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.

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.

Preoperative indicators of clinical outcome following stereotaxic pallidotomy.

We assessed the utility of preoperative clinical assessment and functional brain imaging with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in predicting the clinical outcome of stereotaxic pallidotomy for the treatment of advanced Parkinson's disease (PD). Twenty-two PD patients undergoing posteroventral pallidotomy were assessed preoperatively with the Core Assessment Program for Intracerebral Transplantation (CAPIT) ratings measured on and off levodopa; quantitative FDG/PET was also performed before surgery. Preoperative clinical and metabolic measurements were correlated with changes in off-state CAPIT ratings determined 3 months after surgery. Clinical outcome following pallidotomy was also correlated with intraoperative measures of spontaneous pallidal single-unit activity as well as postoperative MRI measurements of lesion volume and location. We found that unilateral pallidotomy resulted in variable clinical improvement in off-state CAPIT scores for the contralateral limbs (mean change 30.9 +/- 15.5%). Postoperative MRI revealed that pallidotomy lesions were comparable in location and volume across the patients. Clinical outcome following surgery correlated significantly with preoperative measures of CAPIT score change with levodopa administration (r = 0.60, p < 0.005) and with preoperative FDG/PET measurements of lentiform glucose metabolism (r = 0.71, p < 0.0005). Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. We conclude that preoperative measurements of lentiform glucose metabolism and levodopa responsiveness may be useful indicators of motor improvement following pallidotomy. Both preoperative quantitative measures, either singly or in combination, may be helpful in selecting optimal candidates for surgery.

Microelectrode recording during posteroventral pallidotomy: impact on target selection and complications.

OBJECTIVE: To assess the practical usefulness of single-cell microelectrode recording (MER) when performing posteroventral pallidotomy. METHODS: A retrospective comparison of the initial, magnetic resonance imaging-derived coordinates of the pallidotomy target to the final, MER-refined lesion coordinates in 132 consecutive pallidotomies was conducted. The time required to perform the procedure and the surgical complications are reported. RESULTS: MER led to targeting changes in 98% of the cases. In 12%, the MER-refined target was more than 4 mm from the original, image-guided site, which is a targeting error that could adversely affect outcome. Although all components of targeting were affected by MER, laterality and depth were impacted most. The ventral border of the globus pallidus pars interna was located within 1 mm of the magnetic resonance imaging-selected target in only 40% of the cases. On average, only 2.2 MER trajectories were required to perform pallidotomy. During the last 3 years of our study, 85% of the procedures were performed with one or two trajectories. The mean operating time of the operations performed during the last 3 years was 2 hours and 12 minutes. The incidence of intracerebral hemorrhage in our series (1.5%) was no higher than that reported for other large series of stereotactic procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides important targeting information for performing pallidotomy. In particular, the micrometric delineation of the ventral border of the globus pallidus pars interna permits safe lesioning of the posteroventral region of the globus pallidus pars interna with little risk of visual field deficit. These data can be obtained efficiently and without increased surgical risk.

Comparison of anatomic and neurophysiological methods for subthalamic nucleus targeting.

OBJECTIVE: The subthalamic nucleus (STN) has recently become the surgical target of choice for the treatment of medically refractory idiopathic Parkinson's disease. A number of anatomic and physiological targeting methods have been used to localize the STN. We retrospectively reviewed the various anatomic targeting methods and compared them with the final physiological target in 15 patients who underwent simultaneous bilateral STN implantation of deep brain stimulators. METHODS: The x, y, and z coordinates of our localizing techniques were analyzed for 30 STN targets. Our final targets, as determined by single-cell microelectrode recording, were compared with the following: 1) targets selected on coronal magnetic resonance inversion recovery and T2-weighted imaging sequences, 2) the center of the STN on a digitized scaled Schaltenbrand-Wahren stereotactic atlas, 3) targeting based on a point 13 mm lateral, 4 mm posterior, and 5 mm inferior to the midcommissural point, and 4) a composite target based on the above methods. RESULTS: All anatomic methods yielded targets that were statistically significantly different (P < 0.001) from the final physiological targets. The average distance error between the final physiological targets and the magnetic resonance imaging-derived targets was 2.6 +/- 1.3 mm (mean +/- standard deviation), 1.7 +/- 1.1 mm for the atlas-based method, 1.5 +/- 0.8 mm for the indirect midcommissural method, and 1.3 +/- 1.1 mm for the composite method. Once the final microelectrode-refined target was determined on the first side, the final target for the contralateral side was 1.3 +/- 1.2 mm away from its mirror image. CONCLUSION: Although all anatomic targeting methods provide accurate STN localization, a combination of the three methods offers the best correlation with the final physiological target. In our experience, direct magnetic resonance targeting was the least accurate method.

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.

Selection criteria for unilateral posteroventral pallidotomy.

In an attempt to refine the indications for posteroventral pallidotomy (PVP) the authors instituted strict selection criteria which are based on the experience gained from the first 60 pallidotomy patients treated at their institution. In addition to clinical evaluation, all pallidotomy candidates undergo neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron emission tomography (FDG/PET). The data from which these criteria were developed are presented as are early clinical results. The authors demonstrate that these criteria enhance the efficacy of the procedure by assuring therapeutic response and reducing the incidence of post-operative dementia. Their indications and contraindications for pallidotomy are discussed.

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.

Efficacy of bilateral pallidotomy.

Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures.

Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease.

OBJECTIVE: To evaluate whether subthalamic nucleus (STN) stimulation has an effect on the orthostatic regulation of patients with Parkinson disease (PD), we studied cardiovascular regulation during on and off phases of STN stimulation. METHODS: We examined 14 patients with PD (mean age 58.1 +/- 5.8 years, 4 women, 10 men) with bilateral STN stimulators. Patients underwent 3 minutes of head-up tilt (HUT) testing during STN stimulation and after 90 minutes interruption of stimulation. We monitored arterial blood pressure (BP), RR intervals (RRI), respiration, and skin blood flow (SBF). Baroreflex sensitivity (BRS) was assessed as the square root of the ratio of low-frequency power of RRI to the low-frequency power of systolic BP for coherences above 0.5. RESULTS: During the on phase of the STN stimulation, HUT induced no BP decrease, a significant tachycardia, and a significant decrease of SBF. During the off phase of stimulation, HUT resulted in significant decreases in BPsys and RRI and only a slight SBF decrease. HUT induced no change of BRS during stimulation, but lowered BRS when the stimulator was off (p < 0.05). CONCLUSIONS: STN stimulation of patients with PD increases peripheral vasoconstriction and BRS and stabilizes BP, thereby improving postural hypotension in patients with PD. The results indicate that STN stimulation not only alleviates motor deficits but also influences autonomic regulation in patients with PD.

The unbiased estimation of number and sizes of arbitrary particles using the disector.

A three-dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented. Used in combination with ordinary and recently developed stereological methods unbiased estimates of various mean particle sizes and the variance of particle volume are obtainable on sets of two parallel sections with a known separation. The same principle allows the unbiased estimation of the distribution of individual particle volumes in sets of serial sections.

[Atypical symptomatic headache in the developmental period--case report]. / Atipicna simptomatska glavobolja u razvojnom dobu--prikaz slucaja.

The authors report a case of atypical symptomatic headache in developmental age. It is a complex headache in which three etiologic factors are permeated and superposed. The basic mechanism is connected with the presence of vascular congenital malformation (a. trigemini primitiva persistens), second mechanism is associated with immunologic events (leucopenia-dyshematopoiesis) in which central nervous system is secondarily involved with headaches partly superposed and personality features mildly neurotic, which would represent the third etiologic factor. Since it is the case of symptomatic headache as a notorius clinical entity but with peculiar, puzzling, atypical clinical features and course, the authors point to the complexity of this type of headache, diagnostic speculations and difficulties encountered in therapeutical approaches.

[Activity and function of neurons in the globus pallidus in Parkinson's disease]. / Aktivnosti i funkcija neurona globusa palidusa u Parkinsonovoj bolesti.

We investigated the activity and functional distribution of globus pallidus neurons in Parkinson's disease patients and recorded single cell activity of globus pallidus medialis and changes related to the movements of different joints in 31 patients during stereotactic ventral pallidotomy procedure. We showed that discharge rates of 19% of medial globus pallidus neurons were modulated by passive contralateral movements; 77.2% of these pallidal units showed changes related solely to single joint movement and 22.8% showed different patterns of activity in relation to two and more joints. We also identified somatotopically arranged cell clusters that alter the discharge rate with related movements; oro-facial movement-related cells in caudo-ventral region and, leg-related cells in dorso-rostral part and arm-related cells between these two parts of medial globus pallidus. These findings suggest a partial somatotopic organization of human globus pallidus medialis.

[Cerebellitis? Case report of acute cerebellar ataxia in childhood]. / Cerebelitis? Prikaz slucaja decje akutne cerebelarne atasije.

The authors present a severe clinical manifestation of acute cerebellitis with a favorable outcome, most likely of viral etiology, without fever. An emphasis is placed on the value of complex investigations, clinical as well as laboratory ones, and the exclusion of other diseases which come into consideration in differential diagnostics.

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.

[Participation of pentagastrin and oxytocin in organizing neural activity of the dorsal hippocampus during result- and conflict-oriented feeding behavior in rabbits]. / Uchastie pentagastrina i oksitotsina v organizatsii aktivnosti neironov dorsal'nogo gippokampa pri rezul'tativnom i konfliktnom pishchevom povedenii krolikov.

Single unit activity of CA3 dorsal hippocamp has been registered in free moving rabbits. The influence of microiontophoretic application of pentagastrin and oxytocin on neuronal involvement into feeding or defensive behaviour has been studied. The change of the dominant feeding motivation to defensive was shown to cause resettings in the typical feeding activity of most neurons. Microiontophoretic application of pentagastrin induces typical feeding activity even if rabbits demonstrate defensive behaviour. It is believed that pentagastrin presence in perineuronal area leads to the involvement of most hippocampal neurons into the organization of the feeding behaviour.

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.

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.