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Proceedings of the Association of British Neurologists Autumn Meeting, 1–3 October 2003

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ABN MEDAL AWARD 2003

David Aitken Shaw. NEF Cartlidge

Like most Englishmen who have held high office, David Shaw is a Scot. In common with many of his generation he was late into medicine, having served in the Navy in the latter part of the war. His seafaring career was cut short when his landing craft was sunk by a torpedo and he moved to train in medicine. The Navy’s loss has definitely been neurology’s gain.

His early training in Edinburgh with J K Slater excited his interest in neurology and he subsequently became Lecturer at The National Hospital with John Marshall and was one of the earliest neurologists to develop an interest in cerebrovascular disease and stroke.

Henry Miller recognised his talents and brought him to Newcastle to expand research activities into cerebrovascular disease, but David’s interests soon turned to undergraduate education and he rapidly progressed up the medical school hierarchy, becoming Clinical Sub-Dean, and Dean.

His manifest experience and enthusiasm in this area became recognised when as a member of the GMC, he became Chairman of the Education Subcommittee and was largely responsible for the production of the document “Tomorrow’s doctors”.

The statutory recommendations of this document have transformed medical education, resulting in—among other things—a shift of emphasis from factual information to clinical skills. Tomorrow’s doctors are indebted to David Shaw.

He has made considerable contributions to the JCHMT, the University Hospitals Association, the Association of the Study of Medical Education and of course, our own Association, serving as Council member, being Treasurer for many years, and becoming President in 1988.

The Association has chosen wisely to honour David Shaw with the award of its medal for his contributions to neurology, to the Association itself, and to medical education in general. Professor Shaw, we look forward with interest to your presentation on “Pupils of Argyll-Robertson”.

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

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

Design: IST-3 is a multicentre, randomised, controlled trial of intravenous rt-PA (0.9 mg/kg) in patients with acute ischaemic stroke <6 hours of onset. Full protocol can be found at www.ist3.com. The small start up phase (2000–2002) is complete. The expansion phase (2003–2004) aims to: establish up to 50 well organised centres capable of administering rt-PA; further streamline trial procedures; randomise up to 400 patients. The main trial (2005–2009) aims to involve at least 6000 patients from up to 400 centres worldwide.

Results: By 13 May, 107 patients had been recruited from 13 centres in the UK, Italy, Norway, and Belgium. The median time to randomisation was 3.7 hours and median onset to treatment 4.1 hours. At baseline: 75% were aged >70 years; 52% of the patients had total anterior circulation, 38% partial anterior, 7% lacunar, and 3% posterior circulation stroke syndrome. The Data Monitoring Committee has reviewed the accumulating data in confidence and urged us to increase recruitment as rapidly as feasible.

Conclusion: The trial is recruiting patients that might benefit from thrombolysis, but do not precisely meet the current criteria for treatment within the product licence. UK neurologists are invited to support the trial.

037 VASCULAR RISK FACTORS IN CADASIL

S. S. Razvi, R. Davidson, I. Bone, K. W. Muir. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK

Background: Notch 3 mutations on 19p13 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Role of vascular risk factors on the clinical phenotype is unclear.

Methods: Individuals from genetically confirmed CADASIL pedigrees reviewed and details entered on a Progeny 4.5 Database. History of conventional vascular risk factors (diabetes, ethanol excess, smoking, hypercholesterolaemia, ischaemic heart disease, peripheral vascular disease, and hypertension) was sought from the database. These factors were entered into a logistic regression model to predict the onset of vascular events below age 40.

Results: 25 patients (17 male, 9 pedigrees, 21 alive) were reviewed. The age at onset of first vascular event varied from 25–61 years. Six patients had onset of vascular events before age 40. No cases had a history of IHD, PVD, or hypertension. No factors significantly predicted early onset of vascular symptoms. Diabetes and alcohol excess were associated with increased risk of early onset (DM hazard ratio 2.71 (95% CI 0.13 to 55.9), alcohol HR 1.59 (0.04–59.6)) while smoking and hypercholesterolaemia were associated with reduced risk (smoking HR 0.30 (0.02–5.34), cholesterol HR 0.31 (0.03–3.36)).

Discussion: Few cases with a history of conventional vascular risk factors were identified from the database. Age at onset—even within pedigrees—was confirmed to be highly variable in the Scottish CADASIL population. Preliminary analysis suggests that conventional risk factors may exert divergent effects on age at onset.

038 MULTISLICE CT ANGIOGRAPHY AT A TIA CLINIC

S. S. M. Razvi, E. Teasdale, C. Santosh, P. Crawford, I. Bone, K. W. Muir. Departments of Neurology, Medicine for the Elderly, and Neuroradiology, Southern General Hospital, Glasgow, UK

Background: TIA clinics endeavour to promptly identify risk factors amenable to intervention (for example, significant carotid stenosis). Multislice CT angiography (CTA) offers rapid assessment of cervical and intracranial vasculature.

Methods: Retrospective review of patients assessed at a TIA clinic (11 months, 2001–2002). Cerebral imaging was performed using plain CT and CTA covering the aortic arch to circle of Willis. CTA images were reconstructed and analysed by a neuroradiologist.

Results: 168 patients (mean age 64 (SD 12) years) were reviewed. 108 had stroke or TIA (28 stroke, 80 TIA). 64/105 (62%) plain CT scans and 57/80 (71%) CTAs were abnormal, including significant carotid stenosis in 16 (including two complete occlusions), and 41 with other abnormalities (non-significant carotid stenosis, atheromatous disease without stenosis, and one intracranial stenosis). One required additional MR angiography (due to artefact from calcific plaque). Doppler ultrasound detected significant stenosis in only two of the four (with significant stenosis on CTA) examined. All examinations were tolerated. There were no adverse reactions.

Discussion: CT angiography is a safe and well tolerated method of evaluating intra and extracranial vasculature with superior anatomical coverage to Doppler examination.

039 TIME SINCE EVENT AND OTHER DETERMINANTS OF LESION PRESENCE ON DIFFUSION WEIGHTED MR BRAIN IMAGING

U. G. R. Schulz, D. Briley, T. Meagher, A. Molyneux, P. M. Rothwell. Stroke Prevention Research Unit, Department of Clinical Neurology, Radcliffe Infirmary, Oxford; Dept of Neurology, Stoke Mandeville Hospital, Aylesbury; Dept of Radiology, Stoke Mandeville Hospital, Aylesbury; Department of Neuroradiology, Radcliffe Infirmary, Oxford, UK

Background: We have previously showed that ischaemic lesions are often seen on diffusion weighted MR brain imaging (DWI) several weeks after a TIA or minor stroke. However, this may reflect asymptomatic recurrences rather than the presenting event. We therefore performed a longitudinal study with T2 and DW imaging at baseline, 2, 4, 8, and 12 weeks in 10 minor stroke patients with an acute infarct and a cross sectional study in 243 consecutive outpatients, who all had T2 and DWI at a median of 17 days (range 3–60 days) after a TIA or minor stroke. A neurologist and a neuroradiologist reviewed the scans independently.

Results: In the follow up study, the initial lesion was present on the 4 week scan in all patients, and on the 2 month scan in five patients, and no asymptomatic new lesions occurred. In the cross sectional study, DWI was positive in 81/126 stroke patients and 16/117 TIA patients (OR = 10.3; 95% CI 4.8 to 22.0; p⩽0.0001). Lesions were associated with persisting neurological signs (OR = 6.9; 95% CI 3.3 to 14.6; p⩽0.0001), increasing NIH score (p = 0.002), increasing age (p = 0.01), and negatively associated with time since event (p = 0.01).

Conclusion: Ischaemic lesions on DWI commonly persist for several weeks after minor stroke and asymptomatic new lesions are rare. DWI is therefore useful in lesion localisation in outpatients with minor stroke.

040 IS RAPID STROKE ASSESSMENT CLINIC RAPID ENOUGH?

G. Venables, S. N. Salam, C. Doyle, C. Kimura, E. Widjaya. Neurology Department, Sheffield Teaching Hospitals NHS Trust, UK

Objective: The incidence of early stroke after TIA may be higher than previously accepted, later interventions targeting a low risk population. The Sheffield Nurse Led Rapid Stroke Assessment Clinic (RSAC) aims to see patients from general practice with TIA, minor stroke, or amaurosis fugax within five working days. Information was gathered over 26 months from non-attendees to establish the incidence of early stroke.

Methods: A single observer identified all non-attendees and reviewed the notes of those admitted to hospital. GPs were contacted when information was not obtainable and death certificates reviewed. All those with stroke were identified and when possible categorised.

Results: Between October 2000 and December 2002 there were 1452 referrals from GPs to the RSAC. There were 121 non-attendees, 38 of whom (31.4%) had a stroke within 90 days of referral, 27 (71%) within the first 3 days. Thirteen (34.2%) were fatal. 80% were due to cerebral infarction.

Conclusion: Non-attendees had a high risk of stroke in the first few days after TIA, suggesting that highest risk patients were not seen in time; clinical trials are needed to establish whether immediate intervention with antiplatelet drugs, statins, or antihypertensive agents have an impact in these patients.

041 ACUTE CEREBRAL CT EVALUATION OF STROKE STUDY

A. J. Farrall, O. Mielke, R. von Kummer, C. Armit, D. Perry, J. M. Wardlaw. Universities of Edinburgh, Heidelberg, and Dresden

Background: CT scans are difficult to interpret in acute stroke.

Aims: (1) Improve reliability of CT scan interpretation in early stroke and (2) develop a web based CT viewing and coding tool for randomised trials.

Design: We have developed an internet based, interactive CT reading tool. Several hundred readers of different nationalities (European, Canadian, Australian), specialties (general and neuroradiologists, neurologists, geriatricians), and experiences (trainees, consultants) are interpreting about 60 CT scans, to test interobserver and intraobserver reliability. Test CT scans are from several sources and include various acute infarct signs; assessments are entered directly into a database for analysis.

Trial status: By 7 May 2003, 463 physicians had registered and been assigned a test scan (ensures good scan visualisation on local PCs). Of the 463, 269 had successfully completed the test scan. Of the 269, 173 had completed their first 10 scans; 27 have completed 54 scans. The median time for all participants to date, to interpret one scan, is 3 minutes.

Conclusion: Web based CT classification is practical and allows access to large groups of readers. Image quality is good. Further information and registration can be found at www.neuroimage.co.uk. The study is ongoing; we welcome new participants.

042 “FUNNY” STROKES IN EAST ANGLIAN SIBLINGS

K. A. Harkness, E. A. Warburton, P. J. Martin, P. J. Kirpatrick, I. McNamara, H. Firth, N. J. Higgins, C. Borland, J. C. Baron. Addenbrooke’s Hospital, Cambridge; Hinchingbrooke Hospital, Huntingdon, UK

Our first patient presented at age 11 with jerking episodes affecting right arm and leg. CT and EEG were normal and symptoms resolved with carbamazepine. Aged 19 she represented with a clumsy right side and transient aphasia. Her younger brother presented with sudden headache and left visual field disturbance at age 25. Detailed history revealed headache and transient dysphasia 2 years earlier. Cerebral angiography in both siblings showed extensive bilateral moyamoya disease (MMD) affecting both anterior and posterior circulation.

The sister underwent left extradural-intradural synangiosis in 1996 followed by contralateral surgery at 3 months. At recent follow up she had mild clumsiness in right hand and mild migraine like headaches. Her brother recently underwent left external carotid-internal carotid bypass surgery and contralateral surgery is planned. He currently has mild persistent left upper quadrantonopia and mild pyramidal weakness affecting his left arm.

In Japan the familial incidence of MMD is 7–10%. There are few reports in the white population and rarer reports of familial MMD. Sibling pair linkage analysis indicates a gene on 3p 24.2–26 in one Greek and several Japanese families and to 17q25 in other Japanese families. Our siblings are white from unrelated parents and MRA screening of family members is underway.

043 RETRIEVING MEANING AFTER TEMPORAL LOBE INFARCTION

D. J. Sharp, S. K. Scott, R. J. S. Wise. MRC Cyclotron Unit, Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, UK

We investigated the effects of “Wernicke’s area” infarction on function within intact downstream cortical regions involved in accessing word meaning. Nine patients and 19 normal subjects underwent PET activation studies. All subjects made decisions based on the meaning of heard words (Sem) with the control task requiring retrieval of word sound structure. Both groups heard words presented as clear speech (Cl). In addition, the normals heard degraded speech (Deg), making the stimuli more difficult to comprehend. Although the patients’ performance was impaired compared with normals on SemCl, it was no different from normals on SemDeg. SemCl in normals activated the left ventromedial temporal cortex (VMTC) and left prefrontal regions. Comparing patient and control groups, prefrontal involvement was no different, but patients showed significantly less left VMTC activation. Reduced left VMTC activity was also observed when normals performed SemDeg. Further, increasing activity in the right VMTC in the patients predicted accuracy on SemCl. Thus, activation of the left VMTC during controlled retrieval of meaning is reduced by either damage to ipsilateral auditory cortex or degradation of the speech signal; the result of impaired mapping of sound to meaning. Following chronic aphasic stroke, there was evidence for compensatory plasticity within right VMTLC.

044 EARLY ONSET ALZHEIMER’S DISEASE IN A SIB PAIR WITH THE PRESENILIN-1 GENE R269G MUTATION

A. J. Larner, M. Doran. Cognitive Function Clinic, Walton Centre for Neurology & Neurosurgery, Liverpool, UK

Objective: Clinical and neuropsychological findings in two siblings with early onset Alzheimer’s disease (EOAD) with the R269G point mutation in the presenilin-1 (PSEN-1) gene are presented. To our knowledge this is only the second family to be reported with this specific mutation. Findings were compared with previous reports of mutations at this codon.

Results: Age at onset (AAO) was 49 years in both siblings. The brother presented with major depressive disorder resistant to standard pharmacotherapy and requiring ECT. Obsessional behaviour traits, cognitive decline with prominent aphasia, auditory hallucinations, myoclonus, and seizures developed thereafter. The sister presented with cognitive decline with prominent visuospatial dysfunction, associated with behavioural features (agitation with pacing, shadowing behaviour), myoclonus, and tonic-clonic seizures.

Discussion: Behavioural and psychiatric features were prominent in our patients. Clinical details were sparse in the single previously reported family with PSEN-1 R269G mutation (

): AAO was 47 years in the proband, with memory loss, dysfluent speech, and seizures. Another mutation at the same codon, R269H, has been reported in one individual, with AAO 47 years, and visual and auditory hallucinations (

).

Conclusions: EOAD cases with the R269G PSEN-1 mutation show phenotypic heterogeneity within and between families, as seen in EOAD families with other PSEN-1 mutations. Both genetic and epigenetic factors may contribute to phenotype modulation.

045 MEDICAL AND SURGICAL INTERVENTIONS IN THE FIRST 100 CASES OF VARIANT CJD IN THE UK—A RISK FACTOR FOR THE DEVELOPMENT OF THE DISEASE?

A. J. Lowman, D. Everington, H. Ward, R. G. Will. National CJD Surveillance Unit, Western General Hospital, Edinburgh, UK

Introduction: The most likely cause of variant Creutzfeldt-Jakob disease (vCJD) is dietary transmission of abnormal prion protein. However, other routes of infection and the possibility of secondary iatrogenic transmission must be considered. This paper evaluates the evidence for primary or secondary transmission via medical or surgical interventions.

Method: Information regarding the number, type, timing, and place of all medical and surgical interventions was obtained from the families, hospital, and general practice records of the first 100 cases of vCJD referred to the National CJD Surveillance Unit, 60 hospital controls, and 127 community controls.

Results: There may be a trend towards a higher number of medical interventions in cases than controls but this is not significant and numbers are small (p = 0.4). Commonest medical interventions were psychiatric, neurological, and respiratory; the most frequent surgical interventions were abdominal-pelvic, minor surgery, and dentistry. Cases had no excess of higher risk procedures. 16 cases had interventions post-symptom onset. Twelve patient pairs had interventions in the same hospital; mean time between interventions was 13.33 years (range 0.25–38 years).

Conclusion: There is currently no evidence that primary or secondary transmission of vCJD has occurred via these routes. However, many people may be incubating the disease and monitoring must continue in the future.

046 SIGNIFICANT WEIGHT LOSS ASSOCIATED WITH LEVETIRACETAM: FOUR CASE REPORTS

S. Hadjikoutis, T. P. Pickersgill, P. E. M. Smith. Department of Neurololgy, Epilepsy Unit, University Hospital of Wales, Cardiff, UK

Background: Levetiracetam is indicated in refractory partial epilepsy. It has so far shown a favourable side effect profile. We report four cases of significant weight loss associated with levetiracetam. We have not identified any other cases reported in the literature of weight loss associated with levetiracetam.

Results: All four patients (3 female, age range 20–49 years) had localisation related epilepsy. Levetiracetam was introduced as an add on therapy. Within 5–12 months of starting levetiracetam the four patients reported significant weight loss (range 20–35 kg). None of the patients reported decreased appetite during the period of weight loss, however one developed pica craving only toast, cereal, scallops, and caviar. No other change of anti-epileptic treatment was made during the treatment period and no other cause of weight loss was identified. The commencement of levetiracetam was clearly related to the period of weight loss. All patients’ weight was stabilised or increased after reducing the dose of levetiracetam.

Conclusion: Anti-epileptic drugs with a recognised tendency to produce significant weight loss include topiramate and zonisamide. Levetiracetam should also be considered as a potential cause of significant weight loss.

047 VALPROATE INDUCED PARKINSONISM

M. Kellett, K. Easterford, P. Clough, S. Duncan. Greater Manchester Neurosciences Centre, Hope Hospital, Manchester, UK

Following reports of a reversible valproate induced extrapyramidal syndrome, we wanted to determine the incidence in patients in Greater Manchester. Patients were recruited from hospital and community settings. All patients had taken valproate or carbamazepine monotherapy for at least 12 months. Patients with previous neuroleptic, antiemetic, or antidepressant use were excluded. Patients were questioned about their drug history and examined for parkinsonism. Screening examinations were videoed and reviewed blind by a movement disorders specialist. Patients with signs of parkinsonism were scored using the Unified Parkinson’s Disease Rating Scale (UPDRS).

Fifty six patients were assessed (40 valproate, 16 carbamazepine). The mean age, duration of treatment, duration of epilepsy, and seizure frequency was statistically comparable for each group. Three (7.5%) of the patients receiving valproate had unequivocal signs of parkinsonism. Parkinson’s disease in these patients was ruled out by DAT scan. Two patients ceased valproate treatment and their symptoms remitted. There was a significant correlation between the UPDRS score and age (r = 0.409). UPDRS score was not correlated with any other variable. No control patients exhibited extrapyramidal signs. We conclude that there is a low incidence of extrapyramidal signs in patients receiving valproate, but that the presence of these signs is age dependent.

048 WHY DO PSYCHIATRISTS REQUEST EEG?

A. K. Mallik, A. J. W. Davidson, A. C. Mann, J. Bouch, A. J. C. Russell. Department of Clinical Neurophysiology, Southern General Hospital, Glasgow; Gartnavel Royal Hospital, Glasgow, UK

Ninety eight questionnaires were mailed with EEG (electroencephalogram) reports to general adult psychiatrists who had referred patients to West of Scotland EEG departments over a six month period. 89% (87) questionnaires were returned.

The most common reasons for requesting EEG were suspected epilepsy (40%), organic cause of psychosis or depression (20%), exclude epilepsy (14%), exclude structural lesion (2%), and atypical behaviour or psychosis (6%). The referral information suggested a plausible diagnosis of epilepsy in only 5%. 50% of EEGs were reported as normal, 39% showed minor non-specific abnormalities, and 11% showed unequivocal abnormalities.

There was considerable difference between the perceived usefulness of the EEG result by the referring psychiatrist and the neurophysiologist (91% v 17%). However, following EEG, in 50% of patients psychiatrists felt that a psychiatric diagnosis was more secure and epilepsy less likely in 39%.

Recent SIGN guidelines stress the importance of the clinical diagnosis of epilepsy and avoidance of inappropriate EEG. In many cases the reasons for requesting EEG were not clear. EEG was also requested for reassurance that patients did not have epilepsy. The EEG cannot do this.

049 THE UK EPILEPSY AND PREGNANCY REGISTER: INTERIM RESULTS

A. J. C. Russell, J. J. Craig, P. Morrison, B. Irwin, R. Waddell, L. Parsons, I. Robertson, E. Guthrie, J. I. Morrow.

The UK Epilepsy and Pregnancy register is a prospective observational follow up study of the relative risks of antiepileptic drugs (AEDs) in pregnancy. The main outcome measures are the risk of major congenital malformation with exposure to different AEDs. 3206 women with epilepsy have been registered to date, with full outcome data on 2544. Major malformation rates with monotherapy exposure are 3.5% and with polytherapy 6.9%. Lamotrigine monotherapy exposures compare well with those of carbamazepine (2.1% v 2.2%) but rates associated with valproate are significantly higher (6.1%). Numbers for specific polytherapy combinations are still small, but trends include a higher malformation rate of 10% with lamotrigine in combination with valproate.

Although this is now the largest prospective register of its kind and we continue to recruit widely in the UK, we still need more pregnancies to examine other recently licensed AEDs. Greater numbers are also needed to look for drug specific malformation, the effects of specific combinations, and of different drug dosage. The register has stimulated interest and awareness of pregnancy issues over the last seven years, encouraging more informed pre-pregnancy counselling and also leading to follow up studies of child development as well as active collaboration with the international study EURAP.

050 FAMILY HISTORY OF EPILEPSY IN EPILEPSY AND OTHER NEUROLOGICAL CONDITIONS

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

Aim: To determine the frequency of a family history (FH) of epilepsy in patients with epilepsy and other neurological conditions.

Methods: 3386 patients were included. 993 had epilepsy, 2393 had other neurological conditions including headaches, multiple sclerosis, movement disorders, cerebrovascular accidents, and polyneuropathies.

Results: 62 patients with a FH of epilepsy were identified. 54 of the 62 patients had epilepsy. A FH of epilepsy was common in idiopathic generalised epilepsy (22.8%) and uncommon in all other forms (cryptogenic partial epilepsy 2.3%, epilepsy with neurological deficit from birth 2.9%, symptomatic post-natal epilepsy 0.9%). Eight neurological patients with a FH of epilepsy had other neurological conditions without seizures (0.3%). Two patients had tension type headaches, one migraine, one facial nerve palsy, one stroke, two intermittent dizziness and unsteadiness, and one a single simple faint.

Conclusion: Our data suggest that genetic factors contribute to the development of idiopathic generalised epilepsy. A limited role for genetic factors in cryptogenic partial epilepsies and in epilepsies associated with neurological deficits from birth remains possible. Genetic factors appear to be least important in symptomatic postnatal epilepsies. A FH of epilepsy is not more common in patients with neurological conditions without seizures than in the general population.

051 USE OF ANTI-EPILEPTIC DRUG LEVELS: A RETROSPECTIVE AUDIT

R. J. L. Walters. University Hospital of Wales, Cardiff, UK

Introduction: Pharmacokinetic factors and narrow therapeutic index mean that measuring antiepileptic medications may be useful. Scottish Intercollegiate Guidelines identify phenytoin dose changes, possible toxicity, or adherence problems as indications to consider drug level measurement. We undertook an audit to examine adherence to these guidelines.

Method: All Cardiff patients who had undergone antiepileptic drug level measurement in October/November 2002 (total, 114; notes available, 102) were included. We noted the requesting team, test indications, interpretation, effect on management, and results documentation.

Results: Requests for phenytoin (50), lamotrigine (8), valproate (27), carbamazepine (22), phenobarbitone (7) were made from physicians (39), paediatricians (26), neurologists (14), neurosurgeons (14), psychiatrists (7), ITU (2). Toxicity and compliance were queried in 29 (25%) and 10 (9%) respectively. Management decisions were not always logical—for example, toxicity confirmed but dose not changed. All phenytoin levels (except one) were random. Written indication and results were documented in 50% and 48% respectively.

Conclusion: Few indications were compliant with guidelines (34%) in this audit, and some results were not interpreted logically. Widely adopted practices—for example, measuring random phenytoin levels and levels measured directly following loading—require further discussion. This local failure to adhere to national guidelines may well reflect practice elsewhere in the UK.

052 PREGNANT WOMEN WITH PSYCHOGENIC NON-EPILEPTIC SEIZURES

A. Russell, M. Oto, R. Duncan. West of Scotland Regional Epilepsy Service

Background: Psychogenic non-epileptic seizures (PNES, pseudoseizures) may make up 10–20% of patients thought to have intractable epilepsy. The high rate of misdiagnosis and the risks of anti-epileptic drug (AED) use in pregnancy are major concerns. These two issues come together whenever a woman with non-epileptic attacks or suspected non-epileptic disorder becomes pregnant on AED.

Methods: The Glasgow PNES clinic database records prospectively acquired information. We identified 125 women of childbearing age who had attended since 2000. Of these, 23 had had one or more pregnancies on AED. The number of pregnancies ranged from 1–6. Sixteen patients had a final diagnosis of PNES, four had PNES and epilepsy, and three had a clinical diagnosis of PNES awaiting confirmation. All pregnancies in patients with a confirmed diagnosis to date had good outcomes, although all four patients in the process of diagnosis had reported previous miscarriages.

We cross referenced our patients with Scottish registrations to the UK Epilepsy and Pregnancy Register. Twenty three of 709 pregnancies occurred in women suspected of or confirmed as having PNES. Three of these patients appeared on the Glasgow PNES database.

Conclusion: Pregnancy in patients with PNES on AED appears to be common. This highlights the need for improved diagnostic services.

053 GUIDELINES FOR THE INVESTIGATION AND MANAGEMENT OF BONE DISEASE IN EPILEPSY

P. A. Brex, C. Moniz, L. Nashef. Departments of Neurology and Chemical Pathology, Kings College Hospital, London, UK

Patients with epilepsy are at increased risk of sustaining fractures. Predisposing factors include accidental injury and bone disease. Falls may be due to seizures, drug side effects, and reduced mobility. Bone disease may be due to abnormal bone structure (osteoporosis) or poor mineralisation (osteomalacia) and is asymptomatic until a fracture occurs. Epileptic patients appear to have increased bone turnover necessitating a good supply of metabolites. Anti-epileptic drugs (AEDs) contribute to the risks of bone disease through a number of mechanisms. Hepatic enzyme inducing drugs increase the breakdown of vitamin D to inactive metabolites and lead to lower calcium and vitamin D levels, which may still be within the quoted normal range. They also increase the production sex hormone binding globulins, leading to reduced free testosterone and consequently increased osteoclast activity. AEDs may also have direct effects on gut absorption and bone metabolism.

Clinicians advising patients with epilepsy need to be more proactive in the prevention and detection of epilepsy associated bone disease. We propose guidelines and patient information leaflets to aid the clinician in the management of bone disease in epilepsy, highlighting those patients most at risk and providing a structure for their investigation and management.

054 VIDEO EEG RECORDING IN CORK UNIVERSITY HOSPITAL: REPORT OF A FOUR YEAR AUDIT

K. O’Rourke, B. McNamara, B. J. Sweeney. Cork University Hospital, Cork, Republic of Ireland

A clinical audit of 122 video EEG recordings performed over a four year period in a regional neurological unit was carried out in order to provide data regarding the yield of diagnostically helpful and unhelpful recordings done in this setting and in a single centre. A subanalysis of the diagnostically helpful group in terms of the information gained was also carried out. The majority (77%) of recordings were found to be clinically unremarkable; 9.8% of recordings showed non-epileptic seizures. The epileptic recordings were extratemporal (6.5%), temporal (2.5%), myoclonic (1.6%) and absence (0.8%). 1.6% of recordings were diagnostically equivocal. The degree of diagnostic uncertainty as to the nature of a seizure is therefore high when a seizure is captured; the explanation for the high rate of negative recordings is likely to be multifactorial.

055 BOTULINUM TOXIN A: AN EFFECTIVE SYMPTOMATIC TREATMENT FOR SELECTED PATIENTS WITH INTRACTABLE EPILEPSIA PARTIALIS CONTINUA

D. A. Lozsadi, I. K. Hart, A. P. Moore. Walton Centre for Neurology & Neurosurgery, Liverpool, UK

We report a patient with intractable epilepsia partialis continua involving the left arm, which was symptomatically controlled with intramuscular injections of botulinum toxin A.

A 53 year old man with a 14 year history of drug resistant epilepsy secondary to Rasmussen’s encephalitis had virtually continuous and distressing jerking of his left arm. Scalp EEG recording confirmed the diagnosis of epilepsia partialis continua. His medical treatment included five antiepileptic agents. Alterations to his drug regimen failed to control his symptoms. After 1000 μ of botulinum toxin A (Dysport) split between flexor muscles of his left arm, the power and amplitude of the myoclonic jerks diminished greatly, relieving his severe pain and allowing some return of function. This benefit was sustained after reduction of his anti-epileptic medication. Symptomatic relief continued for 5 months and further injection cycles have also been effective.

Though previous attempts to control epilepsia partialis continua with botulinum toxin have not been successful, our case suggests that this approach may be beneficial in a carefully selected patient population.

056 AN AUDIT OF THE USE OF INTRAVENOUS IMMUNOGLOBULIN IN A REGIONAL NEUROSCIENCE CENTRE

B. Daniels, R. Al-Shahi, R. Grant. Department of Clinical Neuroscience, Western General Hospital, Edinburgh, UK

Background: We developed local guidelines for the use of intravenous immunoglobulin (IVIg) for neurological disease, following the recent publication of national guidelines by the ABN (2002) and the RCN (1999).

Methods: One of us (DB) prospectively monitored compliance with our local guidelines in every adult receiving IVIg via the neurology service over 6 months (November 2002–April 2003). Data were collected from case notes and the electronic laboratory results system.

Results: Twenty nine adults received a total of 69 infusions in the 6 month period. 15 adults (52%) were first time recipients of IVIg, of whom 14 (93%) received an information leaflet. Of the new recipients, the indication for IVIg use was unlicensed in eight (53%), six (75%) of whom had a signed consent form in their notes. 11 (73%) of the new recipients had serum stored prior to IVIg administration. All new recipients had pre and post IVIg investigations, but in seven (47%) the battery of tests was incomplete. Every new recipient received sucrose based, non-IgA depleted IVIg, without major side effects.

Conclusions: Although a sizeable proportion of new IVIg users received information leaflets and signed a consent form following the introduction of our local guidelines, blood test monitoring was poor.

057 BRAIN MRI APPEARANCES IN FABRY DISEASE

L. Ginsberg, L. Richfield, S. Goodwin, A. Milligan, A. Valentine, B. Kendall, J. Zuckerman, A. B. Mehta. Royal Free Hospital, London, UK

Background: Fabry disease (alpha galactosidase deficiency) is a lysosomal storage disorder in which glycolipids accumulate in the kidneys, heart, endothelium, skin, peripheral nerves, and other tissues. Cerebrovascular manifestations of Fabry disease are largely due to dilated arteriopathy, predominantly in the vertebrobasilar circulation.

Results: We performed brain MRI scans in 15 male (hemizygote) Fabry patients, before and after enzyme replacement therapy (ERT). None of these patients (aged 23–50 years) had clinical evidence of CNS disease. Scan appearances were normal in eleven patients. In the other four, there were widespread small lesions of high T2 signal in the cerebral white matter. In one patient, some of the lesions showed enhancement with intravenous gadolinium and punctate enhancement in the brainstem was attributed to an ectatic vessel. Three patients showed intriguing high T1 signal in the posterior thalami, raising the possibility of localised parenchymal abnormality.

Conclusion: Brain MRI abnormalities are therefore common in Fabry disease, even in asymptomatic individuals. The scan appearances did not alter systematically with short duration (<1 year) of ERT.

058 THE VALIDITY OF SELF REPORTED DIAGNOSES IN PATIENTS WITH NEUROLOGICALLY UNEXPLAINED SYMPTOMS

A. Schrag, R. J. Brown, M. R. Trimble. Division of Neuropyschiatry and Neuropsychology, Institute of Neurology, London, UK

Objective: To assess the validity of past medical diagnoses reported by patients with neurologically unexplained symptoms (NUS) compared with patients with confirmed neurological disease without suspicion of somatoform illness (ND).

Methods: Twenty one patients with NUS and 16 with ND were interviewed about their current and past medical problems and diagnoses. The accuracy of the reported diagnoses was assessed through examination of their complete general practice notes.

Results: The median total number of previous diagnoses reported by patients with NUS was higher than in controls (6 v 3, p = 0.001). There was no difference in the number of confirmed diagnoses (2 v 2.5). The excess diagnoses reported by patients with NUS not only included functional syndromes (6%), but also organic diagnoses which had either been (1) unequivocally excluded (5%), (2) were based on equivocal findings often found after multiple investigations (9%), or (3) had only been diagnosed clinically (51%).

Conclusion: Reported previous diagnoses should not be taken at face value when the current differential diagnosis includes a functional/somatoform neurological syndrome. Confirming the validity of previous diagnoses from alternate sources may contribute to a diagnosis of somatoform disorder, allowing appropriate management strategies for the current (and past) complaints to be initiated.

059 CONGENITAL HEMIPLEGIA: A POTENTIALLY TREATABLE DISORDER?

J. A. Eyre, M. Smith, F. Villagra, L. Dabydeen, F. Cowan, M. Rutherford, E. Mercuri. School of Clinical Medical Sciences, Department of Child Health, University of Newcastle upon Tyne; Department of Child Health, Imperial College London, UK

Following perinatal damage to one motor cortex, fast conducting ipsilateral corticospinal (CS) projections from the undamaged hemisphere are present in adulthood. Our hypothesis is that during development ipsilateral CS projections from the undamaged hemisphere, which would normally be withdrawn, competitively displace surviving contralateral CS projections from the damaged hemisphere. Subjects with unilateral perinatal stroke involving the motor cortex were studied: (A) 12 longitudinally from birth and (B) 31 when aged between 3–5 years. EMG was recorded from biceps brachii. Transcranial magnetic stimulation (TMS) estimated central motor conduction delays (CMCD). (A) Initially TMS of the infarcted hemisphere evoked responses in contralateral biceps in all subjects. By 2 years responses could not be evoked in six. (B) There were significant positive correlations between severity of hemiplegia and absent or prolonged contralateral CMCDs from the infarcted hemisphere (r2 = 0.66, p<0.001) and abnormally fast ipsilateral CMCDs from the undamaged hemisphere (r2 = 0.63, p<0.001). Withdrawal of surviving contralateral CS projections from the damaged hemisphere and persistence of fast ipsilateral CS projections from the undamaged hemisphere is associated with poor outcome. By analogy with amblyopia, interventions to improve the competitiveness of CS projections from the infarcted hemisphere may improve outcome.

060 CLINICAL TRIALS IN NEUROLOGY: ARE RATING SCALES STABLE ACROSS EUROPEAN COUNTRIES?

J. Hobart, S. Cano, R. O’Connor, S. Kinos, O. Heinzlef, E. Roullet, C. Polman, B. Uitdehaag, C. McGuigan, M. Hutchinson, V. Durastanti, C. Pozzilli, J. Porcel, J. Sastre-Garriga, X. Montalban, E. Mansson, J. Lexell, A. Thompson. Peninsula Medical School, Plymouth; Institute of Neurology, London; Masku Rehab Centre, Finland; Tenon University Hospital, Paris, France; VU Medical Centre, Amsterdam Holland; St Vincent’s University Hospital, Dublin, Ireland; University ‘La Sapienza’, Rome, Italy; Hospital Universitari Vall d’Hebron, Barcelona, Spain; Lund University Hospital, Lund, Sweden

Background: Clinical trials in neurology are frequently multicultural, and increasingly use patient completed rating scales as outcome measures. It is, therefore, essential that rating scales prove they generate stable measurements across different languages and cultures. Such studies are rare and difficult using tradition psychometric methods. We used Rasch technology, a new psychometric method, to examine the stability of the Multiple Sclerosis Impact Scale (MSIS-29) across eight European countries.

Methods: The UK developed MSIS-29 was administered to 50 MS patients in Finland, France, Holland, Ireland, Italy, Spain, and Sweden. Clinical settings and sample characteristics differed across countries. Data from each country were Rasch analysed. Cross cultural stability of item difficulties (differential item functioning (DIF)) was examined by comparing country specific with UK derived (n = 1725) MSIS-29 item calibrations, and examining the impact of differences on person measures (linear transformations of patients’ raw scores).

Results: The MSIS-29 satisfied Rasch measurement criteria in all countries. There was some DIF across countries but in the vast majority of cases these were within accepted limits. Importantly, differences had no impact on the resulting person measures. Rasch technology may have an important role in the evaluation of cross cultural validity. The MSIS-29 may be used in multicentre trials of therapeutic agents across these countries.

061 A MULTIPLEX ASSAY FOR DETECTION OF MICROBE SPECIFIC OLIGOCLONAL IGG IN CEREBROSPINAL FLUID

N. W. S. Davies, P. Morris, R. Howard, G. Keir, M. K. Sharief. GKT School of Medicine, King’s College Hospital; National Hospital for Neurology & Neurosurgery, London, UK

Introduction: The diagnosis of viral CNS infections requires the detection within the CSF of either a pathogenic organism or local synthesis of microbe specific antibodies. We present a novel screening and confirmatory assay to detect microbe specific antibody within CSF.

Methods: CSFs were screened against HSV, VZV, CMV, EBV, Mycoplasma pneumoniae, measles, and enterovirus antigen using a qualitative immunosorbent assay. Where reactivity was found to a specific antigen, paired CSF and serum samples underwent IgG isoelectric focusing (IEF) and antigen specific immunoblotting. Intrathecal synthesis of antigen specific IgG was recorded when bands were found within CSF but not serum.

Results: 120 CSF samples from 98 adults were studied of which 20% had intrathecal synthesis of oligoclonal IgG. 71 samples were from patients thought clinically possible to have a CNS viral infection, and 49 samples were from patients with CNS diseases unlikely to be of viral aetiology. The most frequent positive screen findings were for VZV and HSV, where 70% and 47% showed reactivity. However, IEF and immunoblotting showed local synthesis of HSV or VZV IgG in <10% of these cases. In only one sample was intrathecal synthesis of IgG to more than one organism found.

Conclusion: This sensitive assay detects microbe specific IgG in CSF and its application in clinical practice may improve diagnosis of CNS viral infections, particularly where CSF is obtained late in the disease process.

062 IMPROVEMENT IN COGNITIVE FUNCTION FOLLOWING LIVER TRANSPLANTATION

M. B. Lewis, P. D. Howdle. St James’s University Hospital, Leeds, UK

Introduction: Patients with chronic liver disease frequently experience cognitive dysfunction. The effect of liver transplantation on this dysfunction is uncertain.

Methods: Consecutive patients attending St James’s University Hospital for transplant assessment were invited to participate in the study. Cognitive function was assessed using the MMSE, the Rey auditory verbal learning test, trail-making tests A and B, the Stroop test, and the Benton visual retention test. This assessment was repeated 3–6 months after transplantation. A 10% change in cognitive function scores was defined as clinically significant, giving a sample size of 50. The study was approved by the local research ethics committee.

Results: The median age at transplantation was 51.5 years (IQR 44–58 years) and patients had spent a median of 11 years (IQR 10–16 years) in education. The most common indications for transplantation were alcoholic liver disease (n = 18) and primary biliary cirrhosis (n = 15).

There was a significant improvement (p<0.01) across all the areas of cognitive function tested. Patients remained significantly different from normal controls, however, on all tests other than verbal learning and trail A.

Conclusion: Cognitive function in patients with end stage liver disease improves following liver transplantation, but does not return to normal.

063 OVARIOLEUKODYSTROPHY: A NEW CASE AND FURTHER DESCRIPTION OF THE SYNDROME

A. Ryan, D. Webb, R. P. Murphy. Department of Neurology, Adelaide & Meath Hospital, Tallaght, Dublin, Ireland; Department of Paediatric Neurology, Our Lady’s Hospital for Sick Children, Dublin, Ireland

Ovarioleukodystrophy is a syndrome of primary ovarian failure (POF) associated with white matter changes on cerebral magnetic resonance imaging (MRI). Very recently, this condition was shown to be related to mutations in the eukaryotic initiation factor 2B (eIF2B). We now describe another case of this rare syndrome in an unrelated patient.

The case is that of a 25 year old woman with a normal birth history. Initial developmental milestones were normal but cognitive impairment was apparent at school age. Endocrine evaluation for short stature and delayed puberty was consistent with primary gonadotrophin deficiency and pelvic ultrasound showed the presence of streak ovaries. Her karyotype was normal. At 17 years, she developed dystonic head posturing and progressive ataxia and spasticity. MRI brain revealed diffuse white matter abnormalities in the cerebral hemispheres bilaterally. Extensive investigations for the known leukodystrophies and for causes of ovarian failure were unrewarding.

We describe a case of POF associated with white matter disease, both of unknown origin. The clinical and radiological features bear striking resemblance to previous reports. Primary ovarian failure should be sought in cases of leukodystrophy of unknown cause. Better recognition of this association will allow better patient characterisation and description of the syndrome.

064 SIR ROBERT CARSWELL (1793–1857): PATHOLOGICAL ANATOMIST, ARTIST, AND FIRST TO DESCRIBE THE LESIONS OF MULTIPLE SCLEROSIS

S. R. Thomas, S. Razvi, I. Bone. Neurology Department, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK

A 41 year old man was treated by orchidectomy and adjuvant paraaortic radiotherapy for a testicular seminoma in February 2001. Five months later he presented with symptoms and signs of lumbosacral intrathecal radiculopathy supported by neurophysiological studies and gadolinium enhanced MRI scan of the lumbosacral roots and plexus. Intravenous methyl prednisolone was administered for 5 days followed by oral prednisolone for 8 weeks. Ten sessions of hyperbaric oxygen was also instituted. Over the next year the neurological complaints fully resolved. We report this case of post irradiation lumbosacral radiculopathy because of the unusually short latency, short duration, and the recovery. Usually the course is relentlessly progressive, often to severe disability, although some cases may stabilise. A literature search reveals only one similar case with spontaneous resolution. There is no effective treatment so far and steroid administration has not shown any benefit in the past, and so is unlikely to explain the resolution in this patient. Hyperbaric oxygen corrected a sacral plexopathy caused by pelvic radiation in a single reported case. Further trials with a combination of intravenous methyl prednisolone and hyperbaric oxygen are required and may hopefully reveal promising results.

065 ABNORMAL VOLTAGE GATED SODIUM CHANNEL DISTRIBUTION: A NOVEL MECHANISM OF AXONAL INJURY IN EAE SPINAL CORD?

M. J. Craner, B. C. Hains, A. C. Lo, J. A. Black, S. G. Waxman. Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT 06510; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA

Objective: To identify and delineate the abnormal distribution of voltage gated sodium channels in an experimental model of MS and examine their relation with axonal injury.

Methods: Through application of immunohistochemistry, we examined the distribution of sodium channels Nav1.2 and Nav1.6 in spinal cord of EAE mice and their association with β-APP immunoreactivity, a marker of axonal injury.

Results: Our results show a significant attenuation of Nav1.6 at nodes of Ranvier compared with control that is maximal during relapse (33.2 (SD 8.5)%) compared with remission (69.9 (SD 4.7)%). We observed an increased number of demyelinated axonal profiles with diffuse immunoreactivity for Nav1.2 and Nav1.6 in EAE spinal cord. Moreover we observed that in EAE β-APP+ve axonal profiles were associated with a significant difference in Nav1.6+ve (87.7 (SD 2.7)%) compared with Nav1.2+ve profiles (45.8 (SD 2.6)%).

Conclusions: Axonal loss in MS plays a key role in the development of non-remitting disability and yet the molecular mechanisms that underlie this process are not clearly delineated. These findings extend the evidence implicating that a perturbation of sodium channel expression may not only contribute to the development of conduction block but also subserve a pathway of axonal injury and thereby represents a potential novel therapeutic target.

066 ABNORMALITIES IN NORMAL LOOKING BRAIN TISSUE ARE PRESENT IN EARLY PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS AND CORRELATE WITH DISABILITY: A MAGNETISATION TRANSFER IMAGING STUDY

L. I. Ramió-Torrentà, G. Ingle, J. Sastre-Garriga, G. R. Davies, D. H. Miller, A. J. Thompson. Institute of Neurology, London, UK

Background: Primary progressive multiple sclerosis (PPMS) patients often develop severe disability despite low levels of abnormality on conventional MRI. This may relate to diffuse pathological processes occurring in the normal appearing white matter (NAWM) and grey matter (NAGM). These can be studied with magnetisation transfer imaging (MTI).

Aim: To assess NAWM and NAGM using MTI in early PPMS and to correlate these findings with disability and other MRI measures.

Methods: We studied 43 patients within 5 years of disease onset and 59 controls. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite were scored. Mean, peak height, and peak location from NAWM and NAGM magnetisation transfer ratio histograms (MTR) were measured. PD, T2, T1, and gadolinium enhancing lesion loads were also calculated.

Results: Statistically significant differences were found between patients and controls in MTR parameters. Correlations were found between MTR parameters and disability (EDSS) in both NAWM (r = −0.34, p = 0.024) and NAGM (r = −0.34, p = 0.034). Strong correlations between MTR parameters and T2 lesion loads were found, particularly in NAWM (r = −0.94, p<0.001).

Conclusion: MTR abnormalities are seen in early PPMS, affect both NAWM and NAGM, and are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.

067 BRAIN METABOLITE CHANGES IN THE EARLY CLINICAL STAGES OF PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS

J. Sastre-Garriga, G. T. Ingle, D. T. Chard, L. I. Ramió-Torrentà, M. A. McLean, D. H. Miller, A. J. Thompson. Institute of Neurology, London, UK

Background: Magnetic resonance spectroscopic imaging (MRSI) offers information on chemical components of the normal appearing areas of the brain and could help explain the mechanisms of disease in multiple sclerosis (MS), which are particularly relevant in primary progressive MS (PPMS).

Aim: To evaluate the mechanisms underlying disease progression in PPMS.

Methods: Forty three patients within five years of symptom onset of PPMS and 44 control subjects were studied. MRSI data were acquired from a grid placed above the roof of the lateral ventricles. Concentrations of five metabolites were obtained: choline, creatine, inositol, N-acetyl-aspartate, glutamate-glutamine. Voxels in the grid were considered grey matter (GM) or normal appearing white matter (NAWM). Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were recorded in all patients.

Results: Concentrations of N-acetyl-aspartate and glutamate-glutamine in GM were lower in patients than in controls. In NAWM, inositol levels were higher and N-acetyl-aspartate levels were lower in patients than in controls. EDSS correlated with N-acetyl-aspartate in GM (r = −0.444, p = 0.03) and with inositol (r = 0.412, p = 0.011) and glutamate-glutamine (r = 0.406, p = 0.013) in NAWM.

Conclusions: Metabolite changes occur in early PPMS and differ in GM and NAWM. N-acetyl-aspartate in GM and inositol in NAWM are related to disability in PPMS.

068 NEUROMYELITIS OPTICA (DEVIC’S DISEASE): A 10 YEAR EXPERIENCE IN A REGIONAL CENTRE

A. Jacob, R. Nicholas, M. Boggild. Walton Centre for Neurology & Neurosurgery, Liverpool, UK

Objectives and Methods: Neuromyelitis Optica (NMO) or Devic’s disease is a rare demyelinating syndrome regarded by some authors as a variant of multiple sclerosis (MS). As a preliminary to a planned UK wide study, a retrospective assessment of cases diagnosed within the Walton Centre over the last 10 years was undertaken.

Results: Eight patients (7 female) were identified; mean age of onset was 46.4 years. Five had a relapsing course and three were monophasic. Four patients had other immunologic abnormalities, three of five had positive anticardiolipin antibodies. All patients received steroids and five patients were treated in addition with immunosuppressive and or immunomodulatory agents (azathioprine-5, mitoxantrone-1, betainterferons-1, cyclophosphamide-2, cyclosporin-1). In these five patients, observed relapse rate was substantially reduced on treatment, mean follow up period on treatment was 3.4 years. Early initiation of immunosuppressive treatment tended to favour improved functional outcome.

Conclusions: NMO is a rare disease with a distinct clinical phenotype. Immunological abnormalities, particularly anticardiolipin antibodies, are often associated. Despite the small size of the cohort, outcomes in this group suggest that early immunosuppressive treatment is of benefit. The ongoing nationwide study, which will also explore immunological and genetic markers, will hopefully shed more light on this distinctive disease.

069 CORTICAL MOTOR REORGANISATION IN PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS

O. Ciccarelli, A. T. Toosy, J. F. Marsden, G. T. Ingle, C. A. Wheeler-Kingshott, D. H. Miller, A. J. Thompson. Institute of Neurology, London, UK

Introduction: Previous work has reported differences between patients with primary progressive multiple sclerosis (PPMS) and normal subjects in the functional MRI (fMRI) response to active hand movements. Lower limb function has not been investigated in PPMS despite its importance in determining disability. We developed a lower limb fMRI paradigm which employs active and passive foot movements and applied it to patients with PPMS.

Methods: fMRI was performed on 13 patients and 16 controls for each foot. Active and passive dorsi and plantar flexion was performed using a special bipedal wooden apparatus. SPM99 was used for the analysis.

Results: Cortical regions, including the contralateral cerebellum, showed greater activation in patients than controls during both active and passive tasks. Other regions showed greater activation during active movement alone, such as the ipsilateral supplementary motor cortex, or during passive movement, such as the ipsilateral putamen and thalamus.

Conclusion: Patients with PPMS showed functional changes during active and passive foot movements compared with controls. The use of passive tasks allows the identification of cortical areas that are genuinely adaptive as these are independent of voluntary recruitment, and has the potential to assess the efficacy of rehabilitation.

070 A COMMUNITY BASED STUDY OF RESOURCES, NEEDS, AND WELLBEING OF PEOPLE WITH MULTIPLE SCLEROSIS

K. MacLurg, P. Reilly, E. Evason, D. Whittington, S. A. Hawkins. Queen’s University, Belfast; University of Ulster, Jordanstown

Few studies of the needs of people with MS have been performed in a primary care setting. In Northern Ireland there is a network of general practitioners (GPs) with computerised records. Patients were identified by their GP, consent obtained, and the diagnosis verified. Participants were interviewed in their own homes, according to our protocol by representatives of a market research firm. 149 patients participated. Of these two thirds were female. For the purposes of analysis, we divided the participants into three groups as follows: 23% able to walk more than 500 metres, 41% moderately disabled, and 36% severely disabled (wheelchair or bed bound).

Level of disability was significantly related to employment, receipt of benefits, house alterations, receipt of nursing and personal care, GP attendances, and medication use. The moderately disabled were most likely to attend neurology outpatients.

Unmet needs were greatest for the moderately affected group suggesting a lag time from identification of need to provision of help. Overall physiotherapy was the most common unmet need. More advice and information was also wanted. Scores relating to fulfilment and quality of life did not correlate with disability or resources accessed but did correlate with unmet needs particularly unmet needs for care.

071 META-ANALYSIS OF DOPAMINE AGONIST TRIALS IN EARLY PARKINSON’S DISEASE

N. J. Ives, R. L. Stowe, C. E. Clarke, L. Shah, R. J. Hawker, R. Gray, K. Wheatley. University of Birmingham Clinical Trials Unit (BCTU); City Hospital, Birmingham, UK

Introduction: Although levodopa (LD) remains the standard treatment for Parkinson’s disease (PD), long term therapy leading to motor complications has encouraged increased use of dopamine agonists (DA). We undertook a meta-analysis of 28 published randomised trials of DA in early PD to quantify more reliably the benefits and risks.

Methods: Data on mortality, motor complications, side effects, and withdrawals from treatment were analysed.

Results: There was no significant difference in mortality between DA and non-DA patients (relative risk = 1.03, 95% CI = 0.84 to 1.26; p = 0.8). The risk of developing dyskinesia (0.48, 0.40 to 0.57; p<0.00001), dystonia (0.64, 0.49 to 0.84; p = 0.001), and motor fluctuations (0.74, 0.62 to 0.89; p = 0.002) were significantly lower in patients randomised to DA compared with LD. However, DA patients were more likely to develop oedema (2.90, 2.01 to 4.21; p<0.00001), somnolence (2.73, 2.12 to 3.51; p<0.00001), hallucinations (2.21, 1.50 to 3.27; p = 0.00007), constipation (1.81, 1.35 to 2.41; p = 0.00006), dizziness (1.58, 1.23 to 2.01; p = 0.0003), and insomnia (1.41, 1.07 to 1.86; p = 0.01) compared with non-DA patients. Furthermore, DA treated patients were significantly more likely to drop out of the trial due to adverse events (2.77, 2.26 to 3.40; p<0.00001).

Conclusions: This meta-analysis confirms that patients receiving DAs are less likely to develop motor complications. However, other side effects—which may be more important for patients—are substantially increased. To determine reliably the balance between benefits and adverse effects of DAs, larger trials comparing DAs with levodopa and/or selegiline are needed with patient rated global quality of life as the primary outcome measure.

072 THE MOTOR RESPONSE TO LEVODOPA IN DEMENTIA WITH LEWY BODIES: A COMPARISON TO PARKINSON’S DISEASE WITH AND WITHOUT DEMENTIA

S. Molloy, J. T. O’Brien, I. G. McKeith, D. J. Burn. Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK

Background: A core clinical feature of dementia with Lewy bodies (DLB) is an extrapyramidal syndrome (EPS). Levodopa (Ldopa) is gold standard oral therapy for Parkinson’s disease (PD) but its use in DLB is tempered by concerns of exacerbating neuropsychiatric symptoms.

Aims: To assess the efficacy and tolerability of Ldopa to manage the EPS in DLB and compare the motor response with that in PD and PD with dementia (PDD).

Method: EPS assessment consisted of motor subsection Unified PD Rating Scale (UPDRS), finger tapping (FT), and walking tests (WT). Patients with DLB commenced Ldopa. After 6 months, patients were examined in the “off” state, given Ldopa, and assessed for motor responses. Identical assessments were performed in patients with PD and PDD on Ldopa.

Results: 18 DLB patients commenced Ldopa. Two withdrew prematurely with gastrointestinal symptoms and two with worsening confusion. 14 fasting DLB assessments demonstrated 12.6% (p<0.001) improvement in UPDRS score compared with 20% PD (n = 28, p<0.0001) and 25% PDD (n = 30, p<0.0001) respectively. FT increased 14.5% versus 20% and 28% while WT decreased by 36% versus 41% and 66% respectively

Conclusion: Ldopa was reasonably tolerated in DLB. Patients showed an improvement in EPS most strongly in general mobility. Ldopa therapy may be considered in DLB with troublesome parkinsonism.

073 PARKINSON’S DISEASE AND RESTLESS LEGS SYNDROME: AN UNDER RECOGNISED CAUSE OF DAYTIME MORBIDITY

C. S. Rao, A. Forbes, C. Meilak, A. Gharib, L. Taurah, A. Williams, C. K. Ray. King’s College Hospital, London; University Hospital of Lewisham, London; St Thomas’ Hospital, London, UK

Introduction: Restless legs syndrome (RLS) is the commonest movement disorder during sleep and relaxed wakefulness and its occurrence in Parkinson’s disease (PD) remains controversial. Chronic RLS is known to cause severe sleep disruption.

Methods: All PD patients that were part of an UK prospective audit (PDLIFE) and those attending regional PD clinics at King’s and Lewisham hospitals were screened for RLS using validated questionnaire and polysomnography (PSG) in selected cases. Data were compared to a cohort of idiopathic RLS patients (n = 25).

Results: 46 cases of RLS (mean age 66 years (49–90), mean duration of PD 60.5 months, mean duration of RLS 77 months) were identified among PD using the International RLS Study Group (IRLSSG) criteria. All had symptomatic daytime somnolence and notable sleep disruption. None were diagnosed to have RLS in spite of symptoms prior to current diagnosis. PSG in selected cases showed periodic limb movements and awakening. Specific additional treatment for RLS was required in 39 cases. 11 (24%) had RLS before diagnosis of PD.

Conclusions: RLS is an important cause of sleep disruption in PD and needs to be recognised. The occurrence of RLS preceding PD supports a central dopaminergic basis for origin of RLS.

074 META-ANALYSIS OF SELEGILINE TRIALS IN EARLY PARKINSON’S DISEASE

R. L. Stowe, N. J. Ives, C. Counsell, C. E. Clarke, J. Marro, R. Gray, K. Wheatley. University of Birmingham Clinical Trials Unit (BCTU); Aberdeen Royal Infirmary; City Hospital, Birmingham, UK

Introduction: Increased mortality has been reported with selegiline, and there remains uncertainty about its clinical role in Parkinson’s disease (PD). We undertook a meta-analysis of 13 published randomised trials of selegiline in early PD to quantify more reliably the benefits and risks.

Methods: Data on mortality, motor complications, side effects, need for LD, and treatment withdrawals were analysed.

Results: There was no evidence of increased mortality with selegiline compared with no selegiline: 24% v 22% died, relative risk = 1.14; 95% CI 0.96 to 1.36; p = 0.1. In the few studies reporting motor complications, there was no significant reduction in dyskinesia (0.96; 0.73 to 1.28; p = 0.8), although fewer patients experienced motor fluctuations (0.75; 0.58 to 0.95; p = 0.02) with selegiline. Selegiline patients were less likely to require LD than placebo patients (0.48; 0.40 to 0.58; p<0.00001). There was no significant difference between groups in numbers suffering side effects (1.37; 0.85 to 2.23; p = 0.2) or withdrawing from trial treatment (1.07; 0.87 to 1.31; p = 0.5). However, withdrawals due to adverse events appeared higher in selegiline patients (2.16; 1.44 to 3.22; p = 0.0002), although most of this excess came from just one trial.

Conclusions: Selegiline reduces the requirement for levodopa, and possibly motor fluctuations, without substantial side effects or increased mortality. Because few trials have compared selegiline with levodopa or dopamine agonists, uncertainty remains about the relative benefits and risks of selegiline. Further trials including patient rated quality of life measures are needed.

075 THE CLINICAL UTILITY OF DATSCAN IMAGING OF THE BASAL GANGLIA IN THE ASSESSMENT OF PARKINSON’S SYNDROME

D. J. Tuite, R. F. J. Browne, R. Murphy, B. Hogan. Department of Radiology, The Adelaide & Meath Hospital, Tallaght, Dublin, Ireland; Department of Neurology, The Adelaide & Meath Hospital, Tallaght, Dublin, Ireland

Introduction: To demonstrate the utility of I123-FP-CIT (DaTSCAN) in the assessment of suspected Parkinson’s syndrome.

Materials and Methods: Fifty five patients with suspected Parkinson’s syndrome were recruited into the study. A neurologist assessed all patients and symptom severity was recorded using the Unified Parkinson’s Disease Rating System (UPDRS) Correlation was made imaging findings, disease severity, side of symptom onset, and modification of patient treatment based on imaging findings.

Results: Thirty five presented with unilateral symptoms, of these 33 had abnormal scans. Within this group 31 had reduced isotope uptake on the contralateral side. Three patients had low UPDRS scores but grossly abnormal scans. These patients were atypical in presentation none had any evidence of a Parkinson Plus syndrome (MSA or PSP). Of the two patients who progressed to show evidence of PSP both had grossly abnormal scans. Of the five patients with normal scans, four responded well to alternative therapy. A general trend of increasing UPDRS score reflecting worsening image findings was observed.

Conclusion: DaTSCAN proved useful in the assessment of patients with Parkinson’s syndrome. It showed strong correlation with side of symptom onset and also allowed appropriate characterisation of each patient’s symptomatology.

076 WORKING MEMORY ABILITY IN PARKINSON’S DISEASE IS ASSOCIATED WITH THE COMT VAL108/158MET POLYMORPHISM

T. Foltynie, T. E. Goldberg, S. J. Lewis, A. D. Blackwell, B. Kolachana, D. R. Weinberger, T. W. Robbins, R. A. Barker. Cambridge Centre for Brain Repair, University of Cambridge, Cambridge; Clinical Brain Disorders Branch, Building 10, Center Drive, National Institute of Mental Health, Bethesda, MD 20892, USA; Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, UK

Parkinson’s disease patients show a range of working memory and executive deficits involving dopaminergic transmission in the prefrontal cortex. In this study, we have investigated the impact of catechol-O-methyl-transferase (COMT) val108/158met polymorphisms on performance of the Tower of London test of planning by Parkinson’s disease patients. This task has a complex relation with dopaminergic function, in that both high and low levels of dopamine in the dorso lateral prefrontal cortex impair performance. Patients with high activity COMT genotypes performed significantly better at the task than those with low activity genotypes. We hypothesise that the inferior performance in patients with the low activity COMT genotype is attributable to a state of relative hyperdopaminergic activity in the dorso lateral prefrontal cortex. We suggest that polymorphisms of common genes, which regulate central nervous system dopaminergic transmission, can influence some of the phenotypic manifestations of Parkinson’s disease.

077 A CROSS SECTIONAL MAGNETIC RESONANCE SPECTROSCOPY STUDY IN PSP AND INDETERMINATE PARKINSONISM

A. J. Zermansky, M. J. Firbank, P. English, D. Birchall, D. J. Burn. Department of Neurology, University of Newcastle upon Tyne, UK

Reduction in N-acetyl-aspartate concentration ([NAA]), a neuronal marker detectable by in vivo magnetic resonance spectroscopy (MRS), may indicate neuronal loss or dysfunction. We measured brainstem [NAA] in PSP patients, controls, and patients with unclassifiable parkinsonism to determine the diagnostic utility of this technique and also correlated [NAA] with measures of disease severity.

Methods: Midbrain [NAA] was measured in 17 PSP patients (eight probable and nine possible according to NINDS-SPSP criteria), 13 patients with neurodegenerative parkinsonism of uncertain cause (“indeterminate”), and 13 healthy age matched controls. A 2×2×1 cm voxel of interest (VOI) was placed to include the superior colliculi and as much midbrain as possible. [NAA] was calculated for the volume of brain within the VOI.

Results: Two subjects (one PSP, one indeterminate) were excluded, as their spectra were technically unsatisfactory. In the remaining subjects, mean [NAA] was significantly reduced in the whole PSP group versus controls (p<0.015) and versus indeterminates (p<0.007), and in probable PSP patients compared with indeterminate and control groups (p<0.0001). There were no significant correlations between disease rating scales (Golbe PSP Scale, UPDRS-motor, FAB) and [NAA].

Discussion: Midbrain [NAA] is reduced in PSP and may assist with clinical diagnosis. Longitudinal studies are needed to support this and evaluate potential prognostic application.

078 THE EFFECT OF DIAGNOSIS ON NEED FOR SERVICES: A COMPARISON OF MULTIPLE SCLEROSIS AND PARKINSON’S DISEASE

C. D. Ward, S. Ratib, G. Turpin, M. E. Dewey, S. Fleming, B. Hurwitz, M. von Fragstein. University of Nottingham; Imperial College, London, UK

Background: People with multiple sclerosis (MS) and Parkinson’s disease (PD) demand diagnosis specific services, but how different are their needs? To address this question, we analysed data from a community sample.

Method: For a randomised controlled trial, we ascertained people with MS and PD from Nottingham GPs. We interviewed them at home, using a symptom checklist, the Nottingham Extended Activities of Daily Living schedule, the Braden Scale for skin sore risk, the Nutritional Risk Assessment (NRA), a falls risk checklist, a Self-Efficacy scale, the General Health Questionnaire (GHQ) administered to patients and carers, and the Carer Strain Index (CSI).

Results: There were 53 with PD and 45 with MS. The only striking contrast was in mean ages (70.4 and 49.0 years respectively). The spectrum of symptoms and of disabilities was similar, suggesting comparable needs for services such as continence advice, psychiatry, therapy, and equipment. The proportions reporting at least one fall in 12 months (around 50%) and the frequency of falling risk factors were similar, as were Braden, NRA, self efficacy, CSI, and GHQ scores.

Conclusions: Our findings suggest close parallels between service needs generated by MS and by PD. The case for diagnosis specific services should be based on detailed comparative investigations rather than on assumptions derived from single diagnosis studies.

079 THE ROLE OF TWO SIMPLE QUESTIONS IN IDENTIFYING ELDERLY PATIENTS WITH UNDIAGNOSED PARKINSONISM

C. E. Counsell, J. Gordon, C. Harris. University of Aberdeen, Aberdeen, UK

Background: Elderly patients who develop parkinsonism may not present to their general practitioner. We assessed the usefulness of two questions in identifying elderly patients with undiagnosed parkinsonism as part of an incidence study.

Methods: We added two validated questions about tremor and gait to the annual nurse led check on people over 75 in five general practices. We also collected details of their past medical history and medications. Patients who screened positive to either question, in whom there was no alternative explanation, were invited for an examination by a neurologist who diagnosed parkinsonism according to the UK Brain Bank criteria.

Results: In four months 503 patients were screened (12% of over 75s) of whom 24 refused to participate. 52 (10%) patients gave a positive answer to ⩾1 question, of whom 15 declined further follow up, and 15 had an explanation other than undiagnosed parkinsonism. To date 10 of the remaining 22 patients have been examined and four (0.8% of those screened) had undiagnosed parkinsonism (16% of all incident patients identified so far).

Conclusions: Screening the elderly for undiagnosed parkinsonism has a low pick up rate but can identify a significant number of new patients who would otherwise be missed in an incidence study.

080 DIFFERENTIATING VASCULAR PARKINSONISM FROM TRUE PARKINSONISM: AUDIT OF FP-CIT SPECT IMAGING IN CLINICAL PRACTICE

V. L. Marshall, D. Kolokouris, J. Patterson, D. M. Hadley, D. Wyper, M. F. Dempsey, D. G. Grosset. Departments of Neurology, Clinical Physics, Neuroradiology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK

Background: Vascular parkinsonism (VP) is classically considered as lower body parkinsonism (LBP) due to subcortical ischaemia. However, atypical cases and overlap with Parkinson’s disease (PD) often cause clinical uncertainty. Striatal FP-CIT-SPECT uptake reflects presynaptic dopaminergic function and is progressively reduced in PD but normal in VP (or focally reduced by infarction).

Methods: A prospective Glasgow movement disorder clinic audit of FP-CIT-SPECT, clinical diagnosis, and antiparkinson therapy response in 22 patients with clinical uncertainty between VP and true parkinsonism. Four had LBP. All had structural imaging (small vessel disease/infarctions, n = 15; normal/atrophy, n = 7) and vascular risk factors.

Results: Baseline diagnosis was probable PD in 11 of 22 (50%) (10 had therapy trial; one good response, nine poor). Ten of these 11 had abnormal SPECT (final diagnosis PD); one of 11 had normal uptake, later diagnosed as essential tremor. VP was the baseline diagnosis in 11 (nine no therapy trial, two poor response). Of these 11 cases, four had normal FP-CIT, two had focal striatal lesions interpreted as infarction (final diagnosis VP), and five had dopamine deficit (final diagnosis PD). Six of 22 (30%) had unexpected SPECT results.

Conclusion: Clarification of dopamine status is helpful in clinical practice in differentiating between VP and PD.

081 SUBACUTE PRESENTATION OF MORVAN’S SYNDROME POST-THYMECTOMY

D. A. Cottrell, F. R. W. Fawcett, D. Birchall, A. Vincent, T. J. Walls. Department of Neurology, Newcastle General Hospital, Newcastle upon Tyne, UK

Morvan’s syndrome represents the clinical features of neuromyotonia (Isaacs syndrome) presenting as myokymia, muscle stiffness, cramps, and hyperhidrosis in combination with autonomic dysfunction and encephalopathy. The encephalopathy fluctuates with visual hallucinations, insomnia, and agitation. We describe a case of Morvan’s syndrome presenting subacutely after thymectomy, with unusual clinical symptoms representing a difficult diagnostic challenge. The diagnosis was made on clinical grounds, neurophysiology, and the finding of serum voltage gated potassium channel antibodies (VGKC). This is the first reported case of Morvan’s syndrome presenting post-thymectomy. Thymectomy has previously been proposed as a treatment for Morvan’s syndrome. Morvan’s syndrome normally presents with a slow insidious onset over months to years—some spontaneously remit, others require repeated plasma exchanges (PE), thymectomy, and maintenance high dose immunosuppression; however, most cases have proved fatal. Our case is unique in that presentation was over days and responded to a single course of PE with low dose maintenance immunosuppression. We hypothesise that the surgical procedure may have precipitated a rise in the serum levels of the VGKC antibodies, which were cleared by one course of PE. Although potentially this is a low risk to thymectomy, it is an important complication to recognise because of the dramatic reversibility to treatment.

082 COGAN’S LID TWITCH REVISITED

H. Whye Onn, M. Cleary, R. Metcalfe. Departments of Ophthalmology and Orthoptics, Gartnavel General Hospital; Dept Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK

Cogan first reported this clinical sign in myasthenia in 1965. He described a transient over shoot or twitching of the lids on making a saccade from depression to the primary position. It has also occasionally been reported in other brainstem and oculomotor disorders. Two mechanisms have been suggested: (1) rapid recovery of Levator function on depression, with subsequent rapid fatiguability and (2) central nervous system adaptation to the neuromuscular junction transmission defect.

The incidence of Cogan’s Lid Twitch (CLT) sign has previously only been reported in one small group. Recent observation of CLT in the Miller-Fisher syndrome led us to re-evaluate the use of this test.

We compared the incidence of CLT in myasthenia in patients with other oculomotor/brainstem disorders with a “normal” group. Fifty patients were recruited to each group, from a neuroophthalmology clinic (Dr Metcalfe) and an orthoptic clinic (Marie Cleary).

60% of myasthenics displayed a positive CLT, compared with 6% of those with other oculomotor/brainstem disorders, and none of the “normals”. Myasthenics always showed a transient over shoot, while lid twitch was typical for the non-myasthenics.

This characteristic response makes it a useful clinical test when performed correctly (illustrated by video recordings).

083 CLINICAL EVALUATION OF AUTONOMIC FUNCTION IN PATIENTS WITH GUILLAIN-BARRE SYNDROME

M. A. Al-Zaidi, K. Al-Shaikhli, J. Kimber, A. Y. Al-Memar. Medical City Teaching Hospital, Baghdad, Iraq; Atkinson Morley’s Hospital, London, UK

Autonomic dysfunction in Guillain-Barre Syndrome (GBS) is well recognised but not well described. In a cross sectional multicentre study, 50 patients with GBS were studied for evaluation of autonomic dysfunction (AD) according to methods described by Ewing and Clarke. Mean age at presentation was 21.1 years (range 1–60 years). All patients were studied for symptoms and signs of AD. None of them received IVIG or plasmaphoresis. Autonomic function tests (AFT) were performed in 30 patients. 20 patients (40%) had symptoms of AD, 27 patients (54%) had signs, and 14 patients (28%) had symptoms and signs of AD. Abnormality in AFT was detected in 15 patients (50%) and showed that the parasympathetic derangement was the most frequent followed by sympathetic and combined derangement. Derangement in AFT battery had a highly significant correlation with the development of respiratory paralysis p⩽0.001 and death p = 0.008.

All patients with GBS should be observed for evidence of autonomic dysfunction and nursing care has to be adjusted to take into account the autonomic status of the patient.

084 BRACHIUS PLEXUS HYPERTROPHY IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

L. J. Bradley, T. Wilhelm, R. H. M. King, L. Ginsberg, R. W. Orrell. Department of Clinical Neurosciences, Royal Free & University College Medical School; Department of Radiology, Royal Free Hampstead NHS Trust, London, UK

We present the clinical, MRI, and nerve biopsy findings in three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) which predominantly affected the upper limbs. All had slowly progressive disease over many years. One patient had bilateral shoulder pain as an initial presenting feature with a disease that mainly affected sensation. The other two patients had predominantly motor involvement. In all cases, the lower limbs have not been significantly affected, and the patients remain ambulant. Nerve conduction studies in the upper limbs of both patients demonstrated F wave abnormalities and conduction block consistent with a diagnosis of CIDP. All patients demonstrated significant brachial plexus abnormalities on MRI scanning. In one patient, the brachial plexus nodularity led to a diagnosis of neurofibromatosis being considered, although subsequent nerve biopsy showed onion-bulb hypertrophy. The second patient had a radial nerve biopsy which showed the inflammatory features of CIDP. None of the patients responded significantly to immunomodulatory treatment. The different appearances of the brachial plexus on MRI, in conjunction with the clinical presentations of these patients, suggest that they are unusual variants within the spectrum of CIDP.

085 A PILOT RANDOMISED, DOUBLE BLIND, PLACEBO CONTROLLED EXPLORATORY SAFETY STUDY OF THE USE OF INTERFERON-β 1A IN THE TREATMENT OF GUILLAIN-BARRE syndrome

R. A. C. Hughes, J. Pritchard, I. A. Gray, Z. R. Idrissova, B. R. F. Lecky, I. J. Sutton, A. V. Swan, H. J. Willison, J. B. Winer. Guy’s, King’s & St Thomas’ School of Medicine, London; Walton Centre for Neurology and Neurosurgery, Liverpool; University of Glasgow; Queen Elizabeth Hospital, Birmingham, UK

Objective: The immunomodulatory profile of interferon-beta (IFN-β) predicts a beneficial effect in Guillain-Barré Syndrome (GBS). In this pilot study we aimed to discover whether IFN-β is safe in GBS.

Methods: We recruited non-ambulant GBS patients to a double blind, randomised, placebo controlled trial. In addition to intravenous immunoglobulin (IVIg), patients received placebo or IFN-β1a (Rebif R) subcutaneously three times weekly, 22 μg for the first week, and then 44 μg until they were able to walk 10 metres, or for 24 weeks (whichever was sooner).

Results: We recruited 19 patients between 1999 and 2002. Four of the 13 IFN-β patients and two of the six placebo patients had serious adverse events. We did not encounter any unexpected adverse events and did not consider that any of the serious adverse events were probably or definitely attributable to the study drug. The improvement in disability grades at one month and six months did not differ significantly between the treated and placebo groups.

Conclusions: IFN-β was tolerated and did not have any unexpected adverse interaction with IVIg in GBS.

086 CRITICAL ILLNESS LUMBOSACRAL PLEXOPATHY

M. Mockova, V. P. Misra, R. J. Greenwood, O. Foster. Institute of Neurology, London; The National Hospital for Neurology and Neurosurgery, London, UK

Acute diffuse weakness in critically ill patients in intensive care units has been well described and attributed to critical illness polyneuropathy, myopathy, or defects of neuromuscular transmission. We report two patients who developed acute weakness confined to the lower limbs only during their stay in the intensive care unit. Electrophysiological findings were consistent with lumbosacral plexopathy. Absence of any other pathology was confirmed by laboratory and imaging investigations. We propose a new clinical diagnosis, critical illness lumbosacral plexopathy.

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