J Neurol DOI 10.1007/s00415-014-7378-8
LETTER TO THE EDITORS
Cerebral amyloid angiopathy revealed by rapidly progressing leptomeningeal lesions Armelle Chouraki • Adeline Rollin-Sillaire • Vincent Deramecourt Fahed Zairi • Emilie Le Rhun • Charlotte Cordonnier • Christine Delmaire • Claude-Alain Maurage • Florence Pasquier
•
Received: 10 February 2014 / Revised: 13 May 2014 / Accepted: 14 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Cerebral amyloid angiopathy (CAA) causes intracerebral haemorrhages and is associated with cognitive impairment and Alzheimer’s disease. In autopsy series, the estimated prevalence of CAA is high (20–40 % in nondemented subjects; 50–60 % in dementia) [1]. Brain magnetic resonance imaging (MRI) usually reveals cerebral microbleeds (CMB), white matter (WM) changes, lobar haemorrhages and silent acute cortical ischemic lesions. Convexity subarachnoid haemorrhage (cSAH) and cortical superficial siderosis (cSS) have been recently described [2]. Rarer, inflammatory forms (CAAi) are characterized by the presence of extensive WM and meningeal lesions [3]. Here, we report the case of a 64-year-old woman suffering from a non-inflammatory CAA presenting with an MRI suggestive of leptomeningitis in the clinical context of partial seizure.
The patient was referred to our hospital because of repeated and stereotyped episodes of numbness in the tongue with dysarthria followed by progressive paresthesia and hypoesthesia of the left arm and lower facial area in the last 3 days. Examination revealed epicritic hypoaesthesia and slight hypopallesthesia of the left hemibody. Partial ictal manifestations were confirmed by a right temporal epileptic focus on electroencephalography. Initial brain MRI showed an aspect of leptomeningitis in the right frontal (Fig. 1a, b) and cSS in the right central sulcus (Fig. 1c). Angio-MRI was normal. Three cerebrospinal fluid (CSF) tests showed only a slight hyperproteinorachia (0.7 g/L). All tests in search of an inflammatory, infectious, neoplastic or a paraneoplastic cause were negative except for a positron emission tomography showing uptake of two small axillary lymph nodes (benign). Twelve days after admission, MRI showed a bilateral extension of the pial lesions (Fig. 1d, e, f) still progressing one month after
A. Chouraki A. Rollin-Sillaire (&) V. Deramecourt F. Zairi E. Le Rhun C. Cordonnier C. Delmaire C.-A. Maurage F. Pasquier Univ Lille Nord de France, UDSL, 59000, Lille, France e-mail: [email protected]
E. Le Rhun Neurooncology, Lille University Hospital, 59037 Lille, France
A. Chouraki A. Rollin-Sillaire V. Deramecourt F. Pasquier Laboratory of Excellence DISTALZ, Memory Clinic, EA 1046, Lille University Hospital, 59000 Lille, France V. Deramecourt C.-A. Maurage Department of Pathology, Lille University Hospital, 59000 Lille, France
E. Le Rhun Department of Medical Oncology, Oscar Lambret Center, 59020 Lille, France C. Cordonnier Stroke Unit, Neurology Department, Lille University Hospital, 59000 Lille, France C. Delmaire Department of Neuroradiology, Lille University Hospital, 59000 Lille, France
F. Zairi Department of Neurosurgery, Lille University Hospital, 59000 Lille, France
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J Neurol
Fig. 1 Successive MRI done by the patient. First row: MRI on admission, a Right frontal leptomeningeal hyperintensities on FLAIR sequence. No corresponding hypointensities in T2* or hyperintensities on T1 were observed making the possibility of a large cSAH unlikely. b Gadolinium contrast enhancement of the right frontal meninges; c Cortical superficial siderosis of the right central sulcus evoking cSS. Second row Second MRI. d, e Progression of the FLAIR hyperintensities to the right frontal, temporal, parietal and occipital
areas and appearance of hyperintensities in the left parietal and occipital regions. f Progression of the Gadolinium-enhanced meningeal lesions. We considered this aspect and its progression as linked to a possible inflammatory process caused by the microglial activation detected at the biopsy possibly provoked by the amyloid deposits in the vessels walls. Third Row MRI one month after admission. g, h, i Progression of the leptomeningeal lesions
admission (Fig. 1g, h, e). The left occipital region was biopsied. Histological examination revealed Ab-positive CAA with intense leptomeningeal and cortical perivascular microglial activation without lymphocytic or granulomatous angiitis (Fig. 2).
This case illustrates an unusual presentation of CAA with partial seizures, corresponding to Transient Focal Neurological Symptoms and Signs (TFNSSs), and rapidly progressive leptomeningeal MRI abnormalities. When CAA is revealed by leptomeningeal abnormalities, it is usually
123
J Neurol Fig. 2 Brain and meningeal biopsy of the left occipital region. a Brain and meningeal biopsy stained with hematoxylin-eosin reagent. Note the thickened, hypercellular aspect of the pial mater (asterisk). The leptomeningeal arteriolar walls were eosinophilic and laminated (arrows). b Immunostaining of Ab pathological staining of the leptomeningeal and cortical arteriolar walls. c Immunostaining of CD68, revealing infiltration of the pial matter by macrophages. d Immunostaining of CD3, revealing the presence of only a few scattered T lymphocytes. Scale bar 50 l
associated with angiitis, clinically characterized by a confusional state or an impaired level of consciousness, a rapidly progressive cognitive impairment, sometimes seizures, headaches and/or hallucinations [3–5]. Brain MRI shows WM hyperintensities, sometimes with multiple CMB, usually without leptomeningeal enhancement [3, 4, 6, 7]. A cerebro-meningeal biopsy shows angiodestructive, sometimes granulomatous inflammation, infiltrated by lymphocytes and multinucleated giant cells [3], absent here. However, we noticed intense microglial activation in the leptomeninges and perivascular spaces which has been reported in patients with sporadic severe CAA and lobar cerebral haemorrhage, multiple cortical infarction/CMB and interpreted as a reaction towards the amyloid deposits in the vessels walls [8]. Nonetheless, we cannot totally exclude CAAi since only one biopsy was performed and has maybe missed the characteristic inflammation. TFNSSs constitute the second most commonly described clinical presentation of CAA, characterized by stereotypical episodes of progressive sensory symptoms, partial motor seizures and visual symptoms mimicking aura. They could be related to the haemorrhagic components of CAA (CMB, cSS and cSAH) [1]. Lastly, the main CAA-related MRI findings were absent. Our patient did not meet the Boston criteria for CAA. However, cSS was observed and matched the recently adopted MRI correlates of sporadic CAA [2]. A diagnosis of CAA becomes possible when applying the revised Boston criteria [9, 10].
The clinical and neuroradiological presentations of CAA are heterogeneous and emphasize the need to update the definition of this condition. It would be interesting to test the diagnostic value of combining clinical features with MRI markers and CSF biomarkers (such as Ab40) and compare these improved criteria with the neuropathological examination. Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical standard The manuscript submitted for publication has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
References 1. Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 83:124–137 2. Linn J, Herms J, Dichgans M, Bru¨ckmann H, Fesl G, Freilinger T et al (2008) Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 29:184–186 3. Scolding NJ, Joseph F, Kirby P, Mazanti I, Gray F, Mikol J et al (2005) Ab related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 128:500–515 4. Chung KK, Anderson NE, Hutchinson D, Synek B, Barber PA (2011) Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry 82:20–26
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J Neurol 5. Maia LF (2007) Mackenzie Ian R.A., Feldman HH. Clinical phenotypes of Cerebral Amyloid Angiopathy. J Neurol Sci 257:23–30 6. Kinnecom C, Lev MH, Wendell L, Smith EE, Rosand J, Frosch M et al (2007) Course of cerebral amyloid angiopathy-related inflammation. Neurology 68:1411–1416 7. Eng JA, Frosch MP, Choi K, Rebeck W, Greenberg SM (2004) Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol 55:250–256
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8. Yamada M, Itoh Y, Shintaku M, Kawamura J, Jensson O, Thorsteinsson L et al (1996) Immune reactions associated with cerebral amyloid angiopathy. Stroke 27:1155–1162 9. Smith EE, Greenberg SM (2003) Clinical diagnosis of cerebral amyloid angiopathy: validation of the boston criteria. Curr Atheroscler Rep 5:260–266 10. Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M et al (2010) Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 74:1346–1350
LETTER TO THE EDITORS
Cerebral amyloid angiopathy revealed by rapidly progressing leptomeningeal lesions Armelle Chouraki • Adeline Rollin-Sillaire • Vincent Deramecourt Fahed Zairi • Emilie Le Rhun • Charlotte Cordonnier • Christine Delmaire • Claude-Alain Maurage • Florence Pasquier
•
Received: 10 February 2014 / Revised: 13 May 2014 / Accepted: 14 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Cerebral amyloid angiopathy (CAA) causes intracerebral haemorrhages and is associated with cognitive impairment and Alzheimer’s disease. In autopsy series, the estimated prevalence of CAA is high (20–40 % in nondemented subjects; 50–60 % in dementia) [1]. Brain magnetic resonance imaging (MRI) usually reveals cerebral microbleeds (CMB), white matter (WM) changes, lobar haemorrhages and silent acute cortical ischemic lesions. Convexity subarachnoid haemorrhage (cSAH) and cortical superficial siderosis (cSS) have been recently described [2]. Rarer, inflammatory forms (CAAi) are characterized by the presence of extensive WM and meningeal lesions [3]. Here, we report the case of a 64-year-old woman suffering from a non-inflammatory CAA presenting with an MRI suggestive of leptomeningitis in the clinical context of partial seizure.
The patient was referred to our hospital because of repeated and stereotyped episodes of numbness in the tongue with dysarthria followed by progressive paresthesia and hypoesthesia of the left arm and lower facial area in the last 3 days. Examination revealed epicritic hypoaesthesia and slight hypopallesthesia of the left hemibody. Partial ictal manifestations were confirmed by a right temporal epileptic focus on electroencephalography. Initial brain MRI showed an aspect of leptomeningitis in the right frontal (Fig. 1a, b) and cSS in the right central sulcus (Fig. 1c). Angio-MRI was normal. Three cerebrospinal fluid (CSF) tests showed only a slight hyperproteinorachia (0.7 g/L). All tests in search of an inflammatory, infectious, neoplastic or a paraneoplastic cause were negative except for a positron emission tomography showing uptake of two small axillary lymph nodes (benign). Twelve days after admission, MRI showed a bilateral extension of the pial lesions (Fig. 1d, e, f) still progressing one month after
A. Chouraki A. Rollin-Sillaire (&) V. Deramecourt F. Zairi E. Le Rhun C. Cordonnier C. Delmaire C.-A. Maurage F. Pasquier Univ Lille Nord de France, UDSL, 59000, Lille, France e-mail: [email protected]
E. Le Rhun Neurooncology, Lille University Hospital, 59037 Lille, France
A. Chouraki A. Rollin-Sillaire V. Deramecourt F. Pasquier Laboratory of Excellence DISTALZ, Memory Clinic, EA 1046, Lille University Hospital, 59000 Lille, France V. Deramecourt C.-A. Maurage Department of Pathology, Lille University Hospital, 59000 Lille, France
E. Le Rhun Department of Medical Oncology, Oscar Lambret Center, 59020 Lille, France C. Cordonnier Stroke Unit, Neurology Department, Lille University Hospital, 59000 Lille, France C. Delmaire Department of Neuroradiology, Lille University Hospital, 59000 Lille, France
F. Zairi Department of Neurosurgery, Lille University Hospital, 59000 Lille, France
123
J Neurol
Fig. 1 Successive MRI done by the patient. First row: MRI on admission, a Right frontal leptomeningeal hyperintensities on FLAIR sequence. No corresponding hypointensities in T2* or hyperintensities on T1 were observed making the possibility of a large cSAH unlikely. b Gadolinium contrast enhancement of the right frontal meninges; c Cortical superficial siderosis of the right central sulcus evoking cSS. Second row Second MRI. d, e Progression of the FLAIR hyperintensities to the right frontal, temporal, parietal and occipital
areas and appearance of hyperintensities in the left parietal and occipital regions. f Progression of the Gadolinium-enhanced meningeal lesions. We considered this aspect and its progression as linked to a possible inflammatory process caused by the microglial activation detected at the biopsy possibly provoked by the amyloid deposits in the vessels walls. Third Row MRI one month after admission. g, h, i Progression of the leptomeningeal lesions
admission (Fig. 1g, h, e). The left occipital region was biopsied. Histological examination revealed Ab-positive CAA with intense leptomeningeal and cortical perivascular microglial activation without lymphocytic or granulomatous angiitis (Fig. 2).
This case illustrates an unusual presentation of CAA with partial seizures, corresponding to Transient Focal Neurological Symptoms and Signs (TFNSSs), and rapidly progressive leptomeningeal MRI abnormalities. When CAA is revealed by leptomeningeal abnormalities, it is usually
123
J Neurol Fig. 2 Brain and meningeal biopsy of the left occipital region. a Brain and meningeal biopsy stained with hematoxylin-eosin reagent. Note the thickened, hypercellular aspect of the pial mater (asterisk). The leptomeningeal arteriolar walls were eosinophilic and laminated (arrows). b Immunostaining of Ab pathological staining of the leptomeningeal and cortical arteriolar walls. c Immunostaining of CD68, revealing infiltration of the pial matter by macrophages. d Immunostaining of CD3, revealing the presence of only a few scattered T lymphocytes. Scale bar 50 l
associated with angiitis, clinically characterized by a confusional state or an impaired level of consciousness, a rapidly progressive cognitive impairment, sometimes seizures, headaches and/or hallucinations [3–5]. Brain MRI shows WM hyperintensities, sometimes with multiple CMB, usually without leptomeningeal enhancement [3, 4, 6, 7]. A cerebro-meningeal biopsy shows angiodestructive, sometimes granulomatous inflammation, infiltrated by lymphocytes and multinucleated giant cells [3], absent here. However, we noticed intense microglial activation in the leptomeninges and perivascular spaces which has been reported in patients with sporadic severe CAA and lobar cerebral haemorrhage, multiple cortical infarction/CMB and interpreted as a reaction towards the amyloid deposits in the vessels walls [8]. Nonetheless, we cannot totally exclude CAAi since only one biopsy was performed and has maybe missed the characteristic inflammation. TFNSSs constitute the second most commonly described clinical presentation of CAA, characterized by stereotypical episodes of progressive sensory symptoms, partial motor seizures and visual symptoms mimicking aura. They could be related to the haemorrhagic components of CAA (CMB, cSS and cSAH) [1]. Lastly, the main CAA-related MRI findings were absent. Our patient did not meet the Boston criteria for CAA. However, cSS was observed and matched the recently adopted MRI correlates of sporadic CAA [2]. A diagnosis of CAA becomes possible when applying the revised Boston criteria [9, 10].
The clinical and neuroradiological presentations of CAA are heterogeneous and emphasize the need to update the definition of this condition. It would be interesting to test the diagnostic value of combining clinical features with MRI markers and CSF biomarkers (such as Ab40) and compare these improved criteria with the neuropathological examination. Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical standard The manuscript submitted for publication has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
References 1. Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 83:124–137 2. Linn J, Herms J, Dichgans M, Bru¨ckmann H, Fesl G, Freilinger T et al (2008) Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 29:184–186 3. Scolding NJ, Joseph F, Kirby P, Mazanti I, Gray F, Mikol J et al (2005) Ab related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 128:500–515 4. Chung KK, Anderson NE, Hutchinson D, Synek B, Barber PA (2011) Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry 82:20–26
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J Neurol 5. Maia LF (2007) Mackenzie Ian R.A., Feldman HH. Clinical phenotypes of Cerebral Amyloid Angiopathy. J Neurol Sci 257:23–30 6. Kinnecom C, Lev MH, Wendell L, Smith EE, Rosand J, Frosch M et al (2007) Course of cerebral amyloid angiopathy-related inflammation. Neurology 68:1411–1416 7. Eng JA, Frosch MP, Choi K, Rebeck W, Greenberg SM (2004) Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol 55:250–256
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8. Yamada M, Itoh Y, Shintaku M, Kawamura J, Jensson O, Thorsteinsson L et al (1996) Immune reactions associated with cerebral amyloid angiopathy. Stroke 27:1155–1162 9. Smith EE, Greenberg SM (2003) Clinical diagnosis of cerebral amyloid angiopathy: validation of the boston criteria. Curr Atheroscler Rep 5:260–266 10. Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M et al (2010) Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 74:1346–1350
