Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.

Abstract

In 1976, Trotter et al¹ described a patient with Hodgkin lymphoma (HL), subacute cerebellar degeneration, and antibodies that stained cerebellar Purkinje neurons in a characteristic pattern. These findings were further described in a case series in 1992 by Hammack et al.² This characteristic staining pattern was termed anti-Tr after the lead investigator on the initial report³ and was subsequently identified in other patients with paraneoplastic cerebellar degeneration, about 90% of whom had HL.^4,5 Patients with paraneoplastic cerebellar degeneration typically have progressive nystagmus, limb ataxia, dysarthria, and gait ataxia. Magnetic resonance imaging of the brain may show signs of cerebellar inflammation, and cerebrospinal fluid (CSF) samples may show mild pleocytosis and/or elevated protein levels.⁶ Patients may improve with immunotherapy and/or therapy directed against the tumor, but even treated patients typically have permanent cerebellar dysfunction. Postmortem studies show a loss of cerebellar Purkinje neurons.⁴