J Neurosurg 75:458-460, 1991
Cerebral amyloid angiopathy presenting as multiple intracranial lesions on magnetic resonance imaging Case report DEEPAK AWASTHI, M.D., RAND M. VOORHIES, M.D., JOHN EICK~ M.D., AND WILLIAM T. MITCHELL, M.D. Department of Neurosurgery, Louisiana State University Medical Center, and Departments of Neurosurgery, Radiology, and Pathology, Ochsner Foundation Hospital New Orleans, Louisiana v, Cerebral amyloid angiopathy is recognized as an important cause of spontaneous intracerebral hemorrhage in the elderly normotensive patient. Magnetic resonance (MR) imaging characteristics of this disease entity are rarely mentioned in the literature. The MR imaging findings of an elderly normotensive patient presenting with an acute spontaneous intracerebral hemorrhage secondary to amyloid angiopathy are reported and a brief review of amyloidosis is presented. KEY WORDS
amyloidosis magnetic resonance imaging "
9 amyloid angiopathy 9 intracerebral hemorrhage 9
p
RIMARY cerebral amyloid angiopathy is a subset of cerebral amyloidosis characterized by deposition of amyloid substance in the walls of the cerebral and leptomeningeal vessels. 2 Cerebral amyloid angiopathy has been reported in association with spontaneous intracerebral hemorrhages in normotensive patientsY -9 These hemorrhages tend to be lobar and can be multipleJ '8'9Magnetic resonance (MR) imaging findings of this disease entity are rarely mentioned in the literature. This report describes the MR imaging appearance of cerebral amyloid angiopathy presenting as multiple intracranial lesions. A brief review of amyloidosis is also presented.
Case Report This 78-year-old right-handed white woman was noted to have an acute onset of confusion followed by a brief generalized tonic-clonic seizure. Her medical history was significant for headaches and intermittent confusional episodes during the year prior to admission. There was no history of hypertension, vasculitis, neoplasms, cerebrovascular disease, or trauma. Evaluation at another hospital revealed an agitated, confused, and combative woman with no focal neurological deficits. She was transferred to Ochsner Foundation Hospital after computerized tomography (CT) had revealed a small fight-sided occipital hemorrhage. 458
Examination. On arrival, the patient continued to be confused and agitated. She had no focal neurological deficits; however, neurological examination on the following day revealed mild motor dysphasia, finger agnosia on the right, and left-right confusion. She was less agitated and more lucid than on admission. The multiplicity of neurological findings not corresponding to the area of the hemorrhage led us to obtain a repeat CT scan with contrast enhancement and eventually an MR image with and without contrast enhancement. Precontrast CT of the head demonstrated a 1.5 x lcm intraparenchymal hemorrhage in the right occipital re#on adjacent to the atrium of the right lateral ventricle (Fig. 1). The MR appearance was very unusual and not characteristic of any disease process (Fig. 2). These images demonstrated multiple intracranial lesions. As documented in the CT scan, there was an oval wellcircumscribed area in the right anterior occipital region adjacent to the atrium of the right lateral ventricle with signal characteristics of a recent hemorrhage (Fig. 2). Innumerable subcortical punctate areas of hypointensity were seen on the T2-weighted images, which were not observed on the Tl-weighted images or the CT scan. Following intravenous administration of contrast medium, there was no contrast enhancement. The signal from the posterior fossa structures was unremarkable. The diagnostic possibilities of these images included J. Neurosurg. / Volume 75/September, 1991
Cerebral amyloid angiopathy
FIG. 3. Photomicrograph of the right frontal cortical surface demonstrating several brownish oval punctate lesions (arrowheads). These lesions represent areas of hemorrhage secondary to cerebral amyloid angiopathy. FIG. I. Noncontrast computerized tomography scan demonstrating a 1.5 x 1-cm intraparenchymal hemorrhage in the right anterior occipital region (black arrowhead). neoplasms (metastatic or multifocal glioma), multiple hemorrhages, or an inflammatory or infectious process.
Operation. Based on the above differential diagnosis and lack of specificity of the diagnostic studies (CT scans, MR images, results of lumbar puncture, and electroencephalograms), the patient was taken to surgery and a right frontal craniotomy with open cortical biopsy was performed. Upon opening of the dura, three small brownish oval punctate lesions were seen on the cortical surface (Fig. 3). One of these lesions was biopsied in the routine manner. Sections of the cortical
FIG. 2. Magnetic resonance T2-weighted (TR 2600 msec, TE 90 msec) axial images. Left: Cut approximating the level of the computerized tomography scan, shown in Fig. 1, demonstrating the fight occipital hemorrhage (black arrowhead). In addition, several punctate areas of hypodensity are seen in this image (white arrowhead). Right: Image demonstrating innumerable subcortical punctate areas of hypodensity (arrowheads). These lesions represent multiple punctate hemorrhages.
J. Neurosurg. / Volume 75/September, 1991
brain biopsy revealed a small area of hemorrhage just beneath the pia in the cortex. Within the surrounding neuropil, the small blood vessels demonstrated variable homogeneous eosinophilic stains suggestive of amyloid which was confirmed by staining with Congo red dye and birefringence (Fig. 4). Postoperative Course. The postoperative course was uneventful. On discharge, the patient was alert and oriented with significant improvement in her dysphasia. She had no focal motor or sensory loss upon discharge.
Discussion Amyloidosis denotes a disease complex with the unifying feature of deposition in tissues of nonbranching fibrillar proteins having the common crystallographic characteristics of a beta-pleated sheet? This betapleated sheet conformation is responsible for its characteristic staining by Congo red dye and subsequent green birefringence when viewed through a polarized microscope.
FIG. 4. Photomicrograph of the surgical specimen demonstrating the characteristic birefringence (arrowhead) of amyloid in this stain viewed under the polarized microscope. Congo red, x 200. 459
D. Awasthi, et al. Classification of Amyloidosis Human amyloidosis is associated with multiple pathological conditions having diverse etiologies. Amyloidosis can be classified on the basis of clinical presentation and/or biochemical composition of the amyloid protein. 2 Clinically, it is useful to divide amyloidosis into systemic or localized disease. Systemic amyloidosis can be further subdivided into: 1) primary amyloidosis (no evidence of pre-existing or coexisting disease); 2) amyloid associated with multiple myeloma; 3) secondary or reactive amyloidosis associated with chronic infectious diseases (such as osteomyelitis, tuberculosis, or leprosy) or chronic inflammatory diseases (such as rheumatoid arthritis or ankylosing spondylitis); 4) heredofamilial amyloidosis associated with familial Mediterranean fever and a variety of neuropathic, renal, cardiovascular, and other syndromes; 5) amyloidosis associated with long-term hemodialysis; 6) familial amyloid polyneuropathy; and 7) systemic senile amyloidosis. Localized amyloidosis can be subdivided into endocrine and cerebral types. In endocrine-related amyloidosis, deposits consist of prehormonal or preprohormonal precursor proteins. The endocrine type of amyloidosis consists of tumor-like deposits in isolated organs without evidence of systemic involvement. This includes: 1) medullary carcinoma of the thyroid (procalcitonin); 2) pancreatic islet amyloidosis associated with insulinoma and diabetes mellitus; and 3) atrial amyloidosis (atrial natriuretic protein). Localized cerebral amyloidosis consists of amyloid deposits restricted to the central nervous system (CNS). It includes: 1) Alzheimer's disease; 2) Down's syndrome; 3) Parkinson-dementia of Guam; 4) sporadic cerebral amyloid angiopathy; 5) inherited forms of cerebrovascular amyloidosis (familial cerebral amyloid angiopathy), both the Dutch type and the Icelandic type; and 6) spongiform encephalopathies (CreutzfeldtJakob disease and kuru).
Amyloid Angiopathy The patient reported here exhibited the MR imaging findings of sporadic cerebral amyloid angiopathy. Three forms of amyloid deposits have been recognized in the CNS? They are: 1) the amyloid core of senile plaque; 2) deposits in the arterial and arteriolar walls of cortical and leptomeningeal vessels (congophilic angiopathy); and 3) deposits in the capillary and arteriolar walls with extension into the surrounding brain parenchyma (dysphoric angiopathy). 5 The latter two conditions are together called "amyloid angiopathy." Amyloid angiopathy is frequently present in the cerebral vessels of elderly patients and its incidence increases with age.~ There is a close relationship between amyloid angiopathy and intracerebral hematoma. Amyloid angiopathy is one of the causes of spontaneous intraparenchymal hemorrhage, especially in elderly, normotensive, often demented individuals. 3'5'7"9In contrast to the hypertensive hemorrhages which are pre460
dominantly in the basal ganglia, pons, or cerebellum, hemorrhages from amyloid angiopathy tend to be near the cortical surface in the parietal or occipital area. 6 The patient presented here had an acute hemorrhage in the deep occipital lobe with multiple small cortical hemorrhages.
Magnetic Resonance Imaging Appearance There are no specific MR imaging characteristics of amyloidosis. As a matter of fact, review of the literature does not reveal any thorough investigation of radiological characteristics of amyloid angiopathy. Drayer, ~ in his report on the imaging of the aging brain, discusses cerebral amyloid angiopathy in the context of intracerebral hematoma with an MR image of the lobar hematoma. The present report discusses the MR imaging presentation of cerebral amyloid angiopathy. Although not specific, MR imaging demonstrates that cerebral amyloid angiopathy can present as multiple intracranial lesions. These lesions are especially well visualized on the T2-weighted images. They most likely represent areas of multiple cortical and subcortical punctate hemorrhages in different stages of evolution. Another important point is the lack of enhancement of the multiple intracranial lesions. Multiple cerebral lesions related to an inflammatory or neoplastic process usually demonstrate contrast enhancement. Thus, the above MR imaging findings in an elderly normotensive patient with a spontaneous hemorrhage should raise the possibility of cerebral amyloid angiopathy. References
I. Drayer BP: Imaging of the aging brain. Part I. Normal findings. Radiology 166:785-796, 1988 2. Frangione B: Systemic and cerebral amyloidosis. Ann Med 21:69-72, 1989 3. Gilbert J J, Vinters HV: Amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. Stroke 14:915-923, 1983 4. Glenner GG, Murphy MA: Amyloidosis of the nervous system. J Neurol Sci 94:1-28, 1989 5. Ishii N, Nishihara Y, Horie A: Amyloid angiopathy and lobar cerebral haemorrhage. J Neurol Neurosurg Psychiatry 47:1203-1210, 1984 6. Rengachary SS, Racela LS, Watanabe I, et al: Neurosurgical and immunological implications of primary cerebral amyloid (congophilic) angiopathy. Neurosurgery 7:1-9, 1980 7. Torack RM: Congophilic angiopathy complicated by surgery and massive hemorrhage. A light and electron microscopic study'. Am J Pathol 81:349-366, 1975 8. Tucker WS, Bilbao JM, Klodawsky H: Cerebral amyloid angiopathy and multiple intracerebral hematomas. Neurosurgery 7:611-614, 1980 9. Tyler KL, Poletti CE, Heros RC: Cerebral amyloid angiopathy with multiple intracerebral hemorrhages. Case report. J Neurosurg 57:286-289, 1982 Manuscript received July 3 I, 1990. Accepted in final form January 4, 1991. Address reprint requests to: Rand M. Voorhies, M.D., Department of Neurosurgery, Ochsner Foundation Hospital, 1514 Jefferson Highway, New Orleans, Louisiana 70121.
J. Neurosurg. / Volume 75/September, 1991
Cerebral amyloid angiopathy presenting as multiple intracranial lesions on magnetic resonance imaging Case report DEEPAK AWASTHI, M.D., RAND M. VOORHIES, M.D., JOHN EICK~ M.D., AND WILLIAM T. MITCHELL, M.D. Department of Neurosurgery, Louisiana State University Medical Center, and Departments of Neurosurgery, Radiology, and Pathology, Ochsner Foundation Hospital New Orleans, Louisiana v, Cerebral amyloid angiopathy is recognized as an important cause of spontaneous intracerebral hemorrhage in the elderly normotensive patient. Magnetic resonance (MR) imaging characteristics of this disease entity are rarely mentioned in the literature. The MR imaging findings of an elderly normotensive patient presenting with an acute spontaneous intracerebral hemorrhage secondary to amyloid angiopathy are reported and a brief review of amyloidosis is presented. KEY WORDS
amyloidosis magnetic resonance imaging "
9 amyloid angiopathy 9 intracerebral hemorrhage 9
p
RIMARY cerebral amyloid angiopathy is a subset of cerebral amyloidosis characterized by deposition of amyloid substance in the walls of the cerebral and leptomeningeal vessels. 2 Cerebral amyloid angiopathy has been reported in association with spontaneous intracerebral hemorrhages in normotensive patientsY -9 These hemorrhages tend to be lobar and can be multipleJ '8'9Magnetic resonance (MR) imaging findings of this disease entity are rarely mentioned in the literature. This report describes the MR imaging appearance of cerebral amyloid angiopathy presenting as multiple intracranial lesions. A brief review of amyloidosis is also presented.
Case Report This 78-year-old right-handed white woman was noted to have an acute onset of confusion followed by a brief generalized tonic-clonic seizure. Her medical history was significant for headaches and intermittent confusional episodes during the year prior to admission. There was no history of hypertension, vasculitis, neoplasms, cerebrovascular disease, or trauma. Evaluation at another hospital revealed an agitated, confused, and combative woman with no focal neurological deficits. She was transferred to Ochsner Foundation Hospital after computerized tomography (CT) had revealed a small fight-sided occipital hemorrhage. 458
Examination. On arrival, the patient continued to be confused and agitated. She had no focal neurological deficits; however, neurological examination on the following day revealed mild motor dysphasia, finger agnosia on the right, and left-right confusion. She was less agitated and more lucid than on admission. The multiplicity of neurological findings not corresponding to the area of the hemorrhage led us to obtain a repeat CT scan with contrast enhancement and eventually an MR image with and without contrast enhancement. Precontrast CT of the head demonstrated a 1.5 x lcm intraparenchymal hemorrhage in the right occipital re#on adjacent to the atrium of the right lateral ventricle (Fig. 1). The MR appearance was very unusual and not characteristic of any disease process (Fig. 2). These images demonstrated multiple intracranial lesions. As documented in the CT scan, there was an oval wellcircumscribed area in the right anterior occipital region adjacent to the atrium of the right lateral ventricle with signal characteristics of a recent hemorrhage (Fig. 2). Innumerable subcortical punctate areas of hypointensity were seen on the T2-weighted images, which were not observed on the Tl-weighted images or the CT scan. Following intravenous administration of contrast medium, there was no contrast enhancement. The signal from the posterior fossa structures was unremarkable. The diagnostic possibilities of these images included J. Neurosurg. / Volume 75/September, 1991
Cerebral amyloid angiopathy
FIG. 3. Photomicrograph of the right frontal cortical surface demonstrating several brownish oval punctate lesions (arrowheads). These lesions represent areas of hemorrhage secondary to cerebral amyloid angiopathy. FIG. I. Noncontrast computerized tomography scan demonstrating a 1.5 x 1-cm intraparenchymal hemorrhage in the right anterior occipital region (black arrowhead). neoplasms (metastatic or multifocal glioma), multiple hemorrhages, or an inflammatory or infectious process.
Operation. Based on the above differential diagnosis and lack of specificity of the diagnostic studies (CT scans, MR images, results of lumbar puncture, and electroencephalograms), the patient was taken to surgery and a right frontal craniotomy with open cortical biopsy was performed. Upon opening of the dura, three small brownish oval punctate lesions were seen on the cortical surface (Fig. 3). One of these lesions was biopsied in the routine manner. Sections of the cortical
FIG. 2. Magnetic resonance T2-weighted (TR 2600 msec, TE 90 msec) axial images. Left: Cut approximating the level of the computerized tomography scan, shown in Fig. 1, demonstrating the fight occipital hemorrhage (black arrowhead). In addition, several punctate areas of hypodensity are seen in this image (white arrowhead). Right: Image demonstrating innumerable subcortical punctate areas of hypodensity (arrowheads). These lesions represent multiple punctate hemorrhages.
J. Neurosurg. / Volume 75/September, 1991
brain biopsy revealed a small area of hemorrhage just beneath the pia in the cortex. Within the surrounding neuropil, the small blood vessels demonstrated variable homogeneous eosinophilic stains suggestive of amyloid which was confirmed by staining with Congo red dye and birefringence (Fig. 4). Postoperative Course. The postoperative course was uneventful. On discharge, the patient was alert and oriented with significant improvement in her dysphasia. She had no focal motor or sensory loss upon discharge.
Discussion Amyloidosis denotes a disease complex with the unifying feature of deposition in tissues of nonbranching fibrillar proteins having the common crystallographic characteristics of a beta-pleated sheet? This betapleated sheet conformation is responsible for its characteristic staining by Congo red dye and subsequent green birefringence when viewed through a polarized microscope.
FIG. 4. Photomicrograph of the surgical specimen demonstrating the characteristic birefringence (arrowhead) of amyloid in this stain viewed under the polarized microscope. Congo red, x 200. 459
D. Awasthi, et al. Classification of Amyloidosis Human amyloidosis is associated with multiple pathological conditions having diverse etiologies. Amyloidosis can be classified on the basis of clinical presentation and/or biochemical composition of the amyloid protein. 2 Clinically, it is useful to divide amyloidosis into systemic or localized disease. Systemic amyloidosis can be further subdivided into: 1) primary amyloidosis (no evidence of pre-existing or coexisting disease); 2) amyloid associated with multiple myeloma; 3) secondary or reactive amyloidosis associated with chronic infectious diseases (such as osteomyelitis, tuberculosis, or leprosy) or chronic inflammatory diseases (such as rheumatoid arthritis or ankylosing spondylitis); 4) heredofamilial amyloidosis associated with familial Mediterranean fever and a variety of neuropathic, renal, cardiovascular, and other syndromes; 5) amyloidosis associated with long-term hemodialysis; 6) familial amyloid polyneuropathy; and 7) systemic senile amyloidosis. Localized amyloidosis can be subdivided into endocrine and cerebral types. In endocrine-related amyloidosis, deposits consist of prehormonal or preprohormonal precursor proteins. The endocrine type of amyloidosis consists of tumor-like deposits in isolated organs without evidence of systemic involvement. This includes: 1) medullary carcinoma of the thyroid (procalcitonin); 2) pancreatic islet amyloidosis associated with insulinoma and diabetes mellitus; and 3) atrial amyloidosis (atrial natriuretic protein). Localized cerebral amyloidosis consists of amyloid deposits restricted to the central nervous system (CNS). It includes: 1) Alzheimer's disease; 2) Down's syndrome; 3) Parkinson-dementia of Guam; 4) sporadic cerebral amyloid angiopathy; 5) inherited forms of cerebrovascular amyloidosis (familial cerebral amyloid angiopathy), both the Dutch type and the Icelandic type; and 6) spongiform encephalopathies (CreutzfeldtJakob disease and kuru).
Amyloid Angiopathy The patient reported here exhibited the MR imaging findings of sporadic cerebral amyloid angiopathy. Three forms of amyloid deposits have been recognized in the CNS? They are: 1) the amyloid core of senile plaque; 2) deposits in the arterial and arteriolar walls of cortical and leptomeningeal vessels (congophilic angiopathy); and 3) deposits in the capillary and arteriolar walls with extension into the surrounding brain parenchyma (dysphoric angiopathy). 5 The latter two conditions are together called "amyloid angiopathy." Amyloid angiopathy is frequently present in the cerebral vessels of elderly patients and its incidence increases with age.~ There is a close relationship between amyloid angiopathy and intracerebral hematoma. Amyloid angiopathy is one of the causes of spontaneous intraparenchymal hemorrhage, especially in elderly, normotensive, often demented individuals. 3'5'7"9In contrast to the hypertensive hemorrhages which are pre460
dominantly in the basal ganglia, pons, or cerebellum, hemorrhages from amyloid angiopathy tend to be near the cortical surface in the parietal or occipital area. 6 The patient presented here had an acute hemorrhage in the deep occipital lobe with multiple small cortical hemorrhages.
Magnetic Resonance Imaging Appearance There are no specific MR imaging characteristics of amyloidosis. As a matter of fact, review of the literature does not reveal any thorough investigation of radiological characteristics of amyloid angiopathy. Drayer, ~ in his report on the imaging of the aging brain, discusses cerebral amyloid angiopathy in the context of intracerebral hematoma with an MR image of the lobar hematoma. The present report discusses the MR imaging presentation of cerebral amyloid angiopathy. Although not specific, MR imaging demonstrates that cerebral amyloid angiopathy can present as multiple intracranial lesions. These lesions are especially well visualized on the T2-weighted images. They most likely represent areas of multiple cortical and subcortical punctate hemorrhages in different stages of evolution. Another important point is the lack of enhancement of the multiple intracranial lesions. Multiple cerebral lesions related to an inflammatory or neoplastic process usually demonstrate contrast enhancement. Thus, the above MR imaging findings in an elderly normotensive patient with a spontaneous hemorrhage should raise the possibility of cerebral amyloid angiopathy. References
I. Drayer BP: Imaging of the aging brain. Part I. Normal findings. Radiology 166:785-796, 1988 2. Frangione B: Systemic and cerebral amyloidosis. Ann Med 21:69-72, 1989 3. Gilbert J J, Vinters HV: Amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. Stroke 14:915-923, 1983 4. Glenner GG, Murphy MA: Amyloidosis of the nervous system. J Neurol Sci 94:1-28, 1989 5. Ishii N, Nishihara Y, Horie A: Amyloid angiopathy and lobar cerebral haemorrhage. J Neurol Neurosurg Psychiatry 47:1203-1210, 1984 6. Rengachary SS, Racela LS, Watanabe I, et al: Neurosurgical and immunological implications of primary cerebral amyloid (congophilic) angiopathy. Neurosurgery 7:1-9, 1980 7. Torack RM: Congophilic angiopathy complicated by surgery and massive hemorrhage. A light and electron microscopic study'. Am J Pathol 81:349-366, 1975 8. Tucker WS, Bilbao JM, Klodawsky H: Cerebral amyloid angiopathy and multiple intracerebral hematomas. Neurosurgery 7:611-614, 1980 9. Tyler KL, Poletti CE, Heros RC: Cerebral amyloid angiopathy with multiple intracerebral hemorrhages. Case report. J Neurosurg 57:286-289, 1982 Manuscript received July 3 I, 1990. Accepted in final form January 4, 1991. Address reprint requests to: Rand M. Voorhies, M.D., Department of Neurosurgery, Ochsner Foundation Hospital, 1514 Jefferson Highway, New Orleans, Louisiana 70121.
J. Neurosurg. / Volume 75/September, 1991
