Diffusion-weighted imaging and fluid-attenuated inversion recovery sequence in sporadic Creutzfeldt-Jakob disease One-case report＊☆●

Neurobioimaging Laboratory, IRCCS Centro Neurolesi “Bonino Pulejo”, Messina, Italy

lNTRODUCTlON

Sporadic Creutzfeldt-Jakob disease (sCJD)is a rare transmissible disease characterized by accumulation of pathologic prion protein (PrPSc) in the central nervous system.The polymorphism at codon 129 of the prion protein gene and the PrPSc types 1 and 2 are the basis for a molecular classification of sCJD[1].The most common sCJD subtype (68% of sCJD cases) is characterized by dementia, ataxia and myoclonus.The diagnosis of sCJD is extremely difficult,but magnetic resonance (MR) examination has been found to be especially helpful in identifying sCJD subtype patients.The MR examination plays an important role in the diagnosis of sCJD since basal ganglia (BG)hyperintensities on T2-weighted images have been described as a characteristic finding.With the emergence of more sensitive techniques such as fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted image (DWI), cortical signal increase has also been detected[2], with a sensitivity of 63% for BG hyperintensities on T2-weighted MRI, and a sensitivity of up to 92% in a study including FLAIR and DWI[3].DWI has been shown to be the most sensitive technique for the detection of signal alterations in sCJD patients, especially for cortical hyperintensities.On FLAIR and DWI, signal increase in the cortex has been reported even more frequently than in the BG[4].

In this study, we reported a patient with sCJD in the early stage, who was diagnosed by MR examination before the clinical manifestations.

CASE REPORT

We reported a case of a 45-year-old,right-handed female patient with a probable sCJD.Her familiar medical history was negative for neurodegenerative and other nervous system diseases.

The pathological history began in March 2005 when she observed episodes of dizziness especially during postural changes.At this time, she was diagnosed having the symptom of Mèniére’s disease.In the following month, the symptom persisted, and dizziness become progressively more frequent.A postural instability appeared and the patient received an electroencephalographic and a MR evaluation.Informed consent was obtained from the patient.The electroencephalographic examination was normal (data not shown), but the MR examination on system operating at 1.5 T (Sonata Siemens, Erlangen, Germany) showed BG and thalamic hyperintensities on FLAIR and DWI sequences bilaterally(Figure 1).

Figure 1 Conventional and diffusion-weighted images of a 45-year-old right-handed female patient with a probable sporadic Creutzfeldt-Jakob disease in March 2005.(A)Fluid-attenuated inversion recovery-weighted and (B)diffusion-weighted magnetic resonance images show precocious findings as the combination of basal ganglia,cortical and thalamic hyperintensities in the basal magnetic resonance examination.

She was clinically stable for 1 year.In April 2006, the patient had a very rapid neurological function decline,assessed by clinical neurological examination, with appearance of balance dysfunction, gait abnormality,sphincteric incontinence, aphasia, and cognitive impairment.After hospitalization, the patient underwent another MR examination, genetic analysis for prion protein gene mutation and cerebrospinal fluid examinations.

MR showed a catastrophic picture, with hyperintensity of periventricular white matter and BG.MR also highlighted an obvious thinning of cortex and diffuse white matter, which was associated with an increased volume of the tentorial and subtentorial ventricular system and subarachnoid space bilaterally, showing an obvious cerebral atrophy (Figure 2).

The cerebrospinal fluid examination revealed an increased level of 14.3.3 protein.Genetic analysis showed no prion protein gene mutations.In the same year, the patient had an obvious worsening of cognitive and motor impairment exhibiting progressive dementia,tetraparesis with bending spasticity of the inferior limb,spontaneous myoclonous, speech ability loss and unable eating.

In the same year, she underwent percutaneous endoscopic gastrostomy and was put on a bladder catheter.In 2008 (less than 3 years of disease beginning),the patient died.

Figure 2 Conventional magnetic resonance images of a 45-year-old right-handed female patient with a probable sporadic Creutzfeldt-Jakob disease in April 2006.(A, B)Fluid-attenuated inversion recovery-weighted magnetic resonance images show the catastrophic evolution as the combination of cerebral atrophy as well as white matter,cortical and thalamic hyperintensities in the second magnetic resonance examination.

DlSCUSSlON

The diagnosis of sCJD is difficult using established diagnostic criteria, particularly in the early stage of disease.MR has been shown to be highly sensitive and specific for the diagnosis of sCJD with high interobserver agreement.A combined DWI/FLAIR analysis was performed in a previous study[4].It is not entirely clear whether DWI and FLAIR were available in each patient, and the frequency of hyperintensity was given for combined FLAIR/DWI investigations.The aim of this study was to analyze the diagnostic value of FLAIR and DWI in the early stage of disease and to correlate the clinical evaluation to MR examination during the disease course.

Basal ganglia and thalamic hyperintensities were identified with increasing frequency during the disease course, although this was not apparent for cortical changes.The occurrence of thalamic and BG hyperintensities showed no significant correlation with disease duration or time at which the MR was performed, although this finding may have been influenced by the time of diagnosis and time of MR investigation.In addition, the high frequency of thalamic hyperintensity in the MV2 subtype of sCJD allowed differentiation from MM1 patients[5].As in a previous study, the increased sensitivity on second MR suggests that repeated MR investigations during the disease course may be helpful in the diagnosis of sCJD.

The reason for cortical signal intensity changes in sCJD is not fully understood.Several studies have shown that the intensity of MR changes correlates with the neuropathologic findings (spongiosis, neuronal loss, and astrogliosis)[6-7].In areas that are bright on MR imaging in FLAIR or DWI images, neuropathologic changes are more severe than in areas with normal cortical signal intensity.The hypothesis that MR signal intensity changes reflect pathological conditions is additionally supported by clinical and radiological comparison studies showing that cortical signal intensity changes correlate with clinical signs(e.g., affection of the occipital cortex and visual disturbances or unilateral cortical affection and contralateral motor signs)[8].

The case we reported showed two particular findings: (1)an abnormal MR examination, in a very early stage of the disease,i.e., when the clinical typical manifestations of the disease were not present; (2) a rapid and catastrophic clinical progression associated with a rapid catastrophic MR evolution.

Taken together, our results seem to confirm that in patients with cortical and basal ganglia hyperintensities on MR imaging, the disease course was rapid; a correlation between widespread cortical hyperintensity on FLAIR and disease duration was found in the patient included in this study, even if it is limited to only a case.These findings suggest that DWI and FLAIR are helpful in identifying sCJD patients from the early stage of disease attack.design, performance and data analysis.

Conflicts of interest:None declared.

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