Anatomical characterization of athetotic and spastic cerebral palsy using an atlas-based analysis.

PURPOSE: To analyze diffusion tensor imaging (DTI) in two types of cerebral palsy (CP): the athetotic-type and the spastic-type, using an atlas-based anatomical analysis of the entire brain, and to investigate whether these images have unique anatomical characteristics that can support functional diagnoses. MATERIALS AND METHODS: We retrospectively analyzed the DTI of seven children with athetotic-type, 11 children with spastic-type, and 20 healthy control children, all age-matched. The severity of motor dysfunction was evaluated with the Gross Motor Function Classification System (GMFCS). The images were normalized using a linear transformation, followed by large deformation diffeomorphic metric mapping. For 205 parcellated brain areas, the volume, fractional anisotropy, and mean diffusivity were measured. Principal component analysis (PCA) was performed for the Z-scores of these parameters. RESULTS: The GMFCS scores in athetotic-type were significantly higher than those in spastic-type (P < 0.001). PCA extracted anatomical components that comprised the two types of CP, as well as the severity of motor dysfunction. In the athetotic group, the abnormalities were more severe than in the spastic group. In the spastic group, significant changes were concentrated in the lateral ventricle and periventricular structures. CONCLUSION: Our results quantitatively delineated anatomical characteristics that reflected the functional findings in two types of CP.

Athetotic and spastic cerebral palsy: anatomic characterization based on diffusion-tensor imaging.

PURPOSE: To evaluate the anatomy of deep gray and white matter structures in children with athetotic cerebral palsy (CP) and those with spastic CP by using diffusion-tensor (DT) imaging and to investigate whether these types of CP have unique anatomic correlates that can support their diagnosis and prognosis. MATERIALS AND METHODS: This study was approved by the institutional review board of each participating institution, and written informed consent was obtained from the parents of each patient. DT imaging was used to retrospectively evaluate 19 children with clinically diagnosed athetotic CP (mean age, 3.4 years ± 3.3 [standard deviation]), 26 children with spastic CP (mean age, 3.3 years ± 3.2), and 31 healthy control subjects (mean age, 3.2 years ± 3.0). Fractional anisotropy (FA) and mean diffusivity (MD) were measured with a region of interest (ROI) method. The ROIs were drawn on bilateral deep gray and white matter structures, including projection fibers, association fibers, and commissural fibers. Statistical analysis was performed by using the Kruskal-Wallis test with Bonferroni correction. P < .05 indicated a significant difference. RESULTS: FA values in the athetotic CP group were significantly lower than those in the control and spastic CP groups for multiple structures, including deep gray and white matter (P < .05 and P = .0001, respectively); these differences were also associated with increasing MD (P < .05 and P < .001, respectively). On the other hand, in the spastic CP group, the significantly decreased FA values, compared with those of the normal group, were limited to several white matter structures (P < .05 and P = .0001). CONCLUSION: In children with athetotic CP, the extent of change on DT images due to early brain damage tends to be more diffuse, including multiple brain structures, compared with the changes in children with spastic CP.

Movements and postures of infants aged 3 to 5 months: to what extent is their optimality related to perinatal events and to the neurological outcome?

BACKGROUND: The quality of spontaneous general movements (GMs), assessed in the individual infant, has emerged as one of the most reliable and valid predictors especially of severe neurological impairments. AIMS: To implement a more detailed assessment of GMs and co-existing movements and postural patterns in a rehabilitation clinic, and to examine to what extend is the optimality of movements and postures of infants aged 3 to 5 months related to perinatal events and the neurological outcome. STUDY DESIGN: Prospective study of 41 infants (15 boys and 26 girls; 11 infants born preterm) admitted to the Department of Paediatric Neurology and Rehabilitation of the St. Joseph's Hospital in Kyoto (Japan). OUTCOME MEASURES: Clinical, neurological and psychological status at age 5. RESULTS: Motor optimality at age 3 to 5 months correlated positively with neonatal optimality (r=0.48, p<0.01), especially regarding factors associated with hypoxic events. A non-optimal motor performance (lowest possible scores) predicted cerebral palsy with 100% accuracy. Other adverse outcomes such as developmental delays, developmental coordination disorders, pervasive developmental disorder or attention deficit hyperactivity disorder turned out not to be associated with early motor performance. In 13% of cases absence of fidgety movements proved to be false positives, but their normal appearance along with a smooth concurrent motor performance was solely found in infants with a normal neurological development. CONCLUSION: Assessing the quality of motor performance at age 3 to 5 months considerably improves our ability to identify infants at risk for maldevelopment.

Quantitative diffusion tensor tractography of the motor and sensory tract in children with cerebral palsy.

AIM: the aim of this study was to compare the findings of quantitative diffusion tensor tractography of the motor and sensory tracts in children with cerebral palsy (CP) and typically developed comparison individuals, and also to evaluate the correlation with gross motor function. METHOD: thirty-four children with CP (mean age 2y 2.mo, SD 2y 0mo; 19 with spastic diplegia, eight with hemiplegia, six with spastic quadriplegia, and one with spastic triplegia) and 21 healthy comparison children (mean 2y 1.68mo, SD 2y 8.64mo) were evaluated. The distribution of Gross Motor Function Classification System (GMFCS) levels in the CP group was as follows: level I, 7; level II, 14; level III, 5; level IV, 3; and level V, 5. The following three diffusion tensor imaging (DTI) parameters including tractography were evaluated for each tract (corticospinal tract [CST] and posterior thalamic radiation [PTR]): number of fibres, tract-based fractional anisotropy, and region of interest (ROI)-based fractional anisotropy. We compared each value between the two groups, and correlated each value with the GMFCS level. RESULTS: the number of fibres and ROI-based fractional anisotropy values of both tracts were significantly lower in children with CP than in the comparison group (p<0.05-0.001). Additionally, there was significant negative correlation between GMFCS level and motor-sensory parameters (p<0.001-0.05). INTERPRETATION: DTI parameters of the CST and PTR in children with CP were significantly lower than in comparison children. In addition, these parameters were significantly correlated with GMFCS level.

Symmetrical central tegmental tract (CTT) hyperintense lesions on magnetic resonance imaging in children.

The central tegmental tract (CTT) is mainly the extrapyramidal tract connecting between the red nucleus and the inferior olivary nucleus. There are only a few case reports describing CTT abnormalities on magnetic resonance imaging (MRI) in children. Our purpose was to evaluate the frequency of CTT lesions and their characteristics on MRI, and to correlate the MR imaging findings with clinical features. We reviewed retrospectively the MR images of 392 children (215 boys and 177 girls) ranging in age from 1 to 6 years. To evaluate symmetrical CTT hyperintense lesions, we defined a CTT lesion as an area of bilateral symmetrical hyperintensity in the tegmentum pontis on both T2-weighted images and diffusion-weighted images in more than two slices. We measured the ADC (apparent diffusion coefficient) values of symmetrical CTT hyperintensity, and compared them with those of children without CTT abnormality. CTT lesions were detected in 20 (5.1%) of the 392 children. The mean ADC value for these 20 children was significantly lower than that of the normal CTT (p<0.001). On MR imaging, other than CTT lesions, associated parenchymal lesion included: none (n=6); other abnormalities, including periventricular leukomalacia (n=3); thin corpus callosum (n=3); ventricular dilatation (n=2); encephalopathy (n=2). Clinically, cerebral palsy was the most frequent clinical diagnosis (n=6), accounting for 30%, which was significantly more frequent than the prevalence of cerebral palsy among children without CTT lesions (13%) (n<0.05). CTT lesions were detected in 5.1% of all the children examined. Cerebral palsy was the most frequent clinical diagnosis.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy.

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.

Interference with topoisomerase IIalpha potentiates melphalan cytotoxicity.

We studied the consequences of interfering with DNA topoisomerase IIalpha (topo IIalpha) activity on melphalan-induced cytotoxicity. In order to accomplish our goal we used three different approaches to interfere with topo IIalpha. These include: i) use of three V79 Chinese hamster lung fibroblast-derived mutant cell lines, V507, V511, and V513 that are dysfunctional in topo IIalpha activity; ii) treatment of cells with etoposide (VP-16) which inhibits topo IIalpha through the formation of DNA-enzyme cleavable complex; and iii) exposure of cells to merbarone or ICRF-187 (Zinecard) that inhibits the activity of topo IIalpha by restricting its access to DNA. Based on clonogenic survival assays, all three approaches resulted in a significant potentiation of cytotoxicity of melphalan suggesting that topo IIalpha plays an important role in processing of DNA damage induced by melphalan. Furthermore, using alkaline elution assay, we show that melphalan-induced DNA cross-link formation and its repair is faster in V511 cells compared to the parental V79 cells. However, melphalan-induced sister chromatid exchanges (SCE) are found to be significantly higher in V511 cells compared to V79 cells. In addition, we find an excellent correlation between melphalan-induced SCE and cytotoxicity. These results could be explained on the assumption that topo IIalpha plays an important role in damage processing through excision repair of melphalan-induced DNA cross-links. However, in the absence of topo IIalpha the damages are primarily processed by recombination repair which may be prone to deleterious genetic alterations resulting in increased lethality as the frequency of recombination increases. In summary, our results demonstrate that: i) topo IIalpha deficiency is associated with increased sensitivity to melphalan; ii) deficiency of topo IIalpha is associated with an increase in melphalan-induced SCE; iii) increase in melphalan-induced SCE is associated with an increase in cytotoxicity; and iv) downregulation of topo IIalpha may be a useful approach to modulate the cytotoxicity of melphalan in combination chemotherapy regimens. These results have several important clinical implications. First, interference with topo IIalpha using agents such as VP-16 or ICRF-187 may provide a useful approach to enhance the efficacy of melphalan in combination chemotherapy regimens. Second, tumors which develop resistance to topo IIalpha-directed drugs due to quantitative or qualitative alterations in topo IIalpha may show increased susceptibility to a chemotherapy regimen containing melphalan.