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Researchers compare focused ultrasound and DBS for essential tremor
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
DBS may improve nonmotor symptoms in Parkinson’s disease
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
REPORTING FROM NANS 2019
Key clinical point: Bilateral stimulation of the globus pallidus internus reduces sialorrhea and improves genitourinary symptoms.
Major finding: Patients reported 31% improvement in sialorrhea and 24% improvement in urinary function.
Study details: A prospective study of 34 patients receiving DBS of the STN or GPI.
Disclosures: No funding was reported.
Peripheral nerve stimulation reduces hand tremor
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
REPORTING FROM NANS 2019
Key clinical point: Two randomized trials indicate that peripheral nerve stimulation provides clinical benefits in essential tremor.
Major finding: Peripheral nerve stimulation reduced hand tremor and improved activities of daily living.
Study details: Two randomized, controlled studies including 138 patients with essential tremor and hand tremor.
Disclosures: Cala Health supported the studies.
DBS provides long-term benefits for patients with Parkinson’s disease
LAS VEGAS – , according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.
Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.
Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.
As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.
At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.
PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.
The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.
“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.
The investigators did not report any conflicts of interest.
LAS VEGAS – , according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.
Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.
Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.
As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.
At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.
PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.
The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.
“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.
The investigators did not report any conflicts of interest.
LAS VEGAS – , according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.
Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.
Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.
As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.
At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.
PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.
The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.
“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.
The investigators did not report any conflicts of interest.
REPORTING FROM NANS 2019
Key clinical point: DBS provides sustained improvements in motor and nonmotor symptoms over 2 years.
Major finding: At 1 year, DBS had significantly improved motor scores by 34%.
Study details: An analysis of prospective registry data for 359 patients with Parkinson’s disease who underwent DBS implantation.
Disclosures: The authors reported no study funding or conflicts of interest.