Gamma Knife Radiosurgical Pallidotomy for Dystonia: Not a Fallen Angel
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.273644
Source of Support: None, Conflict of Interest: None
Keywords: Dystonia, Gamma-knife, pallidotomy, stereotactic radiosurgery
Before the advent of deep brain stimulation (DBS) in 1990s, lesioning procedures used to be the gold standard treatment options for the management of intractable movement disorders especially dystonia and essential tremor (ET). Nearly a quarter of century later, stereotactic lesioning is reemerging due to the identification of long-term complications and practical limitations of DBS surgeries. What pushed pallidotomy at the back foot in this race was not lesser suppression of the dystonic movements, but non-realistic extrapolation of the results of stimulation surgeries in Parkinson's disease (PD) to dystonia, and non-willingness in industrial sectors to promote the lesioning. Aziz et al. and Taira et al. have reported the effectiveness of stereotactic lesioning for various generalized and focal dystonias (including task-based dystonias) with stereotactic radio frequency lesioning (RFL). Anecdotal case reports have been published highlighting the value of gamma knife pallidotomy for the treatment of generalized/hemi-dystonias and L-dopa induced dyskinesias. This report concerns our experience with gamma knife pallidotomy and its current value in the clinical practice.
A 24-year-old male patient presented with history of disabling right side hemidystonia. There was history of birth asphyxia. Subsequently, his parents noticed abnormal dystonic posturing at the age of 4 years involving the right half of his body which gradually worsened. The patient did not respond to any medical management and Botulinum injections. MRI of the brain was unremarkable. Neurological examination showed right side hemidystonia with disabling torsional movements [Video 1]. The patient was not able to maintain his posture without support and had frequent falls. He needed help for his daily chores including for washing and wearing his clothes. There was no sign of cognitive impairment, motor or sensory deficit.
Gamma knife pallidotomy was performed to make a lesion in the left posteroventral palladium. The lesion was targeted on standard targets on MRI in relation to the AC-PC line with superimposed functional anatomical Atlas More Details. The GPi (Globus pallidus internal) was targeted as per the parameters decided by Taira et al., 2 mm anterior to the midcommissural point, 20 mm lateral from the midline, and 4 mm inferior to the AC-PC line maintaining a distance of 18 mm from the super lateral edge of the optic tract. A single 4 mm collimator shot was used and 140 Gy radiation was delivered at prescription isodose of 100% with Leksell Perfexion model (Elekta Instruments, Norcross, GA, USA) [Figure 1]a.
Four months following the pallidotomy, the patient showed improvement in his torsional movements. He was able to wear clothes and walk without falling to the ground. By the end of the first year, he still suffered some difficulty in walking but was able to maintain his posture without any support. Eighteen months post treatment he could move with much ease and started and started to work at his family grocery shop. Follow-up MRI at 18 months showed two small lesions in the target area on the MRI [Figure 1]b. Usually the lesion appears well-defined. But in our case we found two separate ill-defined hypo-intensities; the reason for the same could not be definitively elucidated. At six years follow-up, he has 61% improvement in his symptoms [Video 2]. The patient has not develop any motor or visual complaint so far.
As per the current definition, “Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions, causing abnormal and often repetitive movements, postures, or both.” Dystonic movements are typically patterned, twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. As per the distribution of the dystonia, it is classified into a) focal dystonia (involving only one part of the body such as a limb); b) segmental dystonia (multiple body parts); c) hemidystonia (involving half of the body); and d) generalized dystonia (involving one limb and one other non-contiguous body part). Hemi-/generalized dystonia are especially crippling, as the patients become dependent on caregivers for their routine activities. Similarly, task-based dystonias such as musician's dystonia or sports activities dystonia are career-terminating diseases in the young population.,
Historical Use of Gamma Knife Radiosurgery for Dystonia and Changing Patterns of Practice
Historically, patients with movement disorders were among the first chosen candidates for radio surgical lesioning by Leksell and Larsson during the advent of GKRS. This novel concept of stereotactically creating the lesion without any incision on the skull was a revolutionary idea. Despite initial encouraging results, the reports by Duma et al. and Friedman et al. highlighted the complication profile with radio-surgical pallidotomy. The possible reasons for the complications were larger collimator size, multiple targets and inferior planning software. But these two reports vehemently pushed radio-surgical pallidotomy into sabbatical in an era of emerging stimulation surgeries. Over the last six decades, much water has passed under the bridge and radio-surgical technologies and planning softwares have undergone a remarkables improvements by virtue of higher precision, sensitivity, accuracy, and shorter treatment duration.
The major change in the last three decades is the availability of the sophisticated radiological images for exact delineation of the critical intracranial structures. We can easily visualize components of the basal ganglia, the birder between the ventral intermediate nucleus (VIM) of the thalamus, optic pathway, and internal capsule with diffusion MRI tractography images and proton density sequences. Such methodology helps us in planning the track and the target without injuring the adjoining critical neurovascular structures. The last three decades of DBS has also helped us in identifying the earlier unknown targets, nuances of track design and management of untoward complications.
Rand et al. was the first to perform radiosurgical pallidotomy in 8 patients and reported significant improvement in contralateral rigidity, bradykinesia and dyskinesia in 50% of cases. Friedman  however, reported no improvement in all his 4 cases with one patient developing a stroke due to radiation vasculopathy with severe radiation changes in the blood vessels adjacent to the radio-surgical lesion. Young et al. did a comparison of radiosurgery and ablation for 51 patients of Parkinson's disease (PD) in which 29 were treated with radiosurgery and submitted to 34 lesions [Table 1]. He reported comparative improvement in both treatment arms with only one complication in each methodology. The worst outcomes have been reported by Duma et al., who in a series of 18 patients of PD reported improvement in only six (33%) cases. Radio-surgical pallidotomy shows a higher complication rate than thalamotomy. The reasons are manifold: a) the size of a pallidotomy cannot be predicted because of greater penetrance of perforating vessels (lenticulostriate arteries); b) pallidum is shown to have higher radiation sensitivity to hypoxia; and c) iron concentration tends to increase in the palladium with age, which may lead to undesirable production of oxygen free radicals.
Taira et al. have found that primary and tardive dystonias, show excellent long term results with GPi DBS. But, the complication and maintenance profile is worse than PD-DBS as it needs more frequent battery replacement (need for higher current than PD patients), and in cases of severe malware problems, the patient may land into “dystonic storm syndrome” (which is a potentially emergent situation). Encouraged by the reviews of Gross, Taira et al. initially tried lesioning on one side and DBS on the contralateral side. They found comparable results to bilateral GPi DBS. Later, they successfully practiced bilateral GPi pallidotomy especially in young patients with good verbal communication. A successful lesioning provides a permanent cure obviating the risk of life long hardware related complications. Contrary to the popular belief, there is no scientific literature which could methodically compare GPi lesioning with stimulation surgeries. It is a mere extrapolation from the comparative studies of PD, which presumes that stimulation might be more beneficial than lesioning in non-PD dystonia cases. Though literature is more in favor of DBS over lesioning surgeries, there are still uncertainties, such as, a) greater improvement in dystonic patients with phasic movements than in patients with tonic movements; b) the lesser efficacy in patients older than 21 years of age than younger patients (<21 years age); c) whether the disease duration affects the outcome; d) and if the genetic variant has a significant different prognosis than the sporadic variant etc. We candidly admit the fact that DBS is safer than lesioning in view of its reversibility and adjustability yet it comes at a high financial cost, potential psychological implications, and as a control rather than a cure of the disease.
In most of developing countries, financial constraints with implantation and maintenance of the DBS device are the major limitation, not the availability of expertise or the willingness of the treating teams. Many European countries including the NHS Trust of the United Kingdom are facing the same issue with the majority of patients suffering from the movement disorders (personal communication). Other problems include the psychological burden on the patient of feeling dependable on an “alien” device implanted in his brain which can potentially fail mechanically. The old age of these patients and their multiple comorbid illnesses deter them from undergoing investigational procedures such as MRI due to the implanted device. Few insurance companies provide adequate cover for DBS surgeries. In its comparison, lesioning either by GK or RF is a single admission procedure at a much lower price and radio-surgical procedures are majorly covered with insurance.
Why is the GPi the ideal and the most difficult target for all?
Whether stimulation or lesioning, the GPi is a difficult target for the functional neurosurgeons. The reasons are manifold, a) the frequent inability to visualize the correct target; b) technical difficulties in placing electrodes in the posteroventral GPi (the ideal target); and c) the non-forgiving nature of its neighbors, especially internal capsule and optic tract. The GPi is the preferred target to VIM.,, Bilateral pallidal stimulation improves both the action myoclonus and the dystonic symptoms, whereas VIM stimulation mainly improves the myoclonus and tremor. Apart from it, bilateral thalamotomy is undoubtedly associated with significant complications while bilateral pallidotomy is found safe even if performed in one session. However, there is no ideal target for a secondary dystonia hence a normal MRI always predicts a better outcome.
It is important to understand that positioning in lesioning is different from positioning required for the stimulation surgery. For DBS, the GPi is targeted at the level of the AC-PC line or 1 mm above it. On the other hand, the GPi is targeted nearly 4 mm below the AC-PC line for lesioning. The target should be in the posterior one third of the GPi, and it should be away from the medial border to prevent any injury to the internal capsule. One needs to be very careful in choosing the posterior third of the target in relationship to the optic tract as a lesion in the posterior GPi might lead to radiation injury and spillage to the optic apparatus.
Infrequently, visualization of the GPi may be a problem. Many authors have emphasized the value of proton density sequences apart from good T1, T2, and inversion recovery scans in identifying the target. The most common trouble is the delineation of the posterior border or the tail of the GPi (the bull's eye). Rarely, the GPi may show calcification (in patients with Down Syndrome or PKAN). In such a case, proper visualization should be rechecked on a CT scan with fused images on MRI. Calcifications are usually more pronounced in the anterior part of the GPi and it seldom creates any trouble in deciding the optimal target. GPi may be divided into GPi pars medialis and GPi pars lateralis by an accessory lamina. Some patients with secondary dystonia have atrophic narrow GPi, and in those cases, it is better to place the target 1-2 mm anterior than normal or even at the lamina pallida medialis. In some cases of secondary dystonia, the target GPi is completely missing. Large Virchow Robin space may also act as radiological masquerader, which needs to be properly evaluated on a T2 weighted image.,,
For the obvious reasons of industry-driven nature of neurosurgical practices, lesioning is now becoming an “orphan drug”. Many companies have stopped manufacturing lesioning apparatuses after promotion of stimulation surgeries. There is no promotion of lesioning in academic meetings, no keynote or industry sponsored lectures, and hardly any teachers. We are short of enough literature on pallidotomy for dystonia than pallidotomy for PD, as pallidotomy for dystonia was introduced much later than pallidotomy for PD. Thus, DBS had already become the preferred treatment option for PD. Robert E. Gross has raised this issue in a systemic literature review commenting that, “bilateral GPi DBS is neither more effective nor safer than bilateral pallidotomy for primary dystonia, and both are equally ineffective for secondary dystonia”. In countries with limited resources, pallidotomy for dystonia should be preferred to DBS because of obvious financial implications., As there is no definition for remission and cure of dystonia, it would not be an exaggeration to say that DBS may control but not cure dystonia while lesioning may cure it.,, Pallidotomy shows a high response rate, low complication profile, and can become a lifelong cure in experienced hands. Indeed, we do not find it justified to put an enormous financial burden on a poor young patient who would still need lifelong care for frequent battery changes and visits for stimulation from the DBS option.
Statement of Ethics
The authors have no ethical conflicts to disclose. Written consent was obtained from the patient prior to publication of the manuscript and any photographs or images.
We would like to acknowledge the guidance and case management by the late Professor Kanchan Kumar Mukherjee, PGIMER, Chandigarh, for his vision and effort in successfully managing patients.
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Conflicts of interest
There are no conflicts of interest.