Source localization of small sharp spikes: low resolution electromagnetic tomography (LORETA) reveals two distinct cortical sources.

OBJECTIVE: We have investigated the cortical sources and electroencephalographic (EEG) characteristics of small sharp spikes (SSS) by using statistical non-parametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA). METHODS: We analyzed 7 SSS patterns (501 individual SSS) in 6 patients who underwent sleep EEG studies with 29 or 23 scalp electrodes. The scalp signals were averaged time-locked to the SSS peak activity and subjected to SNPM of LORETA values. RESULTS: All 7 SSS patterns (mean 72 individual SSS, range 11-200) revealed a very similar and highly characteristic transhemispheric oblique scalp voltage distribution comprising a first negative field maximum over ipsilateral lateral temporal areas, followed by a second negative field maximum over the contralateral subtemporal region approximately 30 ms later. SNPM-LORETA consistently localized the first component into the ipsilateral posterior insular region, and the second component into ipsilateral posterior mesial temporo-occipital structures. CONCLUSIONS: SSS comprise an amalgam of two sequential, distinct cortical components, showing a very uniform and peculiar EEG pattern and cortical source solutions. As such, they must be clearly distinguished from interictal epileptiform discharges in patients with epilepsy. SIGNIFICANCE: The awareness of these peculiar EEG characteristics may increase our ability to differentiate SSS from interictal epileptiform activity. The finding of a posterior insular source might serve as an inspiration for new physiological considerations regarding these enigmatic waveforms.     

Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.

Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].     

Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP)

The D allozyme of placental alkaline phosphatase (PLAP) displays enzymatic properties at variance with those of the common PLAP allozymes. We have deduced the amino acid sequence of the PLAP D allele by PCR cloning of its gene, ALPP. Two coding substitutions were found in comparison with the cDNA of the common PLAP F allele, i.e., 692C>G and 1352A>G, which translate into a P209R and E429G substitution. A single nucleotide primer extension (SNuPE) assay was developed using PCR primers that enable the amplification of a 1.9 kb PLAP fragment. Extension primers were then used on this PCR fragment to detect the 692C>G and 1352A>G substitution. The SNuPE assay on these two nucleotide substitutions enabled us to distinguish the PLAP F and D alleles from the PLAP S/I alleles. Functional studies on the D allozyme were made possible by constructing and expressing a PLAP D cDNA, i.e., [Arg209, Gly429]PLAP, into wild-type Chinese hamster ovary cells. We determined the k(cat) and K(m), of the PLAP S, F, and D allozymes using the non-physiological substrate p-nitrophenylphosphate at an optimal pH (9.8) as well as two physiological substrates, i.e., pyridoxal-5-phosphate and inorganic pyrophosphate at physiological pH (7.5). We found that the biochemical properties of the D allozyme of PLAP are significantly different from those of the common PLAP allozymes. These biochemical findings suggest that a suboptimal enzymatic function by the PLAP D allozyme may be the basis for the apparent negative selective pressure of the PLAP D allele. The development of the SNuPE assay will enable us to test the hypothesis that the PLAP D allele is subjected to intrauterine selection by examining genomic DNA from statistically informative population samples.     

Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization

The tissue non-specific alkaline phosphatase (TNAP) knock-out mouse is a model of infantile hypophosphatasia displaying impaired bone mineralization, epileptic seizures, apnoea, abnormal apoptosis in the thymus, abnormal lumbar nerve roots, and postnatal death. Administration of vitamin B6 suppresses the epileptic seizures in TNAP-/- mice. This paper examines to what extent the diverse abnormalities seen in these mice are due to impaired utilization of vitamin B6, using two complementary approaches: administration of vitamin B6 to TNAP null mice and deprivation of vitamin B6 in wild-type and TNAP heterozygous mice. Administration of exogenous pyridoxal HCl delayed the onset of epileptic attacks and increased the life span of TNAP-/- mice. The episodes of apnoea ceased and the appearance of lumbar nerve roots improved, but hypomineralization and accumulation of osteoid continued to worsen with age. Control mice fed a vitamin B6-depleted diet developed epileptic seizures indistinguishable from those observed in TNAP-/- mice, abnormal apoptosis in the thymus, and thinning of the nerve roots, but showed no evidence of bone mineralization abnormalities. Depletion of vitamin B6 did not affect the ability of primary cultures of osteoblasts to deposit bone mineral in vitro. While abnormal metabolism of vitamin B6 explains many of the abnormalities in this mouse model of infantile hypophosphatasia, it is not the basis of the abnormal mineralization that characterizes this disease.     

Haemodynamic changes during epidural caesarean delivery

The cardiovascular changes during epidural caesarean delivery were studied, using a non-invasive cardiac output monitor (BoMed NCCOM3-R7). Two different regimens were used to control hypotension (A = 15 ml/kg of 3% dextran 70, B = 7.5 ml/kg of 3% dextran 70 followed by an infusion of 17.5 mg of ephedrine). Cardiac index (CI) and heart rate (HR) increased after delivery and oxytocin administration (P < 0.001) and maximum values were recorded 1-1.5 min after administration of oxytocin. The maximum increase in CI was 76% (A) and 117% (B), in HR 42% (A) and 56% (B), and in SI 23% (A) and 47% (B) compared with values before anaesthesia. The increase in cardiac output after delivery was greater than that measured previously, which might be because impedance cardiac output is a continuous method. It is also suggested that the most pronounced changes are augmented by the use of a bolus injection of 10 units oxytocin i.v.