Headache in Cerebral Hemorrhage Is Associated With Inflammatory Markers and Higher Residual Cavity


  • Rogelio Leira MD, PhD,

  • Mar Castellanos MD, PhD,

  • José Álvarez-Sabín MD, PhD,

  • Exuperio Diez-Tejedor MD, PhD,

  • Antonio Dávalos MD, PhD,

  • José Castillo MD, PhD,

  • on Behalf of the Stroke Project, Cerebrovascular Diseases Group of the Spanish Neurological Society

  • From the Department of Neurology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain (Drs. Leira and Castillo); Department of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain (Dr. Castellanos); Department of Neurology, Hospital Universitari Vall d'Hebrón, Barcelona, Spain (Dr. Álvarez-Sabín); Department of Neurology, Hospital Universitario La Paz, Madrid, Spain (Dr. Diez-Tejedor); and Department of Neurology, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain (Dr. Dávalos).

Address all correspondence to Dr. José Castillo, Department of Neurology, Hospital Clínico Universitario, Santiago de Compostela, Spain.


Background and Purpose.—The mechanisms responsible for headache in patients with intracerebral hemorrhage (ICH) are not completely understood. The present study was undertaken to analyze the headache-associated factors, the possible related biochemical mechanisms, and the headache potential predictors of outcome in spontaneous ICH.

Methods.—We prospectively studied 189 patients from a large cohort of 266 consecutive patients with supratentorial ICH admitted within the first 12 hours of symptoms onset. The presence of headache at stroke onset was evaluated in these patients. The volumes of the initial ICH, peripheral edema at 48 hours, and the residual cavity at 3 months were measured on CT scan. Glutamate, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α levels were measured in blood samples obtained on admission. The Canadian Stroke Scale (CSS) and the modified Rankin Scale were used to evaluate stroke severity and neurological outcome, respectively.

Results.—Headache at onset of stroke was observed in 65 patients (34.4%). Patients who experienced headache had a significantly higher frequency of history of infection (P= .009) or inflammation (P= .045), as well as higher body temperature (P= .021), leukocyte count (P= .038), ESR (P= .011), and mass effect (P= .017) on admission. Plasma concentrations of IL-6 and TNF-α were significantly higher in patients with headache than in those without. Headache was an independent predictor of the residual cavity volume in patients with spontaneous ICH (odds ratio 6.49; 95% CI 2.51 to 16.78; P= .0001).

Conclusions.—Headache at ICH onset is associated with clinical and biochemical markers of inflammation and is an independent predictor of higher residual cavity volume after spontaneous ICH.