M Samuel

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinsons disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement‐related activation of frontal cortical areas in 4 PD patients using H215O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F‐dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinsons Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F‐dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD. Ann Neurol 2000;48:689–695

Motor imagery in normal subjects and Parkinson's disease patients: an H215O PET study.

Motor imagery paradigms can be used to investigate motor preparation. We used positron emission tomography to compare regional cerebral blood flow (rCBF) in patients with Parkinsons disease and normal controls under three conditions: rest, motor imagery and motor execution. In controls, imagery activated bilateral dorsolateral and mesial frontal cortex, inferior parietal cortex and precuneus. Motor execution additionally activated primary motor cortex (p < 0.001). Between-group, for imagery there was relative reduction in dorsolateral and mesial frontal activation in the patient group (p < 0.01). For execution, there was impaired activation of right dorsolateral frontal cortex and basal ganglia (p < 0.01). Our results support the notion that underfunctioning of mesial frontal and dorsolateral prefrontal cortex may underlie motor preparation in Parkinsons disease but also suggest that akinesia may occur in the absence of impaired mesial frontal cortex activation.

Exploring the temporal nature of hemodynamic responses of cortical motor areas using functional MRI

Objective: To use functional MRI (fMRI) to study grouped patterns of cerebral activation and the course of hemodynamic responses during performance of two activation tasks (paradigms) using a hand-held joystick to perform movements in a repetitively fixed direction and movements in freely selected random directions. Background: Evidence from lesion, electrophysiologic, and functional imaging studies implicates prefrontal and mesial frontal cortex in motor preparation and primary motor cortex in motor execution. fMRI can be used to study cerebral activation and has practical advantages over other methods of functional neuroimaging. Methods: We acquired 100 multislice T2* -weighted data sets from five healthy volunteers during performance of each paradigm using conventional fMRI. For each paradigm, rest and movement epochs were alternated every 30 seconds. After coregistration and spatial normalization, we combined the data for group studies. We used statistical parametric mapping to compare the early (first 15 seconds) components of the movement epochs with rest as well as the late (last 15 seconds) components of the movement epochs with rest. Results: During the early phase of both paradigms, significant activation was present in rostral and caudal mesial premotor cortex. Right prefrontal cortex was significantly activated during the early component of freely selected joystick movements. Activation of rostral supplementary motor area was maintained during the late component of freely selected movements but decreased during repetitively fixed movements. In contrast, significant activation in contralateral sensorimotor cortex was maintained during both early and late components of both paradigms. Conclusions: fMRI can detect cortical activation. The temporal resolution of fMRI also allows adaptation of blood oxygenation level-dependent (BOLD) contrast signal to be detected in association cortex. However, the level of BOLD contrast signal in primary motor cortex remained significantly elevated throughout task performance.

Unilateral pallidotomy for Parkinson’s disease: results after more than 1 year

OBJECTIVE To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson’s disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. METHODS Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. RESULTS The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p<0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p<0.005 and p<0.01), and from 50% to 12.5% (p<0.001 and p<0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson’s disease rating scale (UPDRS) motor score in the “off” state remained improved compared with preoperative levels, but less significantly (26%, p<0.001, and 18%, p<0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p<0.005). There was no significant improvement of “on” state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. CONCLUSIONS The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

Firing patterns of pallidal cells in parkinsonian patients correlate with their pre-pallidotomy clinical scores

It is unclear how the disordered activity of cells in the basal ganglia contributes to the symptoms of Parkinsons disease (PD). We recorded from single neurons extracellularly in 3 regions of the globus pallidus (GPe, GPie and GPii) in patients undergoing pallidotomy for PD. Movement-related cell firing patterns, analysed using hidden Markov models, were significantly correlated with patients preoperative clinical scores (off drugs). Responses of cells in GPii correlated best with the scores for specific motor tasks, rather than general ones related to activities of daily living, but the reverse was true for responses from GPe. In both GPii and GPe, a higher score (i.e. greater parkinsonian severity) was associated with greater variability in cell firing rather than an increase in firing rate itself.