MRI-guided focused ultrasound: new hope for drug-resistant neurological conditions

The most common surgical approach to intractable disabling essential tremor (ET) remains DBS, however, not all patients are suitable. MRgFUS may be an appropriate alternative providing safety and efficacy are comparable. In this observational study, Cosgrove et al. explore long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor. This study represents the longest follow-up reported for MRgFUS thalamotomy and one of the largest multi-center cohorts at 5 years for thalamotomy of any method.

Outcomes including Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were recorded by expert neurologists. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. Forty-five and forty patients completed the 4 and 5-year follow-up respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment (p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). At completion of 5-year follow-up, reported adverse effects included paresthesia (8 patients), imbalance (6), unsteadiness (2), gait disturbances (2), limb weakness (2), dysmetria (2), dysgeusia (2), slow movements (1), and head pressure (1), and all were classified as mild (71%) to moderate (29%).

Cosgrove GR, et al. J Neurosurg. 2022 Aug 5; 138(4):1028–1033.

Approximately one-third of the patients with epilepsy eventually become refractory to medication; a small number undergo surgical intervention leaving the majority with sub-optimal treatment. Previous small open-label trials have suggested efficacy of ANT (anterior nucleus of off thalamus) deep brain stimulation in treating refractory epilepsy. This pilot study describes initial safety and feasibility experience from an open-label, single-center clinical trial of ANT FUSA in treatment-refractory epilepsy. Two adult subjects with treatment-refractory, focal-onset epilepsy were recruited and received ANT FUSA using the Exablate Neuro (Insightec) system. Safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) were determined at 3, 6, and 12 months. Safety was assessed by the absence of side effects including new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. Monthly seizure frequency was compared between baseline and post-thalamotomy. Both patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure-free at 12 months, and in the second patient, the frequency reduced from 90 to 100 seizures per month to 3–6 seizures per month.

Krishna et al. Epilepsia. 2023; 64:831–842.

Both radiofrequency pallidotomy and deep brain stimulation (DBS) using high-frequency electrical stimulation have efficacy in reducing motor symptoms in Parkinson’s disease (PD). Although DBS has become the preferred surgical option because of its ability to control bilateral symptoms and adjustability if symptoms are worsening, it remains an invasive surgical procedure compared to FUSA. FUSA involves real-time guidance with MRI to monitor tissue temperature, while ultrasound beams are gradually delivered to target tissue. A previous small open-label study demonstrated that FUSA of globus pallidus internus can improve dyskinesia and reduce the severity of motor signs on the treated side in off-medication state which is maintained for more than 1 year. This multi-center prospective double-blind randomized-controlled trial aimed to evaluate safety and efficacy of unilateral FUSA of the globus pallidus internus and was undertaken in 16 sites across, North America, Europe, and Asia.

Patients with PD with dyskinesia or motor fluctuations and motor impairment in the off-medication state were randomly assigned in a 3:1 ratio, to undergo either FUSA on the opposite side of the most symptomatic side of the body or a sham procedure. Primary outcome at 3 months was defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III) for the treated side in off-medication state or the score on Dyskinesia Rating Scale (UDysRS) in the on-medication state. After a 3-month blinded phase, an open-label phase lasted 12 months.

Of 94 participants recruited, 69 were assigned to FUSA and 25 to the sham procedure; 65 and 22 patients completed the primary outcome assessment. 69% of participants in the FUSA group and 32% in the sham group were deemed to have responded. Of those responding in the active treatment group, 19 met MDS-UPDRS three criteria only, eight met UDysRS criteria, and 18 met both criteria. In the 3-month responders from the active treatment group, 77% continued to have a response at 12 months. Adverse events in the active treatment group include dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.

Krishna V et al., N Engl J Med. 2023 Feb 23; 388(8):683–693.