Cerebral Palsy

We have previously developed a model of near-term intra-uterine hypoxia producing significant neonatal mortality (37%) in a small laboratory animal – the spiny mouse – which has precocial offspring at birth. The aim of the present study was to determine if this insult resulted in the appearance of behavioural abnormalities in those offspring which survived the hypoxic delivery. Behavioural tests assessed gait (using footprint patterns), motor coordination and balance on an accelerating rotarod, and spontaneous locomotion and exploration in an open field. We found that the near-term acute hypoxic episode produced a mild neurological deficit in the early postnatal period. In comparison to vaginally delivered controls, hypoxia pups were able to remain on the accelerating rotarod for significantly shorter durations on postnatal days 1-2, and in the open field they travelled significantly shorter distances, jumped less, and spent a greater percentage of time stationary on postnatal days 5 and 15. No changes were observed in gait. Unlike some rodent models of cerebral hypoxia-ischaemia, macroscopic examination of the brain on postnatal day 5 showed no gross cystic lesions, oedema or infarct. Future studies should be directed at identifying hypoxia-induced alterations in the function of specific brain regions, and assessing if maternal administration of neuroprotective agents can prevent against hypoxia-induced neurological deficits and brain damage that occur at birth. Copyright © 2009 S. Karger AG, Basel.

Acquired prosopagnosia (AP) is characterized by impaired recognition of individual faces following brain damage. The nature of the functional impairment(s) underlying AP remains debated. Recent studies have demonstrated deficient processing of diagnostic information in the region of the eyes (Caldara et al., 2005); other studies suggest that patients fail to judge relative distances between facial features (Barton et al., 2002). We hypothesized that these apparently different observations are related to a common cause. More precisely, we suggest that AP arises due to an impairment of a process that reduces uncertainty about the nature/location of the diagnostic cues for face individualization: the ability to perceive multiple elements of a face as a single global representation (holistic processing). Being impaired at processing individual faces holistically, prosopagnosic patients would tend to perform relatively worse for processing facial areas containing multiple elements (i.e., the eyes), and for elements that are widely spaced apart. Here we tested PS, a single case of AP, at matching unfamiliar faces differing either with respect to local features or inter-feature distances, over the upper and lower areas of the face. A pilot study and Experiment 1 confirmed that PS was extremely poor at using information encompassing the eyes, but was also deficient at perceiving relative distances between features. When uncertainty about the location and nature of the diagnostic cue was removed in Experiment 2, PS’ performance remained below normal range, but she improved substantially. Most interestingly, her pattern of performance across the different conditions appeared qualitatively identical to that of normal controls. In line with previous observations of PS and other cases of prosopagnosia, our findings indicate that the reduced reliance on the area of the eyes and on relative distances between features in AP may have a common underlying cause-the disruption of holistic processing of the individual face.

Meningococcal disease frequently presents neurologic sequels via vascular, metabolic, or inflammatory processes. Understanding the underlying pathogenic mechanisms may influence both treatment and outcome. We present a 2-year-old child affected by Neisseria meningitidis sepsis, who on the second day from clinical onset manifested recurrent partial motor seizures and focal neurologic signs. An early magnetic resonance angiography of the circle of Willis produced normal results, whereas magnetic resonance imaging of the brain disclosed cortical signal abnormalities consistent with cytotoxic edema, without involvement of the adjacent white matter. Six-month follow-up magnetic resonance imaging of the brain indicated faint cortical atrophy in the same regions, although the neurologic picture had resolved. The literature contains few data on early magnetic resonance parenchymal changes, and their pathogenic mechanism is controversial. Diffusion-weighted images may contribute to an understanding of the mechanisms of such brain damage.

To demonstrate induction of delayed central nervous toxicity by disturbing neuronal activities in the developing brain, we administered a single intraperitoneal dose of domoic acid (DA; 1 mg/kg), a potent glutamate receptor agonist, to pregnant female mice at the gestational day of 11.5, 14.5 or 17.5. The dams had recovered from acute symptoms within 24 hr, followed by normal delivery, feeding and weaning. All male offspring mice after weaning were apparently normal in response to handlers during cage maintenance, body weight measurement and to mate mice in group housing conditions. At the age of 11 weeks, our neurobehavior testing battery revealed severe impairment of learning and memory with serious deviances of anxiety-related behaviors. The developed brain of prenatally exposed mice showed myelination failure and the overgrowth of neuronal processes of the limbic cortex neurons. This study indicates that the temporal disturbance of neurotransmission of the developing brain induces irreversible structural and functional damage to offspring which becomes monitorable in their adulthood by a proper battery of neurobehavioral tests.

Exposure to ethanol during prenatal development can have devastating consequences on developing fetuses, the so-called fetal alcohol spectrum disordres (FASD). Among FASD, cases that exhibit all of three criterion; 1) central nervous system dysfunction, 2) prenatal and postnatal growth deficiency, and 3) characteristic cranial/facial abnormalities, referred as fetal alcohol syndrome (FAS). Children born to drinking mothers may suffer from severe brain damage that is expressed by a variety of behavioral alterations. We examined the effects of ethanol exposure during brain development on brain morphogenesis and circadian rhythm using a rat model. Pregnant Sprague-Dawley (SD) rats were fed a liquid diet containing 2.5-5.0% (w/v) ethanol during gestational days 10 to 21. Mean daily ethanol consumption by these dams was 11.53 +/- 2.54 g/kg/day. In rats prenatally exposed to ethanol, ectopias on the cerebral cortex, aberrant distribution of hippocampal mossy fibers, and fusion of cerebellar folia were found. Rats exposed to ethanol during the prenatal or postnatal period suffered from a fragile synchronizing system of circadian rhythms in adulthood. Although the prevalence of FAS in Japan is lower than in the United States, the increasing number of Japanese women with the drinking habit are cause for great concern. However, the preventive action of FAS/FASD has been advanced recently, and now alcoholic beverages carry labels warning of the risk of drinking during pregnancy and breastfeeding of babies. Although little is still known about how ethanol affects brain development, the only and most certain way to prevent FAS/FASD is total abstinence from alcohol during pregnancy and breastfeeding.

BACKGROUND: Post-stroke motor impairments cause difficulty controlling the joints of the affected limbs to produce useful movements. One way to manage this to use an orthosis to control the movement of the affected joints but evidence for their benefit is lacking. OBJECTIVES: To determine the effectiveness of upper or lower limb orthoses on activity and impairment in people with stroke and other non-progressive brain lesions. SEARCH STRATEGY: In February 2007 we searched the trials registers of the Cochrane Stroke, Movement Disorders and Injuries Groups, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2007), MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1983), AMED (from 1985), PsycINFO (from 1967) and RECAL (from 1990), and other databases and trials registers. We screened reference lists, contacted lead authors and other researchers in the field. SELECTION CRITERIA: We included randomised controlled trials of orthoses applied to the upper or lower limb in people with stroke and other non-progressive brain lesions. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials, extracted data, and assessed trial quality. Results for continuous outcomes were combined and analysed using mean difference or standardised mean difference, both with 95% confidence intervals and fixed-effect model. MAIN RESULTS: We analysed 14 trials with 429 participants. The overall effect of lower limb orthoses on walking disability (speed), walking impairment (step/stride length) and balance impairment (weight distribution in standing) was significant and beneficial. There was no significant effect on postural sway (balance impairment) or mobility disability but the numbers of studies and participants were low. However, these were all cross-over trials that looked at the immediate effect while wearing the orthosis; they did not assess the effects of wearing an orthosis over the long term. Upper limb orthoses showed no effect on upper limb function, range of movement at the wrist, fingers or thumb, nor pain. However, this was based on only three trials. AUTHORS’ CONCLUSIONS: A lower limb orthosis can improve walking and balance but the included studies have only examined the immediate effects while wearing the orthosis; the effects of long-term use have not been investigated. An upper limb orthosis does not effect on upper limb function, range of movement at the wrist, fingers or thumb, nor pain, but this conclusion is based on only three trials.

Patients who have experienced significant brain injury (such as hemorrhagic stroke or trauma) can suffer brain damage that leads to altered neurologic functioning. One such ill effect is the development of aberrant mandibular reflexes that may inflict serious trauma to oral and labial tissues. As primary oral health care providers, dental clinicians may be called upon to function as part of the medical team managing the patient. This case report reviews one such scenario in which the unique skills of trained specialists were used to provide a protective oral device to allow for tissue protection and healing. (Quintessence Int 2009;40:457-460).

BackgroundElevated levels of the proinflammatory cytokine soluble CD40 ligand (sCD40L) were reported in subjects with diabetes, impaired glucose tolerance, metabolic syndrome (MS), obesity, and insulin resistance. Metabolic abnormalities might also account for increased sCD40L in subjects with essential hypertension.MethodsSeveral metabolic and vascular correlates of sCD40L levels have been investigated in 90 nondiabetic never-treated essential hypertensive men.ResultsMedian sCD40L level was 8.7 ng/ml (interquartile range: 4.9-11.7). On the basis of sCD40L, subjects were divided by tertiles (thresholds at 6.6 and 11.0 ng/ml). The three groups did not differ for age, body mass index (BMI), smokers, blood pressure (BP), prevalence of nondippers, lipids and lipoproteins, renal function, and albuminuria. Carotid intima-media thickness (IMT: 0.79 +/- 0.22, 0.83 +/- 0.29, and 0.85 +/- 0.30 mm) and percentage of subjects with wall thickening (IMT >0.9 to <1.3 mm: 23, 27, and 27%, respectively) were superimposable in the three groups. No differences were observed in high-sensitivity C-reactive protein (hs-CRP) and no correlation emerged between sCD40L and hs-CRP. An increase through sCD40L tertiles emerged for basal insulin (11.2 +/- 5.6, 14.7 +/- 7.7, and 16.8 +/- 13.5 microU/ml, P = 0.10) and fasting glucose (95 +/- 11, 103 +/- 16, and 105 +/- 14 mg/dl, P = 0.028). Consistently, along with the increase in sCD40L, a worsening in insulin sensitivity was observed, which was expressed as homeostasis model assessment for insulin sensitivity (HOMA%S: 99 +/- 52, 77 +/- 43, and 72 +/- 35, P < 0.05), composite insulin sensitivity index (ISIcomp; Matsuda index: 5.11 +/- 2.65, 3.61 +/- 1.98, and 3.28 +/- 1.87, P = 0.025), or oral glucose insulin sensitivity (OGIS) index (OGIS: 421 +/- 67, 386 +/- 90, and 362 +/- 72, P = 0.004).ConclusionsIn newly diagnosed hypertensive men, sCD40L levels are inversely related to insulin sensitivity, with no correlation with BP, other cardiovascular risk factors, or the degree of subclinical atherosclerosis.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.121American Journal of Hypertension 2009; doi:10.1038/ajh.2009.121.

Infection with cagA-positive Helicobacter pylori is associated with gastric carcinoma. The cagA-encoded CagA protein is delivered into gastric epithelial cells and, upon tyrosine phosphorylation at the C-terminal EPIYA segments, binds and deregulates SHP-2 oncoprotein. Based on the differential alignment of the EPIYA segments, CagA can be subdivided into Western CagA, which is produced by H. pylori isolated in Western countries, and East Asian CagA, which is produced by H. pylori circulating in East Asian countries. Western CagA contains EPIYA-A, EPIYA-B and variable numbers of EPIYA-C segments, whereas East Asian CagA contains EPIYA-A, EPIYA-B and variable numbers of EPIYA-D segments. Upon tyrosine phosphorylation, EPIYA-C and EPIYA-D respectively serve as low-affinity and high-affinity SHP-2-binding sites. We previously reported that systemic expression of East Asian CagA (CagA-ABDD) induces gastrointestinal and hematopoietic malignancies in mice. In this study, we generated transgenic mice that systemically express Western CagA (CagA-ABCCC), the levels of which are comparable to those in mice expressing East Asian CagA. The mice developed gastric epithelial hypertrophy and gastrointestinal tumors and also showed lymphoid abnormality but not myeloid abnormalities such as granulocytosis and myeloid leukemia found in mice carrying East Asian CagA. The incidence of tumors in mice expressing Western CagA was significantly lower than that in mice expressing East Asian CagA. Our results indicate that Western CagA is qualitatively less oncogenic than East Asian CagA. Differential oncogenic potential of geographically distinct CagA isoforms may contribute to the differential prevalence of gastric carcinoma between East Asian countries and Western countries. (c) 2009 UICC.

BACKGROUND: Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae. OBJECTIVES: To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 – Nov 2008), EMBASE (1982 – Nov 2008) and reference lists of published trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI). MAIN RESULTS: Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period. AUTHORS’ CONCLUSIONS: There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.