Neuroinfections - Peacock

Question 1

_CNS INFECTIONS
Overview_

• Life-threatening problems with high associated mortality & potential long-term morbidity
• Presentation may be __,__, or ___
• Clinical findings dictated by anatomic site(s) of involvement, infecting pathogen, & host response
• Vulnerability of CNS to inflammation & edema mandates prompt diagnosis with appropriate therapy if consequences are to be minimized

Answer 1

_CNS INFECTIONS
Overview_

• Life-threatening problems with high associated mortality & potential long-term morbidity
• Presentation may be acute, subacute, or chronic
• Clinical findings dictated by anatomic site(s) of involvement, infecting pathogen, & host response
• Vulnerability of CNS to inflammation & edema mandates prompt diagnosis with appropriate therapy if consequences are to be minimized

Question 2

_CNS INFECTIONS
Classification_

Name:

• Anatomic structures involved (4)
• Class of organisms involved (4)
• Tempo of onset (3)

Answer 2

_CNS INFECTIONS
Classification_

Name:

•Anatomic structures involved (4)

1. Meningitis (Pneumococcal or meningiococcal)

2. Encephalitis (viral from HSV or West Nile)

3. Empyema (subdural and epidural)

4. Brain abcess (cerebritis)

•Class of organisms involved (4)

1. Parasites

2. Bacterial

3. Viral

4. Granulomatous (acid-fast bateria, or fungal)

•Tempo of onset (3)

1. Acute

2. Subacute

3. Chronic

Question 3

What is this?

Answer 3

Cranial CT of Patient with Bacterial Meningitis

Question 4

What is this?

Answer 4

Cranial CT of Patient with Brain Abscess

Question 5

Routes of CNS infection:

1. __-____ spread from remote site of infection or ___ colonization

Microbes enter blood from sites of __ __(ie, lungs) or ____ colonization (ie. nasopharynx) and invade CNS

Organisms must avoid __ __ in blood & be able to attach to __ cells and penetrate blood-brain barrier

•Examples→S. pneumoniae, N. meningitidis, H. influenzae, and enteroviruses

2. Direct spread from __-___ (spread to the bone from a source in nearby tissue) of active infection - Common ___ __ would be from otitis, sinusitis, dental abscesses, & osteomyelitis of skull
3. Access via __ defects
   - direct traumatic inoculation
   - organisms take advantage of __ in physical barriers to enter __
   - anatomic defects may be traumatic, surgical, or congenital in origin

•Examples –> ___ skull fractures, ___ procedures, & _ __ tracts

4. Entry via ___ pathway
5. ____ from infected tissues or ingestion of __ ___.

Answer 5

Routes of CNS infection:

1. Blood-borne spread from remote site of infection or mucosal colonization

Microbes enter blood from sites of remote infection (ie, lungs) or mucosal colonization (ie, nasopharynx) and invade CNS

Organisms must avoid host defenses in blood & be able to attach to neuroendothelial cells and penetrate blood-brain barrier

•Examples→S. pneumoniae, N. meningitidis, H. influenzae, and enteroviruses

2. Direct spread from contiguous-focus (spread to the bone from a source in nearby tissue) of active infection
   - Common contiguous infections would be from otitis, sinusitis, dental abscesses, & osteomyelitis of skull
3. Access via anatomic defects
   - direct traumatic inoculation
   - organisms take advantage of breaches in physical barriers to enter CNS
   - anatomic defects may be traumatic, surgical, or congenital in origin

•Examples –> basilar skull fractures, neurosurgical procedures, & dermal sinus tracts

4. Entry via intraneural pathway
5. Transplantation from infected tissues or ingestion of contaminated foods

Question 6

What is this?

Question 7

What is this?

Question 8

The primary route whereby microbes invade the CNS is via ___-___ ____ of the meninges from a distant site of __ or from a site of ___ colonization.

Answer 8

The primary route whereby microbes invade the CNS is via blood-borne meningeal seeding of the meninges from a distant site of infection or from a site of mucosal colonization.

Question 9

CNS infections can also occur due to limitations of host defense mechanisms:

Since the CNS is an “___ ___” organ system & infection at that site is largely “protected” from systemic host defenses, prompt use of microbicidal antibiotics in management of infection is critical to success.

Why is the CNS considered “___ ___?”

1. No intrinsic __ __-__ system
2. Restricted ___ of traditional host

defense components 2˚ to blood-brain barrier

3. Restricted entry of ___ agents due

to relative __ of ___

Answer 9

CNS infections can also occur due to limitations of host defense mechanisms:

Since the CNS is an “immuno compromised” organ system & infection at that site is largely “protected” from systemic host defenses, prompt use of microbicidal antibiotics in management of infection is critical to success.

Why is the CNS considered “immuno compromised?”

1. No intrinsic lymph node- lymphatic system
2. Restricted mobilization of traditional host

defense components 2˚ to blood-brain barrier

3. Restricted entry of antimicrobial agents due

to relatibe impermeability of cerebrovasculature

Question 10

Answer 10

Question 11

Causative Organisms of CNS Infection:

1. Bacteria (4)

2. Viruses (3)

3. Fungi/AFB (3)

4. Parasites (2)

Answer 11

Causative Organisms of CNS Infection:

1. Bacteria (4)

Streptococcus agalactiae

Streptococcus pneumoniae

Neisseria meningitidis

Listeria monocytogenes

2. Viruses (3)

Enteroviruses

HSV & other herpesviruses

Arboviruses

3. Fungi/AFB (3)

Mycobacterium Tuberculosis

Cryptococcus neoformans

Coccidioides immitis

4. Parasites (2)

Toxoplasma gondii and pallidum

Question 12

CNS infections from microbial factors/host defense category:

1. Capsules that resist ____
2. ____ protease that inactivates immunoglobulin
3. Resistance to natural killing activity of ____
4. ___/___ that attach to endothelial cells
5. ____ for neural tissue

Answer 12

CNS infections from microbial factors/host defense category:

1. Capsules that resist phagocytosis
2. IgA protease that inactivates immunoglobulin
3. Resistance to natural killing activity of serum
4. Fimbrae/pili that attach to endothelial cells
5. Tropism for neural tissue

Question 13

The most common bacterial pathogens causing CNS infections in the US are ____ and _____ whereas ____ are the most common viral pathogen.

Answer 13

The most common bacterial pathogens causing CNS infections in the US are S. pneumoniae and N. meningitis whereas enterovirus are the most common viral pathogen.

Question 14

Epidemiology of CNS infections

1. Age
2. ___ of year
3. ____

· Other ill persons

· Animals/Other

· Environment/Travel

· Remote infection

4. Trauma/Procedures
5. Underlying ____

Answer 14

Epidemiology of CNS infections

1. Age
2. Season of year
3. Exposures

· Other ill persons

· Animals/Other

· Environment/Travel

· Remote infection

4. Trauma/Procedures
5. Underlying conditions

Question 15

Answer 15

Question 16

Bacterial meningitis in neonates is usually due to ____ or ____,

Bacterial meningitis in children and teens is usually due to ___

____ is most common cause of meningitis in adults.

Answer 16

Bacterial meningitis in neonates is usually due to or strep B - agalactiae or e. coli

Bacterial meningitis in children and teens is usually due to N. meningitidis.

S. Pneumoniae is most common cause of meningitis in adults.

Question 17

Epidemology of CNS infections - Seasons and Exposures

1. Summer/Fall: ___ or ___
2. Sibling w/meningitis: ___ or ___
3. Swimming in fresh water lake: ___ ___
4. Handling rodents ___ ___ virus

Exposure to pigeons: ____

Exposure to TBC: ___

Prior meningitis: ___

Head trauma: ___, ___ or ___.

Answer 17

Epidemology of CNS infections - Seasons and Exposures

1. Summer/Fall: Arbovirus or Enterovirus
2. Sibling w/meningitis: Meningococci or H. influenzae (influenced by siblings to get meningitis)
3. Swimming in fresh water lake: Amebaes (Naegleria fowleri) (ameba)
4. Handling rodents Lymphocytic choriomeningitis virus (limping chorus of men rats gave me a headache)

Exposure to pigeons: cryptococci

Exposure to TBC: Mycobacterium Tuberculosis

Prior meningitis: Pneumococcus (new no more)

Head trauma: Pneumococci, GNRs, S aureus (new GNEs giving me a migraine headache with aura)

Question 18

Diagnosing a CNS infection:

Symptoms/signs variable; dependent upon ___ localization, extent of ____, & increased ___

•“Classic findings” may include:

–__, __ and ___ mental status

–___ (meningismus or pseudomeningitis, is a set of symptoms similar to those of meningitis but not caused by meningitis), ____ (exanthem is any eruptive skin rash) that may be associated with fever or other systemic symptoms., contiguous foci of infection, focal neurological signs

•Findings often ___ or ___ in the young & old, & in the ___ host

Answer 18

Diagnosing a CNS infection:

Symptoms/signs variable; dependent upon anatomical localization, extent of infection, & increased ICP

•“Classic findings” may include:

–fever, headache and altered mental status

–meningismus (aka pseudomeningitis, is a set of symptoms similar to those of meningitis but not caused by meningitis), exanthem (any eruptive skin rash) that may be associated with fever or other systemic symptoms., contiguous foci of infection, focal neurological signs

•Findings often muted or atypical in the young & old, & in the immunocompromised host

Question 19

The classic clinical findings associated with CNS infections are:

–___

–___

–____

–__ __

[2 of 4 present in ~__% of patients]

Answer 19

The classic clinical findings associated with CNS infections are:

–Fever

–Headache

–Altered mental status

–Stiff neck (meningismus)

[2 of 4 present in ~95% of patients]

->

Question 20

_CNS INFECTIONS
Diagnostic Approach_

• ____ exam is single most important diagnostic test in pts with suspected CNS infection
• Therefore __ __ is usually mandatory, especially if bacterial meningitis is suspected, unless specific contraindications exist:

–_____ overlying LP site

–Increased __ (stupor/coma, papilledema)

–Long tract signs (hemiparesis)

•Obtain __ __ in all pts (+ in 50-60%)

Answer 20

_CNS INFECTIONS
Diagnostic Approach_

•CSF exam is single most important diagnostic test in pts with suspected CNS infection

•Therefore LP is usually mandatory, especially if __ __ is suspected, unless specific contraindications exist:

–Cellulitis overlying LP site

–Increased ICP (stupor/coma, papilledema)

–Long tract signs (hemiparesis)

•Obtain blood cultures in all pts (+ in 50-60%)

Question 21

CSF Studies:

• Color/Clarity
• Cell counts/WBC diff

–Normal CSF WBC (Adults): ≤___ cells/cu mm

•Chemistries (protein, glucose)

–Normal CSF protein: ≤___ mg/dl

–Normal CSF glucose: >___% of concurrent serum level

• Stains/Smears (Gram)
• Cultures (routine)
• [Multiplex PCRs/Antigen screens]

Answer 21

CSF Studies:

• Color/Clarity
• Cell counts/WBC diff

–Normal CSF WBC (Adults): ≤5 cells/cu mm

•Chemistries (protein, glucose)

–Normal CSF protein: ≤40 mg/dl

–Normal CSF glucose: >40% of concurrent serum level

• Stains/Smears (Gram)
• Cultures (routine)
• [Multiplex PCRs/Antigen screens]

Question 22

• Gram stain (GmS) + in 60-90% of pts with untreated bacterial meningitis
• With prior ATB Rx, positivity of GmS decreases to 40-60%
• REMEMBER: + GmS = Heavy organism burden & worse prognosis

Answer 22

• Gram stain (GmS) + in 60-90% of pts with untreated bacterial meningitis
• With prior ATB Rx, positivity of GmS decreases to 40-60%
• REMEMBER: + GmS = Heavy organism burden & worse prognosis

Question 23

CSF Profile:

•Neutrophilic/low glucose

–___ meningitis

•Lymphocytic/low glucose

–____ meningitis

–____ meningitis

•Lymphocytic/normal glucose

–____ meningitis or ____

–Post-infectious ____

Answer 23

•Neutrophilic/low glucose

–Bacterial meningitis

•Lymphocytic/low glucose

–Tuberculous meningitis

–Fungal meningitis

•Lymphocytic/normal glucose

–Viral meningitis or encephalitis

–Post-infectious encephalomyelitis

Question 24

CSF exam via __ __ is the critical diagnostic step in the patient with suspected CNS infection.

A neutrophilic/low glucose profile is highly suggestive of ___ infection whereas viral disease is typically characterized by a __/___ ___ profile

Answer 24

CSF exam via lumbar puncture is the critical diagnostic step in the patient with suspected CNS infection.

A neutrophilic/low glucose profile is highly suggestive of bacterial infection whereas viral disease is typically characterized by a lymphocytic/normal glucose profile.

Question 25

CNS Infections: Imaging * CCT and MRI useful in evaluating pts with suspected ____ infection (ie, brain abscess) or with localizing findings on neuro exam * May be “overused”→May result in delays in other essential diagnostic studies (LP) & in the initiation of empiric antimicrobial therapy

Answer 25

* CCT and MRI useful in evaluating pts with suspected focal infection (ie, brain abscess) or with localizing findings on neuro exam * May be “overused”→May result in delays in other essential diagnostic studies (LP) & in the initiation of empiric antimicrobial therapy

Question 26

Bacterial Meningitis: * 1-2 cases/100,000 people/yr (~4000 cases & ~500 deaths) * \_\_, \_\_, __ and altered \_\_\_ * Other clinical findings include __ \_\_ palsies/focal motor or sensory deficits (10-20% of pts), seizures (25-30%), & papilledema (\<1%) * \_\_\_ ____ has now emerged as the predominant pathogen (~60-70% cases), esp in the adult * N. meningitidis occurs primarily in children & teenagers

Answer 26

•1-2 cases/100,000 people/yr (~4000 cases & ~500 deaths) **•Fever, HA, meningismus, & altered MS** •Other clinical findings include **cranial nerve** palsies/focal motor or sensory deficits (10-20% of pts), seizures (25-30%), & papilledema (\<1%) **•S. pneumoniae** has now emerged as the predominant pathogen (~60-70% cases), esp in the adult •N. meningitidis occurs primarily in children & teenagers

Question 27

Viral Meningitis: * Most ___ type of meningitis→Often referred to as __ \_\_ * \_\_\_ symptoms than with bacterial disease * “Typical” CSF profile= \_\_\_/\_\_ ___ profile * \_\_\_ are predominant cause; others include flaviviruses, LCMV, & HIV

Answer 27

Viral Meningitis: •Most **common** type of meningitis→Often referred to as **aseptic meningitis** **•Milder** symptoms than with bacterial disease •“Typical” CSF profile=**Lymphocytic/normal glucose** profile **•Enteroviruses** are predominant cause; others include flaviviruses, LCMV, & HIV

Question 28

Viral Encephalitis: * Relatively _____ infection with __ course & outcome * Symptoms & signs typical for CNS infections though meningeal irritation, less prominent & alterations in MS more \_\_\_; focal signs may or may not be present; seizures \_\_\_ * Enteroviruses, arboviruses (eg, _ \_\_ virus), & HSV most common etiologies; new causes emerging * Rx supportive; directed Rx available only for herpesviruses & HIV

Answer 28

Viral Encephalitis: * Relatively **common** infection with **variable** course & outcome * Symptoms & signs typical for CNS infections though meningeal irritation less prominent & alterations in MS more **pronounced;** focal signs may or may not be present; seizures **common** * Enteroviruses, arboviruses (eg, **West Nile v**irus), & HSV most common etiologies; new causes emerging * Rx supportive; directed Rx available only for herpesviruses & HIV

Question 29

Brain Abcess: * Infrequent but not \_\_→~0.3-1.3 cases/100,000 persons/yr * Contiguous spread & blood-borne seeding; 25% cryptogenic * Clinical features include ___ (90%), ___ (57%), ___ changes (67%), ___ (61%) * Dx often suggested by CCT or MRI * LP is contraindicated due to risk of herniation * Infxns often polymicrobial (strep, GNRs, anaerobes) * Other less common etiologies include Nocardia, fungi, M. tuberculosis, T. gondii, & neurocysticercosis (T. solium) * Drainage often necessary component of management in addition to prolonged ATB therapy (6-8 wks)

Answer 29

Brain Abcess: * Infrequent but not **rare**→~0.3-1.3 cases/100,000 persons/yr * Contiguous spread & blood-borne seeding; 25% cryptogenic * Clinical features include **HA (90%), fever (57%), MS changes (67%), hemiparesis (61%)** * Dx often suggested by CCT or MRI * LP is contraindicated due to risk of herniation * Infxns often polymicrobial (strep, GNRs, anaerobes) * Other less common etiologies include Nocardia, fungi, M. tuberculosis, T. gondii, & neurocysticercosis (T. solium) * Drainage often necessary component of management in addition to prolonged ATB therapy (6-8 wks)

Question 30

Principles of Management * Prompt decision-making essential (once diagnosis considered, Rx ASAP if suspect bacterial infection or HSV) * Obtain CSF unless contraindications exist * Use ____ ATB therapies (ie, ATBs which act at the cell wall such as cephalosporins) with good CNS penetration * Add ___ with bacterial meningitis * Identify & correct complicating problems (eg, ­’ed ICP) * Isolate patients with \_\_\_\_ * \_\_\_\_\_s for contacts of meningococcal disease * Vaccines for primary prevention

Answer 30

* Prompt decision-making essential (once diagnosis considered, Rx ASAP if suspect bacterial infection or HSV) * Obtain CSF unless contraindications exist * Use **cidal** ATB therapies (ie, ATBs which act at the cell wall such as cephalosporins) with good CNS penetration * Add **steroids** with bacterial meningitis * Identify & correct complicating problems (eg, ­’ed ICP) * Isolate patients with **N. meningitidis** **•Prophylaxis** for contacts of meningococcal disease •Vaccines for primary prevention

Question 31

Ideally, the decision regarding use of antibiotics in a patient with suspected CNS infection should be made promptly once the diagnosis is considered. If antibiotics are used, ____ agents (i.e., those that act at the cell wall) should be employed whenever possible.

Answer 31

Ideally, the decision regarding use of antibiotics in a patient with suspected CNS infection should be made promptly once the diagnosis is considered. If antibiotics are used, **bactericidal** agents (i.e., those that act at the cell wall) should be employed whenever possible.

Question 32

* CNS infxns associated with high morbidity & mortality * Classification is ___ based * Most pathogens enter CNS via blood-borne seeding * Meningitis is the prototypical CNS infection; age is a major determinant of the likely pathogen * Bacterial meningitis is characterized by a \_\_\_/\_\_ __ CSF profile * Rx of bacterial meningitis should incorporate ___ ATBs that penetrate well into the CSF

Answer 32

* CNS infxns associated with high morbidity & mortality * Classification is **anatomically** based * Most pathogens enter CNS via blood-borne seeding * Meningitis is the prototypical CNS infection; age is a major determinant of the likely pathogen * Bacterial meningitis is characterized by a **neutrophilic/low glucose** CSF profile * Rx of bacterial meningitis should incorporate **bactericidal** ATBs that penetrate well into the CSF