1588 Efficacy of levetiracetam in huntington's disease

Poster Abstracts Background: Pregabalin and gabapentin have been shown to be effective as adjunctive therapy for partial seizures and neuropathic pain disorders. We compared their phamlacokinetic properties in order to identify differences and similarities. Method: The pharmacokinetic properties o f pregabalin and gabapentin were assessed using pharmacology studies that measured absorption, bioavailability, metabolism, and drug-drug interaction properties. Results: Significant pharmacokinetic differences were found. Pregabalin is absorbed rapidly (peak concentrations < 1 hr) yielding plasma concentrations that increase linearly with increasing dose. Ill contrast, gabapentin is absorbed slowly (peak concentrations ~-'3-4 hr), yielding plasma concentrations that do not increase proportionally with dose. Based on plasma concentrations, pregab alin is ~-'2.5 times more potent than gabapentin. Significant differences in bioavailability were also encountered. Pregabalin bioavailability is >90% irrespective o f clinical dose, whereas gabapentin bioavailability drops from 60% to 33% as dose increases from 900 to 3600 mg/day. Pregabalni and gabapentin can be given without regard to food intake since absorption is unaffected by food. Apparent volumes of distribution for pregabalin and gabapentin are 0.5 and 0.8 L/kg, respectively. Neither pregabalin nor gabapentin are metabolized, inhibit the enzymes responsible for tile metabolism of other drugs, nor bind to plasma proteins. Both drugs are elinfinated renally (tl:~ '~ 6hr). Pregabalin renal clearance is < G F R (~70 mL/min) indicating net tubular re-absorption. Gabapentin renal clearance is similar to GFR; however, cimetidine reduces gabapentin renal clearance. Pregabalin can be adnffnistered two- or three-times daily while gabapentin is given three-times daily. Conclusion: Pregabalin, a second generation cx2-~ ligand, was found to have distinct pharmacokinetic advantages over gabapentin. 1585 A P A microcapsulized BCCs transplantation can reverse down-regulation of mRNA expression for GABAA receptor in spinal cord of rats with neuropathic pain

Xu, L l, Jiang, y 1 Xue, y1, Zhang, H 1. 1pL A Genera! Hospital,

Beifing, Beifing, China. Background: To study tile effects subarachnoid transplantation of APA microcapsulized bovine chromaffin cells (BCCs) on expression of m R N A for ct2 and Y2 subunit of GABAA receptor in spinal cord of rats with chronic, constrictive injury(CCI) of sdatic nerve. Methods: SD rats were randomly divided into four groups, each has ten. Normal rats were used as control group (group C). Rats that right sciatic nerve was ligated were used as CCI group. Five to six hmldred empty A P A mJcrocapsules (group APA) or 5× l0 s A P A microcapsulized BCCs (group APA-BCCs) were grated into subarachnoid space of CCI rats 7 days after operation. Allodynia and hyperalgesia were measured by Von-Frey filaments and CO~ laser dividually 7 days after transplantation. After that spinal cord in lumbar four and five was taken out, m R N A expression for GABAA receptor cz2 and 72 subunit was measured by RT-PCR and in situ hybrization. Results: The expression of m R N A for GABAA receptor ~2 and "~'2 subunit in the spinal cord of group CCI and group A P A was lower than that in group C. The expression o f m R N A for GABAA receptor el.2 and ~,~ subunit in group APA-BCCs was higher than that in group CCI and group A P A with abatenlent of allod2affa and hyperalgesia. There was no difference in expression of m R N A for GABAA receptor ~2 and Y2 subunit between group APA-BCCs and group C. Conclusion: The expression of m R N A for GABAa receptor ~.2 and ~,~ subunit in the spinal cord of CCI rats was down-regnlated and subarachnoid transplantation of A P A microcapsulized BCCs can reverse the down-regulation. Recovery of GABAa-nergic neuron activity contributes to the analgesic effect of A P A microcapsulized BCCs subarachnoid transplantation.

Friday, November 11, 2005

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1586 Progressive Cervical Myelopathy revealing an Aflanto Axoidean Dislocation and a Cratdovertehral Junction Malfomlation (a case report) Adali N 1, Louhab N 1, Kissani N 1. 1Neurology Department, CHU

Mohammed VI, Marrakech, Morocco Background: Atlanto mxoidean dislocation malformation is rare and the fact it reveals a craniovertebral junction malformation has never been described as far as we know. Method: Authors report a case of a 42 years old woman with a past of cervical vertebral traumafism one year before her admission. She presented a progressive motor deficit of the 4 limbs and polypnea 3 months before admission. Neurological exarmnation found spastic tetraplegia and sphincter's disorders (urinary incontinence) without ally sonlatosensory disturbances. Results: Cervical medullar MRI and radiography showed C1-C2 block vertebra and atlanto axoidean dislocation with a severe medullar and spinal bulb compression and an atlas occipitalizafion. Patient was immediately operated in neurosurgery department with a medullar decompression and cervical fixation and the out come showed a progressive recovery. Conclusion: Authors underline tiffs exceptional revelation and the possibility of a complex craniovertebral malfomlation that could remain asymptomatic for a long time. 1587 Neurogetfic HyperpyreXia In Creutzl~hlt-Jakoh Disease

Adaul, A M 1, Akuku, 01. 1Departments of Medicine and Surgery,

University Of Nairobi, Kenya Objective: To study the pattern o f occurrence and clinical features of Creutzfeldt Jakob Disease [CJD] in Kenya. Study Design; Prospective, cross sectional, descriptive study of clinical, encephalographic and natural history of Creutzfeldt Jakob Disease, backed by histology in as many patients as possible. Methods: Consecutive patients presenting with the criteria laid down by WHO expert committee for diagnosis of CJD were recruited between January 1990 to May 2004. We analysed the clinical features and electroencephalography of all participants and brain biopsied four of them. Results: There were four definite, seven probable and two possible cases. The electroencephalographic and histological features were classical for sporadic CJD. Three of definite and one of probable cases had persistent hyperpyrexia soon after presentation until the terminal phase. No other cause of their pyrexia was found. Exanffnation of the hTpothalanlo-pitnitary systems was normal in these four patients, except for secondary hypothyroidism. Contusion: Unrelenting hyperpyrexia is seen in about a quarter of our patients. It not affect significantly the prognosis although the sample is small. Due to disruption of the many neuronal systems in CJD, it thought to be neurogenic due to danlage to the hypothalamus. 1588 Eflicaey of Levetixacetam in Huntington's Disease de Tommaso, M ~, Sciruicchio, V a, Specchio, N 1, Di fruscolo, 01, Connio, C 1, Barulli, M 1, De Caro, M 1, Livrea, p1. 1Department of

Psychiatric and Neurological Sciences, University of Bari, Italy Background: Huntington's Disease (HD) is all inherited condition characterised by the coexistence of involuntary movements and progressive dementia. Levetiracetam (LEV) is a novel antiepileptic drug characterised by a wide spectrum of action and good safety profile, without any pharmacological interaction. In animal models, tile effects of LEV are observed in basal ganglia. The aim of tiffs study was to evaluate the efficacy of LEV in the reduction of involuntary movements in H D patients.

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Poster Abstracts

Friday, November 11, 2005

Methods: This was a single-centre, short-term, randornised, open-label, controlled study, conducted in HD patients. For every two patients randomised to receive LEV treatment, one patient was randomised to an untreated control group. Patients were assessed using the Unified Huntington Disease Rating Scale (UHDRS) and Miui Mental State Exanffnation (MMSE) at the first visit and subsequently every 2 months. LEV was administered at a dose o f 500 mg BID for 2 months, and then the dosage was increased to 1000 mg BID for a further 4 months. Results: A total o f 22 patients were enrolled (nine male). Fifteen patients were assigned to the LEV group and seven to the control group. After 6 months, patients treated with LEV demonstrated a significant reduction in involuntary movements and a slight improvement in functional capacity, compared with the control group. No serious adverse events were reported. Conclusion: Results of tiffs short-term, prospective, controlled study indicate that LEV is effective in reducing involuntary movements in HD patients, thus improving their quality of life. 1589 Levetiracetam efficacy in Hallucinogen Persisting Perception Disorders: a prospective study Casa, B 1, Bosio, A 2. JDrug Monitoring Service, New York NY; USA; 2Mater Dei Clinic, Rome, Italy Background: The occurrence of flashbacks following use o f drugs is a recognised condition known as Hallucinogen Persisting Perception Disorders (HPPD), therapy for wlffch is based on neuroleptic and attticonvulsant medication. Tiffs prospective study assessed the efficacy of the novel atttiepileptic drug levetiracetam (LEV) in treating patients with HPPD over a 1-year period. Method: Patients with HPPD were treated with LEV 1500 mg/day (500 mg in the morning, 1000 mg in the evening) for 1 year. Daily flashback frequency and electroencephalogram (EEG) assessments were conducted at Day 0, 15, 30, 60, 90, 180 and 360. The incidence of adverse events was monitored throughout the study. Results: 27 patients (121 males, 6 females), with a mean age of 21.8 (range 18-26) years, were enrolled. At baseline, mean daily flashback frequency was 9.3 (range 1-45) and EEG assessment demonstrated temporal slow patterns in all patients. Over the 1-year treatment period, 20/27 (74.1"/o) patients became flashback-free. After 15 days, 7/27 (25.9%) patients were already without clinical malfffestations, with 6 patients demonstrating > 75% reduction in flashback frequency and 1 demonstrating 50-75% reduction. EEG patterns normalised in 18/27 (66.7%) patients after 30 days and in 23/27 (85.2%) after 90 days. 3/27 (11.1%) patients continued to have flashbacks, despite complete disappearance of EEG abnormalities. Side effects were few in incidence and mild in severity. No patient discontinued treatment. Conclusions: This study demonstrated LEV to be highly efficacious in the treatment of HPPD, with very good tolerability and ease of use. 1590 Tile most large fanfily in Cuba affected by Acute Intermittent Porphyria Asencio, A l, Rodriguez, Y~, Torriente, M a. l"Julio Trigo" General

Hospital, Havana, Cuba; ~ "Julio Trigo'" Medical School, Havana, Cuba Porphyrias are a group of inherited disorders of heme synthesis. Only one normal gene is present to produce a key functional enzyme in heme synthesis. It results in at least a 50% of the normal enzyme aaivity. This reduced level of enzyme results in a buildup of precursors behind the deficient enzyme which then accumulate in body fluids and tissues. The clinical manifestations, cutaneous lesions, neurological dysfunction, and hepatic disease, characteristic to each type of povphyria are due to the toxic nature of these precursor compounds. Acute intermittent porphyria is a autosomal dominant disorder caused by a

defect in porphobilinogen deaminase activity. Many case exist in latent form, but in manifest case it is more frequently seen in women. The estimated prevalence of the disorder is 5-10 case per 100,000 population. Tire latent form of tire disease may exist indefinitely, but certain drugs, infections, and excessive dieting (starvation) can precipitate attacks. The most common drugs are sulfonanffdes and barbiturates (often seen when give Phenobarbital for pain relief with dental surgery). In the acute attack the neurological dysfunction can involve any portion of the nervous system. It is believed that an imbalance in the autonomic innervation of the gut leads to abdominal pain which is commonly associated with the attack. A family which carries acute intermittent porphyria is presented in this work. The number of family members involved makes it the most large one affected by this illness in Cuba. 159I TranSient Global Aulnesia in Hong Kong AuYeung Man, M 1, Tsoi, TH 2. 1Pamela Youde Nethersole Eastern

Hospital, Hang Kong, SAR China Objective: To investigate the clinical characteristics and aetiology of transient global amnesia (TGA) in Clffnese patients. Methods: A prospective case control study was conducted from Nov. 1998 to Dec 2004. Each T G A patient was compared to one transient ischaernic attack (TIA) control and one normal control for presence of vascular risk factors. Results: 55 (136 female) T G A patients were diagnosed from Nov.1998 to Dec 2004. The annual incidence was 1.8/100000. Mean age was 61, range from 38-80. HT, D M and hyperlipidaemia were siguificantly higher in TIA control than TGA. When compared T G A with normal control, migraine was the only significant finding. The mean follow-up in TGA and TIA was 34.8 and 43.8 months respectively. The annual incidence of further cerebrovascular event in TIA group was 10.5¢/o. Neither thromboembolic nor epileptic event was reported in T G A patients. There were 2 recurrences of T G A noted; the annual recurrent rate was 1.2%. Three patients had brain SPECT during amnesic phase; two showed bilateral hippocampal hypo-perfusion, and one had right hippocampal hypo-perfusion. All abnormalities normalized on followup scans. Four patients had DWI performed 24 hours after symptom onset, none revealed any abnormality. Conclusions; The clinical characteristics are similar to Caucasians. No excessive vascular risk factor was found in T G A patients compared with normal control. Neither subsequent cerebrovascular event nor seizure was noted in TGA group. Therefore, both thrombo-embolism and epilepsy are unlikely to be the aetiology, migraine was significantly higher in T G A than control groups, suggesting an aetiological relationslffp. 1592 Opinions, attitudes and practices of Australian Neurologists with regards to Epilepsy and driving Beran, R G 1'2, Ainley, L A E a, Beran, M E 1. JStrategic Health

Evaluators, Sydney, Australia; 2Liverpool District Hospital, Sydney, Australia Background: Austroads, representing all Australian state and territory licensing authorities, promulgated guidelines for fitness to drive. This paper reports neurologists' opinions and practices concerning these guidelines pertaiuing to epilepsy. Method: A piloted, ethics committee approved questionnaire was distributed to Australian Assodation of Neurologists (AAN) members with 80% response rate required as representative. Results: Of 236 potential respondents, ~-'70% returned completed surveys, ~-'9% did not assess epilepsy and r~3 % declined involvement, achieving a representative .~82% response. 70% of completed surveys endorsed the guidelines. Most (177"/o) advocated that doctors determine fitness to drive; 55"/0 excluded GPs as insufficiently knowledgeable