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Mainly subarachnoid amyloid angiopathy with pseudotumoral course
Clinical Neurology and Neurosurgery 141 (2016) 89–91
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Mainly subarachnoid amyloid angiopathy with pseudotumoral course Franco-Macías Emilio a,∗ , Cerdá-Fuertes Nuria a , Rivas-Infante Eloy b , Roldán-Lora Florinda c , Ávila-Polo Rainiero b , Moniche Francisco a a b c
Department of Neurology, Hospital Virgen del Rocío, Seville, Spain Neuropathology Division, Department of Pathology, Hospital Virgen del Rocío, Seville, Spain Neuroradiology Division, Department of Radiology, Hospital Virgen del Rocío, Seville, Spain
a r t i c l e
i n f o
Article history: Received 1 October 2015 Received in revised form 22 October 2015 Accepted 9 December 2015 Available online 17 December 2015 Keywords: Pseudotumoral Subarachnoid Cerebral amyloid angiopathy Microbleeds
1. Introduction Cerebral amyloid angiopathy (CAA) is a common pathology in the elderly characterized by the deposition of amyloid proteins within the leptomeningeal and cortical arteries [1]. Lobar hemorrhage is the most common presentation of the disease [1]. A subset of patients who present with seizures, subacute cognitive decline or headaches and show asymmetric vasogenic edema and microbleeds on MRI, and vasculitis or perivasculitis on neuropathologic examination are diagnosed as CAA-related inflammation (CAA-ri) [2]. In some of these patients the edema is so extensively spread throughout a cerebral hemisphere that the neuroimage may be suggestive of an underlying malignancy. This is considered a pseudotumoral presentation [3]. Recently, CAA has been classified into two types [4]: type 1 that mainly affects cortical capillaries and it is associated with increasing vascular amyloid burden, lobar microbleeds and presence of APOE 4, and type 2 that mainly affects subarachnoid capillaries and it is associated with cortical superficial siderosis, less microbleeds and presence of APOE 2. We report a patient with mainly subarachnoid pathologically proven CAA in whom MRI repeatedly showed absence of microb-
∗ Corresponding author at: Department of Neurology, Hospital Virgen del Rocío, Avda. Manuel Siurot s/n, Seville 41013, Spain. E-mail address: [email protected] (F.-M. Emilio). http://dx.doi.org/10.1016/j.clineuro.2015.12.006 0303-8467/© 2015 Elsevier B.V. All rights reserved.
leeds. Vasculitis was not detected in the neuropathological study despite a severe pseudotumoral course.
2. Case report A right-handed 67-year-old woman presented with acute aphasia. The neurological examination showed aphasia with motor predominance. Brain CT-scan revealed a left frontal hematoma. Laboratory analysis was unremarkable. In addition the MRI revealed contralateral frontal subarachnoid bleeding and no cerebral microbleeds were found on susceptibility-weighted imaging (SWI). A week later the patient worsened showing sleepiness, rightside hemiparesis and global aphasia. A new CT-scan revealed no changes in the volume of the hemorrhage but edema. The patient improved on steroids and only mild dysphasia was present upon discharge. Four months later the patient was again referred to the hospital because of a significant worsening of her residual dysphasia and reappearance of right-side central facial palsy and hemiparesis. Upon admission the patient suffered a partial left frontal seizure. CT-scan showed an extensive subcortical hypodensity spreading throughout the left hemisphere (Fig. 1). MRI revealed an extensive vasogenic edema (Fig. 1). SWI images showed signs of the previous left frontal hematoma and right frontal siderosis and, once more, no microbleeds were found (Fig. 1). A cortical and meningeal biopsy was conducted and it detected amyloid angiopathy mainly
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F.-M. Emilio et al. / Clinical Neurology and Neurosurgery 141 (2016) 89–91
Fig. 1. Brain CT (A) and axial T2WI (B) show an extensive vasogenic edema in the left hemisphere without signs of acute hemorrhage (yellow arrows). Rests of the previous hematoma can be seen in the left frontal lobe (B, blue arrow). Axial SWI (C) shows superficial siderosis in both hemispheres (red arrows) without evidence of microbleeds. Post-gadolinium enhanced T1 W images in axial section (D) reveals leptomeningeal enhancement in the left hemisphere (green arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
involving subarachnoid vessels. There were occasional perivascular T lymphocytes but no true vasculitis (Fig. 2). This time the patient experienced only partially improvement after steroid therapy and she was left with aphasia and cognitive impairment.
3. Discussion CAA is a well-known cause of MRI microbleeds and lobar hemorrhages [1,2]. A subset of CAA patients present as CAA-ri and show vasculitis or perivasculitis on neuropathologic examination [1,2]. In some of these patients it is possible to find a pseudotumoral presentation with extensive vasogenic edema involving an entire hemisphere [4]. The patient reported here presented with a severe biphasic course: lobar hemorrhage followed by a pseudotumoral recurrence four months later. The neuropathological study revealed mainly
subarachnoid CAA with only occasional perivascular lymphocites. The absence of overt vasculitis on the neuropathological examination might be explained by the intake of steroids prior to the biopsy or by having performed the biopsy from a less expressive area. However, the fact was that a true vasculitis could not be demonstrated. After an extensive assessment of the sample no other disease was found, apart from CAA, to account for the symptoms of the patient. MRI did not show microbleeds, neither at onset nor at recurrence of the clinical presentation. Microbleeds are not always detected even in neuropathologically confirmed CAA-ri cases. Up to 13% of the cases might present without microbleeds [5]. On the other hand, considering a recent CAA classification proposal [4], this case resembles the type 2CAA because of its mainly subarachnoid involvement and the absence of microbleeds [4]. Unfortunately, the APOE genotype was not available and we do not know if the patient carried out the 2 allele usually associated to type 2CAA.
F.-M. Emilio et al. / Clinical Neurology and Neurosurgery 141 (2016) 89–91
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Fig. 2. Left temporal cortical and meningeal biopsy. Neuropathological study. PAS stain (A) and amyloid- immunohistochemical (B) showing amyloid laden cortical vessels (black arrows). Amyloid deposits present in seniles plaques are also showed in Fig. 2B (blue arrow). Immunostaining for CD3 (C) revealing a few perivascular T lymphocytes (green arrow). Amyloid- immunohistochemical (D) showing amyloid laden subarachnoid vessels (red arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
The main contribution of this case is the unusual radiological pseudotumoral pattern during the relapse phase with the extensive vasogenic edema and the ipsilateral leptomeninge’s gadoliniumenhancement. Although the patient suffered a seizure and it is known that seizures, particularly status epilepticus, may result in gyral cortical enhancement, we consider the meningeal pathology as the main reason for the enhancement. Leptomeninge’s enhancement with gadolinium has been occasionally described in CAA-ri cases but this finding has not received enough attention even in mainly subarachnoid cases [2]. Beyond simple bleeding, we propose an active role of the meninges in mainly subarachnoid cases of CAA. The involved leptomeninge may trigger an extensive vasogenic edema which could improve on steroids. 3. Conclusion In conclusion, we report a case of histopathologically proven CAA mainly involving subarachnoid vessels and probably representing type 2 of CAA. We underline the following features in this particular presentation: neither microbleeds-despite repeated MRI-nor true vasculitis on neuropathological study, but pseudotumoral course and meningeal enhancement.
Conflict of interest None. References [1] S.M. Greenberg, R. Al-Shahi Salman, G.J. Biessels, M. van Buchem, C. Cordonnier, J.M. Lee, J. Montaner, J.A. Schneider, E.E. Smith, M. Vernooij, D.J. Werring, Outcome markers of clinical trials in cerebral amyloid angiopathy, Lancet Neurol. 13 (4) (2014) 419–428. [2] C. Salvarani, G.G. Hunder, J.M. Morris, R.D. Brown, T. Christianson, C. Giannini, A-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis, Neurology 81 (18) (2013) 1596–1603. [3] S.I. Bekkelund, C.E. Midtbu, L. Arvola, O.P. Eldevik, S. Lindal, Good outcome in a patient treated for cerebral amyloid angiopathy presenting as an expansive process with inflammation and contrast enhancement, Am. J. Neuroradiol. 32 (2011) E75. [4] A. Shoamanesh, S. Martínez-Ramírez, J. Oliveira-Filho, Y. Reijmer, G.J. Falcone, A. Ayres, K. Schwab, J.N. Goldstein, J. Rosand, M.E. Gurol, Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy, Neurology 83 (2014) 1–6. [5] H. Sakaguchi, A. Ueda, T. Kosaka, S. Yamashita, E. Kimura, T. Yamashita, Y. Maeda, T. Hirano, M. Uchino, Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature, J. Neuroinflamm. 8 (2011) 116.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Mainly subarachnoid amyloid angiopathy with pseudotumoral course Franco-Macías Emilio a,∗ , Cerdá-Fuertes Nuria a , Rivas-Infante Eloy b , Roldán-Lora Florinda c , Ávila-Polo Rainiero b , Moniche Francisco a a b c
Department of Neurology, Hospital Virgen del Rocío, Seville, Spain Neuropathology Division, Department of Pathology, Hospital Virgen del Rocío, Seville, Spain Neuroradiology Division, Department of Radiology, Hospital Virgen del Rocío, Seville, Spain
a r t i c l e
i n f o
Article history: Received 1 October 2015 Received in revised form 22 October 2015 Accepted 9 December 2015 Available online 17 December 2015 Keywords: Pseudotumoral Subarachnoid Cerebral amyloid angiopathy Microbleeds
1. Introduction Cerebral amyloid angiopathy (CAA) is a common pathology in the elderly characterized by the deposition of amyloid proteins within the leptomeningeal and cortical arteries [1]. Lobar hemorrhage is the most common presentation of the disease [1]. A subset of patients who present with seizures, subacute cognitive decline or headaches and show asymmetric vasogenic edema and microbleeds on MRI, and vasculitis or perivasculitis on neuropathologic examination are diagnosed as CAA-related inflammation (CAA-ri) [2]. In some of these patients the edema is so extensively spread throughout a cerebral hemisphere that the neuroimage may be suggestive of an underlying malignancy. This is considered a pseudotumoral presentation [3]. Recently, CAA has been classified into two types [4]: type 1 that mainly affects cortical capillaries and it is associated with increasing vascular amyloid burden, lobar microbleeds and presence of APOE 4, and type 2 that mainly affects subarachnoid capillaries and it is associated with cortical superficial siderosis, less microbleeds and presence of APOE 2. We report a patient with mainly subarachnoid pathologically proven CAA in whom MRI repeatedly showed absence of microb-
∗ Corresponding author at: Department of Neurology, Hospital Virgen del Rocío, Avda. Manuel Siurot s/n, Seville 41013, Spain. E-mail address: [email protected] (F.-M. Emilio). http://dx.doi.org/10.1016/j.clineuro.2015.12.006 0303-8467/© 2015 Elsevier B.V. All rights reserved.
leeds. Vasculitis was not detected in the neuropathological study despite a severe pseudotumoral course.
2. Case report A right-handed 67-year-old woman presented with acute aphasia. The neurological examination showed aphasia with motor predominance. Brain CT-scan revealed a left frontal hematoma. Laboratory analysis was unremarkable. In addition the MRI revealed contralateral frontal subarachnoid bleeding and no cerebral microbleeds were found on susceptibility-weighted imaging (SWI). A week later the patient worsened showing sleepiness, rightside hemiparesis and global aphasia. A new CT-scan revealed no changes in the volume of the hemorrhage but edema. The patient improved on steroids and only mild dysphasia was present upon discharge. Four months later the patient was again referred to the hospital because of a significant worsening of her residual dysphasia and reappearance of right-side central facial palsy and hemiparesis. Upon admission the patient suffered a partial left frontal seizure. CT-scan showed an extensive subcortical hypodensity spreading throughout the left hemisphere (Fig. 1). MRI revealed an extensive vasogenic edema (Fig. 1). SWI images showed signs of the previous left frontal hematoma and right frontal siderosis and, once more, no microbleeds were found (Fig. 1). A cortical and meningeal biopsy was conducted and it detected amyloid angiopathy mainly
90
F.-M. Emilio et al. / Clinical Neurology and Neurosurgery 141 (2016) 89–91
Fig. 1. Brain CT (A) and axial T2WI (B) show an extensive vasogenic edema in the left hemisphere without signs of acute hemorrhage (yellow arrows). Rests of the previous hematoma can be seen in the left frontal lobe (B, blue arrow). Axial SWI (C) shows superficial siderosis in both hemispheres (red arrows) without evidence of microbleeds. Post-gadolinium enhanced T1 W images in axial section (D) reveals leptomeningeal enhancement in the left hemisphere (green arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
involving subarachnoid vessels. There were occasional perivascular T lymphocytes but no true vasculitis (Fig. 2). This time the patient experienced only partially improvement after steroid therapy and she was left with aphasia and cognitive impairment.
3. Discussion CAA is a well-known cause of MRI microbleeds and lobar hemorrhages [1,2]. A subset of CAA patients present as CAA-ri and show vasculitis or perivasculitis on neuropathologic examination [1,2]. In some of these patients it is possible to find a pseudotumoral presentation with extensive vasogenic edema involving an entire hemisphere [4]. The patient reported here presented with a severe biphasic course: lobar hemorrhage followed by a pseudotumoral recurrence four months later. The neuropathological study revealed mainly
subarachnoid CAA with only occasional perivascular lymphocites. The absence of overt vasculitis on the neuropathological examination might be explained by the intake of steroids prior to the biopsy or by having performed the biopsy from a less expressive area. However, the fact was that a true vasculitis could not be demonstrated. After an extensive assessment of the sample no other disease was found, apart from CAA, to account for the symptoms of the patient. MRI did not show microbleeds, neither at onset nor at recurrence of the clinical presentation. Microbleeds are not always detected even in neuropathologically confirmed CAA-ri cases. Up to 13% of the cases might present without microbleeds [5]. On the other hand, considering a recent CAA classification proposal [4], this case resembles the type 2CAA because of its mainly subarachnoid involvement and the absence of microbleeds [4]. Unfortunately, the APOE genotype was not available and we do not know if the patient carried out the 2 allele usually associated to type 2CAA.
F.-M. Emilio et al. / Clinical Neurology and Neurosurgery 141 (2016) 89–91
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Fig. 2. Left temporal cortical and meningeal biopsy. Neuropathological study. PAS stain (A) and amyloid- immunohistochemical (B) showing amyloid laden cortical vessels (black arrows). Amyloid deposits present in seniles plaques are also showed in Fig. 2B (blue arrow). Immunostaining for CD3 (C) revealing a few perivascular T lymphocytes (green arrow). Amyloid- immunohistochemical (D) showing amyloid laden subarachnoid vessels (red arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
The main contribution of this case is the unusual radiological pseudotumoral pattern during the relapse phase with the extensive vasogenic edema and the ipsilateral leptomeninge’s gadoliniumenhancement. Although the patient suffered a seizure and it is known that seizures, particularly status epilepticus, may result in gyral cortical enhancement, we consider the meningeal pathology as the main reason for the enhancement. Leptomeninge’s enhancement with gadolinium has been occasionally described in CAA-ri cases but this finding has not received enough attention even in mainly subarachnoid cases [2]. Beyond simple bleeding, we propose an active role of the meninges in mainly subarachnoid cases of CAA. The involved leptomeninge may trigger an extensive vasogenic edema which could improve on steroids. 3. Conclusion In conclusion, we report a case of histopathologically proven CAA mainly involving subarachnoid vessels and probably representing type 2 of CAA. We underline the following features in this particular presentation: neither microbleeds-despite repeated MRI-nor true vasculitis on neuropathological study, but pseudotumoral course and meningeal enhancement.
Conflict of interest None. References [1] S.M. Greenberg, R. Al-Shahi Salman, G.J. Biessels, M. van Buchem, C. Cordonnier, J.M. Lee, J. Montaner, J.A. Schneider, E.E. Smith, M. Vernooij, D.J. Werring, Outcome markers of clinical trials in cerebral amyloid angiopathy, Lancet Neurol. 13 (4) (2014) 419–428. [2] C. Salvarani, G.G. Hunder, J.M. Morris, R.D. Brown, T. Christianson, C. Giannini, A-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis, Neurology 81 (18) (2013) 1596–1603. [3] S.I. Bekkelund, C.E. Midtbu, L. Arvola, O.P. Eldevik, S. Lindal, Good outcome in a patient treated for cerebral amyloid angiopathy presenting as an expansive process with inflammation and contrast enhancement, Am. J. Neuroradiol. 32 (2011) E75. [4] A. Shoamanesh, S. Martínez-Ramírez, J. Oliveira-Filho, Y. Reijmer, G.J. Falcone, A. Ayres, K. Schwab, J.N. Goldstein, J. Rosand, M.E. Gurol, Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy, Neurology 83 (2014) 1–6. [5] H. Sakaguchi, A. Ueda, T. Kosaka, S. Yamashita, E. Kimura, T. Yamashita, Y. Maeda, T. Hirano, M. Uchino, Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature, J. Neuroinflamm. 8 (2011) 116.