More Than Just the “Terrible Twos”: A Case of Resistant Hsv Encephalitis

Jennifer M Ladd, MD* and Dr. Alyssa M Stephany, MD, Duke University, Durham, NC

Meeting: Hospital Medicine 2016, March 6-9, San Diego, Calif.

Abstract number: 903

Categories: Clinical Vignettes Abstracts, Finalist, Pediatric

Case Presentation: A two-year-old boy presented with several weeks of increasing irritability and developmental regression. His parents reported that he often displayed aggressive behavior and screamed inconsolably. They also noticed gait instability and vocabulary loss. Of note, the patient had been appropriately treated for neonatal HSV-2 encephalitis with IV acyclovir and had remained on oral acyclovir suppressive therapy for almost two years. On the day of initial admission, the patient had a generalized tonic-clonic seizure. CSF HSV PCR was negative, but MRI revealed new left parietal hyperintensity, concerning for recurrence of HSV encephalitis. The patient’s seizures were controlled, and he was discharged on IV acyclovir. However, after four weeks of therapy, he had not regained considerable verbal skills and still had intermittent aggressive behavior. His exam was significant only for inconsistent gait ataxia. A follow-up MRI revealed progressive lesions, with continued hyperintensity in the left parietal region and newly affected areas in the corpus callosum and right parietal lobe. Given these worrisome findings despite appropriate treatment, the patient was readmitted. He was continued on IV acyclovir and received empiric IVIG (for possible autoimmune disease) without clinical improvement. Infectious Disease, Neurology, Genetics, and Immunology were consulted, but an extensive work-up was unrevealing – notably, CSF HSV PCR was again negative as were CSF and serum autoimmune panels. Given the lack of a definitive diagnosis, the patient ultimately underwent a brain biopsy. Tissue was PCR positive for HSV-2 DNA. The patient was then started on foscarnet for treatment of presumed acyclovir-resistant HSV encephalitis.

Discussion: Most pediatric hospitalists would include HSV encephalitis in the differential for mental status changes or personality changes in children, as it is well known that HSV is a common cause of sporadic acute encephalitis and has a high mortality rate if untreated. However, it is also important to realize that symptom recurrence in a previously appropriately treated child is not rare – HSV encephalitis can reoccur or a new autoimmune encephalitis can develop. Relapse of HSV encephalitis is estimated to occur in ~25% of pediatric patients (often days to months after initial treatment), but subsequent autoimmune processes, such as anti-NMDA receptor encephalitis, are becoming increasingly recognized. It is therefore critical to include both entities in the differential diagnosis of recurrent symptoms as management (IVIG vs. antiviral agents) and outcomes may differ. Notably, most relapses of HSV encephalitis are treatable with acyclovir. Studies estimate only 0.3% of all herpes infections are resistant to acyclovir. As our patient seemingly failed both IVIG and acyclovir, brain tissue was directly needed to confirm his disease progression – recurrence of HSV encephalitis years out from initial presentation with a presumed acyclovir-resistant virus.

Conclusions: It is crucial to recognize that recurrence of HSV encephalitis is not uncommon in children, even in those with completed prior treatment.

To cite this abstract:

Ladd JM, Stephany AM. More Than Just the “Terrible Twos”: A Case of Resistant Hsv Encephalitis. Abstract published at Hospital Medicine 2016, March 6-9, San Diego, Calif. Abstract 903. Journal of Hospital Medicine. 2016; 11 (suppl 1). https://www.shmabstracts.com/abstract/more-than-just-the-terrible-twos-a-case-of-resistant-hsv-encephalitis/. Accessed November 22, 2019.

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