Critical Care Medicine-Infections and Immunologic Disease>>>>>CNS Infections
Question 4#

A 42-year old woman is brought to the ED from home after she was difficult to arouse from sleep in the morning. She has no significant past medical history but had been complaining of malaise for 1 week as well as new onset headache and fever for 2 days before presentation. She has not had other symptoms except for cold sores, which she gets this time every year. She had also been taking care of her 7-year-old grandson who had fevers and a severe nonproductive cough. In the ED, her vital signs are:

On examination, she is only responsive to noxious stimuli with eye opening and withdrawal of all four extremities. Her pupils are reactive to light bilaterally; there is no nuchal rigidity. Skin examination is normal with no visible rash. Heart, lung, and abdominal examination are unremarkable. During the examination, she has a generalized tonic-clonic seizure and is intubated for airway protection. A head CT is performed, which does not show any acute abnormality. An LP is performed, and results are pending. She is started on vancomycin, ceftriaxone, and dexamethasone for concern of bacterial meningitis. After that, a brain MRI is also performed, which shows altered signal in the left orbitofrontal cortex with enhancement on postgadolinium images.

What further diagnostic and therapeutic interventions are MOST appropriate at this time? 

A. Await results of the LP for further intervention
B. Add Herpes simplex virus (HSV) IgG to the CSF laboratory testing and begin empiric IV acyclovir
C. Add Varicella zoster virus (VZV) IgG to the CSF laboratory testing and begin empiric IV acyclovir
D. Add HSV PCR to the CSF laboratory testing and begin empiric IV acyclovir

Correct Answer is D


Correct Answer: D

The patient’s presentation and imaging findings are classic for HSV encephalitis. Empiric therapy should include high-dose IV acyclovir while awaiting HSV PCR on CSF, which is the test of choice for definitive diagnosis. 

Encephalitis or encephalomyelitis should be considered in the differential diagnosis for any patient presenting with behavioral changes, altered mental status, and/or depressed level of consciousness. In the absence of nuchal rigidity and peripheral symptoms, this should be high on the differential. The presence of parenchymal involvement on brain imaging is virtually diagnostic of encephalitis. Microbiological diagnosis is usually made by serological tests or PCR on CSF.

HSV is the most common cause of encephalitis (including both infectious and noninfectious causes) in adults. 90% of the cases are caused by HSV-1 during primary infection (more common in young adults) or recurrence (more common in older adults) from latent virus reactivation either as peripheral infection spreading to the CNS or de novo reactivation within the CNS. Temporal lobe involvement is pathognomic but less commonly the temporal lobe may be spared with involvement of other areas such as the orbitofrontal cortex, cingulate gyrus, or insula. This patient’s presentation of an episode of orolabial herpes followed by fever, headaches, and altered consciousness is classic for HSV encephalitis. Highdose acyclovir 10 mg/kg/dose IV every 8 hours should be started empirically if HSV encephalitis is a consideration even before diagnostics are performed as mortality is high with delay in therapy. The diagnostic test of choice is HSV DNA PCR performed on CSF. This test is highly sensitive and specific but may be falsely negative very early in the course of the disease. If the clinical suspicion for HSV encephalitis is high, especially if supported by imaging findings, then acyclovir should be continued despite an initial negative PCR and an LP should be repeated with HSV PCR retesting in 3 to 7 days. Serologies are not helpful in the diagnosis of HSV encephalitis either in the serum or on CSF.

VZV is a neurotropic virus that establishes latency in ganglionic cells of the nervous system during primary infection and dermatomal reactivation can occur in times of immunocompromise (old age, immunosuppression, HIV/AIDS). CNS manifestations of infection range from strokes and subarachnoid hemorrhages to arterial ectasias, but encephalitis is also a common presentation. Unlike HSV, VZV IgG detection in CSF is more sensitive than VZV PCR for diagnosis. Treatment is with high-dose IV acyclovir as well.


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