Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy / Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional

Introduction and objectives: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. Material and methods: A single-group pre–posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5–7 years, with Gross Motor Function Classification System levels II–IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. Results: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40–14.71; p<0.001). Conclusions: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).(AU)

Introducción y objetivos: Los niños con parálisis cerebral (PC) experimentan una disminución de la calidad de vida relacionada con la salud (CVRS). El objetivo de este estudio fue evaluar la CVRS de niños con PC antes y después de un programa combinado de alargamiento miofascial percutáneo selectivo (SPML) y fisioterapia funcional. Material y métodos: Se utilizó un diseño de un solo grupo con pretest y postest. Veintiséis niños de mediana edad (5 a 7 años) con PC espástica, niveles II-IV del sistema de la clasificación de la función motora gruesa se sometieron a cirugía SPML y fisioterapia de funcional posquirúrgica durante 9 meses. La versión proxy del cuestionario DISABKIDS-Smiley fue completada por uno de los padres de cada niño. Se realizaron pruebas t dependientes para comparar las puntuaciones medias previas y posteriores a la medición. Resultados: Después de 9 meses de intervención, los niños con PC tenían puntuaciones de calidad de vida significativamente más altas desde el punto de vista estadístico (diferencia de medias: 11,06±9,05; intervalo de confianza del 95%: 7,40-14,71; p <0,001). Conclusión: Este estudio demostró que los niños con PC presentaron una mejor CVRS después de un programa combinado de cirugía SPML y fisioterapia funcional.(AU)

[Artículo traducido] Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional / Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy

Introduction and objectives: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. Material and methods: A single-group pre–posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5–7 years, with Gross Motor Function Classification System levels II–IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. Results: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40–14.71; p<0.001). Conclusions: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).(AU)

Introducción y objetivos: Los niños con parálisis cerebral (PC) experimentan una disminución de la calidad de vida relacionada con la salud (CVRS). El objetivo de este estudio fue evaluar la CVRS de niños con PC antes y después de un programa combinado de alargamiento miofascial percutáneo selectivo (SPML) y fisioterapia funcional. Material y métodos: Se utilizó un diseño de un solo grupo con pretest y postest. Veintiséis niños de mediana edad (5 a 7 años) con PC espástica, niveles II-IV del sistema de la clasificación de la función motora gruesa se sometieron a cirugía SPML y fisioterapia de funcional posquirúrgica durante 9 meses. La versión proxy del cuestionario DISABKIDS-Smiley fue completada por uno de los padres de cada niño. Se realizaron pruebas t dependientes para comparar las puntuaciones medias previas y posteriores a la medición. Resultados: Después de 9 meses de intervención, los niños con PC tenían puntuaciones de calidad de vida significativamente más altas desde el punto de vista estadístico (diferencia de medias: 11,06±9,05; intervalo de confianza del 95%: 7,40-14,71; p <0,001). Conclusión: Este estudio demostró que los niños con PC presentaron una mejor CVRS después de un programa combinado de cirugía SPML y fisioterapia funcional.(AU)

Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy.

INTRODUCTION AND OBJECTIVES: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. MATERIAL AND METHODS: A single-group pre-posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5-7 years, with Gross Motor Function Classification System levels II-IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. RESULTS: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06±9.05; 95% confidence interval [CI], 7.40-14.71; p<0.001). CONCLUSIONS: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).

Improving health-related quality of life in middle-age children with cerebral palsy following selective percutaneous myofascial lengthening and functional physiotherapy. / [Artículo traducido] Mejora de la calidad de vida relacionada con la salud en niños de mediana edad con parálisis cerebral después de un alargamiento miofascial percutáneo selectivo y fisioterapia funcional.

INTRODUCTION AND OBJECTIVES: Children with cerebral palsy (CP) experience decreased health-related quality of life (HRQOL). This study aimed to assess the HRQOL of children with CP before versus after a combined program of minimally invasive selective percutaneous myofascial lengthening (SPML) and functional physiotherapy. MATERIAL AND METHODS: A single-group pre-posttest design was used. Twenty-six middle childhood children with spastic CP, aged 5-7 years, with Gross Motor Function Classification System levels II-IV underwent SPML surgery and 9 months of postoperative functional strength training therapy. The proxy version of the DISABKIDS-Smiley questionnaire was completed by one parent of each child. Dependent t-tests were used to compare mean pre- and post-measurement scores. RESULTS: After the 9-month intervention, the children with CP had significantly higher quality of life scores (mean difference, 11.06 ± 9.05; 95% confidence interval [CI], 7.40-14.71; p < 0.001). CONCLUSIONS: This study demonstrated that children with CP had better HRQOL after a combined program of minimally invasive SPML surgery and functional physiotherapy (ACTRN12618001535268).

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation.

Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18 months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).

Lipid profile and thyroid hormone concentrations in children with epilepsy treated with oxcarbazepine monotherapy: a prospective long-term study.

BACKGROUND AND PURPOSE: To evaluate prospectively the changes and possible associations in lipid and thyroid profiles in children treated with oxcarbazepine (OXC) monotherapy. METHODS: Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), lipoprotein (a) [Lp(a)], free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and gamma-glutamyltransferase (GGT) concentrations were measured in 23 children with epilepsy, before and at 8 and 18 months of OXC monotherapy. RESULTS: Total cholesterol was significantly increased at 8 months (P = 0.033), whereas LDL-C was significantly increased at 8 and 18 months (P < 0.001 and P = 0.004, respectively) of treatment. Lp(a) was significantly increased at 8 months (P = 0.042) and borderline significantly increased at 18 months (P = 0.050) of treatment. FT4 was significantly decreased at 8 and 18 months (P < 0.001 and P = 0.002, respectively), and TSH levels were significantly increased at 8 and 18 months (P = 0.002 and P = 0.001, respectively) of OXC monotherapy. GGT levels were significantly increased at 8 and 18 months (P < 0.001) of treatment. There were no significant alterations in HDL-C, TGs and FT3 levels during the study. Significant positive correlations were found between GGT and LDL-C levels at 8 (r = 0.468, P = 0.024) and 18 months (r = 0.498, P = 0.016), and between TSH and TC at 18 months (r = 0.508, P = 0.013) of treatment. CONCLUSIONS: OXC monotherapy may cause significant and persistent alterations in lipid and thyroid profiles in children with epilepsy. The increase in LDL-C and TC levels may be associated with liver enzymes induction and thyroid dysfunction. Further long-term prospective studies are required to confirm these findings and to determine their clinical significance.

PLP1 gene analysis in 88 patients with leukodystrophy.

Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.

GFAP mutations, age at onset, and clinical subtypes in Alexander disease.

OBJECTIVE: To characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein (GFAP) mutations. METHODS: We present 30 new cases of AxD and reviewed 185 previously reported cases. We conducted Wilcoxon rank sum tests to identify variables scaling with AAO, survival analysis to identify predictors of mortality, and χ(2) tests to assess the effects of common GFAP mutations. Finally, we performed latent class analysis (LCA) to statistically define AxD subtypes. RESULTS: LCA identified 2 classes of AxD. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features. Survival analysis predicted a nearly 2-fold increase in mortality among patients with type I AxD relative to those with type II. R79 and R239 GFAP mutations were most common (16.6% and 20.3% of all cases, respectively). These common mutations predicted distinct clinical outcomes, with R239 predicting the most aggressive course. CONCLUSIONS: AAO and the GFAP mutation site are important clinical predictors in AxD, with clear correlations to defined patterns of phenotypic expression. We propose revised AxD subtypes, type I and type II, based on analysis of statistically defined patient groups.

Natural and lesion-induced apoptosis in the dorsal lateral geniculate nucleus during development.

We investigated natural and lesion-induced apoptosis in the developing rat dorsal lateral geniculate nucleus (dLGN). These lesions involved: i) monocular enucleation, and ii) unilateral ablation of the visual cortex at different postnatal ages before eye opening. We identified dying cells as apoptotic with light and electron microscopy, using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry for active caspase-3. In the dLGN of normal animals, TUNEL+cells were detected during the first postnatal week, with a peak at postnatal day (P) 1. Following enucleation at birth or at P7, the frequency of apoptotic cells in the contralateral dLGN increased significantly at postlesion day (PLD) 1 and returned to normal values by PLD7. In contrast to early lesions, enucleation at P14 did not induce significant changes in apoptosis in the dLGN. Cortical lesions performed at P0, P7 or at P14 induced the death of the overwhelming majority of cells in the ipsilateral dLGN, which led to a severe reduction in size of the nucleus by PLD7 and its complete elimination by adulthood. Double labeling with TUNEL and immunofluorescence for neuronal nuclear protein (NeuN) showed that in both normal and lesioned animals, apoptotic cells were mainly neurons. We suggest that: i) apoptosis in the dLGN occurs during the precritical period of neuronal maturation; ii) developing neurons in the dLGN are more dependent on the integrity of their connections with the visual cortex than with the retina for survival; and iii) lesion-induced apoptosis in the dLGN during development depends on the type and extent of the connectivity affected.

Natural and lesion-induced apoptosis in the rat striatum during development.

We evaluated the pattern of apoptosis in the rat striatum during normal development and in two models of lesion-induced cell death. Lesions included i) unilateral ablations of the cerebral cortex at different postnatal ages, and ii) early postnatal lesions of the catecholaminergic afferent systems of the striatum with 6-hydroxydopamine (6-OHDA). Dying cells were identified as apoptotic using the TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling) method at the light and electron microscopic levels. Moreover, we used immunohistochemistry for the apoptotic markers active caspase-3 and fractin. TUNEL+ cells were present in the striatum during the first four postnatal weeks. Their frequency was high during the first postnatal week and peaked at postnatal day (P)5. Cortical lesions at birth, in contrast to those performed at later stages, induced a significant increase in the frequency of TUNEL+ cells in the ipsilateral striatum, which peaked at seven days postlesion. 6-OHDA lesions resulted in a similar and significant increase in the frequency of TUNEL+ cells in the striatum, which also peaked at P7. We also showed that cortical lesions at P0 and 6-OHDA lesions resulted in a reduction in the frequency, as well as in alterations of the morphology of gamma-aminobutyric acid (GABA)-immunoreactive (ir) neurons in the striatum. We suggest that: i) apoptosis in the striatum is temporally coordinated with maturation events in this area and ii) early developmental lesions of major afferent pathways to the striatum affect both the survival and phenotype of striatal neurons.

Hypomyelination with atrophy of the basal ganglia and cerebellum: follow-up and pathology.

BACKGROUND AND OBJECTIVE: Hypomyelination with atrophy of the basal ganglia and cerebellum is a recently defined disorder. Only a few patients have been described. We report on 11 additional patients and new MRI findings and provide histopathologic confirmation of the MRI interpretation. METHODS: We reviewed the patients' clinical history and present findings. We scored the MRI abnormalities. The histopathology of one patient was re-examined. RESULTS: The patients' early psychomotor development was normal or delayed, followed by increasing extrapyramidal movement abnormalities, ataxia, and spasticity. Mental capacities were variably affected. MRI showed hypomyelination with, on follow-up, evidence of further myelin loss and variable white matter atrophy. The putamen was small or, more often, absent; the head of the caudate nucleus was decreased in size. In contrast, the thalamus and globus pallidus remained normal. Cerebellar atrophy was invariably present. Histopathology confirmed the myelin deficiency, probably related to both lack of deposition and low-grade further loss. The degeneration of putamen was subtotal. The cerebellar cortex was affected, particularly the granular layer. CONCLUSION: Hypomyelination with atrophy of the basal ganglia and cerebellum is a syndrome diagnosed by distinctive MRI findings. Histopathology confirms hypomyelination, low-grade further myelin loss, subtotal degeneration of the putamen, and cerebellar cortical atrophy. All known patients are sporadic, and the mode of inheritance is unclear.

Discrepancy between neuroimaging findings and clinical phenotype in Alexander disease.

We present a case of infantile-onset Alexander disease (AD) with a novel glial fibrillary acidic protein mutation but without clinical evidence of neurologic deterioration. Brain MRI studies showed typical AD findings and increasing size of frontal cavitations. Serial proton MR spectroscopy demonstrated high levels of myo-inositol and lactic acid and decreasing levels of N-acetylaspartate. The degree of demyelination and the timing of the axonal degeneration may determine phenotypic severity of the disease. Conventional neuroimaging techniques cannot always predict the outcome.

Chronic progressive autonomic dysfunction in a dog.

A 3.5-year-old intact male American Pit Bull was presented because of urinary incontinence and dysuria. Constipation, followed by diarrhoea, ocular disturbances and finally regurgitation developed over the next 4 years. Autonomic dysfunction was evidenced by clinical presentation, as well as positive ophthalmic pilocarpine test and subnormal Schirmer tear test. Diagnosis, however, was established through histopathological and immunohistochemical examination. Lesions attributable to inflammatory degenerative neuropathy of the autonomic ganglia, which represents one of the various types of human autonomic failure, were detected.

Brain MRI and proton MRS findings in infants and children with respiratory chain defects.

OBJECTIVE: The aim of this study is to describe neuroimaging patterns in children with respiratory chain (RC) defects using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) and to assess their role in the diagnostic evaluation. METHOD: Neuroimaging studies of 49 children (newborn to 15 years old) with biochemical evidence of RC defect were reviewed. Patients were divided in 3 groups ("definite" = 24, "probable" = 14, "possible" = 11) according to Modified Adult Criteria for the diagnosis of RC defect. Eighty-one MRI studies were reviewed for deep gray and white matter changes, degree of myelination, cerebral and cerebellar atrophy, and 67 proton MRS studies were assessed for the presence or absence of lactate elevation, as well as NAA/Cr ratio. The findings were compared among the 3 groups with chi-square test. RESULTS: All patients with "pure" myopathy had normal imaging studies. In patients with CNS involvement, significant differences in the frequency of imaging abnormalities among groups were found for deep gray matter (43 %/8 %/0 %; p = 0.01) and for the presence of lactate elevation on proton MRS (81 %/31 %/0 %; p = 0.001). CONCLUSION: Brain MRI and proton MRS abnormalities were observed only in association with clinical CNS involvement. Deep gray matter signal abnormalities on structural imaging and lactate elevation on proton MRS were more frequently observed in the "definite" group and represent neuroimaging markers for RC mitochondriopathy.

Mitochondrial dysfunction in a patient with Joubert syndrome.

Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.

Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults.

Three unrelated adult patients with mild hyperglycinemia, infantile hypotonia, mental retardation, behavioral hyperirritability, and aggressive outbursts were screened for glycine decarboxylase (GLDC) mutations; two novel missense mutations (A389V and R739H) were found. Both mutations had a 6 to 8% of normal GLDC activities when expressed in COS7 cells.

Postnatal development of the dopaminergic system of the striatum in the rat.

The dopaminergic innervation of the developing caudate-putamen (patches and matrix) and nucleus accumbens (shell and core) of the rat was examined with light and electron microscope immunocytochemistry, using antibodies against dopamine. Light microscopic analysis showed, in accordance with previous studies, that early in life, dopaminergic fibers were relatively thick and present throughout the striatum. Their distribution was heterogeneous, showing dense aggregations, the so-called dopamine islands. The pattern of innervation became more uniform during the third postnatal week with most of the dopamine islands no longer detectable. For electron microscopic analysis, parts of the caudate-putamen containing dopamine islands or matrix, and of the nucleus accumbens, from the shell and the core of the nucleus, were selected. This analysis revealed that symmetrical synapses between immunoreactive profiles and unlabeled dendritic shafts predominated throughout development but, at the late stages, symmetrical axospinous synapses also became a prominent feature. These findings indicate that: (1) although the caudate-putamen and the nucleus accumbens have different connections and functions, they exhibit similar types of dopaminergic synapses, and (2) the relatively late detection of dopaminergic axospinous synapses suggests that the development of the dopaminergic system in the striatum is an active process, which parallels the morphological changes of striatal neurons and may contribute to their maturation.

Variations of ferritin levels over a period of 15 years as a compliance chelation index in thalassemic patients.

We studied the changing pattern of the distribution of ferritin levels in 430 regularly-transfused patients with thalassemia in an attempt to evaluate compliance of chelation with deferoxamine. The study covered 15 years and was divided in three periods: 1981-1985, 1986-1990, and 1991-1995. The patients were stratified in age-groups. The mean ferritin levels of each period were calculated for each patient individually. The study showed that: (i) When all the patients were compared as a group, there was a significant decrease in mean ferritin between 1981-1985 and 1991-1995, despite a significant change in the patients' mean age; (ii) When patients of same age were compared between periods, there was a decrease in mean ferritin between 1981-1985 and 1991-1995, as well as a decrease in the proportion of patients with ferritin >4000 microg/L, with a parallel increase in the proportion of patients who had ferritin <2000 microg/L; (iii) When the same patients were followed longitudinally, they showed a decrease in their ferritin levels in all age groups with the exception of the late adolescence period. The decrease in iron overload observed in patients on close follow up implies that compliance with chelation therapy has improved with time and therefore, a favourable influence in survival could be expected.

Mucoepidermoid carcinoma of the bronchus.

Bronchoscopy in a 4.5-year-old girl with recurrent pneumonia showed an exophytic endobronchial mass. Biopsy disclosed microscopic and ultrastructural features of a low-grade mucoepidermoid carcinoma. Complete cure was accomplished by surgical removal of the tumor and right lower lobe.