JOURNAL OF THE
Journal of the Neurological Sciences 138 (19961 157-160
Panencephalitic Creutzfeldt-Jakob disease Unusual presentation of magnetic resonance imaging and proton magnetic resonance spectroscopy Woei-Cherng Shyu a’* , Chau-Chin Lee b, Yaw-Don Hsu a, Jiann-Chyun Lin a, Jiunn-Tay Lee a, Wei-Hwa Lee ‘, Wen-Long Tsao a a Department of Neurology, Tri-Service General Hospital and National Defence Medical Center, No. 8, Sec. 3, Tingchow Rd, Taipei, Taiwan, R.O.C. b Department of Radiology, Tri-Seruice General Hospital and National Defence Medical Center, Taipei, Taiwan, R.O.C. ’ Department of Pathology, Tri-Service General Hospital and National Defence Medical Center, Taipei, Taiwan, R.O.C. Received 31 July 1995; revised 16 November 1995; accepted 20 December 1995
Abstract We present serial magnetic resonance imaging (MRI) scans on a biopsy-verified case of Creutzfeldt-Jakob disease (CJD). The initial MRI scan demonstrated increased T2 signal-intensity within the basal ganglia and thalami. Subsequent MRI scans demonstrated a thin cortex, increased T2 signals diffusely within the white matter including U-fibers, and hypointense T2 signals within the basal ganglia, and thalami. Proton magnetic resonance spectroscopy (‘H-MRS) study showed an absence of creatine, choline and N-acetylaspartate signals. By these characteristic findings, serial MRI and MRS studies may be helpful in differentiating CJD from other dementing illnesses. Keywords: Creutzfeldt-Jakob
disease; MRI; MRS; Basal ganglion; Dementia: Spongiform encephalopathy
1. Introduction Creutzfeldt-Jakob rapidly progressive
2. Patient report disease (CJD) dementing
is an uncommon
illness that is usually
within one year. Clinical diagnosis is based on symptomatology and course (Brown et al., 1986). Characteristic histopathologic findings of nerve cell loss, gliosis and spongiform changes in gray matter confirm the diagnosis with sufficient validity. Previous neuroimaging studies suggested that neither magnetic resonance imaging (MRI) nor computed tomographic (CT) scan is associated with a distinct appearance in CJD. However, some authors have presented interesting MRI findings in the various stages of CJD (Falcone et al., 1992; Gertz et al., 1988; Kruger et al., 1990). This report shows serial MRI and proton magnetic resonance spectroscopy (‘H-MRS) studies on a biopsyproven case of CJD with extensive cortical and white matter involvement. The value of MRI and ‘H-MRS in the diagnosis of CJD is discussed as well.
* Corresponding author. Fax: 886 2-3652339. 0022-510X/96/$15.00 0 1996 Elsevier Science B.V. All rights reserved PII SOO22-5 10X(96)00010-X
A 4%year-old woman was admitted with a l-month history of vomiting, lethargy and loss of appetite. At the time of admission,
inattentiveness, non-fluent speech and dystonic movements of the right hand. Motor clumsiness was noted and she could not walk unaided. Her past medical and family histories were unremarkable. Physical examination revealed a staring dull appearance. Neurological evaluation showed alert consciousness with mutism. Mental performance demonstrated poor calculation, and sluggish judgment to person and place. Muscle strength was normal with mild axial rigidity. The deep tendon reflexes were exaggerated without Babinski’s sign. A wide-based, shuffling gait was observed. Myoclonic jerks, muscular rigidity in all limbs, muscle wasting, difficulty in swallowing and incontinence of urine developed gradually. Two months later, she deteriorated to be globally aphatic and bed-ridden. An electroencephalogram showed a continuous, diffuse, theta-delta background slowing activity, and periodic syn-
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of the Neurological Sciences 138 (1996) 157-160
Fig . 1. Axial MR images obtained two months after symptom onset show increased signal intensity within the head of caudate nuclei, putamens and thal.ami on TZ-weighted (repetition time [TR] = 3.0 s, echo time [TE] = 90 ms) (A) and proton-density (TR = 3.0 s, TE = 30 ms) images (B). Repeat MR imaiges, one year after onset, demonstrate marked brain atrophy, thinning of the cortex, diffuse white matter degeneration including subcortical U-fil 3ers. and hypointense signals at basal ganglia on T2-weighted (TR = 3.0 s, TE = 90 ms) (C) and proton-density (TR = 3.0 s, TE = 30 ms) images (D).
Fig. 2. Proton magnetic resonance spectroscopic measurement over a 3 X 3 X3-cm’ crei Itine, choline and N-acetylaspartate peaks (TR = 1.5 s, TE = 270 ms).
region of interest within in the frontal region reveals an absence olr the
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Fig. 3. Sections of cortical gray (A) and subcortical white matters (B) reveal neuronal loss and exntesive spongiform changes (hematoxyline stain, X 200).
chronized sharp delta-wave discharges (1 Hz). Cerebrospinal fluid and other laboratory studies were unremarkable. Cranial MRI (l..5T, Picker) revealed bilateral increased T2-signal intensity at the head of the caudate nuclei, putamens, and thalami on T2-weighted (repetition time [TR] = 3.0 s, echo time [TE] = 90 ms) and protondensity images (TR = 3.0 s, TE = 30 ms) (Fig. 1A,B). One year later, repeat MRI showed severe brain atrophy with a prominently dilated ventricular system, and thinning of the cortex. Diffuse increased signal intensity over the periventricular and subcortical white matter including U-fiber was also observed on T2-weighted images. Furthermore, decreased T2-signal intensity of the atrophic cortex, bilateral basal ganglia, thalami and dentate nuclei was found on T2-weighted and proton-density images (Fig. lC,D). ‘HMRS measurements were applied over a 3 X 3 X 3-cm” region of interest in the frontal region (TR = 1.5 s, TE = 270 ms). It revealed an absence of the creatine (Cr), choline (Cho) and N-acetylaspartate (NAA) peaks (Fig. 2). An open brain biopsy of the right temporal lobe showed severe loss of neurons, hypertrophic glial reaction and vacuolar-spongiform changes in gray matter (Fig. 3A). The white matter was also involved with severe spongiosis and hypertrophic glial proliferation (Fig. 3B). The cortical areas also demonstrated greater intensity of blueness on the Perl’s stain representing a high concentration of ferric iron.
Two years following the onset of illness, she remained in a vegetative and cachexic state, and lived at a chroniccare unit.
3. Discussion CJD is a transmissible spongiform encephalopathy. Various MRI abnormalities have been described in CJD. These include diffuse cortical atrophy, focal symmetrical lesions of occipital gyri (Falcone et al., 1992) bilateral basal ganglion and thalamus lesions (Gertz et al., 1988; Iwasaki et al., 1994) and periventricular abnormality (Kruger et al., 1990). Although white matter lesions are rarely present, severe white matter involvement has been reported in a few postmortem studies (Vallat et al., 1983; Gertz et al., 1988; Kruger et al., 1990). We and others showed an initial involvement of the basal ganglia and thalami, and subsequently diffuse white matter degeneration with severe brain atrophy within one year after the onset of CJD (Uchino et al., 1991). Usually, CJD with white matter changes has a conspicuously slow clinical course, longer duration of illness, and markedly prominent brain atrophy (Mizutani et al., 1981). It has been presumed that ‘panencephalitic’ CJD is a different entity (Vallat et al., 1983). It is believed that white matter degeneration may occasion-
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ally present in CJD, and would develop in the terminal stage of the disease (Kovanen et al., 1985). MR image is superior to CT scan in detecting white matter lesions. From the clinical point of view, it can be difficult to differentiate CJD from other dementing processes with white matter degeneration, such as Alzheimer’s dementia, Pick’s disease, Binswanger’s disease, and progressive supranuclear palsy. Whatever the vascular factor, degenerative or old-age dementia, the white matter changes usually spared the subcortical U-fibers. However, this report and others demonstrate white matter degeneration with a subcortical U-fiber involvement in the cases of CJD (Uchino et al., 1991). Furthermore, ‘H-MRS can demonstrate absence of the Cr, Cho and NAA peaks indicating no neuronal activity, over the region of interest in late-stage CJD. We suggest that serial MRI and ‘H-MRS scans are helpful in differentiating panencephalitic CJD from other dementing processes. The clinical manifestations of extrapyramidal tract dysfunction in CJD are well correlated with basal ganglion lesions. The MRI of this report showed hyper- and hypointense T2-signal changes on serial studies. The differential diagnosis of bilateral basal ganglion lesions on MRI includes ischemic or infarct (intoxication of carbon monoxide, amphetamine and methanol), metabolic (mitochondria encephalomyopathies, Wilson’s and Hallervoden-Spatz diseases), infectious (Japanese encephalitis), and primary neurodegenerative disorders. Aforementioned entities could be excluded by their clinical symptoms and laboratory evaluations. All, with the exception of Hallervoden-Spatz disease, demonstrate increased T2-signal intensity within the basal ganglia. HallervodenSpatz disease often reveals prominent hypointense T2-signals at basal ganglia from primary iron deposition. Increased iron deposition demonstrated by Perl’s stain in this
case is considered to develop after direct neuron cell injury (Cross et al., 1990). In summary, although neuroimaging studies usually reveal no specific findings in the early stage of CJD, serial MRI and MRS studies may be useful in the premortem diagnosis of CJD from other dementing processes.
References Brown P, Cathala F, Castaigne P, Cajdusek DC (19861 Creutzfeldt-Jakob disease: clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol, 20: 597-602. Cross PA, Altas SW, Grossman RI (1990) MR evaluation of brain iron in children with cerebral infarction. Am J Nemo1 Res, 11: 341-348. Falcone S, Ouencer RM, Brown B, Bruce JH, Naidich TP (1992) Creutzfeldt-Jakob disease: focal symmetrical cortical involvement demonstrated by MR imaging. Am J Neural Res, 13: 403-406. Gertz HJ, Henkes H, Cervos-Navarro J (1988) Creutzfeldt-Jakob disease: correlation of MRI and neuropathologic findings. Neurology, 38: 1481-1482. Iwasaki Y, Ikeda K, Tagaya N, Kinoshita M (1994) Magnetic resonance imaging and neuropathological findings in two patients with Creutzfeldt-Jakob disease. J Neurol Sci, 126: 228-23 1. Kovanen J, Erkinjuntti T, Iivanainen M, Ketonen L, Haltia M, Sulkava R, Sipponen JT (1985) Cerebral MR and CT imaging in Creutzfeldt-Jakob disease. J Comput Assist Tomogr, 9: 125-128. Kruger H, Meesmann C, Rohrback E (1990) Panencephalitic type of Creutzfeldt-Jakob disease with primary extensive involvement of the white matter. Eur Neurol, 30: 115-I 19. Mizutani T, Okumura A, Oda M, Shiraki H (19811 Panencephalitic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter. J Neurol Neurosurg Psychiatry, 44: 103- 115. Vallat JM, Dumas M, Covisier N, Leboutet MJ, Loubet A, Dumas P, Cathala F (1983) Familial Creutzfeldt-Jakob disease with extensive degeneration of the white matter. Ultrastructure of peripheral nerve. J Neurol Sci, 61: 261-275. Uchino A, Yoshinaga M, Shiokawa 0, Hata H, Ohno M. (1991) Serial MR imaging in Creutzfeldt-Jakob disease. Neuroradiology, 33: 364367.