Seizure Disorders: The Changes With Age

Summary: Age has a profound influence on our approach to the convulsive disorders. Age is a variable which is an important determinant for risk factors for epilepsy. Age, as a surrogate of brain maturation, is a determinant of the specific characteristics of the seizure disorder in those with epilepsy, and age-related changes in these manifestations can be identified. Age is a determinant for the occurrence of acute symptomatic seizures in several types of metabolic or central nervous system insults. Age is a determinant for prognosis, whether one considers remission, medication withdrawal in those entering remission, relapse following prolonged remission, or mortality. Last, age per se seems to be a risk factor for epilepsy independent of other factors. This seems particularly true for partial seizures.     

Spectral analysis of prespeech sounds (spontaneous cries) in infants with unilateral cleft lip and palate (UCLP): a pilot study.

OBJECTIVE: The objectives of the present study were: (1) to analyze the cry features of infants with cleft lip and palate (UCLP) by means of spectral analysis, (2) to describe changes of the acoustic parameters from birth until 9 months of age, and (3) to compare these data with existing cry data of infants without cleft (control group). DESIGN: The study was designed on a interdisciplinary, prospective, and longitudinal basis. SETTING: Interdisciplinary study: (1) Institute of Anthropology at the Humboldt-University, Berlin; (2) Heidelberg University Hospital: Interdisciplinary Cleft Palate and Craniofacial Center. PATIENTS AND METHOD: The cry parameters of five patients with complete unilateral cleft lip, alveolar ridge, and hard and soft palate were analyzed from birth to 9 months of age. The patients were treated with the same protocol. At the age of 24 months, sensomotor development was assessed using the KIPHARD test. Perceptual judgment of speech, performed after 36 months of life, included nasal resonance, nasal emission of air, articulation disorders, and speech intelligibility. MAIN OUTCOME MEASURE: The cry parameters of fundamental frequency (F(0)), pitch period perturbation quotient (PPQ), and cry duration (Tsam) were analyzed. RESULTS: Contrary to the expectation that laryngeal parameters are not affected by vocal tract malformations, differences of cry parameters were found between the patients with UCLP and the non-cleft group. Particularly, the F(0) and its short-time variability (PPQ) were affected. CONCLUSIONS: The preliminary results of this study showed that F(0) and PPQ of spontaneous cries are influenced in patients with UCLP, and a cry analysis might become a noninvasive tool for early detection of an at-risk status for neuromuscular development and prediction of an at-risk status for later speech and language acquisition in infants with cleft lip and palate. Future research strategies are outlined.     

Magnetic Resonance Imaging of Corticobasal Degeneration

Corticobasal degeneration (CBD) is an adult–onset, progressive parkinsonian syndrome with strikingly asymmetrical features, and signs and symptoms referable to both cerebral cortex and basal ganglia. Although once considered rare, it is now recognized with increasing frequency during life. Eight patients with clinically diagnosed CBD and 8 age– and sex–matched patients with Parkinson's disease underwent high–field–strength magnetic resonance imaging (MRI) of the brain. MRIs were graded by a blinded neuroradiologist using a semiquantitative (0–3) scale. MRI of patients with CBD revealed significantly greater T2–weighted signal hypointensity in the putamena and globi pallidi, and ventricular enlargement. When specifically sought, asymmetrical cortical atrophy was identified in 5 of 8 CBD patients. Increased T2–weighted lenticular signal hypointensity, ventricular enlargement, and asymmetrical cortical atrophy are supportive MRI findings of CBD.     

Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.