Adverse events
In their 2016 trial of FUS, Dr. Elias and his colleagues observed 210 adverse events, which is approximately “what you would expect with a modern day, FDA-monitored clinical trial.” Sensory effects and gait disturbance accounted for most of the thalamotomy-related adverse events. Sensory problems such as numbness or parestheisa persisted at 1 year in 14% of treated patients, and gait disturbance persisted at 1 year in 9%. The investigators did not observe any hemorrhages, infections, or cavitation-related effects from FUS.
In a 2018 analysis of five clinical trials of FUS for essential tremor, Fishman et al. found that 79% of adverse events were mild and 1% were severe (Mov Disord. 2018 May;33[5]:843-7). The risk of a severe adverse event therefore can be considered low, and it may decrease as neurosurgeons gain experience with the procedure, said Dr. Elias.
In the 2000 Schuurman et al. study, the researchers observed significantly fewer adverse events overall among patients with Parkinson’s disease or essential tremor who received DBS, compared with patients who received FUS. Cognitive deterioration, severe dysarthria, and severe ataxia were more common in the FUS group than in the DBS group. Dr. Holloway’s analysis of adverse events in the five more recent trials that she identified yielded similar results.
Although MRI-guided FUS is a precise way to make lesions, functional areas in the thalamus overlap, which makes it more difficult to target only the intended region, said Dr. Holloway. The functional overlap thus increases the risk of adverse events (e.g., sensory impairments, dysarthria, or ataxia). The adverse events that result from FUS may last as long as a year. “Patients will put up anything for about a month after surgery, and then they start to get annoyed,” said Dr. Holloway.
In addition, Schuurman et al. found that FUS entailed a greater risk of permanent side effects, compared with DBS. “That’s the key point here,” said Dr. Holloway. Most of the adverse effects in the DBS group were resolved by adjusting or turning off the stimulator. Hardware issues resulting from DBS are frustrating, but reversible, but a patient with an adverse event after FUS often is “stuck with it,” said Dr. Holloway. The Schuurman et al. data indicated that, in terms of adverse events, “thalamotomy was inferior to DBS,” she added.
Implantation of DBS entails the risks inherent to surgeries that open the skull (such as seizures, air embolism, and hemorrhage). DBS entails a 2% risk of hemorrhage or infection, said Dr. Elias. Furthermore, as much as 15% of patients who undergo DBS implantation require additional surgery.
“FUS is not going to cause a life-threatening hemorrhage, but DBS certainly can,” said Dr. Holloway.
Managing disease progression
Essential tremor is a progressive disease, and older patients are more likely to have exponential progression than linear progression. Data, such as those published by Zhang et al. (J Neurosurg. 2010 Jun;112[6]:1271-6), indicate that DBS can “keep up with the progression of the disease,” said Dr. Holloway. The authors found that tremor scores did not change significantly over approximately 5 years when patients with essential tremor who had received DBS implantation had periodic assessments and increases in stimulation parameters when appropriate.
If a patient with essential tremor undergoes FUS thalamotomy and has subsequent disease progression, DBS may be considered for reducing tremor, said Dr. Holloway. Most adverse events resulting from DBS implantation are reversible with adjustment of the stimulation parameters. A second thalamotomy, however, could cause severe dysarthria and other irreversible adverse events. “Only DBS can safely address tremor progression,” said Dr. Holloway.