Supplementary material
Case Reports
Case 1
A 68 year old man presented with a 2 month history of progressive memory decline and personality change. He had a prior history of polymyalgia rheumatica, and had been treated with oral prednisolone until just prior to the onset of his symptoms. In the month prior to admission, he developed word finding difficulties, temporal and visuospatial disorientation, and poor executive functioning. He had begun to use the colour of the carpet as a method of guiding himself around the house. He had become emotionally labile, with uncharacteristic aggression and irritability, and was also hyperphagic. On initial examination, he had an ataxic gait, with upper limb intention tremor His mini mental state examination was 17/30, with multi-domain deficits. Preliminary investigations revealed no significant abnormalities on brain CT and cerebrospinal fluid (CSF) analysis was acellular, with normal biochemistry. Resting EEG revealed asymmetrical slowing with intermittent periodic discharges. MR brain imaging (Figure 1) showed abnormalities on diffusion weighted imaging typical of sCJD.
By two weeks after admission, he became mute, and developed myoclonus. At this time further CSF analysis showed a positive 14-3-3 immunoassay and a raised S100b level of 1.44. However, NMDAR antibody levels were also persistently positive, at dilutions of 1:80. Although the most likely diagnosis was judged to be sCJD, he was given a 3 day course of high dose intravenous methyl prednisolone, but his clinical state continued to deteriorate and he died nine days later.
Post-mortem results revealed classical changes of sCJD with spongiform change in the cortex, especially over the occipital cortex, basal ganglia and cerebellum. Immunohistochemistry for PrP showed a widespread positive reaction in a similar brain distribution. The patient was homozygous for methionine at codon 129 of the PRNP gene.
Case 2
A 67 year old previously healthy man presented with an 8 month history of behavioral change, cognitive impairment, tremor and ataxia. His family first noticed a problem when the patient became increasingly withdrawn. This was followed by paranoia and irritability, resulting in the relationship with his partner breaking down. Around this time, he started to develop problems with mobility. He was unsteady and had difficulty with stairs due to leg weakness. This was attributed to an L5/S1 stenosis and he was booked for surgery.
By five months the patient required a stick to mobilize due to unsteadiness. He developed a tremor and became increasingly drowsy. His memory worsened, and he forgot appointments and dates. This was followed by formed visual hallucinations and delusional beliefs. In the six weeks preceding admission, he developed myoclonus predominantly affecting the upper limbs.
By admission, at six months, his examination showed dysmetric extraocular movements with frequent saccadic intrusions. He had bilateral dysdiadochokinesia and intention tremor in the upper limbs with occasional spontaneous myoclonus. His gait was broad based and ataxic. His speech was mildly dysarthric. His ACE-R score was 71/100 with deficits in memory and verbal fluency. He was investigated with an MRI brain which showed bilateral caudate, putamen and thalamic high signal in a pattern suggestive of sCJD (Figure 2). His EEG showed non-specific background slowing, and analysis of cerebrospinal fluid (CSF) showed it was acellular with a positive 14-3-3 immunoassay and an elevated S100b level at 1.29.
He developed a colonic pseudo-obstruction, which was managed conservatively. He continued to deteriorate and was transferred to a palliative care hospice and died 6 months later. Some months after discharge to palliative care, his NMDAR antibody came back as positive (titre 1:80),). The results only became available at the terminal stage of his illness and so no treatments were initiated.
Post mortem revealed widespread spongiform change with accompanying neuronal loss and gliosis. Occasional Kuru-type plaques were seen in the cerebellum. He was confirmed to have sCJD of MV2 subtype. There was accompanying mild Alzheimer pathology and moderate to severe arteriosclerosis.
Figure 1.
Figure 2
Legend:
Figure 1: Axial b1000 diffusion trace image shows abnormal high signal (diffusion restriction) in the right caudate nucleus, both frontal lobes, the right parietal and occipital lobes and both cingulate gyri.
Figure 2: Axial b1000 diffusion trace image shows abnormal high signal in caudate and putamen bilaterally.