Dataset Information

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

ABSTRACT:

Objective

To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE.

Methods

We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models.

Results

The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT-S and 0.88 [p = 0.001] for CAVE-S at the testing data).

Interpretation

Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357-370.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC10087209 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

Tanaka Tomotaka T Fukuma Kazuki K Abe Soichiro S Matsubara Soichiro S Ikeda Shuhei S Kamogawa Naruhiko N Ishiyama Hiroyuki H Hosoki Satoshi S Kobayashi Katsuya K Shimotake Akihiro A Nakaoku Yuriko Y Ogata Soshiro S Nishimura Kunihiro K Koga Masatoshi M Toyoda Kazunori K Matsumoto Riki R Takahashi Ryosuke R Ikeda Akio A Ihara Masafumi M

Annals of neurology 20220920 2

<h4>Objective</h4>To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE.<h4>Methods</h4>We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seiz ...[more]

PMID: 36053955

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Project description:Background and Purpose- We investigated cortical superficial siderosis (cSS) progression and its clinical relevance for incident lobar intracerebral hemorrhage (ICH) risk, in probable cerebral amyloid angiopathy presenting with neurological symptoms and without ICH at baseline. Methods- Consecutive patients meeting modified Boston criteria for probable cerebral amyloid angiopathy from a single-center cohort who underwent magnetic resonance imaging (MRI) at baseline and during follow-up were analyzed. cSS progression was assessed by comparison of the baseline and follow-up images. Patients were followed prospectively for incident symptomatic ICH. cSS progression and first-ever ICH risk were investigated in Cox proportional hazard models adjusting for confounders. Results- The cohort included 118 probable cerebral amyloid angiopathy patients: 72 (61%) presented with transient focal neurological episodes and 46 (39%) with cognitive complaints prompting the baseline MRI investigation. Fifty-two patients (44.1%) had cSS at baseline. During a median scan interval of 2.2 years (interquartile range, 1.2-4.4 years) between the baseline (ie, first) MRI and the latest MRI, cSS progression was detected in 33 (28%) patients. In multivariable logistic regression, baseline cSS presence (odds ratio, 4.04; 95% CI, 1.53-10.70; P=0.005), especially disseminated cSS (odds ratio, 9.12; 95% CI, 2.85-29.18; P<0.0001) and appearance of new lobar microbleeds (odds ratio, 4.24; 95% CI, 1.29-13.9; P=0.017) were independent predictors of cSS progression. For patients without an ICH during the interscan interval (n=105) and subsequent follow-up (median postfinal MRI time, 1.34; interquartile range, 0.3-3 years), cSS progression independently predicted increased symptomatic ICH risk (hazard ratio, 3.76; 95% CI, 1.37-10.35; P=0.010). Conclusions- Our results suggest that cSS evolution may be a useful biomarker for assessing disease progression and ICH risk in cerebral amyloid angiopathy patients and a candidate biomarker for clinical studies and trials.

Project description:Cortical superficial siderosis is an established haemorrhagic neuroimaging marker of cerebral amyloid angiopathy. In fact, cortical superficial siderosis is emerging as a strong independent risk factor for future lobar intracerebral haemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cortical superficial siderosis remain elusive. Here we use an in vivo MRI, ex vivo MRI, histopathology approach to assess the neuropathological correlates and vascular pathology underlying cortical superficial siderosis. Fourteen autopsy cases with cerebral amyloid angiopathy (mean age at death 73 years, nine males) and three controls (mean age at death 91 years, one male) were included in the study. Intact formalin-fixed cerebral hemispheres were scanned on a 3 T MRI scanner. Cortical superficial siderosis was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, 11 representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI-defined cortical superficial siderosis. In addition, samples were taken from predefined standard areas of the brain, blinded to MRI findings. Serial sections were stained for haematoxylin and eosin and Perls' Prussian blue, and immunohistochemistry was performed against amyloid-β and GFAP. Cortical superficial siderosis was present on ex vivo MRI in 8/14 cases (57%) and 0/3 controls (P = 0.072). Histopathologically, cortical superficial siderosis corresponded to iron-positive haemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels. Increased severity of cortical superficial siderosis was associated with upregulation of reactive astrocytes. Next, cortical superficial siderosis was assessed on a total of 65 Perls'-stained sections from MRI-targeted and untargeted sampling combined in cerebral amyloid angiopathy cases. Moderate-to-severe cortical superficial siderosis was associated with concentric splitting of the vessel wall (an advanced form of cerebral amyloid angiopathy-related vascular damage) in leptomeningeal vessels (P < 0.0001), but reduced cerebral amyloid angiopathy severity in cortical vessels (P = 0.048). In terms of secondary tissue injury, moderate-to-severe cortical superficial siderosis was associated with the presence of microinfarcts (P = 0.025), though not microbleeds (P = 0.973). Collectively, these data suggest that cortical superficial siderosis on MRI corresponds to iron-positive deposits in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. Cortical superficial siderosis appears to be the result of predominantly advanced cerebral amyloid angiopathy of the leptomeningeal vessels and may trigger secondary ischaemic injury in affected areas.

Dataset Information

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

Objective

Methods

Results

Interpretation

Publications

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

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