Cognitive functioning after pallidotomy for refractory Parkinson's disease.

BACKGROUND: Earlier approaches to pallidotomy for refractory Parkinson's disease had significant complication rates. More recent approaches show fewer complications, but the effect of pallidotomy on cognition is unclear. The current study was conducted to examine the neuropsychological effects of unilateral pallidotomy. METHODS: Neuropsychological testing was performed on patients with medically refractory, predominantly unilateral Parkinson's disease at baseline and after unilateral ventral pallidotomy (n=28) or after an equivalent period without surgery in control patients (n=10). RESULTS: Pallidotomy patients showed no significant changes from baseline to retesting relative to the control group for any measure. Across all of the tests administered, only five of the surgery patients showed a significant decline, and of these five none declined on more than one test. Depression did not relate to preoperative or postoperative cognition. The pallidotomy group showed a significant improvement in motor functioning and activities of daily living whereas the control group did not. These measures were not associated with the neuropsychological test scores at baseline or retest. CONCLUSIONS: Stereotactic unilateral ventral pallidotomy does not seem to produce dramatic cognitive declines in most patients.

Left-right differences in motor thresholds after stimulation of the globus pallidus before pallidotomy.

Left-right upper limb motor threshold differences were found after electrical stimulation of the globus pallidus administered as a neuroprotective measure to avoid lesioning of the internal capsule during stereotactic pallidotomy for treatment of Parkinson's disease. Left sided stimulation resulted in lower thresholds in right handed patients compared with left handed patients. These differences were significant in women, but no significant differences were found in men. In patients undergoing bilateral pallidotomy, the stimulation produced more significant left-right motor threshold differences. In the absence of known sex-related anatomical left-right corticospinal tract differences, the variability was the result of spinal excitability modulations most likely related to handedness.

Metabolic correlates of pallidal neuronal activity in Parkinson's disease.

We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic covariance patterns associated with Parkinson's disease and related disorders previously. Nonetheless, the physiological correlates of these abnormal patterns are unknown. In this study we used PET to measure resting state glucose metabolism in 42 awake unmedicated Parkinson's disease patients prior to unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single unit activity of the internal segment of the globus pallidus (GPi) was recorded intraoperatively in the same patients under identical conditions. The first 24 patients (Group A) were scanned on an intermediate resolution tomograph (full width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned on a higher resolution tomograph (full width half maximum, 4.2 mm). We found significant positive correlations between GPi firing rates and thalamic glucose metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r = 0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus of physiological-metabolic correlation involving the ventral thalamus and the GPi (statistical parametric map: P < 0.05, corrected). Regional covariance analysis demonstrated that internal pallidal neuronal activity correlated significantly (r = 0.65, P < 0.005) with the expression of a unique network characterized by covarying pallidothalamic and brainstem metabolic activity. Our findings suggest that the variability in pallidal neuronal firing rates in Parkinson's disease patients is associated with individual differences in the metabolic activity of efferent projection systems.

Stereotactic pallidotomy for Parkinson's disease: a long-term follow-up of unilateral pallidotomy.

Eleven patients suffering from Parkinson's disease were followed for up to 4 years after unilateral pallidotomy. We observed persistent contralateral improvement and unexpected ipsilateral improvement of motor symptoms. In addition, there was a protracted relief of contralateral dyskinesias and maintenance of relatively stable levodopa dosage.

Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson's disease.

Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site.

Electrical stimulation of the globus pallidus preceding stereotactic posteroventral pallidotomy.

Physiological methods such as microelectrode recording of neuronal activity and electrical stimulation of target structures can improve the safety and efficacy of certain stereotactic surgeries. The globus pallidus (GP) was electrically stimulated in 136 patients with Parkinson's disease prior to unilateral posteroventral pallidotomy to identify functional areas and prevent deficits. We found that electrical stimulation of the GP elicited two principal responses: contractions of the contralateral hand and flashing lights. The mean voltage that evoked motor responses was 4.3 V (range 1.7-9.0 V), while higher intensity was necessary to elicit visual responses (mean 6.8 V; range 3.5-9.9 V). Contralateral tremor, speech impairment, paresthesias, and warm sensations were also elicited.

Wada memory disparities predict seizure laterality and postoperative seizure control.

We examined the efficacy of a memory difference score (DS: right minus left hemisphere memory) during the Wada test (intracarotid amobarbital procedure, IAP) for predicting seizure laterality and postoperative seizure outcome in 70 left speech dominant patients from two epilepsy centers. DS > or = 2, after addition of 1 point to the left hemisphere injection score to account for aphasia, were noted in 71.4% of patients and correctly predicted surgery side for 98.0% of these patients. The DS related significantly to seizure outcome at 1-year follow-up (p < 0.002) and correctly predicted 80% of patients who were seizure-free. Patients whose DS did not correctly predict seizure laterality more frequently required invasive studies to establish seizure onset. The relationship of the DS to laterality did not differ significantly by class of IAP memory stimuli. When seizures originate from the temporal lobe, the IAP memory DS predicts seizure laterality by assessing the functional adequacy of the involved hemisphere and is predictive of seizure control.

Stereotactic ventral pallidotomy for Parkinson's disease.

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.

Anatomic and physiological considerations in pallidotomy for Parkinson's disease.

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.

Ventral intermediate thalamotomy for hemiballismus.

Stereotactic thalamotomy in an unusual case of hemiballismus is reported. This 13-year-old female developed constant left upper and lower extremity flinging movements shortly after cardiac bypass surgery for congenital heart disease at the age of 8. Numerous medications were unsuccessful in controlling these abnormal movements, hence, she stopped attending elementary school for 1 year prior to admission. Under local anesthesia, a stereotactic right ventral intermediate thalamotomy was performed to assist in making precise lesions. There was no postoperative complication. There was an immediate significant improvement. Her ballistic movements in all muscle groups disappeared from both upper and lower extremity, except for residual involuntary movements of her fingers and wrist.

Left temporal neocortex mediation of verbal memory: evidence from functional mapping with cortical stimulation.

We examined the contribution of the temporal neocortex to short-term memory (STM) in 15 patients with left hemisphere language dominance during intraoperative or extraoperative cortical mapping prior to left anterior temporal lobectomy. Recall errors were examined following stimulation during the acquisition, consolidation, and retrieval stages of a verbal STM task. Ten patients showed stimulation-induced recall errors, and five patients showed no significant memory errors. More patients showed errors following stimulation during consolidation than during acquisition or retrieval, possibly because of disrupted transfer of information from the temporal neocortex to the hippocampus. Patients with stimulation-induced recall errors did not differ significantly from patients without memory errors in terms of seizure, demographic, or neuropsychological variables. Patients with resection of sites showing stimulation-induced recall errors had greater postoperative decline in verbal memory than did patients with resection sparing these sites. We suggest that the left temporal neocortex contributes to verbal memory consolidation in patients with chronic epilepsy.

Neurophysiological properties of pallidal neurons in Parkinson's disease.

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.

Multiple subpial transections in the language cortex.

Multiple subpial transections (MST) were made in language cortex in three patients with medically refractory partial epilepsy. All patients were mapped with extra-operative stimulation using subdural grids over the dominant temporal, frontal and parietal convexity. Two patients had anterior temporal lobectomy and MST in posterior language cortex. One patient who had undergone a previous frontal tumour resection had only MST over the frontoparietal convexity, including frontal and parietal language areas. Both patients with MST in the posterior language cortex had postoperative language dysfunction, which had improved significantly by 9 months after surgery. The patient with MST in frontoparietal language areas had improved language functions immediately postoperatively. The two men with anterior temporal lobectomies and MST are seizure-free at 1 year follow-up and the woman with frontoparietal MST has had a > 70% reduction in seizure frequency at 1 year follow-up.

Decreased seizure frequency after withdrawal and reinstitution of antiepileptic drug therapy.

We reviewed the seizure frequencies of 38 patients with medically refractory epilepsy 6 weeks before (baseline) and 3 weeks after withdrawing their antiepileptic drugs (AEDs) for video-EEG monitoring. Seizure frequency during the first 3 weeks after restarting AEDs was diminished compared with baseline (P < 0.05). We found no correlation between seizure frequency and patient age, specific antiepileptic drugs, number of seizures during the video-EEG monitoring, number of days without AEDs, or partial vs total withdrawal of AEDs. Medication tachyphylaxis, functional tolerance, or long term post-ictal depression of the seizure threshold is hypothesized. The diminished seizure frequency after reinstitution of medications in four of five patients who did not have seizures during their hospitalization suggests that drug tachyphylaxis is a relevant mechanism.

Invasive intracranial monitoring, cortical resection and multiple subpial transection for the control of intractable complex partial seizure of cortical onset.

Invasive intracranial monitoring with subdural grids has led to a greater appreciation of cortical function and the discovery of ictal onset either independently or in conjunction with deep structures. With the description of multiple subpial transections the armamentarium for surgical control of intractable seizures has been expanded. Utilizing invasive intracranial monitoring with subdural grids and strips, a large series of patients with intractable complex partial seizures originating in exquisite cortex, and in some cases additionally in deep structures, have undergone surgery. These patients would previously have been judged not to be candidates for surgical control of seizures. We will present 9-month or greater follow-up in an ongoing series of patients undergoing cortical resection and subpial transections in whom there has been a statistical improvement in control or alleviation of their seizure disorder. The report will specifically discuss outcomes as related to exquisite cortex, motor, sensory and language functions, as well as clinical results and EEG.

Anatomic and physiological considerations in pallidotomy for Parkinson's disease.

Our ongoing study of central pallidotomy for the control of Parkison'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 postoperative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkisonian primate model and human Parkinson's disease in terms of physiological recordings and responses. However, we have encountered significant differences between dominant and nondominant 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 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.

Anterior temporal language areas in patients with early onset of temporal lobe epilepsy.

Eighteen consecutive patients undergoing dominant temporal lobectomy underwent preoperative cortical stimulation for language localization. Patients with naming deficits on anterior (4.5 cm from the temporal pole) temporal lobe stimulation had earlier seizure onset vs those without such deficits (5.8 yr vs 12.9 yr; p < 0.04). There was a similar trend for reading errors (6.3 yr vs 12.4 yr; p < 0.052). Resections always spared at least 1 cm anterior to any language area. There was no significant difference in postoperative neuropsychological tests between patients with and without anterior language representation. Early onset of dominant temporal lobe seizure foci leads to a more widespread or atypical distribution of language areas. Individual variability should be considered in epilepsy surgery to reduce postoperative language deficits.