A Causal Classification System for Intracerebral Hemorrhage Subtypes

Abstract

Objective: Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging.

Methods: CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland.

Results: In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort.

Interpretation: CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28.

FIGURE 1

Examples of intracerebral hemorrhage (ICH) subtyping using CLASsification system for ICH Subtypes (CLAS‐ICH) system. (A–C) Axial T2*‐weighted gradient recalled echo and (D) fluid‐attenuated inversion recovery magnetic resonance imaging sequences. (E, F) Axial non‐contrast computed tomography. Every patient is scored in each ICH subgroup (arteriosclerosis [A], cerebral amyloid angiopathy [C], mixed small vessel disease [M], other form of small vessel disease [O], secondary cause [S]) according to the level of diagnostic evidence: (1) well‐defined ICH subtype; (2) possible underlying disease; and (0) absence of evidence of the disease that may have caused ICH. (A) Deep left thalamic ICH with multiple strictly deep microbleeds (A1 C0 M0 O0 S0). (B) Left lobar ICH with multiple strictly lobar microbleeds and disseminated cortical superficial siderosis (A0 C1 M0 O0 S0). (C) Left lobar ICH with multiple hemorrhages (microbleeds and ICH) located both in lobar and deep regions of the brain (A0 C0 M1 O0 S0), (D) Single (ie, without other hemorrhage) left lobar ICH with confluent white matter hyperintensities in a 68‐year‐old man, and normal magnetic resonance angiography (A0 C2 M2 O0 S0). (E) Right lobar ICH with underlying arteriovenous malformation (A0 C0 M0 O0 S1). (F) Right lobar ICH without evidence of small vessel disease on computed tomography and normal computed tomography angiography in a 72‐year‐old woman (A0 C2 M0 O0 S2).

FIGURE 2

Overlap between intracerebral hemorrhage subtypes. Venn diagram showing overlap between ICH subtypes (level 1 or 2) included in CLASsification system for ICH Subtypes (CLAS‐ICH). SVD = small vessel disease.