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Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract. The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.
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UNLABELLED: The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). METHOD: Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. RESULT: The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the "classical" pattern in two patients and a "variant" pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. CONCLUSION: Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the "variant" pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.
Assuntos
Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Adolescente , Adulto , Idade de Início , Biópsia por Agulha , Células da Medula Óssea/patologia , Encéfalo/patologia , Brasil , Proteínas de Transporte/genética , Células Cultivadas , Criança , Feminino , Fibroblastos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Imageamento por Ressonância Magnética , Masculino , Glicoproteínas de Membrana/genética , Mutação , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/patologia , Adulto JovemRESUMO
The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). Method Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. Result The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the “classical” pattern in two patients and a “variant” pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. Conclusion Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the “variant” pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis. .
O objetivo desse estudo foi analisar uma série de casos de pacientes brasileiros com doença de Niemann-Pick tipo C (NP-C). Método Correlação entre manifestações clínicas, alterações laboratoriais, estudo molecular e resposta ao tratamento foram realizadas. Resultado A amostra consiste de 5 pacientes com idade entre 8 e 26 anos. Paralisia do olhar vertical supranuclear, ataxia cerebelar, demência, distonia e disartria estavam presentes em todos os casos. Coloração de filipina na cultura de fibroblastos mostrou padrão “clássico” em dois pacientes e padrão “variante” em três casos. O estudo molecular encontrou mutações no gene NPC1 em todos os alelos. O tratamento com miglustate foi realizado em 4 pacientes. Conclusão Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão “ variante” na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico. .
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Idade de Início , Biópsia por Agulha , Brasil , Células da Medula Óssea/patologia , Encéfalo/patologia , Células Cultivadas , Proteínas de Transporte/genética , Fibroblastos , Imageamento por Ressonância Magnética , Mutação , Glicoproteínas de Membrana/genética , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/patologiaRESUMO
Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. The investigation disclosed pilli torti and thrycorrexis nodosa in the hair, low serum levels of both copper and ceruloplasmin, brain magnetic resonance study showed atrophy and white matter hypointensities on T1-weighted images, electroencephalogram reveals moderate background activity disorganization and epileptiform activity, and muscle biopsy with type 2 fiber atrophy. The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in Menkes disease are discussed.
Assuntos
Ceruloplasmina/análise , Cobre/sangue , Síndrome dos Cabelos Torcidos/diagnóstico , Eletroencefalografia , Eletromiografia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Síndrome dos Cabelos Torcidos/sangueRESUMO
Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. The investigation disclosed pilli torti and thrycorrexis nodosa in the hair, low serum levels of both copper and ceruloplasmin, brain magnetic resonance study showed atrophy and white matter hypointensities on T1-weighted images, electroencephalogram reveals moderate background activity disorganization and epileptiform activity, and muscle biopsy with type 2 fiber atrophy. The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in MenkesÆ disease are discussed.
A doença de Menkes é uma rara desordem neurodegenerativa causada por defeito intracelular na proteína transportadora do cobre. Descrevemos um paciente de 7 meses, masculino, com crises convulsivas, hipoatividade e ausência de contato visual. A investigação demonstrou pilli torti e thrycorrexis nodosa; níveis séricos baixos de ceruloplasmina e cobre; RNM de crânio com atrofia e redução de sinal da substância branca (imagens em T1); eletroencefalograma com moderada desorganização da atividade de base e atividade irritativa; e biópsia muscular com atrofia de fibras do tipo 2. As características clínicas, laboratoriais, genéticas, biópsia muscular e estudo neurofisiológico na doença de Menkes são discutidas.