Cerebral Palsy

PURPOSE: Data linkage of population administrative data is being investigated as a tool for pharmacovigilance in pregnancy in Australia. Records of prescriptions of known or suspected teratogens dispensed to pregnant women have been linked to a birth defects registry to determine if defects associated with medicine exposure can be detected. METHODS: The Pharmaceutical Benefits Scheme is a national claims database that has been linked with population-based data to extract linkages for women with a pregnancy event in Western Australia from 2002 to 2005 (n = 106 074). Records of births to the women who were dispensed medicines in categories D or X of the Australian ADEC pregnancy risk category were linked to the Birth Defects Registry of Western Australia. Population rates of registered birth defects per 1000 births were calculated for each medicine. RESULTS: There were 47 medicines dispensed at least once during pregnancy with 23 associated with a registered birth defect to a woman dispensed the medicine. When the birth defect rate for each medicine was compared with the rate for all other women not dispensed that medicine, most medicines showed an increased risk. Medicines with the higher risks were medroxyprogesterone acetate (OR: 1.8; 95%CI: 1.4-2.3), follitropin alfa (OR: 2.5; 95%CI: 1.2-5.0), carbamazepine (OR: 3.1; 95%CI: 1.7-5.6) and enalapril maleate (OR: 8.1; 95%CI: 1.6-41.7). CONCLUSION: Many known associations between medicines and birth defects were identified, suggesting that linked administrative data could be an important means of pharmacovigilance in pregnancy in Australia. Copyright (c) 2010 John Wiley & Sons, Ltd.

Isolated spinal cord injuries can rarely be found in patients with no traumatic radiological abnormalities of the spine. Stenoses of the medullary canal and degeneration of cervical spine are the predisposing factors. A case report of a 68-year-old patient is described, who developed quadriplegia with cardiac arrest due to isolated cervical spinal cord injury while jumping on a trampoline. Compressions of the spinal cord with intramedullary and epidural haemorrhage between vertebrae C3 and C6 were observed with no traumatic radiological abnormalities of the spine skeleton.

Degeneration of motor neurons contributes to senescence-associated loss of muscle function and underlies human neurodegenerative conditions such as amyotrophic lateral sclerosis and spinal muscular atrophy. The identification of genetic factors contributing to motor neuron vulnerability and degenerative phenotypes in vivo are therefore important for our understanding of the neuromuscular system in health and disease. Here, we analyzed neurodegenerative abnormalities in the spinal cord of progeroid Ercc1 ( Delta/-) mice that are impaired in several DNA repair systems, i.e. nucleotide excision repair, interstrand crosslink repair, and double strand break repair. Ercc1 ( Delta/-) mice develop age-dependent motor abnormalities, and have a shortened life span of 6-7 months. Pathologically, Ercc1 ( Delta/-) mice develop widespread astrocytosis and microgliosis, and motor neuron loss and denervation of skeletal muscle fibers. Degenerating motor neurons in many occasions expressed genotoxic-responsive transcription factors p53 or ATF3, and in addition, displayed a range of Golgi apparatus abnormalities. Furthermore, Ercc1 ( Delta/-) motor neurons developed perikaryal and axonal intermediate filament abnormalities reminiscent of cytoskeletal pathology observed in aging spinal cord. Our findings support the notion that accumulation of DNA damage and genotoxic stress may contribute to neuronal aging and motor neuron vulnerability in human neuromuscular disorders.

Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction. We report 5 children with SOD, originally referred to be evaluated due to short stature, who also presented bilateral optic nerve hypoplasia, nystagmus and development delay. In 4 of the patients, we identified neuroimaging abnormalities of the hypothalamo-pituitary axis such as anterior pituitary hypoplasia (3/5), ectopic posterior pituitary (4/5), thin or absent stalk (3/5) and empty sella (1/5). We also encountered diverse pituitary deficiencies: growth hormone (3/5), adrenocorticotropic hormone (3/5), thyroid-stimulating hormone (2/5) and antidiuretic hormone (1/5). Only one child presented intact pituitary function and anatomy. Although rare, SOD is an important cause of congenital hypopituitarism and it should be considered in children with optic nerve hypoplasia or midline brain abnormalities for early diagnosis and treatment.

OBJECTIVE: To identify in mild head injured children the major differences between those with a Glasgow Coma Scale (GCS) 15 and GCS 13/14. METHOD: Cross-sectional study accomplished through information derived from medical records of mild head injured children presented in the emergency room of a Pediatric Trauma Centre level I, between May 2007 and May 2008. RESULTS: 1888 patients were included. The mean age was 7.6+/-5.4 years; 93.7% had GCS 15; among children with GCS 13/14, 46.2% (p<0.001) suffered multiple traumas and 52.1% (p<0.001) had abnormal cranial computed tomography (CCT) scan. In those with GCS 13/14, neurosurgery was performed in 6.7% and 9.2% (p=0.001) had neurological disabilities. CONCLUSION: Those with GCS 13/14 had frequently association with multiple traumas, abnormalities in CCT scan, require of neurosurgical procedure and Intensive Care Unit admission. We must be cautious in classified children with GCS 13/14 as mild head trauma victims.

BACKGROUND: Detection of hypertensive retinopathy (HR) with direct ophthalmoscopy is part of the assessment of hypertensive patients. Its use has been questioned because of its subjectivity and high interobserver variability. OBJECTIVE: To determine the prevalence of HR in hypertensive patients under outpatient monitoring, the correlation between diagnosis and ophthalmoscopy and angiography, and to correlate it with other target organ damages. METHODS: An observational, analytical and cross-sectional evaluation of 99 patients. Direct ophthalmoscopy and angiography performed by two investigators independently. Classification of RH, as described by Keith, Wagener and Barker. RESULTS: The prevalence of HR of any grade was higher than 90.0% by both methods. On ophthalmoscopy, we observed grade I abnormalities in 51.0%, grade II in 43.0%, with one patient with grade III HR. On angiography, we observed grade I abnormalities in 42.0% and grade II in 52.0%. We detected three patients with grade III HR, two of which were not detected by ophthalmoscopy. Observers’ agreement for the presence and severity of HR was poor with direct ophthalmoscopy and good with angiography. Renal dysfunction, ECG abnormalities (ventricular hypertrophy, pathological Q wave, repolarization abnormalities), and history of stroke were observed in 70.0%, 27.0% and 10.0% of patients, respectively. There was no relationship between the severity of HR and other target organ damages. CONCLUSION: We observed a high prevalence of HR using both methods. Observers’ agreement for the diagnosis and determination of the severity of HR was better with angiography. In our sample, there was no association of the severity of HR with other target organ damages.

Acquisition of new perceptual-motor skills depends on multiple brain areas, including the striatum. However, the specific contribution of each structure to this type of learning is still poorly understood. Focusing on the striatum, we proposed (a) to replicate the finding of impaired rotary pursuit (RP) and preserved mirror tracing (MT) in Huntington’s disease (HD); and (b) to further explore this putative learning dissociation with other human models of striatal dysfunction (i.e., Parkinson’s disease and focal vascular damage) and two new paradigms (i.e., Geometric Figures, GF, and Control Stick, CS) of skill learning. Regardless of the etiology, participants with damage to the striatum showed impaired learning of visuomotor tracking skills (i.e., RP and GF), whereas the ability to learn skills that require motor adaptation (i.e., MT and CS) was not affected. These results suggest a task-specific involvement of the striatum in the early stages of skill learning.

The cerebellum is one of the brain areas, which is selectively vulnerable to forebrain traumatic brain injuries (TBI). Physical exercise in animals is known to promote cell survival and functional recovery after brain injuries. However, the detailed pathologic and functional alterations by exercise following an indirect cerebellar injury induced by a TBI are largely unknown. We determined the effects of treadmill exercise on survival of Purkinje neurons and on a population of reactive astrocytes in the gyrus of lobules VIII and IX of the cerebellum after TBI. The rats were divided into four groups: the sham-operation group, the sham-operation with exercise group, the TBI-induction group, and the TBI-induction with exercise group. Cell biological changes of Purkinje neurons following indirect cerebellar injury were analyzed by immunohistochemistry. TBI induced loss of calbindin-stained Purkinje neurons in the posterior region of the cerebellum and TBI also increased formation of reactive astroyctes in both the granular and molecular layers of the cerebellar posterior region. Treadmill exercise for 10 days after TBI increased the number of calbindin-stained Purkinje neurons and suppressed formation of reactive astroyctes. The present study provides the possibility that treadmill exercise may be an important mediator to enhance survival of Purkinje neurons in TBI-induced indirect cerebellar injury. Copyright © 2010. Published by Elsevier Ireland Ltd.

ABSTRACT: BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and 99mTc -ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations. METHODS: Diffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age-matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes. RESULTS: Cognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal-occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes. CONCLUSION: In CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment.

BACKGROUND: Differentiation between tumor recurrence/vital tumor tissue and radionecrosis based on conventional diagnostic imaging is impossible because of the likeness of the images. In such circumstances advanced MRI techniques (PWI, DWI, 1HMRS) seem to be helpful. The aim of our study was to evaluate the diagnostic effectiveness of PWI, DWI and 1HMRS in the differentiation of the tumor recurrence from radiation related injury. MATERIAL AND METHODS: The retrospective analysis comprised 11 contrast-enhancing lesions observed in 8 patients treated for gliomas with radiotherapy or radiochemotherapy. 5 out of 11 contrast-enhancing lesions were tumor recurrences whereas 6 out of 11 radiation-related injuries. The MR examinations comprised of conventional MR imaging (T1-SE, T1-MPRAGE with CE, T2-TSE, T2 FLAIR) and PWI, DWI, 1HMRS. Mean and maximum rCBV values of each contrast-enhancing lesion were calculated. These values were normalized to normal appearing white matter. Mean normalized ADC ratio to normal appearing white matter and mean ADC obtained from contrast-enhancing lesions were analysed. In 1HMRS only those voxels which were placed in solid part of the contrast-enhancing lesion were analysed and Cho/Cr, Cho/NAA ratios presented. RESULTS: Mean normalized rCBVmax (2.44 +/- 0.73 for tumor recurrence vs. 0.78 +/- 0.46 for radiation injury; p < 0.001) and mean normalized rCBVmean (1.46 +/- 0.49 for tumor recurrence vs. 0.49 +/- 0.38 for radiation injury; p < 0.005) were significantly higher in the recurrent gliomas group than in the radiation injury one. It was observed that normalized rCBVmax higher than 1.7 and normalized rCBVmean higher than 1.25 is highly indicative for recurrent glioma whereas normalized rCBVmax lower than 1.0 and normalized rCBVmean lower than 0.5 is highly indicative for radiation injury. Results obtained in DWI and 1HMRS were not statistically significant different between two analysed groups. Mean ADCce: 1.06 +/- 0.18 x 10-3 mm2/s for tumor recurrence vs. 1.13 +/- 0.13 x 10-3 mm2/s for radiation injury; p = 0.51. Mean normalized ADC: 1.55 +/- 0.39 x 10-3 mm2/s for tumor recurrence vs. 1.55 +/- 0.18 x 10-3 mm2/s for radiation injury; p = 0.98. Median Cho/Cr ratio: (2.16min/max [1.67-3.15] for tumor recurrence vs. 1.34min/max [1.13-2.37] for radiation injury; p = 0.15), median Cho/NAA ratio (1.9min/max [0.86-2.36] for tumor recurrence vs. 2.11min/max [0.97 vs. 2.87] for radiation injury; p = 0.51). CONCLUSIONS: Among the analyzed advanced neuroimaging methods PWI seems to be most reliable in differentiation between tumor regrowth/recurrence and radiation necrosis. In these results mean rCBV is a better differing factor than max rCBV. Proton MR spectroscopy (1HMRS) and DWI do not differentiate analyzed groups with statistical significance, despite tendency to lower ADC values in recurrence group than in radiation injury one.