6/8- Meningitis and Encephalitis Flashcards
What is meningitis (def)?
Diffuse inflammatory process involving the leptomeninges of the brain and spinal cord
Routes of acquisition of meningitis?
- Hematogenous
- Direct extension (from bad infection)
What is the mortality rate for meningitis in the US?
What has been responsible for 55% decrease?
~15% (500 deaths/year)
Decrease with the Hib/pneumococcal vaccine
What age group(s) have highest incidence of disease?
(Per 100,000)
- Under 2 mo: 80.7
- 2-23 mo: 6.9
- 2-10 yo: 0.6
- 11-17 yo: 0.43
- > 65 yo: 1.92
What comprises the leptomeninges?
- Arachnoid mater
- Pia mater (includes subarachnoid space that is typically filled with CSF)
Inflammation of these tissues is what causes the stiff neck
Process of hematogenous dissemination?
What causative organisms?
Hematogenous dissemination:
- Colonization (e..g attach to nasopharyngeal epithelium)
- Local invasion
- Bacteremia (through mucosa -> bloodstream)
- Meningeal invasion (crossing BBB)
- Bacterial replication (e.g. subarachnoid space)
- Subarachnoid inflammation
Ex) pneumococcus, N. meningitides
Why are younger children/neonates more susceptible to meningitis?
Immune systems aren’t as developed
What groups are especially susceptible to hematogenous dissemination?
Age-related:
- Peak 6-24 mo
- Increased in neonates and elderly
When does Neisseria meningitidis invade the blood stream?
- First 2 wks after colonization (before Abs develop)
What are risk factors for hematogenous dissemination (esp. N. meningitidis)?
- Viral-illness (esp influenza)
- Smoking (active and passive)
- Drinking
These compromise nasal mucosa (?)
What different mechanisms underly host deficiencies?
- Asplenia: functional, congenital, acquired
- Antibody dysfunction: congenital, acquired (HIV), prior to natural acquisition (under 2 yo), or decline with age
- Complement deficiency: physiological decrease in newborn or terminal component deficit
What anatomical defects predispose one to meningitis? By what mechanism?
Congenital:
- Dermoid sinus
- Myelomeningocele
Acquired:
- Trauma
- Neurosurgery
- Tumors
These cause meningitis my direct extension
What is this?
Sacral dermoid sinus tract
What is this?
Occipital dermoid sinus tract
Direct extension can occur with what conditions?
Parameningeal focus:
- Sinusitis
- Otitis media
- Osteomyelitis of the skull or vertebral bones
- Intracranial foci (brain abscesses)
Pathophysiology of meningitis in neonates (steps)?
- Source: maternal genital tract
- Aspiration of amniotic fluid
- Lung and/or bloodstream infection
- Meningeal invasion
What bacterial products cause inflammation? Results in what?
Inflammatory bacterial products:
- Endotoxin
- Teichoic acid
- Peptidoglycans
Results in inflammatory mediator release:
- TNF
- Interleukins (IL-1)
- Arachidonic acid
- Metabolites
- Platelet-activating factor
- Interferons
Overall pathophysiology of inflammatory process in meningitis?
- Bacterial products promote release of inflammatory mediators
Inflammatory factors cause (separately and interplay):
- Activation of leukocytes
- Endothelial injury
- Coagulation cascasde
Results in:
- Cytotoxic and interstitial edema -> increased ICP
- Increased BBB permeability -> vasogenic edema
- Thrombosis -> decreased cerebral blood flow
Clinical-Pathologic correlates (meningitis):
___ -> headache, stiff neck (meningeal signs)
___ -> altered consciousness, SIADH, respiratory depression
___ -> ocular palsies, deafness
___ -> focal seizures, focal deficits
___ -> signs of increased cranial pressure
Clinical-Pathologic correlates:
Piaarachnoiditis -> headache, stiff neck (meningeal signs)
Subpial toxic encephalopathy -> altered consciousness, SIADH, respiratory depression
Inflammatory or vascular involvement of CNs -> ocular palsies, deafness
Thrombosis of meningeal vessels -> focal seizures, focal deficits
Hydrocephalus -> signs of increased cranial pressure
What is this?
(T1 MRI with contrast)
- Frontal subdural hygromas (arrows)
- Also enhancing left thalamic infarction 2ndary to penetrating artery spasm (arrowhead)
This pt has pneumococcal meningitis
What is this?
Suppurative meningococcal meningitis
- Subarachnoid space is filled with neutrophils
What is the classic triad (in kids and adults) for diagnosing meningitis? Other manifestations?
- Fever
- Nuchal rigidity
- Change in mental status
Others:
- Photophobia
- Seizures
- Focal neurological deficits
- Petechiae/purpura
- Brudzinki’s sign (not in neonates)
- Kernig’s sign (not in neonates)
What is Brudzinski’s sign?
Severe neck stiffness causes pts hips and knees to flex when the neck is flexed
What is Kernig’s sign?
Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90’
Lumbar puncture results in meningitis?
- CSF cell count: high WBC (if bacterial)
- Glucose: decreased
- Protein: increased
What can be found on the basic metabolic panel in meningitis?
Na to look for SIADH
When would you do diagnostic imaging in the diagnostic process for meningitis?
Before LP if focal neurologic deficit
Where is an LP performed?
L3/L4 or L4/L5
Normal CSF results?
OP: < 20
WBC: < 5
Protein: 15-45
Glucose: 45-80
Stain/Cx: neg/neg
CSF results in bacterial meningitis?
OP: Elevated (more than 20)
WBC: > 1,000
Protein: > 100
Glucose: Decreased (under 40)
Stain/Cx: pos/pos
CSF results in viral meningitis?
OP: Normal (< 5)
WBC: Elevated but < 300
Protein: Elevated; < 150
Glucose: Normal (45-80)
Stain/Cx: neg/pos (culture or PCR)
CSF results in TB?
OP: Greatly elevated
WBC: Elevated but < 500
Protein: > 100
Glucose: Slightly decreased (< 50)
Stain/Cx: +/- pos/pos
CSF results in abscess?
OP: Elevated
WBC: Elevated but < 200
Protein: Elevated
Glucose: Normal (45-80)
Stain/Cx: neg/neg
Bacterial meningitis etiology in pediatric age group?
- Early on, GBS dominates (under 2 mo)
- With older age, more Strep pneumo, Haemophilus and Neisseria
- In 11-17 yo, 2 main cause (about equal): S. pneumo and Neisserria
Bacterial meningitis etiology in adults?
- 18-34 yo: mostly S. pneumo and Neisserria (about equal)
- In older age groups, predominantly Strep pneumo
- >65 yo have significant portion of Listeria as well
- Haemophilus present in all
Empiric therapy for meningitis in:
- Neonates:
- Infants and kids:
- Adults:
- Elderly:
Empiric therapy for meningitis in:
- Neonates: ampicillin and gentamicin
- Infants and kids: vancomycin and 3rd gen cephalosporin (cefoxitime or ceftriaxone)
- Adults: vancomycin and 3rd gen cephalosporin (cefotaxime or ceftriaxone)
- Elderly: vancomycin, 3rd gen cephalosporin and ampicillin (for Listeria)
Case 1:
- 6 hr old male with tachypnea and lethargy
- Full term male born to a 24 yo mom via spontaneous vaginal delivery
- Transferred to NICU for respiratory distress
- LP: WBC 2085 (mostly neutrophils), 10 RBC, protein 245, glucose under 25
What is this?
What is empiric treatment?
Differential: bacterial meningitis
- Group B strep (GBS)
- Grm - rod (E. coli)
- Listeria
Empiric treatment: ampicillin + gentamicin
Pt in this case survived but with neurological impairment.. failed end of therapy hearing screen (hearing loss from meningitis, not gentamicin!)
What is this?
Gram + cocci in chains (Group B strep)
Source of GBS in neonatal meningitis?
What is the presentation (timeline)?
Source: maternal genital tract
- Early onset (1st 7 days of life)
- 80% reduction with intrapartum antimicrobial prophylaxis
- Late onset (7 d- 3 mo)
What percentage of neonates with meningitis have neurologic deficits/sequelae?
33-50% of survivors
(85-90% of those affected)
What is this?
Serratia marcescens meningitis
Case 2:
- 66 yo male with fever and altered mental status
- Hx of diabetes and HTN
- Fever x 3 days (also w/ cough and increased work of breathing)
- CBC with WBC 28,000 (85% neutrophils)
- CT of the brain without contrast was unremarkable
- LP with 2540 WBC (90% neutrophils), 350 protein, glucose < 20
Differential diagnosis?
Empiric management?
DDx:
- S. pneumoniae
- N. meningitidis
- H. influenzae
- Listeria
- Group B strep
Empiric mgmt: Cefotaxime + vancomycin + ampicillin
This ended up being pneumococcal men (Gm stain)
What is this?
Gm + diplococci = Pneumococcus
Streptococcus pneumoniae is the __ most common cause of vaccine-preventable death in the US (__ is the most common cause)
Streptococcus pneumoniae is the 2nd most common cause of vaccine-preventable death in the US (Influenza is the most common cause)
Pneumococcal meningitis is the __ bacterial cause of meningitis inn what age groups?
#1 cause in adults and children
Who has an increased risk of pneumococcal meningitis?
- Elderly
- Alcoholics
- SCD
- HIV
- Trauma
- Cochlear implants
What is the case fatality rate of pneumococcal meningitis? In elderly?
What is common among survivors?
Fatality rate: 13-30% (up to 80% in elderly)
Neurologic sequelae common among survivors
How can pneumococcal meningitis be prevented?
Given to whom?
PCV13 and PPV23 immunization
- Children: 2-59 mo (< 5 yo)
- Individuals > 5 yo with high risk conditions
- Elderly > 65 yo
Case 3:
- 14 yo male with altered mental status, fever
- Athlete, recurrent influenza-like illness with 3 day Hx of increasing fever, sleepiness, altered mental status
- Outside hospital: tachypneic, tachycardic, hypotensive
- CBC with WBC 11 (65% neutrophils)
- Ceftriaxone given and pt transferred
- intubated for respiratory failure, inotropic support
- CSF: WBC 11,000 (96% neutrophils), RBC 250, protein 235, glucose < 20
- Differential diagnosis?
- Empiric mgmt?
Differential diagnosis:
- N. meningitidis
- S. pneumoniae
- H. influenzae
Empiric mgmt: ceftriaxone + vancomycin
This ended up being N. meningitidis (Gm stain)
- Pt slow to wake up, difficulty with speaking and find motor skills (continues to have memory deficits)
What is this?
Neisseria menigitides (Gm -)
What are the primary groups affected by meningococcal disease?
- Infants (6-24 mo)
- Teens
- Young adults
- Outbreaks in military recruits and college students
Peak of meningococcal dz in what months?
Winter or spring months
Prevention of meningococcal dz?
Immunization with MCV4 and MenB vaccine
What is this?
Haemophilus influenzae
Characteristics of H. influenzae:
Gm:
Serotypes:
Characteristics of H. influenzae:
Gm: negative
Serotypes: 6 different (a-f) of polysaccharide capsule with 95% of invasive dz caused by type B
Outcomes of meningitis caused by H. influenzae type B?
- Hearing impairment or neurologic sequelae in 15-30%
- Case-fatality rate 2-5% despite effective antimicrobial therapy
Complications of meningitis?
- Seizures
Hydrocephalus
- Infarction
- Herniation
- Hearing loss
- Focal deficits
- Severe neurologic deficits
- Death
What is encephalitis (def)?
- Presence of inflammatory process in the brain or SC (in association with clinical evidence of neurocognitive dysfunction)
[as opposed to disruption of brain function in absence of direct inflammatory process of the brain parenchyma, as in encephalitis]
Pathogenesis of encephalitis?
- Direct hematogenous invasion of organism (resulting in cellular dysfunction or cytolysis causing generalized encephalitis)
- Extension via neuronal tracts causing focal encephalitis
- Cytolysis leading to perivascular and parenchymal inflammation and focal necrosis
- Some infectious agents cause direct endothelial injury resulting in vasculitis and infarction
Etiologies of encephalitis?
Wide variety of pathogens:
- Viral infections are the most common infectious etiology (Most coommonly enterovirus and HSV)
- Bacterial, fungal, and parasites are other infectious etiologies
- Post-infectious (ADEM)
- Autoimmune
- Prion
In many cases (32-75%) etiology remains unknown
Viral causes of encephalitis?
- HSV 1 and 2
- Enteroviruses (polio, coxsackie, echo)
- Varicella zoster
- Ebstein Barr
- Adenovirus Others (less common)
- Rabies virus
- Arboviruses (WEEV, EEEV, VEEV, St.Louis encephalitis, LaCrosse encephalitis, W. Nile virus)
- Lymphocytic choriomeningitis virus
Case 4:
- 5 week old with fever, altered mental status, and fine pinpoint petechial rash
- Blood, urine, and CSF studies done
- SF with 230 WBC, glucose 30, protein 60, negative Gm stain
Differential Dx?
Enterovirus
Characteristics of enteroviruses?
- Transmission:
- Peak incidence (months):
- Incubation period:
- Diagnosis:
- Treatment:
Transmission:
- Fecal-oral
- Respiratory
- Fomites
- Vertically during peripartum period
Peak incidence: June - Oct (all year long in Houston)
Incubation: 3-6 days
Diagnosis: PCR
Treatment: supportive
Signs and symptoms of encephalitis?
- Fever, headache, nuchal rigidity
- Altered consciousness
- Disorientation, behavioral changes
- Focal neurologic signs or deficits
- Seizures
What do you want to ask in the detailed Hx if suspect encephalitis?
- Recent illnesses
- Exposures (i.e. animals)
- Travel
- Insect bites
- Season
Diagnostic evaluation of encephalitis includes what?
- Detailed Hx
- Physical exam
- Cultures (for bacterial/viral agents)
- Serology (IgG, IgM)
- Antigen, DNA, or RNA detection (PCR)
- Epidemiology investigation
- Diagnostic imaging
Treatment for encephalitis?
- Supportive care
- Antiviral therapy (acyclovir!)
- Antibiotic therapy
- Steroids
Case 5:
- 27 you presents w/ fever, headache, irritability, and difficulty walking
- 14 days ago, got home from summer camping trip - Multiple mosquito bites
- On exam, proximal lower extremity weakness and absence of reflexes
- CSF: 62 WBC (85% lymphocyts), glucose 62, protein 84
Differential diagnosis?
Empiric treatment?
DDx:
- Viral meningoencephalitis
—Arboviruses, W. Nile VIrus
—HSV, Enterovirus, EBV, CMV
- Noninfectious etiologies
Empirical treatment: Acyclovir
In this case, saw W. Nile IgM in blood and CSF
What is the vector for West Nile Virus (WNV)?
Moquito-borne flavivirus
- Culex species
Peak transmission of W. Nile Virus?
Late summer and early fall
Symptoms (and %) in W. Nile virus?
- Mild febrile illness (20%)
- Less than 1% with severe neurologic manifestations (meningitis, encephalitis, and acute flaccid paralysis)
Case 6:
- 11 yo male presents with fever, headache, and AMS
- CSF with 82 WBC, normal glucose, protein 90
- EEG done for possible seizure activity (Focal EEG with prominent intermittent high amplitude slow waves–delta and theta slowing–and continuous periodic lateralized epileptiform discharges from the R temporal lobe)
Differential diagnosis?
Differential diagnosis:
- Herpes simplex encephalitis
What is this?
CT scan of pt with herpes simplex encephalitis with temporal lobe changes
What is one of the only treatable viral encephalitis etiologies?
Treatment?
Herpes simplex virus encephalitis
- Acyclovir (give to all pts until confirm a diagnosis); early treatment can stop viral replication and improve outcome!
Clinical-Pathologic correlates (for meningitis):
Piaarachnoiditis -> ____
Subpial toxic encephalopathy -> _____
Inflammatory or vascular involvement of CNs -> ____
Thrombosis of meningeal vessels -> ____
Hydrocephalus -> ____
Clinical-Pathologic correlates:
Piaarachnoiditis -> headache, stiff neck (meningeal signs)
Subpial toxic encephalopathy -> altered consciousness, SIADH, respiratory depression
Inflammatory or vascular involvement of CNs -> ocular palsies, deafness
Thrombosis of meningeal vessels -> focal seizures, focal deficits
Hydrocephalus -> signs of increased cranial pressure
