Insightec has published prospective multicentre results showing that staged bilateral treatment with the Exablate Neuro magnetic resonance-guided focused ultrasound system improved motor symptoms and medication-related complications in selected adults with advanced Parkinson’s disease. The study supports a United States indication approved in 2025, but its single-arm design and higher rate of persistent neurological effects after the second procedure make careful patient selection central to the technology’s future adoption.
Why the Lancet Neurology publication supports adoption while weakening the simplest efficacy narrative
The publication gives clinicians a fuller evidence base for a procedure that already has United States regulatory approval. Exablate Neuro can be used to create staged lesions in the pallidothalamic tract on opposite sides of the brain, with the second procedure performed at least six months after the first in eligible patients.
The trial enrolled 54 adults with levodopa-responsive Parkinson’s disease and medication-refractory motor complications at nine centres in the United States, Spain and Taiwan. All received an initial unilateral treatment, while 40 progressed to the procedure on the opposite side. Thirty-six completed 12 months of follow-up after bilateral treatment.
Participants experienced a median 32% improvement in the bilateral upper and lower extremity motor score three months after the second procedure. Secondary analyses also found substantial reductions in dyskinesia and time spent in the OFF state, when medication effects have diminished and Parkinson’s symptoms return.
Those results support focused ultrasound as a genuine therapeutic intervention rather than merely a tremor-control technology. The procedure addressed rigidity, slowness, medication fluctuations and involuntary movements across both sides of the body, potentially expanding its relevance to patients whose greatest burden is no longer confined to one limb.
The study’s own interpretation is more cautious than a simple success narrative. Investigators concluded that unilateral treatment produced meaningful benefit, while the second procedure delivered comparatively smaller additional motor gains and increased persistent moderate or severe adverse events. The technology may therefore be valuable for selected patients without becoming a routine bilateral alternative for everyone eligible for advanced therapy.
How staged pallidothalamic tractotomy changes brain circuits without incisions or implants
Exablate Neuro combines magnetic resonance imaging with focused ultrasound energy. Multiple ultrasound beams pass through the skull and converge on a precisely selected point inside the brain, where sufficient heat is generated to create a permanent therapeutic lesion.
The Parkinson’s disease procedure targets the pallidothalamic tract, a bundle of nerve fibres involved in transmitting abnormal movement signals from the basal ganglia toward the thalamus and motor cortex. Interrupting that pathway is intended to reduce excessive signalling associated with rigidity, bradykinesia, dyskinesia and motor fluctuations.
Magnetic resonance imaging allows the treatment team to plan the target, monitor temperature and observe the lesion as it forms. Lower-energy test sonications can be used before the final thermal exposure, enabling clinicians to assess immediate motor effects and look for emerging neurological problems.
The procedure is incisionless and does not require an implanted electrode, pulse generator or connecting lead. This differentiates focused ultrasound from deep brain stimulation, which involves placing electrodes inside the brain and implanting a programmable device beneath the skin.
Avoiding implanted hardware removes risks involving lead migration, battery replacement, device infection and mechanical failure. It may also appeal to patients who decline conventional surgery or who cannot manage years of device programming and maintenance.
The trade-off is irreversibility. Deep brain stimulation can be adjusted, reprogrammed or switched off when symptoms or adverse effects change. A focused ultrasound lesion cannot be removed or electronically modified after it has been created. Precision during treatment and conservative patient selection therefore carry greater importance.
What the 32% bilateral motor improvement means and why it should not be overstated
The primary endpoint measured motor function while participants were off Parkinson’s medication. Median upper and lower extremity scores declined from 33 points before any treatment to 21 points three months after the second procedure, representing an improvement of approximately 32%.
This improvement was statistically significant and remained visible through 12 months. Benefits began after the first procedure, with the second treatment intended to address symptoms on the side of the body not targeted initially.
The analysis should not be interpreted as evidence that bilateral treatment independently created the entire 32% gain. Much of the improvement had already occurred after the first-side procedure because clinicians initially treated the more severely affected side.
The 14 participants who did not progress to bilateral treatment also maintained substantial improvement after the unilateral procedure. Their bilateral motor scores improved by roughly 30% at 12 months when both sides of the body were considered, despite treatment being performed on only one side of the brain.
This finding complicates the value calculation for the second procedure. Patients may gain meaningful overall function from treating the dominant side alone, while adding the opposite side introduces another irreversible lesion and a higher neurological risk.
The absence of a randomized or sham-treated control group creates another limitation. Parkinson’s disease assessments can be influenced by patient expectations, evaluator judgement, day-to-day symptom variation and medication withdrawal conditions. Objective improvements were substantial, but the trial cannot determine how outcomes would compare with continued medication, deep brain stimulation or a sham intervention under identical conditions.
Why the second procedure produced the most important safety warning in the study
Treatment-related adverse events occurred in 21 of the 54 participants after unilateral treatment. Following the second procedure, such events occurred in 22 of 40 patients, with speech, gait and balance problems becoming more frequent.
Ten of the 40 bilaterally treated participants had persistent moderate or severe treatment-related events at 12 months. This means one-quarter of the bilateral group continued to experience clinically important effects a year after the second treatment.
Speech-related events occurred in 28% of patients after the second procedure, compared with 5% after the first. Axial symptoms involving gait, freezing, unsteadiness or imbalance occurred in 25% after the second treatment, compared with 13% following the initial procedure.
Four patients experienced clinically significant moderate speech deterioration involving dysphagia, dysarthria, reduced voice strength or stuttering. One patient developed severe persistent anarthria, meaning an inability to articulate speech. The event was associated with operator error, but it remains relevant because commercial performance depends on how consistently teams reproduce the procedure outside a controlled trial.
The higher bilateral risk is consistent with the history of ablative Parkinson’s surgery. Lesioning one side of a movement pathway can reduce symptoms while leaving the opposite hemisphere available to support speech, gait and other functions. Creating lesions on both sides can reduce that neurological reserve and expose deficits that were not apparent after unilateral treatment.
Staging the procedures by at least six months provides time to evaluate recovery and exclude patients who develop significant speech, swallowing or gait problems after the first intervention. It reduces risk but cannot eliminate the possibility of delayed or cumulative complications after the second procedure.
Why only 40 of 54 participants receiving the first treatment progressed to bilateral therapy
The difference between initial enrolment and bilateral treatment is not a minor statistical detail. Fourteen of the 54 participants did not proceed to the second procedure, meaning the bilateral results were generated in a more selected population than the original cohort.
Eligibility for the second treatment depended on clinical stability and the absence of significant neurological problems after the first procedure. Patients with meaningful speech impairment, swallowing difficulty or moderate-to-severe gait abnormalities were not appropriate candidates for another lesion.
This staged filtering is a safety mechanism and a source of selection bias. The 40 patients receiving bilateral treatment had already demonstrated that they could tolerate the unilateral procedure sufficiently well to be considered again.
Real-world outcome estimates may therefore depend on whether centres apply the same conservative thresholds. Broader use in patients with borderline balance, speech or cognitive function could produce a higher complication rate than the pivotal study.
The dropout between stages also affects the commercial opportunity. Regulatory eligibility does not mean that every patient receiving one procedure will become a candidate for a second. Hospitals and payers must evaluate the bilateral pathway as two linked but separately justified interventions rather than assume that every unilateral patient will complete treatment.
Can focused ultrasound compete with deep brain stimulation rather than merely offering less invasive surgery?
Deep brain stimulation remains an established advanced treatment for appropriately selected patients with medication-responsive Parkinson’s disease, disabling motor fluctuations, tremor or dyskinesia. Its principal strength is adjustability. Clinicians can modify stimulation settings as symptoms evolve and can target different clinical priorities over time.
Focused ultrasound offers a different value proposition. It avoids implanted hardware, surgical incisions and repeated programming. The therapeutic effect appears immediately during treatment, and there is no battery requiring future replacement.
These benefits may be particularly attractive for older patients, individuals concerned about implants, and those living far from specialist centres where repeated device programming would be difficult. Focused ultrasound could also serve patients who are otherwise suitable for advanced intervention but decline conventional neurosurgery.
The comparison becomes less favourable when reversibility and bilateral flexibility are prioritised. Parkinson’s disease progresses over years, while the symptoms requiring treatment may change. A permanent lesion created for current motor complications cannot be adjusted when gait, speech, cognition or medication response evolves.
Deep brain stimulation also has an established evidence base across larger populations and longer follow-up. The new focused ultrasound study provides 12-month bilateral outcomes for 40 treated patients, which is meaningful for regulatory evaluation but limited for understanding five-year or ten-year consequences.
Focused ultrasound is therefore unlikely to replace deep brain stimulation across the full advanced Parkinson’s population. Its nearer-term role is more likely to involve carefully selected patients who value an incisionless, hardware-free intervention and accept the permanence of lesioning.
How skull anatomy, magnetic resonance requirements and neurological status restrict access
Exablate Neuro is not technically suitable for every patient. Ultrasound energy must pass through the skull, and differences in bone density can affect whether adequate energy reaches the target safely.
Patients require computed tomography screening to calculate a skull density ratio. Those below the required threshold may not achieve reliable heating at the target or may face greater procedural difficulty.
The treatment also requires an extended period inside a magnetic resonance imaging scanner while the patient’s head remains immobilised. Individuals with incompatible implants, severe claustrophobia, inability to remain still or other magnetic resonance contraindications may not be eligible.
Advanced kidney disease, unstable cardiovascular conditions, uncontrolled hypertension, bleeding disorders, anticoagulant use and significant cerebrovascular disease can create further exclusions. Psychiatric instability, uncontrolled hallucinations or severe cognitive concerns may also make the risk-benefit profile unacceptable.
These restrictions mean focused ultrasound should not be described as a universally accessible non-surgical procedure. It remains a specialised neurosurgical intervention requiring movement-disorder assessment, neuroimaging, computed tomography screening and a multidisciplinary treatment centre.
The absence of an incision does not make the treatment non-invasive in its biological effect. The system permanently destroys a small region of brain tissue, and the consequences of inaccurate targeting can be severe.
Why operator experience and centre-level training may decide real-world safety
The severe anarthria associated with operator error highlights the importance of procedural standardisation. Focused ultrasound systems provide imaging guidance and thermal monitoring, but clinicians still make critical decisions involving target selection, energy escalation, symptom testing and when to stop treatment.
Commercial expansion beyond high-volume investigational centres may create variability. Teams performing their first procedures may need more time to develop confidence in anatomical targeting and intraoperative neurological assessment.
Insightec has expanded its global treatment network, but bilateral Parkinson’s therapy requires a more demanding training standard than unilateral tremor treatment. Centres need expertise in movement disorders, functional neurosurgery, neuroradiology, magnetic resonance imaging and speech or gait evaluation.
The second-side decision should involve more than technical eligibility. Multidisciplinary teams must determine whether the remaining motor burden justifies the cumulative neurological risk and whether the patient’s speech, balance and swallowing function provide sufficient reserve.
Postprocedure rehabilitation may also influence outcomes. Speech therapy, physical therapy and gait training could help patients compensate for mild deficits, but rehabilitation cannot reliably reverse an inaccurately placed permanent lesion.
The technology’s reputation will depend on whether complications remain concentrated in rare procedural failures or become more common as bilateral use expands. A post-approval study required by the Food and Drug Administration is intended to evaluate safety and effectiveness during routine clinical use.
What reimbursement and hospital economics could determine about wider adoption
Focused ultrasound requires access to compatible magnetic resonance imaging infrastructure, the Exablate Neuro system and a trained multidisciplinary team. Hospitals must invest in equipment, service, procedural time and clinical training before treating sufficient numbers of patients to justify the programme.
The procedure avoids the long-term costs associated with implanted hardware, battery replacement and repeated programming visits. This may create an attractive economic argument over several years, particularly for patients who would otherwise undergo deep brain stimulation.
The initial cost remains substantial, and bilateral therapy involves two separate procedures at least six months apart. Payers may require documentation showing that symptoms remain disabling after the first treatment and that the second procedure is medically justified.
Coverage policies could differ between unilateral and bilateral treatment. A payer may accept focused ultrasound for a dominant-side disability while applying greater scrutiny to a second procedure carrying higher speech and gait risks.
Geographic access presents another challenge. Patients may need to travel to specialised centres for screening, treatment and follow-up. The absence of routine device programming reduces long-term visits, but the initial pathway remains concentrated in tertiary care.
Commercial growth will therefore depend on more than clinical publication. Insightec must support centre development, payer coverage, referral education and consistent selection standards while avoiding expansion that outpaces procedural expertise.
What longer follow-up must show before bilateral focused ultrasound becomes routine
The most important unresolved question is whether motor improvement persists beyond 12 months after the second procedure. Parkinson’s disease continues to progress, and benefits from pathway lesioning may become less meaningful as axial, cognitive or non-motor symptoms emerge.
Longer observation must also establish whether persistent speech and gait problems improve, remain stable or worsen. A complication that appears moderate at 12 months could have greater functional consequences as the patient ages or develops additional Parkinson’s disability.
Future studies should compare focused ultrasound with deep brain stimulation and modern medical management in patients eligible for more than one advanced therapy. Patient-reported quality of life, caregiver burden, independence and healthcare use may be more informative than motor scores alone.
Research should also identify predictors of benefit and harm. Baseline speech performance, gait stability, lesion location, skull characteristics, age, disease duration and cognitive profile could help determine who gains enough from the second procedure to justify the risk.
The Lancet Neurology study confirms that staged bilateral focused ultrasound can reduce disabling Parkinson’s motor complications without incisions or implanted hardware. It also demonstrates why the second procedure cannot be treated as a simple completion of the first.
Insightec has expanded the technological possibility of bilateral Parkinson’s treatment. The decisive clinical challenge is ensuring that relief from dyskinesia and OFF time does not come at an unacceptable cost to speech, balance and everyday independence.
Insightec’s Parkinson’s study shows motor gains, but bilateral treatment raises safety concerns added by Pallavi Madhiraju on
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