Evaluating a New or Changing Headache in a Seriously Ill Patient

  • Justin Yu MD MS
  • Laurie Knepper MD
  • Chauncey Spears MD
  • Robert M Arnold MD

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Background     Evaluating headaches in patients with serious illness presents a diagnostic dilemma as many patients already have “red flags” related to their underlying illness (1). While most headaches will reflect a primary headache disorder, seriously ill patients have a significantly higher risk for life-threatening headache etiologies than the general population. Therefore, in this Fast Fact, we suggest that all seriously-ill adult patients with a new or changing headache be considered for prompt evaluation.

Classification     Primary headache disorders (e.g., migraine, tension, and medication overuse) typically have no underlying secondary cause and are “benign” in the sense that they are not life-threatening. Secondary headaches result from another condition and sometimes are life-threatening. We suggest clinicians frame their consideration of secondary headaches around three broad categories: structural, vascular, and infection (Table) (2).

Classification and Diagnostic Approach to Secondary Headache 

CategoryExamplesRed FlagsDiagnostic ConsiderationsPotential Treatments
StructuralTumorCerebral EdemaAltered mental statusFocal neurologic deficitSeizureHistory of malignancyMRI with contrastCorticosteroidsSurgical decompressionRadiation therapy
VascularStrokeIntracerebralhemorrhage (SAH, SDH, IPH)Vertebral or carotid artery dissectionVenous thrombosisPRESRCVSGiant Cell ArteritisAge >50 yearsSudden onset: “Thunderclap”Focal neurologic deficitAltered mental statusRecent traumaAnticoagulation Temporal artery tendernessBlurred visionAngiographyMRI without contrastCoagulation profileLumbar punctureESR & CRPThrombolysisThrombectomySurgical evacuation or decompressionBlood pressure managementCorticosteroids
InfectionMeningitisEncephalitisAbscessFeverImmunocompromisedRecent CNS surgery or instrumentationBlood CultureCRPRapid HIV testLumbar PunctureMRI with contrastDexamethasoneAntibioticsHardware removal

Abbreviations: SAH, subarachnoid hemorrhage; IPH, intraparenchymal hemorrhage; SDH, subdural hematoma; PRES, Posterior Reversible Encephalopathy Syndrome; RCVS, Reversible Cerebral Vasoconstriction Syndrome; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein 

Special Considerations

  • Cancer – New or worsening headache in patients with solid tumors, especially lung, melanoma, breast, or colon cancer should elicit concern for metastatic disease (3,4). Additional red flags in this population include progressive and indolent headache (>8 weeks), associated nausea/vomiting, and focal neurologic deficits. Clinical signs may lack specificity however, therefore brain MRI with contrast should be considered in all patients with cancer and new or changing headache (5,6). Headaches due to neoplastic meningitis (leptomeningeal metastases) should also be considered. We refer readers to Fast Fact #135 for further detail and diagnostic considerations.
  • Anticoagulation – Intracerebral hemorrhage (ICH) remains a devastating complication of anticoagulation therapy, with an annual rate for patients taking warfarin of 0.3-0.6%, and 0.1-0.2% for those on newer oral anticoagulants (7). Vomiting, and more ominously, decreased consciousness that appears and progresses quickly (i.e., hours) should prompt immediate concern.
  • Age – Risk of a life-threatening secondary HA is 10 times higher in those 65 years and older (8). In one series of patients with new-onset headache, 15% of those 65 years or older had a secondary headache compared with 1.6% of patients younger than 65 years (9).

Determining Diagnostic Course of Action     As new or changing headaches are more likely to represent life-threatening complications in seriously-ill patients than the general population, they should prompt clinicians to consider urgent evaluation. The decision to pursue diagnostic testing, however, is dependent on a patient’s prognosis, location, and overall goals of care. For patients with shorter prognoses and care goals focused on comfort, deferring diagnostic work-up in lieu of aggressive symptom management might be the right decision. On the other hand, for patients with longer prognoses, diagnostic work-up could be worthwhile, even for some with comfort-focused goals of care, since some underlying causes are quite treatable.


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  2. Filler L, Akhter M, & Nimlos P. Evaluation and management of the emergency department headache. Semin Neurol. 2019; 39:20-26.
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  9. Pascual J & Berciano J. Experience in the diagnosis of headaches that start in elderly people. J Neurol Neurosurg Psychiatry. 1994; 57(10):1255-1257.

Authors’ Affiliations: University of Pittsburgh School of Medicine, Pittsburgh, PA (JY, LK, RA). University of Michigan School of Medicine, Ann Arbor, MI (CS).

Conflicts of Interest: The authors have declared no conflicts of interest. 

Version History:  Originally edited by Drew A Rosielle; first electronically published in October 2019