Creutzfeldt-Jakob Disease

Clinical History

A 58 year old previously healthy male patient was referred by the General Practitioner (Family Doctor) to Medical Assessment Unit. His symptoms started as non-specific dizziness and then rapidly progressed over next 3 months. He developed impairment of memory and cognition, cerebellar ataxia, expressive dysphasia and myoclonus.

Imaging Findings

A 58 year old previously healthy male patient was referred by the General Practitioner (Family Doctor) to Medical Assessment Unit. His symptoms started as non-specific dizziness and then rapidly progressed over next 3 months. He later developed impairment of memory and cognition, cerebellar ataxia and expressive dysphasia. His disease progressed relentlessly and on examination was found to have a total loss of speech and voluntary movements with a multifocal stimulus sensitive myoclonus. He had a marked startle response to light and a gegenhalten increase in tone in both his upper limbs. Grasp reflex was present bilaterally. In terms of investigations, EEG revealed periodic complexes. CSF analysis for brain-specific proteins showed CSF S-100b – 1.54 (ref. range <0.38 ng/ml) and CSF 14-3-3 positive. CT head was normal. MRI study of the cranium was performed with a 1.5 T MRI scanner with T1 SE, T2 SE, Proton Density and FLAIR sequences.

Discussion

The MR pictures showed increased signal in the cerebral cortex, putamen and the head of the caudate nucleus on both sides best shown on the T2 weighted and axial FLAIR sequences. There was also increased signal in the peri-aqueductal brain matter. Creutzfeldt-Jakob disease (CJD) is a human prion disease. There are four types: 1) Sporadic CJD; 2) Variant CJD; 3) Genetic CJD; 4) Iatrogenic CJD. The neuropathology of CJD is characterized by 4 main features: - spongiform change, neuronal loss, astrocytosis and amyloid plaque formation. In Sporadic CJD the mean age of onset is 60 years and mean disease duration is 5 months. It is characterized by various early non-specific symptoms like headache, tiredness, sleep or appetite disturbance and depression. There is global brain involvement and cerebellar ataxia, cognitive and memory impairment are common early features. CT scan is usually normal and MRI features include: - Cerebral atrophy, abnormalities (distinct hyperintensities) of signal in anterior basal ganglia, specifically the caudate nuclei and the putamen and in the cortex (cortical ribboning). These changes have been seen with several MRI sequences, including T2 - weighted images, proton density - weighted images, FLAIR images and Diffusion Weighted Imaging (DWI). DWI is the most sensitive MR imaging technique in the diagnosis of CJD (sensitivity ~80%). DWI may also help is early diagnosis and monitoring progression of the disease. EEG (showing periodic complexes) and CSF analysis aid in diagnosis. Variant CJD has a causal association with Bovine Spongiform Encephalopathy (BSE). In contrast to sCJD, in vCJD the mean age of onset is 29 years and mean disease duration is 14 months. vCJD tends to present with behavioral or psychiatric symptoms and with a relatively slower progression. Cerebellar signs are prominent early on. Upgaze paresis, chorea, dystonia and myoclonus often develop. MRI shows a characteristic abnormality in the posterior thalamic region which is highly sensitive and specific for variant CJD. The ‘Pulvinar Sign’ is bilateral symmetrical high signal on the pulvinar nuclei of the thalamus best seen in transverse FLAIR sequences. In addition a 'hockey stick sign' is seen in 75% cases where there is hyperintensity in the dorsomedial nuclei of the thalamus. The pulvinar sign has been found in >90% of pathologically proven vCJD cases. In vCJD as well DWI is more sensitive than conventional MR imaging. Tonsil biopsy (vCJD tends to involve lymphoreticular system) and CSF analysis aid in diagnosis. An absolutely definitive diagnosis of any form of CJD requires neuropathological examination of the brain tissue. All forms of CJD are progressive and ultimately fatal. Currently, there are no treatments that have been shown to slow or halt progression or to reverse the disease.

Differential Diagnosis List

Final Diagnosis

Sporadic Creutzfeldt-Jakob Disease

URL:	https://eurorad.org/case/4872
DOI:	10.1594/EURORAD/CASE.4872
ISSN:	1563-4086