Primary Cerebral Lymphoma presenting with Parkinsonism

JM Foy, WR Primrose, JM Mackenzie

JM Foy, Consultant Physician, Department of Medicine for the Elderly, Woodend Hospital, Eday Road Aberdeen AB15 6XS   Email: Julia.Foy@arh.grampian.scot.nhs.uk

WR Primrose, Consultant Physician, Department of Medicine for the Elderly, Woodend Hospital, Eday Road Aberdeen AB15 6XS   

JM Mackenzie, Consultant Pathologist, Department of Pathology, University Medical School, Foresterhill, Aberdeen AB25 2DZ

SMJ 2006 52(1): 55

 

Abstract

Brain tumour is a rare cause of Parkinsonism with cerebral lymphoma seldom reported as a cause. However, the incidence of this tumour is increasing and we report one such case, which presented with a parkinsonian syndrome and did not respond to medication. The diagnosis of cerebral lymphoma was made at postmortem.

 

Case Report

An 85-year old woman presented with a 6-month history of functional deterioration and generalised aches and pains. Her past medical history included a duodenal ulcer, cerebellar infarction and ischaemic heart disease. Prior to this deterioration she had been living independently.

 

She had signs of parkinsonism including an expressionless face, left hand tremor, markedly increased tone, cogwheel rigidity and brisk reflexes. Hoffman’s sign was present bilaterally, the left plantar response was extensor and there was a positive glabellar tap. Her gait was shuffling. Intellectually she was unimpaired. ESR, FBC, admission screen and thyroid function tests were all normal.

 

A diagnosis of parkinsonism was made although it was noted that the presentation was atypical for Idiopathic Parkinson’s Disease (IPD) because of such a rapid deterioration in her mobility. She was started on L-dopa (Madopar 62.5 three times daily increasing to 125 three times daily).

 

She required admission prior to her review appointment. On examination she was pyrexial and confused. She had bilateral hand tremor, muffled speech and bradykinesia. Full blood count, admission screen, thyroid function tests and C-reactive protein were all normal. She had pyuria but no growth on urine culture. She was treated for urinary tract infection and started on Fluoxetine 20mg for depression. A dopamine agonist (Pergolide titrated up to 250 micrograms three times daily) was added to her L-Dopa preparation.

 

Her pyrexia settled but she remained apathetic and confused and did not improve despite increased anti- parkinsonism medications.

 

An Apomorphine trial (up to 7mg) improved her tremor but not her mobility. A regional blood low brain scan (SPECT) was in keeping with Alzheimer’s disease. A MRI brain scan revealed early cerebral atrophy involving the temporal lobes and an old infarction in the cerebellar hemisphere. An EEG showed diffuse slow wave activity, not typical of Parkinson’s disease, raising the question of a possible diagnosis of Creutzfeldt-Jakob disease. The patient continued to deteriorate and she died 9 months after her initial presentation.

 

A post-mortem examination excluded the diagnosis of Creutzfeldt-Jakob disease. Microscopic examination however, revealed large numbers of perivascular lymphoid cells extending into the surrounding brain tissue with gliosis, demyelination and florid macrophage infiltration. This infiltrate most severely affected the basal ganglia/thalamus region but also involved the midbrain including the substantia nigra. No Lewy bodies were identified. A diagnosis of a primary cerebral lymphoma of diffuse large B cell type was made. There was no evidence that the patient suffered from IPD and her parkinsonism was attributed to involvement of the substantia nigra and the striatum by lymphoma.

  

Discussion

Brain tumours are an uncommon cause of parkinsonism and those associated with parkinsonian syndromes are usually meningiomas or gliomas of various types. Less frequently, craniopharyngiomas, colloid cysts and metastases.1

 

Primary central nervous system lymphoma (PCNSL) is defined as lymphoma limited to the cranial-spinal axis and is rare accounting for less than 5% of all brain tumours.2  The incidence is currently approximately 5 per million persons-years and for unknown reasons over the past two decades it has increased in both immunocompetent and immunodeficient individuals. The most recent data suggests that there is a decrease in the incidence of PCNSL in young males but the incidence continues to increase in older individuals (>60 years).3

 

They are rarely reported as causing parkinsonism4, 5, 6 and in order to do so basal ganglia involvement must be bilateral.7  They are usually present with neurological deficits, cognitive and/or behavioural disturbances or headache.8  Patients with lymphomatous infiltration of the basal ganglia respond poorly to L-dopa as did our patient.

 

Advances in neuroimaging and laboratory analysis of cerebrospinal fluid (CSF) have facilitated diagnosis of PCNSL.9  Characteristic albeit non-diagnostic neuroimaging features are contrast-enhancing lesions with a diameter of at least 15mm in contact with the subarachnoid space and without necrosis.10  Biopsy of these lesions is usually how the definitive diagnosis is made.

 

These features were not seen on this patient’s MRI scan and the earlier cerebellar infarction noted on the scan was confirmed at postmortem to be due to infarction and not lymphoma infiltration.

 

Cytological examination of CSF can also detect lymphoma cells. However, none were detected in our patients CSF.

 

Had an antemortem diagnosis been made treatment options would have included chemotherapy – usually methotrexate and/or radiotherapy. These tumours are very steroid responsive but steroid induced remission is usually short-lived. Opinion is divided as to what is the best regime but in all cases the outlook is poor with an untreated median survival of only 4.6 months. There also are problems after treatment with delay neurotoxicity especially in older patients.11

 

However, the prognosis of this brain tumour has improved more than other brain tumours over the last decade, with a three-fold increase in survival, because of better treatment strategies.12

 

The clinical diagnosis of IPD is only confirmed in approximately 75% of patients at autopsy. This is largely because of some of the cardinal features of akinesia, rigidity and resting tremor can occur in conditions other than Parkinson’s Disease.13

 

The diagnosis of IPD is made by initially identifying parkinsonism features and then excluding alternative diagnoses.14  Our case had parkinsonism but had features suggesting an alternative diagnosis to IPD.

 

This patient’s post mortem examination did not show the pathology of IPD-striatal degeneration with Lewy bodies. The parkinsonism was due to the involvement of the substantia nigra and striatum itself by the infiltrate of lymphoma cells.

 

Key Points

1.      Identify a parkinsonism syndrome – akinesia, rigidity, tremor

2.      Exclude other possible diagnoses

 

Signs in our patient suggest an alternative diagnosis to IPD were early falls/instability, poor response to L-dopa, rapid progression, dementia.

 

References

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6.      Sanchez-Guerra M, Cerezal L, Leno C et al. Primary brain lymphoma presenting as Parkinson’s disease. Neuroradiology. 2001; 43: 36-40.

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10. Buhring U, Herrlinger U, Krings T et al. MRI features of primary central nervous system lymphomas at presentation. Neurology. 14-8-2001; 57: 393-396.

11. Campbell PG, Jawahar A, Fowler MR, Delaune A, Nanda A. Primary central nervous system lymphoma of the brain stem responding favourably to radiosurgery: a case report and literature review. Surg Neurol. 2005; 64: 400-405.

12. DeAngelis LM, Yahalom J, Thaler HT, Kher U. Combined modality therapy for primary CNS lymphoma. J Clin Oncol. 1992; 10: 635-643.

13. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999; 56: 33-39.

      14. Quinn N. Pakinsonism – recognition and differential diagnosis. BMJ. 18-2-1995; 310: 447-452.

 

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