Can Encephalitis Occur Without Fever?
Yes, encephalitis can definitely occur without fever, and this is a critical diagnostic pitfall that clinicians must recognize to avoid delayed treatment and poor outcomes.
Key Clinical Evidence
Fever is explicitly recognized as a non-required criterion for diagnosing encephalitis. According to the International Encephalitis Consortium consensus statement, fever is listed as only one of six minor criteria, with just 2 minor criteria needed for possible encephalitis 1. This means encephalitis can be diagnosed even when fever is completely absent.
Why Fever May Be Absent
The guidelines specifically acknowledge several important scenarios where fever may not be present 1:
- Immunosuppressed patients with encephalitis frequently do not mount a fever response, despite having active brain inflammation 1
- Fever fluctuates and may not be documented at the time of clinical assessment, even in patients with infectious encephalitis 1
- Early in the course of infection, fever may not yet have developed 1
- Timing matters: Some patients develop fever days after initial presentation, as documented in a case where fever didn't appear until the fourth day of admission in confirmed HSV encephalitis 2
Clinical Reality in HSV Encephalitis
Even in herpes simplex encephalitis (the most common treatable viral encephalitis), fever is not universal 1:
- Only 85 out of 93 adults (91%) with confirmed HSV-1 encephalitis were febrile on admission 1
- This means 9% of HSV encephalitis patients had no fever at presentation 1
- More subtle presentations are increasingly recognized with molecular diagnostics, including "low-grade pyrexia rather than a high fever" 1
Autoimmune Encephalitis Considerations
Antibody-mediated encephalitis commonly presents without fever 1:
- It is "uncommon for adult patients to have fever or headache" in VGKC-complex antibody encephalitis 1
- These patients typically present with profound disorientation, confusion, seizures, and memory problems rather than fever 1
- This represents a critical diagnostic challenge, as these patients require immunosuppression rather than antiviral therapy 1
Diagnostic Implications
What Clinicians Should Do
Do not wait for fever to develop before considering encephalitis 1. The major criterion requiring altered mental status lasting ≥24 hours is sufficient to trigger evaluation when combined with other features such as 1:
- Seizures not attributable to a preexisting disorder
- New focal neurological findings
- CSF pleocytosis (≥5 WBC/mm³)
- Brain imaging abnormalities suggestive of encephalitis
- EEG abnormalities consistent with encephalitis
Critical Pitfall to Avoid
The absence of fever should never exclude encephalitis from the differential diagnosis 1. A recent case report emphasizes this danger: a patient with HSV encephalitis initially presented without fever or CSF pleocytosis, and was nearly misdiagnosed as autoimmune encephalitis, which could have led to inappropriate immunosuppressive treatment 2. The patient only developed fever on day 4, highlighting the need for close observation and follow-up testing 2.
Treatment Considerations
Empiric acyclovir should be initiated based on clinical suspicion regardless of fever status 3. The Infectious Diseases Society of America recommends starting IV acyclovir 10 mg/kg every 8 hours immediately in suspected viral encephalitis, as delays in treatment significantly worsen outcomes 3. This recommendation does not require fever as a prerequisite 3.
Special Populations at Higher Risk for Afebrile Encephalitis
- Elderly patients: More likely to have atypical presentations and difficulty mounting fever responses 1
- Immunocompromised patients (HIV, transplant recipients, chemotherapy patients): May have acellular CSF and absent fever despite severe CNS infection 1
- Patients with autoimmune encephalitis: Typically present with subacute onset without fever 1