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An unusual cause of tremor in an elderly man

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Q1: What is the probable diagnosis?

The lumbar spine radiograph shows sclerotic lesions involving the lower lumbar vertebrae. The aspirate shows that the bone marrow is densely populated by clumps of neoplastic cells. The normal haemopoietic cells are almost totally replaced by tumour cells. Neoplastic cells are usually larger than normal haemopoietic cells other than the megakaryocytes, and they are pleomorphic with regards to size, shape, and nuclear characteristic. They are commonly cohesive and therefore occur as tight clumps.1 2 It is usually not possible to predict the tissue of origin from the cytological features of the neoplastic cells in smears of bone marrow aspirates. A provisional diagnosis of metastatic prostatic carcinoma was made based on the presence of an enlarged prostate on clinical examination, osteosclerotic lesions, and neoplastic cells in the bone marrow.

Q2: What other investigations should be done to confirm the diagnosis?

The metastatic tumour cells in the marrow biopsy specimen were positive for prostate specific antigen using immunohistochemistry technique that employed monoclonal antibodies. Computed tomography of the abdomen and pelvis showed an irregular thick walled prostate and enlarged lymph nodes in the para-aortic and pelvic regions. The patient did not consent to a transurethral prostatic biopsy. The serum prostate specific antigen (PSA) level was markedly raised at 120 μg/l. PSA has generally replaced acid phosphatase for the diagnosis and monitoring of prostatic carcinoma as it has greater sensitivity (especially for early invasive carcinoma) and specificity. Marked elevation is indicative of carcinoma, but concentrations are also increased in prostatitis, prostatic ischaemia or infarction, benign prostatic hypertrophy, and acute renal failure. Normal concentrations do not exclude prostatic carcinoma.

Q3: What are the possible causes of the tremor in this patient?

The principal differential diagnoses of a tremor in an elderly man include Parkinson's disease, essential tremor, lesions in the midbrain, cerebellar lesions, endocrine-metabolic diseases such as thyrotoxicosis and hypoglycaemia, and drugs (such as β-agonists, dopamine agonists, alcohol withdrawal, and tricyclic antidepressants). Like all neurological diseases, the single most important step in the diagnostic process is the identification of the site of the lesion. This is almost always possible through a detailed history and thorough physical examination. The physician must be able to characterise the tremor in terms of its site, approximate frequency, amplitude and amplification or reduction in three different positions (rest, posturing of the arms, and during finger-nose testing). Of these features, the latter is the most useful. A tremor, which is present in all three positions, points to a lesion in the superior cerebellar peduncle in the midbrain, near the red nucleus (thus the term “rubral” tremor). Rubral tremors are present at rest, and are typically enhanced by posturing of the arms and more so, by goal directed movements. Parkinsonian tremors, however, abate with movement. Given the presence of titubation, essential tremor and a cerebellar lesion are also possible diagnoses.3 There were, however, no signs of cerebellar dysfunction, and essential tremors do not usually present acutely. The next step in the diagnostic process is to ascertain the nature of the lesion. Given his age and the acute onset of tremors, a midbrain stroke has to be considered first. Computed tomography of the brain did not reveal an infarct or haemorrhage in the midbrain, but the detection of the former is better on magnetic resonance imaging. Given the diagnosis of prostatic cancer, a metastatic midbrain tumour is a possibility, but the history was too rapid, and the brain computed tomography essentially excluded this. The most likely diagnosis is a paraneoplastic syndrome. The fact that the patient's tremors abated after radiotherapy and hormonal treatment and not after medication (clonazepam and later, primidone) is strong evidence for this.3

Learning points

  • Carcinoma of the prostate is a common cause of bone marrow infiltration leading to pancytopenia in an elderly man.

  • The absence of symptoms of prostatism does not exclude diseases of the prostate.

  • Bone marrow examination is a simple and useful diagnostic tool in the diagnosis of non-haematological malignancies infiltrating the bone marrow.

  • The most important step in the diagnosis of tremor is characterisation of the tremor in three different positions.

  • Tremor may be the first presentation of paraneoplastic syndrome.

Discussion

We have demonstrated that this patient had disseminated prostatic cancer. The resolution of the patient's tremor after cancer treatment strongly supports the diagnosis of paraneoplastic syndrome. Small cell lung and ovarian cancers have the highest frequency of paraneoplastic syndromes, although theoretically, any cancer can cause paraneoplastic syndromes.4 The onset of neurological paraneoplastic syndromes is usually acute or subacute. Although tremor alone has never been described as being a paraneoplastic syndrome, tremor as part of subacute cerebellar degeneration and brain stem encephalitis has.4 5 These syndromes, however, typically occur with small cell lung cancer, and tremor is not a major feature. The initial symptoms in these syndromes are gait ataxia, dysarthria, diplopia, vertigo, and oscillopsia.4 The pathogenesis of these syndromes is poorly understood, but may be related to circulating anti-Yo (cerebellar degeneration) and anti-Hu (brain stem encephalitis) autoantibodies.4 5 The most likely site of the lesion in the present case is the superior cerebellar peduncle, presumably due to autoantibodies directed to the midbrain.

Final diagnosis

Disseminated prostatic carcinoma with a paraneoplastic neurological syndrome.

References

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