TIPO DE LA INVESTIGACIÓN
I.3 El Registro Privado y el Registro Público
The search identified 231 published efficacy reports on pallidotomy, of which fifteen met inclusion and exclusion criteria: one study was Level-I, two studies were Level-II and the remain- ing were Level III. A few other studies focusing on safety issues are also critiqued.
PREVENTION OF DISEASE PROGRESSION
No qualified studies were identified.
SYMPTOMATIC CONTROL OF
PARKINSONISM
Level-I Studies
De Bie and colleagues (1999)3 conducted a prospective, single
blind, multicenter, study of 37 patients that were randomized to either (1) unilateral pallidotomy, or (2) the best medical treatment. Patients assigned to surgery underwent macroelectrode stimula- tion guided pallidotomy. Lesion location and size were not veri- fied with microelectrode guidance or postoperative imaging. Pa- tient ages ranged from 44 to 73 years with a mean disease duration of approximately 16 years. Patients were followed for 6 months after surgical treatment. The mean Hoehn and Yahr stages were 4.0 in the “off phase” and 2.5 in the “on phase”. The dose of L- dopa ranged between 86 to 925 mg/day “dopa equivalents.” The primary outcome measure was improvement in the “off” motor exam of the UPDRS. In the pallidotomy group, the mean UPDRS motor score improved from a mean baseline rating of 47.0 to 32.5, whereas the control subjects had a mean baseline score of 52.5 and deteriorated to 56.6. Other assessments included the UPDRS 2 (activities of daily living ADL section), and Schwab and En- gland scales of daily living all showing a significant positive ef- fect of surgery compared to the controls. Nine of the nineteen pa- tients had adverse reactions, two with events that were considered by the author as major, and seven that were considered as minor. The major events in the perioperative period were dysarthria and depressed level of consciousness in one patient and psychosis in another. Four of the seven patients with mild adverse effects still had them at six-month follow-up, and, of the two with major events, one continued with dysphasia, drooling and postural instability
and the second with intermittent hallucinations and psychotic be- havior. This study had an overall quality rating score of 72%.
Level-II Studies
Perrine et al. (1998)4 studied 28 patients over one year who un-
derwent pallidotomy and compared them to 10 control patients, who qualified for surgery but did not desire it immediately. This study assessed neuropsychological morbidity as its primary focus but also collected motor data in the form of the UPDRS motor and ADL data in the two groups. The pallidotomy group showed a change in the mean motor scale from 33.2 at baseline to 10.0 at one year. The control group however deteriorated from a mean score of 27.1 to 31.6. For the ADL scores, the pallidotomy group improved from mean values of 17.4 to 6.6, whereas the control patients deteriorated from a mean score of 17.8 to 20.6. There was no distinction in ON and OFF scores in this report.
Young et al. (1998)5 studied 51 patients with medically refrac-
tory PD underwent stereotactic posteromedial pallidotomy for treat- ment of bradykinesia, rigidity, and L-DOPA-induced dyskinesias. Two comparison groups were examined: 29 patients whose pallidotomies were performed with the Leksell Gamma Knife; and 22 whose surgery involved the standard radiofrequency (RF) method. Clinical assessment as well as blinded ratings of Unified Parkinson’s Disease Rating Scale (UPDRS) scores were carried out pre- and postoperatively. Mean follow-up time was 20.6 months (range 6-48) and all except 4 patients were followed more than one year. Eighty-five percent of patients with dyskinesias were relieved of symptoms, regardless of whether the pallidotomies were performed with the Gamma Knife or radiofrequency methods. About 2/3 of the patients in both Gamma Knife and radiofrequency groups showed improvements in bradykinesia and rigidity, al- though when considered as a group neither the Gamma Knife nor the radiofrequency group showed statistically significant improve- ments in UPDRS scores. One patient in the Gamma Knife group (3.4%) developed a homonymous hemianopsia 9 months follow- ing treatment and 5 patients (27.7%) in the radiofrequency group became transiently confused postoperatively. This study is limited because raw data were not reported, but only percent changes and p values. Because of the similarity of outcomes with the two pro- cedures, the authors suggested however that Gamma Knife pallidotomy may be as effective as radiofrequency pallidotomy in controlling certain symptoms of PD.
Level-III Studies
Kondziolka et al. (1999)6 conducted an open label prospective
analysis of a consecutive series of 58 patients who underwent pallidotomy and were followed for up to 1 year. The mean age was 67 years with a disease duration of 13.3 years. The UPDRS in “on” and “off” periods was evaluated, and this study showed a significant improvement in the total OFF UPDRS score (mean 95.8 to 77.6). The predominant component responsible for the improve- ment was the motor section of the UPDRS, showing a mean change from 58.3 at baseline to 44.7 after surgery. Significant improve- ments were also noted for tremor, rigidity, bradykinesia, and con- tralateral dyskinesia. In the 21 patients who were evaluated after 1 year, improvements in dyskinesia and tremor were maintained. Adverse events were mild and occurred in 9% of the patients in- cluding dysarthria (4) and transient confusion (1).
Giller and colleagues (1998)7 reported experience with
pallidotomy and in a combined article on thalamotomies and
pallidotomies. The only pallidotomy procedure with at least 20 subjects was unilateral and in this group there were 49 subjects, of which 47 received extensive testing. Mean off UPDRS motor scores improved from 42.0 preoperatively to 29.4 at six months (N=27) and to 24.9 at 12 months (N=12). Three patients suffered hemiparesis and one patient had cognitive deficits, infection or confusion. The authors reported that the speech complications were higher in patients undergoing bilateral procedures. Eight patients out of the original 55 patients developed speech problems postop- eratively. All but one had had bilateral surgery and in these seven, four had serious speech problems. In the one unilateral pallidotomy subject with speech problems, the severity of deficit was mild.
Shannon et al. (1998)8 studied 26 patients undergoing
pallidotomy, of which 22 patients had outcome measures reported 6 months post-treatment. The primary outcome measure was UPDRS “off phase” scores which improved at 6 months from mean 49.0 at baseline to 41.7. Contralateral parkinsonian signs improved when the investigators analyzed the collapsed components that referred to that side (mean 16.3 at baseline vs. 12.1 at six months). “On” ratings did not change. Significant complications included one death, three superficial frontal lobe hemorrhages, two signifi- cant cognitive and personality changes, one with subfluent apha- sia, three with signs of frontal lobe dysfunction, and one report of hemiparesis.
Samuel et al. (1998)9 reported the results from 26 patients who
underwent unilateral pallidotomy. Twenty-two subjects were as- sessed for UPDRS motor score improvement (two patients died and two patients were unable to carry out the UPDRS assessment). Following the CAPIT-recommended protocol for examining patients “on/off”over 3 months after sugery, the investigators found that the UPDRS total Off motor score improved from a baseline median score of 53.5 to 42.5. Most effects concerned the contralat- eral side with improvements in rigidity, tremor and bradykinesia. Contralateral dyskinesia also improved. Two patients had fatal complications, one cerebral hemorrhage and one hemorrhagic in- farction. Of the remaining subjects, 15% experienced major com- plications including contralateral facial weakness, contralateral motor hemineglect, severe dysarthria and dysphagia and minor complications including visual field defect in 8%, dysarthria in 27%, dysphagia in 19%, and hypophonia in 15%.
Kishore et al. (1997)10 reported on 23 patients who underwent
unilateral pallidotomy; twenty had six-month follow-up and 11 were evaluated after 1 year. Using the CAPIT protocol recommen- dations for patient evaluation, they studied patients in ON and OFF states, and found that OFF UPDRS total score significantly im- proved from a mean score of 47.3 at baseline to 30.0 (N=20) and 25.5 (N=11). The OFF ADL scores likewise showed progressive improvement from mean baseline function of 23.6 to 17.7 at six months and 17.2 at one year. The results were most prominent for the contralateral side. Adverse effects included a delayed intrac- erebral hemorrhage and death 4%, transient hemiparesis and vi- sual field deficit 12.5% and facial paresis in 1 patient.
Krauss et al. (1997)11 reported six-month data on 36 patients
with advanced PD undergoing unilateral pallidotomy and focused on correlations between lesion size and clinical outcome. They documented significant improvements in motor UPDRS OFF scores (mean 58.1 vs. 33.0), and OFF ADL scores (mean 31.4 vs. 18.2). There was no clear association with lesion size and clinical outcome. Six patients had transient adverse effects from the sur- gery and two infarctions were documented on MR.
Lang et al. (1997)12 described unilateral pallidotomy in 40 pa-
tients followed for 1 to 2 years. Thirty-nine were examined at six months, 27 at one year and 11 at two years. The primary outcome measure was UPDRS total score with secondary outcome mea- sures, Schwab & England, ADL and UPDRS subscores for tremor, rigidity, bradykinesia, postural instability, gait disorders, and dyskinesias. There was a significant improvement in “off” period UPDRS from mean 68.8 to 47.9 at six months and “on” UPDRS from mean 27.6 to 23.6. The Schwab and England scores improved from a mean OFF rating of 39% to 65% and a mean ON rating from 78.2 to 85.2 at six months. All “off” features of parkinsonism improved significantly on the side contralateral to surgery. Ipsilat- eral tremor and rigidity were not changed, but ipsilateral bradyki- nesia improved. Twenty-five patients had adverse effects; most of these were mild, but many of them persisted. These included weak- ness in two subjects, dysarthria in three, dysphagia in two and impaired memory or concentration faculties in three. There was one intracerebral hemorrhage.
Kazumata et al. (1997)13 correlated clinical motor outcome mea-
sures with functional brain imaging using 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in 22 patients with advanced PD receiving stereotaxic unilateral pallidotomy. The clinical outcome following pallidotomy was assessed at three months after surgery and also correlated with intraoperative mea- sures of spontaneous pallidal single-unit activity as well as post- operative MRI measurements of lesion volume and location. They found that unilateral pallidotomy produced clinical improvement in off-state CAPIT scores for the contralateral limbs (mean preop- erative OFF UPDRS 75.3 vs. mean 52.8 after surgery). On the ipsilateral side to surgery, scores also improved from mean OFF UPDRS preoperatively of 59.8 to mean 49.9 after surgery. Clini- cal outcome following surgery correlated significantly with pre- operative measures of CAPIT score, change with L-dopa admin- istration and with preoperative FDG/PET measurements of lenti- form glucose metabolism. Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. The authors concluded that preoperative measurements of lentiform glucose metabolism and L-dopa responsiveness may be useful indicators of motor improvement following pallidotomy.
Melnick et al. (1996)14 investigated the effects of pallidotomy
on postural reactions and other motor parkinsonian deficits. They compared performance by 29 PD patients before and after pallidotomy on tests of balance and function. They assessed the UPDRS, activities of daily living and motor subscales (parts II and III) and posturography before and 3 to 6 months after surgery with patients in the practically defined off state (medication with- held for at least 12 hours). They found a significant improvement in UPDRS motor subscale score after pallidotomy (before surgery, mean 52.4 vs. mean 43.9 after surgery ). There were no significant changes in the UPDRS activities of daily living subscale or aver- age stability scores when the group was examined as a whole. Examination of individual data revealed that 9 (56%) of 16 pa- tients who could stand independently before surgery showed im- provement in either the number of falls or the average stability score. No patient who was unable to stand independently before surgery was able to stand independently after it. They concluded that pallidotomy helped improve overall motor function in patients with parkinsonism and, for some patients, also improved postural stability.
S131
Movement Disorders, Vol. 17, Suppl. 4, 2002
dergoing MRI/electrophysiologically-guided medial pallidotomy. The mean age of patients was 65.5 years (median 66.5). Pallidotomy significantly improved motor function in both “on” and “off” states as measured by Unified Parkinson’s Disease Rat- ing Scale (UPDRS) motor scores and timed tests (Purdue peg- board and counter tapping) in the arm contralateral to surgery 3 months postoperatively. The total UPDRS score improved from mean 82.6 to 63.8. Patients also improved in the UPDRS activity of daily living and complications of therapy scoring. There was also a reduction in L-dopa-induced dyskinesias. Six of 11 patients who could not walk in an “off” state prior to surgery could do so postoperatively. The improvements occurred similarly in patients greater than (n = 11) or less than 65 years (n = 9) at surgery. Neu- ropsychological measures indicated that although the majority of cognitive function remained unchanged in right-handed PD pa- tients following dominant (left) hemisphere pallidotomy, mild spe- cific declines in word generation occurred in some patients. No significant operative complications developed. The findings of this study suggest that unilateral pallidotomy is safe and associated with improved motor functioning in elderly as well as younger PD patients experiencing significant disability despite optimal medi- cal therapy.
PREVENTION OF MOTOR COMPLICATIONS
No qualified studies were identified.
CONTROL OF MOTOR COMPLICATIONS
Of all results related to pallidotomy, the most consistent and clinically significant contribution has been the control of dyskinesias, especially contralateral to the side of the lesion. Kondziolka6 found contralateral dyskinesia dropped from mean
scores of 1.5 to 0.9 by nine months with persistence of effects at 18 months in the 21 patients followed for that duration. In Giller’s7
report using a 0-3 severity rating system, they found dyskinesia dropped from a mean 5.5 preoperatively to 2.1 at two weeks and remained improved. The scores were even more dramatic when only the contralateral dyskinesia ratings were considered (2.5 to 0.2). Shannon found similar improvements using the UPDRS-based dyskinesia ratings, finding significant improvements in both dura- tion score (mean baseline 2.2 vs. 1.0 at six months) and severity score (mean 1.5 vs. 0.5). Kishore10 found contralateral dyskinesia
significantly improved (mean score 7.5 before surgery vs. 3.8 at six months and 4.3 at one year). Krauss11 assessed percent of the
waking day with dyskinesia and documented six-month improve- ment with a change score from baseline man 37.5 to 18.1. Uitti and colleagues15 found the mean Goetz Dyskinesia score improved
from mean 1.4 to mean 1.2 and the Mayo Dyskinesia score from mean 11.6 to mean 7.6 after surgery. “On” time, obtained in nine patients only, improved from a mean 4.1 hours before surgery to mean 8.8 hours after surgery.