Cerebral Palsy

PURPOSE: To determine regional and global left ventricular (LV) functional parameters and to perform segmental wall thickness (SWT) and motion (WM) analysis of dual-source CT (DSCT) with optimized temporal resolution versus MRI. MATERIALS AND METHODS: 30 patients with known or suspected CAD, non-obstructive HCM, DCM, ARVCM, Fallot Tetralogy, cardiac sarcoidosis and cardiac metastasis underwent DSCT and MRI. The DSCT and MR images were evaluated: end-systolic (ESV), end-diastolic LV (EDV) volumes, stroke volume (SV), ejection fraction (EF), and myocardial mass (MM) as well as LV wall thickening and segmental WM applying the AHA model were obtained and statistically analyzed. RESULTS: The mean LV-EDV (r = 0.96) and ESV (r = 0.98) as well as LV-EF (r = 0.97), SV (r = 0.83), and MM (r = 0.95) correlated well. Bland Altman analysis revealed little systematic underestimation of LV-EF (-1.1 +/- 7.8 %), EDV (-0.3 +/- 18.2 ml), SV (-1.3 +/- 16.7 ml) and little overestimation of ESV (1.1 +/- 7.8 ml) and MM (12.8 +/- 14.4 g) determined by DSCT. Systolic reconstruction time points correlated well (DSCT 32.2 +/- 6.7 vs. MRI 35.6 +/- 4.4 % RR-interval). The LV wall thickness obtained by DSCT and MRI showed close correlation in all segments (Ø diff 0.42 +/- 1 mm). In 413 segments (89 %) WM abnormalities were equally rated, whereas DSCT tended to underestimate the degree of wall motion impairment. CONCLUSION: DSCT with optimized temporal resolution enables regional and global LV function analysis as well as segmental WM analysis in good correlation with MRI. However, the degree of WM impairment is slightly underestimated by DSCT.

PURPOSE: To document the imaging abnormalities seen in the central nervous system (CNS) in childhood leukemia or as complications of its treatment. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of 15 children with neurologic complications of leukemia or its treatment were reviewed retrospectively. The first group consisted of patients with CNS abnormalities detected prior to or during treatment, or within three months after completion of treatment. Patients with CNS complications detected by MRI three months following completion of treatment were included in the second group. RESULTS: Among the 15 children, six had two or more different CNS abnormalities. The imaging abnormalities seen in 12 patients prior to or during treatment, or within three months after completion of treatment included orbital, temporal, cerebellopontine angle, and spinal chloroma; bilateral subdural hematoma in the subacute stage; multifocal intraparenchymal hemorrhage; bilateral retinal hemorrhage and detachment; hematoma in the pons and mesencephalon; PRES (posterior reversible leukoencephalopathy syndrome); bilateral leukemic infiltration of the 3(rd), left 7(th), and 8(th) cranial nerves; and meningeal leukemia. Three months after completion of treatment, three patients had CNS complications including radiation necrosis and secondary brain tumor, osteomyelitis of the L3 vertebra, and meningeal leukemia. CONCLUSION: The wide spectrum of CNS abnormalities that occur during and after treatment for leukemia is related to leukemia and to the treatment method. Because many neurologic complications of leukemia are treatable, early diagnosis is essential.

Brain lesions induced in newborn mice by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-willardiine (acting on AMPA-kainate receptors) mimic some aspects of periventricular white matter lesions and neocortical grey matter damage observed in human neonates at risk for developing cerebral palsy. The neonatal mouse brain can be sensitized to excitotoxic damage by IL-1beta exposure similar to that observed in the human situation. Positive modulators of AMPA receptors have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. However whether they can also act as a neuroprotectant in neonatal brain damage has yet to be defined. Therefore the present study uses a well-defined rodent model of neonatal excitotoxic brain lesions to assess the neuroprotective effects of S18986, a positive allosteric modulator of AMPA receptors, as well as its mechanisms of action. In this model, S18986 provided a dose-dependent and long-lasting protection of developing white matter and cortical grey matter against an excitotoxic insult and also when this was combined with a sensitizing inflammatory insult. Neuroprotective effects of S18986 in cortical grey matter involved decreased necrotic and apoptotic cell death. S18986-induced neuroprotection against NMDA receptor-mediated brain lesions was blocked by inhibitors of ERK and PI3 kinase-Akt pathways. S18986 effects were abolished by a neutralizing anti-BDNF antibody and real-time PCR confirmed the stimulation by S18986 of BDNF production in the neonatal brain. The present study provides strong experimental support for the role of S18986 as a candidate molecule for therapy in cases of excitotoxic perinatal brain lesions and identifies BDNF as a key mediator of this S18986-mediated neuroprotection.

Glutamate receptor-mediated neurotoxicity is a major mechanism contributing to hypoxic-ischemic brain injury (HIBI). Memantine is a safe non-competitive NMDA receptor blocker characterized by its low affinity and fast unblocking kinetics. Topiramate is an AMPA/KA receptor blocker and use-dependent sodium channel blocker with several other neuroprotective actions and little neurotoxicity. We hypothesized that the coadministration of memantine and topiramate would be highly effective to attenuate HIBI in neonatal rats. Seven-day-old Sprague-Dawley rat pups were subjected to right common carotid artery ligation and hypoxia for 2 hours, and then were randomly and blindly assigned to one of four groups: vehicle, memantine, topiramate and combination group. Brain injury was evaluated by gross damage and weight deficit of the right hemisphere at 22d after hypoxic-ischemia(HI) and by neurofunctional assessment(foot fault test) at 21d post-HI. Acute neuronal injury was also evaluated by microscopic damage grading at 72h post-HI. Results showed the combination of memantine and topiramate improved both pathological outcome and performance significantly. The drug-induced apoptotic neurodegeneration was assessed by TUNEL staining at 48h post-HI and the result showed no elevated apoptosis in all observed areas. The result of the experiment indicates the combination therapy is safe and highly effective to reduce brain damage after HIBI.

Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography=FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a “trigger episode of somatic pain” on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.

Following stroke or traumatic damage, neuronal death via both necrosis and apoptosis causes loss of functions including memory, sensory perception and motor skills. Since necrosis has the nature to expand, while apoptosis stops the cell death cascade in the brain, necrosis is considered to be a promising target for rapid treatment for stroke. Pure neuronal necrosis occurs when cortical neurons are cultured under serum-free and low-density conditions. Prothymosin alpha (ProTalpha) isolated from conditioned medium after serum-free culture was found to prevent necrosis by recovering the energy crisis due to endocytosed glucose transporters. At a later time point under the same starvation conditions, ProTalpha causes apoptosis, which in turn seems to inhibit the rapidly occurring necrosis by cleaving poly (ADP-ribose) polymerase, a major machinery involved in ATP consumption. Indeed, ProTalpha administered via systemic routes markedly inhibits the histological and functional damage induced by cerebral and retinal ischemia. Although ProTalpha also causes a cell death mode switch from necrosis to apoptosis in vivo, the induced apoptosis was found to be completely inhibited by endogenously occurring brain-derived neurotrophic factor or erythropoietin. Since forced downregulation of ProTalpha deteriorates the ischemic damage, it is evident that ProTalpha plays in vivo neuroprotective roles after ischemic events. Analyses in terms of the therapeutic time window and potency suggest that ProTalpha could be the prototypic compound to develop the medicine useful for treatment of stroke in clinics.

Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) stroke 1 week, 3 months, and 6 months after the stroke. In addition, structural magnetic resonance imaging (MRI) was performed on all patients 1 week and 6 months post-stroke. Based on their performance on a shortened version of the MBEA (Montreal Battery of Evaluation of Amusia), the patients were classified as amusic (n = 32) or non-amusic (n = 21). MRI results showed that the incidence of auditory cortex and frontal lobe damage was significantly higher in the amusic group than in the non-amusic group, but the two groups did not differ in respect to lesion laterality. Cognitively, amusia was associated with general deficits in working memory and learning, semantic fluency, executive functioning, and visuospatial cognition, as well as hemisphere-specific deficits in verbal comprehension, mental flexibility, and visuospatial attention (unilateral spatial neglect). Moreover, the recovery of music perception ability was related to the recovery of verbal learning, visuospatial perception and attention, and focused attention, especially in amusic patients. Together, these results suggest the ability to perceive music is closely linked to other higher cognitive functions.

Sesamol (SML) obtained from sesame seeds (Sesamum indicum, Linn, Pedaliaceae) has been used as a traditional health food in India and other countries since a long time. Besides its good antioxidant activity, SML is currently receiving considerable attention in relation to neurological disorders. Therefore, the present study has been designed to explore the protective role of SML in 3-nitropropionic acid (3-NP)-induced neurotoxicity in animals. Male rats were given 3-NP (10 mg/kg) treatment for 14 days. Various behavioral observations (body weight, locomotor activity), oxidative damage (lipid peroxidation, nitrite level, superoxide dismutase, and catalase enzyme), and mitochondrial enzyme complex functions were also assessed in the striatum, cortex, and hippocampal regions of the brain. 3-NP treatment significantly impaired locomotor activity, motor coordination, body weight, oxidative damage, and mitochondrial enzyme complex functions as compared with vehicle-treated groups. SML (5, 10, and 20 mg/kg) pre-treatment significantly improved body weight, locomotor activity, motor coordination, and attenuated oxidative damage in different regions of rat brain. Besides these, SML treatment also significantly improved mitochondrial enzymes in all regions of the brain as compared with the respective control (3-NP) group. The present study suggests that SML could be used as effective agents in the management of Huntington’s disease.

Physical or chemical damage to peripheral nerves can result in neuropathic pain which is not easily alleviated by conventional analgesic drugs. Substantial evidence has demonstrated that voltage-gated Na(+) channels in the membrane of damaged nerves play a key role in the establishment and maintenance of pathological neuronal excitability not only of these peripheral nerves but also in the second- and third-order neurons in the pain pathway to the cerebral cortex. Na(+) channel blocking drugs have been used in treating neuropathic pain with limited success mainly because of a preponderance of side-effects. We have developed an analogue of mexiletine which is approximately 80 times more potent than mexiletine in competing with the radioligand, (3)H-batrachotoxinin for binding to Na(+) channels in rat brain membranes and also it is much more lipophilic than mexiletine which should enhance its uptake into the brain to block the increased expression of Na(+) channels on second- and third-order neurons of the pain pathway. This analogue, HFI-1, has been tested in three different rat models of neuropathic pain (formalin paw model, ligated spinal nerve model and contusive spinal cord injury model) and found to be more effective in reducing pain behaviours than mexiletine.

This study was designed to determine the nutritional lipid requirement of Manchurian trout and to investigate the effects of lipid concentrations on the antioxidant status in larvae with experimental diets with different lipid levels. Oxidative stress differences between different organs and tissues were also assessed. Manchurian trout larvae were fed for 35 days and, during that period, growth and survival, the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and content of malondialdehyde (MDA) in viscera, muscle, gill and brain of four diets, lipid levels from 15 to 30%, and control treatment were measured. Growth rates were similar, but survival was low, between high and low dietary lipid levels. SOD activity was stimulated in viscera, muscle and brain in high lipid diets, but reduced in gills with increased lipid content. SOD was kept lower in the control group. GPX activity was inhibited in viscera and stimulated in gill, muscle and brain. CAT activities were enhanced by all treatments and showed the lowest values in the control. Lipid peroxidation of the diet was promoted in all organs, excluding the gill which showed no regular pattern. MDA content increased with increased dietary lipid levels in viscera, muscle and brain. Our results indicate that the most appropriate lipid requirement is probably 20-25% and a higher dietary level of lipids might induce oxidative stress in Manchurian trout larvae. The brain and gill were probably the most sensitive organs to oxidative damage.