Journal of Neurology J Neurol (1988) 235 : 435-437 © Springer-Verlag 1988 Cerebral amyloid angiopathy with attenuation of the white matter on CT scans: subcortical arteriosclerotic encephalopathy (Binswanger) in a normotensive patient A . Bogucki I, W. Papierz 2, R. Szymahska t, and R. Staniaszczyk3 Departments of 1Neurology, 2Pathology and 3Diagnostic Imaging, Medical Academy, Kopciflskiego 22, PL 90-153 L6d~,, Poland Summary. Subcortical arteriosclerotic encephalopathy was diagnosed in a 56-year-old female normotensive patient with gradually progressing dementia, pseudobulbar palsy and motor deficits. CT scan showed white matter low attenuation in the frontal and parietal lobes. Neuropathological examination revealed degeneration of the white matter. Amyloid was found in walls of small cortical vessels. The walls of small vessels in the white matter showed severe thickening, fibrosis and hyalinization but not amyloid. Cerebral amyloid angiopathy may be responsible for subcortical arteriosclerotic encephalopathy. Key words: Subcortical arteriosclerotic encephalopathy - Cerebral amyloid angiopathy - Normotensive subject The term subcortical arteriosclerotic encephalopathy (SAE) was introduced by Olszewski [13] for the disease whose clinical picture was described by Binswanger [1]. Olszewski defined its pathological features as extensive hyalinization and intimal fibrosis in the long penetrating arteries and arterioles, multiple small infarcts in basal ganglia and subcortical white matter and diffuse loss of myelinated fibres in the latter with sparing of U-fibres. The clinical picture of S A E is non-specific [4]. The diagnosis in life became possible with computed tomography (CT) [10, 14]. CT in S A E reveals low attenuation of deep hemispheric white matter. SAE is usually related to systemic hypertension [4]. Its emergence in normotensive patients with a typical clinical and CT picture should be carefully evaluated. Case report A female patient had worked in a nickel-plating workshop before she retired prematurely at age 52. A t that time frequent falls, dropping objects out of her hands, and worsening memory were noted. Intellectual deterioration with periods of transient improvement progressed gradually. Two years later the patient became house bound and unable to prepare a meal. Her speech was slow. A t age 54 she was found to have CSF protein 160 mg/dl and an abnormal E E G with bilateral delta slowing. 99mTc brain scans were normal. There were no focal neurological deficits. A slight temporary improvement in intellectual function occurred and lasted some months. Later the patient became dysarthric and had a series of grand mal seizures. CT scan showed severe symmetrical hypodense lesions of the white matter. Offprint requests to: A. Bogucki A t age 56 she was admitted to the Department of Neurology, Medical Academy in Lbd~. She was oriented and gave her date of birth but did not know her age. She demonstrated temporal disorientation. She could find her way to bed and the toilet and feed and dress herself. She was not incontinent. Psychomotor retardation, apathy and difficulty in sustaining attention were prominent. The score on the Dementia Scale [2] was 14 and that on Information-Memory-Concentration Test [2] was 19. There was bilateral palatal weakness, worse on the left, and fight central facial weakness. She was dysarthric but had no difficulty swallowing. A slight weakness of the right arm was associated with mild hyper-reflexia. The strength of the lower extremities was preserved with exaggerated ankle tendon refexes. The right plantar response was extensor. The gait was apraxic. The blood pressure was 140/85 on admission and there was no previous documentation of hypertension. Laboratory data, including complete blood count, V D R L test, glucose tolerance test and total cholesterol level, were normal. E C G showed mild ischaemic changes without any evidence of left ventricular hypertrophy. Doppler ultrasonography revealed a symmetrically reduced flow in the carotid arteries. E E G revealed diffused slowing of background activity with bilateral periodic delta waves. CT scan (Figs. 1, 2) revealed diffuse decreased attenuation of deep white matter in the frontal and parietal lobes on both sides. There was only slight widening of the sulci and no ventricular enlargement (Evans index 0.29). The CT white matter changes had progressed when compared with the scans made 5 months earlier. On the 10th day of hospitalization the patient suddenly became immobile, incontinent and more dysarthric. Prominent dysphagia developed and she had to be fed by stomach tube. She died 9 days later of bilateral bronchopneumonia. Pathology Autopsy revealed bronchopneumonia of the lower lobes and moderate atherosclerosis of the aorta and coronary arteries. There was no left ventricular hypertrophy. Only slight atherosclerosis was found in the carotid and vertebral arteries. The brain after fixation weighed l190g. Slight, diffuse fibrosis of the leptomeninges was observed. Coronal slicing showed a small cystic defect (3 x 6 mm) in the white matter of the left frontal lobe. There were no lesions in the brain stem, cerebellum and spinal cord. Histological slides were stained with haematoxylin-eosin, Congo-red and according to the methods of Bodian, van Gieson, Gordon-Sweet, Kluver-Barrera and Heidenhain. 436 j O o O D D 8 6a Figs. 1, 2. CT scan. Low white matter attenuation in frontal and parietal lobes. Slight widening of the sulci without ventricular dilatation Fig. 3. The frontal lobe. Diffuse pallor of the white matter with relatively spared U-fibres. Heidenhain, × 1.5 Fig. 4. Pallor and rarefaction of the white matter. Kluver-Barrera, × 100 Fig. 5. The frontal white matter. Sclerosed walls and narrowed lumina of small arteries. H & E, × 100 Fig. 6. a Small arteries of the cerebral cortex. Thickening of the walls. H & E, x 250. b The same arteries: amyloid birefringence under polarized light. Congo red, × 250 T h e r e was diffuse r e d u c t i o n of m y e l i n a t e d n e r v e fibres in the white m a t t e r of the c e r e b r a l h e m i s p h e r e s (Fig. 3) a n d to a lesser e x t e n t also in the c e r e b e l l u m . S o m e pallor of the lateral a n d a n t e r i o r funiculi of t h e spinal cord was present. T h e Ufibres were relatively well p r e s e r v e d . Microscopically the w h i t e m a t t e r r a r e f a c t i o n r e s e m b l e d the late effect of o e d e m a (Fig. 4). M i n i m a l sclerotic c h a n g e s were s e e n in large arteries, w h e r e a s m a n y small arteries a n d arterioles of the b r a i n , cere- b e l l u m and t h e i r l e p t o m e n i n g e s s h o w e d severe thickening (fibrosis and hyalinization) of t h e i r walls (Figs. 5 , 6 a ) . T h e walls of the majority of these arteries in the m e n i n g e s a n d cortex s h o w e d amyloid (Fig. 6b). Some affected cortical vessels were occluded with t h r o m b i (usually old-organized ones) a n d s u r r o u n d e d by small areas of i n c o m p l e t e necrosis. In some places perivascular spaces c o n t a i n e d few erythrocytes, h a e m o siderin-laden m a c r o p h a g e s a n d / o r lymphocytes. T h e latter 437 were also seen in the leptomeninges. Blood vessels of the brain stem and spinal cord were generally free of changes except that some leptomeningeal arteries showed slightly fibrotic walls. The cerebral cortex showed both focal and mild diffuse loss of neurons and small, dispersed areas of perivascular scarfing. Senile plaques or neurofibrillary tangles were not present. The grey matter of the basal ganglia, cerebellum, brain stem and spinal cord was not involved. Discussion The pattern of illness of the presented case was typical for SAE. The patient had been exposed to cyanide for several years but her health worsened even after she retired and the neuropathological picture of white matter lesion in cyanide intoxication is different from that found. Dementia, white matter degeneration and cerebral amyloid angiopathy (CAA) coexist in some neuropathological conditions. C A A is a common finding in Alzheimer's disease [5] and the amyloid 13-protein has been identified in both cerebrovascular and plaque amyloid [15, 16]. In Alzheimer's disease, besides congophilic angiopathy in the cerebral cortex the fibrohyaline degeneration may be observed in subcortical arterioles. It occurs in normotensive subjects and is associated with diffuse loss of myelin and scattered infarction in the white matter [3]. Leucoencephalopathy similar to that observed in SAE may be found in elderly normotensive patients with C A A leading to cerebral haemorrhage. In such cases congophilic deposits were seen in small arterial vessels of leptomeninges and cerebral cortex but the arterioles of the white matter did not contain amyloid [9]. We suggest that amyloid deposits in cortical segments of the long penetrating arterioles may be partially responsible for hypoperfusion and hypoxaemia of the deep white matter in our case. Arteriosclerotic thickening of deep perforating vessels with prominent medial hypertrophy is typical of SAE pathology. Vascular changes are presumed to be related to the systemic hypertension and they are similar to those observed in hypertensive encephalopathy. However, hypertrophy of the media of small white matter arteries was found by Okeda [12] to be more pronounced in SAE. In some well-documented cases, however, hypertension was never found [4, 6, 11] and probably other factors were responsible for severe arteriosclerosis. White matter degeneration is the most characteristic pathological feature of SAE. Its pathogenesis remains unknown. It is unclear why the ischaemia in SAE causes diffuse loss of myelinated fibres as well as lacunes. The following hypotheses were proposed by Caplan and Schoene [4]: (1) SAE represents a special type of vascular disease (as suggested by Okeda's study [12]); (2) arteriosclerotic changes reduce the blood flow in subcortical regions and a fall from a raised blood pressure may cause partial ischaemia in wide areas; (3) SAE is a form of hypertensive encephalopathy and local fluid transsudation in which focal cerebral oedema and hypoxia are responsible for the white matter changes (as proposed by Feigin et al. [7, 8]). The absence of hypertension in our case should be noted. Measured blood pressure was never elevated and no indirect pathological features of hypertension (left heart hypertrophy) were found. It is suggested that hypoperfusion and hypoxia are the important factors responsible for development of SAE and the concept of SAE as a late effect of cerebral oedema in systemic hypertension is rather unlikely. The pathological changes in the white matter of our case were striking but no lacunes in the basal ganglia and thalami were observed. In the literature we found one similar case: case 4 presented by De Reuck et al. [6]. Lack of involvement of deep grey structures and relatively well preserved cortex confirm the opinion that the white matter disease is responsible for progressive deterioration of intellectual functioning in SAE. Acknowledgement. This paper is part of a study supported by MZ V R-30. References 1. 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Science 235 : 880-884 Received September 14, 1987 / Received in revised form March 16, 1988 / Accepted March 31, 1988