APPROACH OF MENINGITIS (1).pptx

APPROACH TO CASE OF MENINGITIS
MODERATOR
DR.VARSHA AMBWANI
(DM.NEUROLOGY)
ASSISTANT PROFESSOR
DEPARTMENT OF NEUROLOGY
PRESNTED BY
DR.ALOK KUMAR SINGH
JR -1 MEDICINE

Presentation outline
• Introduction
• Types of meningitis
• Causes
• Clinical presentation
• Investigations
• Lumbar puncture procedure
• Approach in case of suspected meningitis
• Management Algorithm
• Brief overveiw of different types of meningitis

Introduction
DEFINITION
Meningitis is an
inflammation of the
leptomeninges
(arachnoid and pia
mater) surrounding
the brain and spinal
cord, with involvement
of the subarachnoid
space

Types of Meningitis
Based on etiology

• Based on duration
 Acute meningitis
 Subacute meningitis
 Chronic meningitis/Recurrent meningitis
• Based on blood culture
 Septic meningitis
 Aseptic meningitis

Causes of Meningitis
Bacterial
• Neisseria meningitis
• Haemophilus influenzae
• Listeria monocytogenes
• Gram negative bacilli
• Staphylococcus aureus
• Streptococcus agalactiae

Virus
• Enterovirus
• Herpes simplex virus
• Varicella zoster virus
• Adenovirus
• Arboviruses
• Coxsackieviruses types A and B

Fungal
• Cryptococcus neoformans / gattii
• Histoplasma
• Coccidioides
Parasitic
• Taenia solium
• Naeglaria Floweri
• Toxoplasma
• Acanthamoeba

Drug
• Anti-CD3 monoclonal antibody
• Azathioprine
• Ibuprofen
• Other NSAIDs
• Trimethoprim-sulfamethoxazole
Malignancy
• Leukemia
• Lymphoma
• Metastatic carcinomas and adenocarcinomas

Autoimmune
• Sarcoidosis
• Systemic lyupus erythematosus
• Vogt-Koyanagi-Harada syndrome
Other
• Epidermoid cyst
• Postvaccination

Clinical Presentation
Lancet Neurol 2008; 7: 637–48
Common signs and symptoms of acute
bacterial meningitis

 Classic triad of fever, neck stiffness, and headache seen in
only 2/3rd of adults.
 More common in pneumococcal than other bacterial
meningitis.
 1 of the 3 elements present in almost all patients.
 Absence of all 3 rules out acute meningitis with sensitivity of
99-100%.
 Usually history is of 24 to 48 hours.
Clinical Presentation (contd.)

 Rash most commonly seen with meningococcal
disease (92% of meningitis cases with rash).
 Presence of shock, rash or clustering of cases should
raise suspicion of meningococcemia.
Petechial skin rash that accompanies
meningitis due to Neisseria meningitidis.
Fine petechial rash in disseminated infection and
meningitis due to Staphylococcus aureus

 Kernig’s and Brudzinski’s sign have poor sensitivity (5%) with
high specificity (95%)
 Nuchal rigidity has low sensitivity (30%) and specificity
(68%).

 Jolt accentuation test - exacerbation of existing
headache on having the patient rotate his head horizontally
@2-3 times/ sec.
 Sensitivity of 97%, specificity of 60% in a small study, never
been further evaluated extensively.
Lancet Infect Dis 2007; 7:191–200
N Engl J Med 2004;351:1849-59.

Investigations
 ↑ TLC (mean 10,600/cc vs 8900/cc).
 ↓Platelet counts- systemic infection, sepsis.
 **Hyponatremia (serum Na < 135mEq/l) seen in 30% cases.
- Severe (Na <130) in 6%. (resolves spontaneously)
- More common with L. monocytogenes and in
patients with symptoms > 24 hours.
 Blood culture- should be taken immediately, before starting
antibiotics. Positive in 74% cases.
**QJ Med 2007;100:37-

 Acute inflammatory markers - ESR, CRP and Procalcitonin
elevated : distinguish acute bacterial from non bacterial
meningitis.
 Diagnostic lumbar puncture - performed in all cases unless
specific contraindications present-
i) local infection at puncture site
ii) subdural abscess
iii) bleeding diathesis
iv) septic shock- diastolic BP < 60 mm of Hg
v) mass lesion/ ventricular obstruction/ brain shift on
cranial imaging
Investigations (contd.)

Indications for cranial imaging before L.P.
 Non contrast CT scan of the head before L.P. is indicated if
one of the following is present:
i. New onset seizure (within one week of presentation)
ii. Immunocompromised state
iii. Papilledema
iv. Focal neurological signs (excluding hearing loss)
v. Moderate to severe impairment of consciousness (GCS <10)
 Absence of all these features has 97% negative predictive
value for an intra cranial abnormality that would preclude a
lumbar puncture
N Engl J Med 2004;351:1849-59.

Cell type Cell count Glucose Protein
Normal Lymphocytes 0-4 >60% of
blood
glucose
< 0.45
mg/dl
Viral Lymphocytes 10-2000 Normal Normal
Bacterial Polymorphs 1000-5000 Decreased Increased
Tubercular Lymphocytes/
polymorphs
50-5000 Decreased Increased
Fungal Lymphocytes 50-500 Decreased Increased
CSF findings in infectious meningitis

 CSF latex agglutination for pneumococcal and meningococcal
antigen - specificity of 95-100%.
 Sensitivity 70-100% for pneumococci, 30-70% for
meningococcci.
 Pneumolysin in CSF - detected by Cowan 1 Staphylococccal
protein A co-agglutination method.
 Sensitivity and specificity of 91 and 92% respectively.
Indian J Med Res 119, February 2004, pp 75-78

 Examine CSF before or shortly after antibiotics started.
 Submit large volume of CSF ( >5 ml) for microbiology.
 Gram stain and inoculation for culture as soon as possible.
 Centrifuge at high force ( 3000g) for 20 min and stain and
culture the deposit.
 Subculture after 24 hr inoculation in brain heart infusion
broth at 37°C with 5% CO2.
 Storage/ transport of CSF – incubate at 37°C if available or
at room temperature.
 Do not refrigerate.
Methods to improve diagnostic yield of microbiology

Approach in case of suspected meningitis

Overview of different types
of meningitis

Bacterial Menigitis
 Definition- Acute purulent infection within the subarachnoid
space.
 Meninges, subarachnoid space and brain parenchyma
frequently involved together-meningoencephalitis.

Pus covered
surface -
Leptomeninges

 Incidence- 0.6-4/1,00,000 adults in developed nations.
 Upto 10 times higher in developing nations.
 Mortality 16% to 37% despite modern antibiotics.
Epidemiology

Etiology
 In developed world MC organism in both children and adults
is S. pneumoniae ≈ 50%
 N. meningitidis ≈ 25%
 Group B Streptococcus ≈ 15%
 Listeria monocytogenes ≈10%
 H. influenzae < 10%
 Staphylococcal species and gram negative bacilli in special
circumstances.

Common causes of acute bacterial meningitis in resource poor settings
 Tubercular and cryptococcal meningitis common in HIV
 Maybe difficult to distinguish from acute bacterial
meningitis.
Etiology (contd.)

 S. pneumoniae: pneumococcal pneumonia, sinusitis
otitis media, alcoholism, diabetes
mellitus, asplenia, HIV,
hypogammaglobulinemia, complement
deficiency, head trauma,CSF rhinorrhea.
 N. meningitidis: asplenia, complement deficiency.
 L. monocytogenes: neonates, elderly (>60 years),
pregnancy, immunodeficiency.
 Group B streptococcus: neonates, age> 50 years.
Predisposing conditions

Pathophysiology
 Pneumococci colonize the nasopharynx and compete with
resident flora.
 Balance effected by recent antibiotic usage, host immunity,
smoking, over crowding.
 Invade intravascular space via the nasal epithelium.
 Avoid phagocytosis and complement mediated destruction
mainly by virtue of polysaccharide capsule.
 Invade choroid plexus cells and gain access to CSF via
transcytosis.
 Low levels of complements, antibodies and leukocytes in CSF
allow rapid bacterial multiplication.

Invasion of SAS by pathogenic bacteria
Multiplication and lysis of organisms
Release of bacterial cell wall components (endotoxin, techoic acid)
Production of inflammatory cytokines like TNFα, IL-1β, and IL-6
Altered BBB
permeability
Adherence of
leukocytes to
endothelial cells
Alterations in
cerebral blood
flow
Production of
excitatory AA,
reactive O and
N species
↑Permeability of vessels
Leakage of plasma
proteins into CSF
Leukocytes enter CSF,
degranulate and release
cytokines
Cell injury
and death
Exudate obstructs outflow
& resorption of CSF and
Infiltrates vasculature
Cerebral
ischemia
↓ Blood flow ↑ Blood flow
vasogenic edema
Obstructive and
communicating hydrocephalus
Interstitial edema
cytotoxic edema, stroke
seizures
↑ ICP
Coma
DEATH
Hence neuronal injury can progress
even after CSF sterilization.

Right 3rd nerve palsy and severe herpes labialis in a patient of
acute bacterial meningitis

Turbid CSF with fibrous spider clot after 1 hour in pyogenic meningitis

Gram positive diplococci of S.
pneumoniae in CSF.
Neutrophils and gram negative bacilli in
CSF of an elderly patient of E. coli
meningitis
Gram negative rods- H. influenza
Gram negative diplococci of
meningococci in CSF

Bacterial meningitis score (BMS)
Predictor
Points
Present Absent
CSF Gram stain 2 0
CSF protein > 80mg/dl 1 0
CSF ANC>1000/cc 1 0
Peripheral blood ANC >
10,000/cc
1 0
Seizures at or before
presentation
1 0
JAMA. 2007;297:52-60
Differentiating acute bacterial from non
bacterial meningitis (contd.)

 Risk of bacterial meningitis is very low (0.1%) with BMS 0 and
it increases as the score increases:-
– 3% with score 1
– 27% with score 2
– 70% with score 3
– 95% with score ≥ 4
 It has a negative predictive value of 99.9% for acute bacterial
meningitis.
 Validated only in age group of 29 days to19 years. Not
applicable to adults and neonates.
JAMA. 2007;297:52-60
Differentiating acute bacterial from non
bacterial meningitis (contd.)

Prognostic markers
Indicators of poor prognosis in a case of bacterial meningitis
are:-
1. Evidence of systemic compromise – tachycardia (HR>120
bpm), low blood pressure, positive blood culture, raised
ESR, low platelet count.
2. Low CSF leukocyte count (<100/cc).
3. Low score on GCS
4. Advanced age

5. Predisposing conditions like immunocompromised state,
pneumonia, otitis, sinusitis.
6. Cranial nerve palsy
7. Pneumococcal meningitis- 6 times higher chance of
unfavorable outcome compared to meningococcal
meningitis.
N Engl J Med 2004;351:1849-59.
Prognostic markers (contd.)

Suspicion of bacterial meningitis
Immunocompromised, H/O CNS disease, new onset seizures, focal deficits, papilledema, altered sensorium ,
delay in performing lumbar puncture.
Blood culture STAT
Dexamethasone + empirical
antibiotic therapy
CT scan head
Perform lumbar puncture
No C/I to lumbar puncture
Yes
No
Blood culture and lumbar puncture STAT
antibiotic therapy
CSF c/w pyogenic meningitis?
Consider alternate
diagnosis
No
Yes
CSF gram stain positive?
antibiotic therapy
Dexamethasone + targeted
antibiotic therapy
No
Yes
Algorithm for management of suspected bacterial meningitis

Treatment
 Antibiotics are the mainstay of treatment.
 Should be given as early as possible.
 Delay >3 hours independently associated with mortality
Q J Med 2005; 98:291–298

Initial empirical antibiotics
Clinical Infectious Diseases 2004; 39:1267–84

Dosage

Organism specific antibiotics

Duration of antibiotic therapy
 WHO recommendation – 5 day antibiotic therapy
 To be extended if-
– Immunocompromise
– Persistent fever
– Persistent seizures
– Coma

Role of corticosteroids
 Mortality and rate of neurological sequelae remain high
despite appropriate antimicrobial therapy.
 Due to adverse effects of inflammatory cytokines.
 Corticosteroids act by
– inhibiting synthesis of IL-1 and TNF at m-RNA level
– decreasing CSF outflow resistance and
– stabilizing the BBB.
 Once macrophages and microglia activated and TNF
production induced, steroids have less effect.

 Hence steroids to be given early, with or before 1st dose of
antibiotics to have maximum effect.
 Duration of this window of opportunity not described.
 Dose- Dexamethasone 0.15 mg/kg I.V. 6th hourly for 4 days is
the most widely recommended dose.
Role of corticosteroids (contd.)

 Randomized controlled trial of 301 adult patients from the
Netherlands -
N Engl J Med, Vol. 347, N o. 20
Distribution of scores on Glasgow outcome
scale at eight weeks
Role of corticosteroids (contd.)

Supportive treatment
 Treatment of raised ICP –
- Head end elevation (30°-45°)
- IV mannitol (25-100 g 4th hourly)
- Intubation and hyperventilation (PaCO2 25-30 mm of
Hg). Maintain ICP below 20 mm of Hg.
 Maintain blood pressure and urine output.
 Aggressive fluid resuscitation to be avoided for fear
of hyponatremia.

Complications and Outcome

Enlarged lateral ventricles
in a patient with
hydrocephalus - treated by
placing two shunts.

19%
21%
5%
14%
13%
12%
10%
4%
Complications and Outcome (contd.)

Complications and Outcome (contd.)

Prevention
 Vaccination and chemoprophylaxis useful for prevention.
 Chemoprophylaxis reserved for meningococcal disease.
 Only for close contacts, to be given as early as possible.

To memorize …
 Most common organisms are S. pneumoniae and N.
meningitidis.
 Absence of clinical triad, Kerning's and Brudzinski's sign do
not rule out acute bacterial meningitis.
 Start antibiotics early, before lumbar puncture if need be.
 Empirical antibiotics based on age, predisposing condition and
geographical resistance patterns.
 Give dexamethasone with or before 1st dose of antibiotic.
 Imaging not needed before lumbar puncture in all cases.
 Absence of typical CSF findings do not rule out acute bacterial
meningitis.

VIRAL MENINGITIS
 Viral infection of the nervous system can
result in a myriad of clinical
presentations occurring separately or in
combinations including acute or chronic
meningitis, encephalitis, myelitis,
ganglionitis, and polyradiculitis.
 Viruses may also incite para- or post-
infectious CNS inflammatory or
autoimmune syndromes such as acute
disseminated encephalomyelitis
(ADEM) or encephalitis associated with
autoantibodies

• Pathogenesis of VIRAL CNS Infections

Enterovirus
• Leading cause of viral meningitis
– Neonates- fever, vomiting, anorexia, rash, upper respiratory tract
symptoms, meningeal signs (nuchal rigidity, bulging antetrior
fontanelle) +/-
Severe form with hepatic necrosis, myocarditis, necrotizing
enterocolitis, encephalitis
– Children, adults- fever, headache, neck stiffness, photophobia
Anorexia, vomiting, rash, diarrhoea, cough, pharyngitis, myalgia
• h/o community enteroviral outbreaks, rash, conjunctivitis,
pleurodynia, pericarditis, herpangina

Herpesvirus
HSV 2 meningitis
• Neurological complications- urinary
retention, dysaesthesis, paraesthesia,
neuralgia, motor weakness,
paraparesis, difficulty in concentration,
impaired hearing, usually resolve in 3-
6 months
EBV meningitis
• Associated with pharyngitis, lymph
adenopathy, splenomegaly
VZV meningitis
• Associated with diffuse vesicular rash

CSF – Exceptions in Viral Mening0-encephalitis
• Cell counts of several thousand/ μL + low
glucose  infections due to lymphocytic
choriomeningitis virus (LCMV) and
mumps virus.
• PMNs predominate in first 48 h of illness 
Echovirus 9, West Nile virus (WNV) or
mumps
• PMN pleocytosis with low glucose 
Cytomegalovirus (CMV) infections

• Atypical lymphocytes in the CSF  EBV
infection
• Plasmacytoid or Mollaret-like large
mononuclear  WNV encephalitis
• Red blood cells (>500/μL) in the CSF in
a nontraumatic tap  HSV encephalitis

Treatment
• Empirical Antibiotics +
(Acyclovir (HSV) 10mg/kg IVI q8h) for 14-21
days
• Treat raised ICT  Cushing’s triad (HTN,
Bradycardia, Irregular RR)
• Seizures  Antiepileptics

Tubercular meninngitis
 Tuberculosis remains a global health problem, with an
estimated 10.4 million cases and 1.8 million deaths resulting
from the disease in 2015.
 The most lethal and disabling form of tuberculosis is
tuberculous meningitis (TBM), for which more than 100,000
new cases are estimated to occur per year.
 In patients who are co-infected with HIV-1, TBM has a
mortality approaching 50%.

CONTINUED….
 Diagnosis of TBM is often delayed by the insensitive
and lengthy culture technique required for disease
confirmation.
 Antibiotic regimens for TBM are based on those used
to treat pulmonary tuberculosis, which probably
results in suboptimal drug levels in the cerebrospinal
fluid, owing to poor blood–brain barrier penetrance

Pathophysiology of CNS tuberculosis

CSF FINDINGS
CSF appearance- Cog web coagulam
CSF cells - leukocyte 10-1000 cells/µl -
Lymphocytes predominates
CSF glucose - <40 mg/dl
CSF Protein - markedly high (400-5,000
mg/dl)
Chloride content - increased
Acid-fast stain positive in up to 30% of
cases
Culture is positive in 50-70% of cases

Continued
A 6-month course of therapy is acceptable, but therapy should
be prolonged for 9–12 months in patients who have-
• an inadequate resolution of symptoms of meningitis
• positive mycobacterial cultures of CSF during the course of
therapy.
• Dexamethasone therapy is recommended for patients with
tuberculous meningitis. The dose is 12–16 mg/d for 3
weeks,and then tapered over 3 weeks

Case Scenario
History-48 yrs old male patient had h/o low grade fever for past 2 months with h/o
evening rise of temperature. Patient also had h/o weight loss & loss of appetite for last
2 months.
He was brought to casualty with h/o altered sensorium for last 2-3 days
O/E -neck stiffness present
Investigations-
• CSF: appearance clear
• Protein-600mg%(15-45mg%)
• Sugar-30mg% (40-70mg%)
• Chloride-580mg% (116-126mg%)
• Total cells 450/mm3 (≤5 cells)
Lymphocyte -92%
Polymorph -8%

Fungal meningitis
• Typically acquired by the inhalation of
airborne fungal spores.
• The initial pulmonary infection may be
asymptomatic or present with fever,
cough, sputum production, and chest
pain and may later disseminate to
CNS(immunocompromised hosts)

Mode of Infection
MOMOMODEmm
The most common pathogen causing fungal
meningitis is C. neoformans

Treatment
HIV patients
 Induction: liposomal amphotericin B + flucytosine x 2 weeks
followed by 1 wk of fluconazole (1200 mg/day, adult)
 Alternate induction:
fluconazole (400-1200 mg/day, adult) + flucytosine ×2 wk
 Consolidation: oral fluconazole 800 mg/day ×8 wk (minimum)
 Maintenance/secondary prophylaxis: oral fluconazole 200 mg/day
Corticosteroids: not recommended during induction
Antiretroviral therapy (ART) initiation: defer for 4–6 wk from start of antifungal
treatment

Continued…
Organ transplant patients
Induction: lipid-formulation amphotericin + flucytosine ×2 wk (minimum)
Consolidation: oral fluconazole 400–800 mg/day ×8 wk
Maintenance: oral fluconazole 200–400 mg ×6–12 mo
Immunocompetent patients
Induction: amphotericin B/lipid-formulation amphotericin +
flucytosine ×4 wk
Consolidation: oral fluconazole 400–800 mg/day ×8 wk
Maintenance: oral fluconazole 200–400 mg ×6–12 mo
•

Continued…
 If ICP ≥ 25 cm H2O and symptomatic-Therapeutic lumbar puncture
 Target-lumbar puncture (LP) to closing pressure of ≤20 cm H2O
or ≤50% of opening pressure (OP)
 . For persistent symptoms, recheck and treat OP daily until
symptoms abate or ICP stable ×2 days

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