Longitudinal structural brain changes in Friedreich ataxia depend on disease severity: the IMAGE-FRDA study

Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]‐FEMPA PET Study

“…The current study indicates that additional variability may relate to neuroimmune activity, although it remains to be determined whether increased neuroinflammation is a cause or consequence of earlier disease onset. Our observations that neuroinflammatory activity may be maximal early in the disease course mirrors evidence that degeneration of the dentate nuclei and cerebro‐cerebellar pathways also occurs maximally earlier in the FRDA disease course 31,32 . These observations motivate further exploration of inflammation‐degeneration relationships in FRDA, in line with findings in other neurodegenerative diseases where increased TSPO PET radioligand binding anatomically corresponds with areas of structural atrophy 33‐35 …”

“…Our observations that neuroinflammatory activity may be maximal early in the disease course mirrors evidence that degeneration of the dentate nuclei and cerebro-cerebellar pathways also occurs maximally earlier in the FRDA disease course. 31,32 These observations motivate further exploration of inflammation-degeneration relationships in FRDA, in line with findings in other neurodegenerative diseases where increased TSPO PET radioligand binding anatomically corresponds with areas of structural atrophy. [33][34][35] Although glial activation is the most parsimonious interpretation of increased TSPO expression in the human brain, other molecular processes that influence mitochondrial function cannot be discounted.…”

Prediction of the disease course in Friedreich ataxia

“…Despite being to some degree sensitive to the applied (pre-) processing, measures characterising the central nervous system are suffering less from issues regarding objectivity than clinical scales. Characteristic alterations of the spinal cord, brain stem and cerebellum in FRDA have recently been shown 50 , 51 and thus seem like a viable variable to include in predictive modelling of the disease course.…”

Variation in the Accuracy of Endpoint Selection in Clinical Studies for Rare Diseases in Respect of Increasing Knowledge on Disease-Severity Measurement

“…Ulcerative colitis was excluded before review, as the previous study had identi ed it as having insu cient published data using its DSSs. The following 12 rare diseases were included (number of DSSs): acromegaly (3), amyotrophic lateral sclerosis (6), Charcot Marie Tooth disease (5), cystic brosis (5), encephalitis (4), Fabry disease (2), Friedreich ataxia (3), Gaucher disease Type 1 (2), Huntington's disease (2), juvenile rheumatoid arthritis (2), Sjogren's syndrome (2), and Tourette syndrome (3). An overview of the diseases, the composition and publication dates of their rst and composite DSSs and the number of indicators in each has been provided in Table 2 Gaucher Disease Severity Score Index -Type I (2008)…”

“…Ensuring the accuracy of clinical trial endpoints in rare diseases is important not only because trial results inform treatment decisions but also because disease progression for such conditions may remain poorly understood despite growing research attention. 1,2 Further, clinical trials for rare diseases are often small and have low power by default, so optimising measurement accuracy may ensure that endpoints translate to clinically meaningful results. 1 Clinical trials use distinct sets of indicators to observe disease severity, so the accuracy of disease severity measurement is affected by inter-trial variation, 3 which could be bene cial to address.…”