In the JournalsPerspective

Poor outcomes, unidentified causes still common in encephalitis cases

Rodrigo Hasbun, MD, MPH
Rodrigo Hasbun

Findings from a retrospective cohort study showed that testing and treatment for encephalitis is inadequate among all age groups, and is worst among older adults, for whom viral testing is conducted less than half of the time, researchers reported.

“Adults with encephalitis continue to have poor outcomes and unknown etiologies in the majority of patients even in the molecular diagnostic era,” Rodrigo Hasbun, MD, MPH, a professor of infectious diseases at the University of Texas McGovern Medical School, told Infectious Disease News.

According to Hasbun and colleagues, regardless of the age, “encephalitis continues to be surrounded by many unanswered questions and numerous clinical challenges.”

“By comparing older and younger adults with encephalitis we hope to capture meaningful differences in their presentation and outcomes,” they wrote. “The objective of our study was to identify unique features in the older adult population that may suggest associated risk factors, clinical findings, and underlying etiologies that should be studied further and be considered in clinical practice.”

The researchers reviewed 340 cases of encephalitis reported between 2000 and 2017 from 19 hospitals in New Orleans and Houston. Patients were aged 17 years or older.

According to the study, 69% of patients were tested for herpes simplex virus and 24% were tested for varicella zoster virus, whereas 49% were tested for an arbovirus. Only 14% of patients had recorded measurements for anti-N-methyl-D-aspartate (NMDA) receptor antibodies, the researchers said. Adverse clinical outcomes at discharge were reported for 53% of patients.

Older adults had a lower prevalence of HIV and a higher number of comorbidities, and they were less likely to receive adjuvant steroids. Additionally, they were more likely to have a positive arbovirus serology, positive HSV PCR, abnormal CT findings and adverse clinical outcomes (P < .05). Adverse clinical outcomes were independently associated with being aged 65 years or older and having a fever, a Glasgow coma scale score less than 13 and seizures, according to the researchers.

Hasbun and colleagues also reported that more than half of all cases had no known etiology. Specifically, 58.3% of adults aged older than 65 years and 51.6% of adults 65 years or younger had an unknown cause for encephalitis.

Cases of encephalitis with known etiologies among older adults were more frequently caused by viruses, including arboviruses. Despite this, only 48% of all older adults were tested for any arbovirus, according to the study. Furthermore, the testing rate was 33.9% for enterovirus, 21% for varicella zoster virus and 66.1% for HSV, the researchers reported. Moreover, only five of the 62 older adults were assessed for NMDA receptor measurements.

“We fear that these findings for global undertesting is possibly due to perceptions of older individuals where alternative diagnoses, such as delirium or dementia, may lead to delayed or limited screening for encephalitic etiologies,” Hasbun and colleagues wrote.

“We need to increase awareness of the Infectious Diseases Society of America encephalitis guidelines and recommend that all patients with suspected encephalitis undergo a rapid and complete evaluation for the most common viral and autoimmune etiologies,” Hasbun said. – by Marley Ghizzone

Disclosures: Hasbun is a speaker for, and reports receiving research support from, BioFire. Please see the study for all other authors’ relevant financial disclosures.

Rodrigo Hasbun, MD, MPH
Rodrigo Hasbun

Findings from a retrospective cohort study showed that testing and treatment for encephalitis is inadequate among all age groups, and is worst among older adults, for whom viral testing is conducted less than half of the time, researchers reported.

“Adults with encephalitis continue to have poor outcomes and unknown etiologies in the majority of patients even in the molecular diagnostic era,” Rodrigo Hasbun, MD, MPH, a professor of infectious diseases at the University of Texas McGovern Medical School, told Infectious Disease News.

According to Hasbun and colleagues, regardless of the age, “encephalitis continues to be surrounded by many unanswered questions and numerous clinical challenges.”

“By comparing older and younger adults with encephalitis we hope to capture meaningful differences in their presentation and outcomes,” they wrote. “The objective of our study was to identify unique features in the older adult population that may suggest associated risk factors, clinical findings, and underlying etiologies that should be studied further and be considered in clinical practice.”

The researchers reviewed 340 cases of encephalitis reported between 2000 and 2017 from 19 hospitals in New Orleans and Houston. Patients were aged 17 years or older.

According to the study, 69% of patients were tested for herpes simplex virus and 24% were tested for varicella zoster virus, whereas 49% were tested for an arbovirus. Only 14% of patients had recorded measurements for anti-N-methyl-D-aspartate (NMDA) receptor antibodies, the researchers said. Adverse clinical outcomes at discharge were reported for 53% of patients.

Older adults had a lower prevalence of HIV and a higher number of comorbidities, and they were less likely to receive adjuvant steroids. Additionally, they were more likely to have a positive arbovirus serology, positive HSV PCR, abnormal CT findings and adverse clinical outcomes (P < .05). Adverse clinical outcomes were independently associated with being aged 65 years or older and having a fever, a Glasgow coma scale score less than 13 and seizures, according to the researchers.

Hasbun and colleagues also reported that more than half of all cases had no known etiology. Specifically, 58.3% of adults aged older than 65 years and 51.6% of adults 65 years or younger had an unknown cause for encephalitis.

Cases of encephalitis with known etiologies among older adults were more frequently caused by viruses, including arboviruses. Despite this, only 48% of all older adults were tested for any arbovirus, according to the study. Furthermore, the testing rate was 33.9% for enterovirus, 21% for varicella zoster virus and 66.1% for HSV, the researchers reported. Moreover, only five of the 62 older adults were assessed for NMDA receptor measurements.

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“We fear that these findings for global undertesting is possibly due to perceptions of older individuals where alternative diagnoses, such as delirium or dementia, may lead to delayed or limited screening for encephalitic etiologies,” Hasbun and colleagues wrote.

“We need to increase awareness of the Infectious Diseases Society of America encephalitis guidelines and recommend that all patients with suspected encephalitis undergo a rapid and complete evaluation for the most common viral and autoimmune etiologies,” Hasbun said. – by Marley Ghizzone

Disclosures: Hasbun is a speaker for, and reports receiving research support from, BioFire. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Raghavendra Tirupathi

    Raghavendra Tirupathi

    Encephalitis results in considerable morbidity and mortality in the United States and worldwide. Infectious disease physicians should be able to discriminate between the myriad causes of encephalitis to develop a practical approach to diagnostic testing and treatment. This retrospective study by Hansen and colleagues helps shine more light on the clinical and epidemiological risk factors associated with adverse clinical outcomes in patients with encephalitis. Age older than 65 years, fever, seizures and Glasgow coma scale less than 13 were all associated with poor clinical outcomes. This study again affirms the known fact that encephalitis is underdiagnosed in older adults because of confounding morbidities and alternative diagnoses like dementia and delirium. The highlight of the study is also the underutilization of viral testing, with less than 50% of older patients tested for arboviral etiologies despite the high prevalence of viral encephalitis. The clinical picture is worse when it comes to anti-NMDA receptor antibodies, with only 14% of the patients tested for this factor. The researchers also point to the underutilization of empirical steroids in older individuals. Encephalitis is a challenging and notorious disease, and being mindful of the epidemiology and high-risk groups helps us better tailor testing and treatment approaches to this challenging cohort of patients and, in turn, improve clinical outcomes.

    • Raghavendra Tirupathi, MD, FACP
    • Medical Director, Keystone Infectious Diseases/HIV
      Chair, Infection prevention, Summit Health
      Clinical assistant professor of medicine, Penn State University

    Disclosures: Tirupathi reports no relevant financial disclosures.