Continued...

Discussion :-

Thus, given an immunocompetent patient, the absence of a pleocytosis should raise the suspicion of a non-viral cause of the encephalopathy. Similarly, a decreased glucose level should also prompt the search for a non-viral cause. About 20 percent of patients with encephalitis will have RBCs in their CSF profile following a non-traumatic tap, indicating a hemorrhagic encephalitis such as that associated with HSV, Colorado tick fever virus, and sometimes California encephalitis virus (1). PCR amplification of viral nucleic acid in the CSF is a sensitive (75-98%) and specific (100%) test for HSV encephalitis within the first 25-45 hours (2). PCR analysis of the CSF is less invasive and less costly than the traditional brain biopsy, and is therefore becoming the diagnostic test of choice. A brain biopsy does have the advantage, however, of potentially identifying alternative causes of the encephalopathy (1). The PCR test for HSV is not routinely done on CSF samples and must be specifically requested. Results are usually available within 24 hours (4). The initial result may return negative and should be redone if clinical suspicion remains high (6,7). HSV antibody detection in the CSF yields the best results after a week into the illness. Thus, its usefulness is limited to a retrospective confirmation of HSV infection rather than for acute diagnostic purposes. CSF culture for HSV is unreliable and is invariably negative in cases of HSV-1 encephalitis (1). CT, MRI, and EEG are helpful to identify or exclude alternative diagnoses and in determining whether the disease is focal or widespread. Such tests for HSV encephalitis tend to yield focal abnormalities, such as:

1) periodic focal spikes and slow-wave or periodic sharp wave patterns over the temporal lobes on EEG;

2) areas of low absorption, mass effect, and contrast enhancement in the temporoparietal regions of the brain on CT;

3) areas of increased signal intensity in the frontotemporal, cingulate, or insular regions on T2-weighted spin-echo MRI images. The aforementioned findings, however, are not pathognomic for HSV encephalitis (1,4).MRI is a more sensitive test than CT. However, CT is fast and is useful to rule out other causes of encephalopathy, such as acute hemorrhage, shaken infant syndrome, brain tumor, or some conditions that requires immediate neurosurgery. Many authorities recommend performing a CT scan of the head, with and without contrast, prior to obtaining a lumbar puncture (2).A patient with encephalopathy should be evaluated and treated for shock or hypotension. The clinician may place the patient on prophylactic anticonvulsant medication and also consider airway protection in patients with altered states of consciousness. For patients with signs of hydrocephalus and increased intracranial pressure, coughing and straining should be controlled. If the patient is stable, the head should be elevated and neurologic status should be monitored. When aggressive intervention is required, the clinician may consider the use of diuretics (if the patient's circulatory volume is protected) or hyperventilation in an emergency situation. Cerebral edema can also be controlled with steroids, but the use of steroids in HSV encephalitis is controversial (4). Intracranial pressure monitoring is also controversial (2).In general, with the exception of HSV and varicella zoster virus, the viral encephalitides lack specific treatment (Cytomegalovirus and toxoplasma encephalitis do have specific treatments, but they are not usually initiated in the ED) (2).The consensus report on the diagnosis of HSV encephalitis published in 1996 recommends that intravenous acyclovir be given to the patient as soon as the diagnosis is suspected, since early intervention is key (6). Even if the CSF PCR returns negative for HSV, treatment with acyclovir should continue if clinicial suspicion remains high, since the drug is relatively non-toxic, with the major side-effect being transient renal insufficiency (8). Acyclovir should be given at a dose of 10 mg/kg every 8 hours (for a total of 30 mg/kg per day) for 14 days (Acyclovir should be infused slowly over one hour to minimize the risk of renal insufficiency. The dose of 30 mg/kg per day is double that for mucocutaneous/visceral infections because CSF levels of acyclovir only reach 30-50 percent of plasma levels). The dosage should be adjusted for patients with existing renal dysfunction (3). For HIV+ patients, foscarnet (Foscavir), may be a suitable substitute for acyclovir, given the increased incidence of acyclovir-resistant strains of HSV (2).Patient prognosis is dependent upon several host factors as well as the virulence of the virus. For example, rabies, eastern equine encephalitis, and Japanese encephalitis are associated with significant mortality and morbidity, including severe neurologic sequelae. California encephalitis and western equine encephalitis tend to be milder diseases (2). Mortality in untreated patients with HSV encephalitis is about 70%, and many survivors are left with neurologic abnormalities (4). According to National Institute of Allergy and Immune Diseases-Collaborative Antiviral Study Group (NIAID-CASG) trials, of 32 acyclovir treated patients, 81 percent survived. Among the survivors, 46 percent suffered little or no neurologic sequelae, 12 percent were moderately impaired, and 42 percent were severely impaired, requiring continuous supportive care (1). 5-10 percent of surviving patients relapse days to weeks after completion of treatment (4).Factors important in the prognosis of HSV encephalitis are the timeliness of intervention, the age of the patient, and the level of consciousness at the initiation of therapy. For example, patients with a Glasgow coma score of less than or equal to 6, either died or suffered severe neurologic sequelae. Acyclovir can reduce neonatal death by 25 percent, but the rate of morbidity, especially with HSV-2 infections, is still very high (1,3). 40-60 percent of neonatal survivors have developmental abnormalities after 2 years of follow-up care (4).

CLINICAL PEARLS:

1. HSV is the most common cause of viral encephalitis in the United States, accounting for 10 to 20 percent of all cases.
   
   
2. Neonates (infants less than 6 weeks old) have the highest incidence of HSV visceral and/or CNS infection among all age groups.
   
   
3. Individuals with subclinical disease may still shed infectious virus.
   
   
4. In children and adults, there is no relationship between the presence of mucocutaneous lesions and HSV encephalitis. Thus, the presence or absence of such lesions is of no diagnostic value. For neonates, however, pathognomonic lesions have positive predictive value.
   
   
5. Neonates often present with disseminated disease and thus may have signs and symptoms of jaundice, shock, bleeding, or respiratory distress
   
   
6. PCR amplification of viral nucleic acid in the CSF is a sensitive and specific test for HSV encephalitis, and is becoming the diagnostic test of choice. The PCR test for HSV is not routinely done on CSF samples and must be specifically requested.
   
   
7. The initial PCR result may return negative and should be redone if clinical suspicion remains high.
   
   
8. MRI is the preferred imaging study for HSV encephalitis, especially T2 weighted and FLAIR sequences.
   
   
9. Intravenous acyclovir should be given to the patient as soon as the diagnosis of HSV encephalitis is suspected (ie., prior to confirmation).
   
   
10. Even if the CSF PCR returns negative for HSV, treatment with acyclovir should continue if clinical suspicion remains high, since the drug is relatively non-toxic.

References

1. Tyler KL. Aseptic Meningitis, Viral Encephalitis, and Prion Diseases. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL (eds). Harrison's Principles of Internal Medicine, 14th edition. USA, McGraw-Hill, 1998, pp. 2440-2445.
2. Lazoff M. Encephalitis. www.emedicine.com/emerg/topic163.htm (no date, reviewed online September 2000).
3. Corey L. Herpes Simplex Viruses. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL (eds). Harrison's Principles of Internal Medicine, 14th edition. USA, McGraw-Hill Co., Inc., 1998, pp. 1080-1084.
4. Pritz T. Herpes Simplex Encephalitis. www.emedicine.com/emerg/topic247.htm (no date, reviewed online September 2000).
5. Pritz T. Herpes Simplex Encephalitis. www.emedicine.com/emerg/topic247.htm (no date, reviewed online September 2000).
6. Girolami UD, Anthony DC, Frosch MP. The Central Nervous System. In: Cotran RS, Kumar V, Collins T (eds). Robbins Pathologic Basis of Disease, 6th edition. Pennsylvania, W.B. Saunders Co., 1999, pp. 1317-1319.
7. Coren ME, Buchdahl RM, Cowan FM, Riches PG, Miles K, Thompson EJ. Imaging and laboratory investigation in herpes simplex encephalitis. Journal of Neurology, Neurosurgery, and Psychiatry 1999;67(2):243-245.
8. Spuler A, Blaszyk H, Parisi JE, Davis DH. Herpes simplex encephalitis after brain surgery: case report and review of the literature. Journal of Neurology, Neurosurgery, and Psychiatry 1999;67(2):239-242.
9. Carlini ME, Shandera WX. Infectious Diseases: Viral and Rickettsial. In: Tierney LM, McPhee SJ, Papadakis MA (eds). Current Medical Diagnosis and Treatment, 38th edition. Connecticut, Appleton and Lange, 1999, pp. 1256-1259.

Copyrighted:Radiology Cases in Pediatric Emergency Medicine Volume 7, Case 9 Loren Yamamoto, MD, MPH, Professor of Pediatrics, University of Hawaii John A. Burns School of Medicine.Loreny@hawaii.edu

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Last created on 01-07-2006