Early-Onset Dystonia and Visual Impairment Preceding Epileptic Encephalopathy Associated with PIGA Gene Mutation.

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.

Paroxysmal ocular movements - an early sign in Glut1 deficiency Syndrome.

The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.

Memory functioning in children with epilepsy: frontal lobe epilepsy, childhood absence epilepsy, and benign epilepsy with centrotemporal spikes.

Specific cognitive deficits have been identified in children with epilepsy irrespective of results on intelligence tests. Memory deficits are traditionally attributed to temporal lobe epilepsy, whereas the impact of frontal lobe epilepsy on memory functions has remained controversial. The aim of this study was the examination of memory abilities in other childhood common epilepsy syndromes (frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE), and benign epilepsy with centrotemporal spikes (BECTS)) and the influence of epilepsy-related variables. Memory was examined in 90 children with epilepsy (each epilepsy group consisted of 30 children), aged 6-15, and compared with 30 control children. Children with FLE showed significant deficits in verbal and visual memory. In addition, type of epilepsy, earlier age at epilepsy onset, and longer active duration of epilepsy were associated with memory problems. Seizure frequency and treatment, however, did not influence memory performance. This study indicates that children with FLE show greater risk of developing memory deficits than children with CAE or BECTS, thus highlighting the importance of assessing also memory functions in frontal lobe epilepsy.

Seizures as a presentation of a pelvic neuroblastoma in a 5-month-old infant.

Epilepsy is a very uncommon first manifestation of a neuroblastoma. A 5-month-old healthy infant presented with acute onset seizures and developmental regression. Extensive investigation was remarkable for urinary vanillylmandelic acid and homovanillic acid peaks. Abdominopelvic magnetic resonance imaging (MRI) disclosed a presacral unresectable pelvic neuroblastoma. Chemotherapy and monthly dexamethasone pulses were administrated. Seizures stopped 3 days after the first pulse of dexamethasone. At 3-year follow-up, the patient is asymptomatic and has normal neurologic and developmental examinations. This case illustrates an impressive clinical and electroencephalographic (EEG) improvement on corticosteroid therapy, raising several hypotheses, including the possibility of a nonclassic paraneoplastic neurologic syndrome.

Intellectual functioning in children with epilepsy: frontal lobe epilepsy, childhood absence epilepsy and benign epilepsy with centro-temporal spikes.

PURPOSE: The purpose of our study is to describe intellectual functioning in three common childhood epilepsy syndromes - frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS). And also to determine the influence of epilepsy related variables, type of epilepsy, age at epilepsy onset, duration and frequency of epilepsy, and treatment on the scores. METHODS: Intellectual functioning was examined in a group of 90 children with epilepsy (30 FLE, 30 CAE, 30 BECTS), aged 6-15 years, and compared with a control group (30). All subjects obtained a Full Scale IQ ≥ 70 and they were receiving no more than two antiepileptic medications. Participants completed the Wechsler Intelligence Scale for Children - Third Edition. The impact of epilepsy related variables (type of epilepsy, age at epilepsy onset, duration of epilepsy, seizure frequency and anti-epileptic drugs) on intellectual functioning was examined. RESULTS: Children with FLE scored significantly worse than controls on WISC-III Verbal IQ, Full Scale IQ and Processing Speed Index. There was a trend for children with FLE to have lower intelligence scores than CAE and BECTS groups. Linear regression analysis showed no effect for age at onset, frequency of seizures and treatment. Type of epilepsy and duration of epilepsy were the best indicators of intellectual functioning. CONCLUSION: It is crucial that children with FLE and those with a longer active duration of epilepsy are closely monitored to allow the early identification and evaluation of cognitive problems, in order to establish adequate and timely school intervention plans.

[Convulsive status epilepticus in the pediatric emergency department: five year retrospective analysis]. / Estado de mal convulsivo na urgência pediátrica: estudo retrospectivo de cinco anos.

BACKGROUND/AIMS: status epilepticus (SE) is the most common neurological emergency in childhood. It may be associated with high mortality and morbidity, resulting in focal neurologic deficits, developmental disorder and epilepsy. The aims of this study were to describe the epidemiology, mortality and morbidity of convulsive SE and to assess the predictive factors of its neurological, cognitive and behavioral prognosis. MATERIAL AND METHODS: observational, retrospective, analytical study. Clinical files of children admitted to the Pediatric Emergency Department of Hospital Garcia de Orta with a diagnosis of convulsive SE between first January 2002 to 31st December 2006 were analyzed. The studied variables were age at crisis and current age, gender, type of seizure, duration and etiology of seizure, neurological deficit, epilepsy, seizures, psychomotor development and behavior. Regarding the last five variables data from before and after the SE were analyzed. Data analysis was performed with the programs Excel2007® and SPSS® 15.0. RESULTS: 29 children were admitted with 33 episodes of SE aged between nine months and five years, there were no differences in gender distribution (male 12, female: 17 - p = 0.46). The etiology of SE was febrile in 16 children, remote symptomatic in seven related to idiopathic / cryptogenic epilepsy in five children and not classifiable in one case. The mean follow-up was six years and four months. There were no deaths associated with SE. There was deterioration in neurological status in two children (8.7%). Epilepsy was diagnosed following the SE in three (13%) children. CONCLUSIONS: This retrospective review suggests that the SE is associated with a better prognosis than that recorded a few decades ago. A more favorable prognosis was verified in febrile status than in other etiologies.

Ataxia aguda em idade pediátrica? revisão retrospectiva de cinco anos / Acute ataxia in childhood? a five year retrospective review

Objetivos: Caracterizar os casos de ataxia aguda internados em um Serviço de Pediatria e avaliar a sua abordagem no Departamento de Urgência.Métodos: Análise retrospectiva dos registos clínicos das crianças internadas entre janeiro de 2006 e dezembro de 2010 com quadro clínico de alteração da marcha e/ou dos movimentos motores finos com início dentro das últimas 72 horas.Resultados: Foram incluídas 82 crianças, 44 do sexo feminino. A mediana de idade foi de 4 anos. Trinta crianças apresentaram pródromos e 18 tinham história de infecção prévia. Os sintomas concomitantes mais frequentes foram sonolência (46 casos), vômitos (18 casos) e irritabilidade (14 casos). O exame físico não mostrou alterações em dois terços dos casos. Setenta crianças foram sujeitas a pelo menos um exame complementar de diagnóstico. As principais causas identificadas foram intoxicações (53 casos) e ataxia pós-infecciosa (15 casos). Só 16% necessitaram de tratamento específico e a maioria das internações foi de curta duração. Foram referenciados para seguimento em consulta hospitalar 32 casos. Registrou-se uma evolução benigna na maioria dos casos.Conclusões: A atitude face a uma criança com ataxia aguda deve ser ponderada e individualizada, tornando-se difícil a implementação de um protocolo de abordagem uniforme. A maioria dos casos tem um curso benigno e autolimitado, com internação de curta duração e apenas tratamento de suporte. No entanto, causas mais graves devem ser devidamente excluídas. História clínica minuciosa, exame físico e neurológico completos e internação visando a vigilância da evolução clínica são aspectos fundamentais.

Aims: To characterize the cases of acute ataxia hospitalized in a Pediatric Department and to evaluate its approach in the Emergency Department.Methods: Retrospective analysis of medical records of children admitted between January 2006 and December 2010 with clinical gait and/or fine motor movements with onset within the last 72 hours.Results: We included 82 children, 44 girls. The median age was 4 years. Thirty children had prodromes and 18 had a history of previous infection. The most frequent accompanying symptoms were somnolence (46 cases), vomiting (18 cases) and irritability (14 cases). Physical examination showed no changes in two thirds of cases. Seventy children have been subjected to at least one further diagnostic examination. The main causes were poisoning (53 cases) and post-infectious ataxia (15 cases). Only 16% needed specific treatment and most admissions were of short duration. Thirty-two cases were referred for follow-up consultation. The course was benign in most cases.Conclusions: The attitude towards a child with acute ataxia should be careful and individualized, making it difficult to implement a uniform protocol for approach. Most cases have a benign and self-limiting course, with short duration admission and only supportive care. However, serious causes must be properly excluded. Detailed clinical history, complete physical and neurological examination, and hospitalization for monitoring of clinical course are crucial.

Unilateral optic neuritis as a presentation of neurobrucellosis.

Neurobrucellosis manifesting as optic neuritis is a rare disease in childhood. We report a case of neurobrucellosis in a 11 year old girl leading to visual impairment and headache. Physical examination revealed mild oedema of right tibiotarsic joint and optic neuritis. Investigations showed CSF pleocytosis and a Brucella serum agglutination titer of 1/640. Complete reversal of the symptoms was observed after appropriate antibiotic treatment. To our knowledge only four cases of neurobrucellosis manifesting with visual impairment in childhood are previously reported in literature.

Transient idiopathic dystonia in infancy.

AIM: Review of transient idiopathic dystonia cases to improve knowledge on this entity, in relation to frequency, characterization and evolution. METHODS: Retrospective review and characterization of clinical cases seen in paediatric neurology consultation, diagnosed with transient idiopathic dystonia, between February 2001 and June 2009, using clinical files complemented with photographic records and updated information through the physician. RESULTS: Thirteen infants were referred to the paediatric neurology consultation over a period of 8 years, for asymmetric tone, posture and movements of the upper limb with onset before 6 months, with spontaneous favourable evolution and disappearance without sequelae, although the reason for referral was, in most cases, the suspicion of a hemiplegic cerebral palsy. CONCLUSION: Transient changes of tone, posture and movement can be observed during the first months of life. Differential diagnosis is extensive and complex, based on a careful history and neurological examination. Distinction between neurological, neuromuscular and orthopaedic pathology is difficult, particularly at the onset of clinical manifestations. The cases presented are similar to those previously reported by Willemse and Deonna, classified as transient idiopathic dystonia of childhood. Pathophysiology is unknown; some findings support a genetic susceptibility to functional imbalance in brain neurotransmitters and synaptogenesis.

Cerebral tuberculoma presenting as flexion spasms.

A 10-month-old girl was admitted with refractory infantile spasms. Video EEG demonstrated focal epileptic activity, and MRI revealed a conglomeration of annular lesions. Surgical excision was performed and pathology was consistent with tuberculoma. After antituberculous therapy, the outcome was favorable. Despite all investigations, Mycobacterium tuberculosis's mode of transmission was unclear, and both congenital and postnatal acquired forms were considered.