SARVAM KRISHNARPANAM

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 Bed side clinical approach to meningitis case scenarios

1.brief introduction

3.Typcal cases

4.Atypical cases

5.Take home message

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Introduction

• Infections of the nervous system are a global problem.

• Once infection is suspected it is an emergency as time is brain in all situations.
• Suspicion by a physician who has examined and assessed the patient sincerely is the indication to initiate treatment
based on the prevalence pattern in that region.

• CNS infections can be meningitis , Encephalitis, abscess, subdural empyema ,ventriculitis etc .

• Noso comial infections are complications of surgical & other interventions procedures .

• Head injury related infections

• They leave sequelae usually and therefore reducing morbidity and mortality is dependent on timely initiation of
appropriate therapy

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What is meningitis ?
• Lepto-meningitis when the inflamed structure is Pia & Arachnoid,
pachymeningitis if it is Dura.
• IgA proteases, compliment regulatory proteins, capsular
polysaccharides help organisms to attach to nasopharyngeal
epithelium & later cross BBB.
• CNS has low immunoglobulins and compliment mediated host
defences.
• Injury happens due to endo and exotoxins, proinflammatory
cytokines, vascular invasion, and abscess formation.

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Acute meningitis
• Meningitis
• Fever
• Headache Only upto 40%
patients have all
• Altered sensorium these features
• Neck stiffness

• Encephalitis
• Seizures
• Focal deficits

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Bacterial meningitis: clinical features
• Clinical features develop over 24-48 hrs
• Triad – fever, altered mental state and neck stiffness (44%) .
• Symptoms
• Fever (75–95%)
• Headache (80–95%)
• Photophobia (30–50%)
• Vomiting (90% of children; 10% of adults)
• Signs
• Neck stiffness (50–90%) ; absent in comatose pts
• Confusion (75–85%)
• Kernig’s sign (5%)
• Brudzinski’s signs (5%)
• Focal neurological deficit (20–30%)
• Seizures (15–30%)
• Rash (10–15%)

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Repeat CSF after 24 to 48 hours

Viral Bacterial
• Lymphocytes • Poly morphs
• < 1000 cells • > 1000 cells
• CRP not inreased • CRP increased
• CSF lactate < 35 mg • CSF lactate > 35 mg
• Proinflammatory cytokines not increased • Proinflammatory cytokines increased
• CSF protein < than 250 mg • CSF protein > than 35 mg
• Sugar decreases < 3.7 % • Sugar decreases > 95 %

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CNS Infections
HIV -
Bacterial Spirocheate Viral Fungal Parasitic
Related

Tuberculosis Treponema Herpes Virus Cryptococcus Toxoplasma HIV

encephalopathy

Pneumococcal Borrelia Arbovirus Aspergillus Cysticercosis

PCNSL
Leptospira
Meningococcal Rabies Mucor Echinococcosis
PML
Measles Candida
Hemophilus Amoebiasis CMV encephalitis
HIV Histoplasma
Listeria Malaria
Japanese IRIS
Nosocomial Encephalitis

Abscess

Empyema

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Broad classification of meningitis

• 1. Acute pyogenic meningitis

• 2. Acute lymphocytic meningitis

• 3. Chronic progressive meningitis

• 4. Chronic recurrent meningitis

• 5. Iatrogenic meningitis

• 6. Non microbial meningitis

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Case history-1
• A 23 year old person from Karnataka

• Fever & Head ache: 5 days.

• Admitted in a local hospital & treated with injections
• Vomiting: 2 days
• Irrelevant talk,
• and restlessness
2 days

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Case history
• Investigation 1:
• Blood: TLC: 10500/cmm: DC: Polys- 65%, lymph: 35%
• ESR: 45mm/1st hour

• CSF:
TC: 80 cells/cmm, Polys:32%, Lymph: 68%
Protein: 60mg/dL.,
Sugar : 46 mg% against a blood sugar of 102 mg%(normal CSF has 60 to
70%of blood sugar)
Gram stain: negative.
Culture: result: awaited
• CT Scan: Normal;
• X-ray chest: Normal
• Serum HIV test: negative
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 Lumbar puncture before or after imaging? Beware of these
situations

Clinical risk factors for herniation Imaging risk factors

Stupor or coma Lateral shift of cerebral midline structures
Dilated or fixed pupils Loss of suprachiasmatic and basilar cisterns
Fixed deviation of eyes or absent Obliteration or shift of the fourth ventricle
oculocephalic reflex
Papilledema Obliteration of the superior cerebellar and
quadrigeminal plate cisterns
Recent seizures Masses in the cerebral hemisphere or
cerebellum
Decorticate or decerebrate posturing Infarction or occlusion of the superior
sagittal sinus or draining veins
Hemiparesis
Hypertension with bradycardia

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 Case history based diagnosis
• Level 1:
• Viral meningoencephalitis
• Patient was put on Inj.Acyclovir ? The spectrum of acyclovir ?
• Level 2:
• Possibility of partially treated pyogenic meningitis:
• Put on Inj.Ceftriaxine & ampicillin
• Level 3:
• Possibility of acute presentation of TBM
• In addition to viral encephalitis & bacterial meningitis
• ?? Cerebral malaria
• Advised:
• MRI Scan, EEG ,
• repeat CSF for TB-PCR, PCR for HSE
• Z-N stain for mycobacteria.
• Peripheral smear for MP

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Investigations2:
• EEG: Diffuse slowing in theta to delta
range. NO PLEDS
• MRI: Patient could not afford.
• Repeat CSF:
• Traumatic.
• RBC: 16000/cmm; (CSF cells =every 500 RBC 1 WBC)
• WBC: 64 cells, Polys: 28%, Lymphs: 72%
• Protein : 80mg/dL.
• Sugar: 56mg%
• CSF for HSV-PCR & TB-PCR: Negative
• AFB-smear- negative
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Grand rounds
• In acute meningitis time is brain
: Treated elsewhere, with antibiotics; partially treated pyogenic meningitis possible
• .Neurologist discussion.
• Rarely TBM can have acute presentation.
• In 15% of cases CSF sugar can be normal.
• CSF protein may only be mildly elevated in early phase of illness

• Higher the hierarchy more the uncertainty – current case most likely Viral

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Acute meningoencephalitis
• How to diagnose viral encephalitis?
• Can bacterial meningitis mimic viral meningo -encephalitis?
• Can previous antibiotic treatment affect CSF interpretation?
• How to differentiate viral encephalitis from partially treated
bacterial meningitis.?
• If CSF becomes traumatic, how to interpret the CSF
findings?
• How to rule out TBM in such cases?
• When to suspect and fungal and syphilitic meningitis & how
to rule out these conditions

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Laboratory investigations in acute bacterial
meningitis
• Blood:(The3 Cs)
• Culture
• Cell count WBC reduces by 32 % in 1 hr and
• C-reactive protein (CRP) 50% by 2hrs.
Never refrigerate
• Cerebrospinal fluid (CSF) Organisms die if transit time is
• Opening pressure (always raised in ABM) more than few minutes.
• Appearance
• Cell count
• Glucose and the ratio of blood glucose
• (obtained before lumbar puncture)
• Protein
• Gram stain, culture
• Optional: lactate, ferritin, LDH
• Others: CIE, RIA, LPA ,ELISA, PCR
• Body fluid culture
• Petechial fluid, sputum, secretions from oro-pharynx, nose and ear
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How much CSF?

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Some clues 1
• Meningococcal meningitis is suspected when there is rapid evolution
of symptoms with delirium , stupor , purpuric rash , ecchymosis
patches and lividity of the skin esp lower limbs. There can be
associated circulatory shock described as Waterhouse Friderichsen
syndrome.
• Rashes can be also seen in ECHO viruses and Staph aureus infection
• Pneumococcal meningitis is usually associated with upper and lower
respiratory infection or artificial heart valves , splenectomy, auto
splenoctomy conditions like Sickle cell anaemia and alcoholism.
• It can produce cranial nerve palsy like TBM.
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Some clues 2
• Influenzas meningitis is seen in children following ENT or upper respiratory infection.it can
produce seizures.
• H.influenza and Pneumococcus can produce focal deficits due to sub dural effusion.
• If furunculosis ,coagulase positive Staphylococcus is suspected .

• patients with Ventriculo atrial shunts are prone for Coagulase negative Staphylococcus infection.

• Rare infections are common in immune compromised patients like HIV or non HIV related
immunosuppression.
• Adams RD, Kubik CS, Bonner FJ : The clinical and pathological aspects of influenza meningitis.
Arch Pediatr 65:354, 1948. [PMID 18883966]
• 

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Clues in CSF
• Clear CSF in only 2% of ABM but 57% of TBM.
• In bacterial meningitis, WBC count > 1,000 per mm 3 (87%), > 100 per mm3 (99%)
• < 100 WBCs per mm3 is more common in patients with viral meningitis
• Beware
• Lower counts in children, immunocompromised
• Can be acellular CSF in pneumococcal & meningococcal meningitis
• > 10 % of bacterial meningitis - lymphocytic predominance, early in the
clinical course and when < 1,000 WBCs per mm3
• Early stages of tubercular or fungal meningitis and few viral meningitis can
have a neutrophilic pleocytosis
• Partial treatment effect. Does not alter Total WBC count,CSF protein ,CSF
glucose,but culture and polymorphs can change
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CSF Proteins & sugar
• Proteins
• Values <220 mg/dl – strong predictor with respect to viral meningitis
(Spanos et al.,1989).
• In bacterial meningitis usually 100-500 mg/dl
• sugar
• Acute bacterial meningitis <40mg/dl most often
• CSF: Blood glucose ratio <0.23 high predictive value (Spanos et al.,
1989)
• Can be normal in 24 - 50% of patients with bacterial meningitis
(Geisler et al., 1980, Dougherty et al., 1986)
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Gram stain & culture
• “All patients evaluated for suspected meningitis should undergo a
Gram stain examination of CSF”. (Class A-III, Practice guideline for bacterial
meningitis, Clin Infect Dis 2004)
• Sensitivity - 90 % S.pneumoniae, 86% H.influenza, N.meningitides 75%, gram-
negative bacilli 50% and <50% Listeria (Greenlee, 1990)
• CSF culture
• 70-90% in non-treated cases of bacterial meningitis
• <50% after administration of antibiotics

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Bacterial meningitis : extended tests

• Newer tests
• Latex agglutination test – sensitivity 70-100% for S.pneumoniae, 60-100% for
H.influenzae and 33-70% for N.meningitidis; Specificity – 95-100%
• IDSA (infectious disease society of America)practice guideline does not recommend
routine use (Class D-II); may be most useful who has received pre-treatment and
other tests are negative (Class B-III)
• Limulus amoebocyte lysate – gram-negative meningitis, Sensitivity approaching
100%; Specificity 85-100% (Class D-II)

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Bacterial meningitis : extended tests
• PCR for simultaneous detection of N.meningitidis, H.influenzae, and
streptococcii in 304 clinical CSF sample - sensitivity 94% & specificity 96%
• A broad-range PCR can detect small numbers of viable and nonviable organisms
in CSF
• Who have been pretreated with oral or parenteral antibiotics
• In whom Gram’s stain and CSF culture are negative
• “may be useful for excluding the diagnosis of bacterial meningitis, with the potential for
influencing decisions to initiate or discontinue antimicrobial therapy” ( Class B-II IDSA
Practice guideline 2004).

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Bacterial meningitis. extended tests
• Other techniques
• Bacterial genomes
• Broad range rRNA PCR
• Nucleic acid hybridization and Restriction fragment length polymorphism

• Serological markers
• Lactate
• C-Reactive protein
• Procalcitonin
• Cytokines
• Rapid culture method

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Bacterial meningitis : extended tests
• Procalcitonin
• 59 consecutive children sensitivity Serum procalcitonin concentration (using a cut off
of 15.0mcg/L) - 94%,and the specificity-100%.
• In adults, serum concentrations 10.2ng/mL had a sensitivity and specificity of upto
100%
• According to a metanalysis CRP
• For diagnosing ABM sensitivity that ranged from 69% to 99% and a specificity ranged
from 28% to 99%
• In Gram stain negative bacterial meningitis - sensitivity 96%, specificity - 93%, and a
negative predictive value - 99%

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Lab tests helpful in special and difficult situations to diagnose or exclude
Bacterial meningitis

• CSF Lactate
• Not recommended for community acquired bacterial meningitis (Class D-III)
• Superior to CSF:Blood glucose ratio in post-op neurosurgical patients.
>4.0mmol/L suggestive of bacterial meningitis (Class B-II recommendation)
• CRP
• A normal CRP has a high negative predictive value (Class B-II
recommendation)

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 EFNS(European federation of neurological societies)
guidelines - 2008

• Three other helpful and indirect diagnostic markers of ABM

• (a) elevated serum C reactive protein (quantified) in children
(sensitivity:96%,specificity:93%,negative predictive value:99%);
• (b) increased CSF lactate (sensitivity:86–90%,specificity:55–98%, positive predictive
value:19–96%,negative predictive value:94–98%)
• (c) high CSF ferritin (sensitivity:92–96%, specificity:81–100%)
• Bacterial antigen detection- LPA, ELISA, counter-immuno
electrophoresis, co-agglutination - sensitivity: 60–90%, specificity: 90-
100%, predictive positive value: 60–85%, predictive negative value: 80–95%
• Currently available PCR methods – sensitivity 87–100%,and specificity 98–
100%.
• Fluorescence in situ hybridization (FISH) less sensitive but may be
useful for identification of bacteria in CSF samples in some cases.

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Ventricular CSF Vs Lumbar CSF

• Normally – gradient of rising cell count and protein and falling glucose from
ventricle to lumbar
• In ABM – gradient for cell count and protein but not for glucose; no
difference in differential count
• Cell count & protein normal in 12% of pts with ABM
• But all three were normal in 0-5%
• Has a higher yield for bacterial culture

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EFNS guideline algorithm - 2008

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