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\begin{document}

\title{Temporal Lobe Hemorrhage as a Complication of HSV Encephalitis, a Case
Report}



\author[1]{Ashes Rijal}%
\author[1]{Sharmila Chaudhary}%
\author[2]{SANGAM SHAH}%
\author[1]{Asmita Itani}%
\author[1]{Anil Suryabanshi}%
\author[3]{Sangharsha Thapa}%
\affil[1]{Tribhuvan University Institute of Medicine}%
\affil[2]{Maharajgunj Medical Campus, Institute of Medicine}%
\affil[3]{University of Minnesota Medical School Twin Cities}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\begin{abstract}
Herpes simplex encephalitis (HSE) is the most common type of sporadic
encephalitis that inflicts high rates of morbidity and mortality.
Differentiating a progressing encephalitis syndrome from a lobar
hemorrhage as a complication presents a challenge and requires great
vigilance and insight on part of the treating physician.%
\end{abstract}%



\sloppy


\section*{Temporal Lobe Hemorrhage as a Complication of HSV Encephalitis,
A Case
Report.}

{\label{temporal-lobe-hemorrhage-as-a-complication-of-hsv-encephalitis-a-case-report.}}

\section*{Author:}

{\label{author}}

Ashes Rijal\textsuperscript{1,2}, Sharmila Chaudhary\textsuperscript{1},
Sangam Shah\textsuperscript{1}, Asmita Itani\textsuperscript{1}, Anil
Suryabanshi\textsuperscript{1}, Sangharsha Thapa\textsuperscript{3}

\section*{Author's affiliation:}

{\label{authors-affiliation}}

\begin{enumerate}
\tightlist
\item
  Tribhuwan University, Institute of Medicine, Maharajgunj, Kathmandu
  44600, Nepal
\item
  Nepal Health Frontiers, Tokha-5, Kathmandu
\item
  Jacobs School of Biomedical Sciences,University of Buffalo, Department
  of Neurology,Buffalo,USA
\end{enumerate}

\section*{Abstract}

{\label{abstract}}

Herpes simplex encephalitis (HSE) is the most common type of sporadic
encephalitis that inflicts high rates of morbidity and mortality.
Differentiating a progressing encephalitis syndrome from a lobar
hemorrhage as a complication presents a challenge and requires great
vigilance and insight on part of the treating physician.

\section*{Keywords:}

{\label{keywords}}

Herpes simplex encephalitis, Lobar hemorrhage, Encephalitis

\section*{Key clinical message:}

{\label{key-clinical-message}}

This case underlined the importance of having high suspicion for lobar
hemorrhage as a complication of HSV encephalitis and shone light upon
the added complexity it poses on management on an already deadly
disease.

\section*{Introduction:}

{\label{introduction}}

Herpes Simplex Virus (HSV) encephalitis remains one of the most common
causes of fatal sporadic viral encephalitis(1, 2). The causative agent
in beyond the neonatal period is usually HSV-1 but HSV-2 and HSV-1 both
can cause HSV encephalitis (HSE) in neonatal period. The mortality rate
is high in non-treated patients compared to treated ones. The mortality
rate of HSE has been reduced to 28\% from 70\% with development of anti
viral therapy.(3). HSV- encephalitis accounts approximately 10-20
percent of the 20,000 annual viral encephalitis in US(4). Incidence of
HSV encephalitis varies worldwide with incidence reported around 0.7 to
13.8 per 100,000 for all ages. (0.7-12.6 /100000 for adults and
10.5-13.8/100000 for children )(2, 5). Patients with HSV-1 encephalitis
usually presents with altered mentation and consciousness for more than
24 hours, fever, new onset of seizures or focal neurological deficits.
Focal neurological deficits may include any focal cranial nerve
deficits, paraparesis, dysphasia, aphasia or ataxia(6). The diagnosis of
herpes simplex encephalitis is confirmed by positive polymerase
reactions (PCR) results for HSV DNA in the cerebrospinal fluid(CSF)(7).
HSV encephalitis causes perivascular edema and hemorrhagic necrosis of
the brain parenchyma, frequently in orbitofrontal and temporal region.
Magnetic resonance imaging (MRI) performed in the acute course of the
disease helps to get best visualisation of cerebral edema and hemorragic
necrosis(8). However, the occurrence of a frank intracerebral hematoma
in the setting of HSE is rare. We report a case of delayed temporal lobe
hemorrhage managed conservatively in an immunocompetent patient with
HSE.

\section*{Case report:}

{\label{case-report}}

A 37-year-old male presented to our hospital with persistent severe
headache and fever. He was apparently well 8 days back when he had
malaise and moderate headache. Following this, the same day he had fever
of recorded temp of 104F with chills and rigor associated with
generalized myalgia but reported no vomiting, photophobia or loss of
consciousness. The next day he had multiple episodes of vomiting
followed by an episode of loss of consciousness associated with tonic
spasm of body and followed by clonic jerky movements of limbs for about
one minute. It was associated with frothing from the mouth, lateral
tongue bite and deviation of angle of mouth to the left side. There was
no bowel bladder incontinence. It was followed by period of post ictal
confusion for about half an hour where he couldn't speak coherently but
was able to move all four limbs. He was swiftly taken to nearby hospital
and managed as seizure disorder. During the six days stay at the
hospital he did not have another episode of loss of consciousness but
fever and headache persisted which were still moderate in intensity.
Likewise, after the first three days of hospital stay he complained of
increased somnolence and was disorientation to time and place. He
developed irrelevant talking and mutism at other times. Thus,
dissatisfied with the level of care and deteriorating status of patient,
the family members brought him to our hospital after being discharged on
patient request. On presentation, he had a fever of 102F. On CNS
examination his naming, short term, and long term memory were impaired.
His sensory and motor examination were intact. There were no cerebellar
or meningeal signs. Planters were bilateral downgoing. His chest and
cardiovascular examination were within normal limits. Thus with these
background clinical features a provisional diagnosis of viral
encephalitis was made and acyclovir started.

Investigations were sent, including blood investigation, cerebrospinal
fluid (CSF) analysis. Here total white blood cells (WBC)counts were
raised to about 19680 cells/ cu mm\textsuperscript{3} and blood sodium
was 127mEq/L rest were within normal limits. On CSF examination, his
blood count was raised to 200 cells/cu mm with monomorphs of 40\% and
polymorphs of 60\%, sugar level was normal (60), and protein was raised
(159); RBCs were not mentioned. Microbiological exam of CSF showed no
growth on culture and no bacterial cells on gram stain. MRI brain showed
features suggestive of herpes encephalitis involving right temporal lobe
and cingulated gyrus without any signs of hemorrhage as depicted in
figure 1. These findings were supportive of our provisional diagnosis of
viral encephalitis. Thus, CSF Polymerase chain reaction (PCR) was sent
which came positive for HSV 1 DNA. Thus a final diagnosis of HSV 1
encephalitis was made.

However, on day six he began to develop severe headache and begun to be
disoriented to time place and person. Consequently, a head Computed
Tomography (CT) scan of head showed hematoma on right temporal lobe, as
seen on the figure 2. A coagulation profile was done at that time showed
no abnormality. Therefore, he was shifted to medical ICU for close
monitoring of his hemodynamic and neurological status. The headache
persisted for three more days then gradually subsided. To address the
raised ICP head elevation was done, mannitol and hypertonic saline were
used but steroids were not. No surgical interventions were needed. He
was well oriented to time place and person by the end of sixth day of
ICU stay. His naming, short term and long term memory were still
impaired otherwise his neurological exam was the same. Following eight
days of ICU stay he was shifted to general ward. On discharge, his
naming, short term and long term memory function had not still
recovered. Motor and sensory examinations were intact throughout. He had
completed 21 days of acyclovir therapy. He was discharged after 27 days
of hospital stay on levateracetam for seizure prophylaxis and was asked
to come for follow up in 15 days. His assessment 15 days later, he still
had problems with naming, short term and long term memories but was
gradually improving. Rest of the neurological examinations were normal.

\section*{Discussion:}

{\label{discussion}}

Herpes simplex virus is a neuro-tropic virus that enters the body
through the mucosal surface. It travels along the axons through
retrograde transport and lies dormant in the sensory ganglia. The exact
mechanism of transport to CNS is not described but it is postulated that
it is a similar mechanism of retrograde transport along the sensory
nerves, given its predilection to mesiotemporal lobe and orbitofrontal
cortex(9). Once in the CNS, the manifestations of encephalitis prevail.
CNS complications include seizures (38.4\%), status epilepticus (5.5\%),
acute respiratory failure (20.1\%), ischemic stroke (5.6\%) and
intracranial hemorrhage (2.7\%)(10). Thus, intracranial hemorrhage being
rare but fatal consequence in many instance(10). Untreated, the
mortality rate in herpes encephalitis due to its complication can reach
to 70\% and most of the survivors can have serious neurological deficits
like neuropsychiatric or neurobehavior issues. HSE encephalitis needs a
prompt treatment with IV acyclovir for the reduction of mortality and
morbidity from HSV encephalitis and its complication.

The exact mechanism of hemorrhage has not been found but few theories
have been described to show the relationship of HSV encephalitis and
lobar hemorrhages. Vasculitis or transient hypertension caused by
increased ICP plays a major role in having lobar hemorrage. The
hypothesis include the rupture of the small vessels due to these above
causes(11). Magnetic resonance imaging (MRI ) of the brain is the
preferred imaging study; T2 images may be more helpful than T1
images(12).

Our patient's presentation was consistent with HSV encephalitis but
later he developed brain hematoma. Otherwise, the clinical features of
brain hemorrhage were not distinctive and overlapped significantly with
those of HSV encephalitis. It is thus difficult to suspect this
complication on clinical grounds alone. The lack of clinical improvement
or the worsening of initial symptoms, particularly during first to
second week of admission, should lead to this suspicion and be followed
by a neuroimaging study. If the evidences discard the possibility of
structural complication, a lack of improvement with the treatment of
acyclovir may raise concern of acyclovir resistance or treatment adverse
effect. This scenario may warrant the start or switch the therapy to
foscarnet(13).

During management of this complication, supportive care and intensive
monitoring was sufficient, and surgical intervention was not required.
Mannitol was used for management of raised ICP but corticosteroids were
not used, the role of which remains still debatable in this area(14). A
multicenter randomized controlled trial was done to study the role of
corticosteroid in treatment of HSV encephalitis but was prematurely
terminated due to small no of study participants(15). Thus, higher level
of evidence to support the use of corticosteroid is lacking. Intensive
care physicians involvement in the care team seems imminent as up to
32\% require ICU stay and 17\% require mechanical ventilation(16).
Similarly, need for surgical intervention may be as high as 50\%
following intracerebral hemorrhage as reported by Sainz et. al(17).The
neurological outcome in the non-operated group was similar, although in
this case it could be argued that they were less severely affected.
Thus, the role of neurosurgery in these patients is still unclear.

\section*{Conclusion:}

{\label{conclusion}}

In conclusion, herpes simplex encephalitis presents as a potentially
lethal disease if it was not for acyclovir therapy. Even still deceased
burden remains high. Lobar hemorrhage as a complication further
compounds the complexity of management and warrants higher level of care
and demands vigilance in part of the management team to detect any
neurological deterioration which at times may masquerade just as a
progressing encephalitis syndrome.

\section*{Acknowledgement:}

{\label{acknowledgement}}

We will like to acknowledge the patient and his family members for their
cooperation for the study.

\section*{Conflict of Interest:}

{\label{conflict-of-interest}}

Authors' have no conflict of interest to declare

\section*{Authors' Contribution:}

{\label{authors-contribution}}

AR wrote the original manuscript, reviewed and edited the manuscript.
SC, SS, AI, AS and ST reviewed and edited the manuscript.

\section*{Data availability
statement:}

{\label{data-availability-statement}}

All the required information is available in the manuscript itself.

\section*{Ethical consent statement:}

{\label{ethical-consent-statement}}

Written informed consent was obtained from the patient for publication
of case report.

\section*{References:}

{\label{references}}

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11. ElShimy G, Mariyam Joy C, Berlin F, Lashin W. Intracranial
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12. Venkatesan A, Jagdish B. Imaging in Encephalitis. Semin Neurol.
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15. Meyding-Lamadé U, Jacobi C, Martinez-Torres F, Lenhard T, Kress B,
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16. Jouan Y, Grammatico-Guillon L, Espitalier F, Cazals X, François P,
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17. Rodríguez-Sainz A, Escalza-Cortina I, Guio-Carrión L, Matute-Nieves
A, Gómez-Beldarrain M, Carbayo-Lozano G, et al. Intracerebral hematoma
complicating herpes simplex encephalitis. Clin Neurol Neurosurg.
2013;115(10):2041-5.\selectlanguage{english}
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