Cerebral Palsy

Objective: Craniotomy and evacuation is the standard treatment of acute epidural hematoma (EDH). Here, the authors report their experience in nonoperative management of acute EDH in children with mild head injury. Methods: The authors retrospectively reviewed charts of patients with conservatively treated EDH at the Department of Neurosurgery, King Abdulla University Hospital, Irbid, Jordan, between August 2003 and October 2007. All patients had a Glasgow Coma Scale score of 14 or 15, and an initial computerized tomography (CT) scan demonstrating an EDH with or without skull fractures. Follow-up included neurological examination and brain CT. Results: Six children (3 boys, 3 girls) with acute EDH were successfully managed at our department without surgical intervention. The Glasgow Outcome Scale score of all patients was 5, with no posttraumatic sequelae. Follow-up brain CT showed complete resolution of the EDH within 2-3 months. Conclusions: Our results demonstrated that pediatric EDH can be managed nonoperatively. The pronounced increase in the number of CT examinations for patients with head injuries has resulted in a greater proportion of EDH detected in conscious patients. We recommend such treatment be performed in specialized pediatric neurosurgical centers under close neurological observation. Copyright © 2009 S. Karger AG, Basel.

We report an interesting case of delayed frontal abscess caused by a penetrating nonmissile foreign body, a bamboo stick in a 1.5-year-old male child. A parietal craniotomy was performed, and the brain abscess was resected along with the foreign body without any damage to the surrounding brain tissue. He also received the appropriate antibiotics. The child made a good recovery.

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in regulating a myriad of biological processes in virtually all brain cell types, including neurons. We and others have reported recently that drugs which activate PPARgamma are effective in reducing damage to brain in distinct models of brain disease, including ischemia. However, the cell type responsible for PPARgamma-mediated protection has not been established. In response to ischemia, PPARgamma gene is robustly upregulated in neurons, suggesting that neuronal PPARgamma may be a primary target for PPARgamma-agonist-mediated neuroprotection. To understand the contribution of neuronal PPARgamma to ischemic injury, we generated conditional neuron-specific PPARgamma knock-out mice (N-PPARgamma-KO). These mice are viable and appeared to be normal with respect to their gross behavior and brain anatomy. However, neuronal PPARgamma deficiency caused these mice to experience significantly more brain damage and oxidative stress in response to middle cerebral artery occlusion. The primary cortical neurons harvested from N-PPARgamma-KO mice, but not astroglia, exposed to ischemia in vitro demonstrated more damage and a reduced expression of numerous key gene products that could explain increased vulnerability, including SOD1 (superoxide dismutase 1), catalase, glutathione S-transferase, uncoupling protein-1, or transcription factor liver X receptor-alpha. Also, PPARgamma agonist-based neuroprotective effect was lost in neurons from N-PPARgamma neurons. Therefore, we conclude that PPARgamma in neurons play an essential protective function and that PPARgamma agonists may have utility in neuronal self-defense, in addition to their well established anti-inflammatory effect.

Frontotemporal dementia (FTD) and Alzheimer's disease are sometimes difficult to differentiate clinically because of overlapping symptoms. Using diffusion tensor imaging (DTI) measurements of fractional anisotropy (FA) can be useful in distinguishing the different patterns of white matter degradation between the two dementias. In this study, we performed MRI scans in a 4 Tesla MRI machine including T(1)-weighted structural images and diffusion tensor images in 18 patients with FTD, 18 patients with Alzheimer's disease and 19 cognitively normal (CN) controls. FA was measured selectively in specific fibre tracts (including corpus callosum, cingulum, uncinate and corticospinal tracts) as well as globally in a voxel-by-voxel analysis. Patients with FTD were associated with reductions of FA in frontal and temporal regions including the anterior corpus callosum (P < 0.001), bilateral anterior (left P < 0.001; right P = 0.005), descending (left P < 0.001; right P = 0.003) cingulum tracts, and uncinate tracts (left P < 0.001; right P = 0.005), compared to controls. Patients with Alzheimer's disease were associated with reductions of FA in parietal, temporal and frontal regions including the left anterior (P = 0.003) and posterior (P = 0.002) cingulum tracts, bilateral descending cingulum tracts (P < 0.001) and left uncinate tracts (P < 0.001) compared to controls. When compared with Alzheimer's disease, FTD was associated with greater reductions of FA in frontal brain regions, whereas no region in Alzheimer's disease showed greater reductions of FA when compared to FTD. In conclusion, the regional patterns of anisotropy reduction in FTD and Alzheimer's disease compared to controls suggest a characteristic distribution of white matter degradation in each disease. Moreover, the white matter degradation seems to be more prominent in FTD than in Alzheimer's disease. Taken together, the results suggest that white matter degradation measured with DTI may improve the diagnostic differentiation between FTD and Alzheimer's disease.

Brain white matter volume changes were quantified by using voxel-based morphometry in 26 minimal-to-mild Alzheimer’s disease patients receiving cholinesterase inhibitors over 20 weeks. Patients treated with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, did not show those reductions in white matter volume that were observed in patients treated with acetylcholinesterase-selective agents, donepezil and galantamine. This is the first time that dual cholinesterase inhibition has been shown to influence white matter volume specifically. The findings are consistent with a thesis that dual cholinesterase inhibition may have neuroprotective potential. Attenuated loss of brain volumes and delayed/slower long-term clinical decline in patients treated with agents such as rivastigmine may be due to less extensive white matter damage and loss of corticosubcortical connectivity.

The highly pathogenic avian influenza H5N1 viruses usually cause severe diseases and high mortality in infected humans. However, the tissue tropism and underlying pathogenesis of H5N1 virus infection in humans have not been clearly elucidated yet. In this study, an autopsy was conducted to better understand H5N1 virus distributions in tissues of infected humans, and whether H5N1 virus can replicate in extrapulmonary tissues. We found that the lungs had the higher viral load than the spleen, whereas no detectable viruses in tissues of heart, liver, kidney, large intestine, small intestine, or brain. Specifically, the viral load was higher in the left lung (7.1 log10 copies per ml) in relation to the right lung (5.7 log10 copies per ml), resulting in more severe pathological damage in the left lung, and lung tissues contained both positive- and negative-stranded viral RNA. However, there existed a low level of H5N1 viruses in the spleen (3.8 log10 copies per ml), with the absence of positive-stranded viral RNA. Our results indicate that replication of H5N1 viruses mainly occurs in the lungs, and the degree of lung damage is highly correlated with the viral load in the lungs. The low-load viruses in the spleen might be introduced through blood circulation or other ways.

Resuscitation and acute cerebral damage after cardiopulmonary arrest often induce a systemic inflammatory response and subsequently cause multiple organ failure, including acute lung injury (ALI). Sivelestat has been reported to be effective for ALI associated with systemic inflammatory response syndrome (SIRS), but the effectiveness and safety of the drug for infants has not been confirmed. We report a 33-day-old infant who developed acute respiratory distress syndrome (ARDS) following hypoxic encephalopathy immediately after successful resuscitation from cardiopulmonary arrest. Sivelestat was administered continuously for 7 days with no adverse reactions, and consolidations on a chest radiograph were diminished and impaired oxygenation was markedly alleviated. Our experience suggests that intravenous sivelestat offers a new therapeutic strategy for infantile ARDS/ALI, but further investigation of the indication, administration period, and dosage is required.

BACKGROUND AND PURPOSE: Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. RESULTS: Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. CONCLUSIONS: This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Neuroimaging analysis using structural data has begun to provide insights into the pathophysiology of headache syndromes. Several independent studies have suggested a decrease in grey matter in pain-transmitting areas in migraine patients. Most of these data are discussed as damage or loss of brain grey matter, reinforcing the idea of migraine as a progressive disease. However, given what we know about the nature of morphometric changes detectable by the methods we have to date, this interpretation is highly speculative and not supported by the data. It is likely that these changes are the consequence and not the cause of the respective headache syndromes, as they are probably not irreversible and only mirror the proportion or duration of pain suffered. Moreover, structural changes are not headache specific and have to be seen in the light of a wealth of pain studies using these methods. The studies in cluster headache patients prompted the use of stereotactic stimulation of the hypothalamic target point identified by functional and structural neuroimaging. Due to the nature of the methods used and due to a high anatomical variance it is more than questionable to use this point as a definite answer to the source of the headache in clusters and even more so when it is uncritically used in individuals. We need a way to study each patient individually using the functional imaging method with the highest spatial and temporal resolution available to enable us to target the seed point for deep brain stimulation on this individual basis. One of the major future challenges is to understand the behavioural consequences and cellular mechanisms underlying neuroanatomic changes in pain and headache.

INTRODUCTION: Studies of long-term outcome of the shaken baby syndrome (SBS) are scarce, but they usually indicate poor outcome. OBJECTIVES: To describe long-term outcome of a child having sustained a SBS, to ascertain possible delayed sequelae and to discuss medicolegal issues. METHODS: We report a single case study of a child having sustained a SBS, illustrating the initial clinical features, the neurological, cognitive and behavioural outcomes as well as her social integration. RESULTS: The child sustained diffuse brain injuries, responsible for spastic right hemiplegia leading to secondary orthopaedic consequences, as well as severe cognitive impairment, worsening over time: the developmental quotient measured at 15 months of age was 55 and worsened as age increased. At 6 years and 8 months, the child’s IQ had fallen to 40. Behavioural disorders became apparent only after several months and precluded any social integration. The child eventually had to be placed in a specialised education centre at age 5. DISCUSSION AND CONCLUSION: The SBS has a very poor outcome and major long-standing sequelae are frequent. Cognitive or behavioural sequelae can become apparent only after a long sign-free interval, due to increasing demands placed on the child during development. This case report confirms severity of early brain lesions and necessity for an extended follow-up by a multi-disciplinary team. From a medicolegal point of view, signaling the child to legal authorities allows protection of the child, but also conditions later compensation if sequelae compromise autonomy.