Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease

Soong, Bing Wen; Liu, Ru‐Shi

doi:10.1136/jnnp.64.4.499

Cited by 54 publications

(32 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is intriguing to observe that the cerebellar metabolism did not correlate with ICARS or subscores within the patient group, but significant differences were noticed if healthy controls were included. In previous PET studies we have observed cerebellar hypometabolism in asymptomatic SCA2 and SCA3 gene carriers [11,21]. Results from this study demonstrating that the cerebellar hypometabolism does not necessarily correlate with the clinical severity of ataxia may explain why metabolic differences were observed more extensively between SCA patients and healthy controls, but not within the group of patients.…”

Section: Discussioncontrasting

confidence: 39%

Topographic brain mapping of the international cooperative ataxia rating scale

et al. 2007

View full text Add to dashboard Cite

The International Cooperative Ataxia Rating Scale (ICARS) is a 100-point semiquantitative scale designed primarily to assess cerebellar dysfunction. However, little is known of the metric properties of this scale. We assessed the ICARS by rating the severity of cerebellar dysfunction in 27 patients with spinocerebellar ataxias (SCA), three patients with sporadic olivopontocerebellar ataxia and 24 healthy control subjects. [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) study was also performed on each subject. The statistical parametric mapping analyses revealed a significant correlation between the ICARS scores and functional impairment of the frontal regions within SCA patients. The glucose metabolism in the cerebellum, thalamus and caudate nucleus had significant differences between SCA patients and healthy control subjects. The results suggested that the clinical severity of SCA patients correlated with the functional impairment in the frontal regions, the targets of cerebellar efferent projections.

show abstract

Section: Discussioncontrasting

confidence: 39%

Topographic brain mapping of the international cooperative ataxia rating scale

et al. 2007

View full text Add to dashboard Cite

show abstract

“…PET and SPECT studies enable functional analyses beyond structural defects. F18-deoxyglucose PET detected altered glucose utilisation in cerebellum, brainstem, and cerebral cortex already in asymptomatic mutation carriers and thus demonstrated early presymptomatic changes in SCA3 (44). Dopamine transporter PET demonstrated decreased binding in the striatum similar to Parkinson's disease, but without significant asymmetry matching pathoanatomic findings of severe degeneration of the substantia nigra (45,46).…”

Section: Clinical Features Of Sca3 and Neuroimagingmentioning

confidence: 88%

SCA3: Neurological features, pathogenesis and animal models

Rieß

Rüb

Pastore³

et al. 2008

Cerebellum

206

133

View full text Add to dashboard Cite

The most frequent subtype of autosomal dominant inherited spinocerebellar ataxias is caused by CAG repeat expansions of more than 55 units in the ataxin-3 gene. The clinical variability of the phenotype depends on the length of the expanded repeat and the age at onset (and thus indirectly with the repeat size). Anticipation of the phenotype is most frequently associated with repeat expansions in paternal transmission. In this review we describe four clinical subphenotypes and correlate them to the respective repeat expansions. We also provide a detailed description of the neuropathological features. Finally, we discuss the current knowledge on the function of normal and dysfunction of altered ataxin-3 and how this translates to the predicted structure of the protein.

show abstract

“…Several nuclear imaging studies indicate involvement of various brain areas throughout the disease course in SCA3 (table e-3). [31][32][33][34][35] In patients with manifest SCA3, significantly reduced glucose metabolism has been reported in cerebellar hemispheres, vermis, occipital cortex, and brainstem. 31 Additionally, Taniwaki et al 33 found decreased glucose uptake in all cerebral lobes, putamen, and caudate nucleus.…”

mentioning

confidence: 99%

The preclinical stage of spinocerebellar ataxias

et al. 2015

View full text Add to dashboard Cite

The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of degenerative diseases of the cerebellum and connected regions. The discovery of various SCA genes and the subsequent possibility of predictive testing currently allow a genetic diagnosis to be established years or even decades before the actual appearance of ataxia symptoms. A growing body of evidence, however, indicates that this preclinical stage is subject to the earliest pathophysiologic changes. This review article comprehensively summarizes the studies conducted in preclinical carriers of a mutation in one of the SCA genes. From these data, it can indeed be concluded that the preclinical phase in SCA is already characterized by detectable central and peripheral nervous system changes, which are reflected by subtle abnormalities during a careful clinical examination, changes in structural and functional brain imaging, abnormal neurophysiologic measurements, and/or altered motor learning paradigms. As these may be compensated for a long time, ataxia symptoms probably only appear after a certain threshold of dysfunction or degeneration has been exceeded. Detailed knowledge of this disease stage is of particular relevance for a better understanding of the pathogenesis of SCAs, will allow us to determine the optimal point in time for interventions in future therapeutic trials, and points to objective, valid biomarkers to assess disease progression. Further studies will benefit from a consensus-based definition of the preclinical stage, from using one and the same validated ataxia rating scale with one fixed cutoff value, and from applying similar mathematical models to calculate time to predicted disease onset.

show abstract

Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease

Cited by 54 publications

References 20 publications

Topographic brain mapping of the international cooperative ataxia rating scale

Topographic brain mapping of the international cooperative ataxia rating scale

SCA3: Neurological features, pathogenesis and animal models

The preclinical stage of spinocerebellar ataxias

Contact Info

Product

Resources

About