Granulomatous herpes simplex encephalitis in an infant with multicystic encephalopathy: a distinct clinicopathologic entity?
BACKGROUND
Herpes simplex virus encephalitis can manifest as a range of clinical presentations including classic adult, neonatal, and biphasic chronic-granulomatous herpes encephalitis.


METHODS
We report an infant with granulomatous herpes simplex virus type 2 encephalitis with a subacute course and multicystic encephalopathy.


METHODS
A 2-month-old girl presented with lethargy and hypothermia. Computed tomography scan of the head showed multicystic encephalopathy and calcifications. Cerebrospinal fluid analysis by polymerase chain reaction testing for herpes simplex virus 1 and 2, enterovirus, and cytomegalovirus was negative. Normal cerebrospinal fluid interferon-α levels argued against Aicardi-Goutières syndrome. The patient died 2 weeks after presentation. At autopsy, multicystic encephalopathy was confirmed with bilateral gliosis, granulomatous inflammation with multinucleated giant cells, and calcifications. Bilateral healing necrotizing retinitis suggested a viral etiology, but retina and brain were free of viral inclusions and immunohistochemically negative for herpes simplex virus-2 and cytomegalovirus. However, polymerase chain reaction analysis showed herpes simplex virus-2 DNA in four cerebral paraffin blocks. Subsequent repeat testing of the initial cerebrospinal fluid sample using a different polymerase chain reaction assay was weakly positive for herpes simplex virus-2 DNA.


CONCLUSIONS
Granulomatous herpes simplex virus encephalitis in infants can present with subacute course and result in multicystic encephalopathy with mineralization and minimal cerebrospinal fluid herpes simplex virus DNA load. Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. Electronic address: peter.schutz@vch.ca.
Peter W
PW
Schutz
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Pathology, Red Deer Regional Hospital, Red Deer, Canada.
Clarissa T
CT
Fauth
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, Children's and Women's Health Centre of British Columbia, Vancouver, Canada.
Ghada N
GN
Al-Rawahi
Department of Radiology, University of British Columbia, Vancouver, Canada.
Denise
D
Pugash
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada.
Valerie A
VA
White
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Sylvia
S
Stockler
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, Children's and Women's Health Centre of British Columbia, Vancouver, Canada.
Christopher P
CP
Dunham
D001927:Brain Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004279:DNA, Viral / Q000134:cerebrospinal fluid; D003937:Diagnosis, Differential; D020803:Encephalitis, Herpes Simplex / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D018258:Herpesvirus 2, Human; D006801:Humans; D007223:Infant; D014057:Tomography, X-Ray Computed
D004279:DNA, Viral
Aicardi-Goutières syndrome; cerebral mineralization; encephalitis; herpes simplex virus; multicystic encephalopathy; necrotizing retinitis; neurotransmitter abnormality