Parkinson Disease - Top 25

September 2010, Volume 113, Issue 3

Parkinson Disease: Top 25 Cited Articles

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Pallidotomy for Parkinson disease: a review of contemporary literature

Ahmed Alkhani and Andres M. Lozano

Object. The authors conducted an evidence-based review of contemporary published articles on pallidotomy to obtain an appraisal of this procedure in the treatment of Parkinson disease (PD).

Methods. A search of the Pubmed database performed using the key word “pallidotomy” yielded 263 articles cited between January 1, 1992, and July 1, 1999. Articles that included original, nonduplicated descriptions of patients with PD treated with radiofrequency pallidotomy were selected.

In 85 articles identified for critical review, 1959 patients with PD underwent pallidotomies at 40 centers in 12 countries. There were 1735 unilateral (88.6%) and 224 bilateral procedures (11.4%). The mean age of the patients was 61.4 ± 3.6 years and the mean duration of PD symptoms in these patients was 12.3 ± 1.9 years. Microelectrode recordings were used in 46.2% of cases. Outcomes were objectively documented using the Unified Parkinson Disease Rating Scale (UPDRS) in 501 (25.6%) of the cases at 6 months and in 218 (11.1%) of the cases at 1 year. There was a consensus on the benefits of pallidotomy for off period motor function and on period, drug-induced dyskinesias, with variations in the extent of symptomatic benefit across studies. At the 1-year assessment, the mean improvement in the UPDRS motor score during off periods was 45.3% and the mean improvement in contralateral dyskinesias during on periods was 86.4%. The overall mortality rate was 0.4% and the rate of persistent adverse effects was estimated at 14%. Major adverse events, including intracerebral hemorrhages, contralateral weakness, and visual field defects, occurred in 5.3% of patients reported.

Conclusions. Unilateral pallidotomy is effective and relatively safe in the treatment of PD; however, limited data are available on the long-term outcome of this procedure.

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Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance

Boulos-Paul Bejjani, Didier Dormont, Bernard Pidoux, Jérôme Yelnik, Philippe Damier, Isabelle Arnulf, Anne-Marie Bonnet, Claude Marsault, Yves Agid, Jacques Philippon, and Philippe Cornu

Object. Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance.

Methods. Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure—posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately.

Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted.

Conclusions. At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the “off” and “on” medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopainduced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.

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Pallidal stimulation for generalized dystonia

Report of three cases

Volker M. Tronnier and Wolfgang Fogel

✓ Pallidal stereotactic surgery is a well-accepted treatment alternative for Parkinson's disease. Another indication for this procedure is medically refractory dystonia, especially generalized dystonia with abnormal axial and extremity movements and postures. Improvement of dystonia after pallidotomy has been reported in several recent papers. In this report the authors describe three patients with generalized dystonia (two primary, one secondary) and their improvement after bilateral pallidal stimulation at follow-up times of between 6 and 18 months.

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Bilateral simultaneous posteroventral pallidotomy for the treatment of Parkinson's disease: neuropsychological and neurological side effects

Report of four cases and review of the literature

Joseph Ghika, Florence Ghika-Schmid, Heinz Fankhauser, Gil Assal, François Vingerhoets, Alberto Albanese, Julien Bogousslavsky, and Jacques Favre

✓ The authors report the underestimated cognitive, mood, and behavioral complications in patients who have undergone bilateral contemporaneous pallidotomy, as seen in their early experience with functional neurosurgery for Parkinson's disease (PD) that is accompanied by severe motor fluctuations before pallidal stimulation.

Four patients, not suffering from dementia, with advanced (Hoehn and Yahr Stages III–IV), medically untreatable PD featuring severe “on—off” fluctuations underwent bilateral contemporaneous posteroventral pallidotomy (PVP). All patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) protocol without positron emission tomography scans but with additional neuropsychological cognitive, mood, and behavior testing.

For the first 3 to 6 months postoperatively, all patients showed a mean improvement of motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS), in the best “on” (21%) and worst “off (40%) UPDRS III motor subscale, a mean 30% improvement in the UPDRS II activities of daily living (ADL) subscore, and 60% on the UPDRS IV complications of treatment subscale. Dyskinesia disappeared almost completely, and the mean daily duration of the off time was reduced by an average of 60%. Despite these good results in the CAPIT scores, one patient experienced a partially regressive corticobulbar syndrome with dysphagia, dysarthria, and increased drooling. No emotional lability was found in this patient, but he did demonstrate severe bilateral postoperative pretarsal blepharospasm (apraxia of eyelid opening), which interfered with walking and which required treatment with high-dose subcutaneous injections of botulinum toxin. No patient showed visual field defects or hemiparesis, but postoperative depression, changes in personality, behavior, and executive functions were seen in two individuals. Postoperative abulia was reported by the family of one patient, who lost his preoperative aggressiveness and drive in terms of ADL, speech, business, family life, and hobbies, and became more sleepy and fatigued. One patient reported postoperative mental automatisms, such as compulsive mental counting, and circular thoughts and reasoning during off phases; postoperative depression was found in two patients. However, none of the patients demonstrated these symptoms during intraoperative microelectrode stimulation. These findings are compatible with previous reports on bilateral pallidal lesions. A progressive lowering of UPDRS subscores was seen after 12 months, consistent with the progression of the disease.

Bilateral simultaneous pallidotomy may be followed by emotional, behavioral, and cognitive deficits such as depression, obsessive—compulsive disorders, and loss of psychic autoactivation—abulia, as well as disabling corticobulbar dysfunction and apraxia of eyelid opening, in addition to previously described motor and visual field deficits, which make this surgery undesirable even though significant improvement in motor deficits can be achieved.

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Thalamic deep brain stimulation for the treatment of head, voice, and bilateral limb tremor

Jamal M. Taha, Michele A. Janszen, and Jacques Favre

Object. In published series of patients who undergo deep brain stimulation (DBS) of the thalamus the effects of unilateral stimulation on contralateral limb tremor have been reported. The authors detail their experience with bilateral thalamic DBS in the treatment of head, voice, and bilateral limb tremor and compare it with earlier studies of unilateral stimulation.

Methods. Twenty-three patients (six with Parkinson's disease, 15 with essential tremor, and two with multiple sclerosis) underwent 19 bilateral DBS procedures (nine staged, 10 simultaneous) and four procedures contralateral to thalamotomy to control tremor of the head in 10, voice in seven, and limbs in 20 patients. Limb tremor improvement was graded as follows: 4, no tremor; 3, stress-induced tremor; 2, functional improvement; 1, no functional improvement; and 0, persistent tremor. Improvement of head or voice tremor was graded as follows: 4, greater than 75%; 3, between 50% and 75%; 2, between 25% and 50%; 1, less than 25%; and 0, no improvement. The mean follow-up period was 10 months.

Twenty-two patients (96%) demonstrated improved tremor at the last follow-up review. Of 20 patients with bilateral limb tremor, 17 (85%) improved to Grades 3 and 4, two patients (10%) with multiple sclerosis improved to Grade 2, and one (5%) exhibited tremor recurrence 8 months later. Nine (90%) of 10 patients with severe head tremor improved to Grades 4 or 3. Six (86%) of seven patients with voice tremor improved to Grade 3. Seven patients (30%) developed dysarthria, and seven (30%) developed disequilibrium; symptoms reversed in the majority of patients after the stimulation parameters were changed. One patient (4%) developed mild memory decline. There were no deaths.

Conclusions. The following findings are reported: 1) bilateral thalamic DBS and stimulation contralateral to thalamotomy are safe; 2) staging the procedure does not reduce the risk of dysarthria or gait disequilibrium; and 3) head and voice tremor are primary indications for bilateral DBS.

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Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review

Joseph Ghika, Jean-Guy Villemure, Heinz Fankhauser, Jacques Favre, Gil Assal, and Florence Ghika-Schmid

Object. The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease.

Methods. Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image—guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations.

Six patients with a mean age of 55 years (mean 42–67 years), a mean duration of disease of 15.5 years (range 12–21 years), a mean “on/off” Hoehn and Yahr stage score of 3/4.2 (range 3–5), and a mean “off” time of 40% (range 20–50%) underwent bilateral contemporaneous pallidal DBS, with a minimum follow-up period lasting 24 months (range 24–30 months). The mean dose of levodopa in these patients could not be changed significantly after the procedure and pergolide was added after 12 months in five patients because of recurring fluctuations despite adjustments in stimulation parameters. All but two patients had no fluctuations until 9 months. Two of the patients reported barely perceptible fluctuations at 12 months and two at 15 months; however, two patients remain without fluctuations at 2 years. The mean improvements in the UPDRS motor score in the off time and the activities of daily living (ADL) score were more than 50%; the mean off time decreased from 40 to 10%, and the mean dyskinesia and complication of treatment scores were reduced to one-third until pergolide was introduced at 12 months. No significant improvement in “on” scores was observed. A slight worsening after 1 year was observed and three patients developed levodopa- and stimulation-resistant gait ignition failure and minimal fluctuations at 1 year. Side effects, which were controlled by modulation of stimulation, included dysarthria, dystonia, and confusion.

Conclusions. Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations. Major improvements in motor score, ADL score, and off time persisted beyond 2 years after the operation, but signs of decreased efficacy started to be seen after 12 months.

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Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease

Jerrold L. Vitek, Roy A. E. Bakay, Takao Hashimoto, Yoshiki Kaneoke, Klaus Mewes, Jian Yu Zhang, David Rye, Philip Starr, Mark Baron, Robert Turner, and Mahlon R. Delong

Object. The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy.

Methods. Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by “form fitting” the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies.

Conclusions. These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

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

Christian Gross, Alain Rougier, Dominique Guehl, Thomas Boraud, Jean Julien, and Bernard Bioulac

✓ 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.

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Microelectrode-guided posteroventral medial radiofrequency pallidotomy for Parkinson's disease

Oleg Kopyov, Deane Jacques, Christopher Duma, Galen Buckwalter, Alex Kopyov, Abraham Lieberman, and Brian Copcutt

✓ The outcome of radiofrequency-guided posteroventral medial pallidotomy was investigated in 29 patients with recalcitrant Parkinson's disease. Extracellular recordings were obtained in the target region to differentiate the internal from the external globus pallidus, and distinct waveforms were recorded in each region. Stimulation of the target site further verified the lesion location. Of the 29 patients treated during the course of 1 year, none showed any adverse side effects (such as hemianopsia or hemiparesis) from the procedure. Significant and immediate improvement in motor involvement (dyskinesia, rigidity, dystonia, freezing, and tremor) was observed as measured by the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Patients experienced improvements in their condition as measured on a self-rating scale, and their ability to perform the activities of daily living was also significantly improved. Although the onset and duration of the effect of a single dose of levodopa did not change, the number of hours in an “off” state of dyskinesia per day was significantly decreased. These results provide further evidence, in a large group of patients, that posteroventral medial pallidotomy results in significant control of the motor symptoms of Parkinson's disease with a minimum of undesirable side effects.

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Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis

Joachim K. Krauss, J. Michael Desaloms, Eugene C. Lai, David E. King, Joseph Jankovic, and Robert G. Grossman

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid-shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/− 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/− 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia “off” scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.