Abstracts

Rationale: The potential for a 'placebo effect' of sham brain surgery with respect to neurological function, is an increasing concern, especially for neurosurgical interventions to treat disorders such as epilepsy. In the context of surgery to implant diagnostic recording electrodes for epilepsy, there is considerable anecdotal evidence that the implantation of electrodes alone, without any therapeutic intervention, can reduce the incidence of seizures postoperatively (e.g., Katariwala et al., 2001, Shulze-Bonhage et al, 2010). Similar observations of this so-called 'implant effect' have come from clinical trials in which electrodes are implanted for deep brain stimulation; a mean seizure reduction of 67% was observed after the electrodes were inserted but before any stimulation occurred (Lim et al., 2007). This effect may be due to skull injury, damage to the meninges, or irritation of brain tissue by the electrodes, alone or in combination. Here we used a rat model to test the hypothesis that skull injury alone is sufficient to account for a change in seizure severity in the period following surgical damage to the skull.Methods: To test the hypothesis that burr hole placement in the rat skull would be sufficient to attenuate experimental seizures, we placed burr holes (2mm or 3mm in diameter) bilaterally into the parietal region of the skull of Sprague-Dawley rats, leaving the dura intact. An additional (sham operated) group of animals was subjected to all procedures (anesthesia, skin incision, skull exposure, and wound suturing), without burr holes being placed in the skull. We assessed seizure responses to a chemoconvulsant challenge (pentylenetetrazole, 50, 70 or 90mg/kg, ip) at different time points (three days to one month) following the surgery.Results: At three and six days postoperatively, animals with 2.5mm or 3.5mm burr holes displayed a significant (25 - 70%) reduction in seizure severity in response to pentylenetetrazole (50 mg/kg, ip). The seizure response to a challenge dose of 70 mg/kg was significantly attenuated when measured at three, six, and ten days postoperatively. Animals with 3.5mm burr holes also exhibited a significant increase in the latency to seizure onset at these time points. By 30 days postoperatively, the animals with burr holes exhibited seizure responses that were not significantly different from controls. Conclusions: These data support the hypothesis that surgically-induced damage to the skull by itself is sufficient to cause a postoperative attenuation of seizure response in a rat model, suggesting that injury to the skull, unaccompanied by damage to the meninges or brain tissue, can alter brain excitability through a presently unknown mechanism. Our data suggest that this effect persists for weeks after the insult, but that seizure responses eventually recover to preoperative levels. Our results indicate that trephination of the skull in neurosurgical interventions should be considered as a potential contributor to modified neurological outcomes during an extended postoperative period. Supported by F31NS066822