What are beneficial alternatives for patients who have refractory essential tremor? Four studies provide insight into the outcomes of high-intensity focused ultrasound.
Surgical ablation as a treatment strategy for refractory essential tremor (ET) and Parkinson disease has been an option for patients with these conditions for quite some time. With relatively good clinical efficacy, the main disadvantage of this approach is that the surgery is invasive, requires a craniotomy, and exposes patients to the risk of intracranial complications, such as bleeding and infections.
High-intensity focused ultrasound is one of the new approaches to thalamotomy that is being used for patients who have refractory ET or refractory tremors of PD. This procedure, which hundreds of patients have already experienced, relies on the thermal energy of ultrasound, guided by MRI, to achieve non-invasive thalamic ablation.
Several studies have published findings on therapeutic patient response and adverse effects, providing insight into the outcomes of this treatment approach.
A large meta-analysis used data from nine studies, including a total of 160 patients who were treated with MRI guided high intensity focused ultrasound for their ET.1 The pooled percentage improvements in four different quality-of-life measures that are commonly used in ET studies were 62.2%, 62.4%, 69.1%, and 46.5%. Dizziness and ataxia were the most common adverse effects at three months after the procedure, and these effects had significantly resolved at 12 months post procedure.
Thalamotomy treatment is used to control refractory tremors in patients with Parkinson disease (PD), but it does not help control other symptoms of PD, such as bradykinesia or rigidity. A small study by Zaaroor and colleagues2 included 30 patients who had either PD or ET-PD, which is defined as ET with subsequent development of PD. This group underwent unilateral thalamotomy of the ventral intermediate nucleus using MRI guided ultrasound.
After treatment, the mean score of the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) changed from a pre-treatment value of 24.9 to 16.4 at one month, and to 13.4 at six months. Similar improvements were documented using the Clinical Rating Scale for Tremor (CRST) and the Quality of Life in Essential Tremor (QUEST) questionnaire.
Patients experienced some adverse effects during the procedure. These include headaches, dizziness, paresthesia, and nausea, but no complications were noted. Adverse effects after the procedure included ataxia and unsteadiness, and these effects resolved after 3 months.
In another study, researchers took cognitive function into account.3 The study authors noted that some neurosurgical procedures may cause cognitive decline. This prospective trial included 20 participants who underwent magnetic resonance-guided focused ultrasound thalamotomy for treatment of their ET. The result was a 68% improvement in tremor scores in the hand contralateral to the thalamotomy, without any noticeable improvement of tremors in the hand ipsilateral to the thalamotomy. The authors reported minimal cognitive decline, improved memory function, and an improved quality of life.
Because it is a relatively new procedure, MRI guided focused ultrasound thalamotomy does not yet have a long track record with which to observe efficacy or late adverse outcomes. A trial by Chang and colleagues4 reporting relatively delayed outcomes. Of the 76 trial participants initially enrolled in the study, nine were excluded from the two-year follow up due to inadequate ablation or having undergone another neurosurgical treatment in addition to their ultrasound thalamotomy.
A few patients continued to experience paresthesias and gait problems at one-year follow up. At two-year follow up, the patients’ degree of tremor improvement was sustained, and they did not develop new adverse effects that had not already emerged immediately after the procedure.4 While this study’s patient population is small with a short follow-up, the lack of newly emerging adverse effects or decline in efficacy within the first two years may suggest that this treatment option may be one of the beneficial alternatives for patients who have refractory tremors.
1. Mohammed N, Patra D, Nanda A. A meta-analysis of outcomes and complications of magnetic resonance-guided focused ultrasound in the treatment of essential tremor. Neurosurg Focus. 2018;44:E4.
2. Zaaroor M, Sinai A, Goldsher D, et al. Magnetic resonance-guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases. J Neurosurg. 2018 Jan;128(1):202-210.
3. Jung NY, Park CK, Chang WS, et al. Effects on cognition and quality of life with unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. Neurosurg Focus. 2018;44:E8.
4. Chang JW, Park CK, Lipsman N. A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up. Ann Neurol. 2018;83:107-114.