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Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome

2014; Elsevier BV; Volume: 17; Issue: 8 Linguagem: Inglês

10.1111/ner.12150

1525-1403

Genko Oyama, Atsushi Umemura, Yasushi Shimo, Natsuko Nishikawa, Asuka Nakajima, Takayuki Jo, Madoka Nakajima, Hisato Ishii, Daisuke Yamada, Masashi Takanashi, Hajime Arai, Eiji Nanba, Nobutaka Hattori,

Genetic Neurodegenerative Diseases

Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adult-onset hereditary neurodegenerative disease underpinned by expansion of the premutation in the CGG trinucleotide repeats in the fragile mental retardation gene 1 (FMR1) ( 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 (tre-02-56-352-1.) PubMed Google Scholar ). 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. 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 (tre-02-56-352-1.) PubMed Google Scholar , 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 Crossref PubMed Scopus (61) Google Scholar ). The syndrome clinically presents with postural and action tremors, cerebellar ataxia, cognitive deficits, parkinsonism, dysautonomia, and neuropathy ( 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 Crossref PubMed Google Scholar ), 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 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 Crossref PubMed Scopus (49) Google Scholar ). 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. 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 Crossref PubMed Scopus (49) Google Scholar ). In patients with medication refractory FXTAS-associated tremor, ventral intermediate (Vim) nucleus of the thalamus deep brain stimulation (DBS) has been applied ( 5. Leehey MA Munhoz RP Lang AE et al. The fragile X premutation presenting as essential tremor. Arch Neurol. 2003; 60: 117-121 Crossref PubMed Scopus (125) Google Scholar , 6. Peters N Kamm C Asmus F et al. Intrafamilial variability in fragile X-associated tremor/ataxia syndrome. Mov Disord. 2006; 21: 98-102 Crossref PubMed Scopus (37) Google Scholar , 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 Crossref PubMed Scopus (19) Google Scholar , 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 Crossref PubMed Scopus (12) Google Scholar , 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 Crossref PubMed Scopus (14) Google Scholar , 10. Hagerman RJ. Case series: deep brain stimulation in patients with FXTAS. Brain Disord Ther. 2012; 1: 1000104 Crossref Google Scholar ). Out of eight cases of Vim DBS, two have resulted in the worsening of balance and ataxia symptoms ( 5. Leehey MA Munhoz RP Lang AE et al. The fragile X premutation presenting as essential tremor. Arch Neurol. 2003; 60: 117-121 Crossref PubMed Scopus (125) Google Scholar , 10. Hagerman RJ. Case series: deep brain stimulation in patients with FXTAS. Brain Disord Ther. 2012; 1: 1000104 Crossref Google Scholar ). Recently, posterior subthalamic area (PSA) stimulation has been suggested as an alternative option for control of severe tremor beyond essential tremor (ET) ( 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 (Discussion 1038–1042.): 1029-1038 Crossref PubMed Scopus (1) Google Scholar ). 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.