Neuromodulation: Technology at the Neural Interface Received: June 25, 2013
Revised: September 7, 2013
Accepted: November 19, 2013
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12150
LETTER TO THE EDITOR
Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome To the Editor: Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adultonset hereditary neurodegenerative disease underpinned by expansion of the premutation in the CGG trinucleotide repeats in the fragile mental retardation gene 1 (FMR1) (1). The prevalence of the FMR1 premutation is approximately 1/250 in women and 1/800 in men. Therefore, while the prevalence of FXTAS in men is estimated to be approximately 1 in 3000 to 6000 in general population, the prevalence in women is thought to be much lower (1,2). The syndrome clinically presents with postural and action tremors, cerebellar ataxia, cognitive deficits, parkinsonism, dysautonomia, and neuropathy (3), although exact manifestations can be variable among sufferers. Although there is not enough evidence of treatment for FXTAS, tremor in FXTAS can be treated with medications such as primidone, beta blockers, benzodiazepines, and memantine (4). Hall et al. reported that 50% of patients had mild to moderate improvement on primidone, that 37.5% had moderate improvement on beta blockers, and that 25% had moderate improvement on benzodiazepines (4). In patients with medication refractory FXTAS-associated tremor, ventral intermediate (Vim) nucleus of the thalamus deep brain stimulation (DBS) has been applied (5–10). Out of eight cases of Vim DBS, two have resulted in the worsening of balance and ataxia symptoms (5,10). Recently, posterior subthalamic area (PSA) stimulation has been suggested as an alternative option for control of severe tremor beyond essential tremor (ET) (11). Although there is no consensus to date regarding the best DBS target for patients with FXTAS, there has been a concern that the traditional Vim target would provide insufficient benefit, especially in cases of proximal tremor. We conducted a retrospective chart review of a single case of PSA DBS for a patient with the FXTAS mutation. This study was approved by the Institutional Review Board of Juntendo University School of Medicine.
CASE REPORT
www.neuromodulationjournal.com
Address correspondence to: Yasushi Shimo, MD, PhD, Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan. Email: [email protected] For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1 Conflict of Interest: The authors report no conflict of interest.
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
721
A 54-year-old right-handed man with a 4-year history of leftdominant action and postural tremor in his hands was referred to the Juntendo University Movement Disorders Unit for evaluation of DBS. Before referral, he was diagnosed with Parkinson’s disease and treated with amantadine, selegiline, and pramipexole. He received no benefit from his treatment, and the tremor gradually progressed in addition to the development of balance problems and a gait disturbance. On examination, he presented with a disabling leftside dominant postural and action tremor, and mild bilateral resting tremors. His tremor predominantly involved more distal muscles
but also involved some proximal muscles. He also had gaze nystagmus and slurred speech. He could not perform tandem walking without danger of falling, but he was able to walk unassisted and manifested a wide-based gait. Finger-to-nose testing and heel-toknee testing revealed a left-dominant dysmetria and bilateral dyssynergia. Additionally, he presented with gargoylism and mild mental retardation (mini-mental state examination 25/30, The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) intelligence quotient (IQ) 49, Verbal IQ 56, performance IQ 49). His laboratory tests were normal. T2-weighted magnetic resonance imaging (MRI) revealed a diffuse white matter, high-intensity abnormality, but the classical white matter middle cerebellar peduncles (MCP) sign as well as cerebellar atrophy were absent. A DNA test revealed 109 CGG repeats in the FMR1 gene. At the time of surgery, he was taking arotinole 10 mg, zonisamide 200 mg, primidone 1200 mg, clonazepam 1 mg, trihexyphenidyl 4 mg, and alprazolam 1.6 mg, all of which he believed slightly improved his tremors. However, as his ability to perform his activities of daily living (ADL) worsened, he ultimately underwent unilateral DBS lead implantation in his left PSA with the intention of improving his right-hand tremor. A left PSA electrode (Medtronic model 3389 lead, Medtronic, Inc., Minneapolis, MN, USA) was placed using direct MRI targeting and the reference points of the red nucleus and subthalamic nucleus (STN). The crossing of the horizontal line from the center of the STN and the vertical line from the center of red nucleus was considered to be the PSA (12 mm lateral, 7.4 mm posterior, and 5.1 mm below the mid-commissural point, Fig. 1). Microelectrode recording was not performed because the PSA had been a known electrically silent area (11). Macrostimulation revealed excellent tremor suppression in the operating room. Postoperative computed tomography scan confirmed that the lead was placed in the intended location when compared with the preoperative MRI. The stimulation settings (Activa, Medtronic, Inc., Minneapolis, MN, USA) were 0(–)C(+); amplitude 2.6 V; pulse width 60 μsec; frequency 185 Hz. The PSA stimulation had an immediate effect on capturing the tremor, and the
OYAMA ET AL.
Figure 1. Targeting of posterior subthalamic area (PSA): sagittal plane (left) and axial plane (right).
Figure 2. Spiral drawing by the right hand pre- and postoperatively. His tremor markedly improved but ataxic component did not change.
Fahn-Tolosa-Marin Tremor Rating Scale motor score was improved by 57.9% (preoperative, 38; postoperative, 16). Spiral drawing by the right hand markedly improved (Fig. 2). There was an improvement in both ipsilateral (47.3%) and contralateral (68.4%) tremor. The Scale for the Assessment and Rating of Ataxia was not changed (preoperative, 12.5; postoperative, 12.5). His medication was reduced to arotinole 10 mg, zonisamide 200 mg, and primidone 500 mg. As the immediate surgical microlesion effect wore off, stimulation parameters were adjusted to 0(–)C(+), 2.8 V, 120 μsec, 160 Hz. At a six-month follow-up, although his left-side tremor returned to the baseline, his right-side tremor suppression was maintained (Table 1). At an eight-month follow-up visit, he reported that his tremor suppression continued and that he could use his right hand to perform ADL such as using spoon and writing. He also reported that the degree of his tremor increased when the device was turned off at night. Neurological examination revealed no deterioration of speech, swallowing, ataxia, or mini-mental state examination score.
DISCUSSION
722
This case revealed that unilateral PSA DBS improved the postural/ action tremor in FXTAS without coincident worsening of ataxia. www.neuromodulationjournal.com
Additionally, the speech, swallowing, and gait/balance function did not deteriorate. Furthermore, tremor medications, although not discontinued, were successfully reduced. This single case provides some evidence that the PSA target may be beneficial for patients with tremor without worsening ataxia. To our knowledge, there are eight published cases of Vim DBS for patients with FXTAS, but there is no report of the use of the PSA target (5–10). Across cases, Vim DBS improved tremor in FXTAS. Senova et al. reported a 73.4% improvement in the contralateral side and 20.5% in the ipsilateral side (9). The degree of the improvement in these previous cases was similar to our PSA case. In some reported cases, however, the preexisting balance problem worsened (two of eight cases) (5,10), whereas three of eight cases reported improvement in ataxia (3,9). Vim stimulation was reported in ET cases to increase balance and gait issues especially when bilateral DBS leads were employed (12). The literature supporting stimulation-induced gait ataxia in PSA is a rare complication among the few reported cases (13). Unilateral cases may have less balance issues (12). There is emerging evidence of PSA DBS having possible benefits for various tremor disorders (11). Although there is no randomized control study, PSA may be more effective than Vim for ET (14–16), particularly in atypical cases or cases involving proximal tremor (17). Hamel et al. showed the superiority of the PSA site in suppressing ET when compared with a classical Vim target (14). Sandvik et al. reviewed 17 Vim and 19 PSA cases and showed that the optimal DBS lead was located in the PSA in 54% and in the Vim in 12% (15). Additionally, Blomstedt et al. compared 34 Vim cases and 34 PSA cases with ET and reported that tremor was improved in 70% in the Vim group and 89% in the PSA group (16). The degree of improvement in FXTAS cases may be smaller than in ET cases because tremor in FXTAS contains an ataxic component (3,9). Additionally the long-term outcome of the PSA target, including the possibility of tolerance seen in ET (18), remains unclear. Although our case would suggest the PSA as one of several possible targets in medication refractory tremor in FXTAS, benefit should always exceed the potential risk of worsening of comorbid conditions such as ataxia. These symptoms should be carefully monitored over time. In conclusion, the unilateral PSA target may in the future prove relatively safe for suppressing tremor and not inducing ataxia, but more cases will be needed to confirm this finding.
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
LETTER TO THE EDITOR
Table 1. Improvement in Fahn-Tolosa-Marin Tremor Rating Scale (TRS).
TRS motor (total) TRS motor (right side) TRS motor (left side) Face Tongue (resting/postural) Voice Head (resting/postural) Upper extremity (resting/postural/action) (R) (L) Trunk (resting/postural) Lower extremity (resting/postural/action) (R) (L) Handwriting Right drawing A (R) (L) Right drawing B (R) (L) Right drawing C (R) (L) Pouring (R) (L)
Baseline
1 month
3 months
6 months
38 19 19 0 0/0 0 0/0 0/2/2 0/2/2 0/0 0/0/0 0/0/0 1 4 4 4 4 3 3 3 4
16 6 10 0 0/0 0 0/0 0/0/1 0/1/1 0/0 0/0/0 0/0/0 1 1 2 1 3 2 2 0 1
31 10 21 0 0/0 0 0/0 0/1/2 0/3/3 0/0 0/0/0 0/0/0 2 1 4 2 4 1 4 1 3
27 10 17 0 0/0 0 0/0 0/1/1 0/2/2 0/0 0/0/0 0/0/0 2 1 3 2 3 2 4 1 3
Acknowledgement This work was partially supported by grants from the Ministry of Health, Labour and Welfare of Japan.
Authorship Statement Drs. Oyama, Umemura, Shimo, Namba, and Hattori designed and conducted the study, including patient recruitment, data collection, and data analysis. All authors approved the final manuscript. The Ministry of Health, Labour and Welfare of Japan provided funding for the study. Drs. Oyama and Shimo had complete access to the study data.
†
§
Genko Oyama, MD, PhD*; Atsushi Umemura, MD, PhD*†‡; Yasushi Shimo, MD, PhD*‡; Natsuko Nishikawa, MD*; Asuka Nakajima, MD*; Takayuki Jo, MD*; Madoka Nakajima, MD, PhD†; Hisato Ishii, MD, PhD†; Daisuke Yamada, MD*; Masashi Takanashi, MD, PhD*; Hajime Arai, MD, PhD†; Eiji Nanba, MD, PhD§; Nobutaka Hattori, MD, PhD* * Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan ‡ Research and Therapeutics for Movement Disorders, Juntendo University School of Medicine, Tokyo, Japan Department of Research Center for Bioscience and Technology, Tottori University, Tokyo, Japan
REFERENCES 1. Hall DA, O’Keefe JA. Fragile x-associated tremor ataxia syndrome: the expanding clinical picture, pathophysiology, epidemiology, and update on treatment. Tremor Other Hyperkinet Mov (N Y) 2012;2:pii: tre-02-56-352-1.
2. Amiri K, Hagerman RJ, Hagerman PJ. Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 2008;65:19–25. 3. Hagerman RJ, Hall DA, Coffey S et al. Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging 2008;3:251– 262. 4. Hall DA, Berry-Kravis E, Hagerman RJ, Hagerman PJ, Rice CD, Leehey MA. Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome. Mov Disord 2006;21:1741–1744. 5. Leehey MA, Munhoz RP, Lang AE et al. The fragile X premutation presenting as essential tremor. Arch Neurol 2003;60:117–121. 6. Peters N, Kamm C, Asmus F et al. Intrafamilial variability in fragile X-associated tremor/ataxia syndrome. Mov Disord 2006;21:98–102. 7. Ferrara JM, Adam OR, Ondo WG. Treatment of fragile-X-associated tremor/ataxia syndrome with deep brain stimulation. Mov Disord 2009;24:149–151. 8. Xie T, Goodman R, Browner N et al. Treatment of fragile X-associated tremor/ataxia syndrome with unilateral deep brain stimulation. Mov Disord 2012;27:799–800. 9. Senova S, Jarraya B, Iwamuro H et al. Unilateral thalamic stimulation safely improved fragile X-associated tremor ataxia: a case report. Mov Disord 2012;27:797–799. 10. Hagerman RJ. Case series: deep brain stimulation in patients with FXTAS. Brain Disord Ther 2012;1;2:1000104. 11. Blomstedt P, Sandvik U, Fytagoridis A, Tisch S. The posterior subthalamic area in the treatment of movement disorders: past, present, and future. Neurosurgery 2009;64:1029–1038. Discussion 1038–1042. 12. Hwynn N, Hass CJ, Zeilman P et al. Steady or not following thalamic deep brain stimulation for essential tremor. J Neurol 2011;258:1643–1648. 13. Fytagoridis A, Astrom M, Wardell K, Blomstedt P. Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization. Clin Neurol Neurosurg 2013;115:65–71. 14. Hamel W, Herzog J, Kopper F et al. Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor. Acta Neurochir (Wien) 2007;149:749–758. Discussion 758. 15. Sandvik U, Koskinen LO, Lundquist A, Blomstedt P. Thalamic and subthalamic deep brain stimulation for essential tremor: where is the optimal target? Neurosurgery 2012;70:840–845. Discussion 845–846. 16. Blomstedt P, Sandvik U, Hariz MI et al. Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor. Parkinsonism Relat Disord 2011;17:617–620. 17. Xie T, Bernard J, Warnke P. Post subthalamic area deep brain stimulation for tremors: a mini-review. Transl Neurodegener 2012;1;20:1–8. 18. Favilla CG, Ullman D, Wagle Shukla A, Foote KD, Jacobson CE, Okun MS. Worsening essential tremor following deep brain stimulation: disease progression versus tolerance. Brain 2012;135(Pt 5):1455–1462.
Keywords: Ataxia, DBS, posterior subthalamic area, surgery, tremor
723
www.neuromodulationjournal.com
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
Copyright of Neuromodulation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Revised: September 7, 2013
Accepted: November 19, 2013
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12150
LETTER TO THE EDITOR
Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome To the Editor: Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adultonset hereditary neurodegenerative disease underpinned by expansion of the premutation in the CGG trinucleotide repeats in the fragile mental retardation gene 1 (FMR1) (1). The prevalence of the FMR1 premutation is approximately 1/250 in women and 1/800 in men. Therefore, while the prevalence of FXTAS in men is estimated to be approximately 1 in 3000 to 6000 in general population, the prevalence in women is thought to be much lower (1,2). The syndrome clinically presents with postural and action tremors, cerebellar ataxia, cognitive deficits, parkinsonism, dysautonomia, and neuropathy (3), although exact manifestations can be variable among sufferers. Although there is not enough evidence of treatment for FXTAS, tremor in FXTAS can be treated with medications such as primidone, beta blockers, benzodiazepines, and memantine (4). Hall et al. reported that 50% of patients had mild to moderate improvement on primidone, that 37.5% had moderate improvement on beta blockers, and that 25% had moderate improvement on benzodiazepines (4). In patients with medication refractory FXTAS-associated tremor, ventral intermediate (Vim) nucleus of the thalamus deep brain stimulation (DBS) has been applied (5–10). Out of eight cases of Vim DBS, two have resulted in the worsening of balance and ataxia symptoms (5,10). Recently, posterior subthalamic area (PSA) stimulation has been suggested as an alternative option for control of severe tremor beyond essential tremor (ET) (11). Although there is no consensus to date regarding the best DBS target for patients with FXTAS, there has been a concern that the traditional Vim target would provide insufficient benefit, especially in cases of proximal tremor. We conducted a retrospective chart review of a single case of PSA DBS for a patient with the FXTAS mutation. This study was approved by the Institutional Review Board of Juntendo University School of Medicine.
CASE REPORT
www.neuromodulationjournal.com
Address correspondence to: Yasushi Shimo, MD, PhD, Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan. Email: [email protected] For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1 Conflict of Interest: The authors report no conflict of interest.
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
721
A 54-year-old right-handed man with a 4-year history of leftdominant action and postural tremor in his hands was referred to the Juntendo University Movement Disorders Unit for evaluation of DBS. Before referral, he was diagnosed with Parkinson’s disease and treated with amantadine, selegiline, and pramipexole. He received no benefit from his treatment, and the tremor gradually progressed in addition to the development of balance problems and a gait disturbance. On examination, he presented with a disabling leftside dominant postural and action tremor, and mild bilateral resting tremors. His tremor predominantly involved more distal muscles
but also involved some proximal muscles. He also had gaze nystagmus and slurred speech. He could not perform tandem walking without danger of falling, but he was able to walk unassisted and manifested a wide-based gait. Finger-to-nose testing and heel-toknee testing revealed a left-dominant dysmetria and bilateral dyssynergia. Additionally, he presented with gargoylism and mild mental retardation (mini-mental state examination 25/30, The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) intelligence quotient (IQ) 49, Verbal IQ 56, performance IQ 49). His laboratory tests were normal. T2-weighted magnetic resonance imaging (MRI) revealed a diffuse white matter, high-intensity abnormality, but the classical white matter middle cerebellar peduncles (MCP) sign as well as cerebellar atrophy were absent. A DNA test revealed 109 CGG repeats in the FMR1 gene. At the time of surgery, he was taking arotinole 10 mg, zonisamide 200 mg, primidone 1200 mg, clonazepam 1 mg, trihexyphenidyl 4 mg, and alprazolam 1.6 mg, all of which he believed slightly improved his tremors. However, as his ability to perform his activities of daily living (ADL) worsened, he ultimately underwent unilateral DBS lead implantation in his left PSA with the intention of improving his right-hand tremor. A left PSA electrode (Medtronic model 3389 lead, Medtronic, Inc., Minneapolis, MN, USA) was placed using direct MRI targeting and the reference points of the red nucleus and subthalamic nucleus (STN). The crossing of the horizontal line from the center of the STN and the vertical line from the center of red nucleus was considered to be the PSA (12 mm lateral, 7.4 mm posterior, and 5.1 mm below the mid-commissural point, Fig. 1). Microelectrode recording was not performed because the PSA had been a known electrically silent area (11). Macrostimulation revealed excellent tremor suppression in the operating room. Postoperative computed tomography scan confirmed that the lead was placed in the intended location when compared with the preoperative MRI. The stimulation settings (Activa, Medtronic, Inc., Minneapolis, MN, USA) were 0(–)C(+); amplitude 2.6 V; pulse width 60 μsec; frequency 185 Hz. The PSA stimulation had an immediate effect on capturing the tremor, and the
OYAMA ET AL.
Figure 1. Targeting of posterior subthalamic area (PSA): sagittal plane (left) and axial plane (right).
Figure 2. Spiral drawing by the right hand pre- and postoperatively. His tremor markedly improved but ataxic component did not change.
Fahn-Tolosa-Marin Tremor Rating Scale motor score was improved by 57.9% (preoperative, 38; postoperative, 16). Spiral drawing by the right hand markedly improved (Fig. 2). There was an improvement in both ipsilateral (47.3%) and contralateral (68.4%) tremor. The Scale for the Assessment and Rating of Ataxia was not changed (preoperative, 12.5; postoperative, 12.5). His medication was reduced to arotinole 10 mg, zonisamide 200 mg, and primidone 500 mg. As the immediate surgical microlesion effect wore off, stimulation parameters were adjusted to 0(–)C(+), 2.8 V, 120 μsec, 160 Hz. At a six-month follow-up, although his left-side tremor returned to the baseline, his right-side tremor suppression was maintained (Table 1). At an eight-month follow-up visit, he reported that his tremor suppression continued and that he could use his right hand to perform ADL such as using spoon and writing. He also reported that the degree of his tremor increased when the device was turned off at night. Neurological examination revealed no deterioration of speech, swallowing, ataxia, or mini-mental state examination score.
DISCUSSION
722
This case revealed that unilateral PSA DBS improved the postural/ action tremor in FXTAS without coincident worsening of ataxia. www.neuromodulationjournal.com
Additionally, the speech, swallowing, and gait/balance function did not deteriorate. Furthermore, tremor medications, although not discontinued, were successfully reduced. This single case provides some evidence that the PSA target may be beneficial for patients with tremor without worsening ataxia. To our knowledge, there are eight published cases of Vim DBS for patients with FXTAS, but there is no report of the use of the PSA target (5–10). Across cases, Vim DBS improved tremor in FXTAS. Senova et al. reported a 73.4% improvement in the contralateral side and 20.5% in the ipsilateral side (9). The degree of the improvement in these previous cases was similar to our PSA case. In some reported cases, however, the preexisting balance problem worsened (two of eight cases) (5,10), whereas three of eight cases reported improvement in ataxia (3,9). Vim stimulation was reported in ET cases to increase balance and gait issues especially when bilateral DBS leads were employed (12). The literature supporting stimulation-induced gait ataxia in PSA is a rare complication among the few reported cases (13). Unilateral cases may have less balance issues (12). There is emerging evidence of PSA DBS having possible benefits for various tremor disorders (11). Although there is no randomized control study, PSA may be more effective than Vim for ET (14–16), particularly in atypical cases or cases involving proximal tremor (17). Hamel et al. showed the superiority of the PSA site in suppressing ET when compared with a classical Vim target (14). Sandvik et al. reviewed 17 Vim and 19 PSA cases and showed that the optimal DBS lead was located in the PSA in 54% and in the Vim in 12% (15). Additionally, Blomstedt et al. compared 34 Vim cases and 34 PSA cases with ET and reported that tremor was improved in 70% in the Vim group and 89% in the PSA group (16). The degree of improvement in FXTAS cases may be smaller than in ET cases because tremor in FXTAS contains an ataxic component (3,9). Additionally the long-term outcome of the PSA target, including the possibility of tolerance seen in ET (18), remains unclear. Although our case would suggest the PSA as one of several possible targets in medication refractory tremor in FXTAS, benefit should always exceed the potential risk of worsening of comorbid conditions such as ataxia. These symptoms should be carefully monitored over time. In conclusion, the unilateral PSA target may in the future prove relatively safe for suppressing tremor and not inducing ataxia, but more cases will be needed to confirm this finding.
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
LETTER TO THE EDITOR
Table 1. Improvement in Fahn-Tolosa-Marin Tremor Rating Scale (TRS).
TRS motor (total) TRS motor (right side) TRS motor (left side) Face Tongue (resting/postural) Voice Head (resting/postural) Upper extremity (resting/postural/action) (R) (L) Trunk (resting/postural) Lower extremity (resting/postural/action) (R) (L) Handwriting Right drawing A (R) (L) Right drawing B (R) (L) Right drawing C (R) (L) Pouring (R) (L)
Baseline
1 month
3 months
6 months
38 19 19 0 0/0 0 0/0 0/2/2 0/2/2 0/0 0/0/0 0/0/0 1 4 4 4 4 3 3 3 4
16 6 10 0 0/0 0 0/0 0/0/1 0/1/1 0/0 0/0/0 0/0/0 1 1 2 1 3 2 2 0 1
31 10 21 0 0/0 0 0/0 0/1/2 0/3/3 0/0 0/0/0 0/0/0 2 1 4 2 4 1 4 1 3
27 10 17 0 0/0 0 0/0 0/1/1 0/2/2 0/0 0/0/0 0/0/0 2 1 3 2 3 2 4 1 3
Acknowledgement This work was partially supported by grants from the Ministry of Health, Labour and Welfare of Japan.
Authorship Statement Drs. Oyama, Umemura, Shimo, Namba, and Hattori designed and conducted the study, including patient recruitment, data collection, and data analysis. All authors approved the final manuscript. The Ministry of Health, Labour and Welfare of Japan provided funding for the study. Drs. Oyama and Shimo had complete access to the study data.
†
§
Genko Oyama, MD, PhD*; Atsushi Umemura, MD, PhD*†‡; Yasushi Shimo, MD, PhD*‡; Natsuko Nishikawa, MD*; Asuka Nakajima, MD*; Takayuki Jo, MD*; Madoka Nakajima, MD, PhD†; Hisato Ishii, MD, PhD†; Daisuke Yamada, MD*; Masashi Takanashi, MD, PhD*; Hajime Arai, MD, PhD†; Eiji Nanba, MD, PhD§; Nobutaka Hattori, MD, PhD* * Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan ‡ Research and Therapeutics for Movement Disorders, Juntendo University School of Medicine, Tokyo, Japan Department of Research Center for Bioscience and Technology, Tottori University, Tokyo, Japan
REFERENCES 1. Hall DA, O’Keefe JA. Fragile x-associated tremor ataxia syndrome: the expanding clinical picture, pathophysiology, epidemiology, and update on treatment. Tremor Other Hyperkinet Mov (N Y) 2012;2:pii: tre-02-56-352-1.
2. Amiri K, Hagerman RJ, Hagerman PJ. Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 2008;65:19–25. 3. Hagerman RJ, Hall DA, Coffey S et al. Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging 2008;3:251– 262. 4. Hall DA, Berry-Kravis E, Hagerman RJ, Hagerman PJ, Rice CD, Leehey MA. Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome. Mov Disord 2006;21:1741–1744. 5. Leehey MA, Munhoz RP, Lang AE et al. The fragile X premutation presenting as essential tremor. Arch Neurol 2003;60:117–121. 6. Peters N, Kamm C, Asmus F et al. Intrafamilial variability in fragile X-associated tremor/ataxia syndrome. Mov Disord 2006;21:98–102. 7. Ferrara JM, Adam OR, Ondo WG. Treatment of fragile-X-associated tremor/ataxia syndrome with deep brain stimulation. Mov Disord 2009;24:149–151. 8. Xie T, Goodman R, Browner N et al. Treatment of fragile X-associated tremor/ataxia syndrome with unilateral deep brain stimulation. Mov Disord 2012;27:799–800. 9. Senova S, Jarraya B, Iwamuro H et al. Unilateral thalamic stimulation safely improved fragile X-associated tremor ataxia: a case report. Mov Disord 2012;27:797–799. 10. Hagerman RJ. Case series: deep brain stimulation in patients with FXTAS. Brain Disord Ther 2012;1;2:1000104. 11. Blomstedt P, Sandvik U, Fytagoridis A, Tisch S. The posterior subthalamic area in the treatment of movement disorders: past, present, and future. Neurosurgery 2009;64:1029–1038. Discussion 1038–1042. 12. Hwynn N, Hass CJ, Zeilman P et al. Steady or not following thalamic deep brain stimulation for essential tremor. J Neurol 2011;258:1643–1648. 13. Fytagoridis A, Astrom M, Wardell K, Blomstedt P. Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization. Clin Neurol Neurosurg 2013;115:65–71. 14. Hamel W, Herzog J, Kopper F et al. Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor. Acta Neurochir (Wien) 2007;149:749–758. Discussion 758. 15. Sandvik U, Koskinen LO, Lundquist A, Blomstedt P. Thalamic and subthalamic deep brain stimulation for essential tremor: where is the optimal target? Neurosurgery 2012;70:840–845. Discussion 845–846. 16. Blomstedt P, Sandvik U, Hariz MI et al. Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor. Parkinsonism Relat Disord 2011;17:617–620. 17. Xie T, Bernard J, Warnke P. Post subthalamic area deep brain stimulation for tremors: a mini-review. Transl Neurodegener 2012;1;20:1–8. 18. Favilla CG, Ullman D, Wagle Shukla A, Foote KD, Jacobson CE, Okun MS. Worsening essential tremor following deep brain stimulation: disease progression versus tolerance. Brain 2012;135(Pt 5):1455–1462.
Keywords: Ataxia, DBS, posterior subthalamic area, surgery, tremor
723
www.neuromodulationjournal.com
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 721–723
Copyright of Neuromodulation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
