The Fragile X Premutation Presenting as Essential Tremor

Leehey, Maureen A.; Munhoz, Renato P.; Lang, Anthony E.; Brunberg, James A.; Grigsby, Jim; Greco, C.; Jacquemont, Sebastian; Tassone, Flora; Lozano, Andrés M.; Hagerman, Paul J.; Hagerman, Randi J.

doi:10.1001/archneur.60.1.117

Cited by 141 publications

(84 citation statements)

References 28 publications

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“…Clinically, FXTAS is characterized by gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment (Bacalman et al, 2006;Grigsby et al, 2006aGrigsby et al, ,b, 2007aHagerman et al, 2001;Jacquemont et al, 2003;Leehey et al, 2003). Intranuclear eosinophilic astrocytic and neuronal inclusion bodies are found throughout the cortex and in many subcortical areas, and are especially prevalent in the hippocampus (Arocena et al, 2005;Greco et al, 2002;Greco et al, 2006;Iwahashi et al, 2006;Louis, Moskowitz, Friez, Amaya, & Vonsattel, 2006).…”

Section: Introductionmentioning

confidence: 99%

The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

Brega

Goodrich

Bennett

et al. 2008

Journal of Clinical and Experimental Neuropsychology

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation trinucleotide repeat expansion in the fragile X mental retardation 1 gene (FMR1). Symptoms include gait ataxia, action tremor, and cognitive impairment. The objectives of the study were to clarify the nature of the dysexecutive syndrome observed in FXTAS and to assess the contribution of executive impairment to deficits in nonexecutive cognitive functions. Compared to controls, men with FXTAS demonstrated significant executive impairment, which was found to mediate group differences in most other cognitive abilities. Asymptomatic premutation carriers performed similarly to controls on all but two measures of executive functioning. These findings suggest that the impairment of non-executive cognitive skills in FXTAS is in large part secondary to executive dysfunction.

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Section: Introductionmentioning

confidence: 99%

The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

Brega

Goodrich

Bennett

et al. 2008

Journal of Clinical and Experimental Neuropsychology

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“…Along with generalized brain atrophy, the T2 hyperintensity in the MCPs is the most common imaging finding associated with FXTAS. 3 In this case, the imaging finding directly informed the diagnosis and prompted genetic testing. Associated findings on pathology include white matter disease, enlarged inclusion-bearing astrocytes in white matter, and intranuclear inclusions in the CNS.…”

Section: The Clinical Symptoms Of Fxtas Are Variable Andmentioning

confidence: 90%

“…3 The genetic abnormality can be accompanied by FMR1 mRNA elevations and normal to borderline levels of FMR1 protein. 2,4 The prevalence of the premutation is 1 in 259 women and 1 in 813 men.…”

Section: The Clinical Symptoms Of Fxtas Are Variable Andmentioning

confidence: 99%

Pearls & Oy-sters: Fragile X tremor/ataxia syndrome

Eye

Hawley

2015

Neurology

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“…These misdiagnoses include Parkinson's Disease (PD), sporadic cerebellar ataxia and Essential Tremor (ET) [13]. Previous surgical intervention from our collaborators [14][15][16][17][18] represents the first attempt at applying Deep Brain Stimulation (DBS) to manage FXTAS cases and underscores the importance of the syndromic recognition and need for experimental therapeutics.…”

Section: Introductionmentioning

confidence: 99%

“…DBS of the subthalamic nucleus or of the internal segment of globus pallidus has been shown to significantly improve motor complications in severe PD [19], while DBS of the Ventral intermediate (Vim) thalamic nucleus has been shown to reduce tremors in PD and non-Parkinsonian ET [20]. However, a previous attempt at targeting the Vim nucleus bilaterally to treat FXTAS was ineffective because of a lead fracture and suboptimal placement of electrodes [14]. In another case, a positive response to bilateral thalamic stimulation led to a marked reduction of tremor in a 60 year-old male with FXTAS, though gait ataxia persisted [15].…”

Section: Introductionmentioning

confidence: 99%

Case Series: Deep Brain Stimulation in Patients with FXTAS

Hagerman¹,

Pak²,

Ortigas³

et al. 2012

Brain Disord Ther

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Objective: We describe 3 carriers of the FMR1 premutation with the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) whose tremor was significantly improved by bilateral Deep Brain Stimulation (DBS) to Ventral Intermediate nucleus (Vim) of the thalamus.Background: FXTAS is a recently described neurodegenerative disorder caused by CGG expansions of the FMR1 gene within the premutation range (55 to 200 CGG repeats). Individuals with FXTAS typically develop an intention tremor followed by gait ataxia within two years. Vim DBS has been shown to effectively treat tremor in a variety of disorders, including Parkinson's disease and essential tremor.Design/Methods/Results: Three men ages 62, 59 and 70 with FXTAS were treated surgically with bilateral Vim DBS. All patients experienced a significantly beneficial effect on tremor. Ataxia improved in case 1 and temporarily in case 2, but worsened in case 3. All patients experienced mild worsening of dysarthria, although the patients and their families unanimously felt there was a worthwhile benefit overall. Conclusions:These cases provided first hand evidence that bilateral Vim DBS effectively manages tremor in selected patients with FXTAS. DBS may prove to be a viable therapeutic option for treating tremor and/or ataxia with or without other medical therapeutics in patients with FXTAS.

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The Fragile X Premutation Presenting as Essential Tremor

Abstract: The fragile X carrier state may underlie the clinical findings in some older men diagnosed as having essential tremor.

Cited by 141 publications

References 28 publications

The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

Pearls & Oy-sters: Fragile X tremor/ataxia syndrome

Case Series: Deep Brain Stimulation in Patients with FXTAS

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