Tissue reactions to long-term electrical stimulation of the cerebellum in monkeys

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Abstract
Light microscopic and EM analyses were carried out on the stimulated and unstimulated paravermal cortices of 6 rhesus monkeys [Macaca mulatta] that had electrodes implanted on their cerebella for 2 mo. The electrodes and the stimulation regime (10 p[pulses]/s:8 min on, 8 min off) were similar to those used to stimulate the human cerebellum for treatment of certain neurological disorders. Mere presence of the electrode array in the posterior fossa for 2 mo. resulted in some meningeal thickening, attenuation of the molecular layer and loss of Purkinje cells immediately beneath the electrode array. There was no evidence of scarring. After 205 h of stimulation (7.38 .times. 106 pulses) over 18 days, a charge of 0.5 .mu.C/ph [phase] or estimated charge density of 7.4 .mu.C/cm2 per ph resulted in no damage to the cerebellum attributable to electrical stimulation per se. Such a charge/phase is about 5 times the threshold for evocation of cerebellar efferent activity, and might be considered safe for stimulation of human cerebellum. Charge density/phase and charge/phase were directly related to increased cerebellar injury in the 6 other cerebellar cortices stimulated. Leptomeningeal thickening increased with increased charge density. Injury included severe molecular layer attenuation, ongoing destruction of Purkinje cells, gliosis, ongoing degeneration of myelinated axons, collagen intrusion and increased levels of local polysaccharides. In all cases, even with damage that destroyed all conducting elements beneath the electrodes, there was no damage further than 1-2 mm from the edges of the electrode arrays.

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