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NEURORADIOLOGY Table of Contents   
Year : 2006  |  Volume : 16  |  Issue : 4  |  Page : 695-700
Creutzfeldt-Jakob disease, Spongiform encephalopathy, Prion disease, diffusion weighted MRI

Nirman Hitech Diagnostic center, Shri Ram Apartments, Goraswadi, Off S. V. Road, Malad-Kandivali (W), Mumbai- 400067, India

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Date of Submission30-Jun-2005
Date of Acceptance10-Aug-2006

Keywords: Creutzfeldt Jacob disease, Spongiform encephalopathy, prion, Diffusion MRI

How to cite this article:
Gupta A K, Shah J K. Creutzfeldt-Jakob disease, Spongiform encephalopathy, Prion disease, diffusion weighted MRI. Indian J Radiol Imaging 2006;16:695-700

How to cite this URL:
Gupta A K, Shah J K. Creutzfeldt-Jakob disease, Spongiform encephalopathy, Prion disease, diffusion weighted MRI. Indian J Radiol Imaging [serial online] 2006 [cited 2021 Mar 1];16:695-700. Available from:

   Introduction Top

 Creutzfeldt-Jakob disease More Details (CJD) is a rare and fatal neurodegenerative disease of unknown cause. Patients are usually between 50 and 75 years and typical clinical features include a rapidly progressive dementia, associated myoclonus & a characteristic EEG pattern. Diffusion weighted MRI increases the diagnostic accuracy in CJD & may show the most conspicuous abnormalities. Neuropathological examination reveals cortical spongiform change, hence the term "spongiform encephalopathy". Although CJD appears to occur as a predominantly sporadic disorder, it can also occur as a dominantly inherited or infective condition.

   Case Report Top

A 62-year lady complained of headache, nausea, bodyache, and generalized body weakness, more on the left side, since 15 days. She was a recent-onset hypertensive. She was on psychiatric treatment since last five years for endogenous depression and irritability with improvement on regular treatment.

On examination, her BP was 150/110 mm Hg. She had hypokinesia, bradykinesia, rigidity and a monotonous speech. She had gait imbalance and visual hallucinations. Her vision and mentation was normal. ECG showed ST depression V2-V6. Blood Sugar and Urine routine were normal. Unenhanced CT Brain was performed, which did not show any significant abnormality.

MRI Brain was performed in 1.0 Tesla Magnetom Harmony unit (Siemens, Erlangen, Germany). Routine unenhanced spin-echo T1W (TR/TE-660, 14), turbo spin-echo PD-T2W (3500/ 85,14) and turbo FLAIR (660/14) sequences were obtained in multiple planes. Single shot EPI Diffusion sequence was obtained in oblique axial plane in three directions with b value of 100, followed by isotropic image acquisition and ADC maps. Diffuse cortical hyperintense lesions were seen in the right cerebral hemisphere on T2W images, more marked in the parieto-occipital lobes. Similar less marked cortical hyperintense lesions were also seen in the left temporo-parietal regions. The lesions were hyperintense on Diffusion weighted images (DWI) and showed reduced apparent diffusion coefficients [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4]. Subtle cortical hyperintensities were seen on FLAIR images [Figure - 5],[Figure - 6]. The adjacent white matter was spared. The cortical sulci, fissures and cisterns were normal. The thalami, basal ganglia and brainstem were spared.

Few old ischemic lesions were seen in the left cerebellum and both corona radiata. Based on the above characteristic MRI features of bilateral asymmetric cortical T2-hyperintense lesions with restricted diffusion, possibility of Creutzfeldt-Jakob disease (CJD) was raised. Other imaging differential diagnoses included vasculitis and encephalopathy.

The patient subsequently developed myoclonic jerks, predominantly on the left side. She was unable to walk properly and had a wobbling gait. The speech became slurred and the hypokinesia and rigidity progressed. No significant memory impairment was observed. The patient gradually showed severe mental deterioration with loss of vision and was completely bedridden.

EEG showed background activity consisting of theta at five Hz mixed with high voltage generalized delta at three Hz and occasional sharp waves, suggestive of bicortical dysfunction (? encephalopathy). Routine CSF showed no cells or organisms, proteins were 15.8 mgs with 83 mgs sugar. The vasculitis work-up (ANA, p-ANCA, c-ANCA) was negative. The HIV Test was negative. Other routine blood tests did not show any significant abnormality.

Gadolinium-enhanced MRI Brain was performed again after 5 days. An MR Angiogram was also performed using three-dimensional time-of-flight (3D-TOF) imaging. There was progression of the bilateral cortical hyperintense lesions on the FLAIR images [Figure - 8],[Figure - 9] and DWI [Figure - 10],[Figure - 11]. Another hyperintense lesion was seen in the right putamen, not seen on the earlier scan. No abnormal parenchymal or meningeal enhancement was seen. The left posterior cerebral artery showed mild reduced flow signal; rest of the vessels appeared normal [Figure - 12],[Figure - 13]. The progression of the above lesions on the subsequent MRI with a new lesion in the right basal ganglia further substantiate the diagnosis of CJD alongwith the above characteristic rapid mental deterioration of the patient.

   Discussion Top

Creutzfeldt-Jakob disease (CJD) is the most common transmissible spongiform encephalopathy in humans, with a worldwide incidence of 0.5 to 1.0 cases per million per year [1]. The clinical diagnosis of CJD may be suggested in a middle-aged patient with progressive dementia, myoclonus and cerebellar signs. However, this triad overlaps other dementia disorders [2], or it may not be manifested as in the present case. The majority of cases are sporadic (85%), between 10-15% are familial and remainder are iatrogenic. The transmissible agent is hypothesized to be a proteinase-resistant protein (PrP) or prion.

Sporadic CJD disease is regarded as a spontaneous neurodegenerative illness, arising from either a spontaneous prion gene (PRNP) somatic mutation or a stochastic PrP structural change [3]. Genetic CJD is a very rare illness caused by an inherited abnormal gene. Iatrogenic CJD has resulted from neurosurgery, corneal grafting, human dura matter implants or exposure and use of human cadaveric growth hormone (hGH) & human pituitary gonadotrophin (hGNH). Variant CJD results from transmission of infection from bovine spongiform encephalopathy (BSE) in cattle to humans via infectivity in food.

CJD is predominantly a disease of later middle age with mean age of death in late sixties. Three broad categories of symptomatic disease is seen alone or in combination - mental or emotional deterioration, incoordination (especially of gait) and visual disturbance. They represent the earliest abnormality and their progressive severity over a matter of few weeks is almost always the cause for an initial medical contact. As the disease evolves, the metal and emotional deterioration progresses to global dementia; the incoordination advances to the point of inability to walk or sit or take care of oneself and the visual symptoms may progress to apparent blindness. Additional physical abnormalities also become evident, especially involuntary movements, most often in the form of muscle twitching (myoclonus). The progression culminates in a terminal akinetic mute state with myoclonus.

Historically, certain distinctive clinical patterns were recognized & given individual names such as:

1. Heidenhien's variant - dementia with prominent visual symptoms.

2. Brownell-Oppenheimer variant-dementia with prominent cerebellar symptoms.

3. Fatal insomnia - with prominent insomnia.

Three Laboratory Tests provide valuable assistance in difficult or uncertain cases (Tables 1, 2.)

1. EEG: - A periodic sharp wave pattern is seen in two-third of CJD cases. A 'burst wave suppression' pattern may also be seen.

2. CSF 14-3-3 Analysis: - Routine CSF examination is generally unremarkable. The CSF typically contains no inflammatory cells & the presence of a significant pleocytosis should lead to consideration of other diagnosis. The total protein content may be elevated. However, the analysis of CSF for certain brain specific proteins, particularly 14-3-3, may be very useful in diagnosis & is positive in over 90% of patients with CJD [4]. As with the EEG, it is not entirely specific and can be detected in other illnesses such as encephalitis, stroke, hypoxic brain damage and Alzheimer's disease.

3. MRI with Diffusion: - Cerebral imaging is a vital part of the exclusion of other diagnosis & normal brain imaging, in the face of a rapidly progressive devasting encephalopathy, may lead to a consideration of CJD. MRI may show diffuse areas of increased cortical signal bilaterally on T2W and FLAIR images [5]. The DWI demonstrates more accurately the hyperintense lesions [6],[7],[8]. Hyperintense lesions are also seen in the basal ganglia & thalami. The 'Pulvinar sign' - characteristic hyperintense signal in posterior thalamic regions bilaterally, is highly sensitive and specific for variant CJD. DWI is the sequence of choice for the diagnosis of CJD, particularly when other auxiliary tests are negative. DWI also might guide the stereotatic biopsy to an area of increased pathological activity to maximize its efficiency & safeness. Moreover, its short scanning time ensures few artifacts, especially in patients with myoclonus. Significant atrophy is unusual if imaging is undertaken within 3 months of disease onset.

CT scan is of no help in diagnosis, showing no abnormality or nonspecific atrophy. PET and SPECT show hypometabolism in the abnormal areas on the MRI [8]. An absolute definitive diagnosis of any form of CJD requires neuropathalogical examination of brain tissue at autopsy. Rarely a brain biopsy may be performed.

CJD is invariably fatal and there is currently no available treatment for the underlying disease process.

   References Top

1.Brown P. Transmissible spongiform encephalopathies. In Bradley WG, Daroff RB, Fenichel GM, et al (Eds). Neurology in clinical practice Boston: Butterworth-Heinemann, 2000: 1423-1430.  Back to cited text no. 1    
2.Haik S, Brandel JP, Sazdovitch V, et al. Dementia with Lewy bodies in a neuropathalogic series of suspected Creutzfeldt-Jakob disease. Neurology 2000; SS: 1401-1404.  Back to cited text no. 2    
3.R.G. Will, RSG Knight. Prion Diseases. Journal of Neurology, Neurosurgery & Psychiatry 2004; 75: 36.  Back to cited text no. 3    
4.Zerr I, Pocchiari M, Collins S, et al. Analysis of EEG & CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease. Neurology 2000; 55:811-815.  Back to cited text no. 4    
5.Vrancken AFJE, Frigns CJM, Ramos LMP. FLAIR MRI in sporadic Creutzfeldt-Jakob disease. Neurology 2000; 55:147-148.  Back to cited text no. 5    
6.Bahn MM, Parchi P. Abnormal diffusion weighted MRI in Creutzfeldt-Jakob disease. Arch Neurol 1999; 56:577-583.  Back to cited text no. 6    
7.Demaerel P., Heiner L., Robberecht W., et al. Diffusion weighted MRI in sporadic Creutzfeldt-Jakob disease Neurology 1999; 52:205-208.  Back to cited text no. 7    
8.Na DL, Such CK, Choi SH, et al. Diffusion weighted MRI in probable Creutzfeldt-Jakob disease. Arch Neurol 1999; 56:951-957.  Back to cited text no. 8    

Correspondence Address:
A K Gupta
1301, Suchi Heights, Suchidham, General A. K. Vaidya Marg, Malad(E), Mumbai-400097
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-3026.32302

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12], [Figure - 13]

  [Table - 1], [Table - 2]


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