From the Guidelines
When a patient presents with neurological symptoms and positive anti-Tr antibodies, an underlying malignancy should be suspected, with Hodgkin lymphoma being the most common associated cancer. The typical neurological presentation includes progressive cerebellar ataxia, dysarthria, nystagmus, and sometimes vertigo, which often precede the cancer diagnosis by months to years, making the antibody an important early diagnostic marker 1. Management involves treating the underlying malignancy, which may lead to stabilization of neurological symptoms, though complete recovery is uncommon. Immunotherapy with corticosteroids, intravenous immunoglobulin, plasma exchange, rituximab, or cyclophosphamide may be used to address the immune-mediated neurological damage, with earlier treatment generally yielding better outcomes 1. Some key points to consider in the management of these patients include:
- Comprehensive cancer screening, including whole-body PET/CT, to identify any underlying malignancy 1
- Long-term surveillance for malignancy even if initial screening is negative, as the cancer may appear years after neurological symptom onset 1
- Consideration of the potential for brain metastases and the use of systemic therapy and radiotherapy in their management 1
- The importance of early diagnosis and treatment to improve outcomes in patients with anti-Tr antibodies and associated neurological symptoms 1
From the Research
Association between Anti-Tr Antibody Positive Neurologic Symptoms and Cancer
- The presence of Anti-Tr/DNER antibodies has been strongly associated with Hodgkin Lymphoma (HL) and paraneoplastic cerebellar degeneration (PCD) 2, 3, 4.
- Studies have shown that PCD can be the only presenting symptom of a very late relapse of HL, even after 12 years of complete remission 2.
- Anti-Tr/DNER antibody-associated paraneoplastic neurological syndrome can also present with limbic encephalitis and be complicated by tumors other than HL, such as anaplastic large cell lymphoma 5.
- A systematic review of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia found that 91% of patients presented with an associated tumor, with HL being the most common 6.
Clinical Characteristics and Diagnosis
- Isolated cerebellar ataxia is the most common presentation of anti-Tr/DNER antibody-associated cerebellar ataxia, with extracerebellar features being rare 6.
- Abnormal neuroimaging patterns, such as cerebellar atrophy and cerebellar hypersignal, can be observed in some patients 6.
- Cerebrospinal fluid analysis often shows inflammatory changes, and testing for anti-Tr/DNER antibodies is essential for diagnosis 6.
Prognosis and Treatment
- Oncological response to treatment is excellent, with 88% of patients achieving complete response 6.
- However, neurological prognosis is poor, with only 41% of patients showing significant neurological improvement at follow-up 6.
- Treatment with intravenous immunoglobulin, chemotherapy, and radiation therapy can improve symptoms, as seen in a case report of a patient with relapsed HL 2.