Cerebral Palsy

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of phospholipase A2 group VI gene (PLA2G6), but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. J. Comp. Neurol. 518:3771-3784, 2010. (c) 2010 Wiley-Liss, Inc.

We report the case of a 5-year-old girl with persistent chest X-ray abnormalities following an episode of pneumonia who has a complex congenital pulmonary malformation comprising of a congenital pulmonary airway malformation, an intralobar sequestration and two bronchogenic cysts, all present within the same lobe. The observation suggests a common embryological origin of these malformations. Pediatr. Pulmonol. 2010; 45:832-835. (c) 2010 Wiley-Liss, Inc.

Mesial temporal lobe epilepsy (mTLE) with mesial temporal sclerosis (MTS) is a recognized epilepsy syndrome which is successfully treated with mesial temporal lobe resection. However, recent studies suggest that mTLE is more than a "focal" disease process. The objective of our study was to determine the presence and extent of functional abnormalities outside of a defined structural abnormality in epilepsy patients with mTLE. We used a prospective age-matched controlled design to study eight consecutive patients with MTS who were undergoing epilepsy surgery evaluation. Magnetoencephalography was used to localize the sources of electromagnetic abnormality. Proton magnetic resonance spectroscopy ((1)H-MRS) measured integrated peak areas for N-acetyl compounds (NAA) and choline-containing compounds (Cho) to determine regions of metabolic abnormality. All eight subjects had predominant electromagnetic abnormality in the temporal lobe ipsilateral to the MTS. All eight subjects had lower NAA/Cho ratios in the region of electromagnetic abnormality when compared to the homologous contralateral region (P < 0.001). Four subjects had predominant MEG spiking outside the mesial temporal region. Surgery-free outcome for the group with neuroimaging abnormalities outside of the medial temporal lobe is 50%. The region of maximal electromagnetic abnormality is outside the hippocampus in some patients with mTLE. These regions also demonstrate functional abnormalities. Our findings support the concept that mTLE is a more diffuse process than the hippocampal structural abnormality, which may impact surgical outcome.

INTRODUCTION: Developmental venous anomalies (DVA) consist of dilated intramedullary veins that converge into a large collecting vein. The appearance of these anomalies was evaluated on whole-brain computed tomography (CT) digital subtraction angiography (DSA) and CT perfusion (CTP) studies. METHODS: CT data sets of ten anonymized patients were retrospectively analyzed. Five patients had evidence of DVA and five age- and sex-matched controls were without known neurovascular abnormalities. CT angiograms, CT arterial-venous views, 4-D CT DSA and CTP maps were acquired on a dynamic volume imaging protocol on a 320-detector row CT scanner. Whole-brain CTP parameters were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and delay. DSA was utilized to visualize DVA anatomy. Radiation dose was recorded from the scanner console. RESULTS: Increased CTP values were present in the DVA relative to the unaffected contralateral hemisphere of 48%, 32%, and 26%; and for the control group with matched hemispheric comparisons of 2%, -10%, and 9% for CBF, CBV, and MTT, respectively. Average effective radiation dose was 4.4 mSv. CONCLUSION: Whole-brain DSA and CTP imaging can demonstrate a characteristic appearance of altered DVA hemodynamic parameters and capture the anomalies in superior cortices of the cerebrum and the cerebellum. Future research may identify the rare subsets of patients at increased risk of adverse outcomes secondary to the altered hemodynamics to facilitate tailored imaging surveillance and application of appropriate preventive therapeutic measures.

Despite the fact that malignancies are associated with hematological abnormalities, some clinical studies have been unable to detect such a relation. The aim of our study was to detect the prevalence of pretreatment hematologic abnormalities in patients with common solid tumors and to determine if such a profile could be used for prognostic evaluations. We identified all patients in Cancer Center of Sun Yat-sen University who were diagnosed as solid tumors (breast carcinoma, hepatocellular carcinoma, nasopharyngeal carcinoma, esophageal carcinoma, gastric cancer, cervical carcinoma, endometrial cancer, renal cell carcinoma, and non-small cell lung cancer) between January 2000 and August 2009. All subjects were investigated regarding levels of white blood cells, platelets, and hemoglobin concentration. We identified 3,180 patients with solid tumors and 285 patients with benign diseases for the final analysis. The percentages of leukocytosis, anemia, and thrombocytosis in patients with solid tumors ranged from 4.0% to 25.6%, 3.3% to 29.2%, and 2.1% to 9.7%, respectively. The multivariate Cox analysis revealed that anemia was an independent prognostic factor in patients with breast cancer (P = 0.006), hepatocellular carcinoma (P = 0.002), nasopharyngeal carcinoma (P = 0.008), and esophageal carcinoma (P = 0.001). Leukocytosis was an independent prognostic factor in patients with cervical cancer (P = 0.007). The incidence of hematological abnormalities in Chinese patients with solid tumors was relatively lower than that of the counterparts in the Western countries. A pretreatment anemia or leukocytosis can serve as a useful marker to predict outcome of patients in some of the solid tumors.

Pediatric urolithiasis is an endemic disease in Turkey. We evaluated the clinical, radiological and metabolic features of children with urolithiasis in Western Turkey. We retrospectively reviewed the records of 85 children with urolithiasis who were followed-up between 2004 and 2010 in Pediatric Nephrology Department of Celal Bayar University, Manisa. The male/female ratio was 1.23/1. The mean age at diagnosis was 66.1 months (range 3-210 months). Family history of urolithiasis was found in 58 (68.2%) patients. 23 (27%) patients were born from consanguineous marriages. Stones were located in the upper urinary tract in 79 (92.9%) patients. In 66 (77.6%) patients, stones were single-sided and 41 (48.2%) patients had multiple stones. Calcium oxalate stones were the most common one among patients in whom stone analysis was performed (78.5%). Hypocitraturia was the most commonly detected urinary metabolic risk factor. In patients who were under 12 months of age at diagnosis, hypercalciuria was the most commonly seen urinary metabolic risk factor. At the end of follow-up period, 24 patients became free of stone disease and 4 patients had recurrence. In conclusion, metabolic abnormalities are common in pediatric stone patients and are strongly associated with recurrence. Considering that urolithiasis in children is an important risk factor for renal failure, early diagnosis, detailed metabolic evaluation and implementing appropriate treatment and follow-up protocols may prevent recurrence and renal damage.

A variety of conditions other than acute myocardial infarction may cause ST-elevation. Our objective was to evaluate the impact of cardiac magnetic resonance (CMR) on differential diagnosis from a prospective series of patients with suspected ST-elevation myocardial infarction (STEMI) and completely normal coronary arteries. Among 1,145 patients with suspected STEMI, 49 patients had completely normal coronary arteries and entered a prospective registry. CMR was done within 24 h, if possible, and included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after gadolineum administration (global relative enhancement; gRE), and late gadolineum enhancement (LGE). All patients were asked for a follow-up CMR after approximately 3 months. The incidence of patients with suspected STEMI and normal coronary arteries was 4.3% and mean age was 45 +/- 14 years (STEMI group 64 +/- 13 years; P < 0.001). 55% had a recent history of infection. Cardiac biomarkers showed a moderate elevation on admission. There was a significant change from baseline to follow-up for LV end-diastolic volumes (EDV) (P < 0.001), LV mass (P < 0.05), mean T2 ratio (P < 0.05), and LGE volume (P < 0.05). Major diagnostic groups were myocarditis (29%), pericarditis (27%), and takotsubo cardiomyopathy (10%). 18% were regarded as non-diagnostic. The study showed an incidence of 4.3% of patients with suspected STEMI and completely normal coronary arteries. Early CMR was valuable in the evaluation of the differential diagnoses and to exclude myocardial abnormalities in patients with uncertain aetiology. Further studies are needed for the assessment of long-term outcome.

Muscular dystrophies are clinically, genetically, and molecularly a heterogeneous group of neuromuscular disorders. Considerable advances have been made in recent years in the identification of causative genes, the differentiation of the different forms and in broadening the understanding of pathogenesis. Muscle pathology has an important role in these aspects, but correlation of the pathology with clinical phenotype is essential. Immunohistochemistry has a major role in differential diagnosis, particularly in recessive forms where an absence or reduction in protein expression can be detected. Several muscular dystrophies are caused by defects in genes encoding sarcolemmal proteins, several of which are known to interact. Others are caused by defects in nuclear membrane proteins or enzymes. Assessment of both primary and secondary abnormalities in protein expression is useful, in particular the hypoglycosylation of alpha-dystroglycan. In dominantly inherited muscular dystrophies it is rarely possible to detect a change in the expression of the primary defective protein; an exception to this is caveolin-3.

RATIONALE: Repetitive cocaine exposure has been shown to induce GABAergic thalamic alterations. Given the key role of T-type (Ca(V)3) calcium channels in thalamocortical physiology, the direct involvement of these calcium channels in cocaine-mediated effects needs to be further explored. OBJECTIVE: The objective of this study was to investigate the effect of T-type calcium channel blockers on acute and repetitive cocaine administration that mediates thalamocortical alterations in mice using three different T-type blockers: 2-octanol, nickel, and mibefradil. METHODS: During in vitro experiments, whole-cell patch-clamp recordings were conducted in ventrobasal (VB) thalamic neurons from mice treated with acute repetitive cocaine administration (3 x 15 mg/kg, i.p., 1 h apart), under bath application of mibefradil (10 muM), 2-octanol (50 muM), or nickel (200 muM). After systemic administration of T-type calcium channel blockers, we evaluated locomotor activity and also recorded GABAergic neurotransmission onto VB neurons in vitro. RESULTS: Bath-applied mibefradil, 2-octanol, or nickel significantly reduced both GABAergic neurotransmission and T-type currents of VB neurons in cocaine-treated mice. In vivo i.p. pre-administration of either mibefradil (20 mg/kg and 5 mg/kg) or 2-octanol (0.5 mg/kg and 0.07 mg/kg) significantly reduced GABAergic mini frequencies onto VB neurons. Moreover, both mibefradil and 2-octanol were able to decrease cocaine-induced hyperlocomotion. CONCLUSION: The results shown in this study strongly suggest that T-type calcium channels play a key role in cocaine-mediated GABAergic thalamocortical alterations, and further propose T-type channel blockers as potential targets for future pharmacological strategies aimed at treating cocaine’s deleterious effects on physiology and behavior.

Septicemia leads to oxidative stress with overproduction of reactive-oxygen species (ROS) and consumption of endogenous antioxidant enzymes. We tested a twofold hypothesis: (1) does oxidative stress (OxS) induced by sepsis acting alone or in concert with augmented inflammatory processes contributes to sepsis-related vascular dysfunction, and, (2) whether ozone (O(3)) and L: -canavanine (CAV) mitigate the negative impact of the aforementioned phenomena. We investigated the relative impact of treatment with CAV and/or O(3) on vascular OxS associated vascular functional changes in septicemic rats. For this study, 60 male Sprague-Dawley rats were used and divided into six experimental groups (n = 10): control group (C), sham-operated (Sham), septicemic rats (S), S rats treated with CAV (100 mg/kg. i.p; S + CAV), S rats treated with O(3) (1.2 mg/kg, i.p.; S + O(3)) and S rats treated with both O(3) and CAV (S + O(3) + CAV). After 22 h, the mean arterial blood pressure (MAP), the aortic ring vascular reactivity to phenylephrine, abdominal aortic blood flow (AABF), serum tumor necrosis factor-alpha (TNF-alpha) and plasma nitrite/nitrate (NOx) concentration were measured. In addition, hepatic antioxidant enzyme activities sodium dismutase (SOD) and glutathione peroxidase (GSH-Px) were estimated. Septicemia caused significant elevation of serum TNF-alpha (p < 0.001) and plasma NOx (p < 0.001) and significant (p < 0.001) reduction of AABF (p < 0.001), aortic vascular response to phenylephrine (p < 0.001), MAP (p < 0.001) and hepatic SOD and GSH-Px activity (p < 0.001) compared with the C group, while treatment with O(3) and/or CAV induced significant amelioration of all those increases. Abnormalities were attenuated to a similar extent with treatment with both O(3) and CAV. These results suggested that concomitant administration of O(3) and CAV alleviated the compromised vascular reactivity in septicemic conditions and prevent its progression into septic shock compared with each alone.