Dentate nucleus signal loss on susceptibility-weighted MRI as a diagnostic clue to ataxia with oculomotor apraxia type 2: a case report highlighting the importance of neuroimaging patterns in hereditary ataxias

Abstract

Case Presentation: A 51-year-old Brazilian man presented with progressive imbalance that began at age 16, initially noticeable during physical exertion and gradually worsening over time. Over the last 20 years, he has progressed with paresis and distal atrophy of all four limbs. For the past 10 years, he has needed support to walk. His family history revealed similar symptoms in a paternal great-aunt and a maternal aunt. Neurological examination showed head tremor, distal weakness with muscle atrophy, absent reflexes with sensory loss, pes cavus, a wide-based gait with bilateral foot drop, multidirectional nystagmus, and scanning speech. No ocular abnormality was found. Laboratory evaluation showed elevated alpha-fetoprotein levels (37.45 ng/mL). Brain MRI demonstrated diffuse cerebellar atrophy and loss of the normal hypointensity of the dentate nuclei. Nerve conduction studies revealed axonal sensorimotor polyneuropathy. Genetic testing identified a homozygous variant in the SETX gene, confirming the diagnosis of Ataxia with Oculomotor Apraxia Type 2 (AOA2). Discussion: Despite the long duration of symptoms, oculomotor apraxia was absent in this patient, illustrating the phenotypic variability of the condition. The development of increasingly advanced genetic mapping technologies has enabled the identification and diagnosis of several hereditary ataxias. Among these conditions is ataxia with oculomotor apraxia (AOA), a group of autosomal recessive disorders characterized by variable phenotypes. To date, four subtypes have been described, each associated with mutations in a specific gene. AOA2 typically presents later than other forms and is characterized by progressive cerebellar ataxia, sensorimotor peripheral neuropathy, and occasionally chorea. Although oculomotor apraxia gives the disorder its name, it is absent in approximately half of patients. Additional supportive findings include elevated alpha-fetoprotein levels and cerebellar atrophy on MRI, often accompanied by reduction/disappearance of the normal dentate nucleus hypointensity on susceptibility-weighted imaging (SWI) as presented by this patient. This radiological feature has been proposed as a potential marker to help differentiate AOA from other recessive ataxias. The diagnosis is ultimately established through the identification of pathogenic variants in the SETX gene. Final Comments: Given the marked phenotypic variability of AOA2, recognition of characteristic neuroimaging patterns may play an important role in raising diagnostic suspicion. Careful evaluation of the dentate nucleus signal on SWI and FLAIR sequences may provide an important radiological clue that facilitates earlier diagnostic orientation toward AOA2 and guides targeted genetic testing.