1050 Arq Neuropsiquiat r 2002;60(4)
ANGELM AN SYNDROM E: CHARACTERISTICS OF EPILEPSY, ELECTROENCEPHALOGRAPHYC ABNORM ALI-TIES AND CORRELATION TO GENETIC M ECHANISM S (ABSTRACT) * . THESIS. SÃO PAULO, 2001.
KETTE DUALIBI RAM OS VALENTE* *
Angelman syndrome is charact erized by severe men-tal retardation, speech disorder, stereotyped jerky move-ments, peculiar behavioral profile and typical facial t rait s. Eighty to 90% of these patients present epilepsy and sug-gestive electroencephalographic patterns w hich are used as diagnostic criteria and become important w hen the phenotype is not suggestive enough, as in infants. The syn-drome results from distinct genetic mechanisms [deletion (75-80%), paternal uniparental disomy (1-2%), imprinting cent er abnormalit y (2-3%) and UBE3A point mut at ion, found in ¼ of t he negat ive genet ic cases (20-25%)], w hich affect the maternal chromosome 15. The preser-vation of a larger genic contingent is probably related to a milder clinical phenotype as observed in patients w ith-out deletion making its recognition less evident .
The aim of this study w as to analyze the correlation bet w een dist inct genet ic mechanisms t hat det ermine Angelman syndrome and the severity of epilepsy and elec-troencephalographic abnormalities in a series of 26 con-secutive patients w ith clinical and/or genetic diagnosis. Pat ient s w ere classified according t o t heir genet ic studies in cases w ith deletion (n= 19), disomy (n= 3) and negat ive genet ic st udies (n= 4). Sixt y-eight EEGs w ere st udied f or t he charact erizat ion of t he EEG pat t erns, background act ivit y and t he occurrence of elect rogra-phic seizures. Epilepsy w as st udied t hrough clinical his-t ory, V-EEG and file revision and occurred in 84.6% (22/ 26) of t hese pat ient s. Suggest ive EEG pat t erns w ere found in 96.1% (25/26). Prevalence of epilepsy w as
sig-nif icant ly higher in pat ient s w it h delet ion. Param et ers indicat ing severit y of epilepsy such as earlier onset age, higher occurrence of daily, disabling or m ult iple seizu-res, st at us epilept icus and febrile seizures present ed a higher t endency of occurrence in pat ient s w it h dele-t ion. Padele-t iendele-t s w idele-t h disomy did nodele-t presendele-t epilepsy and negat ive cases w ere less severe.
Suggest ive elect roencephalographic pat t erns w ere observed in t he t hree groups. Delt a pat t ern w as t he m ost frequent follow ed by post erior discharges. Thet a pattern w as observed only in patients w ith deletion. Pro-longed, cont inuous or quasicont inuous burst s, as w ell as elect rographic seizures and unspecific int erict al epi-lept iform discharges, w ere predom inant ly observed in pat ient s w it h delet ion. Normal age-relat ed background act ivit y w as m ore f requent in pat ient s w it hout chro-m osochro-m ic delet ion.
We concluded t hat , alt hough epilepsy has been observed in non-delet ion pat ient s, epilepsy w as m ore severe in pat ient s w it h delet ion. This is probably due t o a major involvement of genes, w hich decodify GABA recept ors t hrough t his mechanism. In spit e of t he pres-ence of epilepsy or of a less suggest ive clinical pheno-t ype and regardless pheno-t he genepheno-t ic m echanism involved, EEG could be used as a diagnost ic crit erion in pat ient s in all groups.
KEY W ORDS: Angelm an syndrom e, EEG, epilepsy, genet ic m echanism , delet ion, uniparent al disom y.
TEACHING INFANTILE NEUROLOGY IN BRAZIL: CURRENT ASPECTS, CHALLENGES AND PERSPECTIVES (ABSTRACT)* . THESES. CAM PINAS, 2001.
CARM EN SILVIA SANCHES * *
* Síndrome de Angelman: caract eríst icas da epilepsia, das anormalidades elet rencefalográficas e correlação com os mecanismo genét i-cos. Tese de Dout orado, Universidade de São Paulo (Área Neurologia). Orient adora: M aria Joaquina M arques-Dias.
* * Adrdress: Rua Jesuíno Arruda 901 / 51, 04532-082 São Paulo SP, Brasil. FAX: 11 3079 5493. E-mails: ket t evalent [email protected] / mkv@mat rix.com.br
This st udy int ends t o ident ify how m any and w hich are t he format ion and t raining cent ers in Infant ile Neu-rology in our country and its particularities. Besides, it t ries t o f ind out w het her or not t here are dif f erences bet w een t he services w hich are accredit at ed by t he Nat ional Commission of M edical Residence and t he ser-vices t hat are not accredit at ed by t his Com m ission.
Arq Neuropsiquiat r 2002;60(4) 1051
Cam pinas. The expect at ions of t he com ponent s of 2 groups in t he beginning and in t he end of t he course w ill be evaluat ed.
In the initial part, are w oven considerations about t he medical t eaching and it s charact erist ics. It is presen-t ed brief reporpresen-t aboupresen-t presen-t he beginning of presen-t he m edical at t endance and of t he f oundat ion of t he m edical schools in Brazil. In adit t ion t o t his, it is present ed small hist ory of t he Neurology and of t he Inf ant ile Neurolo-gy in our count ry.
It is approached t he t eaching of Neurology in medi-cal graduat ion course and it is st ood out t he import an-ce of t he M edical Residenan-ce courses t o prepare quali-f ied and m odernized proquali-f essionals in t heir area oquali-f per-f orm ance per-f ront t he new know ledge in M edicine.
At t he end, t he result s of t he researchs are present ed and are w oven considerat ions relat ed t o each resear-ched segm ent .
KEY WORDS: formation and training centers in infan-tile neurology; medical residence in infaninfan-tile neurology.
ANALYSIS OF HLA DQ, DP, DR ALLELES ASSOCIATED WITH M ULTIPLE SCLEROSIS SUSCEPTIBILITY IN A POPU-LATION OF PATIENTS FROM THE RIO DE JANEIRO CITY (ABSTRACT) * DISSERTATION. NITERÓI, 2002.
CLÁUDIO CÉSAR CIRNE SANTOS * *
* Ensino da neurologia infant il no Brasil: aspect os at uais, desafios e perspect ivas (Resumo). Tese de Dout orado, Universidade Est adual de São Paulo (UNICAM P) (Área: Neurologia). Orient adora: Sylvia M aria Ciasca
* * Address: Avenida Salvador M arkow icz, 650 / 16, 12916-400 Bragança Paulist a SP, Brasil.
M ultiple sclerosis (M S) is a chronic inflammatory dise-ase of t he hum an cent ral nervous syst em of put at ively autoimmune origin characterized by multifocal demyeli-nat ion. Genet ic and environment al fact ors are t hought t o be involved in t he pat hogenesis of M S, w it h t he dis-ease considered rare in t ropical count ries, including Brazil. Genet ic st udies indicat e t hat t he major hist ocom-pat ibilit y complex (M HC)/HLA region on chromosome 6p21 cont ains M Spredisposing component (s). How -ever, w hich gene(s) present in t his region are respon-sible f or M S suscept ibilit y in t he brazilian populat ion is st ill an unset t led issue.
This st udy aim ed t o analyze t he frequencies of HLA class II alleles (DQA1* 0102, DQB1* 0602, DPA1* 0301, DRB1* 1501, DRB1* 1503) expression in a group of M S pat ient s from t he Rio de Janeiro cit y. It w as included 42 individuals (73.8% female and 26.2% male) w it h clinically definit e M S w it h age range of 15 t o 55 years. In relat ion t o et hnic background, M S pat ient s w ere of w hit e/caucasian (CA) descendent (76.2%) and (23.8%) black/african-brazilian (AF) descendent . Age-mat ched (16 t o 58 years) cont rol healt hy individuals, consist ed of 53.6% (female) and 46.4% (male) w it h t he follow -ing et hnic background: 58.3% w hit e/caucasian descen-dent and 41.7% black/african-brazilian descendescen-dent. HLA
t yping w as performed by amplificat ion of t he DNA iso-lat ed from peripheral leukocyt es w it h Polymerase Chain React ion (PCR) follow ed by SSOP hybridizat ion.
M S pat ient s show ed a posit ive associat ion for alle-les DQB1* 0602 (Pc= 0.021; RR= 2.40) and DQA1* 0102 (Pc= 0.0041; RR= 3.30). Likew ise, increased frequen-cies of DQB1* 0602 (45.2%) and DQA1* 0102 (35.7%) endow ed st rong correlat ion of t his allele com binat ion w it h disease suscept ibilit y in CA pat ient s. DR2 haplo-t ype frequencies am ong healhaplo-t hy individuals and M S group w as low. Since bot h (CA, AF) et hnic groups of M S patients show ed very low frequencies of DRB1* 1501 and DRB1* 1503 it is suggest ed t hat anot her DRB allele associat ion m ay be conferring suscept ibilit y t o M S in t his populat ion. Finally t he low frequency (RR= 0.36) of DPA1* 0301 allele consist ent ly observed in our M S pat ient s but not in t he cont rol group, indicat e t hat such allele m ay rat her have a prot ect ive role against M S.
In conclusion, genet ic suscept ibilit y t o M S in brazi-lian individuals m ay depend upon a specific allele m o-saic int eract ing at several loci necessary t o reach a crit i-cal t hreshold f or disease developm ent .
KEY W ORDS: m ult iple sclerosis, HLA, aut oim m une disease, dem yelinat ion
* Análise de alelos HLA DQ, DP, DR associados à suscet ibilidade à esclerose múlt ipla numa população de pacient es da cidade do Rio de Janeiro (Resumo). Dissert ação de M est rado, Universidade Federal Fluminense (UFF) (Área: Biologia Celular e M olecular). Orient adoras: Izabel Christ ina P. Frugulhet t i & Thereza Quírico-Sant os. Consult oria: Soniza Vieira Alves-Leon. Financial support : CAPES, CNPq
