Meningitis Encephalitis Flashcards
Anatomy
LAYERS where = meninges • Scalp • Subgaleal space • Skull • Epidural space • Dura mater • Subdural space • Arachnoid • Subarachnoid space – filled with CSF • Pia mater • Cerebral cortex
Morbidity and mortality
☺ Definitely good to know:
Acute complications
Altered mental status, coma Increased intracranial pressure (ICP) Seizures Subdural effusions, abscess Intracerebral abscess Shock Respiratory distress/failure/arrest, apnea Disseminated intravascular coagulation Death
Morbidity and mortality
☺ Definitely good to know:
Sequelae
Focal neurologic deficits: deafness/sensorineural
hearing loss, blindness, paralysis, paresis
CNS structural sequelae/complications:
hydrocephalus, brain abscess, epidural abscess,
subdural abscess/effusion/empyema, cerebral
thrombosis, vasculitis
Seizure disorder
Personality changes
Gait disturbances
Impaired intellectual functioning, cognition
Signs & symptoms - varies with age
Fever
Irritability
Confusion
“Classic” triad: • Fever • Headache (vs *altered mental status) • Neck stiffness Other symptoms could be: • Nausea/vomiting • Photophobia • Rash • Seizures *altered mental status: confusion, irritability, delirium, drowsiness, coma
Characteristic “petechial rash” is usually
located on the trunk and legs and may
rapidly evolve into “purpura
Meningitis symptoms
pearls
• Could be rapid progression (over hours) vs even dayssss • Earlier symptoms? • Fever, headache, irritability, N/V or altered feeding • Later symptoms? • Drowsiness, aches & pain • Even beyond that? • Cold hands and feet • Neck pain or stiffness • Rash • Confusion, delirium • Difficult to wake → coma
pysical sign
spinal cord movement will make some activity urt
KErnig sign
Drudzinski sign
Final words on signs and symptoms?
Remember, in meningitis….
• One large review of 10 critically appraised studies on fever, stiff neck, mental status change
• 99-100% with have 1 of these findings
• 95% will have 2 of these findings
• <50% will have all 3 findings
• In the absence of all 3, many clinicians will rule out meningitis
• Up to 50% of patients will NOT have Brudzinski’s and Kernig’s sign
• NOT all meningitis will have “classic rash”
• You are likely to see this in N. meningitidis
• Not all petechiae or purpuric rash = meningitis
Diagnosis:
Investigations that helps
• Bloodwork
• Regular admission bloodwork
hold abx before getting a culture (at min, get a culture)
• Microbiological
• At minimum, when meningitis is suspected, pre-antibiotic blood culture
• Lumbar puncture for CSF if possible & not contraindicated → culture, fluid
analysis, PCR, (check opening pressure)
• (Full septic work up if applicable)
- Imaging?
- CT head vs MRI brain
- vs ultrasound may be adequate in neonates/infants
Differential
diagnosis
• acute meningitis syndrome may be caused by
a wide variety of infectious agents & may also
be a manifestation of non-infectious diseases
Lumbar puncture
younger pt need sedation
coafulopathy
CSF analysis
see slide 21
k
• Before abx, ↑ WBC with >90% polymorphonuclear leukocytes
• Reduced % of PMNs if received abx prior to LP
• ↓ glucose as transport is impaired
• hypoglycorrachia
• ↑ protein as inflammatory damage to blood vessels within the
meninges → serum leaks into the CSF
• Gram stain – super useful clue for bacterial meningitis
• CSF culture, in the absence of prior abx, remains the most sensitive
test for diagnosis
read
which are common pathogens
see slide 23
no kid dose on exam
Local guideline, if Bugs & Drugs → Adults
> 50 years old, or immunocompromised, alcohol abuse, debilitating illness, pregnancy
S. pneumoniae, L. monocytogenes, N. meningitidis,
Enterobacteriaceae ☺
Ceftriaxone 2g IV q12h plus
Vancomycin 15 mg/kg IV q8-12h plus
Ampicillin 2G IV q4h
Local guideline, if Bugs & Drugs → Adults
Age 18 - 50 years old
Ceftriaxone 2g IV q12h plus
Vancomycin 15 mg/kg IV q8-12h
Duration of therapy
☺ If no organism cultured: 10 - 14 days
Streptococcus pneumoniae 10 – 14 Streptococcus agalactiae 14 – 21 Enterococcus spp 14 Listeria monocytogenes 14 – 21 (ped) ≥ 21 (adult) Neisseria meningitides 7 (ped) 5 - 7 (adult) Haemophilus influenzae 7 (ped) – 10 (adult) Enterobacteriacae 21
You may also see acyclovir added to the above
regimen
• Not that many VIRAL causes that we can treat → fever, headache,
photophobia, stiff neck and altered mental status
• Acyclovir age appropriate dosing, IV q8h sometimes given for HSV 2
meningitis x 10-14 days
• Because HSV is the most common cause of sporadic fatal encephalitis and is
one of the few treatable cause → ppl may be reluctant to stop
• Using encephalitis dose for HSV 1 encephalitis:
• ≤ 12 yo 60 mg/kg/day IV div q8h
• > 12 yo 30 mg/kg/day IV div q8h
• ≥ 18 yo 10 mg/kg (based on IBW or actual BW, whichever is less) IV q8h x 14-
21 days ☺
☺ The role of acyclovir ….
• Remember, current suggestions:
• HSV 2»_space;» HSV 1 for Meningitis
• Do not be surprised about step down from IV Acyclovir to PO valacyclovir 1G TID (adjust
for renal function) to complete total of 7 – 14 days
• The need to and benefit of treating HSV or VZV meningitis remains uncertain
• HSV 1»_space;» HSV 2 for Encephalitis – most will complete IV therapy x 14 - 21
days
• VZV meningitis – 15 mg/kg IV q8h x 10 -14 days
• But more importantly, we are fearful of HSV encephalitis
• The use of ACV supported by RCT to decrease mortality
SteroidsB
What does steroids do? IN BRIEF
• Inhibits synthesis of interleukin 1 (IL-1) and tumor necrosis factor (TNF) at mRNA level • Decreases CSF outflow resistance → brain edema • Stabilizing the blood brain barrier → decreases entrance of more leukocytes Once macrophages/neutrophils are activated and TNF production has been induced = ↓ effect
The conclusion Brouwer 2015?
• Non-significant ↓ mortality – 17.8 vs 19.9 %
• *Significant ↓ rates of hearing loss
• Severe 6.9 vs 9.3 %
• Any 13.8 vs 19%
• *Significant ↓ rates of neurological sequelae
• Pathogen specific (as subgroup analysis, not powered)
• ↓ mortality in Streptococcus pneumoniae – 29 vs 36% with no effect in
Haemophilus influenzae, Neisseria meningitidis
• In children with H. influenzae - ↓ rate of hearing loss 4 vs 12%
* = effect only seen in high-income countries
Can we use any steroids in meningitis, and any
countries??
- Dexamethasone has been investigated most extensively
- Experimental studies
- Methylprednisolone demonstrated lower CNS concentration
- Studies exists where dexamethasone vs PLACEBO
- Most trials use dexamethasone
- Trials in Pediatric & Adult both used dexamethasone
- No beneficial effect in low-income countries
Do we use steroids for every child?
read
• Controversial, except in Hib meningitis → ↓ severe hearing loss in Hib
meningitis
• = Local guideline (B&D): If S pneumoniae or H influenzae or no pathogen
identified, continue dexamethasone for 4 days
Do we use steroids for every adult?
In adults, ↓ mortality and hearing loss in S. pneumoniae meningitis
• meningitis due to S pneumoniae treated with corticosteroids had a lower death
rate (29.9% versus 36.0%)
• No benefit in any other pathogen → discontinue?
• ↑ mortality when steroid is used in Listeria monocytogenes (do not use with listeria)
• = Local guideline (B&D): If S pneumoniae or H influenzae or no pathogen
identified, continue dexamethasone for 4 days
Encephalitis
☺ For this section: I recommend study in detail, all slides related to
HSV for exam.
Herpes simplex virus 1 & 2
• Family: Herpesviridae • DNA virus • Described over 2000 years ago. Classified as a virus in 1940s
Season or geographical • Seasonality: none • Distribution: worldwide
Vectors/Mode of transmission • Transmission: person to person • Prevention: none
Herpes simplex virus 1 & 2
Signs & symptoms
• Acute onset fever, confusion, focal neurologic symptoms • Up to 2/3 have convulsive seizures • Commonly temporal lobes → HSE • Associated with: • meningitis • encephalitis • Most cases are caused by HSV 1 but ~10% are caused by HSV 2
Diagnosis HSV
The typical lesions on the lips or face are not usually seen, because reactivated virus migrates up the Vth cranial nerve toward the CNS rather than toward the periphery. Recall, typically: HSV1 → orofacial disease HSV2 → genital disease
CSF analysis • Lymphocytic pleocytosis • Normal or low glucose • Mild ↑ protein • RBC may be present when hemorrhagic lesions are present • PCR → high specificity and sensitivity BUT • May be falsely NEG until several days into the illness with treatment • Rpt CSF in 24-72 hours may be needed • Imaging et al. • CT scan or MRI: temporal lobe edema, hemorrhage • Can be normal acutely, but by 48 h, >90% will have abnormalities • EEG: activity in temporal lobe(s)
Herpes simplex virus
Treatment • Acyclovir 10 mg/kg IV q8h for 14- 21 days • Use actual or ideal body weight, whichever is less • MUST adjust for renal function • Neurotoxicity • Even if dosed appropriately, can cause crystal nephropathy if inadequate hydration • Insufficient data to support the use of adjunctive corticosteroids
Pearls: • HSV 1 >>>> HSV 2 for encephalitis • Could be from primary infection, reactivation of latent infection, or reinfection • In encephalitis, acyclovir treatment ↓mortality from ~70 to 25% • ¾ dies vs ¼ dies • Long term disability or neurologic impairment occurs in >50% of patients
Enterovirus
Signs & symptoms
• 2
nd most common cause of viral encephalitis in
pediatric, after HSV1
• Incubation 3 - 6 days in most cases
• Mostly asymptomatic, have no “prodrome”
• But If symptomatic, usually:
• Fever, gastrointestinal tract symptoms, or respiratory
tract symptoms before
• Neurologic symptoms of meningitis:
• Headache, fever, stiff neck, irritability, malaise,
photophobia
• Enteroviruses causing meningitis, encephalitis: EVA71
• During some outbreaks of HFMD → severe
neurological complications
Enterovirus
Why do we care?
- Non-polio EV → significant and frequent illnesses in pediatric population
- Non-specific febrile illness → septic work up
- Resp: Coryza, pharyngitis, stomatitis, bronchiolitis, pneumonia
- Derm: hand-foot-and-mouth disease, onchomadesis, nonspecific exanthems
- Neuro: aseptic meningitis, encephalitis, acute flaccid paralysis
- GI/GU: V/D abdominal pain, hepatitis, pancreatitis, orchitis
- Eye: acute hemorrhagic conjunctivitis and uveitis
- Heart: myopericarditis
- Muscle: pleurodynia, other skeletal myositis
