Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor.

BACKGROUND: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease. METHODS: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery. RESULTS: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients. CONCLUSION: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.

Deep brain stimulation of the pedunculopontine nucleus in a patient with freezing of gait.

CASE PRESENTATION: A 54-year-old male patient presenting probable multiple system atrophy with predominant parkinsonism who underwent bilateral deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is presented. The patient had dominant freezing of gait (FOG), levodopa-resistant bradykinesia, and autonomic disturbances, but with a good cognitive condition. METHODS: The patient underwent bilateral DBS of the PPN, which ended with modest benefits. RESULTS AND CONCLUSION: Although he had a short postoperative follow-up (6 months), his neurological status remained stable and PPN DBS provided modest improvements in the gait disorder and freezing episodes. This unusual case suggests that the mesencephalic pedunculopontine region may have a role in locomotor symptoms and the potential to provide a limited improvement in FOG.

Brain penetration effects of microelectrodes and DBS leads in STN or GPi.

OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Bilateral subthalamotomy for advanced Parkinson disease.

BACKGROUND: Unilateral subthalamotomy has been reported to be effective in the treatment of rigidity, bradykinesia, and tremor of the contralateral limb. However, gait, clinical fluctuation, and postural stability are not significantly improved by unilateral lesioning of the STN in the long term. We sought to determine if bilateral surgery of the STN offers more benefits in the treatment of advanced PD. METHODS: Radiofrequency thermal coagulation was performed bilaterally in the STN in 10 patients. Under microelectrode and stereotactic guidance, surgery was directed at the dorsolateral portion of the STN in stages and followed by MRI in each patient to confirm lesion location. Patients have been followed for a median duration of 26 months as measured from the date of first surgery (range, 6-48 months) with UPDRS before and after surgery. RESULTS: Bilateral subthalamotomy demonstrated persistent benefits in bradykinesia, rigidity of the limbs, and consequently the improvement in activities of daily living, motor function, Schwab and England scales. In addition, significant improvement in axial motor features, gait, postural stability, and clinical fluctuation were present with bilateral STN surgeries. The benefits were sustained at the last evaluation period of 36 months. Tremor and drug-induced dyskinesia improved in early postoperative period, but the benefits declined over time. The reduction of daily l-dopa equivalent was 34%. No speech impairment was observed. Mild choreic movement occurred in 2 of 20 procedures that resolved spontaneously in 4 to 8 weeks. CONCLUSION: For advanced PD present with bilateral symptoms, axial motor impairment, or clinical fluctuation, staged bilateral subthalamotomy appears as a safe and effective treatment in the long term.

The impact of ventrolateral thalamotomy on tremor and voluntary motor behavior in patients with Parkinson's disease.

A preferred target for parkinsonian tremor alleviation is the ventrolateral (VL) thalamus. The goal of the present study is to determine how lesions involving the presumed cerebellar and pallidal recipient areas of the "motor" thalamus would alter the tremor and motor behavior of ten patients with Parkinson's disease (PD). Tremor amplitude, power dispersion (a measure of sharpness of the power spectrum of tremor), and power distribution were quantified using a laser displacement sensor prior to, and a week after, VL thalamotomy. As well, the impact of surgery on tremor seen during movement was quantified in a manual-tracking (MT) task. Tremor-induced noise (a measure of the amount of tremor present during movement) and ERROR (difference between subject's performance and target) were quantified. Finally, bradykinesia was assessed with a rapid alternating movement (RAM) task. Duration, range, and amplitude irregularity of wrist pronation-supination cycles were computed. Both motor tasks were quantified using a highly sensitive forearm rotational sensor. Healthy age-matched control subjects were also tested. Magnetic resonance images with an integrated atlas of thalamic nuclei were used to confirm lesion location. Results show that the lesions were centered upon the posterior portion of the ventral lateral (VLp) nucleus of the thalamus, included the posterior part of the ventral lateral anterior nucleus (VLa), and extended posteriorly to encroach upon the most rostral sector of the sensory ventral posterior nucleus (VPLa). VL thalamotomy significantly decreased tremor amplitude in all cases. Power dispersion was increased significantly so that it became similar to that of control subjects. Changes in power distribution indicate that thalamotomy selectively targeted PD tremor oscillations. Tremor detected during the MT task was also markedly decreased, becoming similar to that of controls. Patients also showed significant decrease in ERROR during MT. RAM duration and range were not significantly modified by the surgery, and patients' performance remained impaired compared to healthy control subjects. Collectively, these results suggest that lesions involving the presumed "cerebellar" and "pallidal" recipient sectors of the motor thalamus do not worsen bradykinesia, suggesting that neural circuits other than the pallido-thalamo-cortical loop may be involved in slowness of movement in PD. A review of alternate pathways is presented.

Unilateral stereotactic posteroventral globus pallidus internus pallidotomy for Parkinson's disease: surgical techniques and 2-year follow-up.

With the advent of levodopa (L-dopa) and the recognition of its striking effect on Parkinson's disease (PD), virtually all surgical procedures for PD ceased from the mid 1960s. However, there has been a resurgence of pallidotomy and other stereotactic procedures in the last two decades as physicians realized that most PD patients eventually face medical failure after long-term treatment with L-dopa. Nine PD patients, three men and six women, with an average age of 62 years and disease duration of 13 years underwent unilateral globus pallidus internus (GPi) pallidotomy contralateral to the side with marked akinetic symptoms and drug-induced dyskinesia. All patients were evaluated using the Unified Parkinson's disease Rating Scale (UPDRS) after drug withdrawal and while taking their optimal medical regimen, preoperatively and 6, 12, and 24 months after surgery. There was significant improvement in activities of daily living and motor subscores as well as total UPDRS score in the "off" state at the 2-year follow-up, which mainly resulted from improvement in contralateral bradykinesia and rigidity. Significant improvements in contralateral akinetic symptoms and drug-induced dyskinesia were also observed in the "on" state and were sustained for at least 2 years. Ipsilateral and axial symptoms were not altered by unilateral GPi pallidotomy. The complications of surgery were generally well tolerated. One patient had a small postoperative asymptomatic hemorrhage identified by routine follow-up magnetic resonance imaging. Another two patients developed temporary sexual disinhibition and auditory hallucination, respectively, which resolved spontaneously 2 weeks after surgery. The effect of pallidotomy for alleviation of akinetic parkinsonism is modest but significant, and continues to be effective for at least 2 years. Further analytical studies, especially the correlation of clinical effects and lesion locations, are important not only to provide direct feedback for surgeons to examine the technical accuracy and but also to facilitate understanding of the pathophysiology of PD.

Subthalamotomy for advanced Parkinson disease.

OBJECT: The aim of this study was to determine if subthalamotomy is effective in treating advanced Parkinson disease (PD). METHODS: The authors performed microelectrode mapping-guided stereotactic surgery on the subthalamic nucleus in eight patients with PD. Lesioning was performed using radiofrequency heat coagulation and confirmed with magnetic resonance imaging. Three patients who underwent unilateral and four with bilateral subthalamotomy were evaluated for up to 18 months according to the Unified PD Rating Scale (UPDRS). One patient who underwent unilateral subthalamotomy died 6 months postsurgery. At 3 months into the "off" period after surgery, there were significant improvements in contralateral bradykinesia (p < 0.0002), rigidity (p < 0.0001), tremor (p < 0.01), axial motor features (p < 0.02), gait (p < 0.03), postural stability (p < 0.03), total UPDRS scores (p < 0.03), and Schwab and England scores (p < 0.04). The benefits were sustained at 6, 12, and 18 months, except for the improvement in tremor. At 12 months into the "on" period, significant benefits were present for motor fluctuation (p < 0.04), on dyskinesia (p < 0.006), off duration (p < 0.05), total UPDRS score (p < 0.02), and contralateral tremor (p < 0.05). Benefits for motor fluctuation, off duration, and off-period tremor were lost after the 18-month follow-up period. The levodopa requirement was reduced by 66% for the unilateral and 38% for the bilaterally treated group. Bilateral subthalamotomy offered more benefits than did unilateral surgery for various parkinsonian features in both the on and off periods. Three patients suffered hemiballismus, two recovered spontaneously, and one died of aspiration pneumonia after discontinuation of levodopa. CONCLUSIONS: These findings indicate that subthalamotomy can ameliorate the cardinal symptoms of PD, reduce the dosage of levodopa, diminish complications of the drug therapy, and improve the quality of life.

Contribution of neurophysiological guidance to stereotactic posteroventral pallidotomy for Parkinson's disease.

The usefulness of microrecording guidance to adequately place pallidotomy lesions is not thoroughly accepted. We have analysed in 23 consecutive Parkinsonian patients the deviation of the first recording track (FRT), which was directed to the theoretical stereotactic target, from the sensorimotor area of the internal pallidum, the internal capsule and the center of the lesion. Standard stereotactic co-ordinates were calculated applying a digitized brain atlas adapted to neuro-imaging techniques. The first recording track (FRT) was located out of the sensorimotor area of the pallidum in 13 cases and out of the internal pallidum in 11 cases. In four of these cases the FRT was within the fibers of the internal capsule. The FRT was displaced posteriorly in 9 patients, anteriorly in 11, medially in 9 and laterally in 9. The mean deviation was 1.8 mm (+/- 1.5) in the medial-lateral axis, and 2.5 mm (+/- 1.9) in the antero-posterior plane. In none of the patients the center of the lesion was co-incident with the theoretical anatomical target. The center of the lesion presented a mean deviation from the theoretical anatomical target of 1,4 mm (+/- 1,1) in the medial-lateral, plane, and 2.5 mm (+/- 1.3) in the antero-posterior plane. In addition, 8 patients presented a deviation from the theoretical anatomical target of more than 3 mm in the antero-posterior plane (mean 4.2+/-0.7 mm) and 4 patients presented deviation in the medial-lateral plane of more than 3 mm (mean 3,4+/-0,2 mm). Lesion location was checked by magnetic resonance imaging. All patients improved to a similar extent to that previously reported by the other groups performing pallidotomy under neurophysiological guidance. At 3 months follow-up, pallidotomy ameliorated contralateral bradykinesia in the off condition by 41%, rigidity by 38%, tremor by 52% and dyskinesias by 92%. No major side effects were noted. We conclude that microrecording guidance is a useful tool for avoiding damage to adjacent structures and to precisely localize the sensorimotor area of the internal pallidum in order to obtain optimal clinical results.

High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases.

The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III-V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.

Bilateral posteroventral pallidotomy in advanced Parkinson's disease in three patients.

In this report, we describe the effect of staged bilateral posteroventral pallidotomy in three patients with advanced Parkinson's disease who were all of the young-onset type. Two patients had developed response fluctuations after the use of levodopa, with severe hypokinesia, painful dystonia, and rigidity in the "off" phase and violent dyskinesias in the "on" phase. One patient, in a continuous hypokinetic rigid state, was totally unresponsive to dopaminergic medication. All were at Hoehn and Yahr stage 5 in the "off" phase before surgery. After surgery, the hypokinetic state was reversed and dyskinesias were abolished in all patients. Hoehn and Yahr stages were 3 in the "off" phase postoperatively. Overall functional improvement was marked and lasting after follow-up for 7, 12, and 13 months, respectively. Complications were visual field deficit and transient central facial paresis, both in the same patient. Bilateral posteroventral pallidotomy can ameliorate response fluctuations, hypokinesia, rigidity, and painful dystonia in advanced Parkinson's disease.

Ventroposterolateral pallidotomy.

Recent laboratory experiments have produced increasing evidence that nigral-striatal dopamine deficiency causes an inhibitory hyperactivity in the medial globus pallidus (MGP), where it freezes the initiation of movement and thus causes bradykinesia, rigidity and tremor. Surgical lesions in the ventroposterolateral (VPL) pallidum in man not only improve the parkinsonian bradykinesia, but also the tremor, rigidity, and the L-dopa-induced dyskinesias disappear or diminish. The present study shows that VPL pallidotomy improves several psychomotor functions, such as walking speed and manual dexterity. Right-sided VPL thalamotomy also increases the speed and accuracy in verbal performance. Ventrolateral thalamotomy increases bradykinesia. The findings support the concept that the parkinsonian symptoms in man develop in the MGP. Intact pathways from MGP via thalamus to the premotor and motor cortex seem necessary for normal motor functioning. The author also discusses the mechanisms of pallidotomy and thalamotomy.