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Brain biopsy and patients with atypical presentations of sporadic Creutzfeldt- Jakob disease
  1. IAN R WHITTLE,
  2. ROBERT G WILL,
  3. JAMES W IRONSIDE
  1. Department of Clinical Neurosciences, and Neuropathology Laboratory, Western General Hospital, Edinburgh, EH4 2XU, UK
  1. Mr I R Whittle, Department of Clinical Neurosciences, and Neuropathology Laboratory, Western General Hospital, Edinburgh, EH4 2XU, UK.

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Brain biopsy, or meningeal biopsy, or both are performed to exclude treatable neuropathological disorders in a range of cases in which clinical, neuroradiological, and other investigative findings fail to define a diagnosis. The description of a new clinicopathological variant of Creutzfeldt-Jakob disease shows that some cases of this rare disease may present atypically and the diagnosis in life may depend on brain biopsy.1 Although the Department of Health guidelines on neurosurgical and ophthalmic operative procedures minimise any risk of subsequent iatrogenic transmission 6% of cases of Creutzfeldt-Jakob disease present with a stroke-like disorder with equivocal clinical, electrophysiological, or neuroradiological support for the diagnosis.2 There is, therefore, the potential danger of iatrogenic transmission of Creutzfeldt-Jakob disease after inadvertent brain biopsy of such patients. The Department of Clinical Neurosciences in Edinburgh therefore, created a dedicated set of neurosurgical instruments designated purely for open brain biopsy. These instruments were repacked and sterilised after each biopsy. This precaution was vindicated by the following case.

A 65 year old man presented with a history of headache for some months followed by the acute onset of expressive dysphasia and right hemiparesis. There was subsequently some progression in the weakness and he was admitted to hospital for investigation. There was a history of previous stroke in June 1989 presenting with expressive dysphasia and hemiplegia which recovered completely over two months. The patient was a regular smoker and had previously had an operation for excision of an arterial embolus. Clinical examination disclosed severe expressive dysphasia although his eyes opened appropriately to speech and the patient flexed his limbs. There was a spastic right hemiparesis with bilateral extensor planter responses. Brain CT showed irregular low density in the right cerebellum and low density in the left frontoparietal region. After admission, the patient developed frequent partial seizures and myoclonus and in view of the diagnostic doubt, an open brain biopsy was carried out on 29 April 1992. Pathological examination of this tissue (1 cm3) revealed infarcted and ischaemic cortical and subcortical tissues with no evidence of vasculopathy or vasculitis. No spongiform change was present in the biopsy and no amyloid plaques were present. Immunocytochemistry for prion protein was negative.3 The patient continued to deteriorate postoperatively and died eight weeks later at another hospital. Necropsy was performed and histological examination of the brain led to the diagnosis of Creutzfeldt-Jakob disease. There were spongiform changes evident in a wide distribution throughout the cerebral cortex and prion protein desposition shown by immunocytochemistry in a compositive synaptic and perivascular pattern. In addition, numerous infarcts were noted throughout the brain, particularly in the right occipital lobe, the right temporal lobe, and the thalamus. The brain biopsy tray which had been repacked and resterilised had deliberately not been used on another patient and the instruments were subsequently destroyed.

This case highlights three major points. Firstly, some cases of Creutzfeldt-Jakob disease will present in an atypical fashion. In these patients, because Creutzfeldt-Jakob disease is not high on the differential diagnosis, brain biopsy may be required to exclude treatable causes of progressive dementia. Secondly, brain biopsy in Creutzfeldt-Jakob disease may fail to confirm the diagnosis because the pathological lesions of Creutzfeldt-Jakob disease may be unevenly distributed within the brain and not detectable in small biopsy specimens using standardised neuropathological diagnostic criteria.4 Thirdly, for all patients undergoing brain biopsy, we think that a dedicated set of instruments is appropriate as there may be a delay between performing the operation and obtaining a definitive diagnosis as occurred in this case. Such a precaution minimises the risk of inadvertent iatrogenic transmission. Hopefully, in the not too distant future, advances in “premortem”, non-surgical diagnosis of Creutzfeldt-Jakob disease,5 will render brain biopsy redundant.

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