Feasibility of cerebello-cortical stimulation for intraoperative neurophysiological monitoring of cerebellar mutism

Abstract

Background Cerebellar mutism can occur in a third of children undergoing cerebellar resections. Recent evidence proposes it may arise from uni- or bilateral damage of cerebellar efferents to the cortex along the cerebello-dento-thalamo-cortical pathway. At present, no neurophysiological procedure is available to monitor this pathway intraoperatively. Here, we specifically aimed at filling this gap. Methods We assessed 10 patients undergoing posterior fossa surgery using a conditioning-test stimulus paradigm. Electrical conditioning stimuli (cStim) were delivered to the exposed cerebellar cortex at interstimulus intervals (ISIs) of 8–24 ms prior to transcranial electric stimulation of the motor cortex, which served as test stimulus (tStim). The variation of motor-evoked potentials (MEP) to cStim + tStim compared with tStim alone was taken as a measure of cerebello-cortical connectivity. Results cStim alone did not produce any MEP. cStim preceding tStim produced a significant inhibition at 8 ms (p < 0.0001) compared with other ISIs when applied to the lobules IV-V-VI in the anterior cerebellum and the lobule VIIB in the posterior cerebellum. Mixed effects of decrease and increase in MEP amplitude were observed in these areas for longer ISIs. Conclusions The inhibition exerted by cStim at 8 ms on the motor cortex excitability is likely to be the product of activity along the cerebello-dento-thalamo-cortical pathway. We show that monitoring efferent cerebellar pathways to the motor cortex is feasible in intraoperative settings. This study has promising implications for pediatric posterior fossa surgery with the aim to preserve the cerebello-cortical pathways and thus prevent cerebellar mutism.

Structural damage burden and hypertrophic olivary degeneration in pediatric postoperative cerebellar mutism syndrome

“…At present, IONM is well established for supratentorial functional areas, brainstem and cerebello-pontine angle, but not for monitoring of the cerebellum itself. Recently, the first study was published on IONM of the cerebello-dentato-thalamo-cortical pathway [ 10 ]. The authors demonstrated that direct stimulation of lobules IV, V, and VI in the anterior cerebellum and lobule VIIB in the posterior cerebellum leads to inhibition of primary motor cortex excitability for transcranial electrical stimulation.…”

Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications

“…These include, for example: (i) computation of probabilistic connectivity atlas based on segmentation of the cerebellar peduncles, allowing for comparison of WM integrity between patients and controls diffusion maps (207,208); (ii) application of transcranial magnetic stimulation (TMS) technique to provide either negative or positive inhibitory or facilitatory modulation of the primary motor cortex output using an appropriate cerebellar stimulus to deduce injury to the dentato-thalamiccortical circuit and predict postsurgical development of cerebellar mutism (209); (iii) development and validation of reliable procedures for neurophysiological monitoring of the cerebellocortical connectivity. Preliminary results in this field showed the feasibility of reproducing extra-operative conditioning-test paradigm previously adopted for TMS (210).…”

Novel Asleep Techniques for Intraoperative Assessment of Brain Connectivity

“…In brain tumor surgery IONM is particularly well-established for preservation of the corticospinal tract ( 13 , 14 ), but asleep mapping and monitoring outside the corticospinal system is lacking. The aim of this opinion paper is to discuss two novel potential IONM techniques allowing to map and monitor functions beyond corticospinal motor function in the anesthetized setting, namely, (A) conditioning of motor output ( 15 , 16 ) and (B) cortico-cortical evoked potentials ( 17 , 18 ). These have been performed under total intravenous anesthesia using Propofol (100–150 μg/kg/min) and Fentanyl (1 μg/kg/min) in continuous infusion, and avoiding muscle relaxants after intubation.…”

“…We propose that the CS/TS approach can be successfully performed also by means of direct cortical stimulation in the intraoperative setting, and therefore potentially be used for assessing and potentially monitoring the integrity of specific brain and spine connections, as demonstrated by two recent works from our group, on parietal-motor connectivity ( 15 ) and on cerebello-motor connectivity ( 16 ).…”

“…In the second work we tested the effects of CS applied to the cerebellar cortex onto corticospinal excitability ( 16 ), tested by TS applied transcranially to target the upper limb motor cortex ( Figure 1C ) in 10 anesthetized patients undergoing posterior fossa tumor surgery. Our experimental paradigm is inspired by a well-established CS+TS technique referred to as “cerebellar inhibition” in which the cerebellum and the motor cortex are stimulated by TMS ( 28 , 29 ).…”