What is Encephalitis?
Encephalitis is inflammation of the brain parenchyma (brain tissue itself) associated with neurologic dysfunction, most fundamentally distinguished by altered mental status lasting ≥24 hours. 1
Core Definition and Pathophysiology
Encephalitis represents brain inflammation caused by direct infection, post-infectious immune processes, or autoimmune mechanisms affecting brain tissue. 2 This differs critically from encephalopathy, which involves altered mental status without brain inflammation and can result from metabolic, toxic, or systemic causes. 1
The gold standard for diagnosis is pathologic examination of brain tissue showing inflammation, but this is rarely performed premortem due to procedural risks. 1 In clinical practice, diagnosis relies on surrogate markers of inflammation including:
- CSF inflammatory response (pleocytosis ≥5 WBC/mm³) 1
- Parenchymal abnormalities on neuroimaging 1
- EEG abnormalities consistent with encephalitis 1
However, encephalitis can occur without significant CSF pleocytosis or demonstrable neuroimaging abnormalities, particularly early in disease or in immunocompromised patients. 1, 2, 3
Major Causes
Infectious Etiologies
- Viral: HSV-1 is the most commonly diagnosed cause in industrialized nations, followed by VZV, enteroviruses, CMV, and human herpes viruses 6 and 7 3, 4
- Bacterial: Bartonella henselae, Mycobacterium tuberculosis, Treponema pallidum 3
- Fungal: Cryptococcus neoformans, Coccidioides species 3
- Parasitic: Toxoplasma gondii, cerebral malaria 3
Autoimmune/Post-Infectious
- Acute disseminated encephalomyelitis (ADEM) following infection or vaccination 1, 3
- Anti-NMDAR encephalitis and other antibody-mediated syndromes 1, 3
- Paraneoplastic limbic encephalitis 3
Clinical Presentation
Required Major Criterion
Altered mental status (decreased/altered consciousness, lethargy, personality change) lasting ≥24 hours with no alternative cause identified. 1
Supporting Features (≥2 for possible, ≥3 for probable encephalitis)
- Documented fever ≥38°C within 72 hours of presentation 1
- Generalized or partial seizures (occur in ~33% of cases) not fully attributable to preexisting disorder 1, 2
- New focal neurologic findings 1
- CSF pleocytosis ≥5 WBC/mm³ 1
- Brain parenchymal abnormalities on neuroimaging suggestive of acute encephalitis 1
- EEG abnormalities consistent with encephalitis 1
Additional Clinical Features
- Psychiatric manifestations (behavioral/personality changes) in 41-76% of cases 2
- Speech disturbances in ~59% of patients 2
- Fever may be low-grade or absent, especially in immunosuppressed individuals 2
Critical Diagnostic Pitfalls
Behavioral changes in encephalitis can be misinterpreted as primary psychiatric illness, leading to dangerous diagnostic delays. 2 Subtle mental status changes may be missed using crude assessment tools like Glasgow Coma Scale. 3
Normal CSF and neuroimaging do not exclude encephalitis. 2, 3 MRI demonstrates parenchymal abnormalities in ~90% of cases, but 10% have normal imaging. 2 EEG is abnormal in >80% of cases and should be obtained when distinguishing organic from psychiatric causes. 2
Despite extensive testing, >50% of presumed encephalitis cases remain unexplained etiologically. 1
Prognosis and Long-Term Consequences
Between 30-50% of encephalitis survivors develop long-term neurological or psychiatric sequelae including cognitive deficits, epilepsy, movement disorders, anxiety, depression, and obsessive behaviors. 2 These sequelae may not be immediately apparent at discharge. 2
All encephalitis patients require comprehensive rehabilitation assessment before discharge with a documented rehabilitation plan. 2 Patients should not be discharged without a definitive or probable diagnosis. 2