Faculty Bibliography

Eighteen patients with medically intractable Parkinson's disease that was characterized by bradykinesia, rigidity, and marked 'on-off' fluctuations underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was aided by anatomic coordinates derived from the MRI, intraoperative cell recordings, and electrical stimulation prior to lesioning. A nonsurgically treated group of seven similarly affected individuals was also followed. Assessment of motor function was made at baseline and at 3-month intervals for 1 year. Following the lesioning, patients improved in bradykinesia, rigidity, resting tremor, and balance with resolution of medication-induced contralateral dyskinesia. When compared with preoperative baseline, all quantifiable test scores after surgery improved significantly with the patients off medications for 12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by 38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication requirements were unchanged, but the patients who had had surgery were able to tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces statistically significant reduction in parkinsonism and contralateral 'on' dyskinesia without morbidity or mortality and with a short hospitalization in Parkinson's disease patients for whom medical therapy has failed

Our ongoing study of ventral pallidotomy for the control of Parkinson's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and post-operative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkinsonian primate model and human Parkinson's disease in terms of physiologic recordings and responses. However, we have encountered significant differences between dominant and non-dominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in the globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients

Detection of thermal hypoaesthesia, hyperalgesia, and paradoxical sensation significantly contribute to the diagnosis of polyneuropathy (PNP). There is controversy about the clinical usefulness of detected heat hypoalgesia. In 50 chronic alcoholic patients we compared the prevalence and diagnostic value of heat hypoalgesia (HPT) to that of cold (CT) and warm (WT) hypoaesthesia using a 'Marstock' thermotest. Clinical examination revealed PNP in 56%, cold hypoaesthesia was present in 62%, warm hypoaesthesia in 24%, paradoxical thermal sensation in 10%, cold and heat hyperalgesia in 12%, and heat hypoalgesia in 22%. Only 1 patient (2%) presented with heat hypoalgesia but normal warm and cold thresholds; he reported paradoxical thermal sensation and had PNP. One patient suffered first degree burn injury from heat pain examination. Heat hypoalgesia contributed least to the diagnosis of polyneuropathy (HPT versus CT: P < 0.001). In patients with sensory loss, testing heat hypoalgesia bears some risk of burn injury. In contrast to thermal hypoaesthesia and hyperalgesia, it does not significantly enrich the diagnostic workup of alcoholic polyneuropathies

Six of 48 stroke patients had functionally limiting dysaesthesiae induced by repetitive light touch, joint movement, or neuromuscular electrical stimulation (NMS). Only one of these six patients had a thalamic lesion. Quantitative sensory testing showed substantial impairment of pain and temperature sensation in all six patients, whereas light touch, vibration and position sense, and graphaesthesia were normal (three patients) or relatively spared (three patients). By contrast, none of 15 stroke patients in whom NMS did not evoke dysaesthesiae had clinical evidence of dissociated sensory loss. Conscious perception of joint movement and light touch is mediated mainly by the same population of large myelinated fibres activated preferentially by low intensity electrical stimulation. It is suggested that activation of these non-nociceptive, presumably dorsal column, afferents may contribute to dysaesthesiae in some patients with sensory loss after stroke.

Neuronal properties of the human globus pallidus (GP) are not known. Since GP is the major output of the basal ganglia, it may be involved in the pathophysiology of Parkinson's disease. We studied 12 patients with medically resistant Parkinson's disease by using single cell recording of the GP during stereotaxic pallidotomy to define neuronal firing rate and its modulation during active and passive movements. Different frequency and pattern of single cell activity was found in globus pallidus externus compared with globus pallidus internus. Discharge rates of 19% of GP cells were modulated by passive contralateral movements. Pallidal units were most often related solely to single joint movement. Different patterns of activity in relation to the two different movements of the same joint were often observed. We identified somatotopically arranged cell clusters that alter discharge rate with related movements. These findings suggest at least a partial somatotopic organization of the human GP and similarity with experimental results in both healthy and MPTP monkeys, providing a rationale for surgical or pharmacological targeting of GP for treating Parkinson's disease