HARM revisited: Etiology of subarachnoid hyperintensities in brain FLAIR MRI

Abstract

Background: The hyperintense acute reperfusion marker (HARM) describes a phenomenon with a hyperintense signal in the subarachnoid space in Fluid-Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging (MRI) sequences, presumably based on blood–brain barrier breakdown in acute stroke with reperfusion. However, this imaging phenomenon was described in other medical conditions. Aim: Determination of the prevalence and associated clinical findings of this phenomenon in a large sample of patients with different neurological conditions. Methods: This is retrospective, single-center, observational study of 23,948 cerebral MRIs acquired in a Neurological University Clinic over 5 years. The prevalence of HARM, the underlying diagnosis, and damage pattern were examined by chart analysis; MRI was analyzed regarding the type of acute lesions, extent of microangiopathic lesions, and whether gadolinium-based contrast agent (GBCA) was given. Results: Among the MRI data, 84 images (0.35%) from 61 patients were HARM-positive without a subarachnoid signal abnormality in any other sequence. Etiologies were heterogeneous; 35 patients had a cerebrovascular disease (CVD; 19 patients received recanalization therapy), 12 patients had an inflammatory central nervous system (CNS) disease and 14 patients had epilepsy. GBCA was applied to 64% of the patients. Conclusion: HARM was a rare radiological finding in a range of different neurological pathologies, not limited to stroke, or to previous reperfusion therapy and was not dependent on previous GBCA administration. Our data suggest that the term is too narrow in terms of the concepts of the underlying pathology. We propose to use the term FLAIR Subarachnoid Hyperintensity (“FLASH”) phenomenon which might better reflect the observation that the radiological sign can be associated with a variety of central neurological conditions without a straightforward association with therapy.

Hyperintense Acute Reperfusion Marker Sign in Patients with Diffusion Weighted Image-negative Transient Ischemic Attack HARM Sign in DWI-negative TIA

“…3 A study showed that, when more than 20,000 brain magnetic resonance imaging (MRI) scans were examined, the HARM sign was a rare finding identified in only 0.35% of the scans. 4 However, the HARM sign was observed in 83% of cases of subacute strokes and 10% of TIA cases, indicating that the HARM sign can confirm a cerebral ischemic insult. 5,6 In terms of clinical significance, the HARM sign correlates with hemorrhagic transformation and parenchymal hemorrhage, and it is associated with worse clinical outcomes of stroke.…”

“…3 A study showed that, when more than 20,000 brain magnetic resonance imaging (MRI) scans were examined, the HARM sign was a rare finding identified in only 0.35% of the scans. 4 However, the HARM sign was observed in 83% of cases of subacute strokes and 10% of TIA cases, indicating that the HARM sign can confirm a cerebral ischemic insult. 5,6…”

Subarachnoid CSF Hyperintensities at 7 Tesla FLAIR MRI: A Novel Marker in Cerebral Amyloid Angiopathy

“…The phenomenon can be a sign of pathologies of the subarachnoid space and/or vessel wall permeability. (Althaus et al, 2022;Stuckey et al, 2007) In cerebral amyloid angiopathy (CAA), subarachnoid CSF hyperintensities on non-contrast 1.5T (T) or 3T FLAIR MRI are often considered a sign of acute convexity subarachnoid hemorrhage (cSAH): acute bleeding from the leptomeningeal vessels into the subarachnoid space. (Calviere et al, 2016) It is hypothesized that (repeated episodes of) cSAH can lead to cortical superficial siderosis (cSS), a hallmark hemorrhagic neuroimaging marker of CAA and one of the strongest predictors for intracerebral hemorrhage (ICH).…”