Applied Radiology

Diagnosis

Creutzfeldt-Jakob disease (CJD)

Findings

Magnetic resonance imaging (MRI) of the brain showed gyriform increased signal intensity in the left parietal and occipital lobes, which was seen best on the diffusion-weighted images (DWI) (Figures 1A and B). On a fluid-attenuated inversion-recovery (FLAIR) sequence, these findings were present but were more subtle (Figure 1C). Subsequent laboratory studies were positive for PRP 14-3-3 in the cerebrospinal fluid (CSF).

Discussion

Creutzfeldt-Jakob disease is a subacutely progressive neurological disorder caused by the deposition of prion proteins in the brain. The majority of cases are sporadic, but some cases are familial carrying a prion protein mutation. Variant CJD in humans caused by the transmission of bovine spongiform encephalopathy has caused renewed interest in the disease.¹

Diagnosing CJD may be difficult because of the nonspecific nature and wide range of clinical symptoms. Typical features include rapidly progressive dementia, generalized myoclus, and ataxia. Characteristic electroencephalogram (EEG) findings, known as periodic sharp wave complexes (PSWCs), are seen in only 60% of cases. In the past, diagnosis could be made only on histopathologic analysis following autopsy. Recently, a CSF protein known as 14-3-3 has been shown to be highly sensitive and specific (96% for both) for the diagnosis of CJD in the appropriate clinical setting.¹

Radiology has historically played a limited role in the diagnosis of CJD. Computed tomography is usually normal, but may show atrophic changes that progress rapidly over time. MRI may show increased T2 signal in the basal ganglia, thalamus, occipital cortex, or white matter.² The sensitivity of increased T2 signal in the basal ganglia has been reported to be only 79%.³

Newer MRI sequences have been shown to be useful in diagnosing early lesions in CJD. Diffusion-weighted MRI abnormalities have been shown to be more sensitive than T2-weighted or FLAIR sequences in detecting lesions in patients who were clinically either definite or probable for the diagnosis of CJD based on the World Health Organization criteria. A recent study showed DWI abnormalities in 24 of 26 (92.3%) patients with a subacute clinical presentation, with 100% interobserver agreement between 2 experienced neuroradiologists. These DWI abnormalities included lesions in the cerebral cortex and basal ganglia (45.8%), linear lesions in the cerebral cortex only (41.7%), and lesions only in the caudate heads and putamen (12.5%).³

The specificity of DWI lesions in this study was 92.3% and the sensitivity was 93.8%. The sensitivity of DWI was significantly higher than either FLAIR or T2 sequences. As an added benefit, DWI is more tolerant of motion artifacts than other sequences. This is an advantage since these patients may suffer from myoclonic jerking. The sensitivity of DWI was also greater than either CSF protein 14-3-3 or EEG. Although in the case of CSF protein 14-3-3, this difference was not statistically significant (P = 0.36). These DWI findings could be seen as early as 3 weeks after initial symptom onset.³

Diffusion-weighted imaging is very useful in distinguishing CJD from the differential diagnoses of CJD, including Alzheimer's disease, vascular dementia, and dementia with Lewy bodies. Other causes of similar DWI abnormalities include infectious meningoencephalitis, mitochondrial encephalopathy, lactic acidosis, Wilson's disease, and Wernicke's encephalopathy. These can usually be distinguished from CJD based on clinical and CSF findings. The underlying pathology of these DWI lesions is unknown but may represent spongiform changes or prion protein deposits. These lesions often become less apparent with disease progression.³

CONCLUSION

Radiology now plays a significant role in the diagnosis of CJD. Diffusion-weighted MRI findings allow the radiologist to suggest the diagnosis of CJD early in the course of the disease in the appropriate clinical setting, permitting appropriate treatments to be instituted.

1. Castellani RJ, Colucci M, Xie Z, et al. Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease.Neurology. 2004;63:436-442. Comment in:Neurology. 2004;63:410-411.
2. Grossman RI, Youssem DM, eds. Neuroradiology:The Requisites. 2nd ed. St. Louis, MO: Mosby; 2003:383-384.
3. Meissner B, Kohler K, Kortner K, et al. Sporadic Creutzfeldt-Jakob disease: Magnetic resonance imaging and clinical findings. Neurology. 2004;63:450-456.