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LAS VEGAS – according to two presentations delivered at the annual meeting of the North American Neuromodulation Society. The techniques’ surgical procedures, associated risks, and adverse event profiles may influence neurologists and patients in their choice of treatment.
FUS allows neurosurgeons to apply thermal ablation to create a lesion on the thalamus. MRI guidance enables precise control of the lesion location (within approximately 1 mm) and of the treatment intensity. The surgery can be performed with high-resolution stereotactic framing.
DBS entails the surgical implantation of a neurostimulator and attached leads and electrodes. The neurosurgeon drills a hole of approximately 14 mm in diameter into the skull so that the electrode can be inserted stereotactically while the patient is awake or asleep. The neurostimulator is installed separately.
Both treatments provide functional benefits
In 2016, W. Jeff Elias, MD, director of stereotactic and functional neurosurgery at the University of Virginia in Charlottesville, and his colleagues published the results of a randomized controlled trial that compared FUS with sham treatment in 76 patients with essential tremor. At three months, hand tremor had improved by approximately 50% among treated patients, but controls had no significant benefit(N Engl J Med. 2016 Aug 25;375[8]:730-9). The improvement among treated patients was maintained for 12 months. Disability and quality of life also improved after FUS.
A study by Schuurman et al. published in 2000 (N Engl J Med. 2000 Feb 17;342[7]:461-8) showed that DBS and FUS had similar efficacy at 1 year, said Kathryn L. Holloway, MD, professor of neurosurgery at Virginia Commonwealth University in Richmond. It included 45 patients with Parkinson’s disease, 13 with essential tremor, and 10 with multiple sclerosis who were randomized 1:1 to FUS or DBS. The primary outcome was activities of daily living, and blinded physicians assessed patient videos. Most of the patients who improved had received DBS, and most of the ones who worsened had received FUS, said Dr. Holloway. Among patients with essential tremor, tremor improved by between 94% and 100% with either treatment.
To find more recent data about these treatments, Dr. Holloway searched the literature for studies of FUS or DBS for essential tremor. She analyzed only studies that included unselected populations, blinded evaluations within 1 or 2 years of surgery, and tremor scores for the treated side. She found two studies of FUS, including Dr. Elias’s 2016 trial and a 2018 follow-up (Ann Neurol. 2018 Jan;83[1]:107-14). Dr. Holloway also identified three trials of DBS.
In these studies, reduction of hand tremor was 55% with FUS and between 63% and 69% with DBS. Reduction of postural tremor was approximately 72% with FUS and approximately 67% with DBS. Reduction of action tremor was about 52% with FUS and between 65% and 71% with DBS. Overall, DBS appears to be more effective, said Dr. Holloway.
A 2015 study (Mov Disord. 2015 Dec;30[14]:1937-43) that compared bilateral DBS, unilateral DBS, and unilateral FUS for essential tremor indicated that the treatments provide similar benefits on hand tremor, disability, and quality of life, said Dr. Elias. FUS is inferior to DBS, however, for total tremor and axial tremor.
Furthermore, the efficacy of FUS wanes over time, said Dr. Elias. He and his colleagues conducted a pilot study of 15 patients with essential tremor who received FUS (N Engl J Med. 2013 Aug 15;369[7]:640-8). At 6 years, 6 of 13 patients whose data were available still had a 50% improvement in tremor. “Some went on to [receive] DBS,” said Dr. Elias. “Functional improvements persisted more than the tremor improvement.”
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.
LAS VEGAS – according to two presentations delivered at the annual meeting of the North American Neuromodulation Society. The techniques’ surgical procedures, associated risks, and adverse event profiles may influence neurologists and patients in their choice of treatment.
FUS allows neurosurgeons to apply thermal ablation to create a lesion on the thalamus. MRI guidance enables precise control of the lesion location (within approximately 1 mm) and of the treatment intensity. The surgery can be performed with high-resolution stereotactic framing.
DBS entails the surgical implantation of a neurostimulator and attached leads and electrodes. The neurosurgeon drills a hole of approximately 14 mm in diameter into the skull so that the electrode can be inserted stereotactically while the patient is awake or asleep. The neurostimulator is installed separately.
Both treatments provide functional benefits
In 2016, W. Jeff Elias, MD, director of stereotactic and functional neurosurgery at the University of Virginia in Charlottesville, and his colleagues published the results of a randomized controlled trial that compared FUS with sham treatment in 76 patients with essential tremor. At three months, hand tremor had improved by approximately 50% among treated patients, but controls had no significant benefit(N Engl J Med. 2016 Aug 25;375[8]:730-9). The improvement among treated patients was maintained for 12 months. Disability and quality of life also improved after FUS.
A study by Schuurman et al. published in 2000 (N Engl J Med. 2000 Feb 17;342[7]:461-8) showed that DBS and FUS had similar efficacy at 1 year, said Kathryn L. Holloway, MD, professor of neurosurgery at Virginia Commonwealth University in Richmond. It included 45 patients with Parkinson’s disease, 13 with essential tremor, and 10 with multiple sclerosis who were randomized 1:1 to FUS or DBS. The primary outcome was activities of daily living, and blinded physicians assessed patient videos. Most of the patients who improved had received DBS, and most of the ones who worsened had received FUS, said Dr. Holloway. Among patients with essential tremor, tremor improved by between 94% and 100% with either treatment.
To find more recent data about these treatments, Dr. Holloway searched the literature for studies of FUS or DBS for essential tremor. She analyzed only studies that included unselected populations, blinded evaluations within 1 or 2 years of surgery, and tremor scores for the treated side. She found two studies of FUS, including Dr. Elias’s 2016 trial and a 2018 follow-up (Ann Neurol. 2018 Jan;83[1]:107-14). Dr. Holloway also identified three trials of DBS.
In these studies, reduction of hand tremor was 55% with FUS and between 63% and 69% with DBS. Reduction of postural tremor was approximately 72% with FUS and approximately 67% with DBS. Reduction of action tremor was about 52% with FUS and between 65% and 71% with DBS. Overall, DBS appears to be more effective, said Dr. Holloway.
A 2015 study (Mov Disord. 2015 Dec;30[14]:1937-43) that compared bilateral DBS, unilateral DBS, and unilateral FUS for essential tremor indicated that the treatments provide similar benefits on hand tremor, disability, and quality of life, said Dr. Elias. FUS is inferior to DBS, however, for total tremor and axial tremor.
Furthermore, the efficacy of FUS wanes over time, said Dr. Elias. He and his colleagues conducted a pilot study of 15 patients with essential tremor who received FUS (N Engl J Med. 2013 Aug 15;369[7]:640-8). At 6 years, 6 of 13 patients whose data were available still had a 50% improvement in tremor. “Some went on to [receive] DBS,” said Dr. Elias. “Functional improvements persisted more than the tremor improvement.”
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.
LAS VEGAS – according to two presentations delivered at the annual meeting of the North American Neuromodulation Society. The techniques’ surgical procedures, associated risks, and adverse event profiles may influence neurologists and patients in their choice of treatment.
FUS allows neurosurgeons to apply thermal ablation to create a lesion on the thalamus. MRI guidance enables precise control of the lesion location (within approximately 1 mm) and of the treatment intensity. The surgery can be performed with high-resolution stereotactic framing.
DBS entails the surgical implantation of a neurostimulator and attached leads and electrodes. The neurosurgeon drills a hole of approximately 14 mm in diameter into the skull so that the electrode can be inserted stereotactically while the patient is awake or asleep. The neurostimulator is installed separately.
Both treatments provide functional benefits
In 2016, W. Jeff Elias, MD, director of stereotactic and functional neurosurgery at the University of Virginia in Charlottesville, and his colleagues published the results of a randomized controlled trial that compared FUS with sham treatment in 76 patients with essential tremor. At three months, hand tremor had improved by approximately 50% among treated patients, but controls had no significant benefit(N Engl J Med. 2016 Aug 25;375[8]:730-9). The improvement among treated patients was maintained for 12 months. Disability and quality of life also improved after FUS.
A study by Schuurman et al. published in 2000 (N Engl J Med. 2000 Feb 17;342[7]:461-8) showed that DBS and FUS had similar efficacy at 1 year, said Kathryn L. Holloway, MD, professor of neurosurgery at Virginia Commonwealth University in Richmond. It included 45 patients with Parkinson’s disease, 13 with essential tremor, and 10 with multiple sclerosis who were randomized 1:1 to FUS or DBS. The primary outcome was activities of daily living, and blinded physicians assessed patient videos. Most of the patients who improved had received DBS, and most of the ones who worsened had received FUS, said Dr. Holloway. Among patients with essential tremor, tremor improved by between 94% and 100% with either treatment.
To find more recent data about these treatments, Dr. Holloway searched the literature for studies of FUS or DBS for essential tremor. She analyzed only studies that included unselected populations, blinded evaluations within 1 or 2 years of surgery, and tremor scores for the treated side. She found two studies of FUS, including Dr. Elias’s 2016 trial and a 2018 follow-up (Ann Neurol. 2018 Jan;83[1]:107-14). Dr. Holloway also identified three trials of DBS.
In these studies, reduction of hand tremor was 55% with FUS and between 63% and 69% with DBS. Reduction of postural tremor was approximately 72% with FUS and approximately 67% with DBS. Reduction of action tremor was about 52% with FUS and between 65% and 71% with DBS. Overall, DBS appears to be more effective, said Dr. Holloway.
A 2015 study (Mov Disord. 2015 Dec;30[14]:1937-43) that compared bilateral DBS, unilateral DBS, and unilateral FUS for essential tremor indicated that the treatments provide similar benefits on hand tremor, disability, and quality of life, said Dr. Elias. FUS is inferior to DBS, however, for total tremor and axial tremor.
Furthermore, the efficacy of FUS wanes over time, said Dr. Elias. He and his colleagues conducted a pilot study of 15 patients with essential tremor who received FUS (N Engl J Med. 2013 Aug 15;369[7]:640-8). At 6 years, 6 of 13 patients whose data were available still had a 50% improvement in tremor. “Some went on to [receive] DBS,” said Dr. Elias. “Functional improvements persisted more than the tremor improvement.”
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.
REPORTING FROM NANS 2019
