Carolina Araújo Rodrigues Funayama

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Avaliação de alguns aspectos da aquisição e desenvolvimento da linguagem de crianças nascidas pré-termo

The correction of the age of pre-term infants for the motor evaluation has been the accepted practice but it has not been clear in other areas. This study compared indicators of the acquisition and development of language, considering corrected and chronological ages. Twenty healthy infants born between the 28th and 36th week of gestation (median 32 weeks), weighing 800g to 2380g (median 1590g), 9 AGA and 11 SGA, were followed up to 15 months age. As a reference for normality, evaluation of Costa et al. (1992) was used, which groups predictable behavior in 5 levels. For receptive language, considering the chronological age, normal performance occurred at all levels except for Level I (0-3 months). For expressive language, considering the chronological age, 6 (12%) of the 50 evaluations showed normal performance. With their age corrected, in 16 evaluations (40%) the infants achieved the expected level, mainly at 6 and 12 months age. On the whole, for the chronological age, there was a larger number of AGA with normal performance (p<0.05). We conclude that with the use of the Costa method, it was unnecessary to correct the age for receptive language evaluation, and that, for the expressive, the high frequency of normal results at the corrected ages for 6 and 12 months, suggests that these ages constitute periods of intensification of vigilance.

Classification of cerebral palsy: association between gender, age, motor type, topography and Gross Motor Function

The goal of this study was to assess the relation between gender, age, motor type, topography and gross motor function, based on the Gross Motor Function System of children with cerebral palsy. Trunk control, postural changes and gait of one hundred children between 5 months and 12 years old, were evaluated. There were no significant differences between gender and age groups (p=0.887) or between gender and motor type (p=0.731). In relation to body topography most children (88%) were spastic quadriplegic. Most hemiplegics children were rated in motor level I, children with diplegia were rated in motor level III, and quadriplegic children were rated in motor level V. Functional classification is necessary to understand the differences in cerebral palsy and to have the best therapeutic planning since it is a complex disease which depends on several factors.

Gross Motor Function Classification System Expanded & Revised (GMFCS E & R): reliability between therapists and parents in Brazil

BACKGROUND Several studies have demonstrated the importance of using the Gross Motor Function Classification System (GMFCS) to classify gross motor function in children with cerebral palsy, but the reliability of the expanded and revised version has not been examined in Brazil (GMFCS E & R). OBJECTIVE To determine the intra- and inter-rater reliability of the Portuguese-Brazil version of the GMFCS E & R applied by therapists and compare to classification provided by parents of children with cerebral palsy. METHOD Data were obtained from 90 children with cerebral palsy, aged 4 to 18 years old, attending the neurology or rehabilitation service of a Brazilian hospital. Therapists classified the childrens motor function using the GMFCS E & R and parents used the Brazilian Portuguese version of the GMFCS Family Report Questionnaire. Intra- and inter-rater reliability was obtained through percentage agreement and Cohens unweighted Kappa statistics (k). The Chi-square test was used to identify significant differences in the classification of parents and therapists. RESULTS Almost perfect agreement was reached between the therapists [K=0.90 (95% confidence interval 0.83-0.97)] and intra-raters (therapists) with K=1.00 [95% confidence interval (1.00-1.00)], p<0.001. Agreement between therapists and parents was substantial (k=0.716, confidence interval 0.596-0.836), though parents classify gross motor impairment more severely than therapists (p=0.04). CONCLUSIONS The Portuguese version of the GMFCS E & R is reliable for use by parents and therapists. Parents tend to classify their childrens limitations more severely, because they know their performance in different environments.

Influence of treadmill training on motor performance and organization of exploratory behavior in Meriones unguiculatus with unilateral ischemic stroke: histological correlates in hippocampal CA1 region and the neostriatum.

This study examined the effects of motor stimulation via treadmill on the behavior of male gerbils after external carotid ischemic brain lesion. The animals were assigned to five groups; ischemic with no stimulation (SIG), ischemic with stimulation (SIG 12/24/48/72h after surgery), non-ischemic with no stimulation (CC), non-ischemic with stimulation (CE) and sham, surgery without occlusion with no stimulation (SH). All the animals were tested in the open-field (OF) and rotarod (RR), 4 days after surgery in order to evaluate exploratory behaviors and motor performance. Data were submitted to one-way variance (ANOVA) and Dunnetts post hoc comparisons. SIG and SIG 12 groups showed a significant decrease in motor response (crossing) when compared to the control group (CC) (F=20.65, P<0.05) in the OF. SIG 12 group showed an increase in grooming behavior (F=23.136, P<0.05) and all ischemia groups (SIG, SIG12/24/48/72) spent less time on the RR (F=10.40, P<0.05), when compared to the control group (CC). Histological analyses show extensive lesions in the hippocampus and neostriatum for all groups with ischemia (SIG, SIG12/24/48/72), which are structures involved in the organization of motor behavior. Interestingly, the most pronounced damage was found in animals submitted to motor stimulation 12h after ischemia which can be correlated to the increased number of grooming behavior showed by them in the OF. These findings suggest that motor stimulation through treadmill training improve motor behavior after ischemia, except when it starts 12h after surgery.

Detection of organic acidemias in Brazil.

BACKGROUND Organic acidurias or organic acidemias are inherited metabolic disorders in which organic acids (carboxylic acids) accumulate in tissues and physiologic fluids of affected individuals. They are considered the most frequent metabolic disorders among severely ill children. Patients frequently present acute symptoms in early life. Metabolic acidosis and neurologic symptoms are the most common signs. METHODS Urine specimens obtained from 1,926 children from January 1994 to July 2001 were used in analyses. Venous blood specimens were also collected from some patients. Samples were initially submitted to screening tests for detection of inborn errors of metabolism. Identification and semi-quantitation of organic acids in urine were performed by gas chromatography or gas chromatography coupled to mass spectrometry using capillary column (DB-5) and flame ionization detection. RESULTS Ninety three (4.8%) cases of organic acidemias were diagnosed among 1,926 patients investigated from January 1994 to July 2001. Prompt therapy was instituted after diagnosis in a considerable number of patients and resulted in rapid improvement in their symptomatology, distinct from our previous cases diagnosed abroad where patients representing index cases died before any measure could be taken. CONCLUSIONS Results demonstrate the importance of diagnosing organic acidurias in loco in developing countries despite implied extra costs.

Coexistence of two chronic neuropathies in a young child: Charcot-Marie-Tooth disease type 1A and chronic inflammatory demyelinating polyneuropathy.

We report an 18‐month‐old Charcot–Marie–Tooth type 1A (CMT1A) patient who developed a rapid‐onset neuropathy, with proximal and distal weakness, and non‐uniform nerve conduction studies. The neuropathy responded well to immunomodulation, confirming the coexistence of an inherited and an inflammatory neuropathy. Unexpected clinical and/or electrophysiological manifestations in CMT1A patients should alert clinicians to concomitant inflammatory neuropathy. In addition, this association raises reflections about disease mechanism in CMT1A. Muscle Nerve, 2010

Acidúrias orgânicas: diagnóstico em pacientes de alto risco no Brasil

Objective: to determine the prevalence of organic acidurias in high-risk Brazilian patients. Methods: laboratory techniques for the detection and quantification of organic acids by gas chromatography/mass spectrometry were implemented in Porto Alegre, Brazil. We investigated 1,480 patients suspected of organic aciduria between January 1994 and June 2000. Results: seventy three (4.9%) cases of organic acidemias (acidurias) were diagnosed among the tested individuals. In most of these patients, prompt therapy resulted in rapid symptom improvement; these results are completely different from our previous cases diagnosed in other laboratories in Europe and the United States, where several patients died before any measures could be taken. Conclusions: these results demonstrate the importance of diagnosing organic acidurias in loco even in developing countries, in spite of the extra costs involved.

P300 in individuals with sensorineural hearing loss

INTRODUCTION Behavioral and electrophysiological auditory evaluations contribute to the understanding of the auditory system and of the process of intervention. OBJECTIVE To study P300 in subjects with severe or profound sensorineural hearing loss. METHODS This was a descriptive cross-sectional prospective study. It included 29 individuals of both genders with severe or profound sensorineural hearing loss without other type of disorders, aged 11 to 42 years; all were assessed by behavioral audiological evaluation and auditory evoked potentials. RESULTS A recording of the P3 wave was obtained in 17 individuals, with a mean latency of 326.97ms and mean amplitude of 3.76V. There were significant differences in latency in relation to age and in amplitude according to degree of hearing loss. There was a statistically significant association of the P300 results with the degrees of hearing loss (p=0.04), with the predominant auditory communication channels (p<0.0001), and with time of hearing loss. CONCLUSIONS P300 can be recorded in individuals with severe and profound congenital sensorineural hearing loss; it may contribute to the understanding of cortical development and is a good predictor of the early intervention outcome.

Auditory middle latency response in children with learning difficulties

Summary Introduction: This is an objective laboratory assessment of the central auditory systems of children with learning disabilities. Aim: To examine and determine the properties of the components of the Auditory Middle Latency Response in a sample of children with learning disabilities. Methods: This was a prospective, cross-sectional cohort study with quantitative, descriptive, and exploratory outcomes. We included 50 children aged 8–13 years of both genders with and without learning disorders. Those with disorders of known organic, environmental, or genetic causes were excluded. Results and Conclusions: The Na, Pa, and Nb waves were identified in all subjects. The ranges of the latency component values were as follows: Na = 9.8–32.3 ms, Pa = 19.0–51.4 ms, Nb = 30.0–64.3 ms (learning disorders group) and Na = 13.2–29.6 ms, Pa = 21.8–42.8 ms, Nb = 28.4–65.8 ms (healthy group). The values of the Na-Pa amplitude ranged from 0.3 to 6.8 ìV (learning disorders group) or 0.2–3.6 ìV (learning disorders group). Upon analysis, the functional characteristics of the groups were distinct: the left hemisphere Nb latency was longer in the study group than in the control group. Peculiarities of the electrophysiological measures were observed in the children with learning disorders. This study has provided information on the Auditory Middle Latency Response and can serve as a reference for other clinical and experimental studies in children with these disorders.