0307 Lead-induced attenuation in the aggregation of acetylcholine receptors during the neuromuscular junction formation

Poster Abstracts SFEMG. ~TNF in serum raised to 74.5 pg/ml. Limb muscle biopsy revealed type 2 fiber atrophy without inflammatory change. Possible involvement of differential expression of neural/muscle agrin isoforms in affected nmscle fibers is under investigation by RT-PCR using printers specific to each isoform. Conclusion: In SNMG, an expression in agrin/MuSK system might account for amyotrophy and amyotrophic patterns in SNMG. In addition, activation of an agrin system should play a role in recovery of amyotrophy. 0303 A randoufised lrial to evaluate the elticacy of daily versus alternate day plasma exchange in severe generalised Myasthenia

Singh, S a, Tfikha, I a, Goyal, V ~, Srivastava, T ~, Shukla, G a, Bhasin, R a, Behari, M 1. 1All India Institute of Medical Sc&nces,

New Delhi, India Background: Plasma exchange in myasthenia gravis is routinely used for induction of remission in patients with myasthenic crisis, the schedule of plasma exchange, however, still needs to be established. Method: Thirty three patients with myasthenia gravis with Osserman's stage IIb and III were randomly allocated to receive alternate day (in -- 17) or daily plasma exchange (n - 16). Myasthenia gravis disease scale (MGDS) score was done before and after the procedure. Subjective improvement in symptoms was also noted. Other outcome measures like time taken for weaning off ventilator, removal of nasogastric tube and total duration of hospital stay were also assessed. Four to five sessions of plasma exchange were carded on each patient and 20-25 ml/kg plasma was removed during each session. Results: No statistically significant difference was found in daily vs. alternate day group with regards to change in MGDS score, percentage change in M G D S score at discharge. The total duration of stay in hospital was less in the daily group as compared to the alternate day group (p - 0.054). Complications rate in the two groups were also similar. Conclusion: We conclude from our study that daily and alternate day plasma exchange are similar in their efficacy and complication rates, and as the duration of hospital stay is less with the daily plasma exchange, it can be the preferred method of perfo,~fing plasma exchange in patients with myasthenia gravis to induce remission of symptoms, however larger studies are required to confirm these observations. 0304 TherapeutiCS Slrategefies in Juvenile MyaSilletfia Gravis

Todorovie, S 1. eClinicfor Pediatric Neurology and Psychiatry, Medical

Faculty, University Of Belgrade, Yugoslavia Heading and Background: Over the last 32 years 216 boys and girls have been treated for Juvenile Myasthenia gravis (JMG) at the Clinic for Pediatric Neurology and Psychiatry in Belgrade. Between 19711978, the J M G clfildren (153 of them) were treated solely with attticholinesterase (AHE) drugs, very few of them with lfigh doses of ACTH and only one child with the irradiation of the thymus. Since 1978, till nowadays almost all J M G children (163) were cured with the combination of AHE drugs, thymectomy and corticosteroids. Method: The therapeutic strategies for the last 25 years was: make the correct diagnosis as early as possible and introduce AHE drugs to make the patient comfortable; perfomt the thy,ttectomy immediately after that (we favour transsternal approach); introduce high doses of Prednisolone (2mg/kg) every second day after thymectomy and keep the patient on that dose until it becomes symptom free and completely undependent of AHE drugs. After that reduce gradually the corticosteroid. On very rare occassions the need for some aditional therapy took place (plasma exchange, cyclosporine). Patients with ocular myasthenia were not thy,ttectomised.

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Results and Conclusion: The therapeutic results significantly differ in these two periods: the mortality was lowered from 7.5% to 0.6% and the number of the J M G clfildren, who were relatively easy and rapidly brought up to the full remission (during which they were symptom and medicament free) ascended from 7.5 to definite 74.3% and possible 83.3% (if we include the "fresh" cases approaclfing the full remission). J M G patients who could not be brought to full remission following the recomanded therapy improved a lot, but never achieved the possibility to be taken off the medicaments. It can be concluded that this therapeutic strategies in clfildren with J M G is recomandable. 0305 Muscle Pathological Changes in MuSK Antibody-Positive Myasthenia Gravis

Yoslmnura, T 1, Motomura, M 2, Slfiraishi, H 2, Nakano, J a, Tsujino, A 2, Stfirabe, S 2, Eguctfi, K 2, Tsujihata, M 3. eSchool of health Sciences,

Nagasaki University, Nagasaki, )'apart; 21st Department of Internal Medicine, Nagasaki Unbeersity, Nagsaki, Japan; 3Nagasaki Kita Hospital, Nagasaki Japan Background: Muscle-specific tyrosine kinase(MuSK) antibodies are found in some patients with seronegative myasthenia gravis. MuSK is a surface membrane receptor essential for the development of the neuromuscular junction. The MuSK Ab-positive M G patients often have weakness in a distribution unnsual for M G with antiacechylcholine receptor antibodies, sparing the ocular muscles and predominantly involving neck, shoulder, and respiratory muscles in clinical but show the small changes in motor end-plate morphologically. In some patients, EMG findings suggest myopathy. Here, we observed the muscle pathological changes in MuSK Ab-positive M G patient. Material and Methods: Motor point biopsies from biceps brachti muscles were taken after informed consent from 9 MuSK Ab-positive patients. Muscle specimens were used for light microscopic observation. Other biopsied specimens were fixed in 3% glutaraldehyde for quantitative analysis of neuromuscular junctions electronmicroscopically. Results and confusion: All of the MuSK Ab-positive M G patient showed typerI fiber atrophy but there is no myopathic changes. The posts~taptic area became small and preserved of postsynaptic density. There is no correlation between the degree o f typeII fiber atrophy and changes of postsynaptic area in motor end-plate.The changes of muscle in MuSK Ab-positive M G patient may be nonspecific. 0306 Rapid and suslained response to hyperhmnune goat serum product Ahnspro in a pafien! wiill Myaesthelfa Gravis

Youl, BD 1, Angus-Leppan, H 1, Hussein, N 1, Brooman, I ~, Fitzsimons, RB ~. 1Royal Free Hospital, London, England; Sydney

University, Sydney, Australia Background: A 37 year-old male had presented 7 years previously with generalised limb and bulbar weakness with marked fatiguability. A single fibre E M G study and an Acetylcholine Receptor Antibody test confirmed Myaesthenia Gravis. Removal of a thymoma led to a complete remission. He re-presented one year ago with fatiguable weakitess o f the right upper limb with variable diplopia. The patient was unwilling to undergo steroid therapy and lfis condition worsened. Method: With the informed consent of the patient, the unlicensed hypefimmune goat serum product Aimspro was injected subcutaneously (2ml, 8rag total protein). On examination prior to injection, there was rnild fight ptosis on prolonged upgaze and moderate fatiguing weakness of right shoulder abduction and finger abduction. The patient complained of diplopia, without clinical signs of ophthalmoplegia. A single fibre study of the right EDC showed marked jitter in 10 of 10 pairs with blocking in one.

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Results: Ten minutes after injection diplopia had resolved and there was no evidence of fatiguability. The E M G findings had not changed. The therapeutic effect lasted for 4 days after each injection and the patient is now asymptomafic on lml, subcutaneously, twice a week. Conclusion: Some 15,000 doses o f Aimspro have been given to over 250 patients in the U.K. without significant side effects. The electrotonus technique suggests an effect of Aimspro on voltage gated sodium channel function, probably through the reduction of triggering voltages. A recent report suggesting malfunction of endplate sodium channels by "innocent bystander" damage in Myaesthenia Gravis is noted. 0307 Lead-induced attenuation in the aggregation of aeetylcholine receptors during the neuromuscular junction formation Chen, S, Chert, T, Lin, C. Kaohsiung Chang Gang Memorial Hospital,

Chang Gang University, Kaohsiung Medical University Background: Lead (Pb z+) toxicity may impact mature neuromuscular junction (NMJ) which is known as a peripheral cholinergic synapse and its signaling cascades responsible for development are similar to those for the central synapses. However, the effect of lead exposure on the formation of N M J in mammals is unclear. Methods: A N G 108-15/C2C12 coculture model was used to measu re the acetylcholine receptor (AChR) aggregates formed on the myotubes. A C h R aggregates were identified by a-bungarotoxin under fluorescent microscope. Single dose of lead acetate with final concentrations at 10 3 10 1 or 10 g M was applied to dishes at the beginning of coculturing. Results: Following 3-days exposure, although NG108-15 cells could extend long neurites to nearby myotubes, obvious dose-dependent attenuation in AC.hR aggregation was shown. The averaged area of an AC.hR aggregate and the averaged number o f A C h R aggregates per myotube were both significantly decreased. In addition, the distribution percentages of various sizes of A C h R aggregates showed that almost half o f the A C h R aggregates were formed with a size of 2-5 ~am2 regardless of lead exposure. After treating 10 gM of lead acetate, significantly more A C h R aggregates ranged from 2 to 20 ~maz were formed and significantly less A C h R aggregates larger than 20 pm a were fonned. Conclusion: These results indicated that lead exposure reduced the extent of A C h R aggregation concerning both the size and number of A C h R aggregates. No significant change was found in the total amount of AC.hRs on the myotubes after lead exposure, which indicated that the attenuation of AC.hR aggregation was not caused by reducing the synthesis o f AChRs but by remaining dispersed pattern of AChRs on the myotubes. 0308 Adaptation and feasibility of NES3 for use in Brazil Collares, CF 1'2, Spinosa HS ~, Malloy-Diniz LF 3, Mansur LL 4, Radanovic M 4, Letz R 5. 1 S~o Paulo Poison Control Center, S~o Paulo,

Brazil; 2Applied Pharmacology and Toxicology Laborawry, University of S~o Paulo, Brazil; 3Health Sciences Faculty, FUMEC, Brazil; 4Behm:ioral and Cognitive Neurology Unit, Department of Neurology, University of Sgo Paulo, Brazil," SRollins School of Public Health, Emory University, Atlanta, USA Background: NES3 is a computerized neuropsychological test battery that has been widely used in Occupational and Envirormlental Neurotoxicology. Developing countries, such as Brazil, present intense and improper use ofneurotoxic agents; however, clinical facilities and diagnostic tools are scarce. Therefore, a great opportunity of studying dose-effect relationships in large populations is being missed. Methods: Eight NES3 tests were chosen for adaptation: Digit Span, Visual Span, Line Orientation, Digit-Symbol, Sequences, Finger Tapping, Nanting and the Auditory Verbal LeanaJng Test.

The adaptation was performed according to the current Standards of AERA, APA, N C M E (11999) and ITC Guidelines (2000), including translation, back-translation, and consensus of specialists. Afterwards, a small sample with no history of stroke and motor disorders was selected from private practice for the feasibility study (N - 30). The sample was heterogeneous regarding age, years of education and familiarity with computers. After testing, these individuals evaluated NES3 and a new consensus was held to appreciate suggestions and the adaptation itself. Results: Modifications in certain instructions and some test parameters were needed. Four subjects (13%) had one aborted test, which were completed after repetition o f instructions. Main complaints were admJnistrafion time (13%), tiredness (113%) and boredness (17%). Conclusions: NES3 has good acceptance and is a promising tool for testing Brazilian individuals. A larger and representative sample is needed to assess the validity and reliability o f NES3 as a useful cliuical tool in this country. 0309

Neurological signs and symptoms in patients with chronic PCB poisoning O:usho accident) for more than 36 years Funaya, H x'2, Yamada,T 3, Ohyagi, y2, Ikezoe, K ]'2, Miyoski, T 4, Fujii, N 1, Kira, j2. 1Department of Neurology, National Omuta Hospital,

Fukuoka, Japan; 2Department of Neurology, Neurological Institute, Graduate School of Medicine, Kyushu University 60, Fuk'uoka, Japan; 3Department of Neurology, Aso Iizulra Hospital, Fz&uoka, Japan; 4Department of Neurology, Omuta Rosai Hospital, Fukuoka, Japan Background: The existence of peripheral neuropathy after chronic exposure to polychlorinated biphenyls (PCBs) is still controversial because studies concerning the effects of PCBs on the peripheral nervous system are rare. Objective: The purpose of this study was to determine the correlation between neurological signs and symptoms and the concentration of serum PCBs. Method: Neurological data collected from the results of a nationwide health examination of 450 male and 557 female Yusho victims (chronic PCB poisoning) exposed more than 36 years ago were compared with recent measurements of the serum PCB concentration and patterns. Results: The frequency of sensory disturbance detected by neurological examination was significantly kigher in the group of officially acknowledged victims (male, P - 0.014; female, P - 0.001) than in age-matched controls. Significant differences were not observed between the serum PCB patterns and the neurological findings, but the serum PCB concentration was significantly higher in the group with decreased tendon reflex in officially and non-officially acknowledged female Yusho victims (male, P - 0.994; female, P - 0.014). Conclusion: These results suggest that the long half-life of PCBs and their accumulation in fatty tissue can lead to persistent mild impairment of the peripheral nervous system even long after exposure. 0310 Clinical analysis of longstanding S M O N Konagaya, M x, Matsuoka, y2, Konagaya, y3, Kuru, S ]. 1Suzuka

National Hospital, Suzuka, Japan; 2Higashi Nagoya National Hospital, Japan; 30bu DementiaCare Research and Training Center, Obu, Japan One thousand and tlfirty one longstanding patients with subacute myelo-optico-neuropathy (SMON; 275 males, 756 females; mean age ± SD, 72.9 ± 9.6 years; age at onset 37.6 ± 9.8 years; duration of illness 35.3 ± 4.0 years) were examined in 2002, 32 years after ban of clioquinol. At onset, 66.7% of patients were unable yo walk, and 4.7% complete blindness. At present time, about 41% of patients were still difficult to walk independently, including 15.8% of complete loss of locomotion. 1.6% of patients were in complete blindness and 5.8% had severe visual intpainnent. The majority (95.6-97.7%) of patients extfibited sensory disturbances including superfcial and vibratory