Background: Herpes simplex encephalitis (HSE) is a severe, and often fatal, condition requiring timely diagnosis and treatment. Little is known about the frequency and factors associated with diagnostic delays.
Methods: We conducted a retrospective cohort study using the Truven Health Analytics Commercial Claims and Encounters Database from 2011-2016. We identified case visits where patients were first diagnosed with HSE. We analyzed visits prior to the index HSE diagnosis for HSE-related symptoms, including fever, headache, seizure, neurologic disorder or impaired consciousness. We utilized a time-series change-point analysis and simulation models to identify the window before an HSE diagnosis where diagnostic opportunities began to appear and to estimate the likelihood of actual diagnostic delays.
Results: Our study cohort included 3,390 cases of HSE. There is a dramatic spike in visits with HSE-related symptoms that occurs just prior to the index HSE diagnosis (see figure). Prior to the index diagnosis we identified 2,459 visits, from 938 patients, that contained possible symptoms of HSE. We estimated that approximately 1,355 (CI 1,195-1,490) visits represented likely diagnostic delays with around 20% (CI 18.8-21.0) of patients experiencing at least one missed opportunity. The median duration of diagnostic delays, from first symptoms to diagnosis, was 6 days. Most diagnostic opportunities occurred in outpatient settings, 835 delays (CI 739-944), followed by emergency departments, 313 delays (CI 252-354), and inpatient settings, 259 (CI 226-291).
Diagnostic opportunities involving seizures tended to occur earliest (median 7 days before HSE diagnosis), followed by headaches, neurologic symptoms or changes in mental status (5 days), and finally fever (3 days). Patients with a history of 3 or more visits for chronic migraines, 90 days before HSE, were more likely to experience a diagnostic delay, OR 2.5 (CI 1.4-3.1), and experienced more diagnostic delays 0.8 vs 1.5 delays (P<0.001).
Conclusion: There may be many missed diagnostic opportunities in both inpatient and ambulatory settings. Diagnostic opportunities tended to present with neurologic conditions before fever. Most opportunities occur in outpatient and emergency settings. Patients with a history of migraines may be more at risk for experiencing a delay.