Journal of
J. Neurol. 221,219-224 (1979)
Neurology © by Springer-Verlag 1979
Original Investigations Intracranial Giant Cell Arteritis E. Russi l, M. Aebi 2, R. Kraus-Ruppert 2, and M. Mumenthaler 1 Departments of ] Neurology and 2 Pathology, Inselspital, Bern University, Bern, Switzerland
Summary. A case of giant cell arteritis of intracranial vessels diagnosed by autopsy is described. Giant cell arteritis of the proximal basal brain arteries was exceptionally marked in a man of 60 years. The clinical course, laboratory findings and the pathological alterations of the brain and intracranial blood vessels are described. The case is discussed on the basis of the literature on giant cell arteritis with cerebral symptoms as well as on granulomatous giant cells arteritis of the brain. A separation of these two entities does not seem justified. Key words: Giant cell arteritis - Arteritis, cranial - Granulomatous giant cell arteritis of the brain - Temporal arteritis. Zusammenfassung. Es wird ein Fall von Riesenzellarteriitis der intrakraniellen Gef~ifSe beschrieben, welcher bei der Autopsie diagnostiziert wurde. Bei diesem 60jahrigen Mann war der histologische Befund der Riesenzellarteriitis in den proximalen Abschnitten der Gef~iBe der Gehirnbasis ungew6hnlich ausgepr~igt. Es werden der klinische Verlauf, die Laboratoriumsbefunde und die histologischen Ver~inderungen des Gehirnes und der basalen Hirngef~il3e beschrieben. Der Fall wird anhand der Literatur fiber Riesenzellarteriitis mit zerebralen Symptomen diskutiert unter Einbezug der F~ille tiber granulomat6se Riesenzellarteriitis des Gehirnes. Eine Trennung dieser beiden Krankheitsbilder erscheint den Autoren nicht berechtigt.
The main clinical manifestations of giant cell arteritis are cranial (temporal) arteritis and polymyalgia rheumatica as described in the last century. We recently reviewed these two clinical entities [17]. As a rule large and medium sized cranial arteries are affected, and morphological changes are limited to branches of the external carotid artery. It is however well known that the aorta and its large branches can also show the histological picture of giant cell arteritis [14]. In addition to frequent ophthalmological complications [3, 5] with loss of vision due to Address for offprint requests: Prof. Dr. M. Mumenthaler, Inselspital, Bern University, CH-3010 Bern, Switzerland
0340-5354/79/0221/0219/$1.20
220
E. Russi et al.
a r t e r i a l o c c l u s i o n , c e n t r a l n e r v o u s s y m p t o m s a n d signs d u e to g i a n t cell arteritis o f the e x t r a c r a n i a l p a r t o f the c e r e b r a l c i r c u l a t i o n o r o f the spinal c o r d a r t e r i e s [5a, 23] h a v e r a r e l y b e e n d e s c r i b e d . W e t h e r e f o r e like to p r e s e n t a p e r s o n a l o b s e r v a t i o n a n d discuss m o r p h o l o g i c a l d i a g n o s t i c a n d g e n e r a l aspects.
Case Report A 60-year old white male complained of bifrontal and occipital headache 6 months prior to admission and a weight loss of 10 kg. Diabetes was discovered and treated by diet in December 1976. One month later his vision was blurred. Since March 1977 his personality started to change pregressively. His consciousness became disturbed and he became unsteady on 22 March 1977, and was admitted to a regional hospital the following day. Mild diabetes was confirmed, and physical findings revealed gaze palsy to the left and left motor weakness with bilateral Babinski. Because of an epileptic seizure 5 days later he entered the Neurology Department of Bern University on 29 March 1977. On admission he was dehydrated, restless, awake but sometimes sleepy and disoriented with inappropriate reactions to stimuli. He responded weakly to pain. Respiration was of Cheyne-Stokes type, blood pressure 140/80 mm Hg, heart rate 90min and temperature between 37.4 and 38.0°C. There were no signs of cardiopulmonary insufficiency. Neck movements were free; the temporal artery and other extracranial vessels were inconspicuous. He had increased perioral reflexes, hyperemic conjunctiva, and pupils reactive to light. The ocular fundus, seen only on the left, was normal. There was no longer a gaze palsy and the difference in motility of the extremities haö subsided. Muscular tonus was normal as were the reflexes, but Babinski remained positive on both sides. Laboratory results: sedimentation rate 10 mm in the first hour (maximum on 26 March: 38 mm); Hb 18.1 g%, HKT 54.8% with normal indices, leucocytes 15,300 with normal distribution, thrombocytes 175,000. Quick 100%, lues reaction negative. Electrolytes, total protein, GOT, GPT, CPK normal. Arterial blood gases: pH 7.41, pCO2 45mmHg, pO2 64mmHg, 02 saturation 90.6%, base excess + 3.4 mmol/l. Urea 30 mg%, alkaline phophatase slightly increased. Urine: pH 5, glucose +++, acetone and protein negative. Normal sediment. CSF: pressure 26 cm of CSF, Queckenstedt normal. CSF clear: 30mg% protein, 1 cell/mm 3, mastix normal. EEG: inconstant diffuse generalized abnormality; no side difference, no focal changes, no epileptic potentials. Brain scan: left temporal hyperperfusion. Left carotid angiography normal, including the visible extracranial arteries. Chest X-ray normal. The hospital course was characterized by a changing picture and level of consciousness in spite of rehydratation and insulin medication and large doses of vitamin B1. The patient died 11 April 1977 under the tentative diagnosis of a vascular process in the brain stem.
Material and Methods Specimen of liver, lung and the entire brain (1250g), fixed in buffered 4% neutral formalin were postfixed in the same fixative containing 4% CaCI2. The tissues were embedded in Paraplast. Frozen sections were made, and stained with Oil red O, Sudan black B, Kongo red, hematoxilin/eosin, Weigert's elastic van Gieson, Turnbull's reaction, PAS, and Lendrum's MBS method. According to common practice the PAP method was used for demonstration of immunoglobulins.
Morphologieal Findings Lungs. Lobular, partly necrotizing pneumonia; intimamyofibrosis and elastosis of small arteries which contained mixed thrombotic material.
Intracranial Giant Cell Arteritis
221
Fig. 1A--C. Right middle cerebral artery. A Irregularly damaged internal elastic lamina = 1-1"; Macrophages = 2; proliferated intima = 3; multinucleated giant cells of foreign body type = 4. HE, × 200. B Fragmentation and loss of elastic elements = 1-1"; proliferated intima with fragmentation of elastic lamina = 3; multinucleated giant cells = 4. Weigert's elastic van Gieson, × 80. C Ependymal granulation with eosinophilic Rosenthal fibers. Ventricular ependyma = 1. HE, x 200
Liver. Passive congestion of moderate degree with fatty changes of hepatocytes and vacuolated nuclei; scattered infiltrations of lymphocytes and plasma cells and hemosiderosis of stellate cells in the portal areas.
Central Nervous System. Macroscopically the internal carotid, left anterior cerebral artery, both middle cerebral arteries and the basilar artery showed segmental, greyish and hardened thickening of the vessel walls. The lumina were eccentrically reduced in caliber. Coronal sections through the brain revealed multiple, partly cystic areas of white to brownish softenings measuring up to 20 mm in diameter which were more prominent in the left hemisphere (caudate nucleus, internal capsule, thalamus, cortex of the temporal and parietal lobe) and the internal capsule of the right side. Microscopic examination of various segments of the altered basal arteries revealed foci of intimal proliferation, the lesions containing variable numbers of giant cells of the foreign body
222
E. Russi et al.
type (50 or more nuclei) adjacent to the internal elastic lamina as weil as lymphocytes, plasma cells and macrophages. The internal elastic lamina was fragmented and stained poorly for elastic fibers (Fig. 1B). Immunoglobulin could not be demonstrated. Several leptomeningeal blood vessels contained accumulations of lymphoid cells in the adventitia. In the areas of softening and cavitation within the forebrain an increased number of gitter cells, few siderophages in the border zone and fibrillary gliosis were found. Ependymal granulations were accentuated in the third ventricle and contained glial cells, Lendrum positive eosinophilic Rosenthal fibers and corpora amylacea as well. Based on these morphological findings the diagnosis of giant cell arterities was established.
Diseussion
Cranial arteritis and polymyalgia rheumatica are considered as two main clinical manifestations of giant cell arteritis [1,2, 9, 17, 24]. Peripheral neurological signs and neuropathies [26] are of ischemic etiology and the rare central nervous s y m p t o m s almost always are due to arteritis of an extracranial vessel. The carotid arteries are the site of occlusion [21] as well as the vertebral arteries [27] with secondary brainstem infarction. There are only a few references to giant cell arteritis of the extracranial tracts of cerebral vessels. In 14 postmortems of cranial arteritis and polymyalgia rheumatica Oestberg [19] observed three cases of carotid lesions and 1 thrombosis of the internal caròtid artery. Only one of 16 cases published by the same a u t h o r [20] also showed lesions of the large intracranial arteries at the base of the brain. Wilkinson and Russel [27] reviewed four personal and eight cases in the literature and described the topographic distribution o f histological changes of intra- and extracranial vessels. They stressed the observation that intracerebral arteries never participate in the disease process. Cases with g r a n u l o m a t o u s inflammatory changes involving exclusively the leptomeningeal and intracerebral vessels are known as granulomatous giant cell arteritis [4, 11, 12, 15, 23]. This is well described by Nurick (1972) on the basis o f two personal and 17 cases f r o m the literature [18]. This is a rare, non infectious disease with giant cell arteritis localized in arteries and veins of different size as weil as in capillaries, mostly limited to the central nervous system. Only exceptionally did extracranial vessels also participate. In spite of this remarkable limitation of the histological changes to the vessels of the brain and spinal cord [23] the histological picture of the central nervous system lesions in this disease is quite similar to that seen in giant cell arteritis o f the extracranial vessels. It has therefore been questioned if orte m a y really consider granulomatous giant cell arteritis o f the central nervous system to be a nosological entity [ 12]. Jellinger [ 12] thinks that this disease is simply a particular localization o f giant cell arteritis. The similar histological aspect is one o f the arguments in favor o f this interpretation [ 13]. Other authors argue that the constant limitation of g r a n u l o m a t o u s giant cell arteritis to cerebral vessels and the additional involvement o f small arteries, veins and capillaries point to a nosological entity [6, 15, 18]. In our case, as in most cases o f the literature, the diagnosis was not made ante mortem. There were no signs, no clinical or humoral symptoms suggesting cranial arteritis or other generalized arteriopathy. In our case the morphological
Intracranial Giant Cell Arteritis
223
changes of the brain are weil explained by the findings in the proximal basal arteries and in the intracranial parts of the internal carotid artery. The multiple brain infarctions are due to episodic ischemic lesions. The histological changes were limited to the proximal parts of the anterior, median and basilar arteries in a hitherto unknown degree. No immunoglobulins were found in our material. An ependymitis granularis with Rosenthals fibers has not been described with intracranial giant cell arteritis. Circulating immune complexes entering the cerebrospinal fluid through the choroid plexus could produce a local reaction at the ependymal layer and the underlying glia. Numerous sections of the brain tissue revealed no changes in the small intracerebral arteries. No histological section could be obtained from extracranial arteries. Angiography was negative in our case although changes visible on arteriography are described in the literature [6, 8, 22, 25]. In spite of the normal angiogram we demonstrated significant changes with partial obstruction of the large vessels at the base of the brain. Enzmann described two cases in which angiography showed arteritis [6]. In C r o m p t o n ' s case the arteritis was located in the branches of the ophthalmic artery, the vertebral arteries and other extracranial vessels [5]. The angiographic aspect of cerebral arteritis with localized narrowing and widening of the lumina is not at all specific [6, 25]. A picture similar to giant cell arteritis can be seen in arteritis secondary to collagen diseases, granulomatous giant cell arteritis and metamphetamin arteritis. The first of the two cases described by Enzmann [6] with histologically confirmed giant cell arteritis of the temporal artery could in part successfully be treated with steroids. In the two cases described by Lahl [16] the diagnosis of intracranial giant cell arteritis was made only post mortem. The disease process in these two 42 year-old men was located in the arteries at the base of the brain and leptomeninges which had caused multiple cerebral infarctions as weil as infarctions of the brainstem. These cases as well as those described by Enzmann also had an unspecific prodromal phase with loss of weight, bad general health and headache, which occurred in our case too. In summary giant cell arteritis (arteritis cranialis and polymyalgia rheumatica) is a disease process which is located mainly in large extracranial vessels. The typical histological aspect of this disease which is the same as that of granulomatous giant cell arteritis was found in the intracranial arteries in our patient. There are no strong arguments for separating these two diseases. We think that they are just two different locations of a disease process with identical histological and probably also pathogenetic aspects. The diagnosis of the central nervous localization, as in the case presented here, is clinically difficult. The following points are in favor of this diagnosis: - - subacute and repeated episodes of cerebral ischemia, specially if they point to different locations - - headaches - - general signs and symptoms such as fatigue, loss of weight and fever sometimes high blood sedimentation rate rarely clinical or bioptic symptoms of giant cell arteritis of the temporal artery positive response to corticosteroid treatment. -
-
-
-
-
-
224
E. Russi et al.
References 1. Andrews, J. M.: Giant-cell ("temporal") arteritis. A disease with variable clinical manifestations. Neurology (Minneap.) 16, 963--971 (1966) 2. Appenzeller, O.: Temporal arteritis. Postgrad. Med. 56, 133--141 (1974) 3. Barricks, M. E., Traviesa, D. B., Glaser, J. S., Levy: Ophthalmoplegia in cranial arteritis. Brain 100, 209--221 (1977) 4. Gravioto, H., Feigin, J.: Noninfectious granulomatous angiitis with a predilection for the nervous system. Neurology (Minneap.) 9, 599--609 (1959) 5. Crompton, M. R.: The visual changes in temporal (giant cell) arteritis. Brain 82, 377--390 (1959) 5a. Engelke, W. D., Dörstelmann, D.: Hohes Querschnittssyndrom (C4) durch Riesenzellarteritis (Arteritis temporalis) Horton. Fortschr. Neurol. Psychiat. 47, 91--95 (1979) 6. Enzmann, D., Scott, W. R.: Intracranial involvement of giant cell arteritis. Neurology (Minneap.) 27, 794--797 (1977) 7. Hamrin, B., Jonsson, N., Landberg, T.: Involvement of large vessels in polymyalgia arteritica. Lancet 1965 I, 1193--1196 8. Hinck, V. C., Carter, C. C., Rippey, J. G.: Giant cell arteritis. Am. J. Roentgenol. 92, 769--775 (1964) 9. Hoigné, R., Latscha, U., Mumenthaler, M., et al.: Arteritis temporalis oder Riesenzellarteriitis. Schweiz. med. Wschr. 99, 392--397 (1969) 10. Hollenhorst, R. W., Brown, J. R., Wagener, H. P., Shick, R. M.: Neurologic aspects of temporal arteritis. Neurology (Minneap.) 10, 490--498 (1960) 11. Hughes, J. T., Brownell, B.: Granulomatous giant cell angiitis of the central nervous system. Neurology (Minneap.) 16, 293--298 (1966) 12. Jellinger, K.: Giant cell granulomatous angiitis of the central nervous system. J. Neurol. 215, 175--190 (1977) 13. Jellinger, K.: Granulomatöse Riesenzellangiitis und segmentale noduläre Phlebitis des ZNS. Zbl. allg. Patho. 121, 559 (1977) 14. Klein, R. G., Hunder, G. G., Stanson, A. W., et al.: Large artery involvement in giant cell (temporal) arteritis. Ann. Intern. Med. 83, 806--812 (1975) 15. Kolodny, E. H., Rebeiz, J. J., Caviness, C. V. S. Jr., Richardson, E. P. Jr.: Granulomatous angiitis of the central nervous system. Arch. Neurol. (Chic.) 19, 510--524 (1968) 16. Lahl, R.: Riesenzellarteriitis und ZNS. Schweiz. Archiv. Neurol. Neurochir. Psychiat. 17, 211--239 (1975) 17. Mumenthaler, M.: Giant cell arteritis (cranial arteritis, polymyalgia rheumatica). J. Neurol. 218, 219--236 (1978) 18. Nurick, S., Blackwood, W., Mair, W. G. P.: Giant cell granulomatous angiitis of the central nervous system. Brain 95, 133--142 (1972) 19. Oestberg, G.: Morphological changes in the large arteries in polymyalgia arteritica. Acta Med. Scand. Suppl. 533, 135 (1972) 20. Oestberg, G.: On arteriitis with special reference to polymyalgia arteritica. Acta Path. Microbiol. Scand. Section A, Suppl. 237, 5 (1973) 21. Pollack, M., Blennerhassett, J. B., Clarke, A. M.: Giant cell arteritis and the subclavia steal syndrome. Neurology (Minneap.) 23, 653--657 (1973) 22. Rajjoub, R. K., Wood, J. H., Ommaya, A. K.: Granulomatous angiitis of the brain: a successfully treated case. Neurology (Minneap.) 27, 588--591 (1977) 23. Schraeder, P. L., Lubar, H. S., Thorning, D. R., Dudley, A. W.: Granulomatous arteritis presenting as an acute transvere myelopathy. Wisc. Med. J. 73, 32 (1974) 24. Siegenthaler, W., Siegenthaler, G.: Arteriitis temporalis (Riesenzellarteriitis). Deutsch. med. Wschr. 86, 425--430 (1961) 25. Stanson, A. W., Klein, R. G., Hunder, G. G.: Extracranial angiographic findings in giant cell (temporal) arteritis. Am. J. Roentgenol. 127, 957--963 (1976) 26. Warrell, D. A., Godrey, S., Olsen, E. G. J.: Giant cell arteritis with peripheral neuropathy. Lancet 1968 I, 1010--1013 27. Wilkinson, I., Russel, R.: Arteries of the head and neck in giant cell arteritis. A pathological study to show the pattern of arterial involvement. Arch. Neurol. (Chic.) 27, 378--391 (1972) Received April 2, 1979
J. Neurol. 221,219-224 (1979)
Neurology © by Springer-Verlag 1979
Original Investigations Intracranial Giant Cell Arteritis E. Russi l, M. Aebi 2, R. Kraus-Ruppert 2, and M. Mumenthaler 1 Departments of ] Neurology and 2 Pathology, Inselspital, Bern University, Bern, Switzerland
Summary. A case of giant cell arteritis of intracranial vessels diagnosed by autopsy is described. Giant cell arteritis of the proximal basal brain arteries was exceptionally marked in a man of 60 years. The clinical course, laboratory findings and the pathological alterations of the brain and intracranial blood vessels are described. The case is discussed on the basis of the literature on giant cell arteritis with cerebral symptoms as well as on granulomatous giant cells arteritis of the brain. A separation of these two entities does not seem justified. Key words: Giant cell arteritis - Arteritis, cranial - Granulomatous giant cell arteritis of the brain - Temporal arteritis. Zusammenfassung. Es wird ein Fall von Riesenzellarteriitis der intrakraniellen Gef~ifSe beschrieben, welcher bei der Autopsie diagnostiziert wurde. Bei diesem 60jahrigen Mann war der histologische Befund der Riesenzellarteriitis in den proximalen Abschnitten der Gef~iBe der Gehirnbasis ungew6hnlich ausgepr~igt. Es werden der klinische Verlauf, die Laboratoriumsbefunde und die histologischen Ver~inderungen des Gehirnes und der basalen Hirngef~il3e beschrieben. Der Fall wird anhand der Literatur fiber Riesenzellarteriitis mit zerebralen Symptomen diskutiert unter Einbezug der F~ille tiber granulomat6se Riesenzellarteriitis des Gehirnes. Eine Trennung dieser beiden Krankheitsbilder erscheint den Autoren nicht berechtigt.
The main clinical manifestations of giant cell arteritis are cranial (temporal) arteritis and polymyalgia rheumatica as described in the last century. We recently reviewed these two clinical entities [17]. As a rule large and medium sized cranial arteries are affected, and morphological changes are limited to branches of the external carotid artery. It is however well known that the aorta and its large branches can also show the histological picture of giant cell arteritis [14]. In addition to frequent ophthalmological complications [3, 5] with loss of vision due to Address for offprint requests: Prof. Dr. M. Mumenthaler, Inselspital, Bern University, CH-3010 Bern, Switzerland
0340-5354/79/0221/0219/$1.20
220
E. Russi et al.
a r t e r i a l o c c l u s i o n , c e n t r a l n e r v o u s s y m p t o m s a n d signs d u e to g i a n t cell arteritis o f the e x t r a c r a n i a l p a r t o f the c e r e b r a l c i r c u l a t i o n o r o f the spinal c o r d a r t e r i e s [5a, 23] h a v e r a r e l y b e e n d e s c r i b e d . W e t h e r e f o r e like to p r e s e n t a p e r s o n a l o b s e r v a t i o n a n d discuss m o r p h o l o g i c a l d i a g n o s t i c a n d g e n e r a l aspects.
Case Report A 60-year old white male complained of bifrontal and occipital headache 6 months prior to admission and a weight loss of 10 kg. Diabetes was discovered and treated by diet in December 1976. One month later his vision was blurred. Since March 1977 his personality started to change pregressively. His consciousness became disturbed and he became unsteady on 22 March 1977, and was admitted to a regional hospital the following day. Mild diabetes was confirmed, and physical findings revealed gaze palsy to the left and left motor weakness with bilateral Babinski. Because of an epileptic seizure 5 days later he entered the Neurology Department of Bern University on 29 March 1977. On admission he was dehydrated, restless, awake but sometimes sleepy and disoriented with inappropriate reactions to stimuli. He responded weakly to pain. Respiration was of Cheyne-Stokes type, blood pressure 140/80 mm Hg, heart rate 90min and temperature between 37.4 and 38.0°C. There were no signs of cardiopulmonary insufficiency. Neck movements were free; the temporal artery and other extracranial vessels were inconspicuous. He had increased perioral reflexes, hyperemic conjunctiva, and pupils reactive to light. The ocular fundus, seen only on the left, was normal. There was no longer a gaze palsy and the difference in motility of the extremities haö subsided. Muscular tonus was normal as were the reflexes, but Babinski remained positive on both sides. Laboratory results: sedimentation rate 10 mm in the first hour (maximum on 26 March: 38 mm); Hb 18.1 g%, HKT 54.8% with normal indices, leucocytes 15,300 with normal distribution, thrombocytes 175,000. Quick 100%, lues reaction negative. Electrolytes, total protein, GOT, GPT, CPK normal. Arterial blood gases: pH 7.41, pCO2 45mmHg, pO2 64mmHg, 02 saturation 90.6%, base excess + 3.4 mmol/l. Urea 30 mg%, alkaline phophatase slightly increased. Urine: pH 5, glucose +++, acetone and protein negative. Normal sediment. CSF: pressure 26 cm of CSF, Queckenstedt normal. CSF clear: 30mg% protein, 1 cell/mm 3, mastix normal. EEG: inconstant diffuse generalized abnormality; no side difference, no focal changes, no epileptic potentials. Brain scan: left temporal hyperperfusion. Left carotid angiography normal, including the visible extracranial arteries. Chest X-ray normal. The hospital course was characterized by a changing picture and level of consciousness in spite of rehydratation and insulin medication and large doses of vitamin B1. The patient died 11 April 1977 under the tentative diagnosis of a vascular process in the brain stem.
Material and Methods Specimen of liver, lung and the entire brain (1250g), fixed in buffered 4% neutral formalin were postfixed in the same fixative containing 4% CaCI2. The tissues were embedded in Paraplast. Frozen sections were made, and stained with Oil red O, Sudan black B, Kongo red, hematoxilin/eosin, Weigert's elastic van Gieson, Turnbull's reaction, PAS, and Lendrum's MBS method. According to common practice the PAP method was used for demonstration of immunoglobulins.
Morphologieal Findings Lungs. Lobular, partly necrotizing pneumonia; intimamyofibrosis and elastosis of small arteries which contained mixed thrombotic material.
Intracranial Giant Cell Arteritis
221
Fig. 1A--C. Right middle cerebral artery. A Irregularly damaged internal elastic lamina = 1-1"; Macrophages = 2; proliferated intima = 3; multinucleated giant cells of foreign body type = 4. HE, × 200. B Fragmentation and loss of elastic elements = 1-1"; proliferated intima with fragmentation of elastic lamina = 3; multinucleated giant cells = 4. Weigert's elastic van Gieson, × 80. C Ependymal granulation with eosinophilic Rosenthal fibers. Ventricular ependyma = 1. HE, x 200
Liver. Passive congestion of moderate degree with fatty changes of hepatocytes and vacuolated nuclei; scattered infiltrations of lymphocytes and plasma cells and hemosiderosis of stellate cells in the portal areas.
Central Nervous System. Macroscopically the internal carotid, left anterior cerebral artery, both middle cerebral arteries and the basilar artery showed segmental, greyish and hardened thickening of the vessel walls. The lumina were eccentrically reduced in caliber. Coronal sections through the brain revealed multiple, partly cystic areas of white to brownish softenings measuring up to 20 mm in diameter which were more prominent in the left hemisphere (caudate nucleus, internal capsule, thalamus, cortex of the temporal and parietal lobe) and the internal capsule of the right side. Microscopic examination of various segments of the altered basal arteries revealed foci of intimal proliferation, the lesions containing variable numbers of giant cells of the foreign body
222
E. Russi et al.
type (50 or more nuclei) adjacent to the internal elastic lamina as weil as lymphocytes, plasma cells and macrophages. The internal elastic lamina was fragmented and stained poorly for elastic fibers (Fig. 1B). Immunoglobulin could not be demonstrated. Several leptomeningeal blood vessels contained accumulations of lymphoid cells in the adventitia. In the areas of softening and cavitation within the forebrain an increased number of gitter cells, few siderophages in the border zone and fibrillary gliosis were found. Ependymal granulations were accentuated in the third ventricle and contained glial cells, Lendrum positive eosinophilic Rosenthal fibers and corpora amylacea as well. Based on these morphological findings the diagnosis of giant cell arterities was established.
Diseussion
Cranial arteritis and polymyalgia rheumatica are considered as two main clinical manifestations of giant cell arteritis [1,2, 9, 17, 24]. Peripheral neurological signs and neuropathies [26] are of ischemic etiology and the rare central nervous s y m p t o m s almost always are due to arteritis of an extracranial vessel. The carotid arteries are the site of occlusion [21] as well as the vertebral arteries [27] with secondary brainstem infarction. There are only a few references to giant cell arteritis of the extracranial tracts of cerebral vessels. In 14 postmortems of cranial arteritis and polymyalgia rheumatica Oestberg [19] observed three cases of carotid lesions and 1 thrombosis of the internal caròtid artery. Only one of 16 cases published by the same a u t h o r [20] also showed lesions of the large intracranial arteries at the base of the brain. Wilkinson and Russel [27] reviewed four personal and eight cases in the literature and described the topographic distribution o f histological changes of intra- and extracranial vessels. They stressed the observation that intracerebral arteries never participate in the disease process. Cases with g r a n u l o m a t o u s inflammatory changes involving exclusively the leptomeningeal and intracerebral vessels are known as granulomatous giant cell arteritis [4, 11, 12, 15, 23]. This is well described by Nurick (1972) on the basis o f two personal and 17 cases f r o m the literature [18]. This is a rare, non infectious disease with giant cell arteritis localized in arteries and veins of different size as weil as in capillaries, mostly limited to the central nervous system. Only exceptionally did extracranial vessels also participate. In spite of this remarkable limitation of the histological changes to the vessels of the brain and spinal cord [23] the histological picture of the central nervous system lesions in this disease is quite similar to that seen in giant cell arteritis o f the extracranial vessels. It has therefore been questioned if orte m a y really consider granulomatous giant cell arteritis o f the central nervous system to be a nosological entity [ 12]. Jellinger [ 12] thinks that this disease is simply a particular localization o f giant cell arteritis. The similar histological aspect is one o f the arguments in favor o f this interpretation [ 13]. Other authors argue that the constant limitation of g r a n u l o m a t o u s giant cell arteritis to cerebral vessels and the additional involvement o f small arteries, veins and capillaries point to a nosological entity [6, 15, 18]. In our case, as in most cases o f the literature, the diagnosis was not made ante mortem. There were no signs, no clinical or humoral symptoms suggesting cranial arteritis or other generalized arteriopathy. In our case the morphological
Intracranial Giant Cell Arteritis
223
changes of the brain are weil explained by the findings in the proximal basal arteries and in the intracranial parts of the internal carotid artery. The multiple brain infarctions are due to episodic ischemic lesions. The histological changes were limited to the proximal parts of the anterior, median and basilar arteries in a hitherto unknown degree. No immunoglobulins were found in our material. An ependymitis granularis with Rosenthals fibers has not been described with intracranial giant cell arteritis. Circulating immune complexes entering the cerebrospinal fluid through the choroid plexus could produce a local reaction at the ependymal layer and the underlying glia. Numerous sections of the brain tissue revealed no changes in the small intracerebral arteries. No histological section could be obtained from extracranial arteries. Angiography was negative in our case although changes visible on arteriography are described in the literature [6, 8, 22, 25]. In spite of the normal angiogram we demonstrated significant changes with partial obstruction of the large vessels at the base of the brain. Enzmann described two cases in which angiography showed arteritis [6]. In C r o m p t o n ' s case the arteritis was located in the branches of the ophthalmic artery, the vertebral arteries and other extracranial vessels [5]. The angiographic aspect of cerebral arteritis with localized narrowing and widening of the lumina is not at all specific [6, 25]. A picture similar to giant cell arteritis can be seen in arteritis secondary to collagen diseases, granulomatous giant cell arteritis and metamphetamin arteritis. The first of the two cases described by Enzmann [6] with histologically confirmed giant cell arteritis of the temporal artery could in part successfully be treated with steroids. In the two cases described by Lahl [16] the diagnosis of intracranial giant cell arteritis was made only post mortem. The disease process in these two 42 year-old men was located in the arteries at the base of the brain and leptomeninges which had caused multiple cerebral infarctions as weil as infarctions of the brainstem. These cases as well as those described by Enzmann also had an unspecific prodromal phase with loss of weight, bad general health and headache, which occurred in our case too. In summary giant cell arteritis (arteritis cranialis and polymyalgia rheumatica) is a disease process which is located mainly in large extracranial vessels. The typical histological aspect of this disease which is the same as that of granulomatous giant cell arteritis was found in the intracranial arteries in our patient. There are no strong arguments for separating these two diseases. We think that they are just two different locations of a disease process with identical histological and probably also pathogenetic aspects. The diagnosis of the central nervous localization, as in the case presented here, is clinically difficult. The following points are in favor of this diagnosis: - - subacute and repeated episodes of cerebral ischemia, specially if they point to different locations - - headaches - - general signs and symptoms such as fatigue, loss of weight and fever sometimes high blood sedimentation rate rarely clinical or bioptic symptoms of giant cell arteritis of the temporal artery positive response to corticosteroid treatment. -
-
-
-
-
-
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