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We describe a patient presenting with the clinical phenotype of sporadic CJD and very extensive brain abnormalities on MRI. The final diagnosis was gliomatosis cerebri (GC) and was only proven after a second cerebral biopsy.
A 55 year old female accounts clerk presented in March 2004 with a history of approximately 6 weeks of memory disturbance. She had trouble recalling her children’s birthdays and recent conversations, and performing familiar tasks at work. Her husband also noted some change to her personality, in that she was more gregarious and less cautious than usual. This was in addition to a background of several months’ sleepiness where she would sleep soundly overnight and also require a sleep regularly during the day. There had been no alteration to her weight or appetite during this time. Just prior to initial review she experienced two unexplained episodes of urinary incontinence. Headache was never a feature.
Her medical history was only remarkable for hypothyroidism, treated with thyroxine replacement, and there was no relevant family history.
Physical examination revealed extrapyramidal features with hypomimia and a monotonous hypophonic voice. Her gait demonstrated mild bilateral (asymmetric) reduction in arm swing. Ocular movements were normal. She displayed mild bilateral bradykinesia, but there was no axial or limb rigidity or tremor. Power, co-ordination, reflex examination including plantar responses, and sensation were all normal. She was distractible, had difficulty sequencing tasks, and demonstrated concrete interpretation of common proverbs. In addition, stimulus sensitive myoclonic jerks of both upper limbs were noted. There was no pathological startle response. Her Folstein mini-mental state examination score was 26/30 with one error in orientation and calculation and two errors in recall. However, the frontal assessment battery score was markedly impaired with a score of 8/18. A formal neuropsychological assessment was undertaken confirming severe memory impairment (immediate and delayed story recall scores in the 2nd centile), attention difficulties (digit span memory score in the 9th centile), and evidence of frontal lobe dysfunction (semantic and phonemic fluency scores in the 1st centile). General physical examination was normal, in particular there was no lymphadenopathy or organomegaly, and breast examination was normal.
Baseline biochemistry, haematology, and inflammatory markers were normal. Voltage gated potassium channel antibodies and anti-neuronal (Yo, Hu, Ri) antibodies were not detected. Copper studies and blood lactate were normal. Chest x ray was normal. An EEG demonstrated an excess of intermittent delta activity over both hemispheres, but with a retained normal background post-central alpha rhythm at 9–10 Hz. Neither epileptiform features nor periodic complexes were identified.
Brain MRI demonstrated striking, relatively symmetrical abnormalities affecting predominantly grey matter structures (fig 1). The most prominent feature was symmetrical bilateral basal ganglionic and thalamic enlargement with signal alteration (fig 1, arrows). These structures demonstrated increased signal on T2 weighted images and decreased signal on T1 weighted images with no enhancement following intravenous gadolinium administration. Remarkable sparing of the adjacent white matter tracts, for example, the internal capsules and anterior commissure, was seen. The hippocampi were also affected with the right being more dramatically enlarged. The only infratentorial involvement was in the tectum of the midbrain and a small area of the dorsal medulla oblongata. In view of the extensive imaging abnormalities with focal swelling supratentorially, it was felt that a cerebral biopsy was the most useful investigation to help obtain a formal diagnosis despite the need to quarantine the surgical instruments afterwards. CSF examination, including an assay for the 14-3-3 protein, was considered but not undertaken in view of concerns with the focal areas of swelling.
In view of the clinical presentation coupled with the imaging abnormalities (although extensive), sporadic CJD was considered. A limited right temporal biopsy was undertaken to assess for the presence of prion related and other pathologies. Tissue was examined locally and sent to the regional CJD surveillance unit. No evidence of prion disease was found on histopathologic or western immunoblot examination. Unfortunately, the rest of the tissue did not provide a specific pathological diagnosis on this limited biopsy.
The patient’s state fluctuated considerably, but overall a progression was evident with deepening difficulty in memory and planning. Complex partial seizures consisting of speech, behavioural arrest, and automatism were witnessed. These attacks were controlled well initially with sodium valproate. Due to the continued deterioration, a craniotomy and right temporal lobe excision biopsy were undertaken. The biopsy appearances were consistent with a diffusely infiltrating intrinsic neoplasm composed of glial cells (astroctyes). The pattern of involvement was that of a diffusely infiltrating glioma most consistent with WHO grade II. Together with the MRI evidence of involvement of more than two cerebral lobes, this was diagnostic of GC.
The patient was discharged following the second biopsy procedure without complication. At this time, although remaining ambulant, she required significant prompting and help from her husband in tasks of daily living. However, within several weeks her seizures became difficult to control and she became increasingly somnolent. Radiotherapy planning had commenced but after a prolonged seizure she recovered poorly and was admitted to the local hospice where she regained awareness only briefly before her death in early August, 7 months after symptom onset.
GC is an uncommon, diffusely infiltrating primary cerebral neoplasm and is a diagnosis often made after death. The clinical manifestations may mimic many neurological disorders but parkinsonism is not a common feature. In fact, we could only find one other report in recent literature of parkinsonism as the clinical presentation.1 In this case the diagnosis was only made after death and there were no significant brain MRI abnormalities.
The complex of subacute neuropsychiatric disturbance coupled with parkinsonism and myoclonus is a recognised presentation of sporadic CJD.2 T2 weighted basal ganglionic signal change is also a feature seen in sporadic CJD although in a recent review this only approached a sensitivity of 63%.3 Over 20 alternative diseases were described to have these imaging findings, although GC was not included in this list. Our case highlights the fact that GC can present in a manner mimicking sporadic CJD and should be considered in this context.
Competing interests: none declared
Patient details are published with consent
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