Abstract
The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1–10. CGRP levels were determined via competitive enzyme immunoassay and calculated as “area under the curve” (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11–35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.
Highlights
Spontaneous subarachnoid hemorrhage represents a complex and still devastating neurovascular disease, associated with substantial morbidity and mortality
Each patient had been admitted to hospital within 48 h of ictus in prognostically favorable, good to moderate neurological condition, that means with a Hunt and Hess (HH) score [57] of 1 to 4 or a World Federation of Neurosurgical Societies (WFNS) score [58] of 1 to 4 and an initial Glasgow Coma Scale (GCS) of ≥ 9
After having detected significant correlations between increased area under the curve” (AUC) calcitonin gene-related peptide (CGRP) levels and various health-related quality of life (hrQoL) domains in the univariate analysis, we developed a multivariate model including AUC CGRP, age, gender, treatment modality (MS vs. EV vs. perimesencephalic subarachnoid hemorrhages (pSAH)), site of the aneurysm, HH grade, WFNS grade, Fisher grade, initial GCS, and cerebral vasospasm (CV) to analyze their impact on the respective hrQoL domains
Summary
Spontaneous subarachnoid hemorrhage (sSAH) represents a complex and still devastating neurovascular disease, associated with substantial morbidity and mortality. About 85% of the non-traumatic spontaneous events comprise aneurysmal subarachnoid hemorrhages (aSAH) and 10% are non-aneurysmal perimesencephalic subarachnoid hemorrhages (pSAH) [5]. ASAH and pSAH are two diseases with different evolutions [6]. Compared with aSAH, pSAH represents a subarachnoid hemorrhage (SAH) entity with a very distinct and usually more benign clinical course [6,7,8]. The survivors harbor serious risks of neurological dysfunction, functional disability, and cognitive impairment [9, 10], even months to years after ictus [11, 12]. There is a marked disparity between reattained functional independence in up to 70% [13] of the sSAH patients and considerable long-term neuropsychological deficits [9, 10, 14] in up to 94.6% [15] with a reduced health-related quality of life (hrQoL) in 35% of the patients 1 year after sSAH [12, 16], anxiety (in up to 54%) [11, 17], depression (approaching 61.7%) [17, 18], and, in up to two-thirds [9, 19], the inability to reassume one’s previous occupation [19, 20] [9, 14]
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