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Lecture 5

Prepared and presented by
Marc Imhotep Cray, M.D.

Scanning electron micrograph of Staphylococcus aureus bound to the surface of a human neutrophil. “Granulocytic Phagocytes,” by Frank R. DeLeo and William M. Nauseef.
Meningitis
 Meningitis is a clinical syndrome characterized by inflammation of meninges

Image Description:
 Meningitis in a child with a very
rigid neck
 Cerebral malaria should be in
DDx for this child
 Most bacterial meningitis in
children can now be prevented
by vaccines frequently still not
available in developing countries
Usatine RP. et al. The Color Atlas of Family Medicine. New York:
McGraw-Hill, 2013

Marc Imhotep Cray, M.D.
Etiology and Pathogenesis
Patients with meningitis can present acutely or chronically
distinction helping determine likely etiologies
Most common acute presentations result from bacterial and
aseptic meningitis
 Aseptic meningitis may occur in patients with viral infections
or in association with an adverse drug reaction

 A subacute picture, in which CSF pleocytosis persists for longer
than 4 weeks, is more likely to be associated with fungal or
vasculitic meningitis

Marc Imhotep Cray, M.D.
Pneumococcal meningitis in a patient with
alcoholism.
http://emedicine.medscape.com/article/116
5557-overview

Marc Imhotep Cray, M.D.
Risk Factors
 Meningitis: Risk Factors (HE IS Chief Of SPAIN)
 Head trauma
 Extreme age
 Immunocompromised state
 Sinusitis
 Cancer
 Otitis
 Splenectomy
 Parameningeal infection
 Alcoholism
 Infections (systemic, especially respiratory)
 Neurosurgical procedures

Marc Imhotep Cray, M.D.
Most Common Organisms & Likeliest Bug In Age
Group
 Meningitis: Most Common Organisms (SIN)
 Streptococcus pneumoniae
 Influenzae (Haemophilus)
 Neisseria meningitidis

 Pyogenic Meningitis: Likeliest Bug In Age Group (In order from death to birth)
(She Never Had Entertainment)
 Streptococcus pneumoniae (elderly/>65)
 Neisseria meningitis (young adults)
 Hemophilus influenzae (older infants, kids)
 Escherichia coli (infants)

Marc Imhotep Cray, M.D.
Clinical Manifestations
Signs and Symptoms:
The classic triad of bacteria meningitis consists of following:
 Fever
 Headache
 Neck stiffness

Other symptoms can include nausea, vomiting, photophobia,
sleepiness, confusion, irritability, delirium, and coma
 Pts with viral meningitis may have a history of preceding
systemic symptoms (eg, myalgias, fatigue, or anorexia)

Marc Imhotep Cray, M.D.
Sn & Sx cont.
 Ability to mount an immune responses must be kept in mind when
assessing severity of symptom
 Immunocompromised patients may have a more subtle presentation, yet they are at
very high risk for poor outcome
 In bacterial meningitis, temperature usually exceeds 37.7º C (99.9º F)
 Low-grade fever is more often present in viral meningitis
 Fever may be entirely absent in immunocompromised patients
 Neck stiffness is a specific sign and has a sensitivity of about 70%
 Mental status changes occur in bacterial meningitis in 44% of cases but are
found in only 3% of viral meningitis cases
 Seizures occur in the range of 20% to 25% of patients with bacterial
meningitis focal findings such as cranial nerve deficits are even
 more common, occurring in 25% to 30% of these patients
Temp Conversions:
°C x 9/5 + 32 = °F
Marc Imhotep Cray, M.D. (°F - 32) x 5/9 = °C
Physical Examination
Meningeal signs, most commonly meningismus, are present in
about 88% of cases of bacterial meningitis
Other classic signs are Kernig and Brudzinski signs
 Kernig sign is pain in back upon passive extension of one leg at knee
and thigh
 Brudzinski sign is flexion of legs at thighs when patient’s neck is flexed

 Jolt accentuation of headache is a very sensitive finding for
meningitis
 Elicited by having patient turn head rapidly horizontally a number of
times per second to assess for worsening of headache

Marc Imhotep Cray, M.D.
Kernig and Brudzinski signs

Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders 2008

Marc Imhotep Cray, M.D.
Physical Examination cont.
 Thorough neurologic examination should be performed, with attention
given to accurate assessment of:
 level of consciousness
 presence or absence of cranial nerve deficits
 assessment for papilledema, and
 documentation of any focal motor or sensory defects

 Skin should be carefully examined for lesions Purpura strongly suggests
meningococcal disease
 Petechiae are almost as frequently seen as purpura in meningococcal
meningitis and can occur in rickettsial diseases and sometimes in
pneumococcal meningitis
Marc Imhotep Cray, M.D.
Diagnostic Algorithm

Tunkel AR, Hartman BJ, Kaplan SL, et al: Practice guidelines for the management of bacterial meningitis.
Marc Imhotep Cray, M.D.
Clin Infect Dis 39(9):1267-1284, 2004.
Diagnosis

Marc Imhotep Cray, M.D.
Meningitis Dx based on CSF findings
Cerebrospinal Fluid Findings In Meningitis
Infective WBC Cell Type Protein Glucose Opening
Agent Differential Pressure
Bacterial PMNs
Viral Normal Lymphocytes Normal Normal Normal/
Fungal Normal/ Lymphocytes
Redrawn from: Brown TA, Shah SJ. USMLE Step 1 Secrets 3rd ed. Sanders, 2013

Marc Imhotep Cray, M.D.
Meningitis Dx based on CSF findings (2)

Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders 2008

Marc Imhotep Cray, M.D.
Case 1
A 21-year-old man presents to the emergency department complaining of a
severe headache. Physical examination reveals a fever to 1020F, nuchal rigidity,
and photophobia. You perform a lumbar puncture, which initially reveals
purulent CSF infiltrated with neutrophils, increased protein content, and
decreased glucose content. While you await culture results, you admit the
patient to the hospital and begin empiric broad spectrum antibiotics to treat
his condition.

Marc Imhotep Cray, M.D.
Pyogenic and Viral Meningitis
Pyogenic
 Etiology Pyogenic meningitis: Causes include group B streptococci, E coli,
Listeria in neonates and infants; H influenzae and N meningitidis in children
and young adults; pneumococcus, Listeria, and gram-negative rods in older
adults
 Pathology Pyogenic meningitis: Purulent exudate within leptomeninges;
engorged meningeal vessels; neutrophils within the subarachnoid space

Viral
 Viral meningitis: Causes include HSV virus, Coxsackie virus, echoviruses,
and arboviruses
 Viral meningitis: There may be no abnormality or a mild lymphocytic
infiltrate in subarachnoid space; mild edema may be present

Marc Imhotep Cray, M.D.
Pyogenic and Viral Meningitis (2)
Clinical Manifestations
 Pyogenic meningitis: Headache; photophobia; neck stiffness; fever;
irritability.
 Lab findings: Lumbar puncture shows cloudy CSF with neutrophils,
increased protein, decreased glucose and increased opening pressure

 Viral meningitis: Headache; photophobia; neck stiffness; fever; irritability.
 Lab findings: Lumbar puncture shows lymphocytosis, mildly elevated
protein, and normal glucose

Treatment Pyogenic meningitis: Antibiotics and supportive care
Viral meningitis: Self-limiting illness; acyclovir for HSV meningitis

Marc Imhotep Cray, M.D.
Aseptic meningitis
 Aseptic meningitis can be caused
by a number of drugs and can
also be a manifestation of certain
rheumatologic or other systemic
disorders
A 45-year-old day care provider presents in
August with a fever of 38°C, headache,
photophobia, and neck stiffness. A clinical
diagnosis of meningitis is made. Based on the
epidemiology of meningitis in the United States,
what is the most likely cause of her disease?
(A) Cryptococcus neoformans
(B) Haemophilus influenzae
(C) Neisseria meningitidis
(D) Streptococcus pneumoniae
(E) Viral
Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders 2008
Marc Imhotep Cray, M.D.
Case 2
An 18-year-old girl is brought to the college emergency room by her
roommate. The roommate 4 claimed that the patient had been feeling fine
the night before but this morning had a high fever and was difficult to arouse.
On physical examination, the patient was found to have a temperature of
102°F, to be very lethargic, and to have a petechial rash. Examination of her
cerebrospinal fluid revealed numerous neutrophils and gram-negative
diplococci. Her records indicated that she had received the tetravalent
meningitis vaccine before graduating from high school.

Marc Imhotep Cray, M.D.
Neisseria meningitidis
 Organism: N meningitidis
 Phys Char: Gram-negative diplococcus, 13 serogroups based on polysaccharide
capsule of which A, B, C, Y, W135 are most important
 Etio and Epidem: N meningitidis is a human disease major mode of
transmission is by respiratory droplets from carriers
 Outbreaks can arise when carriers and susceptible individuals are brought
together under crowded conditions such as university dormitories and military
barracks
Clinical Findings: Nasopharynx is portal of entry From nasopharynx, organisms
may reach bloodstream (meningococcemia)
 Meningitis is the most common complication of meningococcemia
o Widespread petechiae and ecchymoses are signs of meningococcemia
o Severe cases can lead to disseminated intravascular coagulation (DIC)

Marc Imhotep Cray, M.D.
Neisseria meningitidis cont.
 Pathogenesis: Major virulence factors is an antiphagocytic polysaccharide
capsule, endotoxin (lipooligosaccharide), IgA1 protease, and pili
 As with N gonorrhoeae, complement is important in immune clearance
through classical pathway
o Individuals with complement deficiencies are at higher risk for dissemination

 Laboratory: Latex agglutination tests are used to diagnose N meningitidis in
cerebrospinal fluid, as are direct Gram stains.
 Latex agglutination is more sensitive than Gram stain of the CSF
however, it is not as sensitive as culture, and a negative test does not
rule out an infectious cause of patient’s symptoms
 Diagnosis N meningitidis can be grown on blood or chocolate agar

Marc Imhotep Cray, M.D.
Neisseria meningitidis cont.
 Treatment and Prevention:
In general, penicillin or third-generation cephalosporins are effective for
treatment
 Often a combination of IV vancomycin and ceftriaxone is used because of their central
nervous system (CNS) penetration and broad coverage
 A vaccine against serogroups A, C, Y, and W135 is available
 B serogroup polysaccharide is a poor immunogen and is therefore not in current
vaccine
o A high percentage of cases involve serogroup B
 Chemoprophylaxis: A single dose of 500 mg of ciprofloxacin is preferred
regimen for prophylaxis of adults against Neisseria meningitidis
 Rifampin can also be used
 Children can be protected using a single dose of ceftriaxone as fluoroquinolones are
contraindicated in children  Damages cartilage in young children

Marc Imhotep Cray, M.D.
Acute meningitis, gross

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

Marc Imhotep Cray, M.D.
Acute meningitis, MRI

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015
Marc Imhotep Cray, M.D.
Acute meningitis, microscopic

Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed., 2015

Marc Imhotep Cray, M.D.
Question
 What adrenal disease should be suspected in a young patient
with bacterial meningitis due to Neisseria meningitidis who also
becomes acutely hypotensive?

Marc Imhotep Cray, M.D.
Waterhouse-Friderichsen syndrome
Ques. What adrenal disease should be suspected in a young
patient with bacterial meningitis due to Neisseria meningitidis
who also becomes acutely hypotensive?
Ans. Waterhouse-Friderichsen syndrome typically causes bilateral
adrenal hemorrhage, which can be rapidly fatal. Responsible
bacterium is Neisseria meningitidis
Sn & Sx:
 septicemia, hypotension
 disseminated intravascular coagulation (DIC)
 adrenal hemorrhage, and
 petechial rash
Marc Imhotep Cray, M.D.
THE END

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Sources and further study:
 Bloch KC. Ch. 4 Infectious Diseases, Pgs. 61-87 In: Hammer GD and McPhee Eds. JS.
Pathophysiology of Disease : An Introduction to Clinical Medicine, 7th Ed. New York: McGraw-
Hill Education, 2014
 Brown TA, Shah SJ Eds. USMLE Step 1 Secrets 3rd ed. Sanders, 2013
 Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders 2008
 Usatine RP. et al. The Color Atlas of Family Medicine. New York: McGraw-Hill, 2013

eLearning (IVMS Cloud)
 Infectious Disease
 Microbial biology & Immune System
 Rural Medicine Global Health (Focus on Ethiopia)

Textbooks:
 Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010
 Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York:
McGraw-Hill, 2016
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