1528
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
[3] Garcia HH, Del Brutto OH, Cysticercosis Working Group in Peru. Neurocysticercosis: updated concepts about an old disease. Lancet Neurol 2005;4:653–61. [4] Salazar Noguera EM, Pineda Sic R, Escoto Solis F. Intramedullary spinal cord neurocysticercosis presenting as brown-sequard syndrome. BMC Neurol 2015;15:1. [5] Verma R, Anand KS, Sharma BB, et al. Neurocysticercosis presenting as parkinsonism. Neurol India 2014;62:110–1. [6] Nash TE, Garcia HH. Diagnosis and treatment of neurocysticercosis. Nat Rev Neurol 2011;7:584–94. [7] Serpa JA, White Jr AC. Neurocysticercosis in the United States. Pathog Glob Health 2012;106:256–60. [8] Flisser A. Taeniasis and cysticercosis due to Taenia solium. Prog Clin Parasitol 1994;4:77–116. [9] Lobato RD, Lamas E, Portillo JM, et al. Hydrocephalus in cerebral cysticercosis. Pathogenic and therapeutic considerations. J Neurosurg 1981;55:786–93. [10] Amelot A, Faillot T. Hydrocephalus and neurocysticercosis: cases illustrative of three distinct mechanisms. J Clin Neurol 2014;10:363–6. [11] Monteiro L, Almeida-Pinto J, Stocker A, et al. Active neurocysticercosis, parenchymal and extraparenchymal: a study of 38 patients. J Neurol 1993;241:15–21. [12] Salazar A, Sotelo J, Martinez H, et al. Differential diagnosis between ventriculitis and fourth ventricle cyst in neurocysticercosis. J Neurosurg 1983;59:660–3. [13] Torres-Corzo J, Rodriguez-della Vecchia R, Rangel-Castilla L. Bruns syndrome caused by intraventricular neurocysticercosis treated using flexible endoscopy. J Neurosurg 2006;104:746–8. [14] Teegala R, Rajesh KG, Raviprasad VY, et al. Emergency neuroendoscopic management of third ventricular neurocysticercosis cyst presented with Bruns
[15]
[16] [17]
[18] [19] [20]
[21] [22] [23]
[24]
syndrome: report of two cases and review of literature. J Korean Neurosurg Soc 2014;55:173–7. Santo AH. Cysticercosis-related mortality in the State of Sao Paulo, Brazil, 1985–2004: a study using multiple causes of death. Cad Saude Publica 2007;23:2917–27. Garcia HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 2002;15:747–56. Proano JV, Torres-Corzo J, Rodriguez-Della Vecchia R, et al. Intraventricular and subarachnoid basal cisterns neurocysticercosis: a comparative study between traditional treatment versus neuroendoscopic surgery. Childs Nerv Syst 2009;25:1467–75. Rajshekhar V. Surgical management of neurocysticercosis. Int J Surg 2010;8:100–4. Rangel-Castilla L, Serpa JA, Gopinath SP, et al. Contemporary neurosurgical approaches to neurocysticercosis. Am J Trop Med Hyg 2009;80:373–8. Rapoport BI, Baird LC, Cohen AR. Third-ventricular neurocysticercosis: hydraulic maneuvers facilitating endoscopic resection. Childs Nerv Syst 2014;30:541–6. Hanak BW, Walcott BP, Codd PJ, et al. Fourth ventricular neurocystercercosis presenting with acute hydrocephalus. J Clin Neurosci 2011;18:867–9. Loyo M, Kleriga E, Estanol B. Fourth ventricular cysticercosis. Neurosurgery 1980;7:456–8. Apuzzo ML, Dobkin WR, Zee CS, et al. Surgical considerations in treatment of intraventricular cysticercosis. An analysis of 45 cases. J Neurosurg 1984;60:400–7. Citow JS, Johnson JP, McBride DQ, et al. Imaging features and surgery-related outcomes in intraventricular neurocysticercosis. Neurosurg Focus 2002;12:e6.
http://dx.doi.org/10.1016/j.jocn.2015.03.030
Primary angiitis of the central nervous system presenting as a mass lesion Calvin Gan a,⇑, Julian Maingard a, Lauren Giles a, Pramit M. Phal b, K. Meng Tan a a b
Department of Neurology, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia Department of Radiology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia
a r t i c l e
i n f o
Article history: Received 18 February 2015 Accepted 4 March 2015
Keywords: Primary angiitis of the central nervous system (PACNS) Vasculitis Magnetic resonance imaging (MRI) Mass lesion Tumour-like lesion Basal ganglia
a b s t r a c t We report a 51-year-old Asian man with primary angiitis of the central nervous system (PACNS) with atypical presentation as a mass lesion. PACNS is an uncommon condition causing inflammation and destruction of the blood vessels of the central nervous system. The aetiology is unclear and multiple mechanisms have been proposed. Its incidence is estimated at 2.4 per million per year, affecting patients of all ages (median 50 years) and more commonly Caucasian men. In Australia, 12 patients fulfilled the diagnostic criteria for PACNS between 1998 and 2009 at The Royal Melbourne Hospital, a university-affiliated tertiary referral centre. The accurate and timely diagnosis of PACNS is very challenging due to disease mimicry and the absence of specific serological tests. This patient illustrates additional diagnostic difficulty with his atypical PACNS presentation as a mass lesion. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Primary angiitis of the central nervous system (PACNS) is an uncommon condition causing inflammation and destruction of the blood vessels of the central nervous system (CNS). The aetiology is unclear and multiple mechanisms have been proposed [1]. Its incidence is estimated at 2.4 per million per year, affecting patients of all ages (median 50 years), and more commonly Caucasian men [1,2]. In Australia, 12 patients fulfilled the diagnostic criteria for PACNS between 1998 and 2009 at The Royal
⇑ Corresponding author. Tel.: +61 425722136. E-mail address: [email protected] (C. Gan).
Melbourne Hospital, a university-affiliated tertiary referral centre [3]. Accurate and timely diagnosis of PACNS is very challenging due to disease mimicry and the absence of specific serological tests [4]. This case report illustrates the additional difficulty of diagnosing PACNS presenting atypically as a mass lesion.
2. Case report A 51-year-old Asian man presented with 2 weeks of confusion, memory difficulty and expressive dysphasia associated with nausea, vomiting and headache. He had stable chronic hepatitis B infection but was otherwise previously well.
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
Fig. 1. Contrast enhanced axial brain CT scan demonstrating a solitary 52 41 38 mm heterogenous enhancing mass centred in the left lentiform nucleus (arrow). There is 7 mm of midline shift. This was highly suspicious for glioblastoma multiforme.
On examination, the patient was alert and orientated to place and person, but not to time. A detailed cognitive assessment was not performed. There was no papilloedema and his neurological
1529
examination was otherwise normal. Initial investigations included a normal chest radiograph, normal full blood examination and serum biochemistry demonstrating mild hyponatraemia (131 mmol/L) and hyperkalaemia (5.3 mmol/L). A brain CT scan revealed a solitary 52 41 38 mm heterogenous contrast enhancing mass centred in the left lentiform nucleus with surrounding white matter hypodensity extending into the left frontal, temporal and parietal lobes, and 7 mm of midline shift (Fig. 1). A provisional diagnosis of glioblastoma multiforme was made. A subsequent MRI demonstrated a large heterogeneously enhancing mass centred in the left basal ganglia involving the temporal lobe, insular cortex and posterior aspect of the gyrus rectus, with extension across the midline and positive mass effect. Additional foci of enhancement were seen in the right frontal lobe and left medulla (Fig. 2). Additionally, multi-voxel magnetic resonance spectroscopy (MRS) demonstrated some areas of elevated choline, N-acetyl-aspartate (NAA) and lactate. The MRI findings suggested a multifocal high grade glioma or CNS lymphoma. A stereotactic left temporal craniotomy for open biopsy was then performed. Frozen section findings suggested lymphoma but formal histology was thought to demonstrate cerebral angiitis. The disparity between the radiological and histological diagnoses led to a second biopsy and external review, ultimately favouring the diagnosis of PACNS over lymphomatoid granulomatosis or angiotropic T-cell lymphoma. Serological testing
Fig. 2. Initial MRI of the brain. (A) Axial T1-weighted, (B) axial T1-weighted gadolinium enhanced, (C) axial T2-weighted, and (D) axial fluid-attenuated inversion recovery (FLAIR) MRI demonstrating a large heterogeneous enhancing mass centred in the left basal ganglia (arrow) involving the temporal lobe, insular cortex and posterior aspect of the gyrus rectus. There was associated extension across the midline with positive mass effect.
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Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
Fig. 3. Follow-up brain MRI 3 months after the initial imaging and after commencing high dose oral prednisolone. (A) Axial T1-weighted, (B) axial T1-weighted gadolinium enhanced, (C) axial T2-weighted, and (D) axial fluid-attenuated inversion recovery (FLAIR) MRI demonstrated a significant decrease in size of the enhancing mass and signal abnormality (arrow).
for cryptococcosis, melioidosis and parasitic infections was negative, while further blood tests and extracranial imaging did not support a haematological or other malignancy. Testing for antinuclear antibodies, antibodies against extractable nuclear antigens and rheumatoid factor were negative. Four months after his initial presentation, the diagnosis of PACNS was settled upon and he commenced treatment with high dose oral prednisolone and monthly intravenous cyclophosphamide. A repeat brain MRI after 6 months of treatment showed that the lesion was substantially smaller with resolution of oedema and mass effect, and residual changes indicating haemosiderosis and encephalomalacia rather than ongoing inflammation (Fig. 3).
3. Discussion Clinical presentations of PACNS are protean and often non-specific, with broad differential diagnoses including malignancy, infection and other connective tissue disease [1]. Headache is the most common presenting symptom, often accompanied by nausea and vomiting, as occurred in our patient [4]. Altered cognitive state, behavioural changes and visual disturbances may also occur. Less common presenting symptoms include seizures, ataxia, coma and cranial neuropathies [5]. Constitutional
features such as weight loss, fevers and lethargy are rare and suggest a systemic cause [6]. Recurrent transient ischaemic attacks or strokes occur in 30–50% of patients with PACNS and result in focal neurological deficits [1,2]. Calabrese et al. [7] proposed three necessary diagnostic criteria for PACNS: an acquired, otherwise unexplained, neurological or psychiatric deficit, classic angiographic or histopathological features of angiitis within the CNS, and no evidence of systemic vasculitis or any disorder that could cause or mimic the angiographic or pathological features of the disease. Brain biopsy remains the gold standard to establish a diagnosis of PACNS [8,9], ideally with an open wedge biopsy of a discrete lesion including grey and white matter, leptomeninges and cortical vessels [10]. Vasculocentric transmural inflammation with damage to the vascular wall, with or without fibrinoid mural necrosis, confirms the diagnosis [11], but segmental involvement results in false negative rates up of to 25% [12]. Our patient further illustrates that histological diagnosis is not always straightforward. CT scans, MRI, magnetic resonance angiography (MRA), and conventional angiography are all useful diagnostic imaging modalities. The sensitivity of MRI is estimated at 90% or better [6,13,14], although findings such as parenchymal or leptomeningeal enhancement, cerebral infarction, intracranial haemorrhage and T2-weighted or fluid-attenuated inversion recovery (FLAIR) hyperintensities are not pathognomonic [11]. The most common finding
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
is infarction in 53–97% of patients, multifocal and/or bilateral in over 80% [2,14]. Differentiation from multiple sclerosis, gliomatosis cerebri [15] and primary intravascular CNS lymphoma [16] may be difficult. MRA and conventional angiography may show multiple and bilateral stenoses in 75% of patients, typically with medium to small vessel involvement distal to the middle cerebral artery bifurcation affecting multiple vessels [17]. High resolution 3-Tesla MRI of the vessel wall may demonstrate enhancement and thickening [18]. Tumour-like mass lesions are rare, seen in only 5–15% of patients [2,19], and are generally indistinguishable from other causes of a mass lesion [17]. This is the first of 13 recognised PACNS patients at our centre to present with radiological features suggestive of a mass lesion [3]. Such patients are often misdiagnosed as high grade glioma because of gadolinium enhancement, T2-weighted hyperintensity, T1-weighted hypointensity, haemorrhage and significant oedema and mass effect [15,16,20,21]. This highlights that mass lesions are an underrecognised entity in PACNS, as suggested by Molloy et al. [21] who found mass lesions in 38 of 737 patients with histologically confirmed PACNS. Both magnetic resonance perfusion (MRP) and MRS were utilised in the diagnostic workup of our patient. MRP and MRS are useful techniques in the imaging of adult intracerebral neoplasms [22]. The utility of MRP in PACNS presenting as a mass lesion has been suggested in isolated case reports [23], however, cerebral blood volume findings are often inconsistent and add little to the imaging diagnosis [16]. Our patient demonstrated some areas of increased choline, NAA and lactate. Typical findings in glioma include high choline, low NAA peaks and high lactate. While this might suggest that MRS is useful in differentiating mass lesion PACNS from malignant glioma, such findings are known to be non-specific [16,24,25]. Marked elevation of glutamate and glutamine peaks have been observed but are not consistent findings [16,23,25]. Good response rates to therapy are seen with early diagnosis and immunosuppressive therapy [2,21,26], particularly high dose corticosteroids combined with intravenous cyclophosphamide [3,12,27,28]. In patients with PACNS presenting as mass lesions, prompt recognition and aggressive immunosuppressive therapy appears to be associated with favourable outcomes and may obviate surgical excision [21]. Should the patient fail to respond to treatment, the diagnosis of PACNS should be reevaluated. Our patient showed rapid improvement in initial imaging findings after the institution of high dose immunosuppression. In conclusion, PACNS presenting as a mass lesion poses a diagnostic challenge, requiring MRI findings to be elucidiated by prompt angiography and/or biopsy so that definitive treatment may be instituted early. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. http://dx.doi.org/10.1016/j.jocn.2015.03.030
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References [1] Hajj-Ali RA, Singhal AB, Benseler S, et al. Primary angiitis of the CNS. Lancet Neurol 2011;10:561–72. [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] Oon S, Roberts C, Gorelik A, et al. Primary angiitis of the central nervous system: experience of a Victorian tertiary-referral hospital. Intern Med J 2013;43:685–92. [4] Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun 2014;48–49:149–52. [5] Salvarani C, Brown Jr RD, Hunder GG. Adult primary central nervous system vasculitis. Lancet 2012;380:767–77. [6] Birnbaum J, Hellmann DB. Primary angiitis of the central nervous system. Arch Neurol 2009;66:704–9. [7] Calabrese LH, Mallek JA. Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine (Baltimore) 1988;67:20–39. [8] Parisi JE, Moore PM. The role of biopsy in vasculitis of the central nervous system. Semin Neurol 1994;14:341–8. [9] Alrawi A, Trobe JD, Blaivas M, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology 1999;53:858–60. [10] Berlit P, Kraemer M. Cerebral vasculitis in adults: what are the steps in order to establish the diagnosis? Red flags and pitfalls. Clin Exp Immunol 2014;175: 419–24. [11] Giannini C, Salvarani C, Hunder G, et al. Primary central nervous system vasculitis: pathology and mechanisms. Acta Neuropathol 2012;123:759–72. [12] Cupps TR, Moore PM, Fauci AS. Isolated angiitis of the central nervous system. Prospective diagnostic and therapeutic experience. Am J Med 1983;74: 97–105. [13] Neel A, Pagnoux C. Primary angiitis of the central nervous system. Clin Exp Rheumatol 2009;27:S95–107. [14] Geri G, Saadoun D, Guillevin R, et al. Central nervous system angiitis: a series of 31 patients. Clin Rheumatol 2014;33:105–10. [15] Qu SB, Khan S, Liu H. Primary central nervous system vasculitis mimicking brain tumour: case report and literature review. Rheumatol Int 2009;30: 127–34. [16] Lee Y, Kim JH, Kim E, et al. Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features. Neuroradiology 2009;51: 651–9. [17] Gomes LJ. The role of imaging in the diagnosis of central nervous system vasculitis. Curr Allergy Asthma Rep 2010;10:163–70. [18] Mandell DM, Matouk CC, Farb RI, et al. Vessel wall MRI to differentiate between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis: preliminary results. Stroke 2012;43:860–2. [19] Abdel Razek AA, Alvarez H, Bagg S, et al. Imaging spectrum of CNS vasculitis. Radiographics 2014;34:873–94. [20] You G, Yan W, Zhang W, et al. Isolated angiitis of the central nervous system with tumor-like lesion, mimicking brain malignant glioma: a case report and review of the literature. World J Surg Oncol 2011;9:97. [21] Molloy ES, Singhal AB, Calabrese LH. Tumour-like mass lesion: an underrecognised presentation of primary angiitis of the central nervous system. Ann Rheum Dis 2008;67:1732–5. [22] Young GS. Advanced MRI of adult brain tumors. Neurol Clin 2007;25:947–73. [23] Muccio CF, Di Blasi A, Esposito G, et al. Perfusion and spectroscopy magnetic resonance imaging in a case of lymphocytic vasculitis mimicking brain tumor. Pol J Radiol 2013;78:66–9. [24] Panchal NJ, Niku S, Imbesi SG. Lymphocytic vasculitis mimicking aggressive multifocal cerebral neoplasm: mr imaging and MR spectroscopic appearance. AJNR Am J Neuroradiol 2005;26:642–5. [25] 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. Case report. J Neurosurg 2007;107:873–7. [26] Kraemer M, Berlit P. Primary central nervous system vasculitis: clinical experiences with 21 new European cases. Rheumatol Int 2011;31:463–72. [27] Fauci AS, Haynes B, Katz P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations. Ann Intern Med 1978;89:660–76. [28] Hajj-Ali RA. Primary angiitis of the central nervous system: differential diagnosis and treatment. Best Pract Res Clin Rheumatol 2010;24:413–26.
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
[3] Garcia HH, Del Brutto OH, Cysticercosis Working Group in Peru. Neurocysticercosis: updated concepts about an old disease. Lancet Neurol 2005;4:653–61. [4] Salazar Noguera EM, Pineda Sic R, Escoto Solis F. Intramedullary spinal cord neurocysticercosis presenting as brown-sequard syndrome. BMC Neurol 2015;15:1. [5] Verma R, Anand KS, Sharma BB, et al. Neurocysticercosis presenting as parkinsonism. Neurol India 2014;62:110–1. [6] Nash TE, Garcia HH. Diagnosis and treatment of neurocysticercosis. Nat Rev Neurol 2011;7:584–94. [7] Serpa JA, White Jr AC. Neurocysticercosis in the United States. Pathog Glob Health 2012;106:256–60. [8] Flisser A. Taeniasis and cysticercosis due to Taenia solium. Prog Clin Parasitol 1994;4:77–116. [9] Lobato RD, Lamas E, Portillo JM, et al. Hydrocephalus in cerebral cysticercosis. Pathogenic and therapeutic considerations. J Neurosurg 1981;55:786–93. [10] Amelot A, Faillot T. Hydrocephalus and neurocysticercosis: cases illustrative of three distinct mechanisms. J Clin Neurol 2014;10:363–6. [11] Monteiro L, Almeida-Pinto J, Stocker A, et al. Active neurocysticercosis, parenchymal and extraparenchymal: a study of 38 patients. J Neurol 1993;241:15–21. [12] Salazar A, Sotelo J, Martinez H, et al. Differential diagnosis between ventriculitis and fourth ventricle cyst in neurocysticercosis. J Neurosurg 1983;59:660–3. [13] Torres-Corzo J, Rodriguez-della Vecchia R, Rangel-Castilla L. Bruns syndrome caused by intraventricular neurocysticercosis treated using flexible endoscopy. J Neurosurg 2006;104:746–8. [14] Teegala R, Rajesh KG, Raviprasad VY, et al. Emergency neuroendoscopic management of third ventricular neurocysticercosis cyst presented with Bruns
[15]
[16] [17]
[18] [19] [20]
[21] [22] [23]
[24]
syndrome: report of two cases and review of literature. J Korean Neurosurg Soc 2014;55:173–7. Santo AH. Cysticercosis-related mortality in the State of Sao Paulo, Brazil, 1985–2004: a study using multiple causes of death. Cad Saude Publica 2007;23:2917–27. Garcia HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 2002;15:747–56. Proano JV, Torres-Corzo J, Rodriguez-Della Vecchia R, et al. Intraventricular and subarachnoid basal cisterns neurocysticercosis: a comparative study between traditional treatment versus neuroendoscopic surgery. Childs Nerv Syst 2009;25:1467–75. Rajshekhar V. Surgical management of neurocysticercosis. Int J Surg 2010;8:100–4. Rangel-Castilla L, Serpa JA, Gopinath SP, et al. Contemporary neurosurgical approaches to neurocysticercosis. Am J Trop Med Hyg 2009;80:373–8. Rapoport BI, Baird LC, Cohen AR. Third-ventricular neurocysticercosis: hydraulic maneuvers facilitating endoscopic resection. Childs Nerv Syst 2014;30:541–6. Hanak BW, Walcott BP, Codd PJ, et al. Fourth ventricular neurocystercercosis presenting with acute hydrocephalus. J Clin Neurosci 2011;18:867–9. Loyo M, Kleriga E, Estanol B. Fourth ventricular cysticercosis. Neurosurgery 1980;7:456–8. Apuzzo ML, Dobkin WR, Zee CS, et al. Surgical considerations in treatment of intraventricular cysticercosis. An analysis of 45 cases. J Neurosurg 1984;60:400–7. Citow JS, Johnson JP, McBride DQ, et al. Imaging features and surgery-related outcomes in intraventricular neurocysticercosis. Neurosurg Focus 2002;12:e6.
http://dx.doi.org/10.1016/j.jocn.2015.03.030
Primary angiitis of the central nervous system presenting as a mass lesion Calvin Gan a,⇑, Julian Maingard a, Lauren Giles a, Pramit M. Phal b, K. Meng Tan a a b
Department of Neurology, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia Department of Radiology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia
a r t i c l e
i n f o
Article history: Received 18 February 2015 Accepted 4 March 2015
Keywords: Primary angiitis of the central nervous system (PACNS) Vasculitis Magnetic resonance imaging (MRI) Mass lesion Tumour-like lesion Basal ganglia
a b s t r a c t We report a 51-year-old Asian man with primary angiitis of the central nervous system (PACNS) with atypical presentation as a mass lesion. PACNS is an uncommon condition causing inflammation and destruction of the blood vessels of the central nervous system. The aetiology is unclear and multiple mechanisms have been proposed. Its incidence is estimated at 2.4 per million per year, affecting patients of all ages (median 50 years) and more commonly Caucasian men. In Australia, 12 patients fulfilled the diagnostic criteria for PACNS between 1998 and 2009 at The Royal Melbourne Hospital, a university-affiliated tertiary referral centre. The accurate and timely diagnosis of PACNS is very challenging due to disease mimicry and the absence of specific serological tests. This patient illustrates additional diagnostic difficulty with his atypical PACNS presentation as a mass lesion. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Primary angiitis of the central nervous system (PACNS) is an uncommon condition causing inflammation and destruction of the blood vessels of the central nervous system (CNS). The aetiology is unclear and multiple mechanisms have been proposed [1]. Its incidence is estimated at 2.4 per million per year, affecting patients of all ages (median 50 years), and more commonly Caucasian men [1,2]. In Australia, 12 patients fulfilled the diagnostic criteria for PACNS between 1998 and 2009 at The Royal
⇑ Corresponding author. Tel.: +61 425722136. E-mail address: [email protected] (C. Gan).
Melbourne Hospital, a university-affiliated tertiary referral centre [3]. Accurate and timely diagnosis of PACNS is very challenging due to disease mimicry and the absence of specific serological tests [4]. This case report illustrates the additional difficulty of diagnosing PACNS presenting atypically as a mass lesion.
2. Case report A 51-year-old Asian man presented with 2 weeks of confusion, memory difficulty and expressive dysphasia associated with nausea, vomiting and headache. He had stable chronic hepatitis B infection but was otherwise previously well.
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
Fig. 1. Contrast enhanced axial brain CT scan demonstrating a solitary 52 41 38 mm heterogenous enhancing mass centred in the left lentiform nucleus (arrow). There is 7 mm of midline shift. This was highly suspicious for glioblastoma multiforme.
On examination, the patient was alert and orientated to place and person, but not to time. A detailed cognitive assessment was not performed. There was no papilloedema and his neurological
1529
examination was otherwise normal. Initial investigations included a normal chest radiograph, normal full blood examination and serum biochemistry demonstrating mild hyponatraemia (131 mmol/L) and hyperkalaemia (5.3 mmol/L). A brain CT scan revealed a solitary 52 41 38 mm heterogenous contrast enhancing mass centred in the left lentiform nucleus with surrounding white matter hypodensity extending into the left frontal, temporal and parietal lobes, and 7 mm of midline shift (Fig. 1). A provisional diagnosis of glioblastoma multiforme was made. A subsequent MRI demonstrated a large heterogeneously enhancing mass centred in the left basal ganglia involving the temporal lobe, insular cortex and posterior aspect of the gyrus rectus, with extension across the midline and positive mass effect. Additional foci of enhancement were seen in the right frontal lobe and left medulla (Fig. 2). Additionally, multi-voxel magnetic resonance spectroscopy (MRS) demonstrated some areas of elevated choline, N-acetyl-aspartate (NAA) and lactate. The MRI findings suggested a multifocal high grade glioma or CNS lymphoma. A stereotactic left temporal craniotomy for open biopsy was then performed. Frozen section findings suggested lymphoma but formal histology was thought to demonstrate cerebral angiitis. The disparity between the radiological and histological diagnoses led to a second biopsy and external review, ultimately favouring the diagnosis of PACNS over lymphomatoid granulomatosis or angiotropic T-cell lymphoma. Serological testing
Fig. 2. Initial MRI of the brain. (A) Axial T1-weighted, (B) axial T1-weighted gadolinium enhanced, (C) axial T2-weighted, and (D) axial fluid-attenuated inversion recovery (FLAIR) MRI demonstrating a large heterogeneous enhancing mass centred in the left basal ganglia (arrow) involving the temporal lobe, insular cortex and posterior aspect of the gyrus rectus. There was associated extension across the midline with positive mass effect.
1530
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
Fig. 3. Follow-up brain MRI 3 months after the initial imaging and after commencing high dose oral prednisolone. (A) Axial T1-weighted, (B) axial T1-weighted gadolinium enhanced, (C) axial T2-weighted, and (D) axial fluid-attenuated inversion recovery (FLAIR) MRI demonstrated a significant decrease in size of the enhancing mass and signal abnormality (arrow).
for cryptococcosis, melioidosis and parasitic infections was negative, while further blood tests and extracranial imaging did not support a haematological or other malignancy. Testing for antinuclear antibodies, antibodies against extractable nuclear antigens and rheumatoid factor were negative. Four months after his initial presentation, the diagnosis of PACNS was settled upon and he commenced treatment with high dose oral prednisolone and monthly intravenous cyclophosphamide. A repeat brain MRI after 6 months of treatment showed that the lesion was substantially smaller with resolution of oedema and mass effect, and residual changes indicating haemosiderosis and encephalomalacia rather than ongoing inflammation (Fig. 3).
3. Discussion Clinical presentations of PACNS are protean and often non-specific, with broad differential diagnoses including malignancy, infection and other connective tissue disease [1]. Headache is the most common presenting symptom, often accompanied by nausea and vomiting, as occurred in our patient [4]. Altered cognitive state, behavioural changes and visual disturbances may also occur. Less common presenting symptoms include seizures, ataxia, coma and cranial neuropathies [5]. Constitutional
features such as weight loss, fevers and lethargy are rare and suggest a systemic cause [6]. Recurrent transient ischaemic attacks or strokes occur in 30–50% of patients with PACNS and result in focal neurological deficits [1,2]. Calabrese et al. [7] proposed three necessary diagnostic criteria for PACNS: an acquired, otherwise unexplained, neurological or psychiatric deficit, classic angiographic or histopathological features of angiitis within the CNS, and no evidence of systemic vasculitis or any disorder that could cause or mimic the angiographic or pathological features of the disease. Brain biopsy remains the gold standard to establish a diagnosis of PACNS [8,9], ideally with an open wedge biopsy of a discrete lesion including grey and white matter, leptomeninges and cortical vessels [10]. Vasculocentric transmural inflammation with damage to the vascular wall, with or without fibrinoid mural necrosis, confirms the diagnosis [11], but segmental involvement results in false negative rates up of to 25% [12]. Our patient further illustrates that histological diagnosis is not always straightforward. CT scans, MRI, magnetic resonance angiography (MRA), and conventional angiography are all useful diagnostic imaging modalities. The sensitivity of MRI is estimated at 90% or better [6,13,14], although findings such as parenchymal or leptomeningeal enhancement, cerebral infarction, intracranial haemorrhage and T2-weighted or fluid-attenuated inversion recovery (FLAIR) hyperintensities are not pathognomonic [11]. The most common finding
Case Reports / Journal of Clinical Neuroscience 22 (2015) 1528–1531
is infarction in 53–97% of patients, multifocal and/or bilateral in over 80% [2,14]. Differentiation from multiple sclerosis, gliomatosis cerebri [15] and primary intravascular CNS lymphoma [16] may be difficult. MRA and conventional angiography may show multiple and bilateral stenoses in 75% of patients, typically with medium to small vessel involvement distal to the middle cerebral artery bifurcation affecting multiple vessels [17]. High resolution 3-Tesla MRI of the vessel wall may demonstrate enhancement and thickening [18]. Tumour-like mass lesions are rare, seen in only 5–15% of patients [2,19], and are generally indistinguishable from other causes of a mass lesion [17]. This is the first of 13 recognised PACNS patients at our centre to present with radiological features suggestive of a mass lesion [3]. Such patients are often misdiagnosed as high grade glioma because of gadolinium enhancement, T2-weighted hyperintensity, T1-weighted hypointensity, haemorrhage and significant oedema and mass effect [15,16,20,21]. This highlights that mass lesions are an underrecognised entity in PACNS, as suggested by Molloy et al. [21] who found mass lesions in 38 of 737 patients with histologically confirmed PACNS. Both magnetic resonance perfusion (MRP) and MRS were utilised in the diagnostic workup of our patient. MRP and MRS are useful techniques in the imaging of adult intracerebral neoplasms [22]. The utility of MRP in PACNS presenting as a mass lesion has been suggested in isolated case reports [23], however, cerebral blood volume findings are often inconsistent and add little to the imaging diagnosis [16]. Our patient demonstrated some areas of increased choline, NAA and lactate. Typical findings in glioma include high choline, low NAA peaks and high lactate. While this might suggest that MRS is useful in differentiating mass lesion PACNS from malignant glioma, such findings are known to be non-specific [16,24,25]. Marked elevation of glutamate and glutamine peaks have been observed but are not consistent findings [16,23,25]. Good response rates to therapy are seen with early diagnosis and immunosuppressive therapy [2,21,26], particularly high dose corticosteroids combined with intravenous cyclophosphamide [3,12,27,28]. In patients with PACNS presenting as mass lesions, prompt recognition and aggressive immunosuppressive therapy appears to be associated with favourable outcomes and may obviate surgical excision [21]. Should the patient fail to respond to treatment, the diagnosis of PACNS should be reevaluated. Our patient showed rapid improvement in initial imaging findings after the institution of high dose immunosuppression. In conclusion, PACNS presenting as a mass lesion poses a diagnostic challenge, requiring MRI findings to be elucidiated by prompt angiography and/or biopsy so that definitive treatment may be instituted early. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. http://dx.doi.org/10.1016/j.jocn.2015.03.030
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