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An Unusual Presentation of Varicella Meningitis:
A Case Report and Review of the Literature
Matthew Patel, Rachel Bierbrier, BHSc, Katina Tzanetos, MD MSc
About the Authors
Matthew Patel is an Undergraduate Medical Student at the Royal College of Surgeons in Ireland.
Rachel Bierbrier is with the Department of Dermatology, McGill University Health Centre, Montreal.
Katina Tzanetos is with the Department of Medicine, University of Toronto
Submitted: August 25, 2018. Accepted: January 14, 2019. Published: November X, 2019.
Abstract
Varicella zoster virus (VZV) primary infection causes chickenpox, often in young children, and
is characterized by vesicular lesions on the face, limbs, and trunk. In immunocompetent hosts,
the infection is usually mild and self-limited. Following infection, the virus remains dormant
in the dorsal root ganglia but can reactivate, replicate and cause herpes zoster (shingles), This
report describes a case of reactivation VZV meningitis without any viral exanthema in a young
healthy male.
Résumé
L’infection primaire par le virus varicelle-zona (VZV) cause la varicelle, souvent chez les jeunes
enfants, et se caractérise par des lésions vésiculaires au visage, aux membres et au tronc. Chez les
hôtes immunocompétents, l’infection est généralement légère et auto-limitée. Après l’infection, le
virus reste dormant dans les ganglions rachidiens, mais il peut se réactiver, se répliquer et causer
le zona (zona). Ce rapport décrit un cas de réactivation de la méningite à VZV sans exanthème
viral chez un jeune homme sain.
Varicella zoster virus (VZV) primary infection causes chickenpox,
often in young children, and is characterized by vesicular lesions
on the face, limbs, and trunk. In immunocompetent hosts, the
infection is usually mild and self-limited. Following infection, the
virus remains dormant in the dorsal root ganglia but can reactivate,
replicate and cause herpes zoster (shingles), a painful vesicular
eruption in a single dermatomal distribution.
1,2
Although herpes
zoster typically presents with this characteristic rash, there are
reports of zoster sine herpete herpes zoster without the presence
of a rash but with pain.
1
Neurologic complications, including
meningitis, encephalitis or myelitis can occur with acute infection
or reactivation of VZV, but is uncommon in immunocompetent
hosts, and even more rare without an exanthema.
3
This report
describes a case of reactivation VZV meningitis without any
viral exanthema in a young healthy male.
Case Report
A 19-year-old male attended the Emergency Department with a
6-day history of fever, worsening headache and neck stiffness. The
headache increased with head movement and was unresponsive
to analgesics. There was no preceding viral illness and he had
no sick contacts. In the 2 days before presentation, he developed
night sweats, myalgias and nausea, and vomiting. There was
no rash, vision changes, focal neurological deficits, confusion
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or personality changes. While camping one week before the
onset of headaches he had suffered multiple mosquito bites,
but no tick bites. There was no history of oral or genital herpes
simplex virus (HSV) lesions. He was in a stable, monogamous,
heterosexual relationship for the past three years.
The patient reported that he did have chickenpox as a child.
There was no medical or surgical history and all his vaccinations
were up to date. He took no medications, smoked a half package
of cigarettes daily for the past two years and consumed 4 to 6
alcoholic beverages weekly. There was no history of recreational
drug use.
On examination, he was alert and oriented with normal vital
signs and was afebrile. His neck was stiff and jolt accentuation
was positive. Kernigs and Brudzinksi’s signs were negative.
There were no focal neurological abnormalities or skin rash.
The remainder of the examination was unremarkable.
His laboratory data showed: white blood cell count
(WBC) 9.2 with a normal differential cell count. A venous gas,
electrolytes, renal and liver tests, chest radiography and non-
contrast computed tomography of the brain were all normal.
Plasma serology for syphilis and HIV was negative. A lumbar
puncture was performed and the cerebrovascular fluid results
are shown in Table 1.
The patient was treated with intravenous (IV) acyclovir
and discharged 3 days later when his symptoms resolved. The
IV acyclovir was continued for a total of 14 days. The patient
returned completely to his usual state of health.
Discussion
VZV is a member of the herpes-virus family. The virus is
transmitted through respiratory droplets or direct contact
with fluid from vesicular skin lesions. Chickenpox results
from a primary VZV infection and is characterized by a typical
vesicular rash that starts on the trunk and spreads to the face
and extremities. After inoculation, the virus remains dormant
in the sensory dorsal root ganglion and may reactivate to cause
herpes zoster (shingles): a painful vesicular unilateral rash with
a dermatomal distribution.
VZV infection will result in at least one complication in
approximately 12% of individuals.
4
Herpes zoster (shingles)
is the most common complication of VZV reactivation and
the most common complication of shingles is post-herpetic
neuralgia (PHN); a severe neuropathic pain persisting for
more than 4 months after the acute rash.
5
Secondary bacterial
infections are not uncommon. More rarely infection with VZV
may cause vasculitis. Ischemic and hemorrhagic strokes, due to
viral infection in cerebral arteries, are described.
6
Neurologic
complications including meningitis, encephalitis, transverse
myelitis and Guillian-Barre syndrome are very rare but have
been reported.
1,6
Central nervous system (CNS) infection complicating shingles
with a rash in young immunocompetent adults is recognized
but unusual. Even rarer are CNS infections with VZV in young
immunocompetent patients without a rash.
7
This report describes
a case of VZV meningitis in a young healthy man without any
rash. The clinical presentation and physical exam findings were
consistent with meningitis but not encephalitis. The cerebral spinal
fluid (CSF) findings of increased protein and white blood cell
counts with lymphocytic predominance supported a diagnosis
of viral meningitis (Table 2). VZV polymerase chain reaction
(PCR) was positive confirming VZV meningitis.
VZV meningitis and encephalitis more commonly occur
in immunocompromised hosts but are increasingly recognized
in immunocompetent hosts. This may reflect the newly easily
available, broad-spectrum PCR testing that allows for diagnostic
confirmation rather than a true change in incidence. Although
uncommon, especially in the absence of the typical shingles
rash, VZV must be considered in the differential diagnosis for
clinically suspected CNS infections. Complete CSF fluid analysis,
including PCR testing, is paramount to confirm the diagnosis.
Empiric therapy with broad-spectrum antibiotics and
acyclovir at doses suitable for meningitis is recommended for
Table 1. Cerebrovascular Fluid Results
CSF Result
White Blood Cell Count 836 (0–5 × 106/L) 95%
lymphocytes
Red Blood Cell Count 30 (0–5 × 106/L)
Xanthochromia Absent
Colour & Clarity Clear & Colourless
Glucose 3.2mmol/L (2.2–3.9)
Protein 0.90 g/L (less than 0.45)
Gram Stain & Culture Negative
PCR for West Nile, Enterovirus and
Herpes Simplex Virus I and II
Negative
PCR for Herpes Varicella Zoster
Virus
Positive
CFS = cerebrovascular fluid; PCR = polymerase chain reaction.
(continued )
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Table 2. The Cerebral Spinal Fluid (CSF) Findings Supporting a Diagnosis of Viral Meningitis
Characteristic Meningitis Encephalitis
Inflammation Inflammation of the meninges Inflammation of the brain parenchyma
Clinical Features Fever
Headache
Vomiting
Photophobia
Irritability
Confusion
Nuchal rigidity
Opisthotonus
Purpuric non-blanching rash
Seizures
Confusion
Attention deficits
Altered judgment
Motor or sensory deficits
Behaviour or personality changes
Speech disorders
Movement disorders
Clinical Sequelae Hearing loss
Recurrent seizures
Problems with memory and concentration
Problems with coordination, balance, movement, behaviour
Vision loss
Loss of limbs
Bone + joint problems
Kidney problems
Learning difficulties
Cerebral palsy
Endotoxin shock
DIC
Persistent fatigue
Weakness
Problems with balance, co-ordination and movement
Physical and motor difficulties
Paralysis
Memory problems
Hearing or vision defects
Personality and behavioural changes
Problems with attention, concentrating, planning and problem
solving
Swallowing problems
Aphasia speech and language problems
Intellectual disability
Coma
Difficulty breathing
Death
Aetiology
Cause Viral: Enteroviruses, HSV, mumps
Most common
Milder illness – usually self limiting
Viral: Enteroviruses, HSV, VZV, mumps, arboviruses, rabies
Bacteria: Neisseria meningitides, Streptococcus pneumonia
Less common
Severe illness
Spread to CNS Haematogenous From sites of primary infection
Adjacent focus of infection
Via bony defect or head injury from nasopharynx Reactivation
Direct implantation via trauma, neurosurgery or other
neurological procedures
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70% reduction of incidence of herpes zoster and post-herpetic
neuralgia.
10
This case of a young healthy male, without viral exanthema,
who had confirmed VZV meningitis is extremely rare with only
a few cases reported in the literature.
7
The case emphasizes the
importance of testing the CSF broadly for pathogens, including
broad-spectrum PCR, in suspected meningitis/encephalitis.
References
1. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R,
Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster
virus. N Engl J Med 2000;342:635–45. Available at: https://www.ncbi.nlm.nih.
gov/pmc/articles/PMC3139357/ = 1
2. Steiner I, Kennedy PG, Pachner AR. The neurotropic viruses: herpes simples
and varicella-zoster virus. Lancet Neurol 2007;6:1015–28.
3. Gnann JW. Varicella-zoster virus, atypical presentations and unusual
complications. J Infect Dis 2002;86:S91–8.
4. Galil K, Choo PW, Donahue JG, Platt R. The sequelae of herpes zoster. Arch
Intern Med 1997;157:1209.
5. Whitley RJ. Varicella-zoster virus infections. In: Kasper D, Fauci A, Hauser
S, Longo D, Jameson J, Loscalzo J. eds. Harrisons Principles of Internal
Medicine, 19
th
edition. New York, NY: McGraw-Hill; 2014. Available at:
http://accessmedicine.mhmedical.com.libaccess.lib.mcmaster.ca/content.
aspx?bookid=1130&sectionid=79738275.
6. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus
vasculopathies: diverse clinical manifestations, laboratory features,
pathogenesis, and treatment. Lancet Neurol 2009;8(8):731–40.
7. Pasedag T, Weissenborn K, Wurster U, Ganzenmueller T, Stangel M,
Skripuletz T. Varicella zoster virus meningitis in a young immunocompetent
adult without rash: a misleading clinical presentation. Case Rep Neurol Med
2014;2014.
8. Government of Canada.Varicella (chickenpox) vaccine: Canadian
immunization guide; Ottawa: Author; 2018.
9. Government of Canada.Update on the use of herpes zoster vaccine. Ottawa:
Author; 2016.
10. Raschilas F, Wolff M, Delatour F, et al. Outcome of and prognostic factors for
herpes simplex encephalitis in adult patients: results of a multicenter study.
Clin Infect Dis 2002 Aug 1;35(3):254–60.
suspected CNS infections. The delay between hospital admission
and acyclovir treatment initiation in viral meningitis beyond
two days is a poor prognostic factor and is associated with an
increased risk of neurologic sequelae.
10
CSF test results will direct
subsequent therapy. Antibiotic therapy should be discontinued
when bacterial CNS infection has been excluded. VZV meningitis,
presenting with or without a preceding rash in immunocompetent
hosts is usually benign and self-limited, with recovery in 1 to 2
weeks.
3
There is controversy over the need for treatment with
acyclovir for VZV meningitis in the absence of encephalitis.
The Infectious Disease Society of America 2008 clinical practice
guidelines recommend treatment of VZV encephalitis with
acyclovir based on low-grade evidence.
After consultation with infectious disease specialists and
the patient, a joint clinical decision to treat with acyclovir was
agreed upon to prevent short- and long-term complications
including subtle cognitive impairment, seizures, cerebritis, and
a CNS vasculopathy.
The Canadian immunization schedule includes a 2-dose
varicella vaccine, which is over 98% effective in preventing VZV
infection. Since its’ introduction to the national immunization
program in the early 2000s, the incidence of childhood varicella
infection, and subsequent VZV related hospitalizations has
decreased.
9
The vaccine is an important public health initiative
as it prevents acute chickenpox infection and its complications.
The vaccine program reduces hospitalizations, outbreak-related
costs and societal costs (missed school and workdays).
There are two vaccines available to prevent herpes zoster,
a live vaccine (Zostavax) and a recombinant vaccine (RZV
Shingrix). The recombinant vaccine is the preferred vaccine and
is recommended for Canadian adults over 50 years old. It may
be given to immunosuppressed individuals and has a proven
Lumbar Puncture Profile
White Blood Cells Bacterial: Raised polymophonucleuocytes – neutrophils
(>2000/mm
3
)
Raised neutrophils early and later raised lymphocytes
(<250/mm
3
)
Viral: Raised lymphocytes
Protein Level Bacterial: Very elevated (>200 mg/dL) Elevated (<150 mg/dL)
Viral: Elevated
Glucose Bacterial: Low (<60% of blood glucose) Normal (>50% blood glucose)
Viral: Normal (>50% blood glucose)
Gluckman S. Viral encephalitis in adults. In: Hirsh M, Mitty J, editors. UpToDate. [Internet]. UpToDate Inc; 2018. [updated 2017 Oct 15; cited 2018 Dec 22]. Available from: https://www
.uptodate.com/contents/viral-encephalitis-in-adults
Table 2. The Cerebral Spinal Fluid (CSF) Findings Supporting a Diagnosis of Viral Meningitis (continued )
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