FLAIR MRI in sporadic Creutzfeldt–Jakob disease

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive and ultimately lethal dementing illness caused by an infectious protein named prion. Besides cognitive decline and psychiatric or behavioral abnormalities, various other neurologic deficits appear. Myoclonic jerking, in particular startle myoclonus, is seen most commonly. The lack of a characteristic clinical course (especially during the initial stages) makes the diagnosis difficult, but the potential transmissibility necessitates early recognition of the disease (for additional information, please access our Web site at www.neurology.org and click on the title link for this article).1 MRI abnormalities of the brain can aid in establishing the diagnosis (for additional information, please access our Web site at www.neurology.org and click on the title link for this article).2,3 We describe a patient with sporadic CJD in whom MRI of the brain revealed signal intensity changes of the cerebral cortex that were best demonstrated on fluid attenuated inversion recovery (FLAIR) images.

A 54-year-old woman was admitted to the hospital in August 1998 with a history of depressed mood and a gradual deterioration of cognitive functions since December 1997. She had increasing forgetfulness and concentration problems and experienced difficulty performing routine activities. Cognition had slowed and declined noticeably. Expressing herself verbally as well as understanding what was being said had become arduous. She noted progressive clumsiness of the hands and exaggerated startle responses. She would sometimes cry or laugh inappropriately, and occasionally she perceived acoustic pseudohallucinations.

Neurologic examination showed bradyphrenia, apraxia, and a mixed aphasia. There was a homonymous left inferior quadrantanopia. She was unaware of her restless, fumbling hand movements. Except for slight ataxia and dysmetria of the arms with diminished left-hand dexterity, motor and sensory functions lively and symmetric with a positive pout reflex, a brisk masseter jerk, and flexor plantar responses. On the Mini-Mental State Examination (MMSE) she scored 18 of 30 points, indicative of a dementing disorder.

Routine blood, urinary, and CSF investigations for infectious, metabolic, toxic, or inflammatory causes were negative.

On FLAIR MRI, extensive hyperintense areas in the cortical gray matter of the cerebral hemispheres were seen (figure, left column). Spin-echo T2-weighted MRI (see figure, right column) revealed cerebral cortical changes that could have been considered normal without knowledge of the hyperintensities on the FLAIR MR images. There was no increased signal intensity of the basal ganglia and thalami.

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Figure. 1 Fluid attenuated inversion recovery (FLAIR) axial MR images (left column: repetition time [TR], 7,282 msec; echo time [TE], 120 msec; inversion time, 2,000 msec; turbo factor, 13) and T2-weighted spin-echo axial MR images (right column: TR, 2,612 msec; TE, 100 msec) of the brain. Extensive hyperintense areas in the cerebral cortex are clearly visible on FLAIR MRI. On T2-weighted spin-echo MRI, changes are seen that could have been considered normal without knowledge of the findings on the FLAIR images. The bilateral basal ganglia and thalami show a normal signal intensity.

An EEG showed a slow background rhythm. There were no discharges of epileptiform activity or periodic sharp-wave complexes.

CSF examination for the 14-3-3 protein was positive. Gene mutation analysis at codon 129 showed homozygosity for methionine.

A brain biopsy revealed spongiform changes in the brain cortex with gliosis and neuronal loss. The diagnosis of sporadic Creutzfeldt–Jakob disease was made.

Within the first 2 months of her stay in our clinic her neurologic condition deteriorated, and on a repeated MMSE she scored 2 of 30 points. Six months after admission she was transferred to a nursing home. She progressively developed uninhibited behavior, cortical blindness, myoclonic jerks, and later a spastic tetraparesis. All ability to communicate was lost and she died 6 months later .

Finkenstaedt et al.2 described the abnormalities of the brain on MRI in the largest series of sporadic CJD patients, and also summarized concisely the findings in previous case reports on this subject. Urbach et al.3 reported four of their own patients and gave an overview of the literature that consists mainly of small case series and case reports. From these studies it can be inferred that MRI in CJD typically shows pathologic signal intensities confined to the basal ganglia and thalami, but is sometimes normal. The abnormal signal changes are generally best visible by conventional spin-echo MRI techniques, such as proton density (PD)- and T2-weighted imaging. The signal changes in the deep gray matter are only occasionally accompanied by hyperintensity of the brain cortex on spin-echo MRI (PD- or T2-weighted imaging) (for additional information, please access our Web site at www.neurology.org and click on the title link for this article).2,3 Focal, abnormal signal hyperintensities of the brain cortex without changes in the basal ganglia or thalami on T2-weighted spin-echo MR images have been reported in only a few patients, and may reflect the (early) stage of the disease or perhaps phenotypic or genotypic CJD variants (for additional information, please access our Web site at www.neurology.org and click on the title link for this article).2-5 However, new variant CJD cannot be differentiated from sporadic CJD by means of MRI.6

FLAIR MRI may show a pathologic signal intensity of the cerebral cortex more clearly in addition to abnormalities on T2-weighted spin-echo MRI.5 The findings in our patient illustrate that when conventional MRI techniques show no or minor abnormalities in cases of suspected Creutzfeldt–Jakob disease, FLAIR MRI should be applied preferentially in view of its high sensitivity for the detection of cortical hyperintensities. If PD- and T2-weighted spin-echo MRI and even FLAIR MR images of the brain are normal, diffusion-weighted MRI, PET, and SPECT have proved to be able to detect cortical changes (for additional information, please access our Web site at www.neurology.org and click on the title link for this article).7 The use of these techniques may therefore also be helpful diagnostically. However, FLAIR MRI is usually more readily available than diffusion-weighted MRI, PET, or SPECT, which favors its use as an initial diagnostic imaging tool.

• Received November 12, 1999.
• Accepted in final form March 17, 2000.