Pallidothalamic Tractotomy after Pallidotomy for Medication‐Refractory Dystonia: Preliminary Short‐Term Results from a Case Series of Five Patients

Abstract

Background

There is limited data regarding the role of pallidothalamic tract (PTT) lesioning after failure of pallidotomy.

Objectives

To report the role of unilateral PTT lesioning in refractory generalized dystonia following bilateral pallidotomy and hemi‐dystonia following unilateral pallidotomy.

Methods

A single‐center retrospective case series.

Results

Five patients underwent unilateral PTT lesioning after the failure of pallidotomy to control dystonia, including status dystonicus in one case. The interval between pallidotomy and PTT lesioning ranged from 2 to 90 months. Pre‐PTT surgery, BFMDRS‐M scores ranged from 20 to 87, and BFMDRS‐D scores ranged from 8 to 23. Immediately post‐PTT surgery, improvement was observed in four patients, with objective improvements ranging between 57.5 and 93.3% in the BFMDRS‐M score. Two patients developed adverse effects: one experienced a mild worsening of post‐pallidotomy dysarthria, and another developed impaired hand dexterity.

Conclusions

Our initial experience suggests that unilateral PTT lesioning holds promise as an option for lesional surgery following pallidotomy, in refractory dystonia.

With the advent of deep brain stimulation (DBS), use of pallidotomy has been minimized. However, pallidotomy offers several advantages. Intracranial lead implantation or regular programming is not needed. It may be considered in patients ineligible for DBS, and is considerably more affordable than DBS. For these pragmatic considerations, pallidotomy continues to be employed for refractory dystonia in many regions of the world, including ours. Bilateral pallidotomy has been beneficial for medication‐refractory dystonia, with a meaningful improvement (above 20% improvement in the Burke‐Fahn‐Marsden Dystonia rating scale [BFMDRS] score) in up to 79% of cases. ¹ However, recurrence of dystonia after bilateral pallidotomy is noted in 19% of patients. ¹ Treatment options in this scenario include continued medical management, repeat lesioning surgery, or DBS. ² , ³ Repeat lesional surgery to expand the original pallidotomy lesion may be considered if the latter is inadequate on an MRI. Pallidothalamotractotomy, or Forel H‐otomy, is a lesional surgery involving the disconnection of the pallidothalamic tract (PTT). Although used in the 1960s–1970s for dystonia, Parkinson's disease (PD) and epilepsy, it gained further attention after its revival in 2005 by Jeanmonod's group. ⁴ PTT lesioning has, thus far, been used either as a standalone unilateral procedure or contralateral to and following a unilateral pallidotomy in dystonia (focal, segmental and generalized). Both radiofrequency ablation and focused ultrasound (FUS)‐guided PTT lesioning procedures have been employed. ⁵ , ⁶ We uniquely report the role of stereotactic unilateral PTT lesioning in refractory generalized dystonia after failure of bilateral pallidotomy failure and hemidystonia after unilateral pallidotomy.

Methods

Patients

Data from five patients who underwent unilateral PTT lesioning at Forel's field H1 for refractory dystonia after initial pallidotomy (bilateral/unilateral) between 2022 and 2024 were retrospectively analyzed. Patients were recruited from the movement disorders clinics. All patients had previously undergone pallidotomy for refractory dystonia, despite which dystonia persisted. Financial considerations precluded DBS surgery in all patients.

Clinical Assessment

All patients underwent detailed assessment by movement disorder specialists. Clinical data were retrieved from records. Dystonia severity was assessed using the BFMDRS for movement (BFMDRS‐M) and disability (BFMDRS‐D). ⁷

Surgical Planning and Considerations

Pre‐operative MRI was done before PTT lesioning. All patients were confirmed to have appropriately located initial pallidotomy lesions of an appropriate size, and repeat pallidotomy was not an option in these cases. All patients underwent surgery under general anesthesia, like pallidotomy, ⁸ after which a stereotactic frame (Leksell Model G, Elekta) was applied. A stereotactic CT scan was performed and later fused with the non‐stereotactic MRI. The anterior and posterior commissures were marked on T2‐weighted images. Indirect targeting of PTT was performed, following the description by Horisawa et al. ⁹ , ¹⁰ A 4 mm monopolar radiofrequency lesioning probe by Elekta was utilized.

Results

The study included five patients (3 males/2 females) (Table 1). Age at onset of dystonia ranged from 3 months to 36 years. Duration of symptoms before pallidotomy ranged from 2 to 14 years. The age at which pallidotomy and PTT were performed ranged from 9 to 41 years and 9 to 49 years, respectively. The interval between pallidotomy and PTT lesioning varied from 2 to 90 months. Four patients with generalized dystonia underwent bilateral simultaneous pallidotomy, while one with hemidystonia underwent unilateral pallidotomy. Follow‐up duration ranged from 6 to 21 months. The etiology of dystonia was idiopathic (2), post‐encephalitis (2), and dyskinetic cerebral palsy (1). Baseline pre‐PTT scores for BFMDRS‐M and BFMDRS‐D were available for four patients; BFMDRS‐M scores ranged from 20 to 87, and BFMDRS‐D scores ranged from 8 to 23. Table 2 presents the effects of PTT lesioning on dystonia. In case 1, there was no change in immediate post‐operative scores. Follow‐up revealed a worsening in BFMDRS‐M and ‐D scores by 10.3% and 17.4% from baseline. Although this patient was not an ideal surgical candidate for PTT lesioning, as pre‐operative imaging had indicated basal ganglia atrophy, he chose to proceed with PTT lesioning after careful discussion of risks/benefits. He had experienced mild dysphagia after pallidotomy, which remained unaffected after PTT lesioning. In case 2, immediate post‐operative BMFDRS‐M and ‐D scores showed improvement by 68% and 16.7%, respectively, and further improved by 72.2% and 41.7% at 6 months of follow‐up. He had experienced dysarthria and dysphagia after pallidotomy, which was mild at the time of PTT lesioning. Post‐PTT lesioning, although dysphagia did not worsen, dysarthria worsened from baseline but did not produce impairment in daily living. Case 3 had improvement by 50% and 12.5% in the BFMDRS‐M and ‐D scores at 3 months of follow‐up, which persisted till 10 months. After 10 months, he developed a progressive worsening of cervical dystonia coupled with a deterioration in BFMDRS scores, along with neck pain and radicular pain involving his upper limbs. He was reevaluated and was found to have cervical compressive myelopathy and was planned for spinal cord decompression surgery. Case 4 was a patient with cerebral palsy who underwent simultaneous bilateral pallidotomy for refractory dystonia. Two weeks later, she developed medically refractory status dystonicus (SD), for which she required mechanical ventilation and intravenous anesthetic agents. Unilateral PTT lesioning was done as a rescue procedure after 45 days of SD. The patient gradually recovered from SD over the ensuing 2 weeks, and intravenous anesthetics were withdrawn. She was weaned from ventilation and discharged on nasogastric feeding. She was also administered onabotulinum toxin (300 units) in sternocleidomastoid, splenius capitis, and cervical and thoracic paraspinal muscles before discharge. At discharge, she was bedridden and on Ryle's tube feeding but had significant amelioration of dystonia. However, she succumbed to pneumonitis 1 month after discharge. In case 5, the patient reported significant improvement in the immediate postoperative period, which was sustained up to at least 6 months, as per telephonic follow‐up. She could not be physically examined, as she was located in a very remote region. She experienced a mild reduction in contralateral hand dexterity post‐operatively, which did not improve on follow‐up. Post‐operative imaging of all patients is provided in Figure 1.

TABLE 1.

Baseline characteristics of five patients who underwent unilateral PTT after pallidotomy for refractory dystonia

S.No.	Age at onset of dystonia (years)	Age at pallidotomy (years)	Age at PTT (years)/sex	Duration of symptoms before pallidotomy (years)	Interval between pallidotomy and PTT (months)	Dystonia (Distribution/Etiology)	Initial procedure	PTT procedure
Case 1	15	17	21/M	2	19	Generalized/Post‐encephalitis	Bilateral Pallidotomy	Right PTT
Case 2	36	41	49/M	8	59	Generalized/Idiopathic	Bilateral pallidotomy	Left PTT
Case 3	28	31	36/M	3	70	Generalized/Idiopathic	Bilateral pallidotomy	Left PTT
Case 4	0.3	9	9/F	9	2	Generalized/HIE	Bilateral pallidotomy	Right PTT
Case 5	4	18	19/F	14	15	Left hemidystonia/Post encephalitis	Right pallidotomy	Right PTT

Abbreviations: HIE, hypoxic ischemic encephalopathy; F, female; M, male; PTT, pallidothalamotractotomy.

TABLE 2.

Outcomes of unilateral PTT after pallidotomy for refractory dystonia

	Pre‐PTT BFMDRS		Immediate post‐PTT BFMDRS		3 month post‐PTT BFMDRS		6 month post‐PTT BFMDRS		Last Follow up BFMDRS		Additional treatment	Adverse events after PTT	Total follow up duration after PTT (months)
S. No.	Motor	Disability	Motor/% change	Disability/% change	Motor/% change	Disability/% change	Motor/% change	Disability/% change	Motor/% change	Disability/% change
Case 1 a	87	23	87/0	23/0	Not available	Not available	96/−10.3	27/−17.4	96/−10.3	27/−17.4	Onabotulinum toxin for left upper and lower limb (560 U), Medications	None. No worsening of post‐pallidotomy dysphagia (mild).	6
Case 2	36	12	11.5/68	10/16.7	10/72.2	7/41.7	10/72.2	7/41.7	10/72.2	7/ 41.7	Botulinum toxin for cervical dystonia, Medications	Patient had mild persistent dysphagia and dysarthria after pallidotomy. He had mild worsening of dysarthria, not hampering ADLs, after PTT	6
Case 3 b	20	8	9.5/57.5	‐	10/50	7/12.5	NA	NA	39/−95	12/−50	Medications	Patient had dysphagia and dysarthria after pallidotomy. No worsening after PTT.	21
Case 4 c	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	Medications	None	NA (patient expired)
Case 5	52	10	3.5/93.3	10/0	NA	NA	NA	NA	NA	NA	Medications	Post‐operative reduction in upper limb dexterity left	6 (telephonic)

Abbreviations: BFMDRS, Burke Fahn Marsden Dystonia Rating Scale; NA, not available; PTT, pallidothalamic tractotomy.

^a Poor presurgical prognosis.

^b Post op cervical myeloradiculopathy.

^c Patient succumbed to pneumonitis 1 month after PTT at home. % change indicates change in score from baseline, expressed as percentage of baseline. A negative score indicates worsening from baseline.

Figure 1.

Post‐operative brain imaging showing the pallidotomy lesion/s (with dotted white arrow) and PTT lesion (with solid white arrow) in (A) Axial CT section of case 1 showing bilateral pallidotomy and right PTT lesion (B) Axial MRI Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) sequence of case 2, 2 months post‐operatively showing bilateral pallidotomy and left PTT lesion (C) Axial MRI T2‐weighted sequence of case 2, 6 months post‐operatively (D) Axial MRI FGATIR sequence of case 3 showing bilateral pallidotomy and left PTT lesion (E) Axial CT of case 4 showing bilateral pallidotomy and right PTT lesion (F) Axial CT of case 5 with right pallidotomy and right PTT lesion.

All patients continued to be on anti‐dystonia medications; the dose could be reduced in case 2 (20%). Two patients continued to be on botulinum toxin therapy.

Discussion

We report the effects of unilateral PTT lesioning following failure of pallidotomy in refractory dystonia. We noted short‐term improvement in dystonia severity in four patients, with relapse in dystonia in one patient at 10 months. Two patients developed adverse effects; one had worsening of post‐pallidotomy dysarthria, and another had impaired hand dexterity.

The PTT comprises two fiber bundles, the lenticular fasciculus and the ansa reticularis, which traverse from the globus pallidus interns (Gp_i) to the ventral‐anterior (VA) and ventrolateral (VL) thalamus. Before entering the thalamus, the fibers converge within a 4 mm diameter at Forel's field H1. Mechanistically, Gp_i over‐inhibits the thalamus, leading to disinhibition of the thalamocortical loop and subsequent cortical excitation. Like pallidotomy, PTT lesioning eradicates the inhibitory control of the Gp_i on the thalamus.

Meyers first described surgical interruption of pallidofugal fibers as a target for PD in 1942. ¹¹ Speigel et al used the term “campotomy” in 1963. ¹² Aufenberg et al introduced the term “pallidothalamotractotomy” in 2005. ⁴ Since then, PTT lesioning has been utilized for PD and dystonia, and has also shown benefit in obsessive‐compulsive disorder ¹³ and epilepsy. ¹⁴

The utility of PTT lesioning has been demonstrated for cervical dystonia (CD). In 1970, Hassler and Dieckman used unilateral ablation of Forel's field H1 and VOI (nucleus ventrooralis internus) of the thalamus in 21 patients with CD. ¹⁵ Of these, 57% showed “good” and the remainder “moderate” outcomes. Adverse effects comprising ataxia and hemiparesis developed in 10 patients. In 1982, the same group used unilateral lesioning of Forel's field H1, VOI and VOA thalamus in 87 patients with CD. Of these, 89% of patients showed varying improvement over a follow‐up of 5 years, with 35% having abolition of the dystonia. However, although these preliminary findings provided a basis for future work, objective measurements of dystonia severity or disability were lacking. PTT lesioning was revived by Jeanmonod's group to relieve severe parkinsonian symptoms in advanced PD using a target close to the thalamus in Forel's field H1. ⁴ A beneficial effect on dystonia was observed by Horisawa et al in a patient with advanced PD with motor fluctuations, dyskinesias and dystonia. ¹⁶ Subsequently, the efficacy of unilateral PTT lesioning in 25 patients with asymmetrical CD was demonstrated by Horisawa et al in 2019 ¹⁷ and further in 35 patients in 2022. ¹⁰ Recently, the same group demonstrated the efficacy of FUS‐guided PTT lesioning in 10 patients with CD. ⁶

We demonstrate the role of PTT lesioning after failure of bilateral pallidotomy in refractory generalized dystonia. PTT lesioning after unilateral pallidotomy for dystonia was previously explored by Horisawa et al in 2019, who did PTT lesioning on the contralateral side, in 11 patients. ⁹ The mean interval between the two procedures was 9.5 ± 3.1 months. The mean follow‐up duration was 11.5 ± 4.2 months. All subscales of BFMDRS‐M improved, except eyes, speech and swallowing. The main adverse effect was reduced speech volume (six patients), which did not interfere with daily activities.

The main concern with offering PTT lesioning after bilateral pallidotomy is its potentially detrimental effects on speech/bulbar function and cognitive/ memory issues, mainly due to impact on the adjacent internal capsule or mammillothalamic tract, respectively.

Novelly, we did PTT lesioning as a rescue procedure for SD in one patient in whom SD developed post‐pallidotomy. PTT was considered when high‐dose anti‐dystonia medications failed to control SD. The effects of pallidotomy and PTT likely synergized to ultimately achieve improvement. Additionally, ipsilateral PTT lesioning after unilateral pallidotomy for a patient with hemi‐dystonia yielded significant benefits. The failure of PTT lesioning in one patient, who had basal ganglia atrophy pre‐operatively, encourages a careful preoperative anatomical evaluation of the PTT to assess procedural viability.

The follow‐up duration in our series ranged from 6 to 21 months, with one patient being followed up by telephone at 6 months, which was a limitation. A longer follow‐up would provide valuable insights into the sustainability of benefit. Additionally, since this was a retrospective study, dystonia scores were not consistently available for all patients. Post‐operative MRI was unavailable for all cases.

Our findings have important implications for patients in whom bilateral pallidotomy is unsuccessful. While DBS certainly offers the advantage of adjusting stimulation parameters to achieve optimal effect, costs remain prohibitive for patients in many regions of the world and access to DBS specialists is limited. In such scenarios, PTT lesioning may be a potential option.

Our initial experience suggests that unilateral PTT lesioning holds promise as a viable option for lesional surgery following bilateral pallidotomy in patients with refractory generalized and hemi‐dystonia. However, a larger patient cohort and extended follow‐up will reveal further insights into the benefits and adverse effects of PTT lesioning after pallidotomy.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique.

D.G.: 1A, 1B, 1C, 3A.

A.D.: 1B, 1C, 3B.

A.A.: 1B, 1C, 3B.

D.M.R.: 1B, 1C, 3B.

R.R.: 1B, 1C, 3B.

A.E.V.: 1B, 3B.

A.S.: 1B, 3B.

A.G.: 1B, 3B.

A.K.S.: 1B, 3B.

M.S.: 1B, 3B.

P.S.C.: 1B, 3B.

K.G.: 1A,1B, 1C, 3B.

Disclosures

Ethical Compliance Statement: The study was approved by the institutional review board (AIIMSA00121/26.10.2023). An informed consent was obtained from all the patients included in the study. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: The study was not funded. All other authors report no financial disclosures. There are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.