Letter: Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial

To the Editor: Laryngeal dystonia (LD) is a disabling task-specific dystonia with limited treatment options once botulinum toxin injections fail to provide sufficient relief.1-4 Novel treatments, such as neuromodulation, merit careful evaluation.5 A recent opinion piece, “Is thalamic deep brain stimulation (DBS) the right target to improve laryngeal dystonia symptoms?” in the journal “Dystonia”, made strong, unfounded claims about a randomized controlled trial that was published in the journal “Neurosurgery” in 2021.6 Open, balanced, and timely scientific exchange is fundamental to academic progress. Therefore, when strong, unfounded claims are made about the ethics or validity of ongoing research, scientific debate should be encouraged. Unfortunately, our letter to the editor of “Dystonia” challenging the opinion piece experienced long unexplained delays before being considered for review, forcing us to withdraw our submission. This lack of timely editorial decision-making is deeply disappointing. The commentary discusses a randomized controlled trial (RCT) examining DBS of the ventral-intermediate (Vim) thalamic nucleus for isolated LD published in “Neurosurgery”7 and advocates for an alternate location of DBS electrodes within the pallidum (GPi-DBS). Comments directed at improving future studies of DBS for LD were most welcome. However, other comments and assertions must be challenged. The opinion piece raised concerns about the level of blinding of the RCT. Although patient blinding proved impractical, observers remained blinded. This is a common issue with DBS trials and does not invalidate the results. Another criticism centered on the choice of outcome measures used. Although we agree there is no perfect outcome measure in the LD field, those used in the trial were the best internationally available and validated to date. To date, the Vancouver RCT on Vim-DBS remains the only systematic neurosurgical study in isolated LD, and is further supported by a separate report suggesting both benefit and safety of Vim-DBS in isolated LD.8 Importantly, no patient in these reports experienced complications. By contrast, evidence for GPi-DBS in isolated LD remains extremely limited. To our knowledge, there is only a single published case of GPi-DBS in a patient with isolated LD.9 All other published GPi DBS patients had LD accompanied by either heterogeneous segmental dystonia, additional cranial or bulbar symptoms, or coexisting tremor.9-12 These reports lack the methodological rigor of the Vim-DBS RCT, with limited imaging, diverse outcome measures, unstandardized diagnostic pathways, and often lacked blinding (either single or double). The opinion piece fails to apply the same critical appraisal to GPi-DBS studies as it does to the Vim-DBS trial. This discrepancy is difficult to reconcile. Since we agree that GPi-DBS might intuitively be the more “obvious” target for isolated LD, the near absence of published cases in isolated LD is notable. This scarcity may reflect limited benefit of GPi-DBS in isolated LD with consequent publication bias. Current evidence suggests that LD patients with broader dystonic involvement may indeed benefit more from GPi-DBS,9-12 whereas those with prominent tremor features may respond better to Vim-DBS.9,13-17 However, the unresolved question is how best to treat isolated LD. Existing data – limited although they are – indicate that Vim-DBS is a promising target that warrants continued, careful investigation. Indeed, the Vop/Vim border has been targeted successfully for other task-specific dystonias, such as musician's dystonia, writer's cramp, or focal hand dystonia.18-20 We fully support the authors' call for higher quality evidence, improved diagnostic frameworks, and refined outcome measures in LD research. However, this goal is not advanced by labeling further research into Vim-DBS as “unethical.” At present, Vim-DBS is the only neurosurgical intervention with published evidence of safety and clinical benefit in isolated LD. A more constructive approach is to encourage collaborative, well-designed studies that clarify which patients may benefit from each target. Avoiding categorical judgments will promote scientific progress and preserve therapeutic options for individuals with severe, treatment-resistant LD.