Biomedical subjects

Martin Fabricius

Publications and source records attributed to Martin Fabricius.

5 recordsLinked to original sources

PubMed2006

Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations.

Progressive ischaemic damage in animals is associated with spreading mass depolarizations of neurons and astrocytes, detected as spreading negative slow voltage variations. Speculation on whether spreading depolarizations occur in human ischaemic stroke has continued for the past 60 years. Therefore, we performed a prospective multicentre study assessing incidence and timing of spreading depolarizations and delayed ischaemic neurological deficit (DIND) in patients with major subarachnoid haemorrhage (SAH) requiring aneurysm surgery. Spreading depolarizations were recorded by electrocorticography with a subdural electrode strip placed on cerebral cortex for up to 10 days. A total of 2110 h recording time was analysed. The clinical state was monitored every 6 h. Delayed infarcts after SAH were verified by serial CT scans and/or MRI. Electrocorticography revealed 298 spreading depolarizations in 13 of the 18 patients (72%). A clinical DIND was observed in seven patients 7.8 days (7.3, 8.2) after SAH. DIND was time-locked to a sequence of recurrent spreading depolarizations in every single case (positive and negative predictive values: 86 and 100%, respectively). In four patients delayed infarcts developed in the recording area. As in the ischaemic penumbra of animals, delayed infarction was preceded by progressive prolongation of the electrocorticographic depression periods associated with spreading depolarizations to >60 min in each case. This study demonstrates that spreading depolarizations have a high incidence in major SAH and occur in ischaemic stroke. Repeated spreading depolarizations with prolonged depression periods are an early indicator of delayed ischaemic brain damage after SAH. In view of experimental evidence and the present clinical results, we suggest that spreading depolarizations with prolonged depressions are a promising target for treatment development in SAH and ischaemic stroke.

Adult↗

PubMed2006

Source analysis of epileptic discharges using multiple signal classification analysis.

Multiple signal classification is an alternative to the traditional dipole fitting source analysis methods. Our aim was to assess the clinical usefulness of this algorithm and to compare the localization of the epileptiform electroencephalography discharges with the regions of altered cerebral blood flow in 10 patients with complex partial seizures undergoing preoperative investigation. We performed multiple signal classification analysis of ictal and interictal discharges, and registered single-photon emission computed tomography. Localization of the ictal, but not the interictal discharges, as determined by multiple signal classification analysis was consistent with the regions showing perfusion changes on the single-photon emission computed tomography. Multiple signal classification analysis is a promising tool in localizing foci in patients with complex partial seizures and may contribute to the preoperative evaluation.

Adult↗

PubMed2005

Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex.

Electrocorticographic (ECoG) activity was recorded for up to 129 h from 12 acutely brain-injured human patients using six platinum electrodes placed near foci of damaged cortical tissue. The method probes ECoG activity in the immediate vicinity of the injured cortex and in adjacent supposedly healthy tissue. Six out of twelve patients displayed a total of 73 spontaneous episodes of spreading depression of the ECoG. Of the remaining 6 patients 1 displayed an episode of synchronous depression of ECoG during surgery. Using the same electrodes we also measured the slow potential changes (SPC) (0.005-0.05 Hz) to test the hypothesis that the ECoG depressions were identical to Leao's cortical spreading depression (CSD), and to be able to record peri-infarct depolarisations (PIDs) in electrically 'silent' cortical tissue. Changes in the SPC indicate depolarization of brain tissue. For the analysis, the SPCs were enhanced by calculating the time integral of the ECoG signal. Spreading ECoG depressions were accompanied at every single recording site by stereotyped SPCs, which spread across the cortical mantle at 3.3 (0.41-10) mm/min (median, range), i.e. at the same speed of spread as the depression of the ECoG activity. The amplitude of the SPCs was 0.06-3 mV. In 4 out of 6 patients the ECoG recovered spontaneously. In 2 patients we subsequently recorded recurrent SPCs, but without recovery of the initial ECoG background activity until 2-5 h later. This represents the first direct recording of PIDs in acutely injured human brain. Evidence from this and our previous study of 14 brain-injured patients suggests that CSDs in acute brain disorders occur at higher incidence in patients <30 years (83%) than above (33%). CSD was recorded in 4 out of 5 traumatic brain injury patients, and in 2 out of 7 patients with spontaneous haemorrhages. We conclude that the spreading ECoG depressions recorded in patients are identical to CSDs recorded in animal experiments. We furthermore provide direct electrophysiological evidence for the existence of PIDs and hence a penumbra in the human brain. We hypothesize that the depolarization events might contribute to tissue damage in acute disorders in the human brain.

Adult↗

PubMed2005

Dynamic changes in brain glucose and lactate in pericontusional areas of the human cerebral cortex, monitored with rapid sampling on-line microdialysis: relationship with depolarisation-like events.

The pathophysiology of peri-lesion boundary zones in acute brain injury is highly dynamic, and it is now clear that spreading-depression-like events occur frequently in areas of cerebral cortex adjacent to contusions in the injured human brain. An automated method to assay microdialysate from peri-lesion cerebral cortex in 11 patients with intracranial haematomas requiring surgery was used. Perfusate (2 microL/min) flowed directly into a flow-injection system for assay of glucose and lactate at intervals typically of 30 secs each. Four channels of electrocorticogram (ECoG) were recorded from a subdural strip adjacent to the catheter. Several patterns of change in metabolites were identified in different time domains. Overall, the number of transient lactate events was significantly correlated with the number of glucose events (r2=0.48, P=0.027, n=10). Progressive reduction in dialysate glucose was very closely correlated with the aggregate number of ECoG events (r2=0.76, P=0.0004, n=11). It is proposed that the recently documented adverse impact of low dialysate glucose on clinical outcome may be because of recurrent, spontaneous spreading-depression-like events in the perilesion cortex.

Adult↗

PubMed2002

Spreading and synchronous depressions of cortical activity in acutely injured human brain.

BACKGROUND AND PURPOSE: Cortical spreading depression (CSD) has been much studied experimentally but never demonstrated unequivocally in human neocortex by direct electrophysiological recording. A similar phenomenon, peri-infarct depolarization, occurs in experimental models of stroke and causes the infarct to enlarge. Our current understanding of the mechanisms of deterioration in the days after major traumatic or ischemic brain injury in humans has not yielded any effective, novel drug treatment. This study sought clear evidence for the occurrence and propagation of CSD in the injured human brain. METHODS: In 14 patients undergoing neurosurgery after head injury or intracranial hemorrhage, we placed electrocorticographic (ECoG) electrodes near foci of damaged cortical tissue. RESULTS: Transient episodes of depressed ECoG activity that propagated across the cortex at rates in the range of 0.6 to 5.0 mm/min were observed in 5 patients; this rate of propagation is characteristic of CSD. We also observed, in 8 of the 14 patients, transient depressions of ECoG amplitude that appeared essentially simultaneous in all recording channels, without clear evidence of spread. CONCLUSIONS: These results indicate that CSD or similar events occur in the injured human brain and are more frequent than previously suggested. On the basis of these observations, we suggest that the related phenomenon, peri-infarct depolarization, is indeed likely to occur in boundary zones in the ischemic human cerebral cortex.

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