What is encephalitis (brain fever)?

What is Brain Fever (Encephalitis)?

Brain fever, medically termed encephalitis, is inflammation of the brain parenchyma that presents with altered mental status lasting at least 24 hours, often accompanied by fever, seizures, or focal neurological deficits. 1

Core Definition and Pathophysiology

Encephalitis represents inflammation of the brain tissue associated with neurologic dysfunction, which can result from infectious agents (viral, bacterial, fungal, or parasitic), post-infectious autoimmune processes, or primary autoimmune conditions. 1, 2 The term "brain fever" is a colloquial expression that captures the typical presentation of fever with brain dysfunction, though it's important to recognize that not all patients with encephalitis will have fever, particularly immunocompromised individuals. 1, 3

The condition differs from encephalopathy, which refers to altered mental status without necessarily having brain inflammation, though these terms are often used interchangeably in clinical practice due to significant overlap. 1, 3

Diagnostic Criteria

According to the International Encephalitis Consortium consensus statement, diagnosis requires:

Major Criterion (Required):

• Altered mental status (decreased consciousness, lethargy, or personality change) lasting ≥24 hours with no alternative cause identified 1

Minor Criteria (2 for possible, ≥3 for probable/confirmed encephalitis):

• Documented fever ≥38°C (100.4°F) within 72 hours before or after presentation 1
• Generalized or partial seizures not fully attributable to a preexisting disorder 1
• New onset focal neurologic findings 1
• CSF white blood cell count ≥5/mm³ 1
• Brain parenchymal abnormality on neuroimaging suggestive of acute encephalitis 1
• EEG abnormality consistent with encephalitis not attributable to another cause 1

Common Causes

Infectious Etiologies:

• Herpes simplex virus (HSV-1 and HSV-2) is the most commonly diagnosed viral cause in industrialized nations 3, 4
• Varicella zoster virus (VZV), enteroviruses, cytomegalovirus, and human herpes viruses 6 and 7 3, 5
• Bacterial causes include Bartonella henselae, Mycobacterium tuberculosis, and Treponema pallidum 3
• Fungal causes include Cryptococcus neoformans and Coccidioides species 3
• Parasitic causes include Toxoplasma gondii and cerebral malaria 3

Autoimmune Causes:

• Anti-NMDA receptor encephalitis (increasingly recognized) 3, 2, 4
• Acute disseminated encephalomyelitis (ADEM) - post-infectious or post-vaccination 3
• Limbic encephalitis (may be paraneoplastic) 3

Clinical Presentation

Patients typically present with a combination of:

• Fever, headache, and confusion 2, 6
• Behavioral changes, personality alterations, or cognitive impairment 2, 4
• Seizures (generalized or focal) 1, 6
• Focal neurological deficits 4, 6
• Movement disorders or autonomic instability 2

The 24-hour duration requirement for altered mental status was specifically chosen to exclude post-ictal states from febrile seizures in children. 1

Critical Diagnostic Pitfalls

• Normal CSF and neuroimaging do NOT exclude encephalitis - CSF may be devoid of cells in immunocompromised patients or early in infection 1, 3
• Fever may be absent - immunosuppressed patients may not mount a fever response 1
• More than 50% of presumed encephalitis cases fail to identify a pathogen, but this does not exclude the diagnosis 1
• Subtle mental status changes may be missed using crude assessment tools like Glasgow Coma Scale 3

Long-Term Consequences

Even after viral clearance, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. 5 Many patients are left with residual physical or neuropsychological deficits requiring long-term multidisciplinary management. 4

Prognosis and Treatment Urgency

Encephalitis remains a global concern due to its high mortality and morbidity. 2, 5 Early intervention with specific treatments (such as aciclovir for HSV encephalitis) can dramatically improve outcomes and reduce mortality rates and sequelae. 4, 6 Prompt diagnosis and administration of both specific and supportive management is essential for better outcomes. 2