Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor and ataxia

Kalus, Sarah; King, John; Lui, Elaine; Gaillard, Frank

doi:10.1016/j.jocn.2015.08.010

Cited by 12 publications

(7 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FXTAS is more common in males than in females, the onset is usually over the age of 50 [ 133 ], with a life expectancy that ranges between 5 and 25 years [ 134 ]. Classical neurological manifestations include kinetic tremor and cerebellar ataxia, but cognitive decline, psychiatric disorders, peripheral neuropathy, and autonomic dysfunction are also frequently described [ 135 , 136 ].…”

Section: X-linked Ataxiasmentioning

confidence: 99%

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review

et al. 2021

View full text Add to dashboard Cite

Purpose Cerebellar ataxias are a large and heterogeneous group of disorders. The evaluation of brain parenchyma via MRI plays a central role in the diagnostic assessment of these conditions, being mandatory to exclude the presence of other underlying causes in determining the clinical phenotype. Once these possible causes are ruled out, the diagnosis is usually researched in the wide range of hereditary or sporadic ataxias. Methods We here propose a review of the main clinical and conventional imaging findings of the most common hereditary degenerative ataxias, to help neuroradiologists in the evaluation of these patients. Results Hereditary degenerative ataxias are all usually characterized from a neuroimaging standpoint by the presence, in almost all cases, of cerebellar atrophy. Nevertheless, a proper assessment of imaging data, extending beyond the mere evaluation of cerebellar atrophy, evaluating also the pattern of volume loss as well as concomitant MRI signs, is crucial to achieve a proper diagnosis. Conclusion The integration of typical neuroradiological characteristics, along with patient’s clinical history and laboratory data, could allow the neuroradiologist to identify some conditions and exclude others, addressing the neurologist to the more appropriate genetic testing.

show abstract

Section: X-linked Ataxiasmentioning

confidence: 99%

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The clinical presentation of FXTAS comprises several major (core) features including intention tremor and cerebellar ataxia, and white matter hyperintensities ( wmhs ) in the middle cerebellar peduncles (the ‘MCP sign’) represent a major radiological feature. However, more recent studies have shown a significant prevalence of wmhs in the splenium of the corpus callosum ( Apartis et al, 2012 ; Kalus et al, 2016 ), or in the basis pontis ( Loesch et al, 2011 ) in FXTAS patients. Parkinsonism, cognitive (memory and executive function) deficits, peripheral neuropathy, cerebral wmhs and generalized brain atrophy have been listed among the minor features of FXTAS ( Jacquemont et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

The Spectrum of Neurological and White Matter Changes and Premutation Status Categories of Older Male Carriers of the FMR1 Alleles Are Linked to Genetic (CGG and FMR1 mRNA) and Cellular Stress (AMPK) Markers

et al. 2018

View full text Add to dashboard Cite

The fragile X premutation (PM) allele contains a CGG expansion of 55–200 repeats in the FMR1 gene’s promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1-specific genetic changes, in a sample of 32 unselected male PM carriers aged 39–81 years. Half of these individuals were affected with FXTAS, while the non-FXTAS group comprised subcategories of non-affected individuals and individuals affected with non-syndromic changes. The dynamics of pathological processes at the cellular level relevant to the clinical status of PM carriers was investigated using the enzyme AMP-activated protein kinase (AMPK), which is a highly sensitive cellular stress-sensing alarm protein. This enzyme, as well as genetic markers – CGG repeat number and the levels of the FMR1 mRNA – were assessed in blood lymphoblasts. The results showed that the repeat distribution for FXTAS individuals peaked at 85–90 CGGs; non-FXTAS carriers were distributed within the lowest end of the PM repeat range, and non-syndromic carriers assumed an intermediate position. The size of the CGG expansion was significantly correlated, across all three categories, with infratentorial and total wmhs and with all motor scores, and the FMR1 mRNA levels with all the wmh scores, whilst AMPK activity showed considerable elevation in the non-FXTAS combined group, decreasing in the FXTAS group, proportionally to increasing severity of the wmhs and tremor/ataxia. We conclude that the size of the CGG expansion relates to the risk for FXTAS, to severity of infratentorial wmhs lesions, and to all three motor scale scores. FMR1 mRNA shows a strong association with the extent of wmhs, which is the most sensitive marker of the pathological process. However, the AMPK activity findings – suggestive of a role of this enzyme in the risk of FXTAS – need to be verified and expanded in future studies using larger samples and longitudinal assessment.

show abstract

“…28 A family history of mental retardation in an older patient presenting with cognitive decline, tremor, and ataxia may suggest fragile-X ataxia tremor syndrome (FXTAS). 29 • Are there other neurological symptoms such as paresthesias, weakness, imbalance, eye movement abnormalities, or brainstem symptoms? Paresthesias and weakness with a distal and asymmetric intention tremor may suggest a neuropathic tremor due to a chronic neuropathy such as chronic inflammatory demyelinating neuropathy.…”

Section: Classifying Tremor By Phenomenologymentioning

confidence: 99%

Approach to Tremor Disorders

Lee

Sarva

2021

Semin Neurol

View full text Add to dashboard Cite

Tremor disorders are diverse and complex. Historical clues and examination features play a major role in diagnosing these disorders, but diagnosis can be challenging due to phenotypic overlap. Ancillary testing, such as neuroimaging or laboratory testing, is driven by the history and examination, and should be performed particularly when there are other neurological or systemic manifestations. The pathophysiology of tremor is not entirely understood, but likely involves multiple networks along with the cerebello-thalamo-cortical pathways. Treatment options include medications, botulinum toxin, surgery, and nonpharmacologic interventions utilizing physical and occupational therapies and assistive devices. Further work is needed in developing accurate diagnostic tests and better treatment options for tremor disorders.

show abstract

Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor and ataxia

Cited by 12 publications

References 3 publications

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review

The Spectrum of Neurological and White Matter Changes and Premutation Status Categories of Older Male Carriers of the FMR1 Alleles Are Linked to Genetic (CGG and FMR1 mRNA) and Cellular Stress (AMPK) Markers

Approach to Tremor Disorders

Contact Info

Product

Resources

About