Meningitis

MENINGITIS

Meningitis is an inflammatory process of the meninges and CSF

♦ Meningitis belt ♦ epidemic zones ♦ sporadic cases

Demography of Meningococcal Meningitis

Causes/Major PathogensType Pathogen (most Common)Bacterial Strep pneumoniae, E-coli, Neisseria

meningitisViral infection Coxsackie Virus, Echovirus, Enterovirus,

Arbovirus, HIV, HSV-2TB meningitis M. TuberculosisProtozoal Infection Toxoplasma Gondii (toxoplasmosis)Fungal infection Cryptococcus neoformans (cryptococcal

meningitis)

Other: Progressive multifocal leukoencephalopathy (PML) Primary CNS lymphoma, HIV-associated dementia (HAD), Painful sensory and motor peripheral neuropathies, Neurosyphilis

Vasculitis of cerebral vessels

Ischemia, cytotoxic edema

Immune Response from Astrocytes+Microglia,

Cytokin Release

Immune Response from Astrocytes+Microglia,

Cytokin Release

Inc. BBB permeabilty Inc. no. of WBC in CSF

Fluid leakage from vessels Inflammation of Meninges Dec. cerebral blood flow

Vasogenic edema Interstitial edema (Inc. ECF)

Cerebral EdemaCerebral Edema

Subarachnoid Space

Microorganisms

Via BloodDirect to CSF

PATHO PHYSIOLOGYPATHO PHYSIOLOGY

Dec. Cerebral blood flow, Ischemia, apoptosis (Brain Death)

Bacterial Viral

More serious, less common Less serious, more common

Immunization available for some

No immunization available

Treatable with antibiotics Treatment includes waiting it out

More common in winter More common in summer/ early fall

MAJOR FORMS OF MENINGITIS

1. Acute pyogenic (bacterial) meningitis

2. Acute aseptic (viral) meningitis

3. Chronic bacterial infection (tuberculosis).

4. Acute focal suppurative infection (brain abscess, subdural and extradural empyema)

Classification

1) Acute Pyogenic Bacterial Meningitis

2) Acute Aseptic (Viral ) Meningitis

• Can follow any viral infection• Less danger • Viral meningitis is usually self-

limiting and treated symptomatically.

• Fever delirium, lethargy, disorientation, malaise, headache most common

• Stiff neck, photophobia, cranial nerve deficits less common

• No focal neurological deficits

• Gastrointestinal symptoms: diarrhea, colitis, esophageal ulceration appear in 12-15% of patients

3) Chronic bacterial infection (tuberculosis/TB Meningitis)

• Antibiotic treatment------ full recovery• Delayed or untreated cases--- can be fatal• Healing by fibrosis cause obliteration of

subarachenoid space--- HYDROCEPHALUS • Brain abscess• Septic shock and skin rashes, why ?

Complications

1) Brain abscess

• Causes : 1. complication of bacterial meningitis 2. bacterial endocarditis 3. pulmonary sepsis : pneumonia……etc 4. other sepsis

Brain abscess cause a space occupying lesion in the brain

• Is due to small skin bleed• All parts of the body are affected• The rashes do not fade under pressure• Pathogenesis: a. Septicemia b. wide spread endothelial damage c. activation of coagulation d. thrombosis and platelets aggregation e. reduction of platelets (consumption ) f. BLEEDING 1.skin rashes 2.adrenal hemorrhage Adrenal hemorrhage is called Waterhouse-Friderichsen

Syndrome. It cause acute adrenal insufficiency and is usually fatal

2) Skin rashes

Physical ExamBrudzinski’s & Kernig’s signNuchal rigidityPapilledema

Lumbar puncture to obtain CSFChemistry (glucose & protein)Cytology (WBC# & %PMN’s)Gram stain or rapid identification test (< 24hrs)

CIE (Counterimmunoelectrophoresis), coagglutination, or latex agglutinationLimulus lysate for gram negative endotoxinPCR (N.meningitidis, S. pneumoniae, H. influenzae, S. agalactiae, L. monocytogenes & enteroviruses)Lactate (>4.2 mmol/L considered positive for bacterial meningitis)Procalcitonin (> 5 micrograms/L suggestive of bacterial meningitis)C-reactive proteins (CRP) (Elevated in bacterial meningitis)

Culture for pathogens (> 24hrs)Blood, Urine, & Sputum Cultures

Work up for Meningitis

Kernig's signThe thigh is flexed on the abdomen, with the knee flexed; attempts to passively extend the knee elicit pain when meningeal irritation is present.

Brudzinski's sign: passive flexion of the neck results in spontaneous flexion of the hips and knees.

Nuchal rigidity:Inability to flex the neck forward passively due to increased neck muscle tone. It occurs in 70% of adult cases of bacterial meningitis

Jolt accentuation maneuver: •The patient is told to rapidly rotate his or her head horizontally; if this does not make the headache worse, meningitis is unlikely.•It helps determine whether meningitis is present in patients reporting fever and headache.

Kernig’s and Brudzinski’s signs have high specificity but low sensitivity(44%) for the diagnosis of meningitis. Jolt accentuation of headache was determined to have a 97% sensitivity and 60% specificity.

It has been suggested that absence of the jolt sign essentially excludes meningitis.

Changes in CSF Normal Viral Pyogenic (Bacterial) Tuberculosis

Appearance Crystal-clear Clear/Turbid Turbid/purulent Turbid/viscous

WBC < 5 mm3 25-500 mm3 > 1000 mm3 < 500 mm3

Mononuclear cells < 5 mm3 10-100 mm3 <50 mm3 100-300 mm3

Polymorph cells Nil Nil 200-300/ mm3 0-200/ mm3

Protein 0.2- 0.4 g/L 0.4-0.8 g/L 0.5-2.0 g/L 1-5g/L

Glucose 40-80 mg/dl 30-70 mg/dl <40 mg/dl 20-40 mg/dl

Harrison's Principles of Internal Medicine, 17`Edition, 2008Harrison's Principles of Internal Medicine, 17`Edition, 2008

CSF Detail Report

Empirical Therapy For ABMAge Common Pathogen Anti microbial

< 1 month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species

Ampicillin plus cefotaxime or ampicillin plus an aminoglycoside

1-23 month Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli

Vancomycin plus a third-generation cephalosporina,b

2-50 yrs N. meningitidis, S. pneumoniae Vancomycin plus a third-generation cephalosporina,b

> 50 yrs S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli

Vancomycin plus ampicillin plus a third-generation cephalosporina,b

a Ceftriaxone or cefotaximeb Some experts would add rifampin if dexamethasone is also given.

•Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] Pub Med•Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] Pub Med

Recommendations for Appropriate use of Antimicrobials at Hospitals in PakistanDepartments of Infectious Disease and Infection ControlSHIFA INTERNATIONAL HOSPITAL ISLAMABAD October 31, 2003

Antimicrobial Agent

Child (>1 month) Adult

Ampicillin 200 (mg/kg)/d, q4h 12 g/d, q4hCefotaxime 200 (mg/kg)/d, q6h 12 g/d, q4hCeftriaxone 100 (mg/kg)/d, q12h 4 g/d, q12hCeftazidime 150 (mg/kg)/d, q8h 6 g/d, q8hGentamicin 7.5 (mg/kg)/d, q8hb 7.5 (mg/kg)/d, q8hMetronidazole 30 (mg/kg)/d, q6h 1500–2000 mg/d, q6hPenicillin G 400,000 (U/kg)/d, q4h 20–24 million U/d, q4hVancomycin 60 (mg/kg)/d, q6h 2 g/d, q12hb

Total Daily Dose and Dosing Interval

aAll antibiotics are administered intravenously; doses indicated assume normal renal and hepatic function.bDoses should be adjusted based on serum peak and trough levels: gentamicin therapeutic level: peak: 5–8 g/mL; trough: <2 g/mL; vancomycin therapeutic level: peak: 25–40 g/mL; trough: 5–15 g/mL.

Harrison's Principles of Internal Medicine, 17`Edition, 2008Harrison's Principles of Internal Medicine, 17`Edition, 2008

Microorganism Duration of therapy, days

Neisseria meningitidis 7

Haemophilus influenzae 7

Streptococcus pneumoniae 10-14

Streptococcus agalactiae 14-21

Aerobic gram-negative bacillia 21

Listeria monocytogenes >21

Duration of Antimicrobial Therapy for Bacterial Meningitis Based on Isolated Pathogen (A-III)a Duration in the neonate is 2 weeks beyond the first sterile CSF culture or >3 weeks, whichever is longer.

Duration OF Therapy For ABM

•Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] PubMed

•Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] PubMed

• Dexamethasone should be initiated 10-20 min prior to, or at least concomitant with, the first antimicrobial dose, at 0.15 mg/kg every 6 h for 2-4 days.

• Adjunctive dexamethasone should not be given to the patients who have already received antimicrobial therapy, because administration of dexamethasone in this circumstance is unlikely to improve patient outcome

Adjunct Steroid Therapy for Infants, Children and Adults

At present, there are insufficient data to make a recommendation on the use of adjunctive dexamethasone in neonates with bacterial meningitis

•Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] Pub Med

•Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1;39(9):1267-84. [120 references] Pub Med

Daily administration of Rifampicin 600 mg (450 mg for weight <55 KG)Isoniazid 300 mgPyrizinamide 1.5 g for <55 Kg & 2 gm for above 55 Kg. (Initial 2 Months)All in combination 30 min before breakfast.Treatment requireFor PTB is six monthsFor bone TB is nine months &For TB meningitis is 1 year.

Management and Treatment Of TBM

The addition of a fourth drug STREPTOMYCIN is left to the choice of the local physicians and their experience, with little evidence to support the use of one over the other

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Chief, Department of Neurology, Crouse Irving Memorial Hospital; Professor, Department of Neurology, State University of New York Upstate Medical UniversityContributor Information and DisclosuresUpdated: Mar 9, 2007 from E medicine web Md

Routine immunization can go a long way toward preventing meningitis. The vaccines against Hib, measles, mumps, polio, meningococcus, and pneumococcus can protect against meningitis caused by these microorganisms.

Vaccines For Meningitis

Bacteria Polysaccharide Vaccine Conjugate Vaccine H. influenzae PRP PRP-OMP (PedvaxHIB, Comvax) S. Pneumoniae PPV23 PCV7 (Prevnar) N. Meningitidis Quadrivalent

A/C/Y/W135 (Menomune)

Quadrivalent A/C/Y/W135 (Menactra)

Monovalent C (Meningitec)

WHO Fact sheet N°141Revised May 2003

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