GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke - A case report

Objective: The paradoxical effects of the hypnotic imidazopyridine zolpidem, widely reported in persistent vegetative state, have been replicated recently in brain-injured and cognitively impaired patients. However, the neuronal mechanisms underlying these benefits are yet to be demonstrated. We implemented contemporary neuroimaging methods to investigate sensorimotor and cognitive improvements, observed in stroke patient JP following zolpidem administration. Methods: We used Magnetic-Resonance-Imaging (MRI) and Magnetic-Resonance-Spectroscopy (MRS) to anatomically and chemically characterize stroke damage. Single-photon-emission-computed-tomography (SPECT) and magnetoencephalography (MEG) were used to identify changes in cerebrovascular perfusion and neuronal network activity in response to sub-sedative doses of zolpidem, zopiclone and placebo. Cognitive improvements were measured using the WAIS-III and auditory-verbal tasks. Results: MRI and MRS revealed a lesion with complete loss of neuronal viability in the left temporal-parietal region; whilst SPECT indicated improved perfusion in the affected hemisphere following zolpidem. MEG demonstrated high-amplitude theta (4-10 Hz) and beta (15-30 Hz) oscillations within the peri-infarct region, which reduced in power coincident with zolpidem uptake and improvements in cognitive and motor function. Conclusions: In JP, functional deficits and pathological oscillations appear coincidentally reduced following administration of low-dose zolpidem. Significance: GABA(A) alpha-1 sensitive desynchronisation of pathological oscillations may represent a biomarker and potential therapeutic target in brain injury. © 2009 International Federation of Clinical Neurophysiology.