Chronic subdural cortical stimulation for phantom limb pain: report of a series of two cases.

Phantom limb pain is a complex, incompletely understood pain syndrome that is characterized by chronic painful paresthesias in a previous amputated body part. Limited treatment modalities exist that provide meaningful relief, including pharmacological treatments and spinal cord stimulation that are rarely successful for refractory cases. Here, we describe our two-patient cohort with recalcitrant upper extremity phantom limb pain treated with chronic subdural cortical stimulation. The patient with evidence of cortical reorganization and almost 60 years of debilitating phantom limb pain experienced sustained analgesic relief at a follow-up period of 6 months. The second patient became tolerant to the stimulation and his pain returned to baseline at a 1-month follow-up. Our unique case series report adds to the growing body of literature suggesting critical appraisal before widespread implementation of cortical stimulation for phantom limb pain can be considered.

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson's disease.

Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson's disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p<0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p=0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p=0.5811; LEDD, p=0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p=0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.

Long-term stabilization of place cell remapping produced by a fearful experience.

Fear is an emotional response to danger that is highly conserved throughout evolution because it is critical for survival. Accordingly, episodic memory for fearful locations is widely studied using contextual fear conditioning, a hippocampus-dependent task (Kim and Fanselow, 1992; Phillips and LeDoux, 1992). The hippocampus has been implicated in episodic emotional memory and is thought to integrate emotional stimuli within a spatial framework. Physiological evidence supporting the role of the hippocampus in contextual fear indicates that pyramidal cells in this region, which fire in specific locations as an animal moves through an environment, shift their preferred firing locations shortly after the presentation of an aversive stimulus (Moita et al., 2004). However, the long-term physiological mechanisms through which emotional memories are encoded by the hippocampus are unknown. Here we show that during and directly after a fearful experience, new hippocampal representations are established and persist in the long term. We recorded from the same place cells in mouse hippocampal area CA1 over several days during predator odor contextual fear conditioning and found that a subset of cells changed their preferred firing locations in response to the fearful stimulus. Furthermore, the newly formed representations of the fearful context stabilized in the long term. Our results demonstrate that place cells respond to the presence of an aversive stimulus, modify their firing patterns during emotional learning, and stabilize a long-term spatial representation in response to a fearful encounter. The persistent nature of these representations may contribute to the enduring quality of emotional memories.

The nucleus accumbens as a potential target for central poststroke pain.

Although deep brain stimulation (DBS) has been found to be efficacious for some chronic pain syndromes, its usefulness in patients with central poststroke pain (CPSP) has been disappointing. The most common DBS targets for pain are the periventricular gray region (PVG) and the ventralis caudalis of the thalamus. Despite the limited success of DBS for CPSP, few alternative targets have been explored. The nucleus accumbens (NAC), a limbic structure within the ventral striatum that is involved in reward and pain processing, has emerged as an effective target for psychiatric disease. There is also evidence that it may be an effective target for pain. We describe a 72-year-old woman with a large right hemisphere infarct who subsequently experienced refractory left hemibody pain. She underwent placement of 3 electrodes in the right PVG, ventralis caudalis of the thalamus, and NAC. Individual stimulation of the NAC and PVG provided substantial improvement in pain rating. The patient underwent implantation of permanent electrodes in both targets, and combined stimulation has provided sustained pain relief at nearly 1 year after the procedure. These results suggest that the NAC may be an effective DBS target for CPSP.