Postherpes simplex encephalitis: a case series of viral-triggered autoimmunity,
synaptic autoantibodies and response to therapy
#MMPMID29774053
Alexopoulos H
; Akrivou S
; Mastroyanni S
; Antonopoulou M
; Dinopoulos A
; Giorgi M
; Konstantinou K
; Kouremenos E
; Lariou M
; Naoumis D
; Pavlidou E
; Pavlou E
; Voudris K
; Vlachoyiannopoulos P
; Dalakas MC
Ther Adv Neurol Disord
2018[]; 11
(?): 1756286418768778
PMID29774053
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BACKGROUND: Recent evidence suggests that patients with herpes simplex virus
(HSV) encephalitis may relapse because of autoimmunity against the
N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV
relapsing encephalopathy associated with antibodies to central nervous system
(CNS) synaptic antigens. PATIENT/METHODS: Sera and cerebrospinal fluid (CSF) from
five patients with HSV encephalitis who relapsed after antiviral therapy were
tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR),
?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR),
Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated
protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies
using cell-based assays. RESULTS: Five patients (two infants, one child and two
adults) developed post-HSV autoimmune encephalitis. The infants, aged 9 months
and 10 months, after prompt and seemingly successful anti-HSV therapy, were
readmitted with typical signs of NMDAR-encephalitis evolving within days, with
NMDAR antibodies detected in both serum and CSF. Although they were promptly
treated with intravenous immunoglobulin (IVIg) and with IVIg followed by
rituximab, respectively, they were both left with psychomotor deficits. A
14-year-old girl with seizures due to HSV encephalitis improved with anti-HSV
therapy. Later, she manifested intractable seizures and she was found positive
for anti-NMDAR antibodies which persist. The two adults were women, aged 58 and
33 years. The first recovered after anti-HSV therapy and remained asymptomatic
for 6 months, until she developed generalized seizures with persisting CSF
anti-NMDAR antibodies; the second, who continued to be encephalopathic after 2
weeks of anti-HSV therapy, tested positive for anti-NMDAR antibodies in the serum
and anti-GABAbR antibodies in the serum and CSF. She recovered fully following
IVIg therapy but her serum anti-GABAbR antibodies persist 34 months later.
DISCUSSION: Infection of the CNS with HSV can trigger CNS autoimmunity associated
not only with anti-NMDAR but also with anti-GABAbR antibodies. These antibodies
can persist in the serum, even without associated symptoms, but their presence in
the CSF is firmly associated with disease development. In contrast to children
and adults who responded well to therapies, the infants had an incomplete
recovery with severe psychomotor deficits probably due to the interference of
anti-NMDAR antibodies with neuro-developmental processes.
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