A 26-year-old previously healthy woman is brought to the emergency department after having an episode of seizure 1 hour ago. She has a 2-day history of fever and headaches, for which she has been taking acetaminophen and ibuprofen without much relief. This morning, her family found her behaving strangely. She has no family history of seizures. There is no recent travel history. Her temperature is 38.9 C (102 F), blood pressure is 120/70 mm Hg, pulse is 110/min, and respirations are 18/min. The patient is lethargic and confused. Hyperreflexia is present. Complete blood count and CT scan of the head are unremarkable. Her cerebrospinal fluid study shows:
Opening pressure 160 mm H2O Protein 100 mg/dL Glucose 55 mg/dL White blood cells 150/mm3 Lymphocytes 90% Polymorphs 10% Red blood cells 200/mm3
Which of the following is the most likely diagnosis in this patient?
Herpes encephalitis is the most common cause of fatal sporadic encephalitis in the United States; beyond the neonatal period, it is most commonly due to herpes simplex virus type 1 (HSV-1). It presents with an acute onset (<1 week duration) of focal neurological findings (altered mentation, focal cranial nerve deficits, ataxia, hyperreflexia, or focal seizures). Fever is present in approximately 90% of patients. Behavioral changes can be seen, and behavioral syndromes such as hypomania, Klüver-Bucy syndrome (hyperphagia, hypersexuality), and amnesia have been reported.
Cerebrospinal fluid (CSF) examination characteristically reveals lymphocytic pleocytosis, an increased number of erythrocytes (due to hemorrhagic destruction of temporal lobes), and elevated protein levels; low CSF glucose levels are generally not seen. Brain imaging shows temporal lobe lesions. MRI is generally preferred to CT (which may be normal in up to 50% of patients). Focal electroencephalogram findings (prominent intermittent high amplitude slow waves) occur in >70%-80% of patients and can be used in some cases as corroborative evidence. Polymerase chain reaction analysis of HSV DNA in CSF (highly sensitive and specific) is the gold standard for diagnosis (replacing brain biopsy). Intravenous acyclovir is the treatment of choice.
(Choices A and C) Meningioma and glioblastoma multiforme can cause focal seizures; however, fever is unlikely, and the CSF examination will not show marked lymphocytic pleocytosis.
(Choice B) Cryptococcal meningitis is often seen in immunocompromised patients (eg, patients with HIV) and would be uncommon in an immunocompetent patient. Classic CSF findings include an elevated opening pressure, low leukocytes with mononuclear predominance, slightly elevated proteins, and low glucose levels. Organisms can be detected by India ink preparation.
(Choices E and H) Intracerebral and subarachnoid hemorrhages are cerebrovascular accidents characterized by severe headache and marked neurological deficits; however, fever would be an unusual finding in the acute setting, and the CSF findings of lymphocytic pleocytosis and elevated protein levels do not support these diagnoses.
(Choices F, G, and I) This patient has evidence of altered brain function (confusion, strange behavior), suggesting encephalitis rather than meningitis. Characteristic CSF findings in bacterial meningitis (not seen in this patient) are markedly increased polymorphonuclear leukocytes and decreased glucose levels. Gram stain may show organisms. Tuberculous meningitis typically has a subacute presentation.
Educational objective:
Herpes simplex virus (HSV) encephalitis mainly affects the temporal lobe of the brain and may present acutely (<1 week duration) with focal neurological findings. The characteristic cerebrospinal fluid findings are lymphocytic pleocytosis, an increased number of erythrocytes, and elevated protein. HSV polymerase chain reaction analysis is the gold standard for diagnosis.