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Cerebral demyelination in Wegener’s granulomatosis
Clinical Neurology and Neurosurgery 106 (2004) 233–236
Cerebral demyelination in Wegener’s granulomatosis Vesna V. Brinar a,∗ , Nada Cikes b , Zeljka Petelin a , Marina Hlavati a , Charles M. Poser c a
Department of Neurology, Faculty of Medicine, University of Zagreb, REBRO Hospital Centre, Kispaticeva 12, 10000 Zagreb, Croatia b Section of Immunology, Department of Medicine, Faculty of Medicine, University of Zagreb, Zagreb, Croatia c Department of Neurology, Harvard Medical School, Boston, MA 02215, USA
Abstract A 38-year-old woman with a history of a granulomatous lesion of the nose, developed blurred vision, ataxic gait, and spastic tetraparesis. The presence of demyelination on the brain MRI led to the diagnosis of cerebral demyelination associated with Wegener’s granulomatosis. Pulse cyclophosphamide administration resulted in some clinical of improvement of her condition. Demyelinating lesions seen in Wegener’s have been ascribed to multiple sclerosis, but in this case, they are much more reminiscent of disseminated encephalomyelitis (DEM). The immunological challenge of the underlying disease, may, in the genetically susceptible person, presumably trigger the appearance of MS lesions. Wegener’s granulomatosis must be considered in the differential diagnosis of MS. © 2004 Elsevier B.V. All rights reserved. Keywords: Wegener granulomatosis; Multiple sclerosis; Disseminated encephalomyelitis; MRI
1. Introduction
2. Case report
Wegener’s granulomatosis (WG) is a necrotizing granulomatous vasculitis that can involve virtually any organ. Capillaries as well as small and medium-sized arteries and veins are affected with histopathologic evidence of inflammatory infiltrates in the walls, leading to thrombosis and occlusion of the lumen [1]. The presence of multinucleated cells within the inflammatory infiltrates is a prominent feature of this disorder, and granulomatous lesions with epithelioid histiocytes arranged wound necrotic foci are common findings. It is a multisystem disorder characterized by necrotizing granulomas in the respiratory tract, often associated with glomerulonephritis and a systemic vasculitis [2–6]. The orbits, heart, skin, and joints are also frequently involved [4]. Peripheral neuropathy or mononeuritis multiplex are the commonest nervous system manifestations. Cerebral and meningeal involvement are uncommon and most often result from direct extension of the granulomas from nose and orbits. In addition, demyelinating lesions can occasionally be seen on T2-weighted MRI that have been said to resemble multiple sclerosis [7–9].
In April 2000, a 38-year-old woman had a granulomatous lesion removed from her nose. The histopathological findings were interpreted as being suspect for “midline granuloma.” Tissue analysis performed at the University of Freiburg could not entirely exclude WG. Reconstruction of the nose was carried out in August 2000, but a second operation had to be performed in January 2001 for a recurrence, which was followed by radiotherapy. In October 2001 she developed ataxic gait and visual problems, and was admitted to an outside hospital. Despite a normal chest X-ray and CSF, and a normal angiotensin converting enzyme (ACE) test, she was originally diagnosed as having sarcoidosis. Brain MRI showed multiple demyelinating lesions (Fig. 1). The CSF had 18/3 cells and 46 mg/100 ml of protein, there were no oligoclonal bands, and tests for neurotropic viruses, Borrelia burgdorferi, Treponema pallidum and parasites were all negative. Visual evoked potentials were delayed bilaterally suggestive of lesions in both optic tracts. A stereotaxic biopsy of the left posterior temporal lesion was performed; the histopathological examination revealed chronic inflammation without evidence of granuloma. Following that procedure, the patient became septic and developed severe spastic tetraparesis. Significant clinical improvement resulted from treatment with
∗
Corresponding author. Fax: +385-1-242-1846. E-mail address: [email protected] (V.V. Brinar).
0303-8467/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2004.02.021
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V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
Fig. 1. MRI October 2001.
antibiotics and plasmapheresis. She was diagnosed as having MS. Starting in October 2002 her neurological status gradually worsened, and she had become wheelchair-bound by March 2003, leading to her admission to our service in June 2003. Neurological examination revealed spastic tetraparesis, and horizontal and vertical nystagmus. Brain MRI showed multiple supra- and infratentorial demyelinating lesions, as well as one gadolinium-ring enhancing lesion (Figs. 2 and 3). Her chest X-ray findings and renal function were normal. The serum antineutrophil cytoplasmic antibodies (ANCA), which are specific for WG were negative, as were other immunological tests for vasculitis. Serum ACE activity, which is elevated in 60% of patients with sarcoidosis, was also negative. In spite of the negative cANCA finding, she was diagnosed as having WG due to the clinical presentation, the history of a granulomatous lesion of the nose, and the MRI finding. Corticosteroids aggravated her condition, but she responded to systemic immunosuppressive therapy with intravenous cyclophosphamide given monthly over a 6-month period. She had a partial remission in that, although she is still spastic and tetraparetic, she is able to walk at home.
3. Discussion The American College of Rheumatology (ACR) [10] established criteria for the diagnosis of WG prior to the introduction of the cANCA test. These consist of clinical nasal or oral inflammation, abnormal chest X-ray, urine sediment evidence of glomerulonephritis and a granulomatous lesion established by biopsy. Two or more of these criteria establish the diagnosis of WG with a sensitivity of 88% and a
specificity of 92% [11]. Our patient met the ACR criteria for the diagnosis of WG. The exact pathogenesis of WG is not known, but it is widely believed that immunologic dysfunction plays a major role [12]. It is generally classified among the vasculitides [11]. The nasal cavity and paranasal sinuses are the most common sites of disease activity, where involvement represents a significant feature of the disease. Pulmonary involvement is reported to occur in more than 80% of patients. The kidneys also are a common site of involvement by Wegener’s granulomatosis, causing glomerulonephritis in as many as 75–80% of patients [1]. Involvement of the CNS is rare and is found in only 2–8% of patients [1,4,6]. The commonest neurological manifestation is a peripheral neuropathy consequent to small-vessel vasculitis, and is a frequent clinical manifestation, occurring in 10.6−21.2% of patients [2,4,6,13]. Intracranial abnormalities are caused by three different mechanisms (13). The first, and most frequent is by direct extension of the granulomatous process from the nose, sinuses, orbits, or mastoid air cells [6]. This leads to direct infiltration of the meninges, the cranial nerves, and, rarely, the surface of the brain by the granulomatous process, with symptoms varying with the site of involvement [5,14]. The second mechanism is by means of a vasculitis which produces ischemic and/or hemorrhagic infarctions [6,15]. The last mechanism is the formation of granulomas in the brain parenchyma remote from the primary site of the disease [6]. This type most often presents clinically with seizures [16]. The diagnosis of WG is usually based on the characteristic microscopic changes of a biopsy specimen in a clinically compatible setting [1,17]. Autoantibodies reactive against the cytoplasm of human neutrophils (cANCA) are found in the serum of 85% of WG [17]. The differential diagnosis includes other forms of destructive sinonasal granulomatous disease such as tuberculosis, syphilis or sarcoidosis and the so-called midline granuloma recently redefined as polymorphic reticulosis and identified as a prelymphomatous state. Our patient’s partial response to immunosuppressive therapy is typical [17–19]. The commonest neuroradiological findings in the CNS consist of dural thickening and contrast enhancement seen on both CT and MRI of the mucosa and bone of the paranasal sinuses. This is also a feature of sarcoidosis and may lead to confusion. Angiography usually fails to demonstrate vasculitis, either because it is rare, or because the small affected vessels are not visible; the former is more likely since gadolinium-enhancement should reveal these changes. Nishino et al. [6] noted that “Histologically or radiologically confirmed vasculitis of the CNS in WG is very rare.” In their series of 324 patients with WG, 109 (33.6%) had neurological involvement; the CNS was affected in only 28 (8.6%): 13 had cerebrovascular accidents, 10 had seizures, 5 had vasculitis. In one patient there was “possible association with MS” but neither clinical nor imaging details were given. Murphy
V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
235
Fig. 2. MRI June 2003.
et al. [7] described “non-specific white matter areas of high signal intensity in T2-weighted images” in 10 of the MRIs of 19 WG patients; the lesions were multiple and were seen in the periventricular and subcortical regions, basal ganglia, mesencephalon and pons. Except for an ill-defined pontine lesion no other illustrations were provided, but three of those patients had symptoms of vasculitis, two of them suspected of having had cerebral ischemia and infarction. Asmus et al. [9] had six patients with focal areas of high signal intensity in the white matter and Provenzale and Allen [8] had four such cases.
We have been unable to find any images of cerebral demyelination in WG similar to the ones in our patient. The absence of the typical appearance of vasculitis in the gadolinium-enhanced MR, and the reported rarity of such CNS involvement, militate against it being the underlying cause of the areas of demyelination. The appearance of the lesions is much more reminiscent of disseminated encephalomyelitis (DEM) than of MS. We presume that the cerebral lesion represents either another manifestation of the autoimmune diathesis underlying WG, or the coincidental occurrence of a postinfectious event in an individual
236
V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
Fig. 3. MRI June 2003 with gadolinium-enhancement.
with an abnormal immune system; in genetically susceptible person, it might have triggered the development of MS. There are no reported cases of the documented association between WG and DEM or MS; nevertheless it is possible that some of the cases mentioned by other authors [5,8,9] could be of that type.
References [1] Hoffman G, Kerr G, Leavitt R, Hallahan C, Lebovics R, Travis W, et al. Wegener’s granulomatosis: an analysis of 158 patients. Ann Int Med 1992;116:488–98. [2] Anderson J, Jamieson D, Jefferson J. Non-healing granuloma and the nervous system. Quart J Med 1975;44:309–23. [3] DeRemee R, McDonald T, Harrison Jr E, Coles D. Wegener’s granulomatosis: anatomic correlates, a proposed classification. Mayo Clin Proc 1976;51:777–81. [4] Fauci A, Haynes B, Katz P, Wolff S. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Int Med 1983;98:76–85. [5] Drachman D. Neurological complications of Wegener’s granulomatosis. Arch Neurol 1963;8:145–55. [6] Nishino H, Rubino F, DeRemee R, Swanson J, Parisi J. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 1993;33:4–9. [7] Murphy J, Gomez-Anson B, Gillard J, Antoun N, Cross J, Elliott J, et al. Wegener’s granulomatosis: MR imaging findings in brain and meninges. Radiology 1999;213:794–9.
[8] Provenzale J, Allen N. Wegener’s granulomatosis: CT and MR findings. AJNR 1996;17:785–92. [9] Asmus R, Koltze H, Muhle C, Spielmann R, Duneker G, Noelle B, et al. MRI of the head in Wegener’s granulomatosis. Adv Exp Med Biol 1993;336:319–21. [10] Leavitt R, Fauci A, Bloch D, Michel B, Duncker G, Arend W, et al. The Amercian College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum 1990;33:1101– 7. [11] Scott D, Watts R. Classification and epidemiology of systemic vasculitis. Br J Rheumatol 1994;33:897–9. [12] Wolfff S, Fauci A, Horn R, Dale D. Wegener’s granulonatosis. Ann Int Med 1974;81:513–25. [13] Dwyer J, Janszen V. Wegener’s granulomatosis with intracerebral and nervous system involvement. J Otolaryngol 1981;10:476–80. [14] Goldberg A, Tievsky A, Jamshidi S. Wegener’s granulomatosis invading the cavernous sinus: a CT demonstration. J Comput Assist Tomogr 1983;7:701–3. [15] Satoh J, Miyasaka N, Yamada T, Nishido T, Okuda M, Kuroiwa T, Shinokawa R. Extensive cerebral infraction due to involvement of both anterior cerebral arteries by Wegener’s granulomatosis. Ann Rheum Dis 1988;47:606–11. [16] Miller K, Miller J. Wegener’s granulomatosis presenting as a primary seizure disorder with brain lesions demonstrated by magnetic resonance imaging. Chest 1993;103:316–8. [17] Sneller M. Wegener’s granulomatosis. JAMA 1995;273:1288–91. [18] Sneller M, Hoffman G, Talar-Williams C, Kerr G, Hallahan C, Fauci A. Analysis of forty-two Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995;38:608–13. [19] Duna G, Galperin C, Hoffman G. Wegener’s granulomatosis. Rheum Dis Clin North Am 1995;21:949–86.
Cerebral demyelination in Wegener’s granulomatosis Vesna V. Brinar a,∗ , Nada Cikes b , Zeljka Petelin a , Marina Hlavati a , Charles M. Poser c a
Department of Neurology, Faculty of Medicine, University of Zagreb, REBRO Hospital Centre, Kispaticeva 12, 10000 Zagreb, Croatia b Section of Immunology, Department of Medicine, Faculty of Medicine, University of Zagreb, Zagreb, Croatia c Department of Neurology, Harvard Medical School, Boston, MA 02215, USA
Abstract A 38-year-old woman with a history of a granulomatous lesion of the nose, developed blurred vision, ataxic gait, and spastic tetraparesis. The presence of demyelination on the brain MRI led to the diagnosis of cerebral demyelination associated with Wegener’s granulomatosis. Pulse cyclophosphamide administration resulted in some clinical of improvement of her condition. Demyelinating lesions seen in Wegener’s have been ascribed to multiple sclerosis, but in this case, they are much more reminiscent of disseminated encephalomyelitis (DEM). The immunological challenge of the underlying disease, may, in the genetically susceptible person, presumably trigger the appearance of MS lesions. Wegener’s granulomatosis must be considered in the differential diagnosis of MS. © 2004 Elsevier B.V. All rights reserved. Keywords: Wegener granulomatosis; Multiple sclerosis; Disseminated encephalomyelitis; MRI
1. Introduction
2. Case report
Wegener’s granulomatosis (WG) is a necrotizing granulomatous vasculitis that can involve virtually any organ. Capillaries as well as small and medium-sized arteries and veins are affected with histopathologic evidence of inflammatory infiltrates in the walls, leading to thrombosis and occlusion of the lumen [1]. The presence of multinucleated cells within the inflammatory infiltrates is a prominent feature of this disorder, and granulomatous lesions with epithelioid histiocytes arranged wound necrotic foci are common findings. It is a multisystem disorder characterized by necrotizing granulomas in the respiratory tract, often associated with glomerulonephritis and a systemic vasculitis [2–6]. The orbits, heart, skin, and joints are also frequently involved [4]. Peripheral neuropathy or mononeuritis multiplex are the commonest nervous system manifestations. Cerebral and meningeal involvement are uncommon and most often result from direct extension of the granulomas from nose and orbits. In addition, demyelinating lesions can occasionally be seen on T2-weighted MRI that have been said to resemble multiple sclerosis [7–9].
In April 2000, a 38-year-old woman had a granulomatous lesion removed from her nose. The histopathological findings were interpreted as being suspect for “midline granuloma.” Tissue analysis performed at the University of Freiburg could not entirely exclude WG. Reconstruction of the nose was carried out in August 2000, but a second operation had to be performed in January 2001 for a recurrence, which was followed by radiotherapy. In October 2001 she developed ataxic gait and visual problems, and was admitted to an outside hospital. Despite a normal chest X-ray and CSF, and a normal angiotensin converting enzyme (ACE) test, she was originally diagnosed as having sarcoidosis. Brain MRI showed multiple demyelinating lesions (Fig. 1). The CSF had 18/3 cells and 46 mg/100 ml of protein, there were no oligoclonal bands, and tests for neurotropic viruses, Borrelia burgdorferi, Treponema pallidum and parasites were all negative. Visual evoked potentials were delayed bilaterally suggestive of lesions in both optic tracts. A stereotaxic biopsy of the left posterior temporal lesion was performed; the histopathological examination revealed chronic inflammation without evidence of granuloma. Following that procedure, the patient became septic and developed severe spastic tetraparesis. Significant clinical improvement resulted from treatment with
∗
Corresponding author. Fax: +385-1-242-1846. E-mail address: [email protected] (V.V. Brinar).
0303-8467/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2004.02.021
234
V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
Fig. 1. MRI October 2001.
antibiotics and plasmapheresis. She was diagnosed as having MS. Starting in October 2002 her neurological status gradually worsened, and she had become wheelchair-bound by March 2003, leading to her admission to our service in June 2003. Neurological examination revealed spastic tetraparesis, and horizontal and vertical nystagmus. Brain MRI showed multiple supra- and infratentorial demyelinating lesions, as well as one gadolinium-ring enhancing lesion (Figs. 2 and 3). Her chest X-ray findings and renal function were normal. The serum antineutrophil cytoplasmic antibodies (ANCA), which are specific for WG were negative, as were other immunological tests for vasculitis. Serum ACE activity, which is elevated in 60% of patients with sarcoidosis, was also negative. In spite of the negative cANCA finding, she was diagnosed as having WG due to the clinical presentation, the history of a granulomatous lesion of the nose, and the MRI finding. Corticosteroids aggravated her condition, but she responded to systemic immunosuppressive therapy with intravenous cyclophosphamide given monthly over a 6-month period. She had a partial remission in that, although she is still spastic and tetraparetic, she is able to walk at home.
3. Discussion The American College of Rheumatology (ACR) [10] established criteria for the diagnosis of WG prior to the introduction of the cANCA test. These consist of clinical nasal or oral inflammation, abnormal chest X-ray, urine sediment evidence of glomerulonephritis and a granulomatous lesion established by biopsy. Two or more of these criteria establish the diagnosis of WG with a sensitivity of 88% and a
specificity of 92% [11]. Our patient met the ACR criteria for the diagnosis of WG. The exact pathogenesis of WG is not known, but it is widely believed that immunologic dysfunction plays a major role [12]. It is generally classified among the vasculitides [11]. The nasal cavity and paranasal sinuses are the most common sites of disease activity, where involvement represents a significant feature of the disease. Pulmonary involvement is reported to occur in more than 80% of patients. The kidneys also are a common site of involvement by Wegener’s granulomatosis, causing glomerulonephritis in as many as 75–80% of patients [1]. Involvement of the CNS is rare and is found in only 2–8% of patients [1,4,6]. The commonest neurological manifestation is a peripheral neuropathy consequent to small-vessel vasculitis, and is a frequent clinical manifestation, occurring in 10.6−21.2% of patients [2,4,6,13]. Intracranial abnormalities are caused by three different mechanisms (13). The first, and most frequent is by direct extension of the granulomatous process from the nose, sinuses, orbits, or mastoid air cells [6]. This leads to direct infiltration of the meninges, the cranial nerves, and, rarely, the surface of the brain by the granulomatous process, with symptoms varying with the site of involvement [5,14]. The second mechanism is by means of a vasculitis which produces ischemic and/or hemorrhagic infarctions [6,15]. The last mechanism is the formation of granulomas in the brain parenchyma remote from the primary site of the disease [6]. This type most often presents clinically with seizures [16]. The diagnosis of WG is usually based on the characteristic microscopic changes of a biopsy specimen in a clinically compatible setting [1,17]. Autoantibodies reactive against the cytoplasm of human neutrophils (cANCA) are found in the serum of 85% of WG [17]. The differential diagnosis includes other forms of destructive sinonasal granulomatous disease such as tuberculosis, syphilis or sarcoidosis and the so-called midline granuloma recently redefined as polymorphic reticulosis and identified as a prelymphomatous state. Our patient’s partial response to immunosuppressive therapy is typical [17–19]. The commonest neuroradiological findings in the CNS consist of dural thickening and contrast enhancement seen on both CT and MRI of the mucosa and bone of the paranasal sinuses. This is also a feature of sarcoidosis and may lead to confusion. Angiography usually fails to demonstrate vasculitis, either because it is rare, or because the small affected vessels are not visible; the former is more likely since gadolinium-enhancement should reveal these changes. Nishino et al. [6] noted that “Histologically or radiologically confirmed vasculitis of the CNS in WG is very rare.” In their series of 324 patients with WG, 109 (33.6%) had neurological involvement; the CNS was affected in only 28 (8.6%): 13 had cerebrovascular accidents, 10 had seizures, 5 had vasculitis. In one patient there was “possible association with MS” but neither clinical nor imaging details were given. Murphy
V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
235
Fig. 2. MRI June 2003.
et al. [7] described “non-specific white matter areas of high signal intensity in T2-weighted images” in 10 of the MRIs of 19 WG patients; the lesions were multiple and were seen in the periventricular and subcortical regions, basal ganglia, mesencephalon and pons. Except for an ill-defined pontine lesion no other illustrations were provided, but three of those patients had symptoms of vasculitis, two of them suspected of having had cerebral ischemia and infarction. Asmus et al. [9] had six patients with focal areas of high signal intensity in the white matter and Provenzale and Allen [8] had four such cases.
We have been unable to find any images of cerebral demyelination in WG similar to the ones in our patient. The absence of the typical appearance of vasculitis in the gadolinium-enhanced MR, and the reported rarity of such CNS involvement, militate against it being the underlying cause of the areas of demyelination. The appearance of the lesions is much more reminiscent of disseminated encephalomyelitis (DEM) than of MS. We presume that the cerebral lesion represents either another manifestation of the autoimmune diathesis underlying WG, or the coincidental occurrence of a postinfectious event in an individual
236
V.V. Brinar et al. / Clinical Neurology and Neurosurgery 106 (2004) 233–236
Fig. 3. MRI June 2003 with gadolinium-enhancement.
with an abnormal immune system; in genetically susceptible person, it might have triggered the development of MS. There are no reported cases of the documented association between WG and DEM or MS; nevertheless it is possible that some of the cases mentioned by other authors [5,8,9] could be of that type.
References [1] Hoffman G, Kerr G, Leavitt R, Hallahan C, Lebovics R, Travis W, et al. Wegener’s granulomatosis: an analysis of 158 patients. Ann Int Med 1992;116:488–98. [2] Anderson J, Jamieson D, Jefferson J. Non-healing granuloma and the nervous system. Quart J Med 1975;44:309–23. [3] DeRemee R, McDonald T, Harrison Jr E, Coles D. Wegener’s granulomatosis: anatomic correlates, a proposed classification. Mayo Clin Proc 1976;51:777–81. [4] Fauci A, Haynes B, Katz P, Wolff S. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Int Med 1983;98:76–85. [5] Drachman D. Neurological complications of Wegener’s granulomatosis. Arch Neurol 1963;8:145–55. [6] Nishino H, Rubino F, DeRemee R, Swanson J, Parisi J. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 1993;33:4–9. [7] Murphy J, Gomez-Anson B, Gillard J, Antoun N, Cross J, Elliott J, et al. Wegener’s granulomatosis: MR imaging findings in brain and meninges. Radiology 1999;213:794–9.
[8] Provenzale J, Allen N. Wegener’s granulomatosis: CT and MR findings. AJNR 1996;17:785–92. [9] Asmus R, Koltze H, Muhle C, Spielmann R, Duneker G, Noelle B, et al. MRI of the head in Wegener’s granulomatosis. Adv Exp Med Biol 1993;336:319–21. [10] Leavitt R, Fauci A, Bloch D, Michel B, Duncker G, Arend W, et al. The Amercian College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum 1990;33:1101– 7. [11] Scott D, Watts R. Classification and epidemiology of systemic vasculitis. Br J Rheumatol 1994;33:897–9. [12] Wolfff S, Fauci A, Horn R, Dale D. Wegener’s granulonatosis. Ann Int Med 1974;81:513–25. [13] Dwyer J, Janszen V. Wegener’s granulomatosis with intracerebral and nervous system involvement. J Otolaryngol 1981;10:476–80. [14] Goldberg A, Tievsky A, Jamshidi S. Wegener’s granulomatosis invading the cavernous sinus: a CT demonstration. J Comput Assist Tomogr 1983;7:701–3. [15] Satoh J, Miyasaka N, Yamada T, Nishido T, Okuda M, Kuroiwa T, Shinokawa R. Extensive cerebral infraction due to involvement of both anterior cerebral arteries by Wegener’s granulomatosis. Ann Rheum Dis 1988;47:606–11. [16] Miller K, Miller J. Wegener’s granulomatosis presenting as a primary seizure disorder with brain lesions demonstrated by magnetic resonance imaging. Chest 1993;103:316–8. [17] Sneller M. Wegener’s granulomatosis. JAMA 1995;273:1288–91. [18] Sneller M, Hoffman G, Talar-Williams C, Kerr G, Hallahan C, Fauci A. Analysis of forty-two Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995;38:608–13. [19] Duna G, Galperin C, Hoffman G. Wegener’s granulomatosis. Rheum Dis Clin North Am 1995;21:949–86.