RESUMO
OBJECTIVE: To evaluate sensitivity to change and discriminant validity of the 20-item Motor Function Measure (MFM-20) in 2-7-year-old patients with spinal muscular atrophy types 1 (SMA1) or 2 (SMA2) treated with nusinersen. METHODS: Children aged 2 to 7 years old with SMA1 or SMA2 treated with nusinersen were assessed at least three times using the MFM-20 over an average follow-up time of 17 months. Evolution of 4-month-standardized MFM-20 scores was calculated for each MFM-20 domain (D1 standing and transfers, D2 axial and proximal, D3 distal) and for the total score (TS). RESULTS: Included in the study were 22 SMA1 subjects and 19 SMA2 subjects. Baseline MFM scores were significantly lower in patients with SMA1 than SMA2 (TS 29.5% vs. 48.3%, D1 4.5% vs. 10.6%, D2 43.6% vs. 72.6%, D3 51.2% vs. 75.0%). When considering the mean change during nusinersen treatment, standardized over a 4-month period, TS was improved for both SMA1 (+ 4.1%, SRM 1.5) and SMA2 (+ 2.8%, SRM 0.89) patients. For SMA1 patients, considerable changes were observed in D2 (+ 6.2%, SRM 0.89) and D3 (+ 6.0%, SRM 0.72), whereas the change in D1 was small (+ 0.5%, SRM 0.44). In SMA2 2 subjects, D3 was improved to a larger extent (+ 4.2%, SRM 0.53) than D1 (+ 1.8% SRM 0.63) or D2 (+ 3.2%, SRM 0.69). CONCLUSION: Our results validate use of MFM-20 to monitor function of young SMA1 and SMA2 subjects treated with nusinersen. Significant motor function improvements following treatment were observed in both SMA1 and SMA2 patients.
Assuntos
Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Criança , Humanos , Pré-Escolar , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Posição Ortostática , Atrofia Muscular Espinal/tratamento farmacológicoRESUMO
Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease that inevitably leads to total loss of autonomy. The new therapeutic strategies aim to both improve survival and optimise quality of life. Evaluating quality of life is nevertheless a major challenge. No DMD-specific quality of life scale to exists in French. We therefore produced a French translation of the English Duchenne Muscular Dystrophy module of the Pediatric Quality of Life Inventory (PedsQLTMDMD) following international recommendations. The study objective was to carry out a confirmatory validation of the French version of the PedsQLTMDMD for paediatric patients with DMD, using French multicentre descriptive cross-sectional data. The sample consisted of 107 patients. Internal consistency was acceptable for proxy-assessments, with Cronbach's alpha coefficients above 0.70, except for the Treatment dimension. For self-assessments, internal consistency was acceptable only for the Daily Activities dimension. Our results showed poor metric qualities for the French version of the PedsQLTMDMD based on a sample of about 100 children, but these results remained consistent with those of the original validation. This confirms the interest of its use in clinical practice.
Assuntos
Distrofia Muscular de Duchenne , Qualidade de Vida , Criança , Humanos , Inquéritos e Questionários , Distrofia Muscular de Duchenne/diagnóstico , Estudos Transversais , Objetivos , Psicometria , Reprodutibilidade dos Testes , PaisRESUMO
BACKGROUND AND PURPOSE: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC. METHODS: We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs. RESULTS: The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants. CONCLUSIONS: Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient.
Assuntos
Coreia , Distonia , Distúrbios Distônicos , Enoil-CoA Hidratase/metabolismo , Doença de Leigh , Transtornos dos Movimentos , Anormalidades Múltiplas , Erros Inatos do Metabolismo dos Aminoácidos , Coenzima A , Distúrbios Distônicos/genética , Humanos , Doença de Leigh/diagnóstico , Doença de Leigh/genética , Transtornos dos Movimentos/genética , Tioléster Hidrolases/deficiência , Valina/metabolismoRESUMO
BACKGROUND AND PURPOSE: Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy caused by KCNJ2 mutations, characterized by a clinical triad of periodic paralysis, cardiac arrhythmias and dysmorphism. The muscle phenotype, particularly the atypical forms with prominent permanent weakness or predominantly painful symptoms, remains incompletely characterized. METHODS: A retrospective clinical, histological, electroneuromyography (ENMG) and genetic analysis of molecularly confirmed ATS patients, diagnosed and followed up at neuromuscular reference centers in France, was conducted. RESULTS: Thirty-five patients from 27 unrelated families carrying 17 different missense KCNJ2 mutations (four novel mutations) and a heterozygous KCNJ2 duplication are reported. The typical triad was observed in 42.9% of patients. Cardiac abnormalities were observed in 65.7%: 56.5% asymptomatic and 39.1% requiring antiarrhythmic drugs. 71.4% of patients exhibited dysmorphic features. Muscle symptoms were reported in 85.7%, amongst whom 13.3% had no cardiopathy and 33.3% no dysmorphic features. Periodic paralysis was present in 80% and was significantly more frequent in men. Common triggers were exercise, immobility and carbohydrate-rich diet. Ictal serum potassium concentrations were low in 53.6%. Of the 35 patients, 45.7% had permanent weakness affecting proximal muscles, which was mild and stable or slowly progressive over several decades. Four patients presented with exercise-induced pain and myalgia attacks. Diagnostic delay was 14.4 ± 9.5 years. ENMG long-exercise test performed in 25 patients (71.4%) showed in all a decremental response up to 40%. Muscle biopsy performed in 12 patients revealed tubular aggregates in six patients (associated in two of them with vacuolar lesions), dystrophic features in one patient and non-specific myopathic features in one patient; it was normal in four patients. DISCUSSION: Recognition of atypical features (exercise-induced pain or myalgia and permanent weakness) along with any of the elements of the triad should arouse suspicion. The ENMG long-exercise test has a high diagnostic yield and should be performed. Early diagnosis is of utmost importance to improve disease prognosis.
Assuntos
Síndrome de Andersen , Síndrome de Andersen/diagnóstico , Síndrome de Andersen/genética , Diagnóstico Tardio , Humanos , Mutação/genética , Mialgia , Paralisia , Estudos RetrospectivosRESUMO
INTRODUCTION: Among the hereditary motor and sensory neuropathies (HMSN), demyelinating forms are the best characterized, with a clear predominance of CMT1A. The axonal and intermediate forms are less described. The aim of this study is to report the genetic diagnosis of Charcot-Marie-Tooth (CMT) according to the nerve conduction velocity (NCV) findings in a pediatric population. METHODS: We retrospectively described a population of HMSN children with a confirmed genetic diagnosis of demyelinated, intermediate, or axonal forms. We compared the results of the genetic analyses with those of motor NCV in median nerve according to whether they were below 25 m/s (demyelinating group); between 25 and 45 m/s (intermediate group), or above 45 m/s (axonal group). RESULTS: Among the 143 children with an HMSN, 107 had a genetic diagnosis of which 61 had an electromyogram. On NCV findings: seven (11%) pertain to the axonal group, 20 (32%) to the intermediate group, and 34 (55%) to the demyelinating group. When NCV was above 45 m/s, CMT2A was the predominant genetic diagnosis (70%) when NCV were below 25 m/s, CMT1A was the predominant genetic diagnosis (71%). Intermediate NCV findings group was the more heterogeneous with seven genetic CMT subgroups (60% CMT1A, CMT1B, CMT1X, CMT2A, CMT2N, CMT4G). CONCLUSION: Taking NCV values between 25 and 45 m/s to define an intermediate group of CMT in children leads to the inclusion of non-typically "intermediate", especially CMT1A. We emphasize the broad spectrum of NCV in CMT1A that justified the systematic search of PMP22 duplication/deletion screening before next generation sequencing panel.
Assuntos
Doença de Charcot-Marie-Tooth , Neuropatia Hereditária Motora e Sensorial , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Criança , Testes Genéticos , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Humanos , Condução Nervosa , Estudos RetrospectivosRESUMO
BACKGROUND: Congenital nemaline myopathies are rare pathologies characterised by muscle weakness and rod-shaped inclusions in the muscle fibres. METHODS: Using next-generation sequencing, we identified three patients with pathogenic variants in the Troponin T type 1 (TNNT1) gene, coding for the troponin T (TNT) skeletal muscle isoform. RESULTS: The clinical phenotype was similar in all patients, associating hypotonia, orthopaedic deformities and progressive chronic respiratory failure, leading to early death. The anatomopathological phenotype was characterised by a disproportion in the muscle fibre size, endomysial fibrosis and nemaline rods. Molecular analyses of TNNT1 revealed a homozygous deletion of exons 8 and 9 in patient 1; a heterozygous nonsense mutation in exon 9 and retention of part of intron 4 in muscle transcripts in patient 2; and a homozygous, very early nonsense mutation in patient 3.Western blot analyses confirmed the absence of the TNT protein resulting from these mutations. DISCUSSION: The clinical and anatomopathological presentations of our patients reinforce the homogeneous character of the phenotype associated with recessive TNNT1 mutations. Previous studies revealed an impact of recessive variants on the tropomyosin-binding affinity of TNT. We report in our patients a complete loss of TNT protein due to open reading frame disruption or to post-translational degradation of TNT.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Miopatias da Nemalina/diagnóstico , Miopatias da Nemalina/genética , Fenótipo , Troponina T/genética , Biópsia , Pré-Escolar , Biologia Computacional/métodos , Feminino , Estudos de Associação Genética/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Imuno-Histoquímica , Lactente , Análise de Sequência de DNA , Deleção de Sequência , Troponina T/metabolismoRESUMO
PURPOSE: Electronic health records are gaining popularity to detect and propose interdisciplinary treatments for patients with similar medical histories, diagnoses, and outcomes. These files are compiled by different nonexperts and expert clinicians. Data mining in these unstructured data is a transposable and sustainable methodology to search for patients presenting a high similitude of clinical features. METHODS: Exome and targeted next-generation sequencing bioinformatics analyses were performed at the Imagine Institute. Similarity Index (SI), an algorithm based on a vector space model (VSM) that exploits concepts extracted from clinical narrative reports was used to identify patients with highly similar clinical features. RESULTS: Here we describe a case of "automated diagnosis" indicated by Dr. Warehouse, a biomedical data warehouse oriented toward clinical narrative reports, developed at Necker Children's Hospital using around 500,000 patients' records. Through the use of this warehouse, we were able to match and identify two patients sharing very specific clinical neonatal and childhood features harboring the same de novo variant in KCNA2. CONCLUSION: This innovative application of database clustering clinical features could advance identification of patients with rare and common genetic conditions and detect with high accuracy the natural history of patients harboring similar genetic pathogenic variants.
Assuntos
Mineração de Dados , Data Warehousing , Criança , Biologia Computacional , Registros Eletrônicos de Saúde , Humanos , Recém-Nascido , Canal de Potássio Kv1.2 , SíndromeRESUMO
Paroxysmal events are usually not directly observed by physicians. The diagnosis remains challenging and relies mostly on the description of witnesses. The effectiveness of videos for seizure diagnosis has been validated by several studies, but their place in clinical practice is not yet clear. The aim of our study was to evaluate the real-life use of videos by child neurologists. We conducted a three-month prospective study in which child neurologists were asked to use a short questionnaire to evaluate all videos that were watched in their clinical practice for an initial diagnosis or during follow-up. A click-off meeting during the French pediatric neurology meeting allowed to recruit participants. A total of 165 questionnaires were completed by 15 physicians over the study period. The physicians were child neurologists working in secondary and tertiary/university hospitals, consulting children with epilepsy. Based on the evaluation of child neurologists, 51% of the videos consisted of epileptic seizures; 40%, nonepileptic paroxysmal events; and 9%, psychogenic nonepileptic seizures. Most of the videos were made on parental initiative. The use of video has modified the first diagnosis hypothesis in 35% of cases. The physicians' feelings regarding the interest of the video used during the diagnostic phase were similar to those of the video used during follow-up. It appears that videos have become a part of the epilepsy clinic and are helpful for diagnosis as well as during follow-up. Unfortunately, one of the limitations of this study is the absence of private practitioner.
Assuntos
Epilepsia , Criança , Eletroencefalografia , Epilepsia/diagnóstico , Humanos , Estudos Prospectivos , Encaminhamento e Consulta , Convulsões/diagnóstico , Gravação em VídeoRESUMO
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting following repeated muscle damage and inadequate regeneration. Impaired myogenesis and differentiation play a major role in DMD as well as intracellular calcium (Ca2+) mishandling. Ca2+ release from the sarcoplasmic reticulum is mostly mediated by the type 1 ryanodine receptor (RYR1) that is required for skeletal muscle differentiation in animals. The study objective was to determine whether altered RYR1-mediated Ca2+ release contributes to myogenic differentiation impairment in DMD patients. The comparison of primary cultured myoblasts from six boys with DMD and five healthy controls highlighted delayed myoblast differentiation in DMD. Silencing RYR1 expression using specific si-RNA in a healthy control induced a similar delayed differentiation. In DMD myotubes, resting intracellular Ca2+ concentration was increased, but RYR1-mediated Ca2+ release was not changed compared with control myotubes. Incubation with the RYR-calstabin interaction stabilizer S107 decreased resting Ca2+ concentration in DMD myotubes to control values and improved calstabin1 binding to the RYR1 complex. S107 also improved myogenic differentiation in DMD. Furthermore, intracellular Ca2+ concentration was correlated with endomysial fibrosis, which is the only myopathologic parameter associated with poor motor outcome in patients with DMD. This suggested a potential relationship between RYR1 dysfunction and motor impairment. Our study highlights RYR1-mediated Ca2+ leakage in human DMD myotubes and its key role in myogenic differentiation impairment. RYR1 stabilization may be an interesting adjunctive therapeutic strategy in DMD.
Assuntos
Desenvolvimento Muscular/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Distrofia Muscular de Duchenne/patologia , Mioblastos/citologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Criança , Pré-Escolar , Distrofina/metabolismo , Humanos , Masculino , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/patologia , Distrofia Muscular de Duchenne/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Retículo Sarcoplasmático/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismoRESUMO
OBJECTIVE: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. METHODS: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types. We made genotypic/phenotypic correlation based on epilepsy-associated missense variant localization over the protein. RESULTS: We found 19 patients carrying a de novo mutation of SCN8A, representing 3% of our cohort, with 9 mutations being novel. Age at onset of epilepsy was 1 day to 16 months. We found two modes of onset: 12 patients had slowly emerging onset with rare and/or subtle seizures and normal interictal EEG (group 1). The first event was either acute generalized tonic-clonic seizure (GTCS; Group 1a, n = 6) or episodes of myoclonic jerks that were often mistaken for sleep-related movements or other movement disorders (Group 1b, n = 6). Seven patients had a sudden onset of frequent tonic seizures or epileptic spasms with abnormal interictal EEG leading to rapid diagnosis of epileptic encephalopathy. Sodium channel blockers were effective or nonaggravating in most cases. SIGNIFICANCE: SCN8A is the third most prevalent early onset epileptic encephalopathy gene and is associated with two modes of onset of epilepsy.
Assuntos
Epilepsia/genética , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Idade de Início , Substituição de Aminoácidos , Anticonvulsivantes/uso terapêutico , Diagnóstico Tardio , Diagnóstico Precoce , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Feminino , Movimento Fetal , Humanos , Lactente , Recém-Nascido , Canal de Potássio KCNQ2/genética , Masculino , Proteínas Munc18/genética , Mutação de Sentido Incorreto , Fenótipo , Gravidez , Estudos Prospectivos , Convulsões/genética , Convulsões/fisiopatologia , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
INTRODUCTION: Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuritis. Our aim in this study was to describe the clinical characteristics and the long-term sequelae of GBS in a French pediatric population. METHODS: In this multicenter, retrospective study we evaluated clinical signs, radiological examinations, laboratory tests, treatments, and outcomes. RESULTS: One hundred ten children were included in this investigation. These children presented with walking difficulties, muscle weakness, and cranial nerve impairment. Electrodiagnostic testing revealed 70% with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and 16% with acute motor axonal neuropathy (AMAN). One hundred children received immunoglobulins. At follow-up, 77% were cured, whereas 9% had sequelae, associated with an axonal form (P < .01) and a short interval between symptom onset and hospitalization (P < .01). The need for intubation was correlated with peripheral facial paralysis (P < .01) and dysautonomia (P < .01). DISCUSSION: Although AIDP and AMAN present in a similar way, the axonal form is associated with a worse outcome.
Assuntos
Paralisia Facial/fisiopatologia , Síndrome de Guillain-Barré/fisiopatologia , Disautonomias Primárias/fisiopatologia , Adolescente , Criança , Pré-Escolar , Paralisia Facial/etiologia , Feminino , França , Síndrome de Guillain-Barré/complicações , Hospitalização , Humanos , Lactente , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Condução Nervosa , Disautonomias Primárias/etiologia , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense ß-glucuronidase (GUSB) variations in exon 3: two novel, c.422A>C and c.424C>T, inherited from his mother, and the rather common c.526C>T, inherited from his father. Expression of these variations in transfected HEK293T cells demonstrated that the double mutation c.422A>C;424C>T reduces ß-glucuronidase enzyme activity. Enzyme replacement therapy (ERT), using UX003 (vestronidase alfa), was started at four months of age, followed by a hematopoietic stem cell allograft transplantation (HSCT) at 13 months of age. ERT was well tolerated and attenuated visceromegaly and skin infiltration. After a severe skin and gut graft-versus-host disease, ERT was stopped six months after HSCT. The last follow-up examination (at the age of four years) revealed a normal psychomotor development, stabilized growth curve, no hepatosplenomegaly, and no other organ involvement. Intriguingly, enzyme activity had normalized in leukocytes but remained low in plasma. This case report illustrates: (i) The need for an early diagnosis of MPS, and (ii) the possible benefit of a very early enzymatic and/or cellular therapy in this rare form of lysosomal storage disease.
Assuntos
Terapia de Reposição de Enzimas , Glucuronidase/genética , Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridose VII/genética , Mucopolissacaridose VII/terapia , Terapia Combinada , Glucuronidase/sangue , Glucuronidase/uso terapêutico , Glucuronidase/urina , Células HEK293 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatomegalia/tratamento farmacológico , Humanos , Recém-Nascido , Leucócitos/enzimologia , Leucócitos/metabolismo , Masculino , Mucopolissacaridose VII/sangue , Mucopolissacaridose VII/diagnóstico , Mutação , Esplenomegalia/tratamento farmacológicoRESUMO
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc.
Assuntos
Neoplasias Encefálicas/genética , Epilepsia/genética , Mutação , Neoplasias Neuroepiteliomatosas/genética , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criança , Epilepsia/diagnóstico , Epilepsia/patologia , Epilepsia/cirurgia , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica , Genes Dominantes , Humanos , Masculino , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/cirurgia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/patologia , Síndrome de Noonan/cirurgia , Fator de Transcrição 2 de Oligodendrócitos , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Lobo Temporal/metabolismo , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Tálamo/metabolismo , Tálamo/patologia , Tálamo/cirurgiaRESUMO
A 21-day-old male infant was admitted with signs of intracranial hypertension. Brain magnetic resonance imaging (MRI) revealed a voluminous mass in the posterior fossa with an intense peripheral enhancement on T1 images with gadolinium. The child was treated secondarily by surgical decompression of the posterior fossa and the lesion was biopsied. The pathological findings indicated infantile hemangioma. Treatment with oral prednisolone was initiated at 3 months, given the lack of tumor involution. Six months after corticotherapy was stopped, repeated MRIs indicated a significant reduction in tumor size and then complete disappearance. Psychometric evaluation was performed at the age of 15 years, showing heterogeneous cognitive disabilities, with verbal abilities superior to nonverbal abilities and delayed motor development. Neurological examination was normal with no focal deficit. To our knowledge, this is the first published case reporting the long-term evolution of a patient with neonatal intracerebral hemangioma. We conclude that psychometric evaluations should be part of the long-term follow-up of children who have had an intracranial capillary hemangioma.
Assuntos
Hemangioma Capilar/tratamento farmacológico , Hemangioma Capilar/cirurgia , Neoplasias Infratentoriais/tratamento farmacológico , Neoplasias Infratentoriais/cirurgia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/cirurgia , Seguimentos , Hemangioma Capilar/diagnóstico por imagem , Hemangioma Capilar/psicologia , Humanos , Recém-Nascido , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/psicologia , Masculino , Resultado do TratamentoAssuntos
Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Interferons/metabolismo , Malformações do Sistema Nervoso/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Doenças Autoimunes do Sistema Nervoso/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , França , Expressão Gênica/efeitos dos fármacos , Humanos , Interferons/genética , Lamivudina/uso terapêutico , Malformações do Sistema Nervoso/metabolismo , Projetos Piloto , Zidovudina/uso terapêuticoRESUMO
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is commonly observed in children with epilepsy. However, factors associated with the development of ADHD and which might help to guide its therapeutic management, remain an issue of debate. METHODS: We conducted a multicenter prospective observational study that included children, aged 6-16 years, with both epilepsy and ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. After inclusion, patients entered a 12-16 week follow-up period during which they were either treated with methylphenidate or they did not receive specific ADHD treatment. ADHD was evaluated with the ADHD Rating Scale-IV. RESULTS: One hundred sixty-seven patients were included, of which 91 were seizure-free during the preinclusion baseline period. At inclusion, the ADHD Rating Scale-IV total score was 30.4 ± (standard deviation) 9.2, the inattentive subscore was 17.3 ± 4.4, and the hyperactive subscore was 13.2 ± 6.6. We did not detect any difference of ADHD Rating Scale-IV scores across patients' age or gender, age at epilepsy onset, epilepsy syndrome, seizure frequency, or number of ongoing antiepileptic drugs. Methylphenidate was initiated in 61 patients, including 55 in whom a follow-up evaluation was available. At the last follow-up, 41 patients (75%) treated with methylphenidate and 39 (42%) of those who did not received ADHD therapy demonstrated ≥25% decrease of ADHD Rating Scale-IV total score (p < 0.001). Response to methylphenidate was greater in girls but was not influenced by any epilepsy-related variables. SIGNIFICANCE: We did not detect any epilepsy-related factor associated with the severity of ADHD. Twenty-five percent of patients did not respond to methylphenidate. A better understanding of the pathologic process that underlies ADHD development in childhood epilepsy might be required to improve therapeutic strategies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Epilepsia/complicações , Metilfenidato/uso terapêutico , Adolescente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Feminino , Seguimentos , Humanos , Masculino , Metilfenidato/efeitos adversos , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To obtain perspective on epilepsy in patients referred to tertiary centers in France, and describe etiology, epilepsy syndromes, and identify factors of drug resistance and comorbidities. METHODS: We performed a cross-sectional analysis of the characteristics of 5,794 pediatric and adult patients with epilepsy included in a collaborative database in France between 2007 and 2013. Comparisons between groups used Student's t-test or Fisher's exact test for binary or categorical variables. Factors associated with drug resistance and intellectual disability were evaluated in multi-adjusted logistic regression models. RESULTS: Mean age at inclusion was 17.9 years; children accounted for 67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in 65%, including those with idiopathic epilepsies. Etiologies differed significantly in adult- when compared to pediatric-onset epilepsy; however, among focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal sclerosis began as often in the pediatric as in adult age range. Drug resistance concerned 53% of 4,210 patients evaluable for seizure control and was highest in progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with focal structural epilepsy and 69% with epileptic encephalopathies were drug resistant; however, 40-50% of patients with West syndrome and epileptic encephalopathy with continuous spike-and-waves during sleep were seizure-free. Ages at onset in infancy and in young adults shared the highest risk of drug resistance. Epilepsy onset in infancy comprised the highest risk of intellectual disability, whereas specific cognitive impairment affected 36% of children with idiopathic focal epilepsy. SIGNIFICANCE: Our study provides a snapshot on epilepsy in patients referred to tertiary centers and discloses needs for diagnosis and treatment. Large databases help identify patients with rare conditions that could benefit from specific prospective studies.
Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Epilepsia , Centros de Atenção Terciária/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/epidemiologia , Criança , Estudos de Coortes , Estudos Transversais , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/terapia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening. METHODS: We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH). RESULTS: We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%. SIGNIFICANCE: Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening.
Assuntos
Epilepsia/genética , Proteínas Munc18/genética , Idade de Início , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Eletroencefalografia , Epilepsias Mioclônicas/genética , Epilepsia/patologia , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Mutação , Estudos Retrospectivos , Deleção de Sequência , Espasmos Infantis/genéticaRESUMO
AIMS: The prognosis of Infantile epileptic spasm syndrome (IESS), relates to the underlying etiology and delay in controlling epileptic spasms. Based on the spasm-free rate, a randomized controlled trial has demonstrated the superiority of combining oral steroids and vigabatrin over oral steroids alone but confirmation in real-life conditions is mandatory. METHODS: We compared two real-life IESS cohorts: a multicenter, retrospective cohort of 40 infants treated with vigabatrin followed by a sequential (ST) addition of steroids, and a prospective, single-center cohort of 58 infants treated with an immediate combination of vigabatrin and steroids (CT). RESULTS: The two cohorts were similar. When the rate of spasm-free infants in the two cohorts was compared on day 14, a significant difference was observed between the ST (27,5 %) and CT cohorts (64 %) (p < 0.0004). This difference remained significant on day 30, with 55 % spasm-free patients in the ST cohort compared to 76 % in the CT cohort (p = 0.03). After the infants had received both vigabatrin and steroids, without taking into account the time point after treatment initiation, no significant difference was observed in the spasm-free rate between the two cohorts (p = 0.38). INTERPRETATION: Real-life data confirm the interest of combination therapy as a first-line treatment for IESS.