Original Paper Eur Neurol 1992;32:86-90 Institut für Neuropathologie, Neurologische Klinik, Institut für Pathologie, Justus-Liebig-Universität. Giessen. FRG KeyWords Vasculitis Central nervous system Carotid artery Plasma cells Cerebral infarct Plasmacellular Angiitis of the Brain-Supplying Arteries with Disseminated Cerebral Necroses Abstract A 55-year-old previously healthy woman developed disseminated neurologi­ cal symptoms together with an organic psychosis over a period of several months. The symptoms progressed continuously despite all therapeutic attempts, and finally the patient died in a state of tetraparesis and coma. Brain biopsy showed necrosis and gliosis of the white matter, but no vasculitic changes. Autopsy revealed numerous necroses of the cerebral cortex and white matter. Signs of inflammation were absent throughout the whole brain. The adventitia of the brain-supplying arteries, especially both carotid arteries, showed a marked cellular infiltrate that consisted mainly of plasma cells and foam cells. The findings represent an unusual type of cerebral vasculitis whose etiology and pathogenesis are unknown. Case Report Introduction A wide spectrum of different vasculitic syndromes may affect the central nervous system. Syphilitic arteritis, Takayasu's arteritis and granulomatous giant cell arteritis predominantly affect large and medium-sized blood ves­ sels, whereas many others mainly involve small vessels (e.g. polyarteritis nodosa, allergic granulomatosis, vasculi­ tis of collagen-vascular disease and hypersensitivity vas­ culitis). Isolated angiitis of the CNS is of special interest for neurologists since the brain is the only target organ for the vasculitic process. The development of effective ther­ apeutic modalities necessitates an exact characterization of the different types of vasculitis [1], The present case belongs to a malignant type of large vessel disease and exhibits unusual clinical and morphological features. Received: January 24. 1991 Accepted: March 25. 1991 A 55-year-old woman developed personality changes and a de­ cline of memory and concentration over a period of 5 months. In an external hospital, cerebral vasculitis was diagnosed, and the patient was treated with corticosteroids. In spite of this therapy, the symp­ toms of cognitive decay deteriorated, and focal neurological signs appeared. On admission to the university hospital, attentiveness was deficient, the patient was not orientated concerning time and place. She had left homonymous hemianopia and slight hemiparesis on the left side. The previous history was unremarkable except for a herpes zoster infection located on the right side of the chest 3 years ago. On admission, EEG revealed diffuse slowing with alpha-theta activity. CT scan showed multiple hypodense areas which were scat­ tered in the white matter of both hemispheres and included as well small parts of the cortex. Ti-weighted MRI revealed multiple hyperintense areas which were located mainly in both temporal lobes, in the right basal ganglia and in the central white matter. After injection of gadolinium DTPA. there was an enhancement in left caudate nucleus. The CSF was analyzed several times. The cell count was always normal, the protein content was slightly elevated with marked autochthonous IgG synthesis with oligoclonal banding. The lactate level was normal. Cerebral angiography showed widely normal arter­ ies except for discrete irregularities of the vessel wall of both carotid arteries. These were interpreted as mild atherosclerosis. A discrete Prof. Dr. W. Schachcnmavr Institut für Neuropathologie Amdtstr. 16 D-W-6300 Giessen (FRG) © 1992 S. Karger AG, Basel 0014-3022/92/0322-0086 $2.75/0 Downloaded by: King's College London 137.73.144.138 - 1/14/2019 11:32:24 AM M. Voßkämper a . K. Böhm'0, C.R. Hornig b , F. Franke c , W. Schachenmayr a Fig. 1. a CT scan 5 months after admission to our hospital. Hypodense areas in the right caput nuclei caudati and in both occipital lobes. Multiple lesions in the white matter of both hemispheres, b In­ travenous injection of contrast medium reveals a remarkable en­ hancement in the left caput nuclei caudati. c CT scan 26 days later. showing a large hvpodense zone in the right hemisphere temporopa­ rietal. d One month later. 2 weeks before death, another large hypodense area is visible in the left hemisphere temporoparietal. The bone defect on the right side is secondary to brain biopsy. pericardial elTusion was detected by eehocardiography. The heart valves were unremarkable. Laboratory tests, including red and white blood cell count, ery throcyte sedimentation rate, dotting tests, serum enzyme analysis, thyroid parameters and immunoelectrophoresis revealed no striking abnormalities. There was a slight decrease in IgG and IgM. The serum zoster-lgA level was elevated, whereas zosterIgM was negative. Antibodies against Borrelia burgdorferi could not be detected in the blood and CSF. Lues serology was negative as well. Other laboratory tests for infectious diseases, including HIV, mumps, measles, Epstein-Barr virus, tuberculosis, brucellosis, cryp­ tococcosis and leptospirosis were negative. There was evidence of former contact with toxoplasmosis. Corticosteroid therapy was continued. Acyclovir as well as zoster hyperimmunoglobulin were administered additionally, because a cerebral zoster infection could not be excluded. The disease, how­ ever. progressed despite all therapeutic attempts. Spasticity of all extremities developed, partial motor seizures of the left side as well as generalized seizures occurred. The mental state worsened contin­ uously, leading to a severe organic psychotic syndrome. The neuro­ logical symptoms worsened, and accordingly the EEG showed in­ creased generalized abnormalities. Repeated CT scans revealed an increasing number of larger hvpodense areas without a prcdelcction for certain areas (fig. I). Two months after admission, the patient developed bilateral amaurosis due to ischemic opticopathv. She died in a state of decere­ bration 10 months after the onset of symptoms. Brain Biopsy Histologic examination of a brain biopsy from the right temporal lobe revealed a normal cortex. The un­ derlying white matter was severely affected, showing abundant lipid-laden macrophages together with marked reactive astrogliosis. Only very few lymphocytes and plasma cells were visible. The aspect was that of demyclination and necrosis, but there was no convincing evi­ dence of inflammation. The blood vessels did not show any abnormalities. Immunohistologic and electron-mi­ croscopic studies failed to elucidate the origin of the lesions. General Pathology 87 Downloaded by: King's College London 137.73.144.138 - 1/14/2019 11:32:24 AM There were not pathological findings of the organ sys­ tems. The left carotid artery was occluded by a fresh focal necrosis of the muscular layer. Note the cellular infiltrate that is thrombus. Mild to moderate atherosclerosis was present in the brain-supplying arteries, accompanied by a marked cellular infiltration of the adventitia. This infiltration consisted mainly of plasma cells, macrophages and veryfew lymphocytes. Adjacent parts were characterized by abundant foam cells. There was a segmental necrosis of the media with scanty lymphocytes and plasma cells in the inner layers of the vessel wall. The lamina elastica interna showed some calcified areas. Granulocytes, epi­ thelioid cells, giant cells or eosinophils were not found (fig. 2). Neuro pathological Investigation The brain weighed 1.360 g. The left internal carotid artery was occluded by a recent thrombus that continued into the left middle cerebral artery and caused territorial infarction on the left side. Coronal sections of both hemi­ spheres showed a great number of necrotic lesions which were irregularly distributed in the white and grey matter: more extended necroses were visible in the right corpus striatum, the right temporobasal cortex and the temporooccipital cortex bilaterally. Furthermore, each section contained many small lesions, which were located within the cortex as well as in the centrum semiovale and with some predilection along the subcortical white matter 88 predominantly confined to the adventitia. The close-up view of the periphery of the vessel wall shows the predominance of plasma cells (b) and foam cells in adjacent areas (c). (fig. 3). The infratentorial part was much less affected, the left cerebellum contained only one organized small in­ farct. The spinal cord was unremarkable. Microscopically the cerebral leptomeninges showed occasional plasma cells containing IgG and IgA immunohistologically. There were no granulocytes. The leptomeningeal blood vessels were widely unremarkable: a few macrophages were visible adjacent to the vessel walls. The cortical and subcortical lesions showed a uniform histological pattern of necrosis with abundant lipid-laden macrophages which were sometimes accumulated around small blood vessels. Very few plasma cells were visible. Reactive astrocytosis was present in the adjacent tissue (fig. 4). Foci with fresh nerve cell necroses were compara­ tively rare. No inflammatory infiltrates were visible at any site within the cerebral lesions. The optic chiasm exhibited an incomplete necrosis with macrophages and reactive astrogliosis. Discussion The case described here was characterized by irresist­ ibly progressing cerebral symptoms (mental alterations, focal neurological signs, seizures, bilateral amaurosis) in a Voßkämper/Böhm/Hornig/Franke/ Schachen mavr Plasmacellular Angiitis Downloaded by: King's College London 137.73.144.138 - 1/14/2019 11:32:24 AM Fig. 2. Longitudinal section of the left internal carotid artery, a Mild thickening of the intima. intact lamina elastica interna and 3b 3a > • ... w •.... ' V > •. V ; : » w : *• v . : ■■ .-vît*' ■ : S T fa - K r ' , • *'• Fig. 3. a Recent, almost complete infarct in the territory of the left middle cerebral artery. Infarct of the right internal capsule, upper operculum and basal ganglia. Several organized necrotic lesions of the white matter and many small cortical and subcortical lesions bilaterally, b The close-up view of the right occipital lobe illustrates the multiplicity and irregularity of the lesions. Fig. 4. a, b Histology of the necrotic brain lesions showing macrophages and reactive astrogliosis. Note the absence of in­ flammation. ; ’C . . *• v ; c . AC •' ’ ’ ( ■'' • Ç -. ; C -A y t • • ■•:* " •• • •»* ».• • . • ;• . •v .. i T - 55-year-old female leading to death in a state of coma and spastic tetraparesis within less than 1 year. Despite exten­ sive clinical investigations, it was impossible to establish a definite diagnosis. All laboratory tests for infectious dis­ eases were negative, the erythrocyte sedimentation rate was normal. Postmortem studies showed a great number of irregularly distributed necrotic lesions together with an unusual inflammatory process of the brain-supplying ar­ teries. The findings, however, failed to fulfill the criteria of any of the hitherto described types of cerebral vascular •■•V. . •• : V- , •• ' • i . ' • •. ... / * ' • * » . . •• . *. V - • . * • *• • disease. General arteriosclerosis was very mild, stenoses of the brain-supplying arteries could not be found, throm­ bosis of the left internal carotid artery occurred a few days before death. Both carotid arteries as well as the basilar artery and the components of the circle of Willis showed plasma cells and foam cells at the periphery of the vessel walls together with focal medionecrosis. Granulocytes were absent, lymphocytes were comparatively rare. It seems reasonable to conclude that the multiple cerebral lesions are secondary to the alterations of the arterial 89 Downloaded by: King's College London 137.73.144.138 - 1/14/2019 11:32:24 AM . ./> •. i walls. Other sources of emboli could not be found: the heart was unremarkable at autopsy. In a descriptive sense, this case can be labelled as an angiitis of brain-supplying arteries. Several vasculitic con­ ditions had to be taken into consideration for differential diagnosis, but could be ruled out in view of the clinical and neuropathological findings. In periarteritis nodosa the necrotizing inflammation involves medium-sized and small arteries. The acute lesions show predominantly polymorphonuclear leuko­ cytic infiltration of the vessel wall: later on, the picture changes to mononuclear cell infiltration. The lesions are widespread throughout the body, central nervous system involvement may occur, but is unusual [2, 3], Allergic granulomatosis is characterized by epithelioid cells, giant cells and eosinophils which could not be found in our case. Giant cell arteritis may lead to obstruction of the internal carotid artery [4], but the morphology of giant cell arteritis was not present in our case [1,5]. Hypersensi­ tivity vasculitis involves the arterioles and capillaries, and not medium-sized and large arteries [2, 3]. Occasionally, systemic lupus erythematosus may lead to primarily neu­ ropsychiatrie manifestations, but microinfarcts would then be the result of small vessel angiitis; moreover, anti­ nuclear antibodies were negative in our case. Since the laboratory tests revealed antibody produc­ tion against the zoster virus, zoster vasculitis was to be suspected. The distribution of the lesions and the histopathological features, however, were not comparable to those of cerebral zoster vasculitis [6]. The inflammatory process of the basal cerebral arteries in this case was to some extent similar to the alterations found in Takayasu’s disease [1,7, 8]: however, the aortic arch was unremarkable, and there was only little intima proliferation. On clinical grounds, the normal erythrocyte sedimentation rate and nonrcspondance to steroid ther­ apy helped to exclude this diagnosis. A vasculitic syndrome restricted to the central nervous system has been described as isolated angiitis of the CNS, primary angiitis of the CNS. or granulomatous angiitis of the CNS [9-12], This entity may involve large intracra­ nial vessels and the internal carotids, but has a predilec­ tion for the small leptomeningcal vessels. The histologic details are those of granulomatous angiitis. The clinical course may be benign with corticosteroid treatment [13]. An unusual syndrome of cerebral vasculopathy associ­ ated with hearing loss and retinal arteriolar occlusions has been described by Monteiro et al. [14], Their cases revealed small vessel sclerosis, numerous microinfarcts with lipid-laden macrophages, but no evidence of inflam­ mation and therefore also differ from our findings. We conclude that the vasculitic process in our case has features that distinguish it from other types of cerebral vasculitis. It is characterized by its restriction to the large brain-supplying arteries. The cellular infiltrate of the ves­ sel wall predominantly consists of plasma cells and foam cells. The cerebral infarcts are most probably due to small embolisms originating from the altered vessel walls. The absence of hemorrhages and the great number of small and smallest necroses may raise the question whether multiple emboli from the carotid arteries can sufficiently explain the pathogenesis. The predominance of plasma cells may suggest an additional humoral factor, but it must be admit­ ted that pathogenesis and etiology remain obscure in this case. The clinical course was malignant and resulted in death in less than 1 year from the onset of symptoms. 1 Lie JT: The classification and diagnosis of vas­ culitis in large and medium-sized blood vessels. Pathol Annu 1987;22:125-162. 2 Titus JL., Kim HS: Blood vessels and lymphat­ ics; in Kissane JM (ed) Anderson’s Pathology, ed 9. Saint-Ixtuis. Mosby. 1990, pp 752-803. 3 Peter HH: Vaskulitidcn. Einteilung Pathogenese und Therapie. Dtsch Arztebl 1989;86:2229. 4 Bogousslavsky J. Deruaz JP. Regli F: Bilateral obstruction of internal carotid artery from giant-cell arteritis and massive infarction lim­ ited to the vertebrobasilar area. Eur Neurol 1985;24:57-61. 5 Jellinger K: Giant cell granulomatous angiitis of the central nervous system. J Neurol 1977: 215:175-179. 6 Blue MC. Roscnblum Wl: Granulomatous an­ giitis of the brain with herpes zoster and vari­ cella encephalitis. Arch Pathol Lab Med 1983: 107:126-128. 7 Molnar P, Hegedus K: Direct involvement of intracerebral arteries in Takayasu's arteritis. Acta Neuropathol (Berl) 1984:63:83-86. 8 Rose AG. Sinclair-Smith CC: Takayasu's arter­ itis. A study of 16 autopsy cases. Arch Pathol Lab Med 1980;104:231-237. 9 Calabrese LH, Mallck JA: Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine 1987;67:20-37. 10 Craven RS, French JK: Isolated angiitis of the central nervous system. Ann Neurol 1985:18: 263-265. 11 Launes J. livanainen M, Erkinjuntti T, Vuorialho M: Isolated angiitis of the central ner­ vous system. Acta Neurol Scand 1986:74:108114. 12 Moore PM: Diagnosis and management of iso­ lated angiitis of the central nervous system. Neurology 1989;39:167-173. 13 van Calenbergh F. van den Bergh V. Wilms G: Benign isolated arteritis of the central nervous system. Clin Neurol Neurosurg 1986:88:267— 273. 14 Monteiro MLR, Swanson RA: Coppeto JR, Cuneo RA. DeArmond S, Prusiner SB: A mi­ croangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar occlusions. Neurology I985;35:l 113-1121. 90 Voßkämpcr/Böhm/Hornig/Franke/ Schachenmayr Plasmacellular Angiitis Downloaded by: King's College London 137.73.144.138 - 1/14/2019 11:32:24 AM References