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Biomedical subjects

Andrew Dean

Publications and source records attributed to Andrew Dean.

6 recordsLinked to original sources
PubMed2006

Fetal arthrogryposis and maternal serum antibodies.

Arthrogryposis multiplex congenital (AMC) describes multiple joint contractures resulting from lack of movement in utero. Antibodies directed at the fetal isoform of the muscle acetylcholine receptor (AChR) have been reported in a small number of asymptomatic mothers of AMC babies. We examined sera from 179 mothers of AMC babies and 20 parous and non-parous controls to look for antibodies to AChR or undefined muscle or neuronal proteins. We found positive AChR antibodies in only three sera (1.5%) from asymptomatic AMC mothers. However, there was reactivity with muscle or with neuronal antigens in 33% of the sera, and reactivity to undefined neuronal antigens was more common in sera from mothers of AMC babies with CNS involvement (p=0.001) than those without. The offspring of mothers with AChR antibodies may benefit from treatment during pregnancy. Other maternal antibodies require further study, but these observations add to the emerging literature on maternal antibodies associated with developmental intrauterine disorders.

Adult↗
PubMed2005

Frameless stereotactic placement of depth electrodes in epilepsy surgery.

OBJECT: Depth electrodes are useful in the identification of deep epileptogenic foci. Computerized tomography-magnetic resonance (CT/MR)- and angiography-guided frame-based techniques are safe and accurate but require four-point skull fixation that limits cranial access for the placement of additional grids and strips. The authors investigated the viability and accuracy of placing depth electrodes by using a commercially available frameless system. METHODS: A slotted, custom-designed adapter was built to interface with the StealthStation Guide Frame-DT and 960-525 StealthFighter. The Cranial Navigation software was used to plan the trajectory and entry site based on preoperative spoiled gradient MR imaging studies. Forty-one depth electrodes were placed in 51 targets in 20 patients. Thirty-one of these electrodes were inserted through the temporal neocortex following craniotomy and placement of subdural grids, whereas 10 were placed through burr holes. All electrodes had contact either within (71%) or touching (29%) the target, 50 of which (98%) provided adequate recordings. Although the mean distance of the distal electrode contact from the intended target was 3.1 +/- 0.5 mm, the mean distance to the edge of the anatomical structure was 0.4 +/- 0.9 mm. Placement via the laterotemporal approach was significantly (p < 0.001) more accurate than that via the occipitotemporal approach. No complication occurred. CONCLUSIONS: Depth electrodes can be placed safely and accurately by using a commercially available frameless stereotactic navigation system and a custom-made adapter. Depth electrode placement to record ictal onsets during epilepsy surgery only requires the contacts to touch rather than to reside within the intended structure. The laterotemporal approach is a more accurate method of placing electrodes than is the occipitotemporal one, likely due to the increased distance from the entry point to the target.

Adolescent↗
PubMed2004

Microglia in the cerebral wall of the human telencephalon at second trimester.

We have recently begun to gain a clearer understanding of the phasing and patterns of colonization of the developing human brain by microglia. In this study we investigated the distribution, morphology and phenotype of microglia specifically within the wall of the human telencephalon from 12 to 24 gestational weeks (gw), a period that corresponds to the development of thalamocortical fibres passing through the transient subplate region of the developing cerebral wall. Sections from a total of 45 human fetal brains were immunoreacted to detect CD68 and MHC class II antigens and histochemically reacted with RCA-1 and tomato lectins. These markers were differentially expressed by anatomically discrete populations of microglia in the cerebral wall: two cell populations were noted during the initial phase of colonization (12-14 gw): (i) CD68++ RCA-1+ MHC II- amoeboid cells aligned within the subplate, and (ii) RCA-1++ CD68- MHC II- progenitors in the marginal layer and lower cortical plate that progressively ramified within the subplate, without seemingly passing through an 'amoeboid' state. At this stage microglia were largely absent from the germinal layers and the intermediate zone. From 14 to 15 gw, however, MHC class II positive cells were also detected within germinal layers and in the corpus callosum, and these cells, which coexpressed CD68 antigen (a marker associated with phagocytosis), further populated the lower half of the telencephalon from 18 to 24 gw. These findings are discussed in relation to developmental events that take place during the second trimester within the wall of the telencephalon.

Antigens, CD↗
PubMed2002

Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system.

Periventricular leukomalacia (PVL) occurring in premature infants, represents a major precursor for neurological and intellectual impairment, and cerebral palsy in later life. The disorder is characterized by multifocal areas of necrosis found deep in the cortical white matter, which are often symmetrical and occur adjacent to the lateral ventricles. There is no known cure for PVL. Factors predisposing to PVL include birth trauma, asphyxia and respiratory failure, cardiopulmonary defects, premature birth/low birthweight, associated immature cerebrovascular development and lack of appropriate autoregulation of cerebral blood flow in response to hypoxic-ischemic insults. The intrinsic vulnerability of oligodendrocyte precursors is considered as central to the pathogenesis of PVL. These cells are susceptible to a variety of injurious stimuli including free radicals and excitotoxicity induced by hypoxic-ischemic injury (resulting from cerebral hypoperfusion), lack of trophic stimuli, as well as secondary associated events involving microglial and astrocytic activation and the release of pro-inflammatory cytokines TNF-alpha and IL-6. It is yet unclear whether activated astrocytes and microglia act as principal participants in the development of PVL lesions, or whether they are representatives of an incidental pathological response directed towards repair of tissue injury in PVL. Nevertheless, the accumulated evidence points to a pathological contribution of microglia towards damage. The topography of lesions in PVL most likely reflects a combination of the relatively immature cerebrovasculature together with a failure in perfusion and/or hypoxia during the greatest period of vulnerability occurring around mid-to-late gestation. Mechanisms underlying the pathogenesis of PVL have so far been related to prenatal ischemic injury to the brain initiated within the third trimester, which result in global cognitive and developmental delay and motor disturbances. Over the past few years, several epidemiological and experimental studies have implicated intrauterine infection and chorioamnionitis as causative in the pathogenesis of PVL. In particular, recent investigations have shown that inflammatory responses in the fetus and neonate can contribute towards neonatal brain injury and development-related disabilities including cerebral palsy. This review presents current concepts on the pathogenesis of PVL and emphasizes the increasing evidence for an inflammatory pathogenic component to this disorder, either resulting from hypoxic-ischemic injury or from infection. These findings provide the basis for clinical approaches targeted at protecting the premature brain from inflammatory damage, which may prove beneficial for treating PVL, if identified early in pathogenesis.

Brain↗