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Case history

image A 65-year-old woman with stage II ovarian cancer and hypothyroidism was admitted to the acute oncology ward with a 5 day history of progressive nausea, gait instability and oscillopsia. Her drug history was remarkable for levothyroxine only. She did not drink alcohol. On examination she manifested a downbeat nystagmus, past pointing; dysdiadochokinesia; and both truncal and gait ataxia.

Radiological investigations failed to reveal an abnormality to explain the patient’s cerebellar signs and symptoms. The only positive laboratory finding was the presence of anti-Yo antibodies in her serum.

What is the differential diagnosis?

What investigations should be done?

What is the treatment and prognosis?

What is the differential diagnosis?

The signs and symptoms are suggestive of a cerebellar lesion. In the context of a person with a known or prior malignancy, cerebellar metastases and paraneoplastic syndromes would be high on the differential diagnosis list. Other conditions to consider include vascular (infarction/ischaemia) and metabolic causes, medications (e.g. anticonvulsants) and thyroid dysfunction. In the context of patients with known cancer, clinicians should be cognisant of cerebellar insults secondary to certain types of chemotherapy medications such as cytarabine and fluorouracil.

What investigations should be done?

Urgent neuroimaging is required to exclude a cerebellar mass. MRI is more sensitive than CT in detecting lesions within the cerebellum and brainstem and should be requested if the initial CT scan is negative. Routine blood tests including thyroid function should be taken. Hypothyroidism is a rare, albeit treatable, cause of cerebellar dysfunction. Vitamin B and E levels should also be measured, as deficiencies may interfere with cerebellar function.

The most likely diagnosis is a paraneoplastic syndrome affecting the cerebellum, in particular paraneoplastic cerebellar degeneration. As a consequence, paraneoplastic biomarkers should be measured in the patient’s serum.

By definition, paraneoplastic syndromes are a heterogeneous group of neurological disorders that are associated with systemic cancer but not with cancer per se or the side effects of its treatment. Although not completely understood, it is conjectured that these syndromes arise as a result of an immunological response directed against shared antigens (in particular the nervous system) that are ectopically released by the tumour.1 It has been suggested that self-antigens may be processed differently in cancer cells, thus inciting a T cell response.2 It is noteworthy that paraneoplastic syndromes may also arise from a non-immune pathophysiological basis. An example is the release by a tumour of hormones, such as parathyroid hormone-related protein leading to hypercalcaemia.

Numerous onconeuronal antibodies have been identified. ‘Well-characterized’ antibodies are summarized in Table 27.1. The presence of any of these antibodies (which are directed against intracellular neuronal proteins) in a patient’s serum is sufficient to establish the presence of a paraneoplastic syndrome, even in if no underlying neoplasia is detected.3 Patients with ‘partially characterized’ antibodies, by contrast, require a ...

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