Person:

Rozman, Peter

Epilepsy is a neurological disorder affecting 50 million people worldwide. It consists of a large number of syndromes, all of which are characterized by a predisposition to recurrent, unprovoked seizures, while differing by degree of focality, clinical manifestation and many other factors. Despite the prevalence of this disorder, relatively little is known about the basic physiological mechanisms that underlie the seizures themselves. Additionally, roughly 25% of patients are refractory to existing therapies. The need for more highly targeted therapies for focal epilepsies has driven decades of research on seizure prediction. While most of these studies have relied on scalp or intracranial EEG, more recent studies have taken advantage of electrodes that capture single- or multi-unit activity. We utilized a linear microelectrode array to capture multi-unit activity in humans with refractory epilepsy with the expectation that such microscale activity may provide a signal in advance of changes on electroencephalography.

Twelve patients underwent long-term monitoring with both clinical electrocorticography (ECoG) and the laminar microelectrode array, which consists of linearly arranged contacts that sample all layers of the human cortex. Multi-unit (300-5000 Hz) power was compared between thirty-minute preictal and interictal time windows.

Several parameters characterizing the multi-unit power were compared between preictal and interictal time windows. Parameters included proximity to seizure focus, depth of recording, and directionality of changes in multi-unit power. Optimization of these parameters resulted in a best-performing classifier with sensitivity and specificity of 0.70 and 0.80, respectively.

These results demonstrate reproducible increases and decreases in multi-unit activity prior to seizure onset and suggest that multi-unit information may be useful in the development of future seizure prediction systems.

Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physicians. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p = 0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p < 0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p < 0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.