Josiane Ranzan

Ischemic stroke in children: a study of the associated alterations

Arterial ischemic stroke (AIS) in children is a relatively rare disease, not yet clearly understood and with a multifactored etiology. It can cause a severe impact on the child and be the first manifestation of a systemic disease. Delayed diagnosis is still common and research on the subject in our field practically does not exist. Prothrombotic disorders have been described as important causative factors of the ischemic event in children. Forty-six patients from zero to 18 years of age diagnosed with AIS were studied in the period between March 2002 and September 2003. Laboratory tests were realised including coagulation proteins and echocardiogram. AIS of the newborn occurred in 37% of the cases. Focal seizures and hemiparesis were the most frequent symptoms; 40% of the patients presented prior pathologies. Abnormalities of the S and C proteins occurred in 22% and 17%. Associated alterations, particularly those that generate a hypercoagulability state, indicate more than one risk factor for this disease in childhood.

Cerebrovascular disease in pediatric patients.

Although rare in childhood, stroke may have a serious impact when it happens in this stage of life. Also, it may be the first sign of a systemic disease. We report 12 cases of patients with stroke treated in the Neuropediatrics Unit of Hospital de Clínicas de Porto Alegre (HCPA) from March 1997 to March 2000. All patients, from term infants to 12-year-old children hospitalized in the Pediatrics Unit of HCPA, had clinical suspicion of stroke, which was later confirmed by radiological studies. Patient follow up ranged from 1 to 6 years (mean = 3.4 years). Presenting symptoms were hemiparesis in 9 patients, seizures in 7, deviation of labial commissure in 3, and loss of consciousness in 1. The increase in the number of cases of childhood stroke identified and later confirmed by noninvasive methods had helped in the determination of different ethiologies of stroke: the most frequent being hematologic, cardiac and genetic diseases. However, our study included 6 newborns with stroke whose ethiology was not identified. Seven children with seizures received phenobarbital. Six term infants had neonatal seizures secondary to stroke and restricted to the first 72 hours of life.Doenca cerebrovascular isquemica (DCVI) e rara na infância, mas quando ocorre, o impacto pode ser muito serio. Pode ser a primeira manifestacao de uma doenca sistemica. Relatamos a ocorrencia de 12 casos de DCVI. Foram diagnosticados e tratados no Hospital de Clinicas de Porto Alegre (HCPA) na Unidade de Neuropediatria de marco de 1997 a marco de 2000. Todos os casos com suspeita clinica de DCVI foram confirmados por avaliacao radiologica de recem-nascidos de termo (RNT) a criancas ate 12 anos de idade, que internaram na Unidade de Pediatria do HCPA. Eles foram acompanhados de um a seis anos (media 3,4 anos). Os sintomas iniciais foram: hemiparesia em 9 pacientes, convulsoes em 7, desvio da comissura labial em 3 e perda da consciencia em um. O aumento do reconhecimento de DCVI em criancas, auxiliado pela confirmacao do diagnostico atraves de exames nao invasivos, tem auxiliado na identificacao da etiologia. As etiologias mais frequentes foram doencas hematologicas, cardiacas e geneticas. Contudo, nosso estudo mostrou 6 recem-nascidos com DCVI em que nao foi identificada etiologia. Sete criancas com convulsoes usaram fenobarbital. Em seis RNT com DCVI as convulsoes estiveram restritas as primeiras 72 horas de vida.

The role of β3 integrin gene variants in Autism Spectrum Disorders--diagnosis and symptomatology.

Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the β3 integrin locus (ITGB3), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P=0.006; Pcorr=0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P=0.008; Pcorr=0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (Pglcorr=0.048; Pindcorr=0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects.

Language and Focal Brain Lesion in Childhood

Childhood ischemic strokes can lead to problems like hemiplegias, epilepsies, cognitive changes (memory and mathematical solutions), and language ability (reading, writing, and aphasias). The purpose of this study was to evaluate language and its aspects in children with unilateral ischemic stroke and associate them with the age during the event, injured side, and occurrence of epilepsy. Thirty-two children between 8 months and 19 years of age were evaluated. Among them, 21 (65%) had a change in their language skills, there being a connection between age and the time of injury (P < .05). The most impaired aspects were their phonology, semantics, and syntax. In this sample, there was a persistent change in the semantic aspect, which is an alert for the early detection of learning and future development problems.

Predictors of Epilepsy in Children With Cerebrovascular Disease.

Post-stroke seizures and epilepsy in children are a common but understudied complication. In this retrospective cohort study, the medical records of 65 children aged 0 to 18 years were analyzed to assess the risk of post-stroke seizures, detect the prevalence of post-stroke epilepsy, and ascertain which risk factors are associated with this condition in children. Forty-two patients (64.6%) had epileptic seizures following stroke (35 early, 7 late-onset), with most (78.5%) occurring in the first 24 hours. Nineteen children (29.2%) developed post-stroke epilepsy, which was significantly more common among patients with late-onset seizures (P = .034). There was a significant association between cortical involvement and development of epilepsy (P = .01). After Poisson regression, the relative risk of epilepsy was calculated as 2.4 in children with late-onset post-stroke seizures (95% confidence interval, 1.4-3.9; P = .001) and 3.7 in children with cortical involvement (95% confidence interval, 1.4-9.7; P = .009).

Treatment of refractory neonatal seizures with topiramate.

OBJECTIVE The objective of this study is to describe the usefulness of topiramate in refractory neonatal seizures. RESULTS We reported the clinical off-label use of topiramate in three cases of refractory neonatal seizures of unclear origin with no response to conventional antiepileptic drugs. In all cases, the seizures were completely controlled with adding topiramate. All patients became seizure free during hospitalization and were followed by approximately 1 year after hospital discharge, with monotherapy with topiramate. COMMENTS The clinical off-label use of topiramate in neonatal seizures is still incipient. When searching publications in this matter, only one report was identified. Because of its efficacy for both seizures and neuroprotection, topiramate could be a useful choice in refractory neonatal seizures.

Optic nerve enlargement and leukodystrophy : an unusual finding of the infantile form of Krabbe disease

Pediatric Neurology Unit, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre RS, Brazil; Genetic Department, HCPA; Medical Genetic Service, HCPA; Professor of the Genetic Department, HCPA; Neuroradiology Department of Hospital Moinhos de Vento, Porto Alegre RS, Brazil; Pediatric Neurologist, Head of the Pediatric Neurology Unit, HCPA. Adjunct Professor, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil; Pediatric Neurologist, Adjunct Professor, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil. Leukodystrophies are a heterogeneous group of inherited neurological disorders characterized by progressive demyelination that causes loss of motor, sensory and intellectual functions leading to a fatal outcome. These disorders result from dysfunctions in myelin metabolism as a consequence of genetic enzymatic defects specific to each leukodystrophy subtype. Krabbe disease (KD), also called globoid cell leukodystrophy (GCL), is inherited in an autosomal recessive pattern and has an estimated incidence of 1 in each 100,000/200,000 live births. It affects the peripheral and central nervous system (CNS). We report on two cases of the infantile form of KD and describe MRI findings that suggest optic nerve enlargement (ONE).

Post‐H1N1 vaccine acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system (CNS) that affects mainly children. Typically it happens after an infection and rarely after vaccination, with compromise of the white matter of the brain and/or spinal cord, characterized by a rapid development of encephalopathy in combination with multifocal and extremely varied neurological deficits. Brain and spinal cord magnetic resonance imaging (MRI) show disseminated demyelization in the CNS. Cerebrospinal fluid (CSF) examination can demonstrate unspecific alterations. We report the case of a previously healthy 8-year-old boy, who had fever, headache and somnolence 12 days after the first dose of vaccine against influenza H1N1. There was no previous history of infection or other vaccines in the previous 30 days, as well as no evidence of ongoing influenza H1N1 infection. The CSF was a crystalline fluid with 45 leukocytes/μL with 100% monocytes, glucose 62 mg/dL, and proteins 27 mg/dL. No infectious pathogens were identified in the blood or in the CSF. The patient had clinical seizures controlled with i.v. diazepam, became aphasic, and developed left hemiparesis. Electroencephalogram indicated slowing background activity with multifocal spikes and one electrographic seizure, after which i.v. phenytoin was initiated. He was transferred to the intensive care unit (ICU) due to coma and necessity of mechanical ventilation and did not have metabolic abnormalities. He was discharged from ICU with residual neurologic deficits, such as aphasia, paresis of extrinsic ocular muscles and ataxia. Brain MRI was compatible with ADEM (Fig. 1). Spine MRI showed no lesion. I.v. methylprednisolone pulse therapy (30 mg/kg per day) was given for 5 days, followed by 4 weeks of oral prednisone (2 mg/kg per day). The patient was discharged from hospital after 30 days. During follow up, a complete remission of symptoms occurred. According to the World Health Organization, in 2009 approximately 40 countries started national campaigns of vaccination against influenza A. Nearly 80 million doses of H1N1 vaccine were distributed and 65 million people were vaccinated. In this sense, rigorous surveillance of side-effects is necessary to establish the vaccine safety. ADEM usually occurs after unspecific viral upper respiratory airway infection. Only 5% are post-vaccine cases, more frequently after vaccination against measles, rubella and mumps. Only two case reports of ADEM after vaccine against H1N1 have been identified on publication database search. Obviously, vaccines are considered safe and provide one of the most cost-effective treatments. Vaccination campaigns have prevented thousands of deaths and disabling consequences, allowing the eradication of some diseases. In contrast, the worrying side-effects, although rare, must be promptly described in order to prevent undesirable events. Even recognizing that this is a description of a single case as well as that the causal association between this vaccine and the neurological alterations could not be totally proved, to our knowledge this paper represents the third description of a case of ADEM identified after H1N1 influenza vaccine. In the present case, early identification and treatment of ADEM were sufficient to ensure complete neurological recovery.

MMMM syndrome (macrocephaly, megalocornea, motor and mental retardation) and refractory epilepsy

Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil: MD, Child Neurologist; MD, Geneticist; Ph.D. Child Neurologist, Pediatric Neurology Residency Program Preceptor; Ph.D. Child Neurologist, Adjunct Professor of Pediatrics, Head of Pediatric Neurology Unit. The Neuhauser syndrome was first described in 1975. Three siblings in the same family and four other sporadic patients were found to have severe mental retardation, hypotonia, seizures, megalocornea (cornea diameter ≥13 mm) and hypoplasic irises, associated with minor dysmorphic findings, such as epicanthal folds, frontal bossing and depressed nasal bridge. Neuhauser suggested a possible recessive autosomal inheritance and called the condition MMR syndrome (megalocornea and mental retardation). Since then, several other cases with similar signs and symptoms were reported in the literature, although some also had different and additional clinical findings . For example, Tominaga et al. described hearing impairment; Balci et al. reported two cases of Neuhauser syndrome with hypoplasia of corpus callosum; Yarar et al. found associated Peter’s anomaly; and Margari et al. cited a transient hypothyroidism during a five year follow up of one case of Neuhauser syndrome. In 1990, Frydman et al. described two patients with the MMR syndrome who had macrocephaly, and called this variation of the Neuhauser syndrome as the MMMM (macrocephaly, megalocornea, motor and mental retardation) syndrome. In 1991, Kimura et al. described a patient with the MMR syndrome associated with hypothyroidism and myelination delay confirmed by cranial magnetic resonance studies. Other findings described in the literature are bifid uvula, diffuse cortical atrophy, micrognathia, scoliosis, short stature, microcrania, hypertelorism, and hypotonia. The heterogeneity of this syndrome led Verloes to suggest 5 subtypes: Subtype 1: a recessive form, as described by Neuhauser, with iris hypoplasia and minor anomalies; Subtype 2: a recessive form, as described by Franky-Temtay, with camptodactyly, scoliosis and growth retardation; Subtype 3: a recessive form, with normal irises, severe hypotonia, relative or absolute macrocephaly and other minor anomalies; Subtype 4: a possible Frydman type, with normal irises, macrocephaly and obesity; Subtype 5: provisionally unclassifiable cases. The objective of this study is to describe a case of Neuhauser-type dysmorphism with refractory epileptic seizures.

Vigor neurológico de recém-nascidos a termo segundo tipo de parto e realização de manobras obstétricas

PURPOSE to evaluate the effect of delivery type and usual obstetric procedures on the neurologic condition of a sample of consecutive term and healthy neonates, in the first 48 hours of life, using the Neurologic Adaptative Capacity Score (NACS) system. METHODS cohort prospective study with 313 neonates, from a neonatology unit: Unidade de Neonatologia e Alojamento Conjunto. The variables analyzed were obstetric variables; clinical outcome: low neurologic vigor phase, evaluated by NACS, at 4, 24 and 48 hours of life. The data have been assessed twice: once with the whole sample and the other comparing the Vigorous Group, whose neonates kept a score of 35 or more during the three evaluations, and the Low Vigor Group, with less than 35 scores during the three consecutive evaluations. Bivariate and multivariate analyses have been done. Possible associations between low neurologic vigor phase and the type of delivery, as well between the low neurologic vigor phase and obstetric variables have been searched. RESULTS in the bivariate analysis, the delivery type and the obstetric variables were not associated with the low neurologic vigor phase. Nevertheless, the association between the amniotic fluid and the low neurologic vigor phase reached values very close to significance and, then, it was included in the multivariate analysis. In the multivariate analysis, the only variable associated with low neurologic vigor was the presence of meconium stained amniotic fluid, which has shown to be 8.1 times more risky for the neurologic scoring, when Vigorous Group and Low Vigor Group were compared. In the analysis of the whole sample, the same risk was 1.7. CONCLUSIONS neither the delivery type, nor the usual obstetric procedures were associated with low neurologic vigor phase. This is useful information, clinically or legally speaking, mainly for obstetricians. According to this sample data, when the term neonate is healthy, the delivery type and the usual obstetric procedures have no impact in the neurologic condition.