HomeStrokeVol. 54, No. 2Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBCortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy Aikaterini Theodorou, MD, Maria Chondrogianni, MD, Eleni Bakola, MD, Georgia Kaloudi, MD, Aikaterini Foska, MD, Smaragdi Michalakakou, MD, Konstantinos Melanis, MD, Georgios P. Paraskevas, MD and Georgios Tsivgoulis, MD Aikaterini TheodorouAikaterini Theodorou https://orcid.org/0000-0001-7229-2610 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Maria ChondrogianniMaria Chondrogianni https://orcid.org/0000-0002-8315-5846 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Eleni BakolaEleni Bakola https://orcid.org/0000-0002-7002-9795 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Georgia KaloudiGeorgia Kaloudi Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Aikaterini FoskaAikaterini Foska https://orcid.org/0000-0002-5164-4952 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Smaragdi MichalakakouSmaragdi Michalakakou https://orcid.org/0000-0001-9027-3050 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Konstantinos MelanisKonstantinos Melanis https://orcid.org/0000-0002-3224-3053 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author , Georgios P. ParaskevasGeorgios P. Paraskevas https://orcid.org/0000-0002-2481-3060 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author and Georgios TsivgoulisGeorgios Tsivgoulis Correspondence to: Georgios Tsivgoulis, MD, Second Department of Neurology, “Attikon” University Hospital Rimini 1, Chaidari, 12462, Greece. Email E-mail Address: [email protected] https://orcid.org/0000-0002-0640-3797 Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece. Search for more papers by this author Originally published5 Jan 2023https://doi.org/10.1161/STROKEAHA.122.041395Stroke. 2023;54:e48–e51Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 5, 2023: Ahead of Print Take Home PointsTFNEs are one of the most common clinical features of CAA, with a prevalence of more than 50% among CAA patients.CAA-related TFNEs should be considered in the differential diagnosis of recurrent, stereotyped episodes with focal neurologic symptoms and characteristic spreading symptomatology.If TFNE are suspected, the brain computed tomography and MRI should be carefully evaluated for possible CAA and antithrombotic treatment should be avoided if a diagnosis of CAA is made.TFNEs with accompanied cSS/cSAH have been associated with higher risk of intracranial hemorrhage among patients with CAA.A 71-year-old functionally independent, right-handed man, with known dyslipidemia and arterial hypertension presented initially due to a transient episode of mixed aphasia, lasting 12 minutes. The patient underwent brain magnetic resonance imaging (MRI), which excluded acute cerebral ischemia and intracranial hemorrhage (ICH). Fluid-attenuated inversion recovery sequences showed multiple (>10) bilateral, small, hyperintense lesions in the subcortical white matter and T2-weighted sequences revealed MRI-visible enlarged periventricular spaces in centrum-semiovale. Susceptibility-weighted imaging revealed linear hypointensities along multiple left cortical regions, mainly in the parietal lobe, consistent with cortical superficial siderosis (cSS; Figure 1). This neuroimaging finding was not described in the report from the outside institution. The patient was diagnosed with a transient ischemic attack and treated with dual-antiplatelet therapy (clopidogrel 75 mg/day plus acetylsalicylic-acid 100 mg/day) for 21 days, followed by clopidogrel 75 mg/day. Due to severe (≥70%), misdiagnosed as symptomatic, left internal carotid artery stenosis, left carotid endarterectomy was performed.Download figureDownload PowerPointFigure 1. Baseline magnetic resonance imaging (MRI). The patient experienced a transient brief episode of mixed aphasia and underwent brain MRI. Susceptibility-weighted imaging (SWI) sequences (A–D, red arrows and circles with dotted lines) showed linear hypointensities along multiple cortical regions in left frontal and parietal lobes. Fluid-attenuated inversion recovery (FLAIR) sequences (E) revealed multiple (>10) small bilateral hyperintense lesions in subcortical white matter and T2-weighted sequences (F) showed MRI-visible enlarged periventricular spaces in centrum-semiovale.Two months later the patient presented with sudden-onset aphasia, right-sided hemiparesis, and sensory deficits. Neurological examination revealed a National Institutes of Health Stroke Scale Score of 7. Brain computed tomography showed acute lobar ICH left frontotemporal with perifocal edema. Brain computed tomography–angiography did not find cerebral aneurysms, vascular malformations, or other abnormal findings. Brain MRI revealed acute lobar ICH and multiple bilateral areas of cSS without any cerebral microbleeds (Figure 2). cSS identified post hoc in previous MRI was identical to the location of current lobar ICH. The patient was diagnosed with probable cerebral amyloid angiopathy (CAA) according to the revised Boston-Criteria v2.01 and ApoE genotype revealed ε2/ε3 alleles. After reevaluation of the patient’s history, we hypothesized that the previous episode of mixed aphasia was a transient focal neurological episode (TFNE) due to underlying cSS.Download figureDownload PowerPointFigure 2. Follow-up magnetic resonance imaging. Susceptibility-weighted imaging (SWI) sequences revealed cortical superficial siderosis in multiple regions (A–D, red arrows) and the acute intracranial hemorrhage in left temporoparietal lobe. E–F, Red circles with dotted lines.Antiplatelet treatment was withdrawn and the patient was treated conservatively with osmotic therapy and tight control of arterial blood pressure. He showed gradual clinical and radiological improvement. Ten days later, he was discharged with an National Institutes of Health Stroke Scale score of 4 to a rehabilitation facility.DiscussionSporadic CAA is a small vessel disease, affecting cortical/leptomeningeal arterioles and is characterized pathologically by deposition of amyloid-Aβ within the cerebrovascular wall.2 It is a disease of the elderly without sex predominance and the clinical spectrum includes spontaneous lobar ICH, cognitive decline, and CAA-related TFNEs.2 The underlying cause in about 74% of spontaneous lobar ICH is CAA. Even in the absence of oral anticoagulation, CAA-related ICH has a high recurrence risk (≈10% per year).CAA-related TFNEs, also called amyloid spells, are attributed to cSS or convexity subarachnoid hemorrhage (cSAH), which is the neuroimaging manifestation of cSS in the acute phase and possibly originates from CAA-affected leptomeningeal vessels.3 In 2010, cSS was included in modified Boston-Criteria v1.5. as an emerging radiological marker,4 and the prevalence of TFNEs and cSS are calculated to be ≈50% among patients with CAA.TFNEs are of brief duration (<30 minutes) and characterized by recurrent, stereotyped episodes of focal symptoms, with spreading progression mimicking a migratory spread.3 More than 50% of patients with TFNEs have predominantly positive symptoms including aura-like spreading paresthesias, limb jerking, and visual paresthesias. Negative symptoms such as sudden-onset limb weakness or aphasia, which resemble transient ischemic attacks are also common.3 The majority of these patients report multiple, stereotyped episodes (≥2), over the course of days, weeks, or years.3CAA-related TFNEs are mostly attributed to cSS, which represents the deposition of chronic blood-breakdown products within the supratentorial, subarachnoid space and along the superficial cortical layers.3 This deposition is responsible for curvilinear hypointense lesions along the leptomeningeal spaces and cerebral convexities, detected in blood-sensitive MRI sequences. Another characteristic neuroimaging feature is cSAH, detected on brain computed tomography as hyperintense lesions limited to the subarachnoid space of the convexities, not extending into the parenchyma, sylvian fissures, ventricles, or basal cisterns. cSAH is also seen in blood-sensitive MRI sequences with characteristic blooming in the same region.5 There is a wide differential diagnosis of cSAH or cSS including reversible cerebral vasoconstriction syndrome, cortical vein or dural sinus thrombosis, aneurysm rupture, etc. However, the most common cause of cSAH in a patient over 60 years is overwhelmingly CAA.6The diagnosis of CAA-related TFNEs relies on identification of a compatible clinical syndrome characterized by TFNEs, often unilateral, usually resolving within 30 minutes.3 Main TFNEs features are the migratory-like spread from one body part to another as well as stereotypic, recurrent episodes. Neuropathologic or neuroimaging evidence of CAA in patients older than 50 years old should also be fulfilled according to the revised Boston-criteria v2.0.1 Not all TFNEs are CAA-related and other possible underlying causes, including migraine with aura, focal seizures, structural lesions, etc should be taken into account. Neurologists should be able to differentiate small diffusion-weighted imaging lesions often close to areas of siderosis detected in patients with CAA-related TFNEs from larger diffusion-weighted imaging lesions in specific vascular territories, seen in ischemic infarcts.3,5Prognosis in CAA-related TFNEs is strongly associated with a higher risk of future symptomatic spontaneous lobar ICH and recurrent cSAH. More specifically, patients with CAA who suffered a cSAH have a 11% risk for future recurrent cSAH and 13% risk for future ICH, respectively.6 Comparing patients with and without cSS, the presence of cSS in CAA patients doubles the risk of any ICH in the future, and in cases with disseminated cSS, the risk is 4× higher.7 Moreover, a recent study showed doubled ICH incidence among patients with motor TFNEs and 4 times higher ICH incidence among patients who received antithrombotic agents.8 Despite the unknown pathophysiological mechanism, the APOE ε2/+ genotype is also associated with higher risk of severe cSS and bleeding risk.9 Consequently, presence and extent of cSS, antithrombotic therapy, and presence of APOE ε2/+ alleles are considered important prognostic risk factors for future ICH.Due to high bleeding risk, especially in the acute phase of cSAH, blood pressure should be tightly controlled and all antithrombotic/anticoagulant medications should be avoided for at least 24 to 48 hours.10 Later and dependent on the indication, their administration should be reevaluated accordingly. In cases with CAA, where transient ischemic attacks or ischemic strokes cannot be excluded as an underlying mechanism of symptoms or in patients with coexisting atrial fibrillation and other vascular risk factors, hypertension, diabetes, and dyslipidemia should be controlled and the option of left atrial appendage occlusion discussed.3 Moreover, antiepileptic medications, including levetiracetam or lacosamide, despite the limited data regarding their effectiveness, may be useful in patients with persistent attacks.3In this case report, we present a patient with CAA-related TFNE, initially misdiagnosed as transient ischemic attack, leading to administration of antiplatelet therapy and carotid endarterectomy for a severe internal carotid artery stenosis, erroneously diagnosed as symptomatic. Two months later the patient experienced a lobar ICH. This case illustrates the possible devastating consequences of not carefully evaluating all available neuroimaging findings and administrating antithrombotics in patients with CAA-related TFNEs; the ICH risk is clearly higher among patients with CAA and cSS/cSAH. In conclusion, this case highlights the importance of a comprehensive understanding of CAA-related TFNEs and continuous vigilance to detect them and avoid therapies with high bleeding risk.Article InformationAcknowledgmentsDr Theodorou contributed to the study concept and design, acquisition of data, interpretation, writing, and critical revision of the article for important intellectual content. Drs Chondrogianni, Bakola, Kaloudi, Foska, Michalakakou, Melanis, and Paraskevas contributed to the acquisition of data and critical revision of the article for important intellectual content. Dr Tsivgoulis contributed to the study concept, analysis and interpretation, and critical revision of the article for important intellectual content.Sources of FundingNone.Disclosures Dr Paraskevas reports compensation from Biogen for consultant services. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see pages e50–e51.Correspondence to: Georgios Tsivgoulis, MD, Second Department of Neurology, “Attikon” University Hospital Rimini 1, Chaidari, 12462, Greece. Email [email protected]gr