10. Chance B, Leigh JS, Clark BJ, et al. Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steadystate analysis of the work/energy cost transfer function. Proc Natl Acad Sci USA 1985;82:8384-8388 11. Berkovic SF, Andermann F, Carpenter S, Wolfe LS. Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med 1986;315:295-305 12. Matthews PM, Arnold DL. Phosphorus magnetic resonance spectroscopy of brain in mitochondrial cytopathies. Ann Neurol 1990;28:839-840 13. Eleff SM, Barker PB, Blackband SJ, et al. Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine. Ann Neurol 1990;27:626-630 14. Wagner PD. Diffusion and chemical reaction in pulmonary gas exchange. Physiol Rev 1978;57:257-312 15. Fox PT, Raichle ME, Mintun MA, Dense C. Nonoxidative glucose consumption during focal physiologic neural activity. Science 1988;241:462-465
Magnetic Resonance Imaging of Creutzfeldt-Jacob Disease Walter J. Milton, MD,* Scott W. Atlas, MD,” Ehud Lam, MD,? and Joan E. Mollman, MDS
We report a biopsy-diagnosed patient with CreutzfeldtJacob disease showing on magnetic resonance images bilateral increased signal intensity in the basal ganglia on long repetition time images. Creutzfeldt-Jacob disease (CJD) is a degenerative process of the brain, induced by a novel infectious agent, and is usually characterized by a rapidly progressive dementia. W e report a biopsydiagnosed patient w i t h CJD with a distinctive magnetic resonance (MR) appearance. Milton WJ, Atlas SW, Lavi E, Mollman JE. Magnetic resonance imaging of Creutzfeldt-Jacob disease. Ann Neurol 1991;29:438-440
Patient Report A 52-year-old woman was admitted with a 2-month history of progressive gait ataxia, postural instability, and a sensation
From the *Department of Radiology, Neuroradiology Section, Hospital of the University of Pennsylvania, and +Division of Neuropathology, Department of Pathology and hbordtory Medicine, and $Department of Neurology, University of Pennsylvania, Philadel-
phia, PA. Received Aug 29, 1990, and in revised form Oct 30. Accepted for publication Nov 2, 1990. Address correspondence to Dr Atlas, Department of Radiology, Neuroradiology Section, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 10104.
438
that her feet were “wobbling and shaking.” At the time of admission, she had developed inattentiveness, confusion, poor concenrration, poor memory, and emotional lability. Her past medical history was unremarkable and she took no medications. Examination demonstrated masked facies, axial rigidity, a staring dull appearance, stooped posture, and a paucity of spontaneous movements. She starded easily to noises and rapid movements. She was oriented to year and “hospital” but could not perform calculations or remember any of three objects after 5 minutes. Strength was normal, but increased tone, asymmetrical cogwheeling, dysmetria, clumsiness, and a shuffling, wide-based gait were observed. Reflexes were normal. Cerebrospinal fluid (CSF) fluid evaluation was normal. Antinudear antibody, rapid plasma reagin, and Lyme titers were negative, as was CSF culture. Ceruloplasmin and urinary copper levels were within normal limits. The electroencephalogram (EEG) showed nonperiodic irritative activity that was more prominent on the left. A recent outside computed tomographic (CT) scan demonstrated only atrophy and no calcification o r other abnormality in the basal ganglia. Magnetic resonance imaging (MRI) was performed (1.5 T, GE Signa, Milwaukee, WI) and demonstrated increased signal intensity in the head of the caudate and putamen bilaterally, and to a lesser extent in the globus pallidus on the long repetition time (TR) images (Fig 1). No mass effect was present, and there was no enhancement after administration of 0.1 mmolikg gadopentetate dimeglumine (Berlex Laboratories, Cedar Knolls, XJ). An open brain biopsy of the right frontal lobe was performed and demonstrated vacuolar changes consistent with spongiform encephalopathy. Electronmicroscopy showed swelling of presynaptic and postsynaptic processes, a feature that is often seen in patients with CJD but not in patients with other types of spongiform changes (Fig 2). The patient continued to deteriorate rapidly, and she died 1.5 months after admission.
Discussion CJD, as well as k u r u and Gersunann-Straussler syndrome in humans and scrapie in sheep, are grouped together as subacute spongiform encephalopathies believed t o be caused by an unconventional virus-like agent or agents { 1). I t has been proposed that the infectious agent is a small, proteinaceous particle that has been labeled “prion” [2]. The disease is uncommon; a 15-year study of all resident citizens of continental France (average population, 52 million) found only 230 verified patients with CJD { 31. Infectivity is believed low, and the infectious agent has not b e e n isolated from blood, saliva, urine, or tears in patients with CJD
Uf. The dementia of CJD begins insidiously but progresses rapidly, a feature that d i s t i n s i s h e s this disease from t h e more c o m m o n dementias such as Alzheimer’s or the Parkinson-dementia complex { 11. Myoclonic jerks occur in almost all patients, frequently manifesting as a startle response, and help to differentiate CJD
Copyright 0 1991 by the American Neurological Association
A
A B
Fig 2. (A) Section of cortex shows spongiform changes in the newopiL (Hemtoxylznand eosin; x 200 before .38% reduction. (B) Electronmicroscopy of correx showing that the spongtjkm changes are in part dae t o dilutation ofpresynaptic andpostsynaptic nearonalpmcesses (center).( x .30,000 beJore 38% redaction.)
B Fig 1. Axial (A) and coronal (B) magnetic resonance images. 3,000130 (repetition timelecho time), throagh the region of the basal gangha demonstratesym?netrica//yincreased signal intensity in the piitamen, caadates, and t o a les.rer extent, the globus pa[lidus, Note involvementof the caudztoplttamen gray matter bridges crossing the internal capsule (best seen on the coronal image).
from other dementias. Cerebellar and extrapyramidal signs are frequently seen with advancing illness [3}. The EEG is abnormal in almost all patients at some stage and may show a characteristic pattern of rhythmic spiking. A compilation of postmortem studies of 150 patients disclosed the following three main pathological forms: frontopyramidal (50 of 150 patients, 33%), occipitoparietal (27 of 150 patients, 18%), and the diffuse cerebral cortical and basal ganglia type (73 of 150 patients, 49%) with (as in the other two types) thalamic, midbrain, cerebellar, or spinal participation, or any of these in combination [4].Our patient is an example of the diffuse cortical and basal ganglia type. The differential diagnosis on MRI of bilateral basal ganglia lesions includes inborn errors of metabolism (Wilson’s disease, Leigh’s disease, Hallemorden-Spatz disease, amino acidopathies, and mitochondrial encephalomyopathies), ischemia or infarction (frequently associated with carbon monoxide, cyanide, or hydrogen sulfide poisoning), primary neurodegenerative disorders such as multiple system atrophy, and neoplasm such as lymphoma or multifocal glioma. All these dis-
Brief Communication: Milton et al: MRI in Creutzfeldt-Jacob Disease
439
orders demonstrate prolonged T2 relaxation except for Hallervorden-Spatz disease, which often shows pronounced hypointensity on the long T R images in the basal ganglia from iron deposition 151. The inborn errors of metabolism usually present in the first decade, and only Wilson's disease was a serious consideration in this patient. The lack of mass effect or contrast enhancement along with the pronounced symmetry of the findings made neoplasm very unlikely. A CT study of 15 patients with proven CJD showed 12 [so%]of the 15 patients as normal and the other 3 [20%] as having varying amounts of atrophy {GI. The conclusion was that a normal CT in a demented patient should suggest CJD. In another study, MRI and CT of 3 patients with CJD showed bilateral cortical atrophy and no apparent white matter changes 171. A recent case report in the literature showed increased signal intensity in the striatum and thalamus, and to a lesser extent in the cerebral cortex, in images obtained with TR 1600 msec and echo time of 35 and 70 msec [S}. The findings in this patient, as well as in our patient, are compatible with involvement of deep gray matter structures in this disorder. Absence of enhancement is compatible with the lack of inflammatory changes seen on pathology. In conclusion, we believe that in a patient with a rapidly progressive dementia, the MRI demonstration of bilateral increased signal intensity on long TR images in deep gray structures should suggest the diagnosis of CJD.
Attention Modulates Somatosensory Cerebral Blood Flow Response to Vibrotactile Stimulation as Measured by Positron Emission Tomography E. Meyer, PhD," S. S. G. Ferguson, BSc,"
R.J. Zatorre, PhD,? B. Alivisatos, PhD,? S. Marrett, MSc," A. C. Evans, PhD," and A. M. Hakirn, MD, PhD"
In human primary somatosensory cortex, the cerebral blood flow response to vibrotactile stimulation of the fingers (110 Hz), as measured by positron emission tomography and H2150,was 13% higher ( p < 0.025) when the subjects attended to the stimulus, compared to when they were simultaneously engaged in a distraction task. This suggests that the physiological response of a primary cortical area can be modulated by the attentive behavior of the subject. Meyer E, Ferguson SSG, Zatorre RJ, Alivisatos B, Marrett S, Evans AC, Hakirn AM. Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography. Ann Neurol 1991;29:440-443
References 1. Davanipour Z, Alter M, Sobel E. Creutzfeldt-Jakob disease. Neurol Clin 1988;4:415-426 2. Prusiner SB. Prions and neurodegenerative diseases. N Engl J Med 1987;317:1571-1581 3. Brown P, Cathala F, Gajdusek P, Gajdusek DC. CreuczfeldtJakob disease: clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol 1986;20:597-602 4 . Kirschbaum WR. Comments on the tabulated cases and compilation of the data. In: Jakob-Creutzfeldt disease. New York American Elsevier Publishing, 1968:114-129 5. Littrup PJ, Gerbarski SS. MR imaging of Hallemorden-Spau disease. J Comput Assist Tomogr 1985;9:491-493 6. Galves S, Cartier L. Computer tomography findings in 15 cases of Creunfeldt-Jakob disease with histological verification. J Neurol Neurosurg Psychiatry 1984;47:1244- 1246 7. Kavanen J, Erkinguntli T, Ketonen L, et al. Cerebral MR and CT imaging in Creutzfeldt-Jakob disease. J Comput Assist Tomogr 1985;9:125-128 8. G e m HJ, Henks H, Cervos-Navarro JC. Creutzfeldt-Jakob disease: correlation of MRl and neuropathologic findings. Neurology 1988;38:1481-1482
Attentional mechanisms and their interactions with sensory perception have been studied with a variety of methodologies [l-41. For example, microelectrode recordings from primary somatosensory cortex of monkeys have allowed identification of a population of neurons that was clearly affected by the attentive behavior of the animals, with respect to a vibrotactile stimulus applied to their hands [l). We used positron emission tomography (PET) to measure the cerebral blood flow (CBF) response of primary somatosensory cortex to vibrotactile stimulation of the hand while the subject either focused his attention on the stimulus or was concurrently engaged in a distraction task.
From the 'Positron Imaging Laboratories, McConnell Brain Imaging Centre, and ?Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. Received Nov 27, 1989, and in revised form Jun 18 and Oct 16, 1990. Accepted for publication Oct 23, 1990. Address correspondence to Dr Meyer, McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
440 Copyright 0 1991 by the American Neurological Association
Magnetic Resonance Imaging of Creutzfeldt-Jacob Disease Walter J. Milton, MD,* Scott W. Atlas, MD,” Ehud Lam, MD,? and Joan E. Mollman, MDS
We report a biopsy-diagnosed patient with CreutzfeldtJacob disease showing on magnetic resonance images bilateral increased signal intensity in the basal ganglia on long repetition time images. Creutzfeldt-Jacob disease (CJD) is a degenerative process of the brain, induced by a novel infectious agent, and is usually characterized by a rapidly progressive dementia. W e report a biopsydiagnosed patient w i t h CJD with a distinctive magnetic resonance (MR) appearance. Milton WJ, Atlas SW, Lavi E, Mollman JE. Magnetic resonance imaging of Creutzfeldt-Jacob disease. Ann Neurol 1991;29:438-440
Patient Report A 52-year-old woman was admitted with a 2-month history of progressive gait ataxia, postural instability, and a sensation
From the *Department of Radiology, Neuroradiology Section, Hospital of the University of Pennsylvania, and +Division of Neuropathology, Department of Pathology and hbordtory Medicine, and $Department of Neurology, University of Pennsylvania, Philadel-
phia, PA. Received Aug 29, 1990, and in revised form Oct 30. Accepted for publication Nov 2, 1990. Address correspondence to Dr Atlas, Department of Radiology, Neuroradiology Section, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 10104.
438
that her feet were “wobbling and shaking.” At the time of admission, she had developed inattentiveness, confusion, poor concenrration, poor memory, and emotional lability. Her past medical history was unremarkable and she took no medications. Examination demonstrated masked facies, axial rigidity, a staring dull appearance, stooped posture, and a paucity of spontaneous movements. She starded easily to noises and rapid movements. She was oriented to year and “hospital” but could not perform calculations or remember any of three objects after 5 minutes. Strength was normal, but increased tone, asymmetrical cogwheeling, dysmetria, clumsiness, and a shuffling, wide-based gait were observed. Reflexes were normal. Cerebrospinal fluid (CSF) fluid evaluation was normal. Antinudear antibody, rapid plasma reagin, and Lyme titers were negative, as was CSF culture. Ceruloplasmin and urinary copper levels were within normal limits. The electroencephalogram (EEG) showed nonperiodic irritative activity that was more prominent on the left. A recent outside computed tomographic (CT) scan demonstrated only atrophy and no calcification o r other abnormality in the basal ganglia. Magnetic resonance imaging (MRI) was performed (1.5 T, GE Signa, Milwaukee, WI) and demonstrated increased signal intensity in the head of the caudate and putamen bilaterally, and to a lesser extent in the globus pallidus on the long repetition time (TR) images (Fig 1). No mass effect was present, and there was no enhancement after administration of 0.1 mmolikg gadopentetate dimeglumine (Berlex Laboratories, Cedar Knolls, XJ). An open brain biopsy of the right frontal lobe was performed and demonstrated vacuolar changes consistent with spongiform encephalopathy. Electronmicroscopy showed swelling of presynaptic and postsynaptic processes, a feature that is often seen in patients with CJD but not in patients with other types of spongiform changes (Fig 2). The patient continued to deteriorate rapidly, and she died 1.5 months after admission.
Discussion CJD, as well as k u r u and Gersunann-Straussler syndrome in humans and scrapie in sheep, are grouped together as subacute spongiform encephalopathies believed t o be caused by an unconventional virus-like agent or agents { 1). I t has been proposed that the infectious agent is a small, proteinaceous particle that has been labeled “prion” [2]. The disease is uncommon; a 15-year study of all resident citizens of continental France (average population, 52 million) found only 230 verified patients with CJD { 31. Infectivity is believed low, and the infectious agent has not b e e n isolated from blood, saliva, urine, or tears in patients with CJD
Uf. The dementia of CJD begins insidiously but progresses rapidly, a feature that d i s t i n s i s h e s this disease from t h e more c o m m o n dementias such as Alzheimer’s or the Parkinson-dementia complex { 11. Myoclonic jerks occur in almost all patients, frequently manifesting as a startle response, and help to differentiate CJD
Copyright 0 1991 by the American Neurological Association
A
A B
Fig 2. (A) Section of cortex shows spongiform changes in the newopiL (Hemtoxylznand eosin; x 200 before .38% reduction. (B) Electronmicroscopy of correx showing that the spongtjkm changes are in part dae t o dilutation ofpresynaptic andpostsynaptic nearonalpmcesses (center).( x .30,000 beJore 38% redaction.)
B Fig 1. Axial (A) and coronal (B) magnetic resonance images. 3,000130 (repetition timelecho time), throagh the region of the basal gangha demonstratesym?netrica//yincreased signal intensity in the piitamen, caadates, and t o a les.rer extent, the globus pa[lidus, Note involvementof the caudztoplttamen gray matter bridges crossing the internal capsule (best seen on the coronal image).
from other dementias. Cerebellar and extrapyramidal signs are frequently seen with advancing illness [3}. The EEG is abnormal in almost all patients at some stage and may show a characteristic pattern of rhythmic spiking. A compilation of postmortem studies of 150 patients disclosed the following three main pathological forms: frontopyramidal (50 of 150 patients, 33%), occipitoparietal (27 of 150 patients, 18%), and the diffuse cerebral cortical and basal ganglia type (73 of 150 patients, 49%) with (as in the other two types) thalamic, midbrain, cerebellar, or spinal participation, or any of these in combination [4].Our patient is an example of the diffuse cortical and basal ganglia type. The differential diagnosis on MRI of bilateral basal ganglia lesions includes inborn errors of metabolism (Wilson’s disease, Leigh’s disease, Hallemorden-Spatz disease, amino acidopathies, and mitochondrial encephalomyopathies), ischemia or infarction (frequently associated with carbon monoxide, cyanide, or hydrogen sulfide poisoning), primary neurodegenerative disorders such as multiple system atrophy, and neoplasm such as lymphoma or multifocal glioma. All these dis-
Brief Communication: Milton et al: MRI in Creutzfeldt-Jacob Disease
439
orders demonstrate prolonged T2 relaxation except for Hallervorden-Spatz disease, which often shows pronounced hypointensity on the long T R images in the basal ganglia from iron deposition 151. The inborn errors of metabolism usually present in the first decade, and only Wilson's disease was a serious consideration in this patient. The lack of mass effect or contrast enhancement along with the pronounced symmetry of the findings made neoplasm very unlikely. A CT study of 15 patients with proven CJD showed 12 [so%]of the 15 patients as normal and the other 3 [20%] as having varying amounts of atrophy {GI. The conclusion was that a normal CT in a demented patient should suggest CJD. In another study, MRI and CT of 3 patients with CJD showed bilateral cortical atrophy and no apparent white matter changes 171. A recent case report in the literature showed increased signal intensity in the striatum and thalamus, and to a lesser extent in the cerebral cortex, in images obtained with TR 1600 msec and echo time of 35 and 70 msec [S}. The findings in this patient, as well as in our patient, are compatible with involvement of deep gray matter structures in this disorder. Absence of enhancement is compatible with the lack of inflammatory changes seen on pathology. In conclusion, we believe that in a patient with a rapidly progressive dementia, the MRI demonstration of bilateral increased signal intensity on long TR images in deep gray structures should suggest the diagnosis of CJD.
Attention Modulates Somatosensory Cerebral Blood Flow Response to Vibrotactile Stimulation as Measured by Positron Emission Tomography E. Meyer, PhD," S. S. G. Ferguson, BSc,"
R.J. Zatorre, PhD,? B. Alivisatos, PhD,? S. Marrett, MSc," A. C. Evans, PhD," and A. M. Hakirn, MD, PhD"
In human primary somatosensory cortex, the cerebral blood flow response to vibrotactile stimulation of the fingers (110 Hz), as measured by positron emission tomography and H2150,was 13% higher ( p < 0.025) when the subjects attended to the stimulus, compared to when they were simultaneously engaged in a distraction task. This suggests that the physiological response of a primary cortical area can be modulated by the attentive behavior of the subject. Meyer E, Ferguson SSG, Zatorre RJ, Alivisatos B, Marrett S, Evans AC, Hakirn AM. Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography. Ann Neurol 1991;29:440-443
References 1. Davanipour Z, Alter M, Sobel E. Creutzfeldt-Jakob disease. Neurol Clin 1988;4:415-426 2. Prusiner SB. Prions and neurodegenerative diseases. N Engl J Med 1987;317:1571-1581 3. Brown P, Cathala F, Gajdusek P, Gajdusek DC. CreuczfeldtJakob disease: clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol 1986;20:597-602 4 . Kirschbaum WR. Comments on the tabulated cases and compilation of the data. In: Jakob-Creutzfeldt disease. New York American Elsevier Publishing, 1968:114-129 5. Littrup PJ, Gerbarski SS. MR imaging of Hallemorden-Spau disease. J Comput Assist Tomogr 1985;9:491-493 6. Galves S, Cartier L. Computer tomography findings in 15 cases of Creunfeldt-Jakob disease with histological verification. J Neurol Neurosurg Psychiatry 1984;47:1244- 1246 7. Kavanen J, Erkinguntli T, Ketonen L, et al. Cerebral MR and CT imaging in Creutzfeldt-Jakob disease. J Comput Assist Tomogr 1985;9:125-128 8. G e m HJ, Henks H, Cervos-Navarro JC. Creutzfeldt-Jakob disease: correlation of MRl and neuropathologic findings. Neurology 1988;38:1481-1482
Attentional mechanisms and their interactions with sensory perception have been studied with a variety of methodologies [l-41. For example, microelectrode recordings from primary somatosensory cortex of monkeys have allowed identification of a population of neurons that was clearly affected by the attentive behavior of the animals, with respect to a vibrotactile stimulus applied to their hands [l). We used positron emission tomography (PET) to measure the cerebral blood flow (CBF) response of primary somatosensory cortex to vibrotactile stimulation of the hand while the subject either focused his attention on the stimulus or was concurrently engaged in a distraction task.
From the 'Positron Imaging Laboratories, McConnell Brain Imaging Centre, and ?Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. Received Nov 27, 1989, and in revised form Jun 18 and Oct 16, 1990. Accepted for publication Oct 23, 1990. Address correspondence to Dr Meyer, McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
440 Copyright 0 1991 by the American Neurological Association
