4-13-14 Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen species

S230

Diagnostic

leukoencephalitis. We report a case of acute myelitis after plasma-derived hepatitis B vaccination. The patient was a 31-year-old man presented with progressive sensory symptoms in extremities that developed 2 weeks after a third vaccination against hepatitis B. MRI of cervicothoracic region revealed swelling and T2 high signal at the level of C4 to C5 cord, and isolated enhancement in the posterior columns between C4 and C5 cord. There was no prodromal events or laboratory results that clearly suggests postinfectious myelitis and other forms of demyelinating disease such as multiple sclerosis. Also, resolution of swelling on the follow-up MR study essentially rule out the diagnosis of a low-grade glioma. The significance of MRI findings and HLA haplotype of the patient will be discussed.

4-13-11

Epilepsy

N. Stojsavljevic,

Center

in 812 deficiency

J. Drulovid,

of Setiia,

D. Sokic, Z. Levi&

School of Medicine,

Uflivenity

of Neurology; Clinical of Belgrade, Yugoslavia

lnsfifufe

Seizures have been seldom described in patients with vitamin 812 deficiency. We report three patients with 812 deficiency who presented with epileptic seizures. Patient 1, a 35 y-o woman, experienced complex partial and generalized tonic-clonic seizures two years before the diagnosis of 812 deficiency. She had no other neurological signs. Despite treatment with carbamazepine, seizures had occurred until hydroxoccbalamin was administered. In patient 2, a 42 y-o man, diagnosis of 812 deficiency was established after a g-year history of generalized tonic-clonic seizures. He had a number of fits monthly despite anticonvulsant medication. On examination, he presented with signs of polyneuropathy and dementia. After administration of hydroxocobalamin he had no further seizures. Patient 3, a 47 y-o woman, experienced generalized tonic-clonic seizures one year prior to the diagnosis of 812 deficiency. After hydroxocobalamin had been introduced, anticonvulsant medication was withdrawn. No further fits occurred in the following year. These cases suggest that epilepsy may be a presenting and unique manifestation of 812 deficiency, with beneficial response to substitutive therapy.

4-l 3-l 2

Multiphasic disseminated encephalomyelitis and multiple sclerosis in children: Diagnostic clues

S. Tenembaum, S. Galicchio, N. Grahana, M. Ferrea, N. Chamoles ‘, N. Fejem-ran. Deparfment of Neurology, Hospital de Pediafrfa “Dr. J.P

Garrahan”, Buenos Aires, Argentina, ’ FE.S.EN. (Fundacidn pare el estudio de las enfermedades neurometabdlicas), Buenos Aires, Argentina Acute disseminated encephalomyelitis (ADEM) has been classically described as a monophasic neurological syndrome (M-ADEM) that may occur after many viral infections. Repeated demyelinating episodes have rarely been published, and in those cases the difference from multiple sclerosis (ME) on purely clinical grounds is very difficult. We present a large group of pediatric patients with a demyelinating condition to establish the prevalence of monophasic and multiphasic disseminated encephalomyelitis (M and MP-DEM), their clinical and paraclinical features, and the differential diagnosis from ME. Methods: clinical charts of 63 pediatric patients with an acquired multifocal demyelinating condition of CNS, either recurrent or non recurrent, diagnosed between 1987-1996, were evaluated. Imaging studies were performed in all the patients: 126 brain and spinal MRls and 22 brain CT scans were compared. Immunologic investigations in blood and CSF were performed in 72% of the patients. To identify the temporal course of the condition, Kurtzke’s expanded disability status scale (EDSS) was applied to the 63 children. Results: with a mean follow-up of 4.6 years (range 6 months-14 years), the evolution of the group was: Xl patients presented clinical and radiological diagnosis of ADEM, 13 patients fulfilled diagnostic criteria of ME, and 3 out of the 50 ADEM-patients presented one or more acute recurrences that differ in clinical and radiological presentation. Correlation between CSF immunological pattern, neuroimaging evolution and impairment scale scores showed significant differences in distinguishing the 3 groups. Conclusions: the M-ADEM was the most frequent demyelinating condition in this pediatric group (75%). The prevalence of MP-DEM was 6%. Normal IgG and negative oligloclonal banding pattern in CSF, the complete or almost complete resolution of demyelinating lesions upon steroid treatment, and the very low scores on impairment scales (EDSS = 2) were significant to classify these recidivant cases as clinical variants of ADEM (MP-DEM), distinguishing them from ME.

I

4-13 13

Steroid-responsive, relapsing-remitting disseminated encephalitis in children

V. Venkataraman,

C. Villar-Cordova,

Neurology and Radiology Houston, Taxas Objective:

To describe

J. Yeakley,

The University four cases

I. Butler. Department

of Taxas-Houston

with clinical

acute Medical

and radiological

of School,

features

sug-

Use of CSF gestive of acute disseminated encephalomyelitis (ADEM) following a viral prodrome with a relapsing and remitting course responding to steroids. Background: ADEM is considered a monophasic illness. Rarely, recurrent episodes of ADEM may occur and the distinction from multiple sclerosis becomes difficult. Distinguishing these two entities have therapeutic and prcgnostic implications. Methods: Chart review of four cases. Results: Ages ranged from 2 to 14 years. Initial symptoms following a viral prodrome included lethargy, seizures, focal weakness and vision loss. Cerebrospinal fluid exam revealed aseptic, lymphocytic pleocytosis in three patients. Magnetic resonance imaging showed enhancing lesions involving brainstem, cerebellum and periventricular white matter. Two had optic nerve and two had spinal cord involvement. Biopsy in two patients was consistent with ADEM. Patients responded to intravenous steroids. All relapsed within two and eight weeks. Three cases had more than two recurrences. Reinstitution of steroids resulted in near complete recovery after each episode. Conclusions: ADEM may present with a polyphasic course. The presence of a viral prodome and the brief intervals between relapses favors this diagnosis. Relapsing ADEM should prompt consideration for longer steroid treatment or alternative therapies.

14-l 3-l 4 1 Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen species U.K. Zettl ‘a’, E. Mix’, J. Zielasek*, M. Stangel 3, H. Meyer-Rienecker ‘, K.V. Toyka’, H.-P. Hartung*, R. Golds. ‘Department of Neurology; Univetsiv

of Restock, German)! *Department of Neurology, Neuroimmunology Branch and Clinical Research Group for Mu/tip/e Sclerosis, Julius-Maximilians-Universitat Wirrzburg, Germany 3 Department of Neurology; Klinikum Benjamin Franklin, Freie lJniversit&t Berlin, Germany This study aims to prove the involvement of reactive oxygen species (ROS) and nitric oxide (NO*) in T cell apoptosis. ROS and NO* are considered important mediators of myelin destruction in autofmmune demyelination. Their role in elimination of autoreactive T cells in these disease conditions via apoptosis induction is unknown. In vitro activated autoreactive CD4+ T cell lines capable of transferring experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN) were exposed to hydrogen peroxide (HsOs), the HsOs releasing hypoxanthine/xanthine oxidase (HXiXO) system or NO.. For detection and quantitation of apoptotic cells, DNA fragmentation was assessed by in-situ tailing with fluorescein-ddUTP and subsequent flow cytometric analysis. H202 applied directly to the cell cultures for 6 h to 18 h at concentrations of 10 PM to 360 PM and Hz02 released by HX/XO caused in a dose-dependent manner apoptosis in 13% to 33% of the peripheral nerve protein P2- and myelin basic protein (MBP)-specific T cell lines. The percentages of apoptotic cells in ovalbumin (OVA)-specific control T cell lines were somewhat lower (8%-24%). NO* released by the penicillamine derivative SNAP induced a higher rate of apoptosis in the myelin-specific Vp8.2~T cell receptor-bearing T cells (38%) MBP-specific (23%) and PP-specific (26%) T cells than in OVA-specific (9%) T cells. The findings suggest a role of ROS and NO* released by infiltrating macrophages in the termination of inflammatory demyelinating processes by elimination of autoreactive and bystander T cells via apoptosis. Recognition of a dual function of ROS and NOa should influence the development of future therapeutic concepts of autoimmune diseases.

14

Diagnostic Use of CSF

14-l 4-01 1 Monitoring of orosomucold concentrations in cerebrosplnal fluld In comparison with CSF cytological findings P. Adam, J. Tichy, P. Nekola,

University,

Prague,

J. Preiningerova.

Dept. of Neurology;

Charles

Czech Republic

In a group of 2148 patients with neurological diseases, cytological and biochemical investigation of CSF were made. For CSF cytological preparations, the sedimentation chamber method was used. Pappenheim and Papanicolaou stains were used as a routine method, special staining methods and immunocytological investigation with monoclonal antibodies were used in indicated cases. CSF and serum levels of orosomucoid were measured using nephelometry (Turbox-Orion analyzer). CSF cytological findings were classified according to the presence of morphological and functional prevalence of cellular elements as a/normal findings or b/lymphocyte clmonocyte dlgranulccyte oligocytcsis or