Biomedical subjects

Martin Merschhemke

Publications and source records attributed to Martin Merschhemke.

7 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↗

PubMed2006

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy.

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.

Adult↗

PubMed2004

Stimulus and potassium-induced epileptiform activity in the human dentate gyrus from patients with and without hippocampal sclerosis.

Hippocampal specimens resected to cure medically intractable temporal lobe epilepsy (TLE) provide a unique possibility to study functional consequences of morphological alterations. One intriguing alteration predominantly observed in cases of hippocampal sclerosis is an uncommon network of granule cells monosynaptically interconnected via aberrant supragranular mossy fibers. We investigated whether granule cell populations in slices from sclerotic and nonsclerotic hippocampi would develop ictaform activity when challenged by low-frequency hilar stimulation in the presence of elevated extracellular potassium concentration (10 and 12 mm) and whether the experimental activity differs according to the presence of aberrant mossy fibers. We found that ictaform activity could be evoked in slices from sclerotic and nonsclerotic hippocampi (27 of 40 slices, 14 of 20 patients; and 11 of 22 slices, 6 of 12 patients, respectively). However, the two patient groups differed with respect to the pattern of ictaform discharges and the potassium concentration mandatory for its induction. Seizure-like events were already induced with 10 mm K+. They exclusively occurred in slices from sclerotic hippocampi, of which 80% displayed stimulus-induced oscillatory population responses (250-300 Hz). In slices from nonsclerotic hippocampi, atypical negative field potential shifts were predominantly evoked with 12 mm K+. In both groups, the ictaform activity was sensitive to ionotropic glutamate receptor antagonists and lowering of [Ca2+]o. Our results show that, in granule cell populations of hippocampal slices from TLE patients, high K+-induced seizure-like activity and ictal spiking coincide with basic electrophysiological abnormalities, hippocampal sclerosis, and mossy fiber sprouting, suggesting that network reorganization could play a crucial role in determining type and threshold of such activity.

Adult↗

PubMed2003

Functional magnetic resonance imaging of human absence seizures.

We studied a patient with idiopathic generalized epilepsy and frequent absences, using electroencephalogram-correlated functional magnetic resonance imaging. Four prolonged runs of generalized spike-wave discharge occurred during a 35-minute experiment. Time-locked activation was observed bilaterally within the thalami in conjunction with widespread but symmetrical cortical deactivation with a frontal maximum. We demonstrate the reciprocal participation of focal thalamic and widespread cortical networks during human absence seizures and suggest reductions in cortical blood flow, in response to synchronized electroencephalogram activity.

Adult↗

PubMed2003

EEG quality during simultaneous functional MRI of interictal epileptiform discharges.

This article concerns the evaluation of the quality of interictal epileptiform EEG discharges recorded throughout simultaneous echo planar imaging (EPI). BOLD (blood oxygen level dependent) functional MRI (fMRI) images were acquired continuously on a patient with intractable epilepsy. EEG was sampled simultaneously, during and after imaging, with removal of pulse and imaging artifacts by subtraction of channel-specific running averages. Contiguous EEG epochs recorded with and without fMRI (fMRI+ve vs. fMRI-ve) were next randomized and presented to two blinded observers. Epileptiform discharges were identified retrospectively, and comparison was made in terms of the number of identified events, their amplitude, and spatiotemporal distribution. A spectral analysis was also performed on the EEG. In the randomized comparison of EEG segments, 80 (fMRI+ve) vs. 69 (fMRI-ve) discharges were noted with good interobserver agreement (69%). There were no significant differences in amplitude or spatio-temporal distribution. Comparison of the events detected and measured by two expert observers demonstrated that the Interictal Epileptiform Discharge (IED) characteristics were indistinguishable with and without scanning. We review briefly the existing literature on EEG recording quality for combined EEG/fMRI.

Artifacts↗

PubMed2003

Reliable callosal measurement: population normative data confirm sex-related differences.

BACKGROUND AND PURPOSE: Corpus callosal cross-sectional area (CCA) may be a clinical indicator of disease progression, but factors influencing callosal morphology in healthy subjects must be determined before comparisons can be made in patients. We sought to define a reliable and easily repeatable method for CCA measurement and to examine the effects of sex, age, handedness, and cerebral volume. METHODS: Neurologically healthy volunteers (age range, 14-68 years; mean age, 32.6 years +/- 12.3 [SD]; 44 men, 56 women; 87 right handed) underwent conventional MR imaging. Data were reoriented in the image space to account for intersubject variations in head position before the midsagittal plane was defined by using midpoints of the anterior commissure (AC), posterior commissure (PC), and interhemispheric fissure (IF). Midsagittal CCA and total cerebral volume were measured and correlated with sex, age, and handedness. RESULTS: The mean CCA was 6.27 cm(2) +/- 0.90. Women had a larger CCA proportional to cerebral volume (6.16 x 10(-3) cm(-1) vs 5.78 x 10(-3) cm(-1) in men; P =.02). The percentage difference for the CCA-cerebral volume from the group mean was +2.6% in women and -3.6% in men. Only a small linear relationship of CCA with cerebral volume was noted (r(2) = 0.15), and CCA was not significantly correlated with age or handedness. CONCLUSION: To our knowledge, this is the largest study of callosal area in a community-based sample of control subjects; such subjects provide controls for future studies. Our findings provide anatomic evidence of sex differences in interhemispheric connectivity. Much CCA variability is independent of cerebral volume.

Adolescent↗

PubMed2002

Simultaneous EEG-Correlated Ictal fMRI.

The ability to continuously acquire simultaneous EEG and fMRI data during seizures presents a formidable challenge both clinically and technically. Published ictal fMRI reports have so far been unable to benefit from simultaneous electrographic recordings and remain largely assumptive. Unique findings from a Continuous EEG-correlated fMRI experiment are presented in which a focal subclinical seizure was captured in its entirety. For the first time dynamic and biphasic Blood Oxygen Level Dependent (BOLD) signal changes are shown using statistical parametric mapping time-locked to the ictal EEG activity localizing seizure generation and propagation sites, with millimeter resolution, to electroclinically concordant gray matter structures. Though presently of limited clinical applicability, a new avenue is opened for further research.

Brain Mapping↗