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ARTICLES: Julián Benito-León, Elan D. Louis, Félix Bermejo-Pareja on behalf of the Neurological Disorders in Central Spain (NEDICES) Study Group Elderly-onset essential tremor is associated with dementia Neurology 2006; 66: 1500-1505 [Abstract] [Full text] [PDF]

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Elderly-onset essential tremor is associated with dementia

Renato P Munhoz, Helio G. Teive   (28 August 2006)

Reply from the Authors

Elan D. Louis, MD, MSc, Julián Benito-León, MD, PhD   (28 August 2006)

Elderly-onset essential tremor is associated with dementia 28 August 2006
Renato P Munhoz, Federal University of Parana Trav. Lange, 225 / 1201, Curitiba PR Brazil 80240-170, Helio G. Teive Send Correspondence to journal: Re: Elderly-onset essential tremor is associated with dementia renatopuppi{at}yahoo.com Renato P Munhoz, et al.	We read with great interest the article by Benito-Leon et al [1] concerning dementia in patients with essential tremor (ET). They found that subjects with onset of ET after age 65 were significantly more likely to be demented than controls, while tremor onset at or below age 65 was not associated with dementia. While the authors discuss peculiar patterns of Lewy body or AD-type pathology as candidates for the pathologic basis underlying this association, they did not mention the possibility that some of these patients may in fact be carriers of the fragile X premutation (FXP). [2,3] The fragile X syndrome with mental retardation and typical physical stigmata results from the expansion of a CGG trinucleotide repeat in the FMR1 gene. Normally, FMR1 has 6 to 40 CGG repeats, while the full mutation results from expansions with more than 200 repeats. Those with intermediate expansions are considered as carriers of the FXP which has recently been reported to be associated with the fragile X-associated tremor/ataxia syndrome (FXTAS), including cases misdiagnosed as ET. [2,4] FXP carriers frequencies are estimated to be 1 per 260 females and 1 per 760 males with a penetrance to FXTAS close to 50% at the age of 60 and up to 100% for individuals older than 80. [3] While cases have been reported in both men and women, FXTAS is probably more frequent in male subjects that present typically with onset in the 6th decade and including additional executive cognitive deficits, variable degrees of peripheral neuropathy and occasionally mild parkinsonism. [2-4] Although relatively more cases of FXTAS have been found in men and 60.4% of the ET cases in the Benito-Leon et al study are female, we think that some of these patients may be FXP carriers and FXTAS should be included as an additional alternative possibility to account for this interesting finding. References 1. Benito-Leon J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study Group. Elderly-onset essential tremor is associated with dementia. Neurology 2006;66:1500-1505. 2. Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet 2004;74:805-816. 3. Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004;291:460-469. 4. Leehey MA, Munhoz RP, Lang AE, et al. The fragile X premutation presenting as essential tremor. Arch Neurol 2003;60:117-121. Disclosure: The authors report no conflicts of interest.
Reply from the Authors 28 August 2006
Elan D. Louis, MD, MSc, Móstoles General Hospital C / Río Júcar S/N, E-28935 Móstoles (Madrid), Spain, Julián Benito-León, MD, PhD Send Correspondence to journal: Re: Reply from the Authors jbenitol{at}meditex.es Elan D. Louis, MD, MSc, et al.	We thank Drs. Munhoz and Teive for their comments although do not agree with their idea that FXTAS should be included as an alternative possibility. An occasional patient with FXTAS manifesting as an ET-like picture has been reported by us [5] and others. [6,7] These studies included hundreds of ET patients in different cohorts consistently showing that patients with ET do not have a higher than expected rate of FMR1 repeat expansions. [8] It is unlikely that the increased prevalence of dementia we observed in the ET patients we studied was due to an increased prevalence of FMR1 repeat expansions in these patients. We expect that the underlying cause(s) for the dementia in ET will become more apparent with rigorous postmortem studies of ET brains. [9] References 5. Garcia Arocena D, Louis ED, Tassone F, et al. Screen for expanded FMR1 alleles in patients with essential tremor. Mov Disord 2004;19:930- 933. 6. Tan EK, Zhao Y, Puong KY, et al. Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort. Neurology 2004;63:362-363. 7. Deng H, Jankovic J. Premutation alleles associated with Parkinson’s disease and essential tremor. JAMA 2004;292:1685-1688. 8. Hall DA, Hagerman RJ, Hagerman PJ, Jacquemont S, Leehey MA. Prevalence of FMR1 repeat expansions in movement disorders. A systematic review. Neuroepidemiology 2006;26:151-155. 9. Louis ED, Vonsattel JPG, Honig LS, Ross GW, Lyons KE, Pahwa R. Neuropathological findings in essential tremor. Neurology 2006;66:1756- 1759. The authors report no conflicts of interest.