Neuropathology of Parkinson's disease after focused ultrasound thalamotomy.

Focused ultrasound (FUS) thalamotomy is an emerging treatment for tremor-dominant Parkinson's disease (PD). We report the first postmortem neuropathologic study of FUS thalamotomy in a 68-year-old man with tremor-dominant PD, which was performed seven months before he died. Although the peak voxel temperature at the target was <54 °C, his tremor improved on intraoperative and postoperative assessments. Additionally, postoperative MRI demonstrated a thalamic lesion. Lewy body-related pathology consistent with PD was detected. There was also a 5-mm lesion in the ventral lateral thalamus characterized by demyelination and neuropil loss, with many lipid-laden macrophages, but no lymphocytic infiltrates and relatively preserved neurons and axons. Additional pathological assessments after FUS thalamotomy are needed to determine if the observed brain changes are typical of this procedure.

Introduction

Purpose Thermal ablation

Study Objective To report the first postmortem neuropathologic findings in a patient with tremor-dominant Parkinson’s disease who underwent MR-guided focused ultrasound thalamotomy.

Animal model / Human subject Homo sapiens, not applicable, 68 years, male

Disease model Parkinson's disease

MRI or image guidance method MR-guided FUS with a stereotactic head frame using an InSightec transducer in a 3 T MRI; volumetric MRI was acquired and fused to the patient’s preoperative MRI and CT for targeting, with the left thalamic target planned by coordinates (14.0 mm lateral to midline, 6.8 mm anterior to the posterior commissure, 2 mm above the commissural plane).

Targeted brain region(s) Thalamus

Target coordinates AP: 6.8 mm anterior to the posterior commissure; ML: 14.0 mm lateral to the midline (left); DV: 2 mm above the commissural plane

Outcomes and Safety

Summary of Outcomes MR-guided FUS thalamotomy produced immediate intra- and postoperative suppression of the patient’s tremor despite peak voxel temperatures of only 51–54 °C, and postmortem showed a 5 × 3 mm ventral lateral thalamic lesion with demyelination and abundant lipid-laden macrophages but relatively preserved neurons and axons. Successful sonication parameters were three therapeutic sonications delivering 16,000 J, 24,000 J and 36,000 J with prolonged durations (~20–35 s) (after alignment sonications totaling ~6,700 J).

Duration of biological effect 7 months

Safety-related matter The patient had improved intra- and postoperative tremor control with no immediate adverse events reported; postoperative MRI showed an expected thalamic lesion with surrounding edema and intralesional blood products, while autopsy revealed no infarction or hemorrhage. The patient developed progressive tetraparesis during subsequent immunotherapy and died 7 months after FUS, a course attributed to his metastatic melanoma/immunotherapy rather than directly to the FUS procedure.

Brain Region

Ultrasound Parameters

Ultrasound instrument Ultrasound transducer (InSightec)

FUS Mode pulsed

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

Treatment frequency single session

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