Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 54, Num. 4, 2006, pp. 418-420

Neurology India, Vol. 54, No. 4, October-December, 2006, pp. 418-420

Case Report

Sporadic onset Creutzfeldt-Jacob disease: Interesting MRI observations

Praveen KS, Sinha S, Chandrasekhar HS, Vijayan J, Taly AB

Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore
Correspondence Address:Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore - 560 029, sanjib_sinha2004@yahoo.co.in

Code Number: ni06143

Abstract

We describe a 60-year-old woman with "probable" sporadic Creutzfeldt-Jacob disease (CJD) who manifested with two months history of rapidly progressive dementia and abnormal behavior, speech and gait abnormality, excessive sleepiness and myoclonic jerks. Scalp EEG showed diffuse slowing of background activity to delta range and triphasic sharp wave complexes occurring periodically twice in one-second interval. Magnetic resonance Imaging (MRI) of brain revealed high signal intensity on T2 weighted image (T2WI) and fluid attenuated inversion recovery sequences in the caudate and putamen bilaterally. Diffusion weighted images showed bilateral symmetric hyperintense signals in the caudate and putamen. The role of MRI in the diagnosis of CJD is discussed.

Keywords: Creutzfeldt-Jacob disease, creutzfeldt-jacob disease, magnetic resonance Imaging, rapidly progressive dementia

Introduction

Creutzfeldt-Jacob disease (CJD) is a rare prion disease of the nervous system characterized by dementia, myoclonus, ataxia and other inconstant neurological signs.[1] It can be sporadic as well as familial and is usually fatal within one year of onset of symptoms.[1] Its diagnosis often rests on EEG. However, some recent studies have reported signal abnormalities in the deeper gray matter nuclei of the brain, which are characteristically observed in the disease.[2],[3]

We report the characteristic magnetic resonance Imaging (MRI) observations of a patient with "probable" sporadic CJD and discuss their significance in the light of current knowledge.

Case Report

A 60-year-old lady manifested with two months history of rapidly progressive illness dominated by dementia in the form of abnormal behavior, irrelevant talk, unprovoked anger and inappropriate cry. During the next one month, she developed unsteady gait, slurring of speech and excessive sleepiness. Later she developed spontaneous jerky movements of legs and became bed-bound, incontinent and unresponsive. She did not have any systemic illness, neurosurgical intervention or hormonal treatment in the past. Her diet was adequate. At admission she had a blank stare with infrequent blinks and absence of vocalization and response to commands. She developed frequent brief-lasting myoclonic jerks involving the limbs, which increased with painful stimuli but not with sound. She developed rigidity of all limbs and stretch reflexes were brisk. Plantar response was flexor. She was subsequently lost to follow-up.

The following investigations were normal: hemogram, platelet count, peripheral blood smear, serum glucose, ammonia, electrolytes, renal, liver and thyroid function tests, X-ray of chest and CT brain (plain and contrast). Lithium was not detectable in the blood. Cerebrospinal fluid (CSF) analysis showed 9 lymphocytes/ cu. mm, protein of 49 mg/dl and glucose of 87 mg/dl. Cytospin analysis of CSF did not reveal any abnormality. Scalp EEG showed diffuse slowing of background activity to delta range (3-5 Hz) and triphasic sharp wave complexes occurring periodically at 2.0 Hz frequencies throughout the record [Figure - 1]A. There was no change in EEG following pain and sound stimuli. Repeat EEG after seven days revealed similar changes. MRI of brain revealed high signal intensity on T2 WI and fluid attenuated inversion recovery (FLAIR) sequences in the caudate and putamen bilaterally. Diffusion weighted images showed bilateral symmetric hyperintense signals in the caudate, putamen and hypointense signal on apparent diffusion co-efficient (ADC) maps in the corresponding areas, suggestive of restricted diffusion [Figure - 1] A, B, C and D.

Discussion

There is no epidemiological data available from India, but the national CJD registry at NIMHANS, Bangalore, India have recorded 85 cases of CJD till September 2005.[4] The diagnostic triad of CJD, i.e., of a progressive dementia, myoclonus and periodic sharp wave EEG activity may not be evident in as many as 25% of patients.[1] According to Master's criteria, our patient had probable sporadic CJD.[5] According to WHO diagnostic criteria (1998), identification of 14-3-3 in the CSF is an accurate test to detect sporadic CJD. It also suggested that MRI might be used to diagnose sporadic CJD.[6] Analysis of CSF 14-3-3 was, however, not carried out due to the lack of facility. Cerebral imaging is considered to be of little value for definite ante-mortem diagnosis and is usually undertaken to exclude other illnesses.[2] However, recent studies have shown that MRI is a valuable diagnostic tool with a reasonable sensitivity of 61-90% and a high specificity of 94%.[7] Zerr et al have found that the sensitivity of MRI in detecting CJD was 70%, irrespective of the subgroup of phenotypes, but was particularly reliable in MV2 patients.[8] The differentiating features of sporadic and variant CJD are listed in [Table - 1]. MRI also helps in differentiating sporadic CJD from variant CJD.[3] In sporadic CJD the T2 prolongation and reduced diffusion are noted in the corpus striatum followed by the neocortex and posterior and medial thalami. But in variant CJD, abnormalities are most frequent in the posterior (pulvinar) and medial thalami followed by periaqueductal grey matter, striatum and less commonly in the neocortex.[9] The" Pulvinar sign" as defined by increased intensity in the pulvinar relative to the anterior putamen, is perhaps the most sensitive marker for variant CJD.[7] Additional involvement of the dorsomedial thalamic nucleus may look like "Hockey-stick" along with pulvinar changes.[7] Bilateral pulvinar sign has a sensitivity of 78% and correlates with histological gliosis.[7] The other notable MRI finding in variant CJD is periaqueductal grey high signal without any cerebral atrophy.[7]

Shiga et al[9] noted that the diffusion weighted MRI had higher sensitivity for CJD (92%) compared to FLAIR sequences (41-59%), T2W (36-50%), EEG (50-78%), CSF protein 14-3-3 (84%) or Neuron-specific enolase (73%). Diffusion weighted MRI is more tolerant for motion artifacts than T2W and FLAIR images[9] and the abnormalities could be detected as early as at three weeks of symptom duration, even before the appearance of periodic triphasic waves on EEG. The combination of FLAIR and diffusion weighted imaging has a sensitivity, specificity and accuracy of over 90% in differentiating CJD from other dementias.[10] The multifocal cortical and subcortical hyperintensities confined to gray matter in diffusion weighted MRI may be more useful than the CSF protein 14-3-3.[11] The pathophysiological basis of restricted diffusion is attributed to accumulation of abnormal vacuoles in the cytoplasm and the microvacuolation of neuritic processes heralding spongiform degeneration.[3]

Matoba et al while studying the serial changes on diffusion weighted MRI in CJD found that the hyperintensity in the basal ganglia and cortex during the early stages had become more extensive and conspicuous while in the later stages there was disappearance of the abnormal signals in the cortex.[12]

The hyperintensities in T2WI and PD correlate with spongiosis in basal ganglia structures, neuronal loss and gliosis. It has also been noted that in sporadic CJD spongiosis is responsible for the signal changes, while gliosis in patients with variant CJD.[1],[6] The exact origin of the periodic triphasic complexes, a characteristic EEG abnormality in CJD,[13] is not known but is hypothesized to originate or be modulated from deeper nuclei, especially thalami.[14] These MRI observations and pathological changes noted earlier provide structural correlate for the electrophysiological changes.
This case highlights that MRI may be an additional tool in the diagnosis of CJD and might help in the better understanding of the pathophysiological process.

References

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