Focused Ultrasound for Parkinson Disease

1.A target for each problem

The choice of target follows the dominant problem. Vim thalamotomy addresses tremor but not the rigidity, bradykinesia, or levodopa-induced dyskinesia that disable most patients with advancing disease. GPi pallidotomy improves contralateral motor signs and, importantly, levodopa-induced dyskinesia. Pallidothalamic tractotomy (PTT) lesions the pallidal outflow fibers (the ansa and fasciculus lenticularis converging in the field of Forel) and aims at the same motor-complication phenotype with a smaller, deeper target. Subthalamotomy (STN) targets the subthalamic nucleus and can improve the full triad on one side, but remains investigational in the United States.

2.The FDA timeline

The regulatory history reads as a stepwise expansion from tremor to motor complications, and from unilateral to bilateral:

• 2018 — unilateral Vim thalamotomy for tremor-dominant Parkinson disease, on the strength of a randomized sham-controlled trial (Bond et al., JAMA Neurol 2017).
• 2021 — unilateral GPi pallidotomy for advanced Parkinson disease with motor complications (mobility, rigidity, or dyskinesia), supported by the randomized trial later reported by Krishna and colleagues (N Engl J Med 2023).
• July 2025 — staged bilateral pallidothalamic tractotomy, the first approved staged bilateral transcranial ablation, supported by the multicentre single-arm trial reported by Dalvi and colleagues (Lancet Neurol 2026).

Two points of accuracy are worth stating plainly. First, the 2025 approval is for the pallidothalamic tract, not the subthalamic nucleus; focused ultrasound subthalamotomy remains investigational in the US despite a supportive European randomized trial (Martínez-Fernández et al., N Engl J Med 2020). Second, "bilateral" here means staged — two separate procedures months apart, not a single bilateral session — and the approval is bounded by the careful selection the trial used.

3.Staged bilateral pallidothalamic tractotomy (Dalvi 2026)

The trial behind the 2025 approval was a prospective, multicentre, single-arm study at nine centres (six US, two Spain, one Taiwan) in adults with idiopathic, levodopa-responsive Parkinson disease and motor complications. Patients underwent unilateral PTT to the symptom-dominant side; those meeting prespecified criteria proceeded to contralateral PTT a minimum of six months later. Fifty-four patients received unilateral treatment and 40 went on to bilateral treatment. The design embedded a safety feature unique to ablation under thermometry: low-temperature thermal neuromodulation (below ~48°C) allows a reversible test of the target before the definitive lesion is made.

The headline efficacy result, on the off-medication summed upper- and lower-extremity motor score, was a median ~32% improvement after bilateral treatment (from a median 33 to 21 points at 3 months post-bilateral), with benefit appearing within a month of the first procedure and sustained to 12 months. Reported in the manufacturer's and clinical coverage, unilateral treatment produced a roughly 50% improvement in the treated-side score — an important framing, because it means much of the benefit is captured by the first side, while the second side adds a smaller motor increment at a higher cumulative risk.

4.The honest reading of the safety data

The safety signal is the substance of the trial, and it is candid. Treatment-related adverse events occurred in 39% after unilateral treatment (with only one patient, 2%, having a persistent moderate event at 6 months) but in 55% after bilateral treatment, and crucially 25% had persistent moderate or severe adverse events at 12 months — predominantly affecting speech, gait, and balance. One patient (3%) developed severe persistent anarthria. The investigators' own interpretation is the right one to carry into clinic: unilateral PTT was safe and effective, but bilateral treatment offered small additional motor gains while meaningfully increasing persistent moderate-to-severe adverse events, consistent with the historical experience of bilateral ablative movement-disorder surgery. Bilateral PTT therefore demands rigorous selection and explicit counselling about cumulative risk — it is an option to be offered cautiously, not a default.

5.Skull density ratio and the bone requirement

Eligibility for every Parkinson target, like tremor, is gated by the skull density ratio (SDR) derived from a screening head CT — the ratio of cortical to marrow bone density across the array, a proxy for how efficiently the skull transmits acoustic energy. The PTT trial excluded patients with an SDR below 0.40, and a screening CT for SDR (and the software skull score) is a mandatory part of work-up for thalamotomy, pallidotomy, and tractotomy alike.

On the common question of whether the bone requirement differs between essential tremor and Parkinson disease: in practice the screening process and the working threshold are essentially the same — a head CT, with an SDR cut near 0.40 (historically the device excluded SDR at or below roughly 0.45 ± 0.05). The Parkinson pivotal trials used an explicit SDR ≥ 0.40 entry criterion. I have not found evidence of a formally different FDA-mandated SDR cutoff for the two indications; the apparent difference patients and referrers perceive usually reflects which target and trial is being discussed and how strictly a given centre applies the threshold, rather than a separate numeric rule for Parkinson disease. What is true is that deeper, smaller targets (PTT, STN) leave less geometric margin, so an inefficient skull is less forgiving for a Parkinson outflow target than for a Vim lesion.

6.Efficiency loss, energy escalation, and the low-SDR patient

The energy story is identical in physics to tremor treatment and worth restating because it changes planning. Each sonication deposits heat not only at the target but in the skull and scalp; cumulative bone heating aberrates the beam, enlarges and blurs the focal spot, and so reduces the heating efficiency (peak temperature rise per joule delivered) of every subsequent sonication. The operator must therefore escalate acoustic power and energy as the session proceeds to reach the next temperature milestone, climbing from a reversible test near 46–50°C to a definitive lesion near 54–60°C.

This escalation runs into a hard energy ceiling: a device maximum, beyond which scalp burns, off-target heating, and acoustic cavitation are risked. For a low-SDR patient the ceiling is reached sooner, and the focal temperature can plateau below the ablative range even at maximum tolerated energy — the dominant mechanism of treatment failure. Planning for a low-ratio skull front-loads high-energy sonications while the skull is still cool and efficiency is highest, and minimizes wasted alignment sonications, exactly as described for tremor. Because the lost energy lands in the scalp, the awake patient feels the climb: scalp heating, pressure, and headache as power rises through the mid range (in practice, on the order of ~500 W and above), and dizziness, vertigo, or frank discomfort at the highest powers used to drive an inefficient skull (roughly ~900 W and above) — approximate, patient-specific practice observations rather than fixed cutoffs, but they explain why a low-SDR Parkinson treatment is both harder on the patient and less certain to complete. The cross-cutting physics, temperatures, and SDR bands are laid out in detail on the essential tremor page.

7.Finding the target: anatomy-driven, not coordinate-driven

The PTT target is white matter, not a nucleus: the pallidothalamic tract where it passes through Forel's field H1 (the thalamic fasciculus), just inferior to the thalamus, after the ansa lenticularis and the fasciculus lenticularis (field H2) have converged. The single most important practical point is that this target is reached by indirect, image-anchored targeting — you start from an atlas estimate and then re-anchor it to structures visible in the individual patient, rather than trusting fixed millimetric coordinates.

The workflow, in order:

• Set the reference frame. Define the anterior and posterior commissures on a high-resolution T2 sequence and mark the intercommissural (AC–PC) line. The target plane sits at, or roughly 0.9–1 mm below, the intercommissural plane.
• Find the two visible landmarks. On T2 the mammillothalamic tract (MTT) appears as a hypointense dot medially and the subthalamic nucleus (STN) as a hypointense band inferolaterally. The PTT lies above the STN and lateral to the MTT — position the target relative to these, then confirm with an atlas overlay (the Morel atlas of the human thalamus and basal ganglia).
• Use coordinates only as a starting estimate. As an atlas starting point (scaled to the patient's intercommissural distance, which ranges ~24–30 mm), the target is on the order of ~8–10 mm lateral to the midline, at or ~1 mm below the AC–PC plane, in the mid-to-posterior subthalamic region. Re-anchor every case to the MTT and STN — the coordinate is a hypothesis, the anatomy is the answer.

8.Building the lesion (MRgFUS): sub-units, planes, and the awake test

The focal spot is a small cigar — roughly 1.5 × 1.5 × 3 mm, long axis cranio-caudal. The standardized PTT lesion is assembled from 5–7 stacked sub-units placed at the intercommissural plane (DV0) and ~1 mm below it (V1), tiled along the tract to cover it while staying off the neighbors above. The sonication ladder is the same as for tremor, but the neurologic test is read against the structures in the table:

• Alignment (sub-therapeutic): confirm on MR thermometry that the heated focal spot sits exactly on the planned target; correct any geometric offset.
• Verification / reversible test (~46–50°C): warm the target to a reversible effect and examine the awake patient — look for improvement in rigidity, tremor, and bradykinesia, and watch for paresthesia (lemniscus / VC thalamus), tonic pull or slurring (internal capsule), or diplopia (red nucleus / oculomotor). Any adverse sign at this temperature is a reason to reposition before committing.
• Ablation (~54–60°C): once the test confirms benefit without deficit, raise the temperature to a permanent lesion, sub-unit by sub-unit, re-checking the patient neurologically between shots.

Because the lesion is permanent and built incrementally, the reversible test phase is the safety net — the discipline of the procedure is to treat every adverse sign at sub-ablative temperature as a targeting error to be fixed, not a side effect to be accepted.

9.The DBS analogs: same circuit, different tool

There is no standard "PTT by DBS" — pallidothalamic tractotomy is an ablative concept (radiofrequency historically, MRgFUS now). DBS engages the same pallidal-outflow circuit either upstream at the GPi (GPi DBS) or in the subthalamic/Forel region. The closest electrode analog to the PTT target is cZI/PSA DBS (caudal zona incerta / posterior subthalamic area): the lead is placed using the STN and red nucleus as T2 landmarks, sitting posteromedial to the STN around Forel's field H, commonly at or just below the AC–PC plane (practical rules of thumb: ~2 mm posterior to the posterior STN border, or ~3 mm below the Vim; ~10–12 mm lateral) — mainly a tremor and dystonia target. The conceptual difference is the trade every ablation-versus-stimulation decision turns on: lesioning interrupts the tract permanently with an awake intraoperative test but no later adjustment; DBS places an adjustable lead and tunes it afterward, at the cost of implanted hardware. The targeting anatomy — Forel's fields, with the MTT, STN, and red nucleus as landmarks — is shared.