Infectious Disease · Neurological Infections
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Herpes simplex encephalitis is the most common cause of sporadic fatal encephalitis in the United States.
The virus exhibits a classic predilection for the temporal lobes, leading to focal neurological deficits.
Patients typically present with the triad of fever, headache, and altered mental status accompanied by personality changes or seizures.
Lumbar puncture revealing lymphocytic pleocytosis, elevated protein, and normal glucose is the hallmark CSF profile.
The gold standard for definitive diagnosis is PCR testing for HSV DNA in the cerebrospinal fluid.
MRI of the brain is the imaging modality of choice and typically demonstrates hyperintensity in the temporal lobes on T2/FLAIR sequences.
Intravenous acyclovir must be initiated immediately upon clinical suspicion without waiting for diagnostic confirmation to reduce mortality.
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A 58-year-old male is brought to the emergency department by his wife due to three days of progressive confusion and behavioral changes. She reports he has been acting strangely, claiming to hear voices and exhibiting uncharacteristic aggression. On examination, the patient is febrile at 101.8°F and appears disoriented to time and place. He has a focal seizure involving his right arm during the evaluation. MRI of the brain shows edema and hyperintensity localized to the medial temporal lobes.
What is the most appropriate next step in management?
Empiric intravenous acyclovir
The patient's presentation of fever, altered mental status, and temporal lobe findings on MRI is classic for HSV encephalitis, necessitating immediate initiation of acyclovir to prevent high mortality.
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Etiology / Epidemiology
Most common cause of sporadic fatal encephalitis in the US; caused by HSV-1 reactivation.
Clinical Manifestations
Acute onset of fever, altered mental status, and temporal lobe features such as olfactory hallucinations, aphasia, and behavioral change.
Diagnosis
PCR of CSF is the gold standard; look for lymphocytic pleocytosis and elevated RBCs.
Treatment
Initiate Acyclovir immediately upon clinical suspicion; nephrotoxicity is a major dose-limiting side effect.
Prognosis
High mortality if untreated; 70% of survivors suffer long-term neuropsychiatric sequelae.
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Epidemiology & Etiology
Herpes simplex encephalitis is the most frequent cause of sporadic fatal encephalitis in the United States, caused predominantly by HSV-1, usually from reactivation of latent virus rather than primary infection; most affected patients are immunocompetent.
Pertinent Anatomy
The virus exhibits a distinct predilection for the temporal lobes and orbitofrontal cortex. This localization explains the classic presentation of olfactory hallucinations and personality changes.
Pathophysiology
Viral replication leads to severe hemorrhagic necrosis and edema within the temporal lobes. The resulting mass effect causes increased intracranial pressure and potential uncal herniation. Inflammation is localized, distinguishing it from diffuse viral encephalitides.
Clinical Manifestations
Look for Klüver-Bucy syndrome features, seizures, and olfactory hallucinations.
Diagnosis
Append: "A negative PCR in the first 72 hours does not exclude HSE — continue acyclovir and repeat the CSF PCR in 3–7 days if clinical suspicion remains high."
Treatment
Append: "Treat for 14–21 days (21 days is standard for confirmed HSV encephalitis in adults)."
Prognosis
Untreated mortality exceeds 70%. Even with treatment, survivors often face cognitive impairment, amnesia, and seizure disorders. Long-term follow-up is required to monitor for neuropsychiatric sequelae.
Differential Diagnosis
Varicella Zoster Encephalitis: presence of dermatomal rash
West Nile Virus: associated with flaccid paralysis
Bacterial Meningitis: CSF shows neutrophils and low glucose
Autoimmune Encephalitis: slower onset, often associated with teratomas
Brain Abscess: ring-enhancing lesion on MRI