Paraneoplastic Cerebellar Degeneration (PCD) Associated with PCA-1 Antibodies in Established Cancer Patients

Paraneoplastic cerebellar degeneration (PCD) is a rare set of neurological disorders arising from tumor-associated autoimmunity against antigens within the cerebellum. Anti-Purkinje cell cytoplasmic antibody 1 (PCA-1), or anti-Yo, is the most commonly linked antibody and is classically associated with breast and ovarian cancers. Here we report case series of PCA-1 associated PCD in patients with known breast or ovarian cancer diagnosis not receiving immunotherapy. These cases highlight recognizing PCA-1 paraneoplastic syndrome triggered by cytotoxic chemotherapy, surgery, tumor recurrence and associated with development of second cancer. Diagnosis of the syndrome requires neurological workup with lumbar puncture (LP) with cerebrospinal fluids (CSF) studies, serum and CSF paraneoplastic antibody panel, and neuroimaging. Inpatient admission for prompt workup and initiation of treatment is recommended. Treatment most commonly includes immunosuppression with corticosteroids, plasmapheresis, and/or intravenous immune globulin (IVIG); however, we postulate that other immune modulating treatments may warrant consideration. In established cancer patients developing this syndrome, workup and treatment of tumor recurrence or development of second malignancy is recommended. These cases highlight the need for early recognition of the syndrome in patients receiving non immune based chemotherapy, for prompt workup and treatment.

Influence of Autoimmune Antibody Testing on the Use of Immunotherapy on an Inpatient Neurology Service

Objective: To determine the frequency of autoimmune antibody testing in an inpatient neurology setting and its influence on immunotherapy use on an inpatient neurology service. Methods: A retrospective descriptive cohort study of patients admitted to the neurology inpatient service at a large tertiary academic medical center who had autoimmune and/or paraneoplastic antibody testing performed between 10/1/2017 and 10/1/2018. Characteristics of patients’ initial clinical presentation, antibody testing results, test timing in relation to initiating immunotherapy, and final diagnosis using consensus criteria were extracted and analyzed. Case reports of patients with positive antibody panels are presented. Results: Of 1,604 patients, 50 patients (3.1%) had an antibody panel sent. Tests resulted after an average of 17 days (range 7-27). The most common clinical presenting symptom in those with a panel sent was encephalopathy. There were 5 (10%) positive serum panels and no positive CSF panels. Only one of these 5 patients had autoimmune encephalitis and was treated with immunotherapy. Of those with negative serum and CSF panels, 15 were treated acutely with empiric immunotherapy and the remainder with supportive care. Of those treated with immunotherapy, 14/15 (93%) were treated before the panel tests resulted. Four patients who had negative panels but were empirically treated met consensus criteria for an autoimmune-mediated neurologic process. Conclusion: Our study suggests that the results of antibody testing did not influence inpatient neurologists’ decision to treat with immunotherapy as most treatments began prior to final results being available.

Into a Shaking Limbo: Case Report of a Nonneoplastic Limbic Encephalitis with Faciobrachial Dystonic Seizures and Parkinsonism

This case report describes a rare but classic presentation of a non-paraneoplastic, antibody-mediated limbic encephalitis. The clinical course did put us in a limbo as it evolved from seizure to Parkinsonism and then from metastasis to stroke, before it finally announced itself by its pathognomonic finding. Knowledge of this rare condition is important as early identification and treatment can change the course.

Paraneoplastic Diseases of the Central Nervous System

Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death. There are several classical neurological paraneoplastic phenotypes including subacute cerebellar degeneration, limbic encephalitis, encephalomyelitis, and dorsal sensory neuropathy. The patient’s clinical presentations may be suggestive to the treating clinician as to the specific underlying paraneoplastic antibody. Specific antibodies often correlate with the specific underlying tumor type, and malignancy screening is essential in all patients with paraneoplastic neurological disease. Prompt initiation of immunotherapy is essential in the treatment of patients with paraneoplastic neurological disease, often more effective in cell surface antibodies in comparison to intracellular antibodies, as is removal of the underlying tumor.