Cerebral Palsy

OBJECTIVES: We evaluated the relationships between upper extremity (UE) kinetics and the energy expenditure index during anterior and posterior walker-assisted gait in children with spastic diplegic cerebral palsy (CP). METHODS: Ten children (3 boys, 7 girls; mean age 12.1 years; range 8 to 18 years) with spastic diplegic CP, who ambulated with a walker underwent gait analyses that included UE kinematics and kinetics. Upper extremity kinetics were obtained using instrumented walker handles. Energy expenditure index was obtained using the heart rate method (EEIHR) by subtracting resting heart rate from walking heart rate, and dividing by the walking speed. Correlations were sought between the kinetic variables and the EEIHR and temporal and stride parameters. RESULTS: In general, anterior walker use was associated with a higher EEIHR. Several kinetic variables correlated well with temporal and stride parameters, as well as the EEIHR. All of the significant correlations (r>0.80; p<0.005) occurred during anterior walker use and involved joint reaction forces (JRF) rather than moments. Some variables showed multiple strong correlations during anterior walker use, including the medial JRF in the wrist, the posterior JRF in the elbow, and the inferior and superior JRFs in the shoulder. CONCLUSION: The observed correlations may indicate a relationship between the force used to advance the body forward within the walker frame and an increased EEIHR. More work is needed to refine the correlations, and to explore relationships with other variables, including the joint kinematics.

Although the introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of acquired immunodeficiency syndrome (AIDS) morbidity and mortality, the prevalence of human immunodeficiency virus (HIV)-associated dementia (HAD) has actually risen, due to the increasing life expectancy of the infected subjects. To date, several aspects of the HAD pathogenesis remain to be dissected. In particular, the viral-cellular protein interplay is still under investigation. Given their specific features, two viral proteins, Tat and Nef, have been mainly hypothesized to play a role in HIV neuropathology. Here we show that HIV-1 Nef has an effect on the transcriptional levels of a cellular protein, anaplastic lymphoma kinase (ALK), that is preferentially expressed in the central and peripheral nervous system at late embryonic stages. By its overexpression along with Nef, the authors demonstrate ALK ability to influence, at least in the U87MG astrocytic glioma cells, the mytogen-activated protein kinase (MAP-K)-dependent pathway. Moreover, although in the absence of a physical direct interaction, Nef and ALK activate matrix metalloproteinases (MMPs), which are likely to contribute to blood-brain barrier (BBB) damage in HAD. Finally, in the in vitro model of glioblastoma cells adopted, Nef and ALK show similar effects by increasing different cytochines/chemokines that may be relevant for HAD pathogenesis. If confirmed in vivo, these data may indicate that, thanks to its ability to interfere with specific cellular pathways involved in BBB damage and in central nervous system (CNS) integrity, Nef, along with specific cellular counterparts, could be one of the viral players implicated in HAD development.

OBJECTIVES:: 1) To investigate the neural substrate of impaired activities of daily living (ADL) in dementia with Lewy bodies (DLB) and 2) to explore, in the context of cognitive reserve, if hypometabolism was more pronounced in well-educated patients at the same level of everyday impairment. METHODS:: Twenty-one patients with DLB underwent an extensive clinical evaluation including cerebral positron emission tomography with F-fluoro-2-deoxy-glucose scanning. First, brain areas were identified, where ADL performance and glucose metabolism were significantly correlated, controlling for individual differences in cognitive and motor dysfunction. Second, it was tested if there was a significant negative association between metabolism and years of education in brain regions associated with ADL performance. Again, a correction for cognitive and motor impairment was deployed. RESULTS:: There was a significant association between glucose hypometabolism and impaired ADL performance in an extensive brain cluster located in the right temporoparietal cortex. Furthermore, schooling and metabolic rate were inversely associated in the right Brodmann area 19, controlling for ADL performance. CONCLUSIONS:: The study suggests that 1) certain brain metabolic alterations are specifically associated with the loss of everyday competence, even if differences in cognition and motor function are taken into consideration and 2) well-educated patients can offset more brain damage until reaching the same degree of ADL impairment as their less educated counterparts. These results extend the literature on cognitive reserve to a region-specific effect on ADL performance.

Schizophrenia is a complex neuropsychiatric disorder in which symptoms can be classified as either positive, such as delusions and hallucinations, or negative, such as blunted affect and social withdrawal. However, the mechanisms underlying this disease are poorly understood. There is evidence that reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. Ketamine has been used to induce a schizophrenia-like condition as an animal model in which to study this condition. In the present study we tested the effects of sub-anesthetic doses of ketamine on various parameters of oxidative stress in the brain of rats. Our results indicate that lipid peroxidation and tissue protein oxidation were affected by varying sub-anesthetic doses of ketamine in multiple cerebral structures. Additionally, the activity of the antioxidant enzymes CAT and SOD was measured and was also found to be altered in most of the structures tested. In conclusion, we observe an increase in oxidative damage marked by an increase in lipid peroxidation, oxidative protein damage and a decrease in enzymatic defenses, in an animal model of schizophrenia. Given that oxidative stress could be related to schizophrenia, these findings may explain, at least in part, the mechanisms underlying in this disease.

ABSTRACT BACKGROUND AND PURPOSE Within the spectrum of reversible neuroimaging abnormalities induced by status epilepticus (SE) tumor-like lesions (TLL) have been rarely described. Their etiology, pathophysiology, and long-term outcome remain uncertain. These issues could be clarified by long-term magnetic resonance imaging (MRI) studies in TLL induced by presenting SE. METHODS Prospective multi-sequence MRI and clinical and electroencephalographic long-term (18 to 60 months) follow-up studies were performed in 3 patients with reversible TLL induced by presenting SE. RESULTS In the peri-ictal MRI, TLL are hypointense in T1-weighted, hyperintense in T2-weighted, and fluid-attenuated inversion recovery images with a marked subcortical component and sulci effacement. The diffusion and MR-spectroscopy studies disclosed intermixed areas of increased/decreased diffusivity associated with a lactate peak and a decreased N-acetylaspartate. At long-term follow-up, none of the patients had seizure recurrence or electroencephalographic epileptiform abnormalities; MRI showed residual focal atrophy and gliosis associated with neuronal loss/dysfunction. CONCLUSIONS SE per se may induce TLL. MRI multi-sequence studies disclosed that they are mainly formed by focal vasogenic and cytotoxic edema resulting from the hypermetabolism associated with seizure activity. In spite of a clinical favorable long-term outcome, the demonstration of irreversible brain damage argues in favor of immediate treatment of SE. J Neuroimaging 2009;XX:1-6.

INTRODUCTION: After completing a craniotomy, whenever possible, it is crucial to replace and fix the removed bone flap to the cranium; this in order to keep the brain’s protection as well as for cosmetic purposes. Visible skull defects might cause patients psychosocial problems and, most importantly, expose the brain to accidental damage. A fixation device should not only provide optimal attachment of the flap to the skull but also allow fast bony healing to avoid possible pseudoarthrosis and/or osteolytic changes. METHODS: After performing 12 different craniotomies on 4 human cadaver heads the skull flaps were replaced using traditional sutures and a new skull fixation device; for each fixation technique a load-bearing test was performed and the results compared. RESULTS: Bone flaps fixed with the “Skull Grip” showed a strong fixation with optimal plastic deformation when compared to flaps held by sutures that showed less resistance to pressure and could be easily dislocated. CONCLUSION: The “Skull Grip” has shown to be a reliable, effective, and stronger bone flap fixation superior to suturing technique.

People vulnerable to depression are at increased risk of relapse if they live in highly critical family environments. To explore this link, we used neuroimaging methods to examine cortico-limbic responding to personal criticisms in healthy participants and participants with known vulnerability to major depression. Healthy controls and fully recovered participants with a past history of major depression were scanned while they heard praising, critical, and neutral comments from their own mothers. Prior to scanning, the formerly depressed and the control participants were indistinguishable with respect to self-reported positive, negative, or anxious mood. They also reported similar mood changes after being praised or criticized. However, formerly depressed participants responded to criticism with greater activation in the amygdala and less activation in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) than did controls. During praise and neutral commentary, amygdala activation was comparable in both groups, although lower levels of activation in the DLPFC and ACC still characterized formerly depressed participants. Vulnerability to depression may be associated with abnormalities in cortico-limbic activation that are independent of mood state and that remain even after full recovery. Criticism may be a risk factor for relapse because it activates the amygdala and perturbs the affective circuitry that underlies depression.

Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected through Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings, including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long-term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies, and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

BACKGROUND:: Clinical studies and research in animals have established that alcohol consumption during pregnancy produces irreversible developmental anomalies. Deficits in fine motor performance are often noted in infants diagnosed with fetal alcohol syndrome. However, the effects of alcohol on the spinal motoneurons have not been examined. In this study, the morphometric alterations in spinal motoneurons were assessed as a result of prenatal alcohol exposure. METHODS:: Pregnant Sprague Dawley rats were administered with 1.0 ml of 20% ethyl alcohol per 100 gm body weight via intraperitoneal injections, and unexposed rats served as controls. Rats were perfused through the left cardiac ventricle and a complete laminectomy was performed. Spinal cord sections from the L4-5 segments were cut serially and stained for cresyl fast violet. Sections were also subjected to TUNEL assay for detection of apoptosis. Observations were made between 1 and 4 weeks after birth. RESULTS:: Morphologic characteristics of motoneurons in the alcohol-exposed group of rats were altered. Counts and measurements revealed significant reduction in number and size of alcohol-exposed spinal motoneurons at all time points studied. CONCLUSIONS:: Prenatal exposure to alcohol showed cytotoxic effects whereby it adversely affected both motoneuron growth and differentiation in utero. Birth Defects Research (Part A) 2009. (c) 2009 Wiley-Liss, Inc.

Esophageal atresia and/or tracheoesophageal fistula (EA/TEF) are severe congenital anomalies. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of these defects is lagging. Many genes and genetic pathways have been implicated in the development of EA/TEF, but only a few genes have been shown to be involved in humans, in animals, or in both. Extrapolating data from animal models to humans is not always straightforward. Environmental factors may also carry a risk, but the mechanisms are yet to be elucidated. This review gives an overview of the current state of knowledge about both genetic and environmental risk factors in the etiology of EA/TEF. Birth Defects Research (Part A) 2009. (c) 2009 Wiley-Liss, Inc.