PP14.3 – 2698: Prolonged cortical hyperexcitability during burst-suppression associated with glycine receptor antibodies

Abstract

Objective Stimulus sensitivity in the context of burst–suppression has been recognised, whereby signs only emerge after 24 hours of barbiturate infusion and disappear when this is reduced. We report clinical neurophysiological findings in a 15 year old child with persistent burst-suppression stimulus sensitivity, with a prior history of stimulus sensitive jerks. She developed a clinical picture of progressive encephalomyelitis with rigidity and myoclonus (PERM) and was subsequently found to have glycine receptor antibodies. Methods Continuous EEG recording with concomitant stimulation using a strobe light. Results 1. We observed stimulus sensitivity in our patient in response to tactile, visual and auditory stimulation, persisting for days after withdrawal of the barbiturate. 2. In a normal cortex, the neurons usually have a refractory period within the first 2.5s after the end of the preceding burst. In our patient we were able to elicit a burst within this refractory period, indicating cortical hyperexcitability. 3. An abnormal end of train response was seen, suggestive of altered inhibition and excitation mechanisms. 4. This child was subsequently shown to have glycine receptor antibodies. Conclusion Glycine receptors are expressed in brainstem, spinal cord and thalamus. We hypothesize that inactivation of the glycine receptor at the level of the thalamus results in reduction of hyperpolarisation and consequent increase in excitation, thus causing hyperexcitability. Other stimulus induced discharges (SIRPIDs) are also thought to arise via thalamocortical activation combined with hyperexcitable cortex. This study implicates the glycinergic pathway in cortical hyperexcitability and provides novel insights into the pathophysiological mechanisms underlying stimulus sensitivity, possibly facilitated by the barbiturate infusion in an intensive care setting, as in our case.