Thalamotomy, pallidotomy and subthalamotomy in the management of Parkinson’s disease

html xmlns=”http://www.w3.org/1999/xhtml” xmlns:mml=”http://www.w3.org/1998/Math/MathML” xmlns:epub=”http://www.idpf.org/2007/ops”>


Chapter 17 Thalamotomy, pallidotomy and subthalamotomy in the management of Parkinson’s disease


Malco Rossi, Daniel Cerquetti, Jorge Mandolesi and Marcelo Merello



Introduction


Surgery for movement disorders, especially for “athetosis” and parkinsonism, was introduced mainly by Leriche, Foerster, Putnam, Meyers and Bucy at the end of the 19th century and beginning of the 20th. They included posterior rhizotomy, cortical resection of the premotor area, pedunculotomy, cordotomy, anterior choroidal artery ligation and ablation of subcortical areas, such as the caudate and oral parts of the putamen and globus pallidus. Clinical benefits on tremor and rigidity were observed in approximately half of the patients, but aphasia, focal epilepsy, transient hemiparesis and permanent hemiplegia were frequent side effects, reaching a mean morbidity and mortality of 50 and 15%, respectively, which was excessively high for an elective surgery. These open functional procedures were soon abandoned or limited to severe cases [1].


In 1947, Spiegel and Wycis carried out the first effective stereotactic surgery for intractable pain, psychiatric disorders and epilepsy. In 1953, they published a series of cases of pallidal and ansa lenticularis lesions, known as “pallidoansotomy,” in 50 parkinsonian patients, improving tremor in 78% but inducing permanent hemiplegia in 4% of patients and with a mortality of 3% [2]. Posteroventral pallidotomy was introduced and replicated extensively afterwards by Leksell’s group, who found better outcomes with lesions in the posteroventral portion of the globus pallidus, relieving tremor and rigidity in up to 90% of the cases, with minimal neurological deficits and mortality [3].


At the same time, ventrolateral thalamotomy was introduced by Hassler and Riechert, and Cooper extended this procedure with chemical lesions [4, 5]. Thalamotomy became rapidly the preferred surgical strategy for Parkinson’s disease (PD), because of a higher effectiveness for tremor and an equal response to rigidity, with fewer complications than pallidotomy [6]. However, bradykinesia relief received little attention at that time. Lesions in the posterior part of the ventrolateral thalamus (ventral oral posterior [VOP] and ventral intermediate nucleus [VIM]) were effective for tremor, and lesions in the anterior part (ventro oralis anterior [VOA]) were better for rigidity and levodopa (l-DOPA)-induced dyskinesias. Lesions in the subthalamic region (Forel’s field H and zona incerta) were published a few years later than pallidotomy and thalamotomy, with comparable results, but were then abandoned for a long time [7].


In the late 1960s and early 1970s, standard ablative procedures were cataclysmically relegated by the introduction of levodopa as an efficient and easily administered dopamine replacement therapy for motor features of PD. Thalamotomy for severe and levodopa-refractory tremor was still performed occasionally for medication-refractory tremor. By that time, more than 37,000 stereotactic procedures had been achieved, mostly for PD and with a marked decline in morbidity and mortality (approximately 10 and 1–5%, respectively) in comparison with open functional procedures. Surgical therapy for PD was clearly refined [1].


However, some circumstances led ablative procedures by lesioning to regain their place in the treatment of motor symptoms of PD. The most important one was the development of disabling motor fluctuations and dyskinesias after 5–10 years of chronic levodopa use. Furthermore, there have been important advances in the understanding of basal ganglia pathophysiology and the mechanisms underlying the causes of parkinsonism, in addition to improvements in stereotactic techniques with CT and MRI imaging and the refinement of neurophysiological mapping with microelectrode recordings. Finally, modifications in the pallidum target to the medial posteroventral portion (globus pallidus internus [GPi]) led to a significant effect on bradykinesia. The pioneering work of Laitinen revitalized pallidotomy [8]. In the 1990s, unilateral posteroventral pallidotomy was the most common surgical procedure for PD and was soon followed by experimental results on subthalamotomy [9], which led to the development of deep-brain stimulation (DBS).


Since bilateral lesions were associated with a higher incidence of side effects, such as speech problems, dysphagia and cognitive impairment [10], the development of DBS pioneered by the French group of Grenoble replaced ablative procedures at most of the centers, due to its reversibility, adjustability and lower side effects in bilateral procedures [11]. However, DBS is not exempt from complications, such as electrode misplacement, infection, hardware failures and improper device programming, and in many cases, ablative procedures are still a valid option as an alternative to DBS therapy. In this chapter, we will discuss the advantages and disadvantages of ablative procedures and the rationale for still considering them as a useful therapeutic tool within the surgical armamentarium for treatment of movement disorders.



Indications


Stereotactic functional neurosurgery is mostly indicated for PD patients with medication-induced complications despite best medical treatment. As mentioned above, DBS has become the preferred surgical treatment due to several advantages over ablative surgery, such as programmability and reversibility.


Despite the usefulness of DBS, ablative surgery for PD treatment should not become underestimated, since there remain several situations where thalamotomy, pallidotomy or subthalamotomy may provide an alternative option to. Low financial position or absence of health insurance able to cover the cost of devices, inability or distant access to frequent follow-up care and programming, poor commitment to DBS programming by the patient and family, allergic reactions to or rejection of implanted materials, infection or scarring caused by system parts, immunocompromised status that increases risk of infections (e.g CD4 counts below 200/μl or high human immunodeficiency virus load) and lack of expertise in DBS management at small centers are some of the situations where ablative surgery might be preferred over DBS [12]. Ablative surgery may also be chosen after failure of DBS therapy due to misplacement of electrodes, electric malfunctioning, defective contacts, wiring fractures, damaged insulation, mechanic aggression to system parts during or after surgery, improper implant setting, anchoring problems, loose contact screws, current leakage due to blood, fluids or debris in connectors, lead overheating after MRI, lack of tolerance to stimulation or inadmissible side effects, and loss of efficacy of DBS [13, 14]. In addition, some particular indications and novel techniques for noninvasive ablative procedures on certain targets (gamma knife radiosurgery and high-intensity focused ultrasound) may enlarge the possibilities of the standard radiofrequency thermolesion, although they remain at an experimental level [15–17].


As a rescue option in certain DBS therapy-failure cases, a limited thermolesion could also be performed through the DBS electrodes before explanting them [18]. However, this indication should be carefully evaluated, as DBS electrodes are not designed to be able to transport radiofrequency power, or to tolerate overheating. Special care should be taken, and intervention of a multidisciplinary professional team is advised. As DBS electrodes do not have a temperature sensor, it is not possible to directly measure tip overheating, and temperature at the lesion site during radiofrequency power injection should be estimated very carefully. Serious injuries to the patient might be caused using these nonstandardized and nonapproved techniques.


The usefulness of thalamotomy for medically intractable tremor or tremor-predominant PD has been well established [19]. However, as will be further described in detail, the subthalamic nucleus (STN) or globus pallidus are usually preferred as the target because of offering additional improvements in bradykinesia and rigidity.


Surgery should be indicated by a specialist in movement disorders, discussed and consented properly with a multidisciplinary team about the benefits, risks, type of surgery and target, and performed in specialized centers after a realistic discussion with the patient and his or her family to avoid or minimize false expectations.



Patient selection


One of the most critical factors for a favorable outcome is appropriate patient selection. The vast experience accumulated over the past years has permitted the development of clinical inclusion and exclusion criteria to select the most adequate patients to undergo surgery. A detailed description will be found in other chapters of this book.


A comprehensive and standardized assessment should follow a battery of timed motor and neuropsychological tests named The Core Assessment Program for Surgical Interventional Therapies in Parkinson’s disease (CAPSIT-PD) recommendations, which includes “on” and “off” evaluation of Unified Parkinson’s Disease Rating Scale (UPDRS) scores, dyskinesias types, severity and duration, an “on”/“off” home diary, quality-of-life scales and a neuropsychological evaluation for cognition and mood [20]. Nonmotor symptoms should also be addressed.


In brief, the ideal PD candidate would be one with at least 5 years of disease duration, with an excellent response to levodopa but marked bradykinesia; severe “off” states; troublesome medication-resistant tremor or disabling dyskinesias during the “on” state, despite best medical treatment; no or minimal axial compromise, dysarthria or nonmotor features, specially cognition and behavior; preferably younger than 75 years old; no comorbidities; a normal MRI; and a supportive family. Such an ideal profile is hard to find, and most patients do not fit all of these criteria. Currently, the mean disease duration of those patients undergoing surgery is 12 years, but recent studies suggest that surgery could be used at early stages of the disease, during the first 3 years after the development of motor fluctuations [21, 22].



Surgical procedure



Patient preparation


Although the approach may differ between centers, in most cases ablative procedures are performed with the patient being awake. To prevent the development of drug-induced dyskinesias and allow parkinsonian motor signs to be maximized during intraoperative procedure and neurological assessments, all parkinsonian medication should be stopped the previous night.



Target planification


CT- and MRI-based stereotactic techniques have become the standard techniques for target planning. They determine stereotactic coordinates according to target definitions, trajectory planning, anatomic landmarks, safety regions and other surgical concerns [23, 24]. Specific software performs image fusion and tridimensional reconstruction.



Target confirmation


Some techniques are commonly used to confirm anatomical structures and functional regions, such as microelectrode recording (MER), which is widely used and is employed to register extracellular activity. This is very useful in helping to determine the somatosensory regions of the target and confirm the boundaries of the explored areas [25, 26]. By means of single or multiunit recognition of the registered neuronal activity, it is possible to determine with high accuracy the optimal region of the target to be operated on. One group reported that MER led to targeting changes in 98% of 132 consecutive pallidotomies, and in 12% of these cases, the MER-refined target was more than 4 mm from the original, MRI-guided site [27]. Other advantages of MER are decreased lesion size and side effects, which together enhance the results of surgery [26]. Additionally, MER allows neuronal discharge recording for research purposes. Nonetheless, a critical review of the literature in 1999 found a higher rate of severe complications, such as hemorrhage and mortality, when microelectrodes were used, in both lesion and DBS surgeries, without increasing the accuracy of target localization and lesion size, or improving clinical outcome, which was also found in two meta-analysis [28, 29]. Another meta-analysis showed that intracranial hemorrhage risk increased from 0.25 ± 0.2 without MER to 1.3 ± 0.4 when MER was used, and this might be explained by an increased number of electrode trajectories and/or by injuries caused by the sharper tip of the microelectrodes [30]. However, 85% of the pallidotomies conducted in a large study were performed with only one or two trajectories, which minimized this risk [27]. Randomized trials may be necessary to clarify these issues.


Despite the benefits offered by MER, there are some controversies concerning the use of this technique [29, 31]. Other centers prefer macroelectrode-based mapping. According to the electrode characteristics, different methods may be employed. While some groups rely only on neuroimaging techniques combined with electrical macrostimulation of the target area [32, 33], others use macro-electrodes for impedance recording to differentiate between gray matter, white matter and cerebrospinal fluid (CSF) space. In addition, macrostimulation and lesioning may be carried out with the same macroelectrode. Additionally, local field potential (LFP) recording can be helpful as an additional tool to map the trajectory toward the optimal target region [34]. Sometimes, specific LFP recording electrodes are used, but it is very common to use DBS electrodes to register these potentials [35]. However, these last devices are not used during ablative procedures.


The development of other techniques that provide additional clinical information to the electrophysiological recording may also help in improving the outcome of patients undergoing ablative surgery, such as the intraoperative apomorphine test to check lesion efficacy on dyskinesias [36].



Lesioning technique


Radiofrequency thermolesion is the preferred method for the ablative procedure. Electrical macrostimulation through the lesion electrode tip is generally applied at various frequency rates and intensities (usually 2, 50, 150 and 300 Hz with pulse durations ranging from 100 to 300 ms and currents from 0.5 to 10 mA or voltages from 0.5 to 5 V, depending on the electrode specifications), while looking for either beneficial or deleterious effects. Once macrostimulation has been applied and the target finally approved to undergo a lesion procedure, a transient and reversible intervention is usually performed before delivering the radiofrequency energy necessary to overheat the electrode tip and produce a permanent tissue lesion. This temporary lesion is commonly implemented by controlling the tip temperature not to exceed 41–42 °C for 30–60 s and allows a realistic simulation of what the ablation will perform in that place. Afterwards, neurological and functional assessments are carried out and, if the patient response was satisfactory, the permanent lesion protocol is executed. The electrode tip temperature is then raised and electronically controlled up to 75–80 °C for 60–90 s, and by using different tip configurations (usually 0.7–2.1 mm diameter and 2–10 mm tip exposure), lesions of various extensions and volumes are produced in the surrounding tissue. The size and shape of the lesion volume will be directly related to the tip temperature, elapsed time during energy injection and tip configuration. Different groups use their own lesion protocol in order to “shape” the desired ablated volume. According to the surgical plan, it is common practice to perform several lesions in the mapped area, thus enlarging single lesion volumes produced by each procedure up to the desired ablative therapy. Several lesions can be done throughout a single tract, or single lesions in different tracts, or a combination of both.


While producing the lesion, potential side effects such as neurological and clinical manifestations are carefully examined. The feasibility of performing an additional lesion, if needed, will greatly depend on the clinical response to the previous lesion. Bilateral ablations can be conducted during the same surgical procedure or in two stages, after a few days, weeks or months, according to the experience of different centers. Some centers submit patients to control CT scans and/or MRI imaging right after surgery for safety purposes (e.g. hemorrhages, CSF loss, pneumocephalus, lesion misplacement) Alternatively, between 48h and 3 months postoperatively, MRI can be performed to confirm lesion placement and volume [10, 37].



Outcomes


Standardization of surgical procedures and clinical evaluations prior to and after surgery are necessary in order to compare outcomes across different surgical targets and techniques, such as lesions or DBS. Unfortunately, only a few studies have been methodologically comparable or were controlled and randomized, and comparable efficacy within ablative procedures and between them and DBS is still a matter of debate.



Thalamotomy


Thalamotomy produces improvements in PD patients with drug-resistant tremor when VIM is used as the target and has also an antidyskinetic effect by lesioning VOA and VOP. In some cases, it reduces rigidity, but it has no (or depreciable) effect on bradykinesia or postural instability and gait disability [38, 39]. A retrospective study analyzed the outcome of 42 PD patients (of whom two underwent bilateral surgery) with a mean follow-up of 52 months and found that 86% of the patients had resolution of or moderate-to-marked improvement in their contralateral tremor, with a concomitant improvement in function. None experienced tremor recurrence. The mean daily dose of levodopa was slightly reduced by approximately 138mg at a mean of 53.4 months after thalamotomy. Five patients experienced preoperative levodopa-induced dyskinesias, which were considerably improved independently of the reduction in levodopa intake [19]. This positive effect on dyskinesias was reported previously in all 13 PD patients operated on in one study, especially those with Vo-complex lesions [39]. A summary of a large series reported improvement of tremor in 80–90% of the patients and functional improvement in 30–50%. Tremor amplitude normalizes after thalamotomy, from an average of 10 mm pre-surgery to less than 0.5 mm after the surgical procedure, but tremor characteristics in the frequency domain do not regain normal values [40, 41].


In addition to motor symptoms, unilateral thalamotomy improves quality of life according to the 36-Item Short Form Health Survey (SF-36) and 39-item Parkinson’s Disease Questionnaire (PDQ-39) in general areas and also in ones specific to PD, such as self-ratings of stigma and bodily discomfort [42].


A second thalamotomy, contralateral to the initial side, has been indicated after a mean interval of 56 months because of deterioration of activities of daily living (ADLs) due to the progression of the symptoms on the nontreated side. In a study, five out of nine patients benefitted from this staged bilateral procedure. However, as will be mentioned below, bilateral thalamotomy results in a prohibitively high rate of cognitive and speech problems, preventing its use in PD patients [19, 38, 43].


A randomized study compared the efficacy of unilateral thalamotomy (23 PD patients) versus unilateral or bilateral thalamic DBS (22 PD patients) for the treatment of drug-resistant tremor [44]. The primary outcome measure was the change in functional abilities as measured by the Frenchay Activities Index, which assesses 15 ADLs, such as domestic tasks, leisure or work-related activities, and other activities. An increase of 4 points in the score indicates an improvement in the patient’s ability to perform at least two of these activities and an increase of 5 points indicates a clinically relevant improvement in the ability to perform ADLs. Secondary outcome measures were the severity of tremor, the number of adverse effects and patients’ assessment of the outcome. The difference between groups in the Frenchay Activities Index at 6 months was 4.7 points (95% confidence interval [CI]: 1.2–8.0; P < 0.05) in favor of DBS and 7.0 points (95% CI: 2.4–11.6; P < 0.05) after 5 years. Tremor suppression was achieved irrespective of age, disease duration and baseline disease severity. In those patients with bilateral tremor who underwent contralateral electrode implantation after 6 months, functional outcome was better at long-term follow-up than in those who did not undergo contralateral surgery but was not quite as good as in those who underwent bilateral stimulation. Absolute values of the functional score in both treatment groups declined after 5 years, back to baseline in the stimulation group and below baseline in the thalamotomy group, in concurrence with disease progression. However, most patients in both groups still experienced satisfactory tremor suppression at 5 years.


Studies comparing the clinical outcome of thalamotomy with that of pallidotomy are scarce [45].



Pallidotomy


A randomized rater-blinded study of unilateral posteroventral medial pallidotomy in 14 advanced PD patients reported that motor scores in the “off” state and drug-induced dyskinesias were improved by 30 and 92%, respectively, after 6 months postsurgery. Gait and postural instability improved less (<25%). Rigidity, bradykinesia and tremor were improved mainly on the contralateral side but also ipsilaterally, although to a lesser extent [46]. This study was extended to 39 patients, with 27 of them examined at 1 year and 11 at 2 years. The positive effects on dyskinesias and the total scores for “off”-period parkinsonism, contralateral bradykinesia and rigidity were sustained in the 11 patients examined at 2 years. The improvement in ipsilateral dyskinesias was lost after 1 year, and the improvements in postural stability and gait lasted only 3–6 months [47].


The Sweden group of Hariz, Bergenhein and Laitinen followed Lars Leksell’s technique introduced in the 1950s and reported a 10-year follow-up review of 13 PD patients who were part of a large series of 38 patients who received posteroventral pallidotomy (11 unilateral and two staged bilateral procedures) between 1985 and 1990 [8]. There was an important alleviation of rigidity and bradykinesia in almost all of the patients. Contralateral tremor, if it was initially controlled by surgery, remained improved, although additional surgeries were needed in some patients. Most patients exhibited a gradual recurrence of akinesia and an increase in gait freezing. Dyskinesias were successfully abolished without recurrence or induction of them contralateral to the pallidotomy, despite increases in dopaminergic medication due to disease progression. The lack of availability of comprehensive validated rating scales at that time made critical assessment of the results difficult [48].


Schuurman and Speelman evaluated the effect of unilateral pallidotomy in 19 patients enrolled in a randomized, single-blinded, multicenter trial comprising 37 patients who had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonia or bradykinesia. Nineteen patients underwent unilateral pallidotomy and the rest were postponed for 6 months. They found that the median UPDRS motor subscore during the “off” period improved by 31% following surgery. During the “on” phase, the dyskinesia rating scale improved by 50% in patients who underwent pallidotomy compared with no change in those who did not. Because patients were aware of the treatment allocation, a part of the measured effect could be explained by the placebo effect. This study was extended to 32 patients and to 1-year follow-up for the original 19 patients operated. The positive effects of unilateral pallidotomy on contralateral rigidity, bradykinesia and tremor, as well as on dyskinesias, were maintained, and functioning in ADLs and quality of life were improved after the 1-year follow-up [49].


We conducted a prospective case–control study in which we followed over 1 year 10 PD patients with indication for pallidotomy who did not undergo surgery because of lack of financial support and10 PD patients who did undergo pallidotomy. A significant reduction in ADL scores and UPDRS motor scores, and in the subsets addressing rigidity, bradykinesia and tremor, as well as dyskinesias, was found in the group who were operated on [37].


Vitek et al. [50] performed the first randomized trial comparing unilateral pallidotomy with medical treatment in 18 PD patients in each group. At the 6 month follow-up, patients receiving pallidotomy had a statistically significant reduction of 32% in the total UPDRS score compared with those randomized to medical therapy (5% increase). They also showed improvement in tremor (abolished in 70% of the patients), rigidity (an average of 55% improvement in 88% of the cases) and bradykinesia (average 40% of improvement). Gait and balance improvement of 32 and 34%, respectively, at the 1-year follow-up was no longer observed at 2 years. A significant improvement in both drug-induced dyskinesias (improved in all and completely relieved in 70%) and motor fluctuations after pallidotomy was found at 6 months and maintained for 2 years. An ipsilateral improvement was observed also for bradykinesia, rigidity and dyskinesias. No significant levodopa dosage reductions were achieved following surgery. Surprisingly, no significant differences in ADL subscores were found in the two treatment groups.


A long-term follow-up study (3.5–5.5 years) of a cohort of 20 patients who had undergone unilateral posteroventral pallidotomy found a sustained improvement in “off” state contralateral motor signs and contralateral dyskinesias during “on” but not in other “on”-state parkinsonian signs [51].


Regarding ADLs, in 2001, a meta-analysis of 12 studies reporting ADL outcome found that unilateral pallidotomy successfully enhanced functional outcome in PD patients [52], which was also found in our meta-analysis [28].


Merello et al. [53] prospectively randomized a group of 13 PD patients to receive a unilateral thermolesion or DBS on the posteroventral GPi to compare the efficacy and safety of both procedures. Patients improved in the “off”stage on average by 29% of the motor UPDRS score contralateral to the side of either type of surgery. Tremor, rigidity and bradykinesia also improved significantly, regardless of the procedure type. The safety of both techniques was comparable.


Esselink et al. [54] reported 1- and 4-year outcomes of a randomized, multicenter, observer-blind comparison of unilateral pallidotomy (n = 14) versus bilateral STN-DBS (n = 20) in advanced PD patients. They showed a significant long-term superiority in the efficacy of bilateral STN-DBS over pallidotomy with respect to motor UPDRS score during the “off” state (46 vs 27%, respectively). However, no significant differences between the two procedures were found regarding ADL score, drug-induced dyskinesias severity or levodopa dosage, possibly due to the small sample size included.


Fewer results have been published for bilateral pallidotomy. One study found a 53% improvement in UPDRS scores after bilateral pallidotomy (n = 8) compared with a 27% improvement after a unilateral procedure (n = 12), but at the expense of a greater deterioration in verbal fluency, dysarthria and sialorrhea. The role of bilateral pallidotomy remains uncertain, and when possible, a combined procedure including unilateral pallidotomy and contralateral DBS might be preferred when bilateral DBS is not possible [33, 55, 56].


An interesting finding is the appearance of transient abnormal involuntary movements such as hemichorea or hemiballism during macrostimulation or thermolesion and may predict a better motor outcome following pallidotomy [57].


In summary, pallidotomy exerts its main effect on limb dyskinesias and “off”-state dystonia, and also shows a good response for rigidity, bradykinesia and tremor. Although one meta-analysis including 17 studies with unilateral pallidotomy found improvement of axial symptoms, such as postural instability and gait disability during “on” and “off” periods [58], the beneficial effect usually waned beyond 1 year of follow-up [51]. Pallidotomy also has almost no positive effect on speech and nonmotor symptoms. Almost always, those clinical features that responded better were those responsive to levodopa. The benefits were sustained in a mean follow-up of 10 years. Motor scores may worsen over time, possibly due to disease progression, but loss of surgical benefit cannot be ruled out. Lesions that involved the caudal portion of the GPi are more effective in providing long-term improvement in tremor, rigidity and bradykinesia than lesions that only partially involve this territory or involve the globus pallidus externus (GPe).



Subthalamotomy


There is less experience with subthalamotomy in comparison with the abovementioned procedures, in part because of the potential risk of intractable hemiballism. However, subthalamotomy was explored in more depth after success of STN-DBS for PD and the need to offer less expensive alternatives to DBS in some countries or to offer an option for patients living at large distances from the implantation center or having an underlying general condition precluding DBS. No randomized controlled trials have been conducted, but several case series have been reported.


Su et al. [59] showed in 12 patients with unilateral dorsolateral subthalamotomy extending to the pallidofugal fibers, and followed up after 1 year, a 38% improvement in UPDRS-ADL and motor scores during the “on” state, including rigidity (79%), tremor (66%) and bradykinesia (40%). A daily dopaminergic medication dosage reduction of 42% was accomplished. Axial motor features, gait, postural stability, “off”-state tremor and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. It should be noted that five out of 12 patients had STN-DBS surgery 1–3 months before subthalamotomy and two simultaneously. However, none of them had DBS implanted after subthalamotomy and while in the off-stimulation and off-medication state, their UPDRS scores were not significantly different from the presurgical scores.


Recently, the effects of unilateral subthalamotomy were reported in 89 PD patients, of which 25 were followed for up to 3 years [60]. A marked improvement in contralateral parkinsonian features was obtained during both “on” and “off” states, with an average of 20–50% reduction. Axial and ipsilateral to the lesion, features were not modified and progressed steadily. The levodopa daily dosage was reduced by 45, 36 and 28% at 12, 24 and 36 months after surgery, respectively. Despite this reduction, which also occurs after STN-DBS, levodopa-induced dyskinesias were not significantly decreased in comparison with the stimulation procedure, but at least they were not increased contralateral to the lesion, while they continued to worsen in the nonoperated side. Fourteen patients (15%) developed postoperative hemichorea or hemiballism, which required pallidotomy in eight. Interestingly, these 14 patients had significantly higher levodopa-induced dyskinesia scores before surgery than the rest of the patients. There was no evidence of cognitive impairment resulting from surgery.


Bilateral subthalamotomy was reported in 18 advanced PD patients, with reductions in the UPDRS motor scores during “off” and “on” states by means of 50 and 35%, respectively [61]. Not only did rigidity, tremor and bradykinesia improve markedly but also ADL scores. Levodopa daily doses were reduced by 47%, which in turn decreased levodopa-induced dyskinesias by 50%. This finding contrasts with those obtained after unilateral procedures. The motor benefit persisted for a follow-up of 3–6 years.


Another study evaluated the effect of unilateral subthalamotomy in 17 asymmetrical tremor-dominant PD patients and unilateral subthalamotomy plus contralateral STN-DBS in four PD patients with bilateral features. All patients were at an advanced stage of the disease. Ninety percent of the lesions extended beyond the STN to involve pallidofugal fibers (H2 field of Forel) and the zona incerta. All patients were followed up at least for 1 year. Tremor, bradykinesia and rigidity improved markedly. Dopaminergic medication dosage was reduced to approximately half, together with a significant reduction in dyskinesias and motor fluctuations. Cognition was mostly unaffected [62].


Merello et al. [10] compared the efficacy and safety of different surgical approaches to STN in a prospective randomized study involving 16 patients who underwent bilateral STN-DBS, bilateral subthalamotomy or unilateral subthalamotomy plus contralateral STN-DBS and were followed for 1 year after surgery. Total and motor UPDRS scores, as well as drug-induced dyskinesias, improved significantly at the 1-year follow-up, regardless of the procedure administered and without statistically significant differences between treatment modalities. Dopaminergic medication dosage dropped to a similar degree after surgery in all groups.


A recent prospective, randomized, double-blinded pilot study compared unilateral pallidotomy and unilateral subthalamotomy in six and four advanced PD patients, respectively. Both approaches were equally safe and effective regarding motor and ADL measures. Levodopa-equivalent daily intake was significantly reduced in the subthalamotomy group [63].


In conclusion, subthalamotomy improves bradykinesia, rigidity and tremor, and allows reductions of levodopa dosage. The beneficial effects are comparable to those of pallidotomy or STN and GPi stimulation. Although the risk of hemiballism is a concern, its frequency is not as high as previously expected. The role of bilateral subthalamotomy in patients unable to receive DBS merits further exploration in large, randomized controlled trials with longer follow-up periods.


The Movement Disorder Society Evidence-based Medicine Review Update in 2011 for the motor symptoms treatments of PD concluded that unilateral pallidotomy is efficacious and clinically useful as a symptomatic adjunct to levodopa and in the treatment of motor fluctuations and dyskinesias, whereas thalamotomy is likely efficacious and possibly useful as a symptomatic adjunct to levodopa therapy. There is insufficient evidence for subthalamotomy as a treatment for motor fluctuations and dyskinesia or as a symptomatic adjunct to levodopa therapy [64].Unfortunately, the diverse combinations of procedures for PD patients and the lack of standardized outcome measures and side effects reported, in addition to scarcely controlled randomized and long-term studies, preclude low qualifications by evidence-based reviews. However, these reviews hardly mirror the reality of the clinical setting. As an example, the lack of double-blind, controlled randomized trials of thalamotomy or thalamic DBS for essential tremor mean that these procedures are classified as “Level C, possibly effective” according to the recent evidence-based guideline update of the American Academy of Neurology [65], which does not reflect properly the great efficacy of these techniques in clinical practice.


The clinical effects of thalamotomy, pallidotomy and subthalamotomy are shown in Table 17.1.


Tags:
Feb 16, 2017 | Posted by in NEUROLOGY | Comments Off on Thalamotomy, pallidotomy and subthalamotomy in the management of Parkinson’s disease

Full access? Get Clinical Tree
Get Clinical Tree app for offline access