Ataxia-telangiectasia (A-T) remains an incurable disease with limited treatment options. The progression of clinical trials is hindered by the lack of diagnostic and disease progression biomarkers for A-T. Here, we report our observation of a potential diagnostic tool, the lack of hypointensity of the dentate nuclei (DN), A-T.

Classic A-T patients present in childhood where individuals are usually wheelchair-bound in their teens with cerebellar ataxia and extrapyramidal symptoms. Their life expectancy is significantly reduced with an increased risk of malignancy and immune defects. Patients with variant A-T have reduced residual ataxia telangiectasia mutated (ATM) kinase function, manifesting with milder, later presenting disease. The heterogeneous phenotype of variant A-T leads to diagnostic delays of sometimes decades. The increased risk of malignancy in A-T patients and carriers is an important justification for focusing on MRI diagnostic tools for this disease. Furthermore, the current lack of A-T imaging biomarkers limits the development and evaluation of novel therapies.

We have previously reported microbleeds in supratentorial regions in A-T.1 2 Abnormal hypointensity of the usually iron-rich DN has been reported in a single case report of A-T with microbleeds3 and other genetic ataxias, such as ataxia with oculomotor apraxia.4 5 In this current study, we have evaluated DN hypointensity as a potential diagnostic imaging signature for A-T from our UK National A-T cohort, using the Gupta visual rating scale.6

Our cohort of 26 A-T patients is reviewed annually or biannually at the National Paediatric or Adult A-T clinics, UK. Uncontrasted MRI brain imaging was performed as part of routine clinical care for adult patients (Health Research Authority Integrated Research Application System 204229). Paediatric patients were scanned as part of the Childhood A-T Neuroimaging Assessment Project (CATNAP; UK National Research Ethics Service references 14/EM/1175 and 18/SW/0078).7 The cohort included 16 classic A-T …