Viral meningitis is a common problem, with an estimated 2,500-4,000 cases per year in the UK. It is caused by a variety of viruses, most commonly enteroviruses. While often considered self-limiting, viral meningitis can cause significant short-term symptoms like headaches and longer-term issues like fatigue, as well as incurring high healthcare costs. More research is needed to better understand pathogenesis, improve diagnosis, identify treatment options, and evaluate long-term outcomes.

1. Viral Meningitis: a real pain in
the neck!
A current review of viral meningitis.
Dr Fiona McGill
Clinical Research Fellow, Liverpool Brain Infections Group
Specialist Registrar in Infectious Diseases and Medical
Microbiology

2. Outline
• Background
• How big is the problem.
• What causes viral meningitis.
• What happens to people who have viral
meningitis
– In the short term - symptoms
– In the longer term - consequences
• What are the outstanding unanswered
questions.

3. Meningitis
• What do people think of when they think of meningitis?
– “Panic, really serious illness”
– “rash, glass test, projectile vomiting, sore neck, dislike of bright
light, scary bananas”
– “Aaaaaaaaaaaaaagh!”
– “inflammation of the stuff round the brain, membrane? I don't know”
– “Affects small children, every parent’s nightmare, nearly always fatal”
– “Headaches, rashes that don’t disappear, aversion to bright
lights, vomiting and nausea”
– “that's not good. Then the test u r supposed to do with the glass for
blotchy skin, high temperature, difficulty breathing, vomiting possibly”
– “'serious' and mainly of kids/young people, the glass test”
– “It is extremely dangerous, can kill”
– “Scary, serious, unpredictable, rash”
– “serious illness, rash, glass test”

4. Meningitis
• What do people think of when they think of meningitis?
– “Panic, really serious illness”
– “rash, glass test, projectile vomiting, sore neck, dislike of bright
light, scary bananas”
– “Aaaaaaaaaaaaaagh!”
– “inflammation of the stuff round the brain, membrane? I don't know”
– “Affects small children, every parent’s nightmare, nearly always fatal”
– “Headaches, rashes that don’t disappear, aversion to bright
lights, vomiting and nausea”
– “that's not good. Then the test u r supposed to do with the glass for
blotchy skin, high temperature, difficulty breathing, vomiting possibly”
– “'serious' and mainly of kids/young people, the glass test”
– “It is extremely dangerous, can kill”
– “Scary, serious, unpredictable, rash”
– “serious illness, rash, glass test”

6. What is meningitis?
• Meningitis
– Inflammation of the meninges
• What are meninges?
– Lining of the brain.

7. What is meningitis?
• Often caused by infection
– Bacteria
– Viruses
– Fungi, parasites, tuberculosis, HIV.......

8. What is a virus?
Viruses Bacteria
• Very small (10nm-300nm) • Larger – can be seen with a
• Live inside cells normal microscope
(1000nm)
• Difficult to grow in a lab
• Most grow easily given the
right conditions
• Can live out with cells

9. Viral Meningitis
• How big is the problem?
– 2009-2010 data
• HES 3434 cases
• HPA 260 notified cases
– Finnish study
• 7.6/100,000 (adults)
– 50% of all meningitis related hospital admissions
• c. 2500 – 4000 cases a year in the UK

10. Viral Meningitis - causes
• Lots!
• Enteroviruses
– Same family as poliovirus
– Gut bug
– Can be fatal in very young children
– Spread by poor hygeine
– Outbreaks
– Seasonal

11. • Herpesviruses
– Herpes simplex virus type 2
• Spread sexually – often asymptomatically
• Very few have current/history of genital disease
• Amount of people infected worldwide with HSV-2 is
increasing
• Can recur (most don’t!)
• Can occur with a first infection, or several years after
infection

12. • Varicella Zoster virus
– Chickenpox/Shingles
– Often occurs without rash
– Can occur at time of first infection or as a
reactivation

13. • Arboviruses
– Arthropod Borne Viruses
– Not present in UK but are in Europe/USA
– Think of in travellers
– Toscana Virus, West Nile Virus, Tick Borne
Encephalitis

14. • HIV
– Causes an “aseptic” meningitis
– Normally at time of first infection
– Can occur later in disease
– If missed may mean patient not diagnosed until
have advanced disease or ‘AIDS’
– 30% of patients diagnosed with HIV could have
been diagnosed earlier

15. • Others
– Mumps
– Other herpes viruses
• EBV, CMV, HSV-1, HHV-6/7
– Parechoviruses (normally in young children only)
• Many remain without a specific bug

16. Undiagnosed Meningitis
• 30-40% of patients with clinical viral meningitis

17. Undiagnosed Meningitis
• Lack of knowledge and investigations not
requested/done %age done
HSV-1 PCR (n=100) 92
HSV-2 PCR 92
EV PCR 89
VZV PCR 82
Parecho PCR 64
HIV ag/ab (n= 37) 41
• Current diagnostics inadequate
• New/emerging pathogens

18. Clinical Features

19. Demographics
Age and Gender Distribution between different aetiologies
Median Age %age female n
Control 37 67.4 92
ASM 32.5 62.7 102
SBM 59.5 35.7 28
Encephalitis 47.5 60 10
Median Age %age female N
Enterovirus 30 65.1 43
HSV-2 43 78 9
VZV 40 60 5
Unknown 32.5 58 38
ASM

20. Clinical Features
• Common
– Headache
– Fever
– Photophobia
– Neck Stiffness
– Nausea and vomiting
• Less common
– Rash
– Myalgia
– Very few have concurrent (or previous) genital lesions

21. Clinical Features of Different Viruses
Headache Photophobia Neck Stiffness Fever N and/or V
Enterovirus Ihekwaba et 100% 82% 77% 37.8+/-0.8 91%
al (n=22)
Meningitis 100% 91% 77% 67% 47%
NW (n=43)
VZV Ihekwaba et 76% 25% 38% 37.3+/-1.0 50%
al (n=8)
Meningitis 100% 60% 20% 60% 80%
NW (n=5)
HSV-2 Ihekwaba et 100% 63% 100% 37.8+/-0.6 100%
al (n=8)
Meningitis 100% 67% 56% 44% 56%
NW (n=9)
Ihekwaba UK, Kudesia G, McKendrick M. Clinical Features of viral Meningitis in Adults: significant
differences in Cerebrospinal Fluid Findings among Herpes Simplex Virus, Varicella Zoster Virus and
Enterovirus Infections. CID 2008:47. 783-789.

22. Outcomes

23. What are the longer term outcomes for
people with viral meningitis?
•Viral meningitis is often quoted as being a
benign self-limiting illness
•Doesn’t tend to maim or kill
•However
• individual consequences
• fatigue
• cost implications1
• psychosocial
• evidence of poor neuropsychological
outcomes2
• recurrences
1) Khetsuriani et al, Viral Meningitis associated hospitalisations in the US, 1988-1999. Neuroepidemiology. 2003; 22: 345-352
2)Schmidt et al, Neuropsychological sequelae of bacterial and viral meningitis. Brain (2006):129:333-345

24. Individual impact
• 2500-4000 individuals
– Significant impact at the individual level
– I am nowhere near being back to normal and anticipate it being months until I am.
– Since being home I have found it hard to concentrate, had memory loss, muffled ears, sleep
apnoea, racing heart, shooting pains down my legs, loss of co-ordination, sore and stiff neck
and back, speech problems, shakes, photophobia on occasion, tics and twitches and felt
depressed.
– It lasted for only a week but I can honestly say that was the worst seven days of my life. I
wouldn't wish meningitis on my worst enemy.
– I had never felt so unwell.
– it was the scariest thing I have ever had to experience
– I now have really bad headaches and my back is always sore with shooting pains through it.

25. Economic sequelae
• Healthcare costs
• Loss of earnings
• Young, fit people
• Indirect costs
• Carers etc…
• 1.3 billion USD over a 5 year period
Khetsuriani et al, Viral Meningitis associated hospitalisations in the US, 1988-1999.
Neuroepidemiology. 2003; 22: 345-352

26. Neuropsychological sequelae
Domain BM (%) VM (%) Control (%) P value
Attention 39 42.6 20.0 Ns
Executive 63.6 48.3 25.0 Ns
Function
Short term 58.6 39.5 15.4 <0.01
memory
Verbal learning 31 25.0 10.0 Ns
Schmidt et al, Neuropsychological sequelae of bacterial and viral meningitis. Brain
(2006):129:333-345

27. Recurrences
• Mollaret’s/recurrent benign lymphocytic
meningitis
• All viruses have been reported
• HSV-2 by far the commonest

28. Recurrences
Herpes viruses – latency and reactivation
• Herpes viruses are characterised by the ability to
establish latency
– Remains present in the host
– No active replication
– Always retain ability to reactivate
• Reactivation
– Triggers
– Associated with immune status
– More frequently with HSV than VZV (normally only
once)
– Normally asymptomatic

29. Recurrences
Recurrent genital HSV-2
• Genital recurrences common
– Asymptomatic and symptomatic
– Asymptomatic more common
– Infection with HSV-2 globally is rising
– Infection with HSV-2 significantly increases risk of
HIV infection
– Antivirals reduces clinical disease and detectable
genital shedding but don’t reduce transmission or
HIV acquisition

30. Recurrences
Recurrent HSV-2 meningitis
Finnish study
665 patients with lymphocytic meningitis
37 had recurrent meningitis (5.6%)
28 had HSV-2 in CSF (76%)
27-30% of pts with HSV-2 in CSF had previous
episodes of meningitis
3 patients had recurrent genital herpes (8%)
Prevalence of RLM 2.7/100000
Prevalence of HSV-2 ass RLM 2.2/100000
Kallio-Laine et al. Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2.
EID. 15(7) :1119-1122

31. Recurrences – does prevention work?
101 patients with HSV-2 meningitis
Randomised to Valaciclovir or placebo
Treated for one year and followed up for a further year
Recurrent meningitis commoner in patients who took valaciclovir than in
those who were on placebo
?Dose not right
?unable to completely eradicate/prevent virus once it has established latency

32. Research questions

33. Research questions
• Pathogenesis
• Diagnostics
• Treatment options
• Longer term outcomes
– Recurrences
– Economics

34. Pathogenesis
• Current work is very patchy
– Based on work on polio
• Why do some people get recurrent disease?
– Immune defects

35. Diagnostics
• The polymerase chain reaction has greatly
improved things
• Still significant number of people not getting a
diagnosis
– Requires education
– New approach
• Gene expression profiling

36. New approaches to diagnostics
• Gene expression profiling
– gene expression
A - TB meningitis
B - Cerebral Malaria
C – Bacterial meningitis
Griffiths, M, Hemingway C
Newton, C Levin, M;
unpublished

37. Treatment options
No proven, licensed treatments for any of the common causes of
viral meningitis
– ?Aciclovir
• Enterovirus
– Pleconaril • HIV
• Reduced symptoms by a – Antiretrovirals
day or so • Others
• Potential for interactions – Supportive
deemed too high for clinical – ?steroids
benefit, never licensed
– ?immunoglobulin
– ?immunoglobulin
• Herpes viruses

38. HSV-2 meningitis - to treat or not to treat
• US Study (2009)
– Retrospective review of HSV-2 in CSF
– 19 cases of meningitis, 74% female, only 2 had history of prior
genital herpes, one had concurrent herpes
– Treatment variable
– None to 21 days of IV Aciclovir and everything in between.
• Need for a properly conducted trial

39. Longer term outcomes
• How much does viral meningitis cost the NHS
in the UK?
• Are there neuropsychological consequences?

41. How common is it?
Patients admitted with suspected meningitis who have
a lumbar puncture (spinal tap)
1. Control patients
 Symptoms of meningitis, normal lumbar puncture
findings.
2. Meningitis
 Viral, bacterial, other....

42. Adults ≥16
Admitted to hospital with suspected
meningitis
Lumbar Puncture
Aseptic Suspected
Control meningitis Bacterial
(ASM) Meningitis
(SBM)
Viral Others
meningitis TB

43. How common is it?
• C.30 hospitals in the North of England

44. What happens to people with viral
meningitis?
• Follow-up with questionnaires for a year after
admission
– Headaches
– Quality of life
– Brain functioning
– Economics

45. Suspected
Aseptic Bacterial
Control meningitis Meningitis
5 x questionnaires at 6, 12, 24 and 48 weeks

46. Improving diagnosis
• Looking at genes expressed in the
host/patient
• Are their differences between
controls and meningitis?
• Are they different between patients who have
viruses and those who have bacteria?
• Are they different between different viruses?
• Blood and spinal fluid
c/o M.Griffiths

47. Pathogenesis
• HSV is so prevalent why do some people
develop meningitis and others don’t?
– Examine differences in DNA from pts with
meningitis and those without
– Both patient and viral/bacterial DNA
– Compare differences in pathogen DNA from
different sites e.g. CSF and genital

48. Thanks
• You – for listening
• MRF
• LBIG and Prof Solomon etc…..
• Doctors and Nurses at all the sites involved in
my study
• All the patients in the study
Any questions?