11-JUN-1999 BSDS
`JOURNAL OF NEUROLOGY -BERLIN-
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`BOSTON SPA
`LS23 780
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`8i::ITISH LiBRARY
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`Sawai (IPR2019-00789), Ex. 1033, p. 001
`
`

`

`1 Neural (1999) 246 [Suppl 1]: l/1-I/196
`© Springer-Verlag 1999
`
`ABSTRACTS
`
`Ninth Meeting of the
`European Neurological Society
`5-9 June, 1999, Milan, Italy
`Abstracts of Symposia, Free Communications
`and Posters
`
`The abstracts have been reviewed by:
`J. Berciano, J. Bogousslavsky, T. Brandt, G. Comi, D. A. S. Compston, S.
`DiDonato, H.-P. Hartung, J. G. Hildebrand, G. Kennard, G. Krarup, D. Leys,
`I. Milonas, G. Said, A. Steck, P. Scheltens, F. Vander Meche, J. Van Gijn
`
`for RMS
`se only
`
`llllllllllllllllllllllllllllllllllllllllllllllllll
`49266549
`16.FEt{l4 4 Q 0 0 5
`s
`
`Return Date:
`
`Request Ref. No.
`13556 LOAN S
`If no other library indicated please return ~§:-
`The British Library Document &lpply Centre, Boston Spa,
`Wetherl5y, West Yorkshire, LS23 7BO
`
`Sawai (IPR2019-00789), Ex. 1033, p. 002
`
`

`

`I/2
`
`Contents
`
`Abstracts of the Symposia
`Presidential Symposium: Neuro-Oncology
`Prospects in glioma therapy
`I/3
`Primary central nervous system lymphoma in
`immunocompetent patients
`I/3
`Paraneoplasia: recent developments
`
`I/3
`
`Symposium 2: Advances in management of Parkinson's disease
`How accurately can we diagnose idiopathic Parkinson's disease?
`I/4
`The role of glial cells in the neurodegeneration
`of Parkinson's disease
`I/4
`Anita Harding lecture:
`Biochemical and functional organization of the basal ganglia
`The role of subthalamic nucleus in the pathophysiology
`of Parkinson's disease: recent lessons from surgery
`I/5
`
`I/4
`
`Symposium 3: Functional imaging of the nervous system -
`The anatomy of cognition
`The anatomy of cognition- "brain plasticity"
`Perception and attention
`I/5
`
`I/5
`
`Language, communication and numeracy
`Memory for words and places
`I/6
`
`Symposium 4: Protein neuropathology of degenerative disorders
`The roles of mutant presenilins and APP
`in familial Alzheimer's disease
`l/6
`APP and amyloid in cells, slices and brain of transgenic mice
`Huntington's disease and polyglutamine disorders
`I/7
`Prions and the immune system
`I/7
`
`I/6
`
`Symposium 5: Controversial treatments in neurology
`The implementation of b-interferon in multiple sclerosis
`Thrombolysis in acute stroke
`I/8
`What is the goal of surgical treatment in Parkinson's disease?
`Dealing with new drugs in epilepsy
`I/8
`
`I/8
`
`l/8
`
`Abstracts for Oral Sessions
`
`l/ ll
`I/ 12
`
`I/8
`Cerebrovascular disorders - 1
`I/9
`Cerebrovascular disorders - 2
`I
`Amyotrophic lateral sclerosis and motor neurone disease -
`Amyotrophic lateral sclerosis and motor neurone disease - 2
`Infectious disorders of the nervous system
`I/13
`Multiple Sclerosis -
`I l/14
`Immunology- I
`I/15
`Immunology- 2
`I/17
`I/18
`Muscle Disorders- 1
`Muscle Disorders- 2
`I/19
`I/20
`Multiple Sclerosis - 2
`I/22
`Multiple Sclerosis - 3
`Cerebrovascular disorders -3
`General Neurology - I
`l/24
`Peripheral neuropathy -
`I
`I/25
`Peripheral neuropathy - 2
`I/26
`Neurogenetics - l
`l/28
`Neurogenetics - 2
`I/29
`Neuro-oncology - I
`Ii30
`Neuro-oncology - 2
`I/31
`Higher functions disorders
`Prion disease and dementia
`Multiple Sclerosis - 4
`I/35
`Multiple Sclerosis - 5
`I/36
`
`l/32
`I/33
`
`I/23
`
`I/40
`
`I/37
`
`General Neurology - 2
`Epilepsy
`I/38
`Peripheral neuropathy - 3
`Neuro-ophthalmology
`I/41
`Neurogenetics - 3
`I/42
`Neurogenetics - 4
`I/43
`Functional imaging
`I/44
`Extrapyramidal disorders - I
`Extrapyramidal disorders - 2
`
`I/46
`I/47
`
`Abstracts for Poster Sessions
`
`Poster Session 1
`Neurobiology
`I/48
`Higher function disorders
`Neuro-immunology
`I/54
`Amyotrophic lateral sclerosis and Motor neuron disease
`Multiple Sclerosis
`I/60
`Neuro-Ophthalmology & Neuro-Otology
`Neuro-oncology
`I/67
`Pain & Headache
`l/69
`Extrapyramidal disorders
`
`I/49
`
`I/70
`
`I/65
`
`I/57
`
`Poster Session 2
`Neurobiology
`I/70
`Clinical neurophysiology
`I/71
`Cerebrovascular disorders
`I/74
`I/81
`Higher functions disorders and dementia
`I/84
`Epilepsy, Encephalopathy, Encepahlitis
`Amyotrophic lateral sclerosis & Motor neuron disease
`Multiple Sclerosis
`I/89
`Pain & headache
`I/92
`
`I/87
`
`Poster Session 3
`I/94
`Clinical neurophysiology
`I/97
`Cerebrovascular disorders
`Higher functions disorders and dementia
`General neurology
`I/105
`History of neurology
`I/!08
`Multiple Sclerosis
`I/109
`Peripheral neuropathy
`I/113
`
`Poster Session 4
`Clinical neurophysiology
`I/117
`Cerebrovascular disorders
`I/118
`Dementia and Higher functions disorders
`Extrapyramidal disorders
`I/124
`Epilepsy
`I/127
`I/129
`General neurology
`I/134
`Multiple Sclerosis
`Peripheral neuropathy
`I/136
`
`I/101
`
`I/122
`
`Poster Session 5
`I/139
`Sleep disorders
`I/140
`Neurobiology
`Child neurology
`I/141
`Cerebrovascular disorders
`Extrapyramidal disorders
`Multiple Sclerosis
`l/155
`Neuro-Oncology
`I/158
`
`Poster Session 6
`Neurogenetics
`I/161
`Infection nervous system
`I/!73
`Multiple Sclerosis
`Muscle Disorders
`I/178
`
`I/144
`I/!46
`
`I/170
`
`Sawai (IPR2019-00789), Ex. 1033, p. 003
`
`

`

`I/36
`
`3 timepoints (5 minutes=3.2%, 20 minutes=2.5%, 40 minutes=I.S%, p <-
`0.0005). Such changes were apparent in all MS subgroups. These findings
`suggest the presence of widespread low-grade and possibly chronic BBB
`leakage in NA WM and ANEL that may contribute to disease progression
`in MS.
`
`142
`THE PATHOGENESIS OF RELAPSING REMITTING MULTIPLE
`SCLEROSIS [MS]; DESIGN OF A LARGE LONGITUDINAL STUDY.
`CMB Griffin, DH Miller, AJ Thompson. NMR Research Unit, Institute of
`Neurology, University College London, UK.
`
`We report the design of a unique serial multi parameter study aimed at ex(cid:173)
`amining the temporal relationship between inflammation,demyelination
`and axonal loss in early MS. At least fifty patients will be recruited with
`relapsing remitting disease of less than 3 years duration with an EDSS < 3.
`Follow up will be over at least 3 years as follows; M. R. I. Triple dose
`gadolinium enhanced images of brain and cord[ inflammation]. Magnetisa(cid:173)
`tion transfer imaging[demyelination]. Proton spectroscopic imaging[ax(cid:173)
`onal loss]. Hypointense lesion load[axonal loss]. Diffusion tensor imag(cid:173)
`ing[white matter fibre tract integrity] 3D volume imaging of the brain and
`cord [to quantify atrophy;a marker of axonal loss and demyelination] Tl
`relaxation measurements [possibly correlating with gliosis]. Clinical:
`Kurtzke expanded disability status scale, U.S. National M.S. society task(cid:173)
`farce composite scale; visual analogue of fatigue, modified fatigue impact
`scale, short form 36, Queen Square Disease Impact Scale. These will elu(cid:173)
`cidate the relationship between evolving pathology and functional impact.
`Immunological: Blood; C reactive protein,soluble adhesion molecules,sol(cid:173)
`uble T. N. F. alpha,nitric oxide metabolites. Urine; neopterin and free light
`chains. This study will elucidate the mechanisms of irreversible tissue
`damage [especially axonal loss] which is likely to result in clinical pro(cid:173)
`gression.
`
`Multiple sclerosis - 5
`
`143
`ERAZIMUS: EARLY AZATHIOPRINE VERSUS BETA-INTERFERON
`TREATMENT IN MULTIPLE SCLEROSIS. RESULTS OF PILOT
`SAFETY STUDY. Moreau T, Blanc S, Riche G, Confavreux C (Depart(cid:173)
`ment of Neurology, H6pital de I'Antiquaille and H6pital de Ia Croix(cid:173)
`Rousse, Lyon, France)
`
`As single therapies, both recombinant interferon beta and azathioprine
`have shown proven efficacy in patients with relapsing-remitting Multiple
`Sclerosis (MS). The current single-center open pilot study is designed to
`evaluate the safety and tolerance of interferon beta-! a (A VONEXTM) in
`combination with azathioprine (IMUREL™) for the treatment of relaps(cid:173)
`ing-remitting MS. Thirty patients already receiving azathioprine treatment
`for at least 6 months for relapsing-remitting MS have been enrolled. Three
`different dose groups of I 0 subjects each have been made up: 50 mg, 100
`mg or 150 mg daily. After enrollment, the patients received the first intra(cid:173)
`muscular injection of interferon beta- Ia (6 MIU) followed by a weekly in(cid:173)
`jection for 4 months. The safety profile of the combination was evaluated
`through hematology and biochemistry laboratory parameters and clinical
`tolerance performed at specific time points throughout the study. A sec(cid:173)
`ondary objective is to produce information on the effects of the combina(cid:173)
`tion about residual concentrations of neopterin and 6-thioguanine nu(cid:173)
`cleotide levels. Our results confirm the biological and clinical safety and
`tolerance of the combination of interferon beta-! a and azathioprine.
`
`144
`ORAL FUMARIC ACID ESTER (FAE) IN RELAPSING-REMITTING
`MULTIPLE SCLEROSIS (RRMS). A SHORT TERM, OPEN, CLINI(cid:173)
`CAL, IMMUNOLOGICAL AND MAGNETIC RESONANCE IMAG(cid:173)
`ING (MRI) CONTROLLED PHASE II TRIAL. Schimrigk S, Meier D,
`Brune N, Krane M, Hellwig K, Hoffmann V, Rieks M*, Pohlau D*,
`Przuntek H. Department of Neurology, St Josef Hospital, 44791 Bochum,
`Ruhr University Bochum, Germany; * Sauerlandklinik Hachen, Germany
`FAE (Fumaderm®) initially proven to be effective in the treatment of pso(cid:173)
`riasis also showed a semi-selective immuno-modulating influence on T(cid:173)
`cells. FAE seem to be very effective in up-regulating TH 2-type cytokines
`especially IL-4, IL-10 and TGF-. According to the hypothesis that MS is
`caused by autoreactive T-cells, triggered by the dysbalance of TH 1- and
`TH 2-type cytokines, we investigated peripheral blood lymphocytes (PBLs)
`
`from patients with RRMS under FAE treatment. Methods and subjects:
`FAE therapy was investigated in regards to effectiveness and safety in a
`small explorative group of 10 patients over six months. Intracellular TH 1-
`type cytokines (IL-2, IL-4, IL-l 0, TNF-a, TGF-[3, IFN-y) of
`and TH 2-
`PBLs from patients with RRMS were detected. Serial Tl weighted MRI
`with triple dose Gd-DTPA during the study phase were performed regu(cid:173)
`lary. Primary outcome parameter of the study was the reduction of active
`Gd enhancing lesions in Tl weighted MRI. Results: FAE decrease signif(cid:173)
`icantly the amount of active lesions and lesion load of Gd-enhancing le(cid:173)
`sions in Tl weighted MRI. The cytokine balance changed significantly in
`favor of the THTtype cytokines. Cliuically 7/10 patients remained stable
`or improved under FAE therapy during the study. One drop out because of
`stomach disturbances and two not drug related drop outs. Conclusion: In
`our small group of patients with RRMS oral FAE therapy was effective
`most probable due to the selective immunomodulation of THrtype cy(cid:173)
`tokines. The influence on serial Tl weighted MRI is striking. The clinical
`use of oral fumaric acid ester as a possible relevant drug for the treatment
`of multiple sclerosis is now conceivable.
`
`145
`EFFECTS OF GLATIRAMER ACETATE ON MRI MEASURED DIS(cid:173)
`EASE ACTIVITY: RESULTS OF A RANDOMISED, DOUBLE BLIND,
`PLACEBO-CONTROLLED MULTICENTRE STUDY. G. Comi 1, M.
`Filippi 2 for the Copaxone MRI Study Group. 'Clinical Trials and 2Neu(cid:173)
`roimaging Research Unit, Department of Neuroscience, Scientific Institute
`Ospedale San Raffaele, University of Milan, Italy.
`
`Glatiramer acetate is a mixture of synthetic polypeptides which suppresses
`both acute and chronic experimental allergic encephalomyelitis. Two dou(cid:173)
`ble-blind, placebo-controlled trials demonstrated that glatiramer acetate
`reduces relapse rate in patients with relapsing-remitting multiple sclerosis
`(RRMS). The aim of this study was to determine the effects of daily s. c.
`injection of 20 mg glatiramer acetate on MRI-measured disease activity in
`RRMS, during a 9-month double blind placebo-controlled phase, followed
`by a 9-month open label phase. One or more relapses in the two years prior
`to study entry and at least one enhancing lesion on the screening MRI
`scans were required for enrollment. Brain MRI was performed monthly
`during the double blind phase. The primary end-point was the total num(cid:173)
`ber of enhancing lesions. Two hundred thirty-nine patients were enrolled
`( 119 received glatiramer acetate and 120 placebo). There was a significant
`reduction in the total number of enhancing lesions in the treated group
`(29% reduction in LOCF adjusted mean, p=0.003, 35% reduction on data
`as is p=0.0007). Differences in favor of glatiramer acetate were also found
`for: mean number of new enhancing lesions (30% reduction, p=0.0029),
`number of new T2 lesions (35% reduction, p= 0.00 I), median change from
`baseline in volume of enhancing lesions (p=0.0098), median change from
`baseline of T2 lesion load (p=0.0245). The relapse rate was also reduced
`in glatiramer acetate compared to placebo group (-33%, p=O.Oll7). In
`RRMS glatiramer acetate significantly reduced the MRI disease activity
`and burden. This effect mirrored the reduction of clinical activity.
`
`146
`T-CELL DEPLETED AUTOLOGOUS BONE MARROW TRANS(cid:173)
`PLANTATION FOR MULTIPLE SCLEROSIS; TRANSPLANTATION
`RELATED TOXICITY AND EARLY RESULTS IN THREE PA(cid:173)
`TIENTS. J. P. A. Samijn, M. R. Schipperus, P. A. van Doom, J. J. Cor(cid:173)
`nelissen, J. W. B. Moll, C. A. M. Huisman, B. Lowenberg and F. G. A.
`van der Meche. Department of Neurologyand hematology, Erasmus Med(cid:173)
`ical Center Rotterdam.
`
`Based on animal models and clinical observations autologous stem cell
`transplantation and bone marrow transplantation (BMT) may be effective
`therapies for several autoimmune diseases. Phase II studies with different
`conditioning regimens have been initiated worldwide to evaluate if BMT
`can halt disease progression in patients with malignant multiple sclerosis
`(MS). We selected patients by predefined criteria: definite MS according
`to Poser's criteria, an expanded disability status score (EDSS) ~ 3 within
`two years and progression of disability in the years prior to inclusion. Cur(cid:173)
`rent EDSS had to be between 5 and 7. The patients received total body ir(cid:173)
`radiation (2x5Gy) and cyclophosphamide ( 120 mg/kg). Anti-thymocytic
`immunoglobulins were administered for in vivo T-cell depletion. This was
`followed by CD34 selected autologous BMT. Supportive care and isola(cid:173)
`tion methods were according to standard procedure. In three patients (m,
`30 yr; m, 39 yr; f, 48 yr) the transplantation procedure has been completed.
`All patients suffered from general malaise. Liver function disturbances
`and moderately severe toxicodermia were observed in two patients. Two
`
`Sawai (IPR2019-00789), Ex. 1033, p. 004
`
`

`

`1/61
`
`measurement of CNS atrophy has been proposed as a surrogate marker for
`disease progression. We evaluated the enlargement of the ventricular sys(cid:173)
`tem as a marker for brain atrophy with magnetic resonace imaging (MRI)
`and transcranial sonography (TCS) to look for an association between ven(cid:173)
`tricular system diameter and disability, cognitive performance and mood
`in a group of MS patients. Methods: 74 MS patients (48 f, 26m, mean age
`42 y) were included. Disability was assesed by the expanded disability sta(cid:173)
`tus scale (EDSS). Neuropsychlogical test batteries and routine depression
`scales were administered. All patients were submitted to a standardized
`TCS and MRI-protocol. For TCS we applied a color-coded- phased array
`ultrasound system with a 2.5 MHz transducer (Siemens Sonoline Ellegra).
`Ventricular width of the third ventricles and the frontal horns were mea(cid:173)
`sured by two independent investigators. Results: Interobserver reliability
`was high for the measurement of ventricle size (MRI r = 0.9, TCS r = 0.8
`III. for ventricle). Comparison of the data for the diameter of the ventricu(cid:173)
`lar system obtained by TCS and MRI yielded a significant correlation (r =
`0.9 III. for ventricle). There was a significant correlation between the di(cid:173)
`ameter of the third ventricle and disability measured by EDSS. In addition
`TCS and MRI data correlated significantly with the neuropychological
`tests. Correlation with the with of the frontal horns was substantially lower
`for both imaging techniques. No correlation was found between diameter
`of the ventricles and depression scales. Conclusion: The study demon(cid:173)
`strates a correlation between ventricular size, disability and neuropsy(cid:173)
`chological perfo1mance and suggests that the ventricular size in MS is a
`robust parameter for the purpose of such COITelative studies. Moreover it
`was shown that TCS is a valuable method for the assessment of the ven(cid:173)
`tricluar system in MS patients. Therefore this easy applicable teci1nique
`will be further evaluated in serial studies to elucidate the relation between
`inflammation and tissue destruction and for the evaluation of putative
`treatments.
`
`P272
`ORAL FUMARIC-ACID ESTER THERAPY (FAE) INFLUENCE T(cid:173)
`HELPER CELL APOPTOSIS IN PERIPHERAL BLOOD L YMPHO(cid:173)
`CYTES (PBLS) AND SOLUBLE INTERCELLULAR ADHESION
`MOLECULE-I (SICAM-1) IN SERUM OF PATIENTS WITH RELAPS(cid:173)
`ING-REMITTING MULTIPLE SCLEROSIS (RRMS). Brune N, Schim(cid:173)
`rigk S, Meier D, Krane M, Rieks M*, Hoffmann V, Hellwig K, Ptihlau D',
`Przuntek H. Department of Neurology, St. Josef Hospital, 44791 Bochum,
`Ruhr University Bochum, Germany, * Sauerlandklinik Hachen, Germany
`
`Relapses in RRMS are assumed to be induced by autoreactive TH 1-type
`lymphocytes whereas remissions are associated with TH2-type cytokine
`pattern, a deletion of autoreactive T-cells and decline of inflammation.
`Th,-type cytokines are able to induce apoptosis in autoreactive T-cells and
`down regulate inflammatory processes mediated by adhesion molecules
`like siCAM-1. FAE (Fumaderm®) a potent immunomodulator known to
`alter TH 1- towards a THTtype cytokine pattern in vitro and in vivo. We in(cid:173)
`vestigated the influence of oral FAE therapy, as a possible treatment for
`patients with RRMS during an open phase II prospective study. Materials
`and Methods: We examined 10 patients with definitive RRMS. The inves(cid:173)
`tigation over 28 weeks was divided into a baseline section (6 weeks), a
`treatment period (18 weeks) and a post-study section (4 weeks). During
`the investigation, we detected T-cell apoptosis of PBLs using the annexin(cid:173)
`V-binding-method by flowcytometry. Additionally we measured serum
`levels of siCAM l by enzyme linked immunosorbent assay (ELISA). Re(cid:173)
`sults: Operating with those techniques, we were able to correlate the alter(cid:173)
`ation in T-helper cell apoptosis with the observed TH 2 -type cytokine shift
`under drug therapy. We found an increased (50%) rate of apoptosis in T(cid:173)
`helper cells after 6 weeks of treatment which declined to baseline levels
`afterwards in accordance to the IL-l 0 producing lymphocytes. Serum con(cid:173)
`centrations of siCAM-1 remained stable throughout the entire investiga(cid:173)
`tion. Conclusion: FAE (Fumaderm®) seem to have beneficial effects on
`the disease course during the study. Soluble !CAM-I as a proposed long(cid:173)
`term marker of the disease activity remains stable. The rate ofT-helper
`cell apoptosis correlates directly with the observed IL-l 0 induction.
`
`P273
`IN VITRO STIMULATION 0~'< PERIPHERAL BLOOD LYMPHO(cid:173)
`CYTES WITH CALCIUM MONOMETHYLFUMARATE (CAMF) IN(cid:173)
`FLUENCE PRODUCTION OF INTRACELLULAR TH 1- AND TH,(cid:173)
`TYPE CYTOKINES IN A SPECIFIC MANNER.Schimrigk S, Krane M,
`Hellwig K, Hoffmann V, Rieks M*, Ptihlau D*, Prwntek H. Depmtment
`of Neurology, St Josef Hospital, 44791 Bochum, Ruhr University Bo(cid:173)
`chum, Germany; * Sauerlandklinik Hachen, Germany
`
`T-helper lymphocytes classified as TH 1- and THrtype lymphocytes, de(cid:173)
`pending on their different cytokine pattern, have different functions in the
`immune system. TH 1-type cytokines like IFN-y and TNF-a are predomi(cid:173)
`nantly pro-inflammatory and TH 2-type cytokines like IL-4 and IL-10 can
`down regulate inflammation. We investigated the influence of CaMF on
`the TH 1- and TH 2- type cytokine pattern of peripheral blood lymphocytes
`in vitro. Methods: PBLs from healthy donors were stimulated in vitro with
`CaMF in different concentrations (50, 100 and 200J.!M) and with different
`incubation times (24, 48 and 72h). Controls without stimulation were in(cid:173)
`cluded. Cytokines were measured after single stimulation in culture plates.
`TH 1-type cytokines (IL-2, IFN-y, TNF-a) and TH2-type cytokines (IL-4,
`IL-10, TGF-) were detected intracellular by flowcytometry. Results: We
`found a dose dependent influence on intracellular TH 1- and TH2-type cy(cid:173)
`tokine production. There is a marked decrease in the production of TH 1-
`type cytokines and a significant increa~e of TH,-type cytokines after a 24h
`incubation time. The substance affected primarily CD4 positive cells. Dis(cid:173)
`cussion: The changes in the intracellular cytokine pattern after stimulation
`of PBLs in vitro with CaMF are reproducible and suggest a possible pro(cid:173)
`tective role of this substance in inflammatory diseases.
`
`P274
`
`INTERFERON BETA-I B IN THE TREATMENT OF RELAPSING-RE(cid:173)
`MITTING MULTIPLE SCLEROSIS: CLINICAL AND MRI RESULTS.
`Ozakbas S, Idiman E, Cakmakci H, Yener GG, Kovanlikaya I.Dokuz Ey(cid:173)
`lul University, School of Medicine, Departments of Neurology and Radi(cid:173)
`ology.Izmir Turkey
`
`Several evidences suggest that immunopathological factors are critically
`involved in the pathogenesis of multiple sclerosis (MS). Some clinical tri(cid:173)
`als demonstrated that interferon beta-! b reduces the frequency and sever(cid:173)
`; ty of exacerbations, slow the accumulation of disability and supressed
`magnetic resonance imaging (MRI) activity and lesion accrual. In this
`study, seventeen relapsing-remitting MS patients (2 male and 15 female),
`who has short disease period and 2 relapse in the last two years, have re(cid:173)
`ceived 8 million unit interferon beta-! b every other day subcutaneously
`for nine months. They are evaluated clinically and on the base of MRI in
`the second, forth, sixth and ninth months. Clinical evaluation was per(cid:173)
`formed with expanded disability status scale (EDSS). Mean age was
`32.29 ± 5.45, mean disease duration was 2.44 ± 0.61 years, mean EDSS
`score was 2.20 ± 0.41 and mean relapse rate was 2.06 ± 0.90 in the last two
`years. Mean MRI score (which was assigned depending on the volume and
`number of lesions) was 44.12. EDSS scores were significantly decreased
`in the forth (p=0.0277), sixth (p=0.0015) and ninth (0.0015) months of the
`treatment. MRI scores were significantly decreased in the forth (p=0.0409),
`sixth (p=O.OOI9) and ninth (p=0.0007) months. No serious side effect was
`seen during the therapy. We concluded that interferon beta-lb might de(cid:173)
`crease both clinical disability and MRI lesions.
`
`P275
`
`CORTICOSTEROID INDUCED GENE EXPRESSION IN PERIPH(cid:173)
`ERAL BLOOD MONONUCLEAR CELLS OF MULTIPLE SCLEROSIS
`PATIENTS DETECTED BY eDNA MICROARRA YS. Weilbach F.X.,
`Gold, R. and Toyka K.V.Department of Neurology, Julius-Maximilians(cid:173)
`Universittit, Wlirzburg, Germany.
`
`The eDNA microarray technique is a recently introduced method to si(cid:173)
`multaneously survey the expression of multiple genes synchronously. This
`method has been applied to cell cultures and tissue specimens to detect
`transformation- or differentiation-induced gene expression. Using Cion(cid:173)
`tech microarrays we have monitored the change of gene expression pat(cid:173)
`terns induced by standard intravenous steroid pulse therapy for treatment
`of MS relapses in human PBMCs ex vivo. Total RNA was isolated from
`density gradient purified lymphocytes of freshly accessed blood samples.
`dCTP32 labeled eDNA was then hybridized to human eDNA expression
`array membranes. Simultaneous autoradiographic analysis of 588 genes
`indicated an increase in the expression of several transcription, differenti(cid:173)
`ation and proliferation factors in 5 patients. Upregulated genes included
`granulocyte colony stimulating factor receptor-!, LFA-1, interferon
`gamma induced protein, PDGF, IL-2, Interleukin-1 Receptor Type II,
`whereas prothymosin alpha, calgranulin B, thymosin-beta and connective
`tissue growth factor were downregulated. Amongst these are genes hith(cid:173)
`erto not described as steroid-responsive in lymphocytes or PBMCs. This
`technique may be applied to PBMCs ex vivo and allow to detect and mon(cid:173)
`itor disease specific or treatment induced gene expression patterns in a
`easily accessible material. Funding: University Research Funds
`
`Sawai (IPR2019-00789), Ex. 1033, p. 005
`
`