Association between paraneoplastic rhombencephalitis and hypertrophic olivary degeneration

Hypertrophic olivary degeneration (HOD) is a condition caused by interruption of white matter tracts within the dentato-rubro-olivary pathway (DROP), resulting in inferior olivary T2 hyperintensity and enlargement on MRI. Olivary atrophy may be seen as a sequela of HOD.1 HOD has been described in association with brainstem infarcts, tumours, demyelination and vascular lesions such as cavernous malformations.2 However, HOD can also be seen in the absence of any lesion in the DROP and is sometimes idiopathic.3 Rhombencephalitis refers to inflammation involving the brainstem and/or cerebellum and can rarely be caused by paraneoplastic syndromes. Several neural specific antibodies are classically associated with paraneoplastic rhombencephalitis, including anti-Ma2 and antineuronal nuclear antibody type 2 (ANNA2 or anti-Ri). Kelch-like protein 11 (KLHL11) IgG is another recently described serological biomarker that has a strong association with paraneoplastic rhombencephalitis.4 The tumours frequently associated with paraneoplastic rhombencephalitis include testicular seminoma, breast cancer, small cell lung cancer and gynaecological malignancies. Brain MRI is often normal or shows progressive brainstem and cerebellar atrophy. MRI in these patients can also rarely show brainstem T2 hyperintensity and enhancement. A recently reported KLHL11 rhombencephalitis patient was incidentally noted to have left-sided HOD caused by a dentate lesion.4 However, no clear association between paraneoplastic rhombencephalitis and HOD has been previously suggested, even in comprehensive reviews.5 Here, we report six patients with onconeural antibody-associated paraneoplastic rhombencephalitis who developed HOD. Electronic medical records were queried to identify patients evaluated at our institution from 2005 to 2020 whose serum and/or cerebrospinal fluid demonstrated seropositivity to any of the following autoantibodies: type-1 antineuronal nuclear antibody (ANNA1/anti-Hu), KLHL11, Ma2, ANNA-2 (anti-Ri), Purkinje cell antibody type 1 (PCA-1, anti-Yo), collapsin response mediator 5 (CRMP5 or anti-CV2), amphiphysin and PCA-Tr (DNER). This revealed 177 total patients (KLHL11, n=24; Ma2, n=11; ANNA-1, n=60; ANNA-2, n=14; …