Postgrad Med J: first published as 10.1136/pgmj.68.801.584 on 1 July 1992. Downloaded from Postgrad Med J (1992) 68, 584- 586 C) The Fellowship of Postgraduate Medicine, 1992

Clinical Reports Cerebellar manifestations ofprostatic carcinoma J. McLoughlin, J.C. Gingell, G. Harper' and A. Hinchliife' Department of Urology, Southmead Hospital, Westbury-on-Trym, Bristol BSIO SNB and 'Department of Surgery, Weston Hospital, Weston-Super-Mare, UK

Summary: We present two patients known to have prostate cancer who presented with acute cerebeliar signs. The neurological deficit of the first patient was due to a paraneoplastic cerebeliar manifestation and progressed, despite evidence of response of the primary prostate tumour to hormonal manipulation. The second case, resulting from a solitary cerebeliar metastasis, was amenable to surgical intervention and subsequent hormonal manipulation. This latter patient has experienced no recurrent neurological signs after a period of7 years follow-up. This is the first report of a paraneoplastic cerebellar deficit and, to our knowledge, only the sixth case of parenchymatous cerebeliar metastasis of prostatic origin to appear in the literature.

Introduction Intracranial deposits develop in 12-25% of all rectus muscle and rotatory nystagmus. Despite patients with systemic malignancy, of which 16% extensive investigation: (cranial) computed tomo-copyright. are to the cerebellum.' In contrast to other graphy (CT), magnetic resonance imaging (MRI), tumours, parenchymatous brain metastases result- cerebrospinal fluid (CSF) examination and oligo- ing from prostate cancer are uncommon, occurring clonal band analysis, VDRL, electroencephalo- in only 1.5-1.9% of patients.2'3 Neurological graphy (EEG) and visually evoked potentials disorders experienced by patients with malignancy (VEP), no cause was found to account for the are not, however, exclusively the result of metas- physical findings. Temporary discontinuation of tatic invasion. Paraneoplastic neurological and cyproterone acetate did not improve the physical muscular manifestations may develop, even before signs. During this period, the PSA declined to http://pmj.bmj.com/ the underlying cancer is evident. To date, no case 2 ng/ml. Over the next 8 months, despite PSA levels of either paraneoplastic cerebellar degeneration remaining < 1.5 ng/ml whilst the cerebellar deficit (PCD) nor opsoclonus myoclonus associated with stabilized, the ophthalmic defect progressed associ- prostatic carcinoma has been described. ated with bizarre eye movements. A diagnosis of paraneoplastic cerebellar degeneration, secondary Case 1 to carcinoma of the prostate, was made. The eye movements were attributed to an associated opsoc- A 67 year old male was diagnosed as having lonus myoclonus. on September 24, 2021 by guest. Protected carcinoma of the prostate in 1989. This was poorly differentiated and involved 95% of prostatic chip- pings examined histologically after transurethral Case 2 resection. Initial investigations revealed a prostate specific antigen (PSA) level of 47 ng/ml (normal In 1984, carcinoma of the prostate was diagnosed range 0-4 ng/ml) and the clinical stage of the in a 71 year old man presenting with chronic tumour as T3 NX MO.4 Cyproterone acetate was retention of urine. The tumour was initially staged commenced at this time. as T4 NX M1.4 His serum prostatic acid phospha- Three months later, the patient developed a tase level was determined to be 5.0 IU/ml at rapidly progressive cerebellar deficit associated diagnosis (normal range 0-1 IU/ml). In the days with truncal ataxia, pseudobulbar palsy, diplopia following admission, the patient developed pro- and transient migratory paresis ofthe right inferior gressive leg weakness, headaches, poor concentra- tion and lack of co-ordination of his left arm. His clinical condition rapidly progressed to semi-con- Correspondence: J. McLoughlin, M.S., F.R.C.S. sciousness, associated with an up-going left-sided Accepted: 10 December 1991 plantar reflex. An urgent cranial CT scan revealed Postgrad Med J: first published as 10.1136/pgmj.68.801.584 on 1 July 1992. Downloaded from CLINICAL REPORTS 585 an isolated cerebellar space occupying lesion, for Table I Previously described paraneoplastic manifesta- which the patient underwent a posterior fossa tions of prostatic malignancy craniotomy and excision of the tumour. Histo- logical examination revealed this to be an adeno- Endocrine carcinoma with a positive reaction to PSA Cushing's syndrome a metastatic Inappropriate antidiuretic hormone production immunohistochemistry, deposit Hypercalcaemia without associated bone metastases originating from a primary prostatic carcinoma. Hypophosphataemia Postoperatively, his mental picture improved Haematological markedly and he subsequently underwent trans- Anaemia urethral resection of the prostate and bilateral Non-bacterial thrombotic endocarditis subcapsular orchidectomy, at which time confirm- Disseminated intravascular coagulation ation of the prostatic primary tumour was obtain- Hypercoagulability ed. Over a period of review of 7 years, the patient Thrombophlebitis has remained well with no residual neurological Neurological no rise in serum Necrotizing myelopathy deficit, acid phosphatase levels Carcinomatous neuromyopathy (and later PSA levels), nor evidence of new intra- Cutaneous and muscular cranial lesions on MRI. Areas ofincreased uptake, Dermatomyositis observed on the isotope bone scans at the time of Migratory paraneoplastic erythema diagnosis, resolved competely during this period, Non-specific with no abnormality detectable on the most recent Cachexia and anorexia isotope examination. (Based on Matzkin, H. & Braf, Z."6)

Discussion Cerebellar metastases usually arise from lung, small cell lung tumours,"I carcinomas of the breast, gastrointestinal and cutaneous primaries.5 breast,'2 uterus and ovary'3 or with Hodgkin's copyright. Cerebellar deposits of prostatic origin are extre- lymphoma,'4 and in children, with neuroblas- mely rare, an extensive literature search revealing toma.'5 This is the first case report describing this only five previous case reports.',3'6,8 The mechan- complication in relation to prostate cancer. Matz- ism by which the intracranial contents are invaded kin and Braf'6 fail to discover any similar syndrome by tumour is controversial, this possibly being one in an extensive literature review. The classical of retrograde infiltration of the valveless vertebral syndrome consists of truncal and appendicular veins ofBateson and Virchow-Robin spaces which, ataxia, often associated with dysarthria and mild during Valsalva manoeuvre, allow pelvic blood to global symptoms associated with mild cerebellar http://pmj.bmj.com/ reach the base of the skull and subsequent dural atrophy. Pathologically, there occurs diffuse loss of veins.' Cerebellar metastases generally carry a poor Purkinje cells, sometimes accompanied by a pro- prognosis, possibly because they are often a mani- liferation of Bergman astrocytes and loss of festation of disseminated malignancy. Indeed, this granule cells. A proportion have more widespread feature has led some authors to suggest that they clinical and pathological abnormalities. Anti- are part of a multi-step cascade process, occurring neuronal antibodies have been identified in the secondary to bone and pulmonary involvement.3 serum and cerebrospinal fluid ofsome patients with Cerebellar deposits are usually solitary, in contrast PCD, suggesting an autoimmune aetiology. on September 24, 2021 by guest. Protected to supratentorial deposits, this feature making The term opsoclonus myoclonus describes them amenable to surgical resection. Gilman et al.5 bizarre, rhythmic, multidirectional, high-ampli- proposed that, wherever possible, surgical inter- tude conjugate saccadic eye movements, exacer- vention should be undertaken for solitary lesions, bated by attempts at visual pursuit. In adults, fewer subsequent reports supporting this proposal3"9 with than 20 cases of opsoclonus myoclonus have been occasional reports ofprolonged survival in patients reported'7 - none of which was associated with with otherwise favourable parameters.5 prostate cancer. Only occasionally do patients with The first patient developed a cerebellar deficit of otherwise classical PCD develop opsoclonus. This non-mestastatic, paraneoplastic, origin. Previously group of patients differs from those with classical described paraneoplastic phenomena relating to PCD by a more rapid onset of symptoms, a prostate cancer are listed in Table I. Possibly the predominance oftruncal over appendicular ataxia, best known non-metastatic, neurological compli- absence of dysarthria and in some cases the cation of malignancy is paraneoplastic cerebellar presence of severe encephalopathy. Pathologically degeneration (PCD), albeit affecting less than 1% there is a relative preservation of cellular Purkinje of patients with cancer.'0 Previous reports have cells,'4 in contrast with other paraneoplastic synd- described this syndrome in adults associated with romes and possibly explaining why remission has Postgrad Med J: first published as 10.1136/pgmj.68.801.584 on 1 July 1992. Downloaded from 586 CLINICAL REPORTS been reported in some cases.'4 Whilst the logical deficit of the first man, with a reduced documented eye movements of the second patient tumour burden, continued to progress despite were not exacerbated by visual pursuit movements, biochemical evidence of response of his primary they were otherwise typical of opsoclonus. tumour to hormonal manipulation. It is perhaps a paradox that the second patient These two cases serve to illustrate the unpredic- with disseminated carcinoma obtained symptom tability of the course of prostate cancer and also relief and possibly even cure from his disease allow further insight into the complex immuno- following resection of the metastasis and subse- logical aspects of cancer biology which interact quent androgen deprivation, whilst the neuro- with host defences, modulating the final outcome.

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logical Napoli 1989, 11: 21-24. http://pmj.bmj.com/ on September 24, 2021 by guest. Protected