By Santosh Murthy, MD
Synopsis: The early diagnosis of spontaneous intracerebral hemorrhage (ICH) is important to initiate rapid interventions, such as lowering blood pressure and reversing the effects of antithrombotic medications. Plasma assays of glial fibrillary acidic protein may become a useful tool for the prehospital diagnosis of ICH, but it needs further study before adoption in the clinical setting.
Source: Kalra LP, Zylyftari S, Blums K, et al. Rapid diagnosis of intracerebral hemorrhage in patients with acute stroke by measuring prehospital GFAP levels on a point-of-care device (DETECT). Neurology. 2025;105(2):e213823.
Spontaneous intracerebral hemorrhage (ICH) has the highest morbidity and mortality among stroke subtypes. Similar to ischemic stroke, the management of ICH has shifted toward ultra-early interventions such as intensive blood pressure control and reversal of anticoagulation therapy, which are associated with improved long-term outcomes. Therefore, timely diagnosis of ICH is of paramount importance. The gold standard test to diagnose an ICH is a non-contrast computed tomography (CT) scan of the head. However, there are logistic delays in obtaining head CT scans, which include time to transport patients from the field to the hospital and lack of CT scanners, especially if patients are transported to rural or small community hospitals. The pre-hospital setting is a great opportunity to identify ICH patients early and initiate interventions quickly.
In this context, Kalra and colleagues describe a novel point-of-care assay that measures glial fibrillary acidic protein (GFAP) in the plasma. The prospective study included 353 patients with an acute stroke within six hours of symptom onset. Notably, patients younger than 18 years of age and those with a recent stroke, intracranial hemorrhage, traumatic brain injury (TBI), or a history of brain tumor, were excluded. Blood samples were collected in the prehospital phase, and plasma GFAP measurements were performed on a proprietary device about 15 minutes after arrival at the hospital.
The gold standard was the final diagnosis categorized as ICH, ischemic stroke, or stroke mimic. The median GFAP levels were 208 pg/mL in ICH, 30 pg/mL in ischemic stroke, and 48 pg/mL in patients with a stroke mimic. The optimal GFAP cutoff point to differentiate ICH from ishemic stroke and stroke mimic was 55 pg/mL (area under the curve [AUC] of 0.880) with a sensitivity at this threshold of 80.3% and specificity of 77.6%.
The authors also found that the diagnostic accuracy of GFAP decreased with increasing age and was highest in the age group < 72 years (AUC of 0.944) compared to the other two groups, 72-83 years of age (0.907) and > 83 years of age (AUC of 0.790). Furthermore, the predictive accuracy of GFAP in diagnosing ICH in anticoagulated patients was 89.7%, and a cutoff of 150 pg/mL resulted in a sensitivity of 75% and a specificity of 100%.
Although these findings show promise for the prehospital detection of acute ICH, it is important to note the limitations of this study, which were the small sample size, low accuracy in detecting small ICHs, lack of external validation, and acquiring whole blood samples that needed processing to measure GFAP on plasma samples.
Commentary
The prehospital diagnosis of acute ICH has assumed importance in recent times with the emergence of the “Code ICH” paradigm, which emphasizes the “time is brain” concept used widely in the management of acute ischemic stroke. While this is important in all ICH patients, secondary analyses of large trials showed that ultra-early (< 2 hours) intensive control of blood pressure resulted in lower rates of hematoma expansion and translated to lower mortality and better functional outcomes. Along the same lines, time to reversal of anticoagulation also is associated with lower disability in ICH patients.
The field of stroke also has seen the evolution of mobile stroke units equipped with portable CT scanners, which can significantly expedite hyperacute therapies for stroke, such as blood pressure control and administration of thrombolysis. However, fiscal constraints and the size of large metropolitan cities mean that the majority of patients with stroke-like symptoms will be attended to by the conventional ambulances, which do not have CT scanning capabilities. A simple blood test with a high predictive accuracy for ICH can aid in the prehospital selection of patients with an ICH.
That said, GFAP testing also is approved for TBI, since structural brain damage can lead to high GFAP levels. Similarly, other conditions, such as brain tumors, also may result in elevated GFAP levels. Therefore, larger prospective confirmation and validation is warranted to study the predictive accuracy of GFAP testing to include patients with preexisting neurological disorders.
Santosh Murthy, MD, is Assistant Professor of Neurology, Weill Cornell Medical College.
