An old question, a new technology: Bilateral ablation in Parkinson’s disease 

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Ablative surgery has a complicated legacy in our field. Pallidotomy, thalamotomy, and subthalamotomy have a long history in the treatment of movement disorders, but once deep brain stimulation arrived in the 1990s, radiofrequency lesioning procedures were largely abandoned in most centers. Bilateral ablations have an even more complicated story; radiofrequency bilateral pallidotomy, for example, was associated with unacceptable rates of speech and gait complications. MR-guided focused ultrasound (MRgFUS) has reopened the question: incisionless, image-guided, with real-time thermometry and stepwise energy delivery that allows subthreshold testing before a definitive lesion. In July 2025, the FDA approved staged bilateral pallidothalamic tractotomy for Parkinson’s disease with motor fluctuations or dyskinesia. The trial behind that approval, now published in The Lancet Neurology, moves the discussion from whether both sides can be treated to how we identify the patients for whom the second side is worth it. 

Previous studies of MRgFUS ablations in Parkinson’s disease explored mainly unilateral lesions. Unilateral thalamotomy has been approved for tremor-dominant Parkinson’s disease since 2018 and unilateral pallidotomy for motor complications since 2021. Unilateral subthalamotomy, tested in a randomized trial and followed prospectively with sustained benefit at long-term follow-up, improves all cardinal motor features of parkinsonism (tremor, bradykinesia and rigidity) on the treated side, and remains a valuable option for patients with markedly asymmetric manifestations. Pallidothalamic tractotomy extends the same logic: the tract arises from the internal pallidum, and its course allows smaller, lower-energy lesions than a pallidotomy. 

This prospective, open-label, single-arm study enrolled patients at nine centers across three continents. Fifty-four patients underwent unilateral pallidothalamic tractotomy to the symptom-dominant side; 40 proceeded to the contralateral side at least six months later, after meeting prespecified safety criteria. The primary endpoint was the percent change in MDS-UPDRS part III off-medication upper and lower extremity (ULE) score at three months after the second procedure. 

After unilateral treatment, the treated-side ULE score improved by a median of 53% at three months and the part III off-medication total score by 30%, with benefit sustained through 12 months. Treatment-related adverse events occurred in 39% of patients, almost all mild, and only one patient (2%) had a persistent clinically significant event at six months. 

After the second procedure, combined ULE scores were 32% better than baseline, a number that includes everything the first side had already improved. Off-medication time also improved mainly after the first treatment: the proportion of patients reporting it fell from 80% at baseline to 33% after the first side, then to 32% after the second. Dyskinesia followed a somewhat different pattern: reported by 50% at baseline, 18% after unilateral treatment, and 0% after bilateral treatment, with total MDS-UPDRS part IV scores improving 67% from baseline. 

Treatment-related adverse events followed the second procedure in 55% of patients; 25% had persistent moderate (n=9) or severe (n=1) events at 12 months, predominantly affecting speech, gait, and balance, including one patient with severe persistent anarthria. These figures deserve context: the trial applied independent speech, visual field, and neuropsychological monitoring, a level of scrutiny most surgical series do not, so mild events that could go unrecorded elsewhere are captured here. For perspective, the Veterans Affairs cooperative trial reported moderate-to-severe speech problems at 24 months in 28% of pallidal and 35% of subthalamic DBS patients, with balance disorder in roughly 30% of each, though the comparison must be made cautiously, since DBS is reversible and ablations are not. 

To interpret these findings, we have to take into consideration some limitations. The study was open-label and not sham-controlled, and no repeat baseline was obtained before the second procedure, so progression during the interval cannot be separated from the effect of the second lesion. Also, a learning curve is evident: three centers treated 70% of patients while three treated only one each, and a first-in-kind multicenter experience tends to capture a technique that is not yet completely mature and refined. 

The pallidothalamic tract is not the only bilateral option under investigation. Staged bilateral subthalamotomy has been explored in a small prospective series, with significant motor improvement and adverse events that were mostly mild and transient, though speech was also affected in some patients. Target choice, lesion size, and energy protocol plausibly shape the speech and gait profile. 

What the field needs now is better evidence on the second side. Which patients tolerate contralateral treatment remains largely undefined: whether baseline axial and speech performance predicts risk, whether the interval between procedures matters, whether tighter targeting and smaller lesions preserve benefit while sparing corticobulbar and corticospinal tracts, and how these events evolve beyond 12 months. Registries capturing real-world staged experience, and prospective studies designed specifically around second-side selection, can answer questions that a 40-patient single-arm trial cannot. 

For now, unilateral pallidothalamic tractotomy is an effective incisionless option for appropriately selected patients. Second-side treatment should be considered in patients with disabling contralateral symptoms who remain free of speech and gait impairment after the first procedure, counselled frankly about cumulative risk: a threshold for careful selection, not a reason to leave it unexplored.