MEDLINE Abstracts: Treatment of Essential Tremor
MEDLINE Abstracts: Treatment of Essential Tremor
What's new concerning treatments for essential tremor? Find out in this easy-to-navigate compilation of MEDLINE abstracts compiled by the editors at Medscape.
Schwalb JM, Riina HA, Skolnick B, et al
J Neurosurg. 2001;94:1010-1012
The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe 3 patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region. Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.
Brin MF, Lyons KE, Doucette J, et al
Neurology. 2001;56:1523-1528
Objective: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand.
Background: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and1 double-masked study of essential hand tremor.
Methods: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer.
Results: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness.
Conclusion: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.
Koller WC, Lyons KE, Wilkinson SB, et al
Mov Disord. 2001;16:464-468
Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, 7 were explanted prior to 24 months, 11 were lost to long-term follow-up, and 3 died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and 1 patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures. (Copyright 2001 Movement Disorder Society.)
Ceballos-Baumann AO, Boecker H, Fogel W, et al
Neurology. 2001;56(10):1347-1354
Background: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex.
Methods: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during 3 experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation.
Results: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation.
Conclusions: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.
Krauss JK, Simpson RK Jr, Ondo WG, et al
Neurosurgery. 2001;48:535-541
Objective: To rationalize the technique and reduce the costs associated with chronic deep brain stimulation of the thalamus for treatment of refractory tremor.
Methods: The efficacy and safety of a modification in surgical techniques was prospectively assessed in 94 patients with tremor. Bilateral electrodes were implanted in 29 patients, and 65 patients received unilateral implants. Forty-five patients had Parkinson's disease tremor, 42 patients had essential tremor, and 7 patients had kinetic tremors of different causes. In all instances, intraoperative stimulations to analyze the thresholds of intrinsic and extrinsic responses were performed directly with the implanted leads. The electrodes were repositioned until satisfactory results were achieved. The pulse generators were implanted directly after the first step in the same operative session. Patients were not subjected to interoperative test stimulation trials.
Results: Postoperative improvement of tremor at a mean follow-up of 11.9 months was rated as excellent in 47 patients (50%), marked in 37 patients (39%), moderate in 8 patients (9%), and minor in 2 patients (2%). There was no persistent morbidity related to surgery. In patients with Parkinson's disease, the symptomatic improvement of tremor was rated as excellent in 51% of patients, marked in 36%, moderate in 11%, and minor in 2%. In patients with essential tremor, symptomatic outcome was classified as excellent in 57% of patients, marked in 36%, moderate in 5%, and minor in 2%. Six of the 7 patients with kinetic tremor achieved marked symptomatic improvement, and 1 patient experienced moderate improvement. Forty patients experienced stimulation-related side effects. Side effects were mild in general, and they were reversible with a change in electrical parameters. They occurred more frequently in patients who had bilateral stimulation.
Conclusion: Excellent to marked improvement of tremor is achieved in the majority of patients with physiological target determination via implanted leads in thalamic deep brain stimulation. Interoperative test stimulation trials are unnecessary. Modifications in technique may help to reduce the costs of the related hospital stay.
Obwegeser AA, Uitti RJ, Witte RJ, et al
Neurosurgery. 2001;48:274-281
Objective: We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed.
Methods: Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed.
Results: Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < .001), lower-limb (P < .01), and midline (P < .001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < .01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < .001) and postural (P < .01) tremors and ipsilateral postural tremor (P < .05). Activities of daily living improved after unilateral surgery (P < .001) and additionally after bilateral surgery (P < .05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants.
Conclusion: Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible
Pahwa R, Lyons KE, Wilkinson SB, et al
Mov Disord. 2001;16:140-143
Objective: To compare outcome in essential tremor (ET) patients who have undergone either thalamotomy or deep brain stimulation (DBS) of the thalamus.
Background: Although both thalamotomy and thalamic DBS are effective surgical treatments of tremor, it is not known if one procedure is superior to the other.
Design/Methods: Thirty-five ET patients underwent thalamotomy between 1994-1998. Data on 18 patients were excluded. The remaining 17 patients were matched for age, sex, side of surgery, and tremor severity to 17 ET patients who underwent thalamic DBS. There were 9 men and 8 women in each group. The mean age of the thalamotomy group was 74.4 years and that of the thalamic DBS group was 73.1 years.
Results: There were no significant differences between any efficacy outcome variables comparing thalamotomy to DBS of the thalamus at baseline or follow-up visits. The surgical complications were higher for the thalamotomy group as compared to the DBS group. However, a larger number of DBS patients underwent repeat surgeries due to problems with the device and the leads.
Conclusion: Although the efficacy is similar for thalamotomy and DBS of the thalamus for ET, thalamotomy is associated with a higher complication rate. DBS of the thalamus should be the procedure of choice for the surgical treatment of ET in most cases.
Ondo W, Almaguer M, Jankovic J, Simpson RK
Arch Neurol. 2001;58:218-222
Background: Unilateral thalamic deep brain stimulation (DBS) is accepted as an effective treatment for essential tremor (ET) and the tremor of Parkinson's disease (PD). There are, however, relatively little data concerning bilateral thalamic DBS and no thorough comparisons between the 2 methods.
Methods: To assess the relative benefit of a staged second contralateral DBS placement in patients with PD and ET, we compared preoperative baseline assessments with those at 3 months after the initial implantation, and again at 3 months after the second contralateral implantation. The assessments included the Unified Parkinson's Disease Rating Scale for patients with PD (n = 8) and a modified Unified Tremor Rating Assessment for patients with ET (n = 13). The design included open and blinded (unknown activation status) assessments.
Results: Overall, after the second implantation, all specific measures assessing tremor contralateral to that side improved in patients with PD and ET, generally without sacrificing those contralateral to the first side implantation. Midline tremors (face and head) improved only after the second side implantation. In patients with ET, functional and subjective scores tended to further improve after the second placement; however, patients with PD had less subjective improvement. Hand tremor scores in patients with ET randomized to "on" stimulation improved from 6.7 +/- 0.9 to 1.3 +/- 1.2 (P < .005). The scores of patients with PD randomized to on stimulation improved from 9.3 +/- 1.0 to 1.0 +/- 0.5. (Data are given as mean +/- SD.) Tremor scores did not change from baseline in those patients randomized to "off" stimulation in either group. Adverse events related to stimulation increased after the second implantation in both groups.
Conclusions: Bilateral thalamic DBS is more effective than unilateral DBS at controlling bilateral appendicular and midline tremors of ET and PD. Despite this, overall functional disability only improved in patients with ET, possibly secondary to more problematic adverse events in patients with PD, especially balance problems. Bilateral DBS should be considered when unilateral DBS does not offer satisfactory benefit, especially in patients with ET.
Obwegeser AA, Uitti RJ, Turk MF, et al
Mayo Clin Proc. 2001;76:87-89
Thalamic deep brain stimulation is becoming increasingly popular for the control of drug-refractory tremor. Implantable cardiac pacemakers and defibrillators are commonly used therapeutic modalities. Concerns exist about the potential interactions between these 2 devices in the same patient, but no experience has been reported previously. We describe a patient with essential tremor who had a deep brain stimulator implanted into the left ventral intermediate nucleus of thalamus, who subsequently needed an implantable cardioverter-defibrillator. Despite concerns about possible interactions between the 2 types of implanted electrical devices (ie, a situation similar to drug-drug interactions), the deep brain stimulator and the implanted pacemaker-defibrillator functioned appropriately, and no interaction occurred in our patient.
Gunal DI, Afsar N, Bekiroglu N, Aktan S
Neurol Sci. 2000;21:315-317
Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for 4 weeks, each separated by a 2-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.
Pacchetti C, Mancini F, Bulgheroni M, et al
Neurol Sci. 2000;21:349-353
This study aimed to improve botulinum toxin's (BTX) efficacy and to reduce its unwanted effects in the treatment of functional disability due to essential tremor (ET) of the hand. Twenty patients with disabling ET, not responding to conventional pharmacological therapy, were enrolled in this open-label study. Activities of daily living self-questionnaire (ADLS) and severity tremor scale (STS) were used to establish patients' functional disability and tremor severity. Accelerometry and surface electromyography were used to identify the arm muscles with tremorogenic activity during impaired positions. Global rating was used to measure treatment efficacy and unwanted effects. BTX type A was injected into the muscles principally responsible for impaired positions. After BTX treatment, there was a significant reduction in both severity and functional rating scales scores (ADLS and STS) and of tremor amplitude as measured with accelerometry and EMG. Adverse effects were limited to a slight third finger extension weakness in 15% of patients. BTX injections are effective and safe in reducing disability due to ET, if based on the criterion of functional selection.
MEDLINE Abstracts: Treatment of Essential Tremor
What's new concerning treatments for essential tremor? Find out in this easy-to-navigate compilation of MEDLINE abstracts compiled by the editors at Medscape.
Revision of Deep Brain Stimulator for Tremor. Technical Note
Schwalb JM, Riina HA, Skolnick B, et al
J Neurosurg. 2001;94:1010-1012
The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe 3 patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region. Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.
A Randomized, Double Masked, Controlled Trial of Botulinum Toxin Type A in Essential Hand Tremor
Brin MF, Lyons KE, Doucette J, et al
Neurology. 2001;56:1523-1528
Objective: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand.
Background: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and1 double-masked study of essential hand tremor.
Methods: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer.
Results: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness.
Conclusion: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.
Long-Term Safety and Efficacy of Unilateral Deep Brain Stimulation of the Thalamus in Essential Tremor
Koller WC, Lyons KE, Wilkinson SB, et al
Mov Disord. 2001;16:464-468
Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, 7 were explanted prior to 24 months, 11 were lost to long-term follow-up, and 3 died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and 1 patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures. (Copyright 2001 Movement Disorder Society.)
Thalamic Stimulation for Essential Tremor Activates Motor and Deactivates Vestibular Cortex
Ceballos-Baumann AO, Boecker H, Fogel W, et al
Neurology. 2001;56(10):1347-1354
Background: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex.
Methods: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during 3 experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation.
Results: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation.
Conclusions: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.
Concepts and Methods in Chronic Thalamic Stimulation for Treatment of Tremor: Technique and Application
Krauss JK, Simpson RK Jr, Ondo WG, et al
Neurosurgery. 2001;48:535-541
Objective: To rationalize the technique and reduce the costs associated with chronic deep brain stimulation of the thalamus for treatment of refractory tremor.
Methods: The efficacy and safety of a modification in surgical techniques was prospectively assessed in 94 patients with tremor. Bilateral electrodes were implanted in 29 patients, and 65 patients received unilateral implants. Forty-five patients had Parkinson's disease tremor, 42 patients had essential tremor, and 7 patients had kinetic tremors of different causes. In all instances, intraoperative stimulations to analyze the thresholds of intrinsic and extrinsic responses were performed directly with the implanted leads. The electrodes were repositioned until satisfactory results were achieved. The pulse generators were implanted directly after the first step in the same operative session. Patients were not subjected to interoperative test stimulation trials.
Results: Postoperative improvement of tremor at a mean follow-up of 11.9 months was rated as excellent in 47 patients (50%), marked in 37 patients (39%), moderate in 8 patients (9%), and minor in 2 patients (2%). There was no persistent morbidity related to surgery. In patients with Parkinson's disease, the symptomatic improvement of tremor was rated as excellent in 51% of patients, marked in 36%, moderate in 11%, and minor in 2%. In patients with essential tremor, symptomatic outcome was classified as excellent in 57% of patients, marked in 36%, moderate in 5%, and minor in 2%. Six of the 7 patients with kinetic tremor achieved marked symptomatic improvement, and 1 patient experienced moderate improvement. Forty patients experienced stimulation-related side effects. Side effects were mild in general, and they were reversible with a change in electrical parameters. They occurred more frequently in patients who had bilateral stimulation.
Conclusion: Excellent to marked improvement of tremor is achieved in the majority of patients with physiological target determination via implanted leads in thalamic deep brain stimulation. Interoperative test stimulation trials are unnecessary. Modifications in technique may help to reduce the costs of the related hospital stay.
Quantitative and Qualitative Outcome Measures After Thalamic Deep Brain Stimulation To Treat Disabling Tremors
Obwegeser AA, Uitti RJ, Witte RJ, et al
Neurosurgery. 2001;48:274-281
Objective: We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed.
Methods: Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed.
Results: Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < .001), lower-limb (P < .01), and midline (P < .001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < .01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < .001) and postural (P < .01) tremors and ipsilateral postural tremor (P < .05). Activities of daily living improved after unilateral surgery (P < .001) and additionally after bilateral surgery (P < .05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants.
Conclusion: Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible
Comparison of Thalamotomy to Deep Brain Stimulation of the Thalamus in Essential Tremor
Pahwa R, Lyons KE, Wilkinson SB, et al
Mov Disord. 2001;16:140-143
Objective: To compare outcome in essential tremor (ET) patients who have undergone either thalamotomy or deep brain stimulation (DBS) of the thalamus.
Background: Although both thalamotomy and thalamic DBS are effective surgical treatments of tremor, it is not known if one procedure is superior to the other.
Design/Methods: Thirty-five ET patients underwent thalamotomy between 1994-1998. Data on 18 patients were excluded. The remaining 17 patients were matched for age, sex, side of surgery, and tremor severity to 17 ET patients who underwent thalamic DBS. There were 9 men and 8 women in each group. The mean age of the thalamotomy group was 74.4 years and that of the thalamic DBS group was 73.1 years.
Results: There were no significant differences between any efficacy outcome variables comparing thalamotomy to DBS of the thalamus at baseline or follow-up visits. The surgical complications were higher for the thalamotomy group as compared to the DBS group. However, a larger number of DBS patients underwent repeat surgeries due to problems with the device and the leads.
Conclusion: Although the efficacy is similar for thalamotomy and DBS of the thalamus for ET, thalamotomy is associated with a higher complication rate. DBS of the thalamus should be the procedure of choice for the surgical treatment of ET in most cases.
Thalamic Deep Brain Stimulation: Comparison Between Unilateral and Bilateral Placement
Ondo W, Almaguer M, Jankovic J, Simpson RK
Arch Neurol. 2001;58:218-222
Background: Unilateral thalamic deep brain stimulation (DBS) is accepted as an effective treatment for essential tremor (ET) and the tremor of Parkinson's disease (PD). There are, however, relatively little data concerning bilateral thalamic DBS and no thorough comparisons between the 2 methods.
Methods: To assess the relative benefit of a staged second contralateral DBS placement in patients with PD and ET, we compared preoperative baseline assessments with those at 3 months after the initial implantation, and again at 3 months after the second contralateral implantation. The assessments included the Unified Parkinson's Disease Rating Scale for patients with PD (n = 8) and a modified Unified Tremor Rating Assessment for patients with ET (n = 13). The design included open and blinded (unknown activation status) assessments.
Results: Overall, after the second implantation, all specific measures assessing tremor contralateral to that side improved in patients with PD and ET, generally without sacrificing those contralateral to the first side implantation. Midline tremors (face and head) improved only after the second side implantation. In patients with ET, functional and subjective scores tended to further improve after the second placement; however, patients with PD had less subjective improvement. Hand tremor scores in patients with ET randomized to "on" stimulation improved from 6.7 +/- 0.9 to 1.3 +/- 1.2 (P < .005). The scores of patients with PD randomized to on stimulation improved from 9.3 +/- 1.0 to 1.0 +/- 0.5. (Data are given as mean +/- SD.) Tremor scores did not change from baseline in those patients randomized to "off" stimulation in either group. Adverse events related to stimulation increased after the second implantation in both groups.
Conclusions: Bilateral thalamic DBS is more effective than unilateral DBS at controlling bilateral appendicular and midline tremors of ET and PD. Despite this, overall functional disability only improved in patients with ET, possibly secondary to more problematic adverse events in patients with PD, especially balance problems. Bilateral DBS should be considered when unilateral DBS does not offer satisfactory benefit, especially in patients with ET.
Simultaneous Thalamic Deep Brain Stimulation and Implantable Cardioverter-Defibrillator
Obwegeser AA, Uitti RJ, Turk MF, et al
Mayo Clin Proc. 2001;76:87-89
Thalamic deep brain stimulation is becoming increasingly popular for the control of drug-refractory tremor. Implantable cardiac pacemakers and defibrillators are commonly used therapeutic modalities. Concerns exist about the potential interactions between these 2 devices in the same patient, but no experience has been reported previously. We describe a patient with essential tremor who had a deep brain stimulator implanted into the left ventral intermediate nucleus of thalamus, who subsequently needed an implantable cardioverter-defibrillator. Despite concerns about possible interactions between the 2 types of implanted electrical devices (ie, a situation similar to drug-drug interactions), the deep brain stimulator and the implanted pacemaker-defibrillator functioned appropriately, and no interaction occurred in our patient.
New Alternative Agents in Essential Tremor Therapy: Double-Blind Placebo-Controlled Study of Alprazolam and Acetazolamide
Gunal DI, Afsar N, Bekiroglu N, Aktan S
Neurol Sci. 2000;21:315-317
Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for 4 weeks, each separated by a 2-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.
Botulinum Toxin Treatment for Functional Disability Induced by Essential Tremor
Pacchetti C, Mancini F, Bulgheroni M, et al
Neurol Sci. 2000;21:349-353
This study aimed to improve botulinum toxin's (BTX) efficacy and to reduce its unwanted effects in the treatment of functional disability due to essential tremor (ET) of the hand. Twenty patients with disabling ET, not responding to conventional pharmacological therapy, were enrolled in this open-label study. Activities of daily living self-questionnaire (ADLS) and severity tremor scale (STS) were used to establish patients' functional disability and tremor severity. Accelerometry and surface electromyography were used to identify the arm muscles with tremorogenic activity during impaired positions. Global rating was used to measure treatment efficacy and unwanted effects. BTX type A was injected into the muscles principally responsible for impaired positions. After BTX treatment, there was a significant reduction in both severity and functional rating scales scores (ADLS and STS) and of tremor amplitude as measured with accelerometry and EMG. Adverse effects were limited to a slight third finger extension weakness in 15% of patients. BTX injections are effective and safe in reducing disability due to ET, if based on the criterion of functional selection.
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