Biomedical subjects

Michelle Hildebrandt

Publications and source records attributed to Michelle Hildebrandt.

4 recordsLinked to original sources

PubMed2007

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗

PubMed2005

Postoperative routine EEG correlates with long-term seizure outcome after epilepsy surgery.

We investigated the correlation of interictal epileptiform discharges (IED) in routine EEG 6 and 24 months after epilepsy surgery with regard to long-term seizure outcome. In 148 patients (74% temporal lobe epilepsy (TLE), 26% extratemporal epilepsy) EEG results (IED present or absent) were correlated with the postoperative outcome using the Engel classification 6 and 24 months after resection (PO6m and PO2y, respectively). Self-evaluation was conducted 3 and 5 years after resection (PO3y and PO5y, respectively). Ninety-one patients (62%) were seizure-free 5 years after resection; 88% of them showed no IED in PO6m. Twenty-eight patients (19%) displayed IED in routine EEG 6 months after resection; 61% of them had recurrent seizures at PO5y, whereas of 120 patients without IED only 33% had recurrent seizures at PO5y; p=0.01. Absence of IED in PO6m and PO2y correlated with good outcome: 71% without IED remained seizure-free, whereas only 25% with IED at PO6m and PO2y remained seizure-free; p=0.001. Seizure-free patients (Engel 1) and patients with less favourable outcome (Engel 3-4) at PO6m and PO2y rarely changed categories of outcome during the following years (p<0.001). Half of the patients with favourable seizure reduction (Engel 2) changed to seizure-free (Engel 1) or to a worse outcome category (Engel 3-4). Postoperative routine EEG is a good prognostic instrument for the prediction of long-term seizure outcome, especially for TLE. It predicts the running up and down of fits in patients with rare seizures (Engel 2).

Adolescent↗

PubMed2005

Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies.

Cortical dysplasias comprise a variable spectrum of clinical, neuroradiological and histopathological findings. We report about a cohort of 25 pediatric patients (mean age 8.1+/-4.8 years) with severe drug-resistant early onset focal epilepsies (mean duration 2.1+/-0.4 years), mental/psychomotor retardation, and multilobar epileptogenesis. Compared to age-matched biopsy controls, microscopical inspection of neurosurgically resected specimens revealed dysplastic neurons with/without balloon cells in only 7 patients. According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. All other patients presented with rather subtle but statistically significant neuroanatomical abnormalities. We identified increased numbers of ectopic neurons in white matter and cortical gliosis. However, most intriguing was our finding of a microcolumnar arrangement of cortical neurons in layer III. These microcolumns can be statistically defined as vertical lining of more than eight neurons (two times standard deviation of cell countings obtained from controls). In addition, neuronal perikarya were significantly smaller in epilepsy patients. Although histological abnormalities occurring during postnatal maturation of the brain challenge any neuropathological classification in this group of young patients, we propose that these findings are classified according to FCD type I. Our observations support a concept compatible with regional loss of high-order brain organization.

Adolescent↗

PubMed2004

CD34-immunoreactive balloon cells in cortical malformations.

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylor's type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.

Adolescent↗