Faculty Bibliography

OBJECTIVE:For more than a decade, motor cortex stimulation has been used to treat difficult central and peripheral neuropathic pain syndromes. This prospective study uses the McGill Pain Questionnaire, a visual analog scale (VAS) score, and an inventory of drug consumption to review the results of treating patients with trigeminal neuropathic pain via motor cortex stimulation. METHODS:Ten patients underwent motor cortex stimulation between 1999 and 2002. Implantation was performed via intraoperative neuronavigation and cortical mapping for stimulation site targeting. Nine patients had trigeminal neuropathic pain from postherpetic neuralgia, surgical injury, or unknown cause, and one patient had pain of central origin. Patients were evaluated with multimodality scales before, immediately after, and at designated intervals after surgery. Eight patients underwent permanent implantation after a trial evaluation. In two patients, the stimulating electrodes were removed after an unsuccessful trial. One of these patients had a lateral medullary infarct leading to central pain, and in another patient, there was no explanation for the pain. RESULTS:The average duration of pain before surgery was 6 years. Postoperatively, there was an 88% rate of immediate pain relief (>50% on VAS) and a 75% rate of pain relief at mean follow-up of 10 months (range, 3-24 mo). Mean preoperative McGill Pain Questionnaire total pain rating index was 57 (higher than that observed in causalgia) for patients who did not undergo implantation and 53 for those who underwent implantation. Mean McGill Pain Questionnaire pain rating index at mean follow-up of 10 months was 24 (55% decrease). Mean VAS preoperatively was 9 in patients with stimulator implants and 8 in those whose stimulator was removed after the trial. Immediate postoperative mean VAS score was 1. This score stabilized 3 months after surgery. Patients with implanted stimulators reduced their pain medication dose by a mean of more than 50%. Three patients with facial weakness and sensory loss regained both strength and discriminative sensation during stimulation. In another patient, dysarthria improved. In a review of the literature, 29 (76%) of 38 patients with neuropathic facial pain treated with motor cortex stimulation achieved greater than 50% pain relief. CONCLUSION/CONCLUSIONS:These results provide further support for the use of motor cortex stimulation in facial neuropathic pain and document pain improvement as measured by multidimensional scales. Observations of motor and sensory improvements during stimulation suggest that stimulation alters cortical plasticity and inhibits thalamic hyperactivity.

The Wnt signaling pathway plays a critical role in embryogenesis and tumorigenesis. However, biological roles of Wnt growth factors have not been fully characterized in prostate development and the pathogenesis of prostate cancer. In this study, we used Wnt3a-conditioned medium (Wnt3a-CM) and purified Wnt3a proteins to investigate whether there is a direct effect of Wnt3a on androgen receptor (AR)-mediated transcription and to determine its role in the growth of prostate cancer cells. We demonstrated that Wnt3a-CM either induces AR activity in the absence of androgens or enhances AR activity in the presence of low concentrations of androgens, whereas purified Wnt3a showed a pronounced effect in the presence of low concentrations of ligands. We also showed that Wnt3a-CM and the purified Wnt3a enhance the level of cytosolic and nuclear beta-catenin, suggesting an involvement of beta-catenin in this regulation. Moreover, treatment of LNCaP cells with Wnt3a-CM and purified Wnt3a significantly enhances cell growth in the absence of androgens. Our findings demonstrate that Wnt3a plays an important role in androgen-mediated transcription and cell growth. These results suggest a novel mechanism for the progression of prostate cancer.

We present a case report of a 65-year-old patient who had a subcortical infarct and a right spastic hemiparesis that occurred 19 months before being treated with an investigational therapy consisting of low frequency subthreshold epidural motor cortex electrical stimulation delivered during structured occupational therapy repeated daily for three weeks. Before treatment the patient's affected arm rested in a flexion posture and he was unable to flex or extend the fingers. After three weeks of treatment, the resting tone of his arm had improved and he was able to grasp a pen and write letters. The Fugl-Meyer motor scale score improved from 36 to 46 and this improvement was sustained for four weeks after the conclusion of rehabilitation therapy. This is the first patient to be entered into a randomized clinical feasibility and safety study assessing functional improvement in stroke patients treated with epidural cortical stimulation concurrent with occupational therapy (an investigational therapy).

Some treatments under development to improve motor outcome after stroke require information about organization of individual subject's brain. The current study aimed to characterize normal inter-subject differences in localization of motor functions, and to consider these findings in relation to a potential treatment of motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects examined right index finger tapping, shoulder rotation, or facial movement. The largest activation cluster in left sensorimotor cortex was identified for each task, and its center expressed in Talairach stereotaxic coordinates. Across subjects, each task showed considerable variability in activation site coordinates. For example, during finger tapping, the range for center of activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis. The mean value for center of activation was significantly different for all three coordinates for all pairwise task comparisons. However, the distribution of activation site centers for the finger task overlapped with the other two tasks in the x- and y-axes, and with the shoulder task in the z-axis. On average, the center of activation for the three motor tasks were spatially separated and somatotopically distributed. However, across the population, there was considerable overlap in the center of activation site, especially for finger and shoulder movements. Restorative therapies that aim to target specific body segments, such as the hand, in the post-stroke motor system may need to map the individual brain rather than rely on population averages. Initial details are presented of a study using this approach to evaluate such a therapy.