1 - Department of Neuroradiology, Centro Hospitalar Universitário de Lisboa Central, E.P.E., Lisbon, Portugal
2 - Department of Pediatrics, Hospital do Divino Espírito Santo de Ponta Delgada, E.P.E.R., Azores, Portugal
- XVII Congresso da SPNR, 25 e 26 de Novembro de 2022, Lisboa
Introduction: PLA2G6-associated neurodegeneration (PLAN) comprises a group of rare autosomal recessive neurodegenerative disorders caused by loss-of-function mutations in PLA2G6 gene. Although clinical and imaging features frequently overlap, three main phenotypes were described based primarily on the age of onset and disease progression, namely infantile neuroaxonal dystrophy (INAD), atypical NAD, and PLA2G6-related dystonia-parkinsonism. INAD patients present during the first 2 to 3 years of life, and rapidly progressive neurological deterioration and fatal outcome in the first decade are characteristic. Diagnosis was previously only possible by histopathologic demonstration of widespread distal axonal degeneration with spheroid bodies (hallmark for neuroaxonal dystrophy), but detection of biallelic PLA2G6 pathogenic variants has become the gold standard.
Methods & Results: We report two cases of genetically confirmed INAD with focus on the key role of MRI as part of the diagnostic workup and in the patient selection for PLA2G6 genetic testing. Both male patients presented with psychomotor delay and regression under the age of 2. Symptoms progressed over time leading to severe disability (truncal hypotonia, hyperreflexia and spasticity), and one of the patients developed epilepsy. Brain MRI showed bilateral cerebellar and optic nerves/chiasm atrophy, and hypointensities of globi pallidi and substantia nigra on susceptibility-weighted imaging. Though less conspicuous, hypertrophy of the clava (gracile tubercles on dorsal medulla) was also noted in both cases.
Conclusion: Clava hypertrophy is a known early imaging finding highly suggestive of PLAN/INAD. As in the cases reported, it is useful in the differential diagnosis of symmetrical cerebellar atrophy and iron deposits in the basal ganglia. Therefore, radiologists should be aware of this feature that may help to guide genetic testing allowing prompt confirmation of the diagnosis. However, hypertrophy of the clava is not pathognomonic for PLAN and can be seen in other rare causes of pontocerebellar atrophy.
Keywords: PLAN; MRI; hypertrophy of the clava; cerebellar atrophy