ACUTE AMNESIA AND GOOD LONG TERM OUTCOME

C. Donaghy, T. Rado, J. M. Gibson.Royal Victoria Hospital, Belfast, Ireland

Voltage gated potassium channel (VGKC) antibody associated Limbic Encephalitis (LE) has only very recently been described and is thought to be an autoimmune non-paraneoplastic, potentially treatable form of LE. The natural history and breadth of clinical phenotype remains largely undetermined and the condition is most probably under and misdiagnosed.

We report the case of a 60 year old man who presented with acute amnesia and complex partial seizures. Coronal Flair MRI revealed bilateral high signal in the medial temporal lobes and CSF examination was normal. VGKC antibodies were elevated at >3000 pM. FDG-PET was negative for underlying malignancy. Neuropsychological testing confirmed a circumscribed amnesic syndrome involving anterograde and retrograde episodic memory with relative preservation of semantic memory. He was treated with oral corticosteroid at gradual reducing doses and at one year continues to show improvements in memory function.

Neurologists should be alert to the possibility of an acute amnesic state being the presenting feature of this condition, as early appropriate treatment may limit severe permanent neurological damage. This case adds weight to the postulation that the condition is monophasic and highlights the potential for improvement much beyond the acute illness.

036 THE UK MULTIPLE SCLEROSIS (MS) DATABASE: A TOOL FOR MS CARE AND RESEARCH

B. Hoddell on behalf of UK MS Database User GroupDepartment of Neurology, University of Oxford, UK

The UK MS database is a bespoke, modular, system developed in consultation with UK neurologists as a tool to support multidisciplinary management of MS. The system has been freely available within the UK for three years and has been reconfigured to also act as the data collection tool for the monitoring study associated with the risk-sharing scheme (RSS).

The system is now in use in over 70 centres, in only 27 of those is the system being used solely for collection of data required by the RSS. Records on over 14 000 patients (up to 20% of the UK MS population) are available on the system, ranging from basic demographics to full clinical data.

Of 14 667 for whom data are available 69% are female. The majority of the patients have relapsing remitting disease, reflecting the fact that the system is based in the main in acute neurology units. A minimum of 16% are currently receiving disease modifying treatment (compared with a national figure of approximately 10%). In a number of centres detailed data on many other aspects of the disease are available, including EDSS, symptomatic management, and co-morbidities. A variety of examples will be presented and other aspects of the system, such as letter generation and potential for data analysis and collaboration, will be discussed.

037 DIAGNOSTIC YIELD OF BRAIN BIOPSY IN NEUROLOGY PATIENTS AT ATKINSON MORLEY HOSPITAL (AMH), 1993–2002

S. O’Riordan, S. Omer.Department of Neurology, Atkinson Morley Wing, St. George’s Hospital, London, UK

Aims: To review the role of brain biopsy as a diagnostic tool in patients admitted under the care of neurologists at AMH.

Methods: We reviewed all brain biopsy reports January 1993–December 2002. We included only biopsies performed on patients admitted under neurologists. We reviewed in detail records of patients referred for reasons other than suspected solid tumour.

Results: 186 brain biopsies were included. 147 were performed to confirm suspected solid tumour (diagnostic yield 97%). 24 patients were referred with “white-matter lesions” (71% yield). 13 of these were referred with a suspected diagnosis of cerebral vasculitis. This was confirmed in one patient but alternative diagnoses were reached in seven (cerebral amyloid angiopathy, progressive multifocal leucoencephalopthy, malignant angioendotheliosis, and small vessel disease). Open and stereotactic biopsies had similar yield. 15 biopsies were performed for other reasons including early dementia and meningeal enhancement (53% yield). In the 39 patients referred with diagnoses other than solid tumours, mortality was 2.5% and morbidity 2.5%.

Conclusions: In this series, brain biopsy had a high yield in the setting of solid intracerebral tumour. It was useful in suspected cerebral vasculitis in that it often allowed an alternative diagnosis to be reached. Morbidity and mortality were low.

038 NEUROPATHOLOGICAL FEATURES OF MULTIPLE SCLEROSIS (MS) CAN BE SEEN IN A HUMANISED MOUSE MODEL OF EAE WITH HETEROGENEOUS CLINICAL ASPECTS

J. S. Tzartos, J. A. Palace, M. Esiri, L. Fugger.Departments of Clinical Neurology and Neuropathology, Radcliffe Infirmary, Oxford, UK; Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

We are studying an experimental model of MS, which uses mice humanised with MHCII and TCR derived from MS patients. The similarities to MS are: (a) in some of the mice spontaneous disease occurs without the need for antigen immunisation, or transfer of T-cells; (b) clinical heterogeneity with relapsing or progressive, with mild or severe and fulminant clinical manifestations; (c) pathological heterogeneity (inflammation, demyelination, and axonal damage). We are studying the relationship of the clinical and pathological features, and the influence the MHCII, TCR and other immunomodulatory molecules have on these features. In preliminary experiments using immunohistochemical techniques we have observed T-cells, macrophages, and activated microglia forming focal lesions in correlation with demyelination and axonal damage. Using computer analysis we are now trying to quantify our results. We should then be able to test the effect and mechanisms of action of immunomodulatory drugs on clinical and neuropathological symptoms. Availability of a relevant experimental model of MS will be very important for the screening of MS drugs.

039 A PHARMACOGENETIC SCREEN OF 100 INTERFERON REGULATED GENES IN RELATION TO (NON-) RESPONSIVENESS TO IFN-β TREATMENT IN MULTIPLE SCLEROSIS

S. Cunningham, S. Heggarty, C. Graham, S. Hawkins, G. McDonnell, A. Droogan, O. Gray, K. O’Rourke, M. Hutchison, K. Vandenbroeck.Applied Genomics Group, McClay Research Centre, School of Pharmacy, The Queen’s University of Belfast, 97 Lisburn Road, Belfast, Ireland; Centre of Medical Genetics, The Queen’s University of Belfast; Neurology Department, Royal Victoria Hospital, Belfast, Ireland; St.Vincents Hospital, Dublin, Ireland

Individual responses of MS patients to recombinant interferon-beta (rIFN-β) treatment are known to be heterogeneous. Percentage of responding patients to treatment is estimated between 30–50%. It is unknown which factors determine this heterogeneity. Genes transcriptionally affected by IFN-β, normally have within their promoter regions typical DNA motifs, termed interferon stimulated response elements (ISREs). Binding of IFN-β-activated transcription factor to such IRSEs has been shown to result transcriptionsal induction or repression of the target gene. We have examined 100 genes for mutations within or close to IRSEs, with the hypothesis that mutations within or close to these elements can modify responsiveness to IFN. Applying a pooled DNA approach, pools where constructed from Irish MS patients (classified as clinical responders, non-responders and those with high neutralisng antibody titre against IFN-β) and healthy subjects. Examination of these genes entailed sequencing of DNA fragments containing the ISRE motif and transcription initiation or ATG start codon. Fragments were studied for polymorphic differences in allele frequencies of mutations, for both disease susceptibility and IFN response status within pooled DNA. To date a number of these response associations have been confirmed in individual samples within eight genes, all demonstrating response associations p < 0.05.

040 INTERLUKIN-4 (IL-4) and IL-4 RECEPTOR (IL-4R) POLYMORPHISMS: INFLUENCE ON CLINICAL COURSE OF MULTIPLE SCLEROSIS (MS)

V. Suppiah, S. Heggarty, A. Droogan, G. McDonnell, S. Hawkins, A. Goris, B. Dubois, A. Antiguedad, M. Mendibe, I. Alloza, K. Vandenbroeck.Applied Genomics Research Group, School of Pharmacy, The Queen’s University of Belfast, Belfast Ireland; Neurology Department, Royal Victoria Hospital, Belfast, Ireland; Rega Institute for Medical Research, Leuven, Belgium; Hospital de Cruces, Bilbao, Spain

The intricate balance between the Th1 and Th2 cytokines of the immune system play an important role in the pathogenesis of MS. We have studied the role of polymorphisms in the prototypic Th2 cytokine IL-4 and its receptor (IL-4R) in MS. We focused on the Q551R SNP in IL-4R and on the +33 SNP in IL-4, both of which are known to be functional on a phenotypic level with the rarer allele in Caucasians being associated with higher levels of IL-4 expression. We studied these polymorphisms in MS patients and controls from Northern Ireland, Basque country, and Belgium. We found that in both Basque and Northern Irish MS patients the IL-4 +33 SNP showed a distinct distribution between patients with relapsing-remitting (RR) and primary-progressive (PP) MS. In both populations, the CC genotype (low IL-4 production) was significantly higher in patients with PP compared to those with RR MS. These data are suggestive for the IL-4 gene being a disease-modifier rather than an MS susceptibility gene. We did not confirm previous reports indicating a role for IL-4 polymorphisms in late onset of disease or severity. The Q551R SNP in the IL4R gene was not associated with susceptibility or clinical parameters of MS.

041 POLYMORPHISMS IN THE INTERFERON-GAMMA GENE MODIFY SEX-ASSOCIATED RISK FOR MULTIPLE SCLEROSIS

S. Heggarty, I. Alloza, S. Cunningham, O. Kantarci, B. Weinshenker, A. Droogan, G. McDonnell, S. Hawkins, A. Goris, B. Dubois, K. Vandenbroeck.Applied Genomics Research Group, School of Pharmacy, The Queen’s University of Belfast, Belfast, Ireland; Mayo Clinic and Foundation, Rochester, USA; Neurology Department, Royal Victoria Hospital, Belfast; Rega Institute for Medical Research, Leuven, Belgium

Interferon-gamma is a crucial mediator of CNS-based inflammation. Its involvement in MS has been documented extensively. We have recently found evidence that polymorphic variants of this gene are associated with MS in a sex-restricted manner. In the resent study, we performed a high-resolution screen of single nucleotide polymorphisms in this gene in MS patients and controls from three different locations (Northern Ireland, Belgium, and USA) totalling 3000 samples. We have identified haplotypes specifically associating with MS in men, but not in women. Our data extend the concept of gender bias in MS, by revealing a genetic component that may work complementary to additional sex-specific risk factors such as sex hormones. Remarkably, haplotypes associating with lower risk for men to contract this disease are those known to result in higher level production of IFN-g. Therefore, this work challenges the concept of IFN-gamma being a disease-promoting factor in MS. Further analysis is going on to unravel the complex interplay of factors involved in gender bias.

042 SPINOCEREBELLAR ATAXIA TYPE 17: EXTENSION OF PHENOTYPE WITH PUTAMINAL RIM HYPERINTENSITY ON MAGNETIC RESONANCE IMAGING

D. C. Allen, C. T. Loy, A. J. Wills, G. V. Sawle, S. J. Tabrizi.National Hospital for Neurology & Neurosurgery, Queen Square, London; Department of Neurology, Queens Medical Centre, Nottingham, UK; Department of Neurodegenerative diseases, Institute of Neurology, Queen Square, London, UK

We report a 50 year old Caucasian woman who presented with an 8-year history of involuntary movements, unsteadiness, and cognitive decline. There was no family history of neurological illness.

Examination revealed multi-domain cognitive deficits affecting memory, spelling, praxis, visuoperceptual, visuospatial skills, and frontal lobe function. Jerky ocular pursuit movements, gaze impersistence, and hypometric saccades were noted. She was dysarthric, had generalised chorea, dystonic posturing of her arms, and a wide-based, unsteady gait.

MRI brain showed marked cerebellar atrophy and hyper-intensity of the putaminal rim.

This phenotype carries a wide differential including Huntington’s disease, spinocerebellar ataxia (SCA-3 type 3), dentatorubropallidoluysian atrophy (DRPLA), inherited prion disease, neuro-acanthocytosis, and neuroferritinopathy.

Striatal hyperintensity on MRI has also been reported in a range of conditions, including SCA-2, DRPLA, neuro-acanthocytosis, mitochondrial cytopathy and multiple system atrophy (MSA).

Investigations for these disorders were negative but TATA-binding protein gene testing revealed CAG trinucleotide repeat expansions of 47/39, confirming the diagnosis of SCA type 17 (SCA-17). This dominantly inherited spinocerebellar ataxia was first described in 1999, and can manifest with a variety of clinical phenotypes encompassing ataxia, dementia, and extrapyramidal features.

This is the first case of SCA-17 reported to show MRI signal change in the basal ganglia, and extends the phenotypic manifestation of this disorder.

043 SPONDYLOEPIPHYSEAL DYSPLASIA (SED) PRESENTING WITH CERVICAL MYELOPATHY

AndersonK, LaingR, DickD.Addenbrookes Hospital, Norfolk,UK; Norwich University NHS Trust, Norwich, UK

A 32 year old lady presented with a 3 month history of progressive weakness and spasticity in all four limbs. A cervical myelopathy was diagnosed following magnetic resonance imaging (MRI) of her cervical spine. She went on to have successful cervical cord decompression.

At the age of 7 years the patient had been diagnosed as having Morquio syndrome, an autosomal recessive disease associated with short stature and skeletal abnormalities. In fact the patient had gone on to have two affected children with an asymptomatic partner in a non-consanguinous relationship.

The diagnosis was reviewed and revised on the basis of the recently available genetic testing now available for SED—an autosomal dominant condition associated with mutations in the COL2A1 gene. The patient was tested and found to have a missense mutation within the COL2A1 gene thus confirming the diagnosis. The causes of short stature and skeletal abnormalities are reviewed. SED is rare but is almost always associated with progressive cervical cord compression and early intervention is recommended in these patients. A correct diagnosis has implications for both genetic counselling as well as the long term health of the patient.

044 THE OUTCOME OF REFERRAL OF PATIENTS WITH FUNCTIONAL NEUROLOGICAL SYMPTOMS OR PSYCHIATRIC DISORDERS FOR PSYCHOLOGICAL THERAPY FROM A GENERAL CLINIC – A PILOT STUDY

G. S. Kishore, A. Blair, K. Scholes, M. Reuber.Department of Psychiatry, Doncaster Royal Infirmary, Doncaster; Health Psychology Service, Walton Hospital, Chesterfield, UK; Academic Neurology Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK

Introduction: Reports suggest that 10–30% of patients presenting to neurologists have problems, which could be addressed by psychotherapy. In preparation for a systematic trial, we wanted to determine how many patients presenting to a district neurology clinic take up the offer of psychotherapy, and how many complete treatment.

Method: Follow-up information on all patients referred by one neurologist to a clinical psychology service over one year was obtained from a postal questionnaire, the psychology database, hospital and general practice records. Patients were seen by a psychologist 6 to 8 weeks after referral and offered brief, individually tailored psychotherapy.

Results: 33 of 603 patients seen by one neurologist in a district hospital were referred for psychotherapy (5.5%). 85% of patients had functional symptoms, 15% primary psychiatric disorders (anxiety or depression). The commonest symptoms were non-epileptic seizures, pain and motor weakness; mean symptom duration was 3.4 years. Seven of 33 patients (21.2%) failed to attend for the initial psychology assessment, six (18.2%) dropped out of therapy, and 20 (60.6%) completed treatment.

Conclusion: General neurologists commonly see patients who could benefit from psychotherapy. Nearly 4/5 of patients referred for psychotherapy attend an assessment visit and 3/5 patients complete treatment.

045 NEURORADIOLOGY IN A DISTRICT GENERAL HOSPITAL

M. O. McCarron, C. Sands, P. McCarron.Department of Neurology, Altnagelvin Hospital, Londonderry, Ireland; Department of Epidemiology and Public Health, Queen’s University, Belfast, Ireland

Background: District General Hospitals (DGH) are acquiring more Neurologists. The standard of DGH neuroimaging reports has seldom been assessed.

Objective: To assess the accuracy of general radiology neuroimaging reports in a DGH.

Methods: Computerised tomography (CT) and magnetic resonant imaging (MRI) scans were selected at the discretion of a neurologist for neuroradiology reporting over a 12 month period. Outcomes were: (a) disagreement in primary diagnosis/finding; (b) disagreement in secondary diagnosis/finding or differential diagnoses; (c) disagreement in primary or secondary findings; (d) length of general radiology reports compared with neuroradiology reports; (e) number of suggestions by a neuroradiologist for further investigations; and (f) subgroup analysis of primary findings for CT and MRI scans.

Results: Scans from 100 patients were analysed; 54 men and 46 women, mean age 48 (SD 17). In 18% of patients the primary finding/diagnosis differed, (five of 19 CT scans only and 13 of 81 patients who had MRI scans). Secondary finding/diagnosis or differential diagnoses differed in 29%. Primary or secondary findings differed in 40%. Neuroradiologists provided more detailed reports than general radiologists (mean word count 140 vs 58, p  =  0.005). Neuroradiologists suggested further investigations in 14 patients.

Conclusion: DGH neurologists require timely access to neuroradiology (CT and MRI) reporting.

046 TRIGEMINAL NEURALGIA AS A PRESENTING FEATURE OF LHERMITTE DUCLOS DISEASE

C. McGuigan, J. Britton, D. Wren.Departments of Neurology and Neuroradiology, Atkinson Morley Wing, St. George’s Hospital, London, UK

Lhermitte-Duclos disease (LDD) is a rare dysplastic gangliocytoma of the cerebellum that usually presents in the third or forth decades of life with headaches, ataxia, or signs of raised intracranial pressure. We report the case of a 38 year old man with a 9-month history of lancanating pain across his left cheek. Eating triggered the pain and each episode lasted thirty to 60 seconds. His only significant medical history was an excision of a haemangioma from his neck. A diagnosis of trigeminal neuralgia was made and carbamazepine commenced. Subsequent examination revealed jerky pursuit eye movements. An MRI scan of brain was organised and revealed a large left sided mass lesion in the posterior fossa, confirmed following later excision to be LDD. Trigeminal neuralgia has not previously been reported in association with LDD.

The pathogenesis of LDD remains unclear. An association between the condition and Cowden Syndrome—an autosomal dominant multiple hamartoma-neoplasia syndrome—has been identified with associated lesions including cutaneous haemangiomas (as in this case), adenomas, and adenocarcinomas. The syndrome is the result of mutations in the phosphatase and TENsin (PTEN) homologue tumour suppressor gene on chromosome 10. The diagnosis of LDD should therefore prompt screening for neoplasia and genetic counselling offered.

047 VIRAL VECTORS FOR IMMUNISATION AGAINST POTASSIUM CHANNEL Kv1.2

K. M. McKnight, M. M. McMenamin, N. Horwood, Y. Hart, M. Wood, J. Palace, B. Lang, A. Vincent.Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK; Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK; Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK; Kennedy Institute of Rheumatology, Imperial College, London, UK

Antibodies to voltage gated potassium channels (VGKC) have recently been reported in sera of patients with limbic syndromes. In our study, sera from 139 patients with seizures were assayed for antibodies to VGKC. These antibodies were present in 16 patients, with the highest titres found in patients presenting with an encephalopathic illness associated with cognitive problems or confusion.

There is a need to create an animal model of this condition by inducing VGKC antibodies in the periphery that then cross the blood brain barrier and alter behaviour. To begin to do this, we are using a viral vector to over-express potassium channel antigens for immunisation, with or without green fluorescent protein (GFP) as a marker. We cloned the Kv1.2 potassium channel sub-unit and put it into an adenoviral vector with GFP. HEK cells transfected with the plasmid or with the adenoviral vector, show strong green fluorescence and high numbers of 125I-dendrotoxin binding sites (dendrotoxin binds to VGKC). All mice inoculated with this viral vector produce antibodies to GFP, and a proportion to VGKC. Thus we have established this approach as a feasible strategy to generate an immune response to this ion channel protein.

048 THE COMPREHENSIVE NEUROLOGICAL EXAMINATION IN 1897 COMPARED WITH 2002 – FROM HUTCHISON’S CLINICAL METHODS

A. McNeill, C. Warlow.Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK

Introduction: Investigative techniques have presumably reduced the importance of physical examination in diagnosis. The hypothesis that modern diagnostic techniques have made the need for medical students and non-neurological specialists to learn a comprehensive neurological examination obsolete was investigated by analysing the 1897 and 2002 editions of Hutchison’s Clinical Methods.

Methods: The nervous system chapters were compared with respect to length of the sections on examination, and investigative techniques. The chapters on respiratory and cardiovascular systems served as a control. It was not possible to compare the information on history taking.

Results: The text on neurological examination in 2002 was almost 50% longer than that in 1897 (29 632 vs 19 110 words) while sections on investigative techniques were almost the same (2300 words vs 1850 words). Between 1897–2002 several manoeuvres were added to the neurological examination and none removed. In contrast, in the cardiovascular and respiratory chapters the text devoted to physical examination shrank with removal of several techniques such as cardiac percussion. The 2002 book had sections on echocardiography, chest x ray, etc, which were not in the 1897 book.

Conclusions: The introduction of modern investigative techniques has not been paralleled by a reduction in what is regarded as a comprehensive neurological examination, unlike in cardiology and respiratory medicine.

049 FRAGILE X-ASSOCIATED TREMOR/ATAXIA (FXTAS) SYNDROME IN A WOMAN UNMASKED BY CHEMOTHERAPY

J. P. O’Dwyer, M. Sweeney, J. Crown, D. E. Barton, M. Hutchinson.Department of Neurology, St. Vincent’s University Hospital, Dublin, Ireland

Aims: FXTAS is characterised by tremor, gait ataxia, cognitive impairment, and occasionally parkinsonism, usually in male premutation carriers of the FMR1 gene. The aim is to describe FXTAS in a woman, which became clinically apparent after a single dose of chemotherapy

Case Report: A 70 year old woman developed an acute onset gait ataxia, postural tremor of the upper limbs, and titubation after starting carboplatin and docetaxel (in non-toxic doses) for metastatic breast cancer. She has two sons with Fragile-X mental retardation syndrome. Chemotherapy was stopped and she improved to her baseline of mild gait ataxia and head tremor and mild cognitive impairment. Docetaxel alone was recommenced with no deterioration. MRI brain showed atrophy of the posterior vermis and cerebellar hemispheres. PCR and southern blotting identified her as a premutation carrier with 95 CGG repeats (normal < 55)

Conclusion: Only five women have been reported with FXTAS, and in one of these, autopsy showed intraneuronal inclusions. In this woman, a subclinical FXTAS became symptomatic due to chemotherapy. Such patients may be more susceptible to toxic insults.

050 EMAIL TELENEUROLOGY TO THE DEVELOPING WORLD: THE EXPERIENCE OF THE SWINFEN CHARITABLE TRUST

V. Patterson, S. Read, M. Kamal, K. Youngberry, R. Swinfen, P. Swinfen.Royal Victoria Hospital, Belfast, Ireland; Royal Brisbane and Womens Hospital, Brisbane, Australia; Centre for the Rehabilitation of the Paralysed, Dhaka, Bangladesh; Centre for Online Health, Brisbane, Australia; Swinfen Charitable Trust, Canterbury, UK

Neurological diseases are very common in the developing world and neurologists are very scarce so that neurologically inexperienced doctors often have to deal with complicated neurological patients. In 1999 the Swinfen Charitable Trust (SCT) set up an email telemedicine service, which included neurology, between the Centre for the Rehabilitation for the Paralysed (CRP) in Dhaka, Bangladesh and specialists mostly based in the UK. Clinical or radiological images could be attached to the emails. SCT now services 17 countries and last year dealt with 289 referrals. 98 neurological referrals have been made, comprising 12% of the total. The referrals have originated mainly in Bangladesh (59%) and Nepal (28%). Most referrals were extremely complex, weakness was the commonest symptom, and reasonably definite diagnoses were reached in over 80%. Two wheelchair-bound patients with a probable diagnosis of dysimmune neuropathy gained the ability to walk unaided. Eventual outcomes are difficult to obtain in this group of patients but face-to-face review of five patients seen at CRP revealed diagnostic discordance in only one. Satisfaction of referring doctors was high. Email is an effective way to connect neurologists in the industrialised world with neurological patients and their doctors in the developing world.

051 THE ROLE OF THE ACUTE DOPAMINERGIC CHALLENGE REVISITED

H. Seow, S. Kamath, N. Marshall, N. Bajaj.Department of Neurology, Queen’s Medical Centre, Nottingham, UK; Derbyshire Royal Infirmary, Queen’s Medical Centre; Department of Care of the Elderly Medicine; Queen’s Medical Centre, Derbyshire Royal Infirmary, Queen’s Medical Centre; Department of Neurology, Queen’s Medical Centre

Clarke and Davies in 2000, concluded that acute dopaminergic testing (ADT) “add(s) nothing while causing significant adverse events and additional cost”. We chose to audit all ADT carried out in our department between 2002–2004, to see if a role remained for acute testing.

Results: In the majority of challenge tests (28/36), ADT was the test of choice and had defined advantages over chronic levodopa testing (CDT).

Conclusions: We believe ADT has a role in specific patients. CDT is reliant on subjective patient assessment and side effects of chronic therapy may limit a therapeutic dose being achieved. Details of CDT carried out by referring physicians are often lacking and may have been inadequate.

CDT is often avoided in the younger patient because of the possibility of “priming”. The efficacy and dose equivalence of subsequent oral chronic agonist challenges in these patients has not been validated and non-responders may go on to ADT in any case.

Both ADT/CDT continue to have a role in differentiating IPD from other Parkinsonian conditions. The cost equivalence of day-case ADT versus 2–3 months of CDT, outpatient assessment and GP monitoring may be comparable.

To further enhance ADT we propose a double blinded test protocol which is standardised across centres.

052 NEW LEVODOPA/CABIDOPA/ENTACAPONE (STALEVO®) PROVIDES BETTER QUALITY OF LIFE FOR PARKINSON’S DISEASE PATIENTS AND SAVES COSTS TO THE SOCIETY

L. J. Findley, H. Turunen, M. Apajasalo, A. Lees.Essex Neurosciences Unit, Oldchurch Hospital, Essex, UK; Orion Pharma, Espoo, Finland; Reta Lila Weston Institute of Neurological Studies, London, UK

Objective: Using entacapone with levodopa improves motor control and patient functionality in Parkinson’s disease (PD) patients experiencing wearing-off. We aimed to evaluate the cost effectiveness of Stalevo vs standard of care (SoC) in the UK.

Methods: Cost effectiveness was analysed using a Markov model and probabilistic sensitivity analysis. Data was obtained from UK naturalistic burden-of-illness studies and the pivotal studies of entacapone. Analysis was performed from societal perspective including total direct costs and from the UK National Health Service (NHS) perspective including only costs to NHS.

Results: In 10 years, Stalevo provided significantly more quality-adjusted life years (QALYs) than SoC, +1.04 QALYs/patient. Direct costs to society decreased by £10 200/patient. Costs to NHS increased by £3240/patient. Thus, to the NHS there was an incremental cost of £3100/QALY gained. In sensitivity analyses Stalevo either saved costs or remained below 30 000£/QALY with >96% probability, both from NHS and societal perspective. Furthermore, in total direct costs Stalevo provided savings to society with a probability of 77%.

Conclusion: Treatment with Stalevo is cost effective. In the long term, Stalevo provides better quality of life for patients. Although costs to NHS increase slightly, the incremental cost/QALY gained is low. Furthermore, for the UK society as a whole Stalevo saves costs.

053 TREATMENT CHANGE IN THE FIRST 12 MONTHS OF PARKINSON’S DISEASE TREATMENT

I. P. Keary, S. Buchan, J. R. Playfer, L. J. Findley.Strategen Ltd, Royal Liverpool University Hospital, Liverpool, UK; Essex Neuroscience Unit, Old Church Hospital, Essex, UK

Prescription and resource use data were collected on 3597 new Parkinson’s disease patients from general practices distributed across the UK (using Compufile’s DIN-LINK dataset).

Retention on initial treatment was significantly higher (p < 0.05) in those patients receiving levodopa (60%) than those receiving dopamine agonists (44%). Overall levels of add-on (p < 0.05) and switch (p < 0.05) were lower in levodopa patients (n  =  2581; add-on 14.1%; switch 2.9%) as compared to patients receiving any dopamine agonist (n  =  138; add-on 29.7%; switch 19.6%).

Retention of patients on their original treatment was related to the lowest levels of consultations, referrals, outpatient visits, and hospital admissions; the number per patient of the latter three criteria being half that observed in patients who switched treatment.

These results confirm that levodopa is very effective in new Parkinson’s disease patients. This may indicate that a beneficial and cost effective strategy would be one that optimises and extends the use of levodopa in this patient group. Further research is required to ascertain whether the high dropout rate of patients on dopamine agonist monotherapy is observed when dopamine agonists are used in combination with levodopa therapy, and whether strategies to extend the duration of levodopa may provide a more effective treatment.

054 DIFFERENTIATING DRUG-INDUCED PARKINSONISM (DIP) FROM PARKINSON’S DISEASE (PD) WITH FP-CIT SPECT (DaTSCAN): PRELIMINARY RESULTS

V. Marshall, J. Patterson, D. Hadley, K. Grosset, D. Grosset on behalf of the UK FP-CIT StudyDepartments of Neurology and Neuroradiology, Institute of Neurosciences, Southern General Hospital, Glasgow, UK

Background: Brain FP-CIT SPECT (DaTSCAN) is abnormal in PD and normal in DIP, which can be mistaken for PD.

Aim: To assess the clinical usefulness of DaTSCAN in uncertain parkinsonian conditions with differential diagnosis of PD or DIP.

Methods and results: 35 patients (mean age 63 (SD 14) years) underwent SPECT in five centres. The referring clinician recorded clinical details pre- and post-scan. Pre-scan diagnosis was judged most likely PD in 10/35 (29%); DaTSCAN was abnormal in keeping with the clinical diagnosis in 8/10 (80%) and normal in 2/10 (20%), and was amended post-scan to DIP in these two cases. Pre-scan diagnosis was DIP in 25/35 (71%); DaTSCAN was normal (or focal lesion due to structural change, e.g. infarction) in keeping with the clinical diagnosis in 21/25 (84%) and abnormal in 4/25 (16%); in 3/4 post-scan diagnosis was changed to PD; in 1/4 the changes suggested vascular parkinsonism. Mismatch between pre-scan clinical diagnosis and scan result occurred in 6/35 (17%). Common culprit drugs for DIP were dopamine depletors (n  =  8) and traditional neuroleptics (n  =  6). Valproate-induced DIP occurred in two.

Conclusion: DaTSCAN disagrees with “most-likely” diagnosis pre-scan in nearly one fifth of cases with amendment of post-scan diagnoses in line with scan results. It is a useful diagnostic aid in uncertain parkinsonian conditions with differential between PD and DIP.

055 SYDENHAM’S CHOREA WITH ANTI-BASAL GANGLIA ANTIBODIES, NEW-ONSET DIABETES MELLITUS, AND PROMINENT BASAL GANGLIA CALCIFICATION

S. O’Riordan, S. Bigham, H. R. Cock.Department of Neurology, Atkinson Morley Wing, St. George’s Hospital, London, UK

Case report: We report a 29 year old woman who presented with a severe generalised asymmetric, choreiform movement disorder, mild encephalopathy, and prominent mutism. This developed within 2 weeks of a mild pharyngitis. She took no regular medications, was not pregnant, and had no family history of movement disorder. Investigations: blood glucose was 21 mmol/l; she was not acidotic. ASOT was raised at 200 IU/ml. Anti-basal ganglia antibodies were detected in serum. Oligoclonal banding was present in CSF. CT and MRI brain demonstrated marked basal ganglia calcification. EEG was abnormal with episodic forms in the temporal areas and generalised mini-spike and wave discharges. Calcium, parathyroid hormone, and vitamin D were normal. Haemoglobin, ESR, caeruloplasmin, copper, CSF lactate, and thyroid function were normal. Vasculitis screen, lupus anticoagulant and HIV test were negative. Echocardiogram and ECG were normal.

Outcome: Diabetic control was quickly achieved and sodium valproate was used to treat the chorea, which resolved over several weeks.

Conclusion: We report an unusual case of Sydenham’s chorea in a young woman with prominent basal ganglia calcification and new-onset diabetes mellitus. We propose that the presence of basal ganglia calcification and diabetes may have predisposed this patient to development of a severe post-streptococcal movement disorder. (Video available).

056 THE BASAL GANGLIA CHOLINERGIC NEUROCHEMISTRY OF PROGRESSIVE SUPRANUCLEAR PALSY (PSP)

N. M. Warren, M. A. Piggott, D. J. Burn.Medical Research Council; Newcastle General Hospital, Newcastle, UK

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder with motor and cognitive dysfunction. There is no effective treatment either for symptomatic relief or disease modification. This relates in part to a lack of knowledge of underlying neurochemical abnormalities.

We measured, autoradiographically, muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum and pallidum of pathologically confirmed cases of PSP (n  =  17), and controls (n  =  52). M2 receptors were visualised with 4.8 nM [3H]AF-DX 385 in the presence of 10 nM dicyclomine, and M4 measured by subtraction of M2 density from combined M2/M4 binding (AF-DX alone).

In both PSP and control groups M2 and M4 binding was highest in the caudate and putamen. In PSP, there was a reduction in M2 and M4 receptors in the posterior caudate (p < 0.01 for both receptors) and a reduction in M2 receptors in the posterior putamen compared to controls (p < 0.01). M4 receptors were elevated in PSP in the internal globus pallidus (GPi) (p < 0.01).

The reduction in posterior striatal M2 receptors in PSP cases is most likely due to loss of cholinergic interneurones. The reduction of posterior caudate M4 receptors suggests loss of medium spiny projection neurons bearing these receptors. Knowledge of receptor status in PSP may lead to a greater understanding of neuronal selective vulnerability and refine targeting of cholinomimetic therapeutic agents.

057 TACROLIMUS INDUCED CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY AND ISCHAEMIC STROKE

S. Bigham, A. Nitkunan, H. Cock.Clinical Neurosciences, St George’s Hospital Medical School, London, UK

Background: Tacrolimus (FK506) is a potent immunosuppressive drug, most widely used following organ transplantation. Rarely patients have been reported as having a severe demyelinating neuropathy, occurring between 2 and 10 weeks after commencement of tacrolimus and responding well to intravenous immunoglobulin or plasmapheresis. Tacrolimus has also been associated with an increased risk of thromboembolic events. We report the case of a 59 year old man with both chronic inflammatory demyelinating polyneuropathy (CIDP) and a transient ischaemic attack (TIA) on tacrolimus.

Results: : BK underwent liver transplant for post-operative multiorgan failure, and started on Tacrolimus. Six weeks later he developed increasing weakness in his legs, and by the time of presenting to us at 3 months he was unable to stand unaided. The diagnosis of CIDP was confirmed on nerve conduction and CSF studies and his immunosuppressive therapy was changed to mycophenolate. Following intravenous immunoglobulin the patient has made substantial improvement. During investigation for his CIDP, he suffered a witnessed episode of expressive dysphasia lasting for one hour with no other deficit. Aspirin was commenced.

Discussion: This case highlights the importance of considering novel drugs as the cause of a patient’s symptoms, and that not doing so can lead to diagnostic delay.

058 CHILDHOOD ONSET DEMYELINATING NEUROPATHY AND CATARACTS: A POTENTIALLY TREATABLE DISORDER

C. B. Carroll, D. Majumdar, J. B. Winer, N. P. Davies.Birmingham Muscle and Nerve Centre, Department of Neurology, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK

Patient/Methods: We present a case of an 18 year old man who was the product of a consanguineous marriage and was initially referred to the paediatric clinic at the age of 10 years with a history of moderate learning difficulties, behavioural problems, and leg weakness. He was found to have distal wasting with bilateral pes cavus and lens opacities. Nerve conduction studies performed at that time revealed a severe demyelinating peripheral neuropathy. A presumptive diagnosis of CMT1 was made but genetic analysis did not confirm this.

On review in the adult neuromuscular clinic, the association of neuropathy and cataracts suggested only a narrow differential diagnosis.

Investigations/Results: Plasma cholestanol and urinary bile alcohols were elevated.

Conclusions: The patient had cerebrotendinous xanthomatosis (CTX). The typical presentation is with an axonal peripheral neuropathy and tendon xanthomata. Our case had no xanthomata and a demyelinating neuropathy.

This case illustrates that the diagnosis of CTX should be considered in young patients presenting with a combination of peripheral neuropathy and cataracts. If detected in early evolution, this disorder is potentially treatable with combination therapy of chenodeoxycholic acid and pravastatin.

059 A NOSOLOGICAL CASE STUDY OF BROWN-VIALETTO-VAN LAERE SYNDROME USING NEUROPHYSIOLOGICAL AND PROTON MAGNETIC RESONANCE SPECTROSCOPY TECHNIQUES

A. Cifelli, A. Goddard, P. P. Choudhary, N. Bajaj.Departments of Neurology, Radiology, Neurophysiology, Queen’s Medical Centre, Nottingham, UK

We present the case of a 60 year old man who developed bilateral optic neuropathies and deafness, lower motor neurone (LMN) facial weakness, transient stridor, and wasting of the small muscles of both hands over 3 months at the age of 12 years. The extent and distribution of his neurological deficits remained essentially static thereafter. A biochemical and haematological workup, CSF analysis including oligoclonal bands, lysosomal enzyme screen, luetic and Borrelia serology, testing for Kennedy’s disease, MELAS, MERRF, and NARP were normal or negative. NCS/EMG showed neurogenic changes in the upper limbs with normal sensory potentials. Central motor conduction times were normal. Brain MRI demonstrated diffuse small vessel ischaemic changes in the white matter. Magnetic resonance spectroscopy (MRS) of the precentral gyrus grey matter did not disclose any metabolic abnormalities.

A diagnosis of Brown-Vialetto-Van Laere syndrome (BVVLS) was formulated, on the basis of involvement of the II, VII, VIII, IX, and X cranial nerves with evidence of anterior horn cell disease in the upper limbs, and exclusion of alternative differential possibilities.

BVVLS is a very rare condition and our case contributes to the delineation of its natural history. Neurophysiology and MRS support the nosographic categorisation of BVVLS as a purely LMN entity.

060 MYCOPHENOLATE MOFETIL FOR DYSIMMUNE NEUROMUSCULAR DISEASES: EXPERIENCE IN A GENERAL NEUROLOGY UNIT

C. Donaghy, V. Patterson.Royal Victoria Hospital, Belfast, Ireland

Introduction: Mycophenolate mofetil (MM) is a relatively new immunosuppressant that is being increasingly used in the treatment of dysimmune neuromuscular disease. Our aim was to review the use of MM for dysimmune neuromuscular disease in a general neurology unit serving Northern Ireland.

Method: We identified patients retrospectively through neurology clinics and reviewed their case notes.

Results: We identified 18 patients treated by four consultant neurologists, eight with myasthenia gravis (MG), five with polymyositis (PM)/dermatomyositis (DM), four with dysimmune neuropathies, and one with a syndrome comprising antibody-positive MG, an anterior horn cell disorder and a femoral neuropathy. Four patients (22%) discontinued MM due non-serious and reversible side effects. Ten (56%) showed possible clinical efficacy, six remaining in remission for over 2 years. This group included four of the five patients with PM/DM. Patients on 2 g/day did better than those on 1 g/day. In four patients MM was clearly ineffective.

Conclusion: MM is reasonably safe with no major adverse effects. Our results for patients with PM/DM are encouraging, as little literature exists about MM in these conditions. We suggest that MM is a reasonable first-line immunosuppressant in patients with dysimmune neuromuscular disease and it should be compared with azathioprine in a randomised controlled trial.

061 MUSCLE SAMPLING IN INCLUSION BODY MYOSITIS

M. E. Farrugia, D. Hilton-Jones.Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder affecting predominantly quadriceps and finger flexor muscles. There are often concerns that a quadriceps biopsy will yield “end-stage”, non-diagnostic findings when the muscle is very wasted, while a deltoid biopsy may not be diagnostic because the muscle is often clinically unaffected. We studied 34 case notes retrospectively from patients with IBM, diagnosed on clinical and/or pathological grounds. All had a muscle biopsy (deltoid or quadriceps); four patients were biopsied twice, giving a total of 38 samples (17 quadriceps and 21 deltoid).

All patients but one had quadriceps weakness and wasting, 65% of patients had deltoid weakness, and 38% had wasting. In 71% of biopsies, pathological findings were supportive of a diagnosis of IBM (“definite” or “possible” by Griggs’ criteria). Although the remaining biopsies (29%) showed non-specific pathology, all patients ran a clinical course typical of IBM.

In 19 patients, biopsies (10 deltoid, 9 quadriceps) were diagnostic even when the muscle was obviously wasted. Conversely, three deltoid biopsies supported a diagnosis of definite IBM even though the muscle was clinically unaffected.

We conclude that sampling clinically unaffected muscles (including deltoid) can still yield positive pathological findings for IBM. Selection of muscle sampling should not be limited to quadriceps if IBM is being considered, nor should quadriceps be excluded as a biopsy site unless wasting is extreme.

062 BLINDNESS IN A CASE OF TETANUS

H. Hughes, D. Blackburn.Department of Neurology, Queen’s Medical Centre, Nottingham, UK

Introduction: Tetanus is a rare disorder in the developed world but remains an important cause of death worldwide. In the United Kingdom it has been frequently associated with intravenous (IV) drug users. Intensive care management has lowered the mortality especially from respiratory failure. However, the marked autonomic instability is still a major cause of mostly cardiac morbidity.

Case Report: We report the case of a 27 year old IV drug user who was admitted with trismus, neck pain, and muscular spasms. She had abscesses on her legs from sub-cutaneous heroin injection. Clostridium perfrinogens (sensitive to penicillin and metronidazole) and staphylococcus aureus (sensitive to flucloxacillin and erythromycin) was grown from these and her Tetanus antitoxin was measured by ELISA and found to be 0.047 iu/ml (0.01–0.1 suggests needs a boost). She spent 26 days on ITU but on the second day after discharge to a regular ward it became apparent that she was unable to see. Although she did not complain of visual loss to the doctors and nurse, she was unable to count fingers or appreciate different colours. She was only able to see shadows. Her pupils were dilated but reacted briskly to light. An MRI was performed and revealed bilateral occipital lobe hyperintensities that did not correspond to one vascular territory in keeping with reversible posterior leucoencephalopathy syndrome (RPLS). This was confirmed by a clinical improvement back to normal vision over 5–7 days and a repeat MRI, which showed resolution of the changes seen previously. She made an excellent recovery from the tetanus.

Conclusion: This case emphasises that tetanus is still a cause of severe disease in the UK, especially in IV drug users, and we report the first case of RPLS complicating tetanus that we are aware of.

063 THE GENETIC DIAGNOSIS OF CONGENITAL MYASTHENIC SYNDROMES (CMS)

S. Man, J. Cossins, P. J. Clouston, G. Burke, J. Palace, A. Seller, J. Newsom-Davis, D. Beeson.Oxford Genetics Laboratories, Churchill Hospital, Headington, UK; Neurosciences Group, Weatherall Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford, Oxford, UK; Myasthenic Centre, Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK

Objective: To describe a genetic diagnostic service for CMS.

Background: CMS are caused by mutations in genes involved in neuromuscular transmission. The Oxford Myasthenia Centre, supported by NSCAG (DoH), provides a nationwide service for the genetic diagnosis of CMS. Full mutation screening is offered for genes encoding the acetylcholine receptor (AChR) α, β, δ, and ε subunits, and rapsyn (postsynaptic proteins), choline acetyltransferase (ChAT, a presynaptic protein), and ColQ that anchors synaptic acetylcholinesterase. Functional analysis is available to determine the pathogenicity of novel mutations.

Results: Since April 2002, we have completed 110 full mutation screens, 75 carrier tests, and 46 diagnostic confirmations. A molecular diagnosis of CMS has been confirmed in 57 patients. Four case studies illustrate this service. In three of these, four novel mutations were found in the AChR-ε and rapsyn genes, including missense and single amino acid deletions. Two were confirmed to be pathogenic by functional analysis. The final case study describes prenatal diagnosis in a family harbouring ChAT mutations.

Conclusions: The fully integrated clinical and molecular diagnostic service provided by the Oxford Myasthenia Centre has enabled a definitive diagnosis to be established in many families with suspected CMS, allowing informed genetic counselling, disease prognosis and appropriate treatment.

064 A STING IN THE TALE – A UNIQUE CASE OF WASP-INDUCED AUTOIMMUNE NEUROMYOTONIA

M. R. Turner, A. Madkhana, G. C. McGavin, P. G. Sarrigiannis, R. P. Kennett, A. Vincent, G. C. Ebers.Department of Neurology, The Radcliffe Infirmary, Oxford, UK; The Oxford University Museum of Natural History, Oxford, UK; Department of Neurophysiology, The Radcliffe Infirmary, Oxford, UK; Department of Clinical Neurology, University of Oxford, UK

A 54 year old suffered an anaphylactic reaction to multiple stings from the “yellow jacket” wasp Vespula germanica. Four weeks later he developed sudden-onset twitching of the muscles, notably deltoids and quadriceps, associated with hyperhidrosis and insomnia. On admission creatine kinase was over 10 000 IU/l, which settled with bed rest. In the absence of both rigidity and myoglobinuria, this was ascribed to the “trauma” of continuous muscle activity (video to be shown). Neuromyotonia was confirmed neurophysiologically and voltage-gated potassium channel auto-antibodies were detected. He remained refractory to therapy with carbamazepine, intravenous immunoglobulin/methylprednisolone, and mexiletine. The end of a 5-day course of plasma exchange 8 weeks after onset coincided with the abatement of symptoms.

Neuromyotonia (described eponymously in part by Isaacs and Morvan) has been associated with a number of clinical conditions, including malignancy, severe polyneuropathies, and drugs e.g. penicillamine, none of which applied to our patient. The toxins of the Timber and Mojave rattlesnakes (Crotalus horridus/scutulatus) can also directly induce neuromyotonia. Pompilidotoxins from the rare spider wasp have been demonstrated in vitro to modulate synaptic transmission and slow sodium channel inactivation. Demyelinating lesions have been described in the context of the more common yellow jacket wasp sting, but not neuromyotonia to date.

065 ACUTE ISCHAEMIC STROKE MANAGEMENT: NUMBERS NOT TREATED

M. Armstrong, M. O. McCarron.Acute Stroke Unit, Altnagelvin Hospital, Londonderry, Ireland

Background: There is good evidence that acute stroke units (ASU) and thrombolysis within 3 hours of symptom onset benefit patients with acute ischaemic stroke (AIS).

Objective: To determine the proportion of patients with AIS who were admitted to a District General Hospital within 3 hours of stroke onset and the proportion of AIS patients denied admission to an ASU.

Methods: 100 consecutive AIS patients were enrolled in the study between March 2004 and November 2004. Demographic characteristics, time to admission, National Institute of Health Stroke Score (NIHSS), Oxfordshire Community Stroke Project classification, neuroimaging results, and admissions to the ASU were all prospectively recorded.

Results: There were 59 men and 41 women, mean age 68.8 years (SD 12). Mean NIHSS was 6.7 (6.6). 43% of patients were in hospital within three hours, 31% within two hours. Patients admitted within 3 hours had more severe strokes than patients admitted after 3 hours (NIHSS 8.7 vs 4.7, p  =  0.003). 33% of AIS patients were never admitted to the ASU.

Conclusion: This study confirms that there is no justification for the perception that delays in presentation prevent thrombolytic therapy for AIS patients. ASU service infrastructure needs to increase patient access.

066 ANTIPLATELET AGENTS FOR SECONDARY STROKE PREVENTION: HAS PRIMARY CARE TAKEN ON BOARD THE RCP GUIDANCE?

C. Doyle, M. S. Randall, G. S. Venables.Royal Hallamshire Hospital, Sheffield, UK

Introduction: Clear trial evidence exists for antiplatelet agents in the secondary prevention of stroke. The Royal College of Physicians (RCP) guidelines recommend that all patients with a presumed ischaemic stroke are commenced on antiplatelet therapy. Sheffield delivers rapid access stroke services via a nurse lead clinic. We review our four year experience of the incidence of anti-thrombotic therapy at time of referral.

Methods: A structured nurse led consultation for access to stroke services operates in Sheffield. Medication at referral is recorded and stored on a computer database. We reviewed the database for patients receiving antiplatelet or anticoagulant medication at the point of access.

Results: In four years 2728 patients have been reviewed. Over the four years the percentage of patients with possible stroke not on anti-thrombotic therapy has not changed.

2000/2001: 19.6% CI (16.3%–23.1%)

2001/2002: 19.5% CI (16.6%–22.6%)

2002/2003: 23.5% CI (20.4%–26.8%)

2003/2004: 22.6% CI (19.7%–25.7%)

A CT suggesting ischaemia was found in 169 (28.9%) of these patients. Clinical or CT contraindications were shown in 160 (27.4%) patients.

Conclusions: Consistently patients being referred for stroke are not on anti-thrombotic therapy. Assuming GPs correctly refer only stroke or TIA patients, because treatment prevents 5/1000 recurrent strokes (Cochrane review), then three patients remained at risk of further events. A further 169 patients may have benefited from treatment because of ischaemia on their CT scan.

067 ASCENDING MYELOPATHY FOLLOWING SPINAL CORD INJURY IS PROBABLY DUE TO VENOUS INFARCTION

S. Hunt, V. Patterson.Royal Victoria Hospital, Belfast, Ireland

Ascending myelopathy is a rare, ill-understood, and potentially fatal complication of spinal cord injury. The following case suggests that it has a treatable cause.

A 35 year old man sustained a fracture of L1 with total flaccid paraparesis, sensory level to L1 and loss of sphincter control. Seven days later he noticed ascent of his sensory level onto his abdomen and over the next 11 days to T2. On day 20 he had weakness of triceps, wrist flexors, finger extensors, and abductors with impaired position sense in the fingers. Tendon reflexes were present. Initial MRI of the cervical cord was normal, but on day 18 showed cord swelling and irregular high signal on T2-weighted images. CSF was acellular with a protein of 3.8 g/l and the presence of blood-breakdown products. He was treated with full-dose intravenous Heparin for presumed venous infarction of the cord and within 24 hours there was objective improvement. He was converted to warfarin and at 6 months his sensory level was at T4 with normal hand function and no signs. MRI showed cord atrophy.

MRI, CSF findings, and rapid response to heparin all suggest that venous infarction is the cause of this ascending myelopathy.

068 LOCATION-SPECIFIC VOLUME OF EARLY PERIHAEMATOMA OEDEMA

P. McCarron, M. J. Alberts, M. O. McCarron.Department of Epidemiology and Public Health Medicine, Queen’s University of Belfast, Belfast, Ireland; Department of Neurology, Northwestern University Medical School, 710 N. Lake Shore Dr, Room 1420, Chicago, USA; Department of Neurology, Altnagelvin Hospital, Londonderry, Ireland

Background: Amyloid ε-protein (AE) induces the expression of matrix metalloproteinase-9 (MMP-9), which rises following ICH. We hypothesised that lobar ICH locally increases MMP-9 and causes larger perihaematoma oedema volumes than deep ICH.

Objective: To compare deep and lobar oedema:haematoma ratios.

Methods: Consecutive patients admitted to Duke University Medical Center with a CT-proven diagnosis of a supratentorial ICH documented within 24 hours of onset were studied. Patients with secondary ICH, intraventricular extension, or surgical intervention were excluded. Age and oedema:haematoma volume ratios for patients with deep ICH and lobar ICH were compared using the Student t test.

Results: Of 44 patients 19 had deep ICHs, mean ICH volume 14.5 ml (SD 12.7), mean oedema volume 10.9 ml (12.4). Twenty-five patients had lobar ICHs, mean ICH volume 26.9 ml (28.7) and mean oedema volume 19.8 ml (23.8). Patients with lobar ICH were older than patients with deep ICH (mean age 65.7 years vs 57.4 years, p  =  0.009). The mean oedema:hematoma volume ratios were similar for lobar and deep ICH patients (0.83 vs 0.81, p  =  0.93).

Conclusion: There are no major location-specific quantitative differences in early perihaematoma oedema. Further research should determine whether perihaematoma oedema formation beyond 24 hours differs between deep and lobar ICH.

069 USE OF ARCH AORTOGRAPHY FOR ASSESSMENT OF CAROTID STENOSIS PRIOR TO STENTING OR SURGERY: THE SHEFFIELD EXPERIENCE

M. S. Randall, V. Berczi, R. Balamurugan, D. Shaw, T. Cleveland, P. Gaines, G. S. Venables.Sheffield Teaching Hospital Foundation NHS Trust, Sheffield, UK

Introduction: Accurate assessment of carotid artery stenosis (NASCET/ECST criteria) ensures that only appropriate carotid intervention occurs following stroke or TIA. Ultrasound and magnetic resonance angiography (MRA) can be used to select patients for surgery. However, MRA alone may not fully assess the anatomy to allow carotid stenting to be performed safely. We review the outcomes of >300 arch angiograms comparing the safety profile of arch aortography with published figures for selective catheter angiography.

Methods: Independent review of medical records from the last 3 years of patients undergoing arch aortagram for carotid assessment was performed. Peri-procedural (0–6 hours) wound, cardiovascular, and neurovascular complications were recorded.

Results: In total 308 procedures were performed. No focal neurological deficits occurred. Two patients (0.6%) were noted to be mildly disorientated with no focal neurology post angiography. Cardiovascular complications (angina, arrhythmia, or hypotension) occurred in 10 (3.2%) patients. One of these patients had undergone a new technique using larger contrast boluses. No wound complications extending hospital stay occurred.

Conclusions: Experienced stenting centres performing pre procedure non selective carotid angiography can quote lower neurological complication rates than for selective carotid angiography. Newer spin techniques using larger contrast boluses can contribute to higher cardiovascular morbidity and should be used cautiously.

070 PLASMA D-DIMER LEVELS IN INTRACRANIAL VENOUS THROMBOSIS

D. S. Sokhi, S. E. Price, S. Kitchen, P. D. Griffiths.Sheffield Teaching Hospitals NHS Trust, Sheffield, UK; Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK; University of Sheffield, Sheffield, UK; Academic Unit of Radiology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK

Objective: Plasma D-dimer levels routinely help diagnose some thrombo-embolic disorders. We measured D-dimer in cases with suspected intracranial thrombo-embolic pathology, specifically intracranial venous thrombosis (ICVT) and idiopathic intracranial hypertension (IIH).

Methods: 53 patients (10 males; average age = 30.0 years) recruited prospectively had D-dimer samples taken within a week of diagnostic magnetic resonance imaging (MRI). Samples from 19 adult healthy volunteers provided a D-dimer cut-off at 538 ng/ml. All samples were processed using VIDAS (bioMérieux sa, France). The reporting neuroradiologist and laboratory personnel were blinded to patients’ clinical information. Results were analysed using the 2-tailed Mann-Whitney U test.

Results: Nine patients with ICVT had significantly raised D-dimer compared to the rest (p < 0.05) [VIDAS range  =  174–7600 ng/ml; six patients were above cut-off value]. 20 patients with unremarkable radiology (“MRI-normal”) had significantly lower D-dimer levels (p < 0.01)[VIDAS range  =  26–847 ng/ml], even when compared to 15 with other brain pathologies (intracranial haemorrhage, tumours, vasculitis)[VIDAS range  =  152–1906 ng/ml], but not when compared to nine with IIH (VIDAS range  =  168–1061 ng/ml). Sensitivity and specificity, respectively, in diagnosing ICVT was 67% and 71%, and in “MRI-normal” cases was 50% and 84%.

Conclusion: D-dimer levels in “MRI-normal” and ICVT, but not IIH, patient categories differ significantly, and infer high specificities for diagnosing either category by serum sampling.

071 THE EVALUATION OF A NOVEL “GOAT SERUM” THERAPY (AIMSPRO) IN MULTIPLE SCLEROSIS

G. Burke, A. Cavey, P. M. Matthews, J. A. Palace.Clinical Neurology, Radcliffe NHS Trust, Oxford, UK

Anecdotal reports suggest dramatic immediate clinical improvement when goat serum (Aimspro) is given to patients with multiple sclerosis (MS).

This is the first randomised, double blind, placebo controlled study of this treatment and was designed to explore the effect of short-term administration of Aimspro in MS patients with chronic visual impairment from optic neuritis.

Twelve MS subjects were recruited, who had a history of optic neuritis and residual visual impairment. Objective neurophysiological, functional MRI, and visual field assessments were performed and results compared between groups treated with either Aimspro or placebo.

Both Aimspro and placebo were well tolerated and there were no serious adverse events. Treatment with Aimspro showed no significant benefit in the primary or secondary outcome measures of visual evoked potential amplitude or latency, or the amplitude of the BOLD response in the fMRI experiments. Although a visual field outcome improved (p < 0.05) this change was not significant when compared directly to that with placebo (p  =  0.34).

This study was exploratory and was powered to assess a short term and large improvement after three treatment doses. The major visual deficit in most patients was peripheral and the improvement seen in this outcome needs further exploration.

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