Chapter Two

Central Nervous System (CNS)

infections
Ola Ayesh
2022

1
• Central Nervous System (CNS) infections
include a wide variety of clinical conditions
and etiologies:
• meningitis,
• meningoencephalitis, ‫ھون ﺑﺎﻟدﻣﺎغ ﻧﻔﺳﮫ ﻣﻣﻛن ﺑﺳﺑب‬
‫ﻋدوى ﺑﻛﺗرﯾﺔ او اﺳﺑﺎب اﺧرى‬

• encephalitis,
• brain and meningeal abscesses,and
‫ھﺎي ﺑﺗﺻﯾر ﻣﺛﻼ اذا ﺑدي ادﺧل ﺗﯾوب ﻻﻗﻠل اﻟﺿﻐط ﺟوا‬

• shunt infections.‫اﺑدﻣﺎغ وﯾﺻﯾر ﻋدوى‬

• The focus of this chapter is meningitis.

2
 PATHOPHYSIOLOGY
‫اﻣور ﺣﺗدﺧل‬
BBB

• Central nervous system infections are the result

of:
• Hematogenous spread from a primary infection
site. ‫ﻻﻧﮭم ﻗراب ﻣن اﻟدﻣﺎغ ﻓﺎذا ﻣﺎ‬
‫ﻋﺎﻟﺟﺗﮭم ﻣﻣﻛن ﯾﻧﺗﻘﻠوا‬
• Seeding from a parameningeal
focus(nasopharynx, middle ear, paranasal
sinuses).
• Reactivation from a latent site. ‫ﺑﺣﺎﻟﺔ ﺿﻌف ﺟﮭﺎز اﻟﻣﻧﺎﻋﺔ ﺑﺻﯾر‬
Reactivation

• Trauma, or
• congenital defects in the CNS.
3
• Passive and active exposure to cigarette
‫اﻟﻠﻲ ﻋﻧدھم ﺿﻌف ﺳﻣﻊ‬

smoke and the presence of a cochlear implant

‫ﺑزرﻋوﻟﮭم ھﯾك اﺷﻲ ﻓﺧطر اﻟﻌدوى ورادة‬

that includes a positioner, both increase the

risk of bacterial meningitis.

4
• CNS infections may be caused by a variety of
bacteria, fungi, viruses, and parasites.
‫ھﺎد ﻻزم ﺗﺧﺑر اﻟﺻﺣﺔ ﻣﺷﺎن ﯾﻌرﻓوا ﻣﯾن ﻣﺧﺎﻟطﮫ وﯾﻌطوا‬
prophilaxis
‫وﺑرﺿو ﻻﻧﮫ ﺧطﯾر وھو و‬

• The most common causes of bacterial meningitis are

viral encephilities

• Streptococcus pneumoniae, group B Streptococcus,

• Neisseria meningitidis,
• Haemophilus influenzae, and
• Listeria monocytogenes,

5
• The critical first step in the acquisition of
acute bacterial meningitis is nasopharyngeal
colonization of the host by the bacterial
pathogen.
• The bacteria first attach themselves to
nasopharyngeal epithelial cells and are then
phagocytized into the host’s bloodstream.

6
• A common characteristic of most CNS
bacterial pathogens (eg, H. influenzae,
Escherichia coli, and N. meningitidis) is the
presence of an extensive polysaccharide
capsule that is resistant to neutrophil
phagocytosis and complement opsonization.

7
• The neurologic sequelae of meningitis occur
due to the activation of host inflammatory
pathways.
• Bacterial cell death causes the release of cell
wall components such as lipopolysaccharide
LPS, lipid A (endotoxin), lipoteichoic acid,
teichoic acid, and peptidoglycan, depending
on whether the pathogen is gram-positive or
gram-negative.

8
• These cell wall components cause capillary
endothelial cells and CNS macrophages to release
cytokines (interleukin-1 (IL-1), tumor necrosis factor
(TNF), and other inflammatory mediators).
• Products of the cyclooxygenase –arachidonic acid
pathway( prostaglandins and thromboxane) and
platelet activation factor PAF are also released.
• Proteolytic products and toxic oxygen radicals cause
an alteration of the blood–brain barrier, whereas
platelet-activating factor activates coagulation, and
arachidonic acid metabolites stimulate vasodilation.

9
• These events lead to cerebral edema, elevated
intracranial pressure, cerebrospinal fluid (CSF)
pleocytosis( increased cell count), decreased
cerebral blood flow, cerebral ischemia, and
death.

10
11
 CLINICAL PRESENTATION
• Clinical presentation varies with age; generally, the
‫ﻣﻊ اﻟﺻﻐﺎر ﺻﻌب ﺗﺣدد اﻻﻋراض ﻟﻛن ﻣرﯾض ﻣراﺟﻌﺔ‬

younger the patient, the more atypical and the less

‫وﺣرارة دون اﺳﮭﺎل و ﺟﻲ اي‬
‫ﻓﻛر ﺑﮭﺎد داﺋﻣﺎ‬

pronounced is the clinical picture.

• Patients may receive antibiotics before a diagnosis of
‫وﻣﻧﮫ ﺑﺟوز اﻟﺑﻣرﯾض ﯾﻣوت ﻻﻧﮫ ﻓﻘد‬
‫اﻟوﻗت‬
meningitis is made, delaying presentation to the
hospital.
• Prior antibiotic therapy may cause the Gram stain ‫وﻣﻧﮫ ﺣﺗﻰ ﺑﻘدر اﻋرف ﻣن ھذول‬

and CSF culture to be negative, but the antibiotic

therapy rarely affects CSF protein or glucose.

12
• Classic signs and symptoms include:
• fever,
‫ﺗﯾﺑس ﺑﺎﻟرﻗﺑﺔ‬

• nuchal rigidity,
‫اﻛﯾد ﻣﺎ ﺑﺗﺷوﻓﮭﺎ ﻋﻠﻰ اﻻطﻔﺎل‬

• altered mental status,

• chills,
• vomiting, ‫ﺑرﺿو ھﺎي اﻛﯾد ﻣﺎ راح ﺗﻌرﻓﮭﺎ ﻟﻠطﻔل‬

• photophobia, and
• severe headache.
• Kernig and Brudzinski signs may be present but ‫ﺿﻌﯾﻔﺔ ﻋﻧدھم‬

are poorly sensitive and frequently absent in ‫ﺑﺗﺣﻛﻲ اﻧﮫ ﻓﻲ ﻣﺷﺎﻛل ﺑﺎﻻﻋﺻﺎب وﻣﻊ اﻻﻋراض ﻣﻣﻛن‬
‫ﺗﻘول اﻧﮫ ﻣﻣﻧﺟﺎﯾﺗس او ﻻ‬

children.

13
14
• Clinical signs and symptoms in young children
may include:
‫ھﺳﺎ ﻧﺎﻓوخ اﻟطﻔل ﺑﻛون ﻣﻔﺗوح وﻣﻧﮫ ﻣﻊ اﻻﯾدﻣﺎ‬

• bulging fontanelle, ‫واﻻﻧﻔﻼﻣﯾﺷن ﺑﺻﯾر ﯾﻛﺑر‬

• apneas,
‫اول اﺛﻧﯾن‬

• purpuric rash, and

• convulsions,
• in addition to those just mentioned.

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17
18
 SIGNS AND SYMPTOMS AND
LABORATORY TESTS

• Purpuric and petechial skin lesions typically indicate

meningococcal involvement, although the lesions
may be present with H. influenzae meningitis.
• Rashes rarely occur with pneumococcal meningitis.

19
‫اﻟراش اﻟﻠﻲ ھون ﻣﺎ ﺑﺗروح ﻟﻣﺎ ﺗﺷﯾل‬
‫اﻟﻛﺎﺳﺔ‬

‫‪20‬‬
21
 SIGNS AND SYMPTOMS AND
LABORATORY TESTS
• Bacterial Meningitis Score is a validated clinical decision
tool aimed to identify children older than 2 months with
CSF pleocytosis who are at low risk of ABM.
• This tool incorporates clinical features such as :
✓ positive CSF Gram stain,
✓ presence of seizure,
✓ serum absolute neutrophil count of 10,000 cells/mm 3
or more (≥10 × 109/L),
✓ CSF protein ≥80 mg/dL (≥800 mg/L), and
✓ CSF neutrophil count ≥1000 cells/mm3 (≥1 × 109/L).

22
 ‫ﺑﻌدھﺎ ﺑﺟوز ﺗﺳﺗﻣر ﻧﻔﺳﮫ او ﻻ‬
‫ﺣﺳب اﻟﻣزرﻋﺔ‬

• Treatment is recommended when one or

more criteria are present.
‫ﻻﻧﮫ ﻋﻧدك ﻛﺛﯾر اﺟﺳﺎم ﻣﺿﺎدة وﻛﻣﺎن ﺑﻛﺗﯾرﯾﺎ ﺗﺣﻠﻠت‬

• An elevated CSF protein of 50 mg/dL or more ‫ﻻﻧﮫ اﻟﺑﻛﺗﯾرﯾﺎ وﻛل ت‬

‫ﻣﺳﺑﺑﺎت اﻻﻟﺗﮭﺎب ﺑدھﺎ ﻏﻠوﻛوز‬
and a CSF glucose concentration less than 50%
of the simultaneously obtained peripheral
value suggest bacterial meningitis

23
• Gram stain and culture of the CSF are the
most important laboratory tests performed for
bacterial meningitis.
• When performed before antibiotic therapy is
initiated, Gram stain is both rapid and
sensitive and can confirm the diagnosis of
bacterial meningitis in 75% to 90% of cases.

24
• Polymerase chain reaction (PCR) techniques can be
used to diagnose meningitis caused by N.
meningitidis, S. pneumoniae, and H. influenzae type b
(Hib).
• Latex fixation, latex coagglutination, and enzyme
immunoassay tests provide for the rapid
identification of several bacterial causes of
meningitis, including S. pneumoniae, N. meningitidis,
and Hib.
• The rapid antigen tests should be used in situations in
which the Gram stain is negative.
• Diagnosis of tuberculosis meningitis employs acid-
fast staining, culture, and PCR of the CSF.
25
‫وﺣﺗﻰ اﻟﻛوﻧﺳﯾﻛوﻧس ﺻﻌب ﻟذﻟك ﻛﻧﺎ ﻧﺣﻛﻲ‬
‫ھو ﺧطﯾر وﻻزم ﺗﺣﻛﻲ ﻟﻠﺻﺣﺔ واﻟﺦ ﻟﮭدف‬
‫اﻧﻘﺎذ اﻻرواح‬

‫‪26‬‬
 TREATMENT
• Goals of Treatment: ‫ﻣﺎ ﺑدي ﯾﻧطرش وﻻ ھﺎي اﻻﻋراض‬

• Eradication of infection with amelioration of signs and

symptoms preventing morbidity and mortality.
• Initiating appropriate antimicrobials, providing
supportive care, and preventing disease through
timely introduction
‫ﻟﻠﻣﺧﺎﻟطﯾن وﺣﻧﺣﻛﻲ ﻛم‬
of vaccination and
chemoprophylaxis.
• The administration of fluids, electrolytes, antipyretics,
analgesia, and other supportive measures are
particularly important for patients presenting with
acute bacterial meningitis.
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 PHARMACOLOGIC TREATMENT
• Empiric antimicrobial therapy should be instituted as soon
as possible to eradicate the causative organism.
• Antimicrobial therapy should last at least 48 to 72 hours or
until the diagnosis of bacterial meningitis can be ruled out.
• Continued therapy should be based on the assessment of
‫ﯾﻌﻧﻲ ﻣﻣﻛن ﯾﺿل ﻧﻔﺳﮫ ﻣﺛﻼ‬

clinical improvement, cultures, and susceptibility testing

‫ ﻣﻼﺣظﺎت‬:
results. ‫اذا ﻛﺎن ﻣﺣدد ﻧوع اﻟﺑﻛﺗﯾرﯾﺎ ﻣﻌﻧﺎﺗﮫ ﻣش اﻣﺑرﯾك ﺑﺗروح ﻟﻠﺣﻛﻲ ﻣش اﻟﺟداول‬
‫ﻟو ﻣﺣدد اﻋراض اﻣﺷﻲ ﺣﺳب اﻻﯾﻣﺑرك‬

• Once a pathogen is identified, antibiotic therapy should be

‫ﻛﻣﺎن ﻧﻘطﺔ اذا ﻗﺎﻟت ﻓﯾرﺳت ﻻﯾن ﯾﻌﻧﻲ ﻓﯾرﺳت‬
‫واﻟدواء اﻻﻓﺿل‬
‫ﻟو ﻗﺎﻟت ﻋﻼج ﺑﺗﺣط اي واﺣد‬
‫ﺑﺎﻟذات اﻟﮫ‬
tailored to the specific pathogen. ‫اذا ﻣﺎ ﻛﻧت اﻋﻣل ﻟﻣﺑر وﺗﺣدﯾد ﺑﺎﻟزﺑط ﻻ ﺗﻧﺗظر وااﻋطﻲ ﻻﻧﮫ‬
ABM
• The first dose of antibiotic should not be withheld even ‫ﺧطﯾر ﻛﺛﯾر وﯾﺎ دوﺑك ﯾﺗﺣﻣﻠﮫ اﻟﻣرﯾض وﻧﻧﻘذه‬

when lumbar puncture is delayed or neuroimaging is being

performed.
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• With increased meningeal inflammation, there
will be greater antibiotic penetration.
• Problems of CSF penetration were traditionally
overcome by direct instillation of antibiotics
intrathecally, intracisternally, or intraventricularly.
• Advantages of direct instillation, however, must
be weighed against the risks of invasive CNS
procedures.
• Intrathecal administration of antibiotics is
unlikely to produce therapeutic concentrations in
the ventricles possibly owing to the unidirectional
flow of CSF.‫اﻟﻣﺿﺎدات اﻟﺣﯾوﯾﺔ‬
‫ﻣن ﻏﯾر اﻟﻣﺣﺗﻣل أن ﺗﻧﺗﺞ ﺗرﻛﯾزات ﻋﻼﺟﯾﺔ ﻓﻲ‬
‫اﻟﺑطﯾﻧﯾن رﺑﻣﺎ ﺑﺳﺑب أﺣﺎدي اﻻﺗﺟﺎه‬
‫ﺗدﻓﻖ اﻟﺳﺎﺋل اﻟﻧﺧﺎﻋﻲ‬
‫اي اﻟﻘﺻد اﻧﮫ ﺑﻌﯾد‬

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30
Dexamethasone as an Adjunctive Treatment for
Meningitis

• In addition to antibiotics, dexamethasone is a commonly

used therapy for the treatment of pediatric meningitis.

• Current recommendations call for the use of adjunctive

dexamethasone in infants and children with H. influenzae
meningitis.
• The recommended IV dose is 0.15 mg/kg every 6 hours
for 2 to 4 days, initiated 10 to 20 minutes prior to or
concomitant with, but not after, the first dose of
‫ﺑﺑﻌدھﺎ ﻣﻠوووش ﻓﺎﺋدة ﻋﻠﻣﯾﺔ‬
antimicrobials

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• Clinical outcome is unlikely to improve if
dexamethasone is given after the first dose of
antimicrobial and should therefore be avoided.
• If adjunctive dexamethasone is used, careful
monitoring of signs and symptoms of gastrointestinal
(GI) bleeding and hyperglycemia should be
employed.

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34
‫ﺣدﻧﺎھﺎ وﻣش اﻋراض اذا ﻣش‬
‫اﯾﻣﺑرك ﺗﻌﺎل ھون‬

Neisseria Meningitidis (Meningococcus)

35
 Neisseria Meningitidis (Meningococcus)

• The presence of petechiae may be the primary clue

that the underlying pathogen is N. meningitidis.
• Approximately 60% of adults and up to 90% of
pediatric patients with meningococcal meningitis
have purpuric lesions, petechiae, or both.
• N. meningitidis meningitis is the leading cause of
bacterial meningitis in children and young adults in
the United States and around the world.
• Most cases occur in the winter or spring, at a time
when viral meningitis is relatively uncommon.
36
• Approximately 10 to 14 days after the onset of the
disease and despite successful treatment, the patient
develops a characteristic immunologic reaction of
fever, arthritis (usually involving large joints), and
pericarditis. Pericarditis is swelling and irritation of the
thin, saclike tissue surrounding the heart
(pericardium).

• The synovial fluid is characterized by a large number

of polymorphonuclear cells, elevated protein
concentrations, normal glucose concentrations, and
sterile cultures.
• Deafness unilaterally, or more commonly bilaterally,
may develop early or late in the disease course.

37
 TREATMENT AND PREVENTION
• Third-generation cephalosporins (ie, cefotaxime and
‫اذا ﺣﻛﺎﻟك اﻋراض‬

ceftriaxone) are the recommended empiric treatment

for meningococcal meningitis
• Close contacts of patients contracting N. meningitidis
meningitis are at an increased risk of developing
meningitis.
• Prophylaxis of contacts should be started only after
consultation with the local health department.
• In general, rifampin, ceftriaxone, ciprofloxacin, or
azithromycin is given for prophylaxis.
• For regions with reported ciprofloxacin resistance, one
dose of azithromycin 500 mg is recommended for
prophylaxis.
38
 Streptococcus Pneumoniae
(Pneumococcus or Diplococcus)

39
 Streptococcus Pneumoniae
(Pneumococcus or Diplococcus)
• S. pneumoniae is the leading cause of meningitis in
patients 2 months of age or older in the United States.
• Neurologic complications, such as coma and seizures,
are common.
• The treatment of choice until susceptibility of the
organism is known is the combination of vancomycin
plus ceftriaxone.
• Penicillin may be used for drug-susceptible isolates
with minimum inhibitory concentrations of 0.06
mcg/mL or less, but for intermediate isolates
ceftriaxone is used, and for highly drug-resistant
isolates a combination of ceftriaxone and vancomycin
should be used.

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• A high percent of S. pneumoniae is either
intermediately or highly resistant to penicillin.
• Ceftriaxone and cefotaxime have served as
alternatives to penicillin in the treatment of penicillin-
resistant pneumococci.
• Therapeutic approaches to cephalosporin resistant
pneumococcus include the addition of vancomycin and
rifampin.
• Meropenem is recommended as an alternative to a
third-generation cephalosporin in penicillin
nonsusceptible isolates.
• IV linezolid and daptomycin have emerged as
therapeutic options for treating multidrug-resistant
gram-positive infections.

41
• The Centers for Disease Control and Prevention (CDC)
recommends use of 23-valent pneumococcal vaccine
(PPV 23) for persons over 65 years of age; persons 2 to
64 years of age who have a chronic illness, who live in
high-risk environments, and who lack a functioning
spleen; and immunocompromised persons over 2
years, including those with human immunodeficiency
virus (HIV) infection.
• All healthy infants younger than 2 years of age should
be immunized with the 13- valent pneumococcal
conjugate vaccine (PCV13) at 2, 4, 6, and 12 to 15
months.
• PCV13 should be used in series with PPV23 for all
adults who are 65 years of age or older.

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Haemophilus Influenzae

43
 Haemophilus Influenzae

• In the past, H. influenzae was the most common

cause of meningitis in children 6 months to 3
years of age, but this has declined dramatically
since the introduction of effective vaccines.

• Because approximately 20% of H. influenzae are

ampicillin resistant, many clinicians use a third-
generation cephalosporin (cefotaxime or
ceftriaxone) for initial antimicrobial therapy.
• Cefepime and fluoroquinolones are suitable
alternatives regardless of β-lactamase activity.

44
• Prophylaxis of close contacts should be started
only after consultation with the local health
department and the CDC.
• Vaccination with Hib conjugate vaccines is
usually begun in children at 2 months.
• The vaccine should be considered in patients
older than 5 years with sickle cell disease,
asplenia, or immunocompromising diseases.
Asplenia means the
absence of a spleen

45
Listeria Monocytogenes

46
 Listeria Monocytogenes

• L. monocytogenes is a gram-positive, diphtheroid-like

organism and is responsible for 10% of all reported
cases of meningitis in those older than 65 years.
• The combination of penicillin G or ampicillin with an
aminoglycoside results in a bactericidal effect.
• Patients should be treated a minimum of 3 weeks.
• Combination therapy is given for the first 7-10 days
with the remainder completed with penicillin G or
‫ﻣﻊ اﺳﺗﻛﻣﺎل اﻟﺑﺎﻗﻲ ﺑﺎﻟﺑﻧﺳﻠﯾن ﺟﻲ أو‬
ampicillin alone.‫اﻷﻣﺑﯾﺳﻠﯾن وﺣده‬.

• Trimethoprim–sulfamethoxazole and meropenem may

be an effective alternative because adequate CSF
penetration is achieved with these agents.

47
 Gram-Negative Bacillary Meningitis
‫اﻟﻣرﺿﻰ اﻟﻣﺳﻧون اﻟﻣﺻﺎﺑون ﺑﺎﻟوھن ﻣﻌرﺿون ﺑﺷﻛل ﻣﺗزاﯾد ﻟﺧطر اﻹﺻﺎﺑﺔ‬
‫اﻟﺗﮭﺎب اﻟﺳﺣﺎﯾﺎ ﺳﺎﻟب اﻟﺟرام وﻟﻛﻧﮫ ﻋﺎدة ﻣﺎ ﯾﻔﺗﻘر إﻟﻰ اﻟﻧﻣط اﻟﻛﻼﺳﯾﻛﻲ‬
‫ﻋﻼﻣﺎت وأﻋراض اﻟﻣرض‬

• Elderly debilitated patients are at an increased risk of

gram-negative meningitis but typically lack the classic
signs and symptoms of the disease.
• Optimal antibiotic therapies for gram-negative bacillary
meningitis have not been fully defined.
• Meningitis caused by Pseudomonas aeruginosa is
initially treated with an extended-spectrum β-lactam
such as ceftazidime or cefepim, or alternatively
aztreonam, ciprofloxacin, or meropenem.
• The addition of an aminoglycoside— usually
tobramycin—to one of the above agents should also be
considered.

48
• If the pseudomonad is suspected to be antibiotic
resistant or becomes resistant during therapy, an
intraventricular aminoglycoside (preservative-free)
should be considered along with IV aminoglycoside.
• Gram-negative organisms, other than P. aeruginosa,
that cause meningitis can be treated with a third- or
fourth-generation cephalosporin such as cefotaxime,
ceftriaxone, ceftazidime, or cefepime
• Therapy for gram-negative meningitis is continued for a
minimum of 21 days. ‫وﻣﻣﻛن ﯾطول ﺗﺎ ﺗﺗﻐﯾر‬

• CSF cultures may remain positive for several days or

more on a regimen that will eventually be curative.

HP , 2/14/2023 ,1:23:59 PM

49
definitive

50
51
Mycobacterium tuberculosis:

52
53
 ‫اﺳﺗﺧدام اﻟﺟﻠوﻛوﻛورﺗﯾﻛوﯾد ﻣﺛﯾر ﻟﻠﺟدل‬

• The use of glucocorticoids is controversial.

• Corticosteroids are commonly used in addition to
antituberculous drugs for treating people with the
condition.
• These drugs help reduce inflammation of the
surface of the brain and associated blood vessels,
and are thought to decrease pressure inside the
brain, and thus reduce the risk of death.
• Prednisone ( oral) 60-80 mg/day, or
• Dexamethasone (IV)0,2 mg /Kg/day tapered over
‫ﻗﺑل ﻛﺎن ﻣﮭم ﺗﻛون ﻗﺑل اﻟﺟرﻋﺔ او ﻻ وﻣﻊ اﻻطﻔﺎل‬
4-8 weeks ‫ھون ﻏﯾر‬

54
Cryptococcus neoformans

55
• Current guidelines recommend 2 weeks of
amphotericin B (0.7–1.0 mg/kg per day)
intravenously in combination with flucytosine
100mg/kg/day as first line therapy for
treatment of cryptococcal meningitis.
• AIDS patients require life long maintenance
therapy using fluconazole after the initial
treatment.

56
Viral Meningitis

57
• Acyclovir 10mg/Kg every 8 hours for 2-3
weeks.
• Foscarnet in cases of resistance is used ( dose
should be calculated depending on renal
function)

58
DONE

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