RESUMO
Among 25 patients diagnosed with Angelman syndrome, we detected 21 with deletion and 4 with paternal uniparental disomy (UPD), 2 isodisomies originating by postzygotic error, and 1 MII nondisjunction event. The diagnosis was obtained by molecular techniques, including methylation pattern analysis of exon 1 of SNRPN and microsatellite analysis of loci within and outside the 15q11-q13 region. Most manifestations present in deletion patients are those previously reported. Comparing the clinical data from our and published UPD patients with those with deletions we observed the following: the age of diagnosis is higher in UPD group (average 7 3/12 years), microcephaly is more frequent among deletion patients, UPD children start walking earlier (average age 2 9/12 years), whereas in deletion patients the average is 4 (1/2) years, epilepsy started later in UPD patients (average 5 10/12 years) than in deletion patients (average 1 11/12 years), weight above the 75th centile is reported mainly in UPD patients, complete absence of speech is more common in the deleted (88.9%) than in the UPD patients because half of the children are able to say few words. Thus, besides the abnormalities already described, the UPD patients have somewhat better verbal development, a weight above the 75th centile, and OFC in the upper normal range.
Assuntos
Síndrome de Angelman/genética , Pai , Impressão Genômica , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Repetições de Microssatélites/genéticaRESUMO
A heterogeneous group of patients with congenital muscular dystrophy associated with clinical or radiologic central nervous system involvement other than the severe classic form with merosin deficiency, muscle-eye-brain disease, and Walker-Warburg syndrome is described. A probable hereditary or familial occurrence could be suggested in all patients. One merosin-positive patient presented severe motor incapacity and cerebral atrophy without any clinical manifestation of central nervous system involvement. A second patient, also merosin-positive, had moderate motor and mental handicap, and epilepsy with no changes in neuroimaging. A third patient, found to have partial merosin deficiency by muscle biopsy, manifested severe psychomotor retardation and cerebral atrophy with foci of abnormal white-matter signal on magnetic resonance imaging. Finally, two merosin-positive siblings with microcephaly, mental retardation, and an incapacitating progressive neuromuscular course, exhibited cataracts without defects of neuronal migration or brain malformation. This report emphasizes the broad clinical spectrum and heterogeneity of merosin-positive congenital muscular dystrophy with associated central nervous system involvement, and illustrates the importance of further studies on clinical, immunohistochemical, and genetic grounds for identifying new subsets of congenital muscular dystrophy.
Assuntos
Encefalopatias/genética , Distrofias Musculares/genética , Atrofia , Encéfalo/patologia , Encefalopatias/diagnóstico , Criança , Pré-Escolar , Diagnóstico Diferencial , Distrofina/genética , Feminino , Seguimentos , Humanos , Lactente , Laminina/genética , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/patologia , Distrofias Musculares/diagnóstico , Distrofias Musculares/patologia , Exame NeurológicoRESUMO
We report on two siblings that have been followed for 14 years, with merosin-positive congenital muscular dystrophy (CMD), cataract, retinitis pigmentosa, dysversion of the optic disc, but no cerebral anomalies, except for microcephaly and slight mental retardation (MR). The younger child had three generalized seizures easily controlled by anticonvulsant therapy. Both children presented hypotonia from birth, delayed psychomotor development, generalized muscular weakness, and atrophy and joint contractures of knees and ankles. The course of the disease, apparently static during the first 10 years of life, became progressive during the second decade with loss of deambulation by the age of 13. Creatine kinase was increased in both children. Bilateral cataract was diagnosed at 6-months of age. In spite of the occurrence of microcephaly, MR was slight and the siblings acquired reading and writing skills after the aged 10. Head magnetic resonance imaging showed normal results in both siblings. The classification of these cases within the broad spectrum of CMD is difficult since most of the known muscle-eye-brain syndromes generally show severe MR and brain anomalies. We consider these cases as corresponding to the rarer syndromes of merosin-positive CMD with associated features such as cataract and MR that were particularly emphasized during the 50th ENMC International Workshop on CMD [Dubowitz V. Workshop report: 50th ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1997;7:539-547]. Further genetic, pathological, neuroradiological, and immunocytochemical studies will be necessary for better elucidation of the classification and pathogenesis of CMD.
Assuntos
Catarata/diagnóstico , Deficiência Intelectual/diagnóstico , Laminina/metabolismo , Distrofias Musculares/congênito , Distrofias Musculares/diagnóstico , Adolescente , Biópsia , Criança , Deficiências do Desenvolvimento/diagnóstico , Distrofina/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Sarcolema/metabolismoRESUMO
We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > or = 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Frutose/análogos & derivados , Adolescente , Anticonvulsivantes/farmacocinética , Criança , Pré-Escolar , Feminino , Seguimentos , Frutose/farmacocinética , Frutose/uso terapêutico , Humanos , Masculino , Projetos Piloto , TopiramatoRESUMO
Subacute sclerosing panencephalitis (SSPE) is an inflammatory neurodegenerative disease related to the persistence of measles virus. Although its frequency is declining because of measles eradication, we still have some cases being diagnosed. With the aim to describe epidemiological aspects of SSPE in Brazil, we sent a protocol to Child Neurologists around the country, 48 patients were registered, 27 (56%) were from the southeast region, 34 (71%) were male and 35 (73%) white, 27 (56%) had measles, 9 (19%) had measles and were also immunized, 7 (14%) received only immunization, 1 patient had a probable neonatal form. Mean time between first symptoms and diagnosis was 12 months (22 started with myoclonus or tonic-clonic seizures, 7 (14%) with behavioral disturbances); 36 patients (75%) had EEG with pseudoperiodic complexes. Follow up performed in 28 (58%) patients showed: 12 died, 2 had complete remission and the others had variable neurological disability. Our data shows endemic regions in the country, a high incidence of post-immunization SSPE and a delay between first symptom and diagnosis.
Assuntos
Sistema de Registros , Panencefalite Esclerosante Subaguda/epidemiologia , Adolescente , Adulto , Fatores Etários , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Sarampo/imunologia , PrognósticoRESUMO
We studied 253 children aged <15 years. Phase 1 included 193 children with migraine (1.1 and 1.2) divided into two groups (<10 and > or = 10 years). We studied the relationship between age and migraine type, headache characteristics, and associated symptoms of the International Headache Society (IHS) definition. A higher frequency of migraine with aura, pulsatile quality, and unilateral location was observed in older children. In phase 2 we studied 176 children with headache (excluding migraine with aura), comparing diagnostic criteria, definition items, sensitivity, and specificity. The results showed that item B of the definition was the most frequent cause of exclusion in the 1.7 diagnostic group. Compared with Vahlquist and the IHS, the Prensky criteria were the most sensitive. Sensitivity was >70% for pain of moderate/severe intensity, duration between 2 and 48 h, isolated photophobia, isolated phonophobia, and aggravation with physical activity. Specificity was >70% for nausea, vomiting, phonophobia and photophobia, isolated photophobia, aggravation with physical activity, and isolated phonophobia. Based on three alternative definitions, each modifying one item of the IHS definition, the sensitivity and specificity of these alternative definitions were compared with the "extended" criteria (children with migraine without aura and migrainous disturbance, according to the IHS criteria, grouped together). Exclusion of headache duration increased sensitivity by 10%, compared to restrictive IHS criteria, without decreasing specificity.
Assuntos
Transtornos de Enxaqueca/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
The authors describe the case of a typical Angelman syndrome patient. The proband presents developmental delay, mental retardation, macrostomia, wide-spaced teeth, seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic and molecular studies showed a maternal deletion of 15q11q13. These results are in agreement with the clinical diagnosis of Angelman syndrome.
Assuntos
Síndrome de Angelman/complicações , Epilepsia/etiologia , Deficiência Intelectual/etiologia , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/genética , Criança , Cromossomos Humanos Par 15 , Feminino , HumanosRESUMO
Children, 47, with various types of severe drug-resistant epilepsy were entered into a prospective, add-on, open trial with vigabatrin. Patients with West syndrome and idiopathic generalized epilepsies were excluded. Seven children had the drug withdrawn, five because of increase in seizure frequency and two because of adverse effects. Drug efficacy, measured according to seizure type, showed a 100% decrease in seizure frequency in 18.6% of partial seizures and 17.3% of the generalized seizures. There was a higher than 50% decrease in 39.5% of partial and 60.8% of generalized seizures, and less than 50% decrease or increase in seizure frequency in 41.8% and 21.8% of partial and generalized seizures, respectively. Vigabatrin mean dosage during phase 3 was 63.6 mg/kg per day (S.D. = 30.5), ranging from 19.3 to 110.5 mg/kg per day. Parametric statistical analysis (Student's t-test) of seizure frequency between phases 1 and 3 showed a significant decrease in seizure frequency for partial (P = 0.022), and generalized seizures (P < 0.0001). Drug-related adverse effects were observed in 18/47 cases (38.3%), consisting mainly of irritability, hyperactivity, dizziness, somnolence and gastrointestinal symptoms.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Ácido gama-Aminobutírico/análogos & derivados , Adolescente , Anticonvulsivantes/efeitos adversos , Brasil , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Vigabatrina , Ácido gama-Aminobutírico/efeitos adversos , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean = 23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range = 1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean = 16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p < 0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.