- Email: [email protected]
Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells
674
Case Reports / Journal of Clinical Neuroscience 17 674–676
Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells J.A. Kinsella a,b,*, W. O’Brien b, G.M. Mullins b, J. Brewer c, S. Whyte b a b c
Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children’s Hospital, Trinity College Dublin, Tallaght, Dublin 24, Ireland Department of Neurosciences, Gosford Hospital, Gosford, New South Wales, Australia Department of Anatomical Pathology, Pacific Laboratory Medicine Services, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
a r t i c l e
i n f o
Article history: Received 31 October 2008 Accepted 24 September 2009
Keywords: Primary angiitis Central nervous system Giant cell Mass effect Angiography
a b s t r a c t Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.1,2 Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and/or leptomeninges, similar to that seen in Takayasu’s or giant cell arteritis.1–3 We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis.
1. Case report A previously well 80-year-old right-handed woman presented with a 2-month history of worsening mobility, left-hand weakness and short-term memory impairment. A CT scan 4 weeks earlier showed chronic small vessel ischaemic changes with diffuse atrophy. Her medical history included an ischaemic stroke with excellent recovery, hypercholesterolaemia, schizophrenia, and chronic reactive anaemia. Medications included aspirin/dipyridamole combination, atorvastatin and olanzapine. She was an ex-smoker and a very occasional drinker. On examination, she was alert and orientated with normal vital signs. She scored 17/30 on the Mini-Mental State Examination. Neurological assessment revealed mild left upper limb weakness, mild incoordination in all limbs and brisk upper limb reflexes. Examination was otherwise unremarkable. Routine haematological and biochemical profiles revealed a normocytic normochromic anaemia (haemoglobin 98 g/L), thrombocytosis (platelets 507 109/L), hyponatraemia (sodium 129 mmol/L) and elevated C-reactive protein (34.6 mg/L). A noncontrast CT scan demonstrated extensive right temporoparietal and occipital hypodensity with lateral ventricular compression and midline shift. A contrast-enhanced CT scan demonstrated a small, probable vascular lesion in the right parietal lobe with surrounding oedema, which was suspicious for neoplasm (Fig. 1a). Oral dexamethasone was commenced. A thorough physical examination and a CT scan of the thorax and abdomen were normal. Full vasculitic screening tests for anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, extractable nuclear antigens, anti-double-stranded DNA and complement C3 and C4 were negative. Cerebrospinal fluid analysis showed normal glucose (3.5 mmol/L), mildly elevated protein (0.67 g/L), negative bacterial and fungal cultures, a negative herpes simplex virus polymerase chain reaction and no malignant cells on formal cytology. MRI revealed extensive bilateral vasogenic oedema with significant mass effect, multiple bilateral petechial haemorrhages and extensive chronic white matter ischaemic changes, but no focal * Corresponding author. Tel.: +353 873151924; fax: +353 14143031. E-mail address: [email protected] (J.A. Kinsella).
Ó 2009 Elsevier Ltd. All rights reserved.
mass (Fig. 2a–e). An intracranial magnetic resonance angiogram (MRA) was normal. Cerebral angiography demonstrated normal intracranial vessels (Fig. 1b). A repeat MRI 1 week later showed multiple new foci of acute ischaemia bilaterally with a minor reduction in oedema. A leptomeningeal and cortical biopsy showed focal necrotising vasculitis with giant cells in a superficial cortical blood vessel, consistent with primary cerebral angiitis (Fig. 3a,b). Fibrin was abundant within the vessel walls and giant cells and lymphocytes had infiltrated the vessel walls. Congo red staining for amyloid was negative. The patient reported an episode of jaw claudication 6 months earlier, with spontaneous resolution and no recurrence. However, a temporal artery biopsy was not performed as symptoms were absent during admission and there was no temporal artery tenderness on examination. Treatment was changed to prednisolone 60 mg daily. The patient received one dose of intravenous (iv) cyclophosphamide 1150 mg and a subsequent MRI revealed resolving vasogenic oedema with no new lesions (Fig. 2f). Wholebody MRA showed no evidence of vasculitis. The patient was discharged with mild cognitive impairment. She received two further doses of iv cyclophosphamide 1150 mg before commencing lifelong oral prednisolone and a 2-year course of oral cyclophosphamide. At follow-up the patient was clinically well, with no new lesions visible on MRI. 2. Discussion PACNS is rare and causes symptoms and signs of CNS dysfunction including headache, personality change, cognitive abnormalities, seizures and cranial neuropathies. Laboratory findings include elevated inflammatory markers, particularly the erythrocyte sedimentation rate, and CSF analysis may reveal elevated opening pressure, raised protein levels and/or lymphocytic pleocytosis.1–3 Angiographic findings include focal and/or diffuse small or large vessel changes including beading, occlusions, aneurysms, vessel wall irregularities or, rarely, an avascular area with mass effect. Cerebral angiography is primarily used for diagnosis, although MRA and CT angiography may also be useful. MRA is limited to visualisation of larger cerebral vessels and MRI find-
Case Reports / Journal of Clinical Neuroscience 17 674–676
675
Fig. 1. (a) Contrast-enhanced axial CT scan showing a focal contrast-enhancing vascular lesion in the right parietal lobe with significant surrounding oedema (arrow). (b) Cerebral angiogram (internal carotid artery, lateral view) demonstrating normal intracranial vessels with no definite features of vasculitis. The peripheral apparent ‘‘beading” appearance is due to ‘‘end-on” vessel views.
Fig. 2. (a) Axial T2-weighted MRI demonstrating predominantly posterior bilateral subcortical vasogenic oedema with parietal, frontal and occipital involvement on the right. The area of contrast-enhancement seen on the CT scan did not represent an angioma or arteriovenous malformation on MRI. (b) Axial fluid-attenuated inversion recovery (FLAIR) appearances. (c) Axial gradient echo sequence showing multiple foci of ‘‘blooming” in bilateral cerebral and brainstem distributions representing hypointense haemosiderin deposits consistent with microhaemorrhages (arrows). (d) Axial T1-weighted MRI without gadolinium showing significant mass effect. (e) Axial T1-weighted MRI with gadolinium showing meningeal enhancement posteriorly and over the temporal lobes. (f) Axial FLAIR MRI after treatment with prednisolone and cyclophosphamide demonstrating marked interval reduction in mass effect.
ings include single or multiple infarcts and/or haemorrhages. CT and MRI are less sensitive than angiography in diagnosing PACNS; however, studies have demonstrated the presence of typical PACNS angiographic abnormalities in biopsy-negative cases and, conversely, normal angiographs in biopsy-proven cases.4 Cerebral angiography in PACNS reportedly has a sensitivity of 56% to 90%,2,5–7 and brain biopsy a sensitivity of 53% to 83%.2,7–9 Histopathological changes in PACNS include granulomatous inflammation of small arteries and arterioles, with multinucleated
giant cells, lymphocytes, macrophages and/or granulomas. There may be fibrinoid necrosis in the vessel wall and inflammation in the leptomeningeal and/or parenchymal vessels may be patchy, leading to false-negative biopsies.7,9,10 Differential diagnoses include reversible cerebral vasoconstriction syndrome, although these patients typically present with acute, severe headaches sometimes described as ‘‘thunderclap” in nature.11 Other differentials include secondary cerebral vasculitis (such as that associated with Behçet’s disease, polyarteritis
676
Case Reports / Journal of Clinical Neuroscience 17 674–676
the clinical outcome was not influenced by immunosuppressive therapy.10 Imaging differentials in this instance include encephalitis or meningoencephalitis, gliomatosis cerebri, chronic hypertensive encephalopathy or background amyloid angiopathy. Lumbar puncture in a patient with these imaging appearances should be performed with caution and only after the clinical signs of raised intracranial pressure have been excluded. Several patients and patient series of PACNS have been reported.12–17 However, our patient is unique as, to our knowledge, she is the only reported patient with biopsy-proven PACNS with giant cells with significant cerebral mass effect and a normal angiogram. In angiogram- and biopsy-negative cases of suspected PACNS, where a high index of clinical suspicion exists, it is appropriate to commence immunosuppressive therapy early, as prognosis in untreated PACNS is very poor. References
Fig. 3. (a) Leptomeningeal biopsy showing vessels typical for primary angiitis of the central nervous system within the superficial cortex close to the leptomeningeal surface (hematoxylin and eosin [H&E] 100). (b) Leptomeningeal biopsy demonstrating the cortical vessel wall with infiltrate of giant cells and lymphocytes amid fibrinoid change – features consistent with focal necrotizing vasculitis with giant cells (H&E 400) (This figure is available in colour at www.sciencedirect.com).
nodosa), amyloid angiopathy, other connective tissue disorders including systemic lupus erythematosus, or bacterial infections such as Treponema pallidum and Borrelia burgdorferi. Primary treatment is with immunosuppressive therapy, mainly cyclophosphamide. However, one study found that in a small subset of patients with presumed PACNS and nondiagnostic brain biopsies, doi:10.1016/j.jocn.2009.09.031
1. Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum 1997;40:1189–201. 2. Salvarani C, Brown Jr RD, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol 2007;62:442–51. 3. Calabrese LH, Mallek JA. Primary angiitis of the CNS: report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine 1987;67:20–37. 4. Kadkhodayan Y, Alreshaid A, Moran CJ, et al. Primary angiitis of the central nervous system at conventional angiography. Radiology 2004;233:878–82. 5. Moore PM. Neurological manifestations of vasculitis: update on immunopathogenic mechanisms and clinical features. Ann Neurol 1995;37:S131–41. 6. Vollmer TL, Guarnaccia J, Harrington W, et al. Idiopathic granulomatous angiitis of the central nervous system: diagnostic challenges. Arch Neurol 1993;50:925–30. 7. Duna GF, Calabrese LH. Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system. J Rheumatol:662–7. 8. Alrawi A, Trobe JD, Blavis M, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology 1999;53:858–60. 9. Chu TC, Gray L, Goldstein B, et al. Diagnosis of intracranial vasculitis: a multidisciplinary approach. J Neuropathol Exp Neurol 1998;57:30–8. 10. Alreshaid AA, Powers WJ. Prognosis of patients with suspected primary CNS angiitis and negative brain biopsy. Neurology 2003;61:831–3. 11. Calabrese LH, Dodick DW, Schwedt TJ, et al. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007;146:34–44. 12. Lie JT. Primary (granulomatous) angiitis of the central nervous system: a clinicopathologic analysis of 15 new cases and a review of the literature. Hum Pathol 1992;23:164–71. 13. Beppu T, Inoue T, Nishimoto H, et al. Primary granulomatous angiitis of the central nervous system: findings of magnetic resonance spectroscopy and fractional anisotropy in diffusion tensor imaging prior to surgery. J Neurosurg 2007;107:873–7. 14. Ay H, Sahin G, Saatci I, et al. Primary angiitis of the central nervous system and silent cortical hemorrhages. Am J Neuroradiol 2002;23:1561–3. 15. Salvarani C, Brown RD, Calamia KT, et al. Primary CNS vasculitis with spinal cord involvement. Neurology 2008;70:2394–400. 16. Singh S, John S, Joseph TP, et al. Primary angiitis of the central nervous system: MRI features and clinical presentation. Australas Radiol 2003;47:127–34. 17. Lee SY, Chu K, Park KI, et al. Diffusion-weighted MR findings in isolated angiitis of the central nervous system (IACNS). Acta Neurol Scand 2003;108:346–51.
Case Reports / Journal of Clinical Neuroscience 17 674–676
Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells J.A. Kinsella a,b,*, W. O’Brien b, G.M. Mullins b, J. Brewer c, S. Whyte b a b c
Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children’s Hospital, Trinity College Dublin, Tallaght, Dublin 24, Ireland Department of Neurosciences, Gosford Hospital, Gosford, New South Wales, Australia Department of Anatomical Pathology, Pacific Laboratory Medicine Services, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
a r t i c l e
i n f o
Article history: Received 31 October 2008 Accepted 24 September 2009
Keywords: Primary angiitis Central nervous system Giant cell Mass effect Angiography
a b s t r a c t Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.1,2 Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and/or leptomeninges, similar to that seen in Takayasu’s or giant cell arteritis.1–3 We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis.
1. Case report A previously well 80-year-old right-handed woman presented with a 2-month history of worsening mobility, left-hand weakness and short-term memory impairment. A CT scan 4 weeks earlier showed chronic small vessel ischaemic changes with diffuse atrophy. Her medical history included an ischaemic stroke with excellent recovery, hypercholesterolaemia, schizophrenia, and chronic reactive anaemia. Medications included aspirin/dipyridamole combination, atorvastatin and olanzapine. She was an ex-smoker and a very occasional drinker. On examination, she was alert and orientated with normal vital signs. She scored 17/30 on the Mini-Mental State Examination. Neurological assessment revealed mild left upper limb weakness, mild incoordination in all limbs and brisk upper limb reflexes. Examination was otherwise unremarkable. Routine haematological and biochemical profiles revealed a normocytic normochromic anaemia (haemoglobin 98 g/L), thrombocytosis (platelets 507 109/L), hyponatraemia (sodium 129 mmol/L) and elevated C-reactive protein (34.6 mg/L). A noncontrast CT scan demonstrated extensive right temporoparietal and occipital hypodensity with lateral ventricular compression and midline shift. A contrast-enhanced CT scan demonstrated a small, probable vascular lesion in the right parietal lobe with surrounding oedema, which was suspicious for neoplasm (Fig. 1a). Oral dexamethasone was commenced. A thorough physical examination and a CT scan of the thorax and abdomen were normal. Full vasculitic screening tests for anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, extractable nuclear antigens, anti-double-stranded DNA and complement C3 and C4 were negative. Cerebrospinal fluid analysis showed normal glucose (3.5 mmol/L), mildly elevated protein (0.67 g/L), negative bacterial and fungal cultures, a negative herpes simplex virus polymerase chain reaction and no malignant cells on formal cytology. MRI revealed extensive bilateral vasogenic oedema with significant mass effect, multiple bilateral petechial haemorrhages and extensive chronic white matter ischaemic changes, but no focal * Corresponding author. Tel.: +353 873151924; fax: +353 14143031. E-mail address: [email protected] (J.A. Kinsella).
Ó 2009 Elsevier Ltd. All rights reserved.
mass (Fig. 2a–e). An intracranial magnetic resonance angiogram (MRA) was normal. Cerebral angiography demonstrated normal intracranial vessels (Fig. 1b). A repeat MRI 1 week later showed multiple new foci of acute ischaemia bilaterally with a minor reduction in oedema. A leptomeningeal and cortical biopsy showed focal necrotising vasculitis with giant cells in a superficial cortical blood vessel, consistent with primary cerebral angiitis (Fig. 3a,b). Fibrin was abundant within the vessel walls and giant cells and lymphocytes had infiltrated the vessel walls. Congo red staining for amyloid was negative. The patient reported an episode of jaw claudication 6 months earlier, with spontaneous resolution and no recurrence. However, a temporal artery biopsy was not performed as symptoms were absent during admission and there was no temporal artery tenderness on examination. Treatment was changed to prednisolone 60 mg daily. The patient received one dose of intravenous (iv) cyclophosphamide 1150 mg and a subsequent MRI revealed resolving vasogenic oedema with no new lesions (Fig. 2f). Wholebody MRA showed no evidence of vasculitis. The patient was discharged with mild cognitive impairment. She received two further doses of iv cyclophosphamide 1150 mg before commencing lifelong oral prednisolone and a 2-year course of oral cyclophosphamide. At follow-up the patient was clinically well, with no new lesions visible on MRI. 2. Discussion PACNS is rare and causes symptoms and signs of CNS dysfunction including headache, personality change, cognitive abnormalities, seizures and cranial neuropathies. Laboratory findings include elevated inflammatory markers, particularly the erythrocyte sedimentation rate, and CSF analysis may reveal elevated opening pressure, raised protein levels and/or lymphocytic pleocytosis.1–3 Angiographic findings include focal and/or diffuse small or large vessel changes including beading, occlusions, aneurysms, vessel wall irregularities or, rarely, an avascular area with mass effect. Cerebral angiography is primarily used for diagnosis, although MRA and CT angiography may also be useful. MRA is limited to visualisation of larger cerebral vessels and MRI find-
Case Reports / Journal of Clinical Neuroscience 17 674–676
675
Fig. 1. (a) Contrast-enhanced axial CT scan showing a focal contrast-enhancing vascular lesion in the right parietal lobe with significant surrounding oedema (arrow). (b) Cerebral angiogram (internal carotid artery, lateral view) demonstrating normal intracranial vessels with no definite features of vasculitis. The peripheral apparent ‘‘beading” appearance is due to ‘‘end-on” vessel views.
Fig. 2. (a) Axial T2-weighted MRI demonstrating predominantly posterior bilateral subcortical vasogenic oedema with parietal, frontal and occipital involvement on the right. The area of contrast-enhancement seen on the CT scan did not represent an angioma or arteriovenous malformation on MRI. (b) Axial fluid-attenuated inversion recovery (FLAIR) appearances. (c) Axial gradient echo sequence showing multiple foci of ‘‘blooming” in bilateral cerebral and brainstem distributions representing hypointense haemosiderin deposits consistent with microhaemorrhages (arrows). (d) Axial T1-weighted MRI without gadolinium showing significant mass effect. (e) Axial T1-weighted MRI with gadolinium showing meningeal enhancement posteriorly and over the temporal lobes. (f) Axial FLAIR MRI after treatment with prednisolone and cyclophosphamide demonstrating marked interval reduction in mass effect.
ings include single or multiple infarcts and/or haemorrhages. CT and MRI are less sensitive than angiography in diagnosing PACNS; however, studies have demonstrated the presence of typical PACNS angiographic abnormalities in biopsy-negative cases and, conversely, normal angiographs in biopsy-proven cases.4 Cerebral angiography in PACNS reportedly has a sensitivity of 56% to 90%,2,5–7 and brain biopsy a sensitivity of 53% to 83%.2,7–9 Histopathological changes in PACNS include granulomatous inflammation of small arteries and arterioles, with multinucleated
giant cells, lymphocytes, macrophages and/or granulomas. There may be fibrinoid necrosis in the vessel wall and inflammation in the leptomeningeal and/or parenchymal vessels may be patchy, leading to false-negative biopsies.7,9,10 Differential diagnoses include reversible cerebral vasoconstriction syndrome, although these patients typically present with acute, severe headaches sometimes described as ‘‘thunderclap” in nature.11 Other differentials include secondary cerebral vasculitis (such as that associated with Behçet’s disease, polyarteritis
676
Case Reports / Journal of Clinical Neuroscience 17 674–676
the clinical outcome was not influenced by immunosuppressive therapy.10 Imaging differentials in this instance include encephalitis or meningoencephalitis, gliomatosis cerebri, chronic hypertensive encephalopathy or background amyloid angiopathy. Lumbar puncture in a patient with these imaging appearances should be performed with caution and only after the clinical signs of raised intracranial pressure have been excluded. Several patients and patient series of PACNS have been reported.12–17 However, our patient is unique as, to our knowledge, she is the only reported patient with biopsy-proven PACNS with giant cells with significant cerebral mass effect and a normal angiogram. In angiogram- and biopsy-negative cases of suspected PACNS, where a high index of clinical suspicion exists, it is appropriate to commence immunosuppressive therapy early, as prognosis in untreated PACNS is very poor. References
Fig. 3. (a) Leptomeningeal biopsy showing vessels typical for primary angiitis of the central nervous system within the superficial cortex close to the leptomeningeal surface (hematoxylin and eosin [H&E] 100). (b) Leptomeningeal biopsy demonstrating the cortical vessel wall with infiltrate of giant cells and lymphocytes amid fibrinoid change – features consistent with focal necrotizing vasculitis with giant cells (H&E 400) (This figure is available in colour at www.sciencedirect.com).
nodosa), amyloid angiopathy, other connective tissue disorders including systemic lupus erythematosus, or bacterial infections such as Treponema pallidum and Borrelia burgdorferi. Primary treatment is with immunosuppressive therapy, mainly cyclophosphamide. However, one study found that in a small subset of patients with presumed PACNS and nondiagnostic brain biopsies, doi:10.1016/j.jocn.2009.09.031
1. Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthritis Rheum 1997;40:1189–201. 2. Salvarani C, Brown Jr RD, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol 2007;62:442–51. 3. Calabrese LH, Mallek JA. Primary angiitis of the CNS: report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine 1987;67:20–37. 4. Kadkhodayan Y, Alreshaid A, Moran CJ, et al. Primary angiitis of the central nervous system at conventional angiography. Radiology 2004;233:878–82. 5. Moore PM. Neurological manifestations of vasculitis: update on immunopathogenic mechanisms and clinical features. Ann Neurol 1995;37:S131–41. 6. Vollmer TL, Guarnaccia J, Harrington W, et al. Idiopathic granulomatous angiitis of the central nervous system: diagnostic challenges. Arch Neurol 1993;50:925–30. 7. Duna GF, Calabrese LH. Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system. J Rheumatol:662–7. 8. Alrawi A, Trobe JD, Blavis M, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology 1999;53:858–60. 9. Chu TC, Gray L, Goldstein B, et al. Diagnosis of intracranial vasculitis: a multidisciplinary approach. J Neuropathol Exp Neurol 1998;57:30–8. 10. Alreshaid AA, Powers WJ. Prognosis of patients with suspected primary CNS angiitis and negative brain biopsy. Neurology 2003;61:831–3. 11. Calabrese LH, Dodick DW, Schwedt TJ, et al. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007;146:34–44. 12. Lie JT. Primary (granulomatous) angiitis of the central nervous system: a clinicopathologic analysis of 15 new cases and a review of the literature. Hum Pathol 1992;23:164–71. 13. Beppu T, Inoue T, Nishimoto H, et al. Primary granulomatous angiitis of the central nervous system: findings of magnetic resonance spectroscopy and fractional anisotropy in diffusion tensor imaging prior to surgery. J Neurosurg 2007;107:873–7. 14. Ay H, Sahin G, Saatci I, et al. Primary angiitis of the central nervous system and silent cortical hemorrhages. Am J Neuroradiol 2002;23:1561–3. 15. Salvarani C, Brown RD, Calamia KT, et al. Primary CNS vasculitis with spinal cord involvement. Neurology 2008;70:2394–400. 16. Singh S, John S, Joseph TP, et al. Primary angiitis of the central nervous system: MRI features and clinical presentation. Australas Radiol 2003;47:127–34. 17. Lee SY, Chu K, Park KI, et al. Diffusion-weighted MR findings in isolated angiitis of the central nervous system (IACNS). Acta Neurol Scand 2003;108:346–51.