HSV Meningitis

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HSV Meningitis

• K Tyler (USA)

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HSV Meningitis

• 1-7 of all cases of aseptic meningitis
• HSV-2 gtgt HSV-1
• 50 of cases primary (pts seronegative) and 50
  of cases secondary (pts already seropositive)
• 20-45 with meningitis have recurrent episodes

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HSV-2 Meningitis Genital Herpes

• Complication of primary genital herpes
• In 13 men, 36 women
• 85 with 1st episode HSV meningitis have
  associated genital lesions preceding meningitis
• Range 2-14 d mean 9 d
• Range 3-27 days mean 7.5 5.9 d
• Only 30-60 with recurrent HSV-2 meningitis have
  a history of genital herpes

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HSV Meningitis-Diagnosis

• CSF lymphocytic pleocytosis, elevated protein,
  normal glucose
• CSF HSV PCR positive in 85-100
• CSF culture
• 80 positive with 1st attack
• 0 with recurrent episodes
• HSV CSF antigen detection?
• 70 with 1st attack
• 0 with recurrences
• Intrathecal (CSF) HSV IgG?
• ? sensitivity (40-85)

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CSF in 1o Recurrent HSV-2 Meningitis
FIRST(27) RECURRENT (7)

• WBC/mm3 431316 280170
• (4-1100)
  (77-546)
• Mononuclear Cells 367293 85 263166 94
• (4-1070)
  (72-528)
• Protein (mg/dL) 160110 10030
• (0.4-3.0)
  (0.7-1.5)
• Glucose (mg/dL) 5413 6316
• (27-81)
  (41-87)

Bergstrom et al., JID 162322, 1990
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CSF in HSV Encephalitis vs. Meningitis
Encephalitis Meningitis

• WBCs/mm3 202 (2-667) 484 (58-1888)
• lt10 cells/mm3 19 12
• Lymphs 76 (16-97) 87 (43-100) ns
• RBCs/mm3 2518 (0-27,566) 54 (0-711) ns
• Protein mg/dL 73 (22-146) 129 (75-281)

Simko et al., CID 35417, 2002
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Complications of HSV-2 Meningitis (27 cases)

• None 37
• Recurrent meningitis 19
• Urinary retention 15
• Recurrent headaches 15
• Paresthesia/Dysesthesia 15
• Neuralgia 11
• Weakness/Paraparesis 11
• Difficulty concentrating 7
• Hearing loss 4
• Sequelae _at_ 6 mos 0

Bergstrom et al. JID 162322,1990
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HSV Meningitis - Morbidity

• Recurrent meningitis (20-45)
• Recurring myelitis or radiculitis (5-10)
• Bowel or bladder problems plus leg weakness
  and/or paresthesias
• Legs radicular pain, weakness, paresthesias
• Headache (5-10)
• Fatigue, difficulty concentration (5-10)

Aurelius et al. Scand JID 34278, 2002
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Causes Recurrent Aseptic Meningitis

• Infectious
• Drug-related hypersensitivity
• Rheumatologic disorders
• Recurrent inflammatory disease
• Uveomeningitic syndromes (VKH)
• Intracranial/Intraspinal cysts tumors
• Headache neuro. deficits with CSF Lymphocytosis
  (HandL)
• Mollarets (Idiopathic)

DeBiasi Tyler, 2000
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Definition of Recurrent Meningitis

• gt2 episodes meningitis
• Symptom-free intervals
• Normal CSF between episodes
• Must be differentiated from chronic meningitis
• Culture versus Aseptic

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• HSV in recurrent (Mollaret) meningitis
• HSV-1 Culture n1 Steele et al., 82
• HSV-1 PCR n1 Yamamoto et al., 91
• HSV-2 PCR n3 Picard et al., 93
• HSV-2 PCR n1 Cohen et al., 94
• Recurrent meningitis after genital herpes
• n5-12 Bergstrom et al., 90
• n3 Berger et al., 91

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Herpes simplex virus infection as a cause of
benign recurrent lymphocytic meningitisTedder
DG, Ashley R, Tyler KL, Levin MJAnnals of
Internal Medicine 121334-338, 1994

• Design Prospective Cohort Study
• Setting Tertiary referral center
• Population 20 consecutive patients with
  recurrent meningitis
• 13 met study criteria
• Exclusions (7) - PMN pleocytosis (3), inadequate
  acute CSF specimen (2), lt3 attacks (1), SLE (1)

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Benign Recurrent Lymphocytic MeningitisClinical
Features

• Sex 9 women (69), 4 men (31)
• Age 38.5 11 yrs (26-73)
• Attacks 4.7 1.7 (3-9)
• Duration attacks 6.3 2.7 days (3-14)
• Duration illness 8.4 5.2 yrs (2-21)
• 23 (3/13) Hx genital herpes-none at time of
  study episode of meningitis

Tedder DG et al., Annals Internal Medicine
121334, 1994
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Benign Recurrent Lymphocytic MeningitisCSF
Profile

• 443 432 cells (48-1600), 58-98 lymphs
• 93 gt 50, 86 gt100, 63gt250, 24 gt500, 15gt1000
• Protein 122 50 (41-240) mg/dL
• 77gt100, 23gt150, 8gt200
• Glucose 55 15 (41-102) (all gt50 serum)

See Tedder et al. Ann Intern Med 121334, 1994
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Benign Recurrent Lymphocytic MeningitisCSF PCR
Antibody Studies
Tedder et al. Annals Intern Med, 121334, 1994
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Role of HSV in Benign Recurrent Lymphocytic
Meningitis

• HSV is the major cause of benign recurrent
  lymphocytic meningitis
• Viral cultures are almost always negative
• PCR (or CSF Ab studies) are required to
  demonstrate HSV infection
• Most patients do not have a history of genital
  herpes have no clinical evidence of genital
  lesions at time of meningitis

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HSV Meningitis- Rx(Category III)

• No controlled trials, all anecdotal data
• Acyclovir of possible benefit
• 5-10 mg/kg q8h iv x 7-10d for seriously ill
• 800 mg po 4-5x/day x 10 days ?
• 200 mg 4x/day with onset genital lesions x 5-gt10
  d
• Other oral antiviral drugs likely to be
  effective?
• Famciclovir 500 mg 3x/day x 10 days?
• Valaciclovir 1000 mg 3x/day x 10 days?
• Prophylaxis for pts with recurrent meningitis?
• Acyclovir 200 mg 4x/day
• Famciclovir 250 mg 2x/day
• Valaciclovir 500 mg 1x/day

See Bergstrom Alestig Scand JID 22239, 1990