Neurophysiological effects of ischaemia
Creators: name: Sarai, Pawandeep
Publisher: name: Imperial College London
Year: 2022

description: Spinal cord injury (SCI) and paralysis remains a tragic complication of thoraco-abdominal aortic aneurysm (TAAA) surgery, despite advances in surgical and medical management. A survey of vascular anaesthetists showed availability of intra-operative spinal cord monitoring to detect an injury and subsequently guide remedial interventions, is variable across the United Kingdom and Ireland, despite clear evidence of its benefit. This research sought to explore the potential benefits of transcranial magnetic stimulation (TMS) and near infrared spectroscopy (NIRS) as alternative, more accessible monitors of ischaemic SCI. TAAA surgery has several nuances that required greater investigation if TMS was to be utilised in theatre. Firstly, the motor evoked potentials (MEPs) of peripheral vascular disease (PVD) patients were characterised. PVD is the primary pathology underlying TAAA and the MEPs of this cohort of patients showed no difference beyond that which would accountable by aging compared to healthy, younger controls. Also, it was demonstrated that over an hour of repeated single-pulse TMS, a time-frame similar to when the spinal cord is at greatest risk intra-operatively and a need for intense monitoring, the variability of the MEPs was no different to controls. A second feature of TAAA surgery is the need to render the surgical field bloodless, thus providing a clear operative space for the surgeons to work in. This is achieved using arterial clamps, the unintended consequence of which is an ischaemic nerve block (INB). An INB has been used as a research tool to initiate changes in cortical excitability. Deafferentation of distal limb structures and subsequent disinhibition of the motor cortical output to non-ischaemic muscles ipsilateral to the INB, manifested as increased MEPs. Through the use of a novel, low pressure INB applied to the lower limb, an increase in MEP amplitude in muscles proximal to the INB occurred. It was further shown that this increase in cortical excitability extended to the contralateral legs muscles and to arm muscles. Simultaneous recordings of somatosensory evoked potentials (SSEP) from stimulation of the tibial nerve, also distal to the INB, demonstrated a reduction in SSEP amplitude but not a complete deafferentation as previously assumed. Investigations into the mechanisms underlying these finding was then performed. Using quantitative sensory testing whilst an INB was performed, the loss of Aβ and Aδ indicated the deafferentation required to initiate changes in motor cortical excitability. The preservation of C-fibre function could account for the unexpected finding where participants with exaggerated punctate sensation had greater increases in MEPs and possible cortical excitability. Paired-pulse TMS paradigms explored the potential neuronal networks responsible for the increase in MEPs of the contralateral muscles. A reduction in interhemispheric inhibition was seen from the deafferented motor cortex to the intact motor cortex, whilst no change in intrahemispheric pathways was seen. The final chapter of this thesis explores the use of TMS and NIRS under surgical conditions. Despite numerous obstacles to patient recruitment, not withstanding a pandemic, a case series is presented with meaningful data which can be used to guide future study. Under the correct anaesthetic regimen, TMS induced MEPs can be recorded. The limited sample size was unable to determine if changes in cortical excitability occur in these conditions during surgery utilising a thigh INB however. In the second clinical investigation, NIRS was used to measure paraspinal muscle oxygen saturations levels (rO2), believed to correlate with intra-spinal oxygenation. This was performed alongside traditional intraoperative neuromonitoring of spinal cord with transcranial electrical stimulation (TES) MEPs. Paraspinal rO2 appeared to follow changes in the haemodynamic status of the patients, where a low rO2 would reflect a low blood pressure. One patient experienced a paraparesis, with a recoverable reduction in MEP amplitude and paraspinal rO2. Another patient who later died without clinical confirmation of paralysis, had a precipitous and permanent reduction in both MEPs and rO2, likely reflecting a SCI. A third patient where a decrease in MEPs and paraspinal rO2 was seen had remedial interventions initiated to prevent a possible SCI, which resulted in a return of both measures close to baseline. Future work should look to explore the changes in cortical excitability secondary to iatrogenic limb ischaemic during TAAA surgery and how this impacts TMS-induced MEP characteristics and their interpretation in detecting a SCI. It should also explore their use alongside NIRS to detect both intra-operative and post-operative SCI and to guide their management.