Journal of the Neurological Sciences 325 (2013) 154155

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Journal of the Neurological Sciences

journal homepage: www.elsevier.com/locate/jns

Short communication

The occular syndrome in herpes simplex type 1 encephalitis

Aasef G. Shaikh , Pichet Termsarasab, David E. Riley, Bashar Katirji
Department of Neurology, Case Western Reserve University, Cleveland, OH, United States

a r t i c l e

i n f o

Article history:
Received 20 October 2012
Received in revised form 31 October 2012
Accepted 1 November 2012
Available online 4 December 2012
Keywords:
Downbeat nystagmus
Oscillopsia
Vertigo
Cerebellum

a b s t r a c t
A woman with herpes simplex virus type 1 (HSV1) encephalitis had downbeat nystagmus. The nystagmus
was robust in primary gaze but attenuated during upgaze, suggestive of the occulus involvement. FLAIR
and T2-sequences of the brain MRI revealed cerebral lesions typical of HSV1, but also patchy hyperintensities
in bilateral occuli. Cerebrospinal uid polymerase chain reaction conrmed HSV1 infection. Encephalopathy
and downbeat nystagmus gradually improved with acyclovir therapy.
2012 Elsevier B.V. All rights reserved.

1. Introduction
Frontal and temporal cerebral necrosis is the classic feature of
herpes simplex type-1 (HSV1) encephalitis [1]. However, in immunocompromised subjects HSV1 may affect infratentorial structures leading
to atypical clinical presentations [24]. We describe a case of orid
HSV1 encephalitis that uniquely progressed to manifest downbeat nystagmus and correlating lesions in bilateral occuli.
2. Case report
A 57-year-old woman with a history of non-small cell lung cancer
was treated with dexamethasone. A cluster of ve clonic seizures
prompted hospitalization. The patient was drowsy and mute but
followed verbal commands. Downbeat nystagmus developed two
days later. The nystagmus was robust in primary gaze, but attenuated
during upgaze (video clip). There was a marked limitation of downgaze
due to strong upward drifts of the eyes. The amplitude or the direction
of the nystagmus did not change during rightward or leftward gaze
holding. The quick phase of the nystagmus frequently interrupted
pursuit eye movements. Remaining neurological examination was
unremarkable.
Fluid attenuated inversion recovery (FLAIR) and T2-weighted sequences of the brain MRI revealed hyperintense signal in left temporal
lobe, left posterior sub-frontal region, left insula, and bilateral hippocampi, consistent with HSV1 encephalitis (Fig. 1A). Patchy hyperintensities
in both cerebellar occuli were seen in FLAIR sequences (Fig. 1B).

Corresponding author at: Department of Neurology, Case Western Reserve University,

11100 Euclid Avenue, Cleveland, OH 44106-5040, United States. Tel.: +1 313 850 8604.
E-mail address: aasefshaikh@gmail.com (A.G. Shaikh).
0022-510X/$ see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jns.2012.11.002

There was no abnormal MRI enhancement in the posterior fossa after

gadolinium injection. CSF disclosed 22 nucleated cells (6% neutrophils and 94% mononuclear cells), glucose was 56 mg/dL (normal
range: 4070 mg/dL), and protein was 136 mg/dL (normal range:
1545 mg/dL). Paraneoplastic antibodies (anti-MA, anti-TA, antiNMDA, striational antibody, P/Q type calcium channel, N-type
calcium channel, ANNA 1-3, PCA 1, PCA 2, PCA TR, amphiphysin antibody, CRMP IgG, and AGNA-1) and CSF polymerase chain reaction
(PCR) for Varicella zoster virus, cytomegalovirus, and EpsteinBarr
virus were negative. CSF PCR conrmed HSV1 infection. There
was a gradual improvement of encephalopathy and downbeat
nystagmus with parenteral acyclovir therapy (650 mg every 8 h for
two weeks).
3. Comment
Seizures, encephalopathy, frontal and temporal cortex hyperintensities in FLAIR MRI sequence, and reactive PCR were typical ndings of HSV1 encephalitis that were also noted in our patient. The
downbeat nystagmus that emerged after two days and its correlation
with the MRI lesions in both occuli is the unique feature of this case.
The viral infection might have started in the cerebral hemispheres
and progressed to the cerebellum. The cross-immune etiology is
another speculation. Hypothetical cross-immune attack might have
been directed to the specic antigen exclusively present in the occuli. There was a delay in the emergence of the downbeat nystagmus.
Therefore it is possible that the infection had occurred at typical
supratentorial locations; as cross-immune reactions ensued, both
occuli got affected and the nystagmus emerged. In support of our
speculation, the only other reported case of the downbeat nystagmus
was also seen at a two-day latency since the presentation for an
unspecied type of herpes encephalitis [5]. In this autopsied case,

A.G. Shaikh et al. / Journal of the Neurological Sciences 325 (2013) 154155

155

Fig. 1. Fluid attenuated inversion recovery (FLAIR) sequence of the brain MRI showing hyperintense signal (arrows) in the left temporal lobe (A), bilateral hippocampi (A), and
bilateral cerebellar occuli (B).

brainstem and cerebellum were histologically normal, but in both areas

there were multiple foci of normal neurons containing HSV antigen [5].
Downbeat nystagmus is one of the classic clinical manifestations of
the occulus lesion [6]. Floccular inhibition keeps the eyes steady during downgaze. Hence, disruption of such inhibition results in a slow upward drift of the eyes followed by a downward corrective saccade (the
quick phase or the beat), hence the name downbeat nystagmus [7,8].
Asymmetry in the vertical smooth pursuit pathway, or unequal neural
tone in the central vestibular connections of the vertical semicircular canals and otoliths, can also cause downbeat nystagmus in patients with
brainstem or cerebellar lesions [9]. The nystagmus in our patient was
likely a manifestation of the occular lesions that were visible in MRI
[6]. The lack of MRI contrast enhancement in the posterior fossa that
might have indicated a metastatic lesion, the negative paraneoplastic
panel, and the response to acyclovir suggested a likelihood that downbeat nystagmus in our patient was related to HSV1 affecting the
occulus.
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.jns.2012.11.002.
Conict of interest
The authors have no conict of interest.

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