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Clinical Medicine Neuro Infectious Disorders Month 2 Week 4
Clinical Medicine Neuro Infectious Disorders Month 2 Week 4
54
Medical
Graduate
10/22/2018

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Term
meningitis organism prevalence change from 1970s to 1990s
Definition
Streptococcus pneumoniae ̄ 26%
Neisseria meningitidis ̄ 58%
Group B Streptococcus ̄ 4%
Haemophilus influenzae ̄ 35%
Listeria monocytogenes ̄ 46%
Term
Acute vs Chronic Meningitis
Definition
-Defined by duration of signs and symptoms
-Acute <4 weeks
-Chronic >4 weeks
Term
Causes of Meningitis
Definition
- Bacteria
• Community-acquired - S. pneumoniae, N. meningitidis,
Group B Streptococcus
• Post-op or hospital acquired – MRSA, Pseudomonas aeruginosa
• Infants/Elderly Listeria monocytogenes
- Viruses
• Enterovirus, Coxsackie virus, Echovirus, HSV-2, Arbovirus, Adenovirus, Measles virus, Influenzae virus
- Fungi
• Coccidioides, Cryptococcus
- TB
Term
[image]
Definition
So what's going on here? Well, this is the pathophysiology. You can read through this. Basically, you get seeded. And usually you get seeded with these organisms through the nasopharyngeal area. They then penetrate. They get in. They get into the sinuses. They work their way across the blood-brain barrier. And they get into the brain.

One of the most interesting cases of meningitis I ever saw was a person that had surgery. They'd been intubated. The intubation led to bacterial flora from the mouth getting into the sinuses. They developed a sinus infection which then infected the sinus bones, so they developed an osteomyelitis in their sinuses. And then it eroded through and got into their brain.

So that doesn't happen that often. But that's kind of the seeding mechanism. Usually, it gets into the nasopharyngeal area and then crosses into the blood-brain barrier.

With bacteria, you get a huge inflammatory response in all the spaces and the spinal fluid. And this is all-- see all this white stuff kind of coating this autopsy brain? All that white, that's all pus. That's all inflammatory process. That's all white cells. That's all bacteria.
Term
Bacterial Meningitis
Definition
• Inflammatory response to bacterial infection of the pia- arachnoid and CSF of the subarachnoid space.
Term
Meningitis Risk Factors
Definition
- Age
• Infants are at higher risk for bacterial meningitis than people in other age groups.
- Community setting
• Larger groups of people gather together. College students living in dormitories and military personnel.
- Certain medical conditions
• There are certain diseases, medications, and surgical procedures that may weaken the immune system or increase risk of meningitis in other ways.
- Travel
• Travelers to the meningitis belt in sub-Saharan Africa may be at risk for meningococcal meningitis.
Term
Clincal Presentation
• Acute meningitis
Definition
• Abrupt or rapid onset
• “flu-like” prodrome – myalgias • Fever
• Headache
• Nuchal stiffness
• Altered sensorium
• Rash
Term
meningitis Physical Exam- What’s Important?
Definition
• Nuchal rigidity (30%)
- Brudzinski and Kernig sign
• Rash
- Noted in 66% of patients with meningococcal, but may also beseen with Haemophilus and Streptococcus
• Focal neurologic signs (33%)
- More common with pneumococcal
• Altered consciousness (69%)
• Papilledema (3%)
Term
meningitis Systemic infection clinical findings
Definition
Fever Myalgia Rash
Term
meningitis Meningeal inflammation clinical findings
Definition
Neck stiffness Kernig/Brudzinski Cranial nerve palsies
Term
meningitis Cerebral vasculitis clinical findings
Definition
Focal neurologic abnormalities Seizures
Term
meningitis Elevated intracranial pressure clinical findings
Definition
Change in mental status Headache
Cranial nerve palsies Seizures
Term
meningitis Special Groups- Presentation
Definition
• Neonates- no meningismus, but temperature instability, listlessness, refusal to eat, jaundice, diarrhea
• Adults co-morbid conditions- lethargy, obtundation, confusion, no fever
• Neutropenic patients- very subtle presentation, change in mental status
- Secondary to inability to mount an inflammatory response
Term
meningitis CT Indications
• Guidelines for performing CT scan before LP
Definition
• Recent seizures (<1 week)
• Immunocompromised
• History of CNS disease
• Altered mental status
• Abnormal gaze or facial palsy
• Abnormal language or inability to answer 2 questions or follow 2 commands
• Visual field abnormalities
• Arm or leg drift
Term
meningitis CSF Studies
• CSF Cell count
Definition
• Non-specific
• WBC count > 2,000/mm3 was predictive of bacterial meningitis • Neutrophil count >100 was also predictive
• WBC count < 1,000/mm3 noted in 20% of patients
• Listerial infection presents with low WBC and a mononuclear cell predominance
Term
meningitis CSF Studies
• CSF Culture
Definition
• The Gold Standard
• Positive in 85% of cases with a CSF WBC >1000/mm3
• Varies with organism
- H. influenzae 96%
- S. pneumoniae 87%
- N. meningitidis 80%
• Positive cultures lower in patients on antibiotics prior to LP
• 24 hours of pretreatment drops rate to 59%
Term
meningitis CSF Studies
• CSF Gram stain
Definition
• Cheap and well-validated
• Study of just under 4000 patients with bacterial meningitis 45% of CSF culture negative patients had a positive Gram stain (Bryan, 1990)
- 44% of the patients in this study had been pre-treated with antibiotics
• Sensitivity of Gram stain varies by organism
Term
meningitis CSF Studies
• Latex agglutination tests
Definition
• Provides results in less than 15 minutes
• Detect antibodies against the capsular polysaccharides og the pathogen
• Recommended for patients with suspected bacterial meningitis with negative Gram stain and culture
• Have a high sensitivity
- Sensitivity drops with pre-treatment with antibiotics • Sensitivity decreased from 60% to 9% for meningococcal meningitis (Bronska, 2006)
• Overall use is limited
Term
meningitis CSF Studies
• Polymerase chain reaction (PCR)
Definition
• Nucleic acid amplification tests
• Use limited by testing availability and time to perform
• High diagnostic accuracy (88-100%)
• Test for H. influenzae, S. pneumoniae, and N. meningitidis
• Meningococcal testing being used widely in suspected meningococcal meningitis with negative cultures
• Studies being done on L. monocytogenes • Results unclear at this time
• Also used in viral meningitis
Term
meningitis CSF Studies
• CRP
Definition
• An acute phase reactant
• Synthesized by the liver
- In response to interleukin 6 which is produced during infection and
inflammation
• Activates classical complement pathway
• Secretion starts in 6 hours, peaks in 36 hours
• Elevated levels suggestive of bacterial infection, but do not establish the diagnosis
Term
meningitis Treatment- Empirical
Definition
• Ceftriaxone 4 g IV daily or 2 gm IV Q 12, or Cefotaxime 2 gm IV Q 4, plus
• Vancomycin 1.5 gm IV Q 12
• In newborn or over age 50 add Ampicillin 2 gm IV Q 4 or
penicillin 2.4 gm IV Q 4
• If PCN allergic, ask for details:
- Rash : use cephalosporin
- Anaphylactic : use Aztreonam 2 gm IV Q 8
Term
meningits Treatment
• Corticosteroids
Definition
• Reduce the inflammation caused by infection
• Dexamethasone leads to a reduction in hearing loss and other neurological sequelae
• No reduction in overall mortality
• Improves outcomes in adults and reduces mortality in patients with S.
pneumoniae meningitis
• Inhibits synthesis of cytokines causing inflammation
• Decreases CSF outflow resistance
• Stabilizes blood-brain barrier
• Give before or with 1st dose of antibiotics for 4 days
Term
meningistis treatment duration of therapy in days by organism
Definition
Neisseria meningitidis
7
Haemophilus influenzae
7
Streptococcus pneumoniae
10-14
Streptococcus agalactiae
14-21
Aerobic gram-negative bacilli
21
Listeria monocytogenes
≥ 21
Term
meningitis management algorithm
Definition
[image]
Term
meningitis prevention
Definition
- Vaccines
• H. influenzae type B vaccine
• Pneumovax
• Meningococcal vaccine
• All should be administered to any asplenic patient
- Exposure to meningococcus
• Rifampin 600 mg PO BID x 4 doses or Ciprofloxacin 500 mg single dose (adults) or ceftriaxone 125 mg IM single dose
• Only for intimate contacts: spouse, boyfriend/girlfriend, household contacts
• Not needed for: classmates, co-workers, HCWs (ER personnel, EMTs, etc)
Term
Acute Bacterial Meningitis: DDx
Definition
• Bacterial, viral, fungal, TB meningitis
• Drug-induced hypersensitivity meningitis
• Carcinomatous or lymphomatous meningitis • Viral encephalitis
• Tick-borne bacterial infections
• Brain abscess
• Subdural empyema
• Venous sinus thrombosis
• Autoimmune (e.g., Sarcoid, SLE)
Term
Acute Bacterial Meningitis: Complications
Definition
• Decreased intellectual function • Memory impairment
• Cerebral edema
• Hydrocephalus
• Septic shock, multisystem organ dysfunction • Septic venous sinus thrombosis
• Arteritis
• Cranial nerve palsies (hearing)
• Seizure
Term
Viral Meningitis
Definition
- Enteroviruses cause 85-95% of cases
• Include Enterovirus, Coxsackie virus, and Echo virus • Cause 30,000 to 75,000 cases per year
• Typically noted summer/fall
• Fecal-oral spread
- Other viruses
• Mumps (viral meningitis and encephalitis)
• Herpesviruses (HSV-1, HSV-2, Varicella-zoster, CMV, EBV)
• HIV
• Lymphocytic choriomeningitis virus
- Cannot distinguish initially from bacterial meningitis
- Severe HA, photophobia, nuchal rigidity, fever
- May be preceded by a few weeks by viral gastroenteritis
• Ask patient if he/she had the “stomach flu” some time in the past couple weeks
- Almost never involves brain (meningoencephalitis) • Pt never obtunded, no history of seizure
- Disease is self-limited, resolves after 7 to 10 days without treatment
- No serious sequelae
Term
Viral Meningitis- CSF
Definition
• Low numbers of WBCs : 10 to 500
- PMNs predominate early, Monos or Lymphocytes later
• CSF to serum glucose ratio usually = 50%
• Protein may be high
• Gram stain, culture and bacterial antigens negative • Enteroviral PCR positive about 70% of time
Term
Approach to Viral Meningitis
Definition
• Treat like bacterial meningitis until the 72 hr culture comes back negative, or...
• Enteroviral PCR comes back positive
• Consider acyclovir if CSF HSV PCR positive
- HSV meningitis is self-limited
Term
How do we distinguish viral from bacterial based on labs?
Definition
- Gram stain
• Positive in bacterial meningitis 50-90% of time • Decrease to 7-41% if on oral antibiotics
- CSF results that suggest bacterial
• Glucose <40 mg/dl
• Protein >200 mg/dl
• WBC count >1000/μL with >80% neutrophils • Opening pressure > 300 mm
- Classic findings not always noted
• 12% of bacterial meningitis patients do not have any of the classic findings
• Half of viral meningitis cases may have elevated neutrophils
Term
Chronic Meningitis: Causes
Definition
lBacterial
-Partially treated acute meningitis/parameningeal infection
-Mycobacterium tuberculosis
-Lyme Disease
-Syphilis
lFungal
-Cryptococcus neoformans
lProtozoal
-Toxoplasma gondii
lHelminthic
- Cysticercosis
lMeningeal/parameningeal infections
lMalignancy
lNoninfectious inflammatory d/o
lChemical meningitis
Term
Chronic Meningitis: Pathophysiology
Definition
lInflammation causes obstruction of CSF-hydrocephalus, increased ICP
lCognitive changes, cranial nerve deficits, seizures, myelopathy, stroke
lRadiculopathies/Myelopathies
Term
Chronic Meningitis: Signs and Symptoms
Definition
lHA
lNeck pain
lChange in mental status lWeakness
lVisual changes lNumbness
Term
Chronic Meningitis: Evaluation
Definition
lH&P (including recent travel/search for systemic disease) lLP
lPredominance of mononuclear cells
lCT/MRI-brain/spinal cord
lBlood Work lCXR
lUA etc.
Term
Brain Abscess: Epidemiology and Risk
Factors
Definition
• Focal, suppurative infection within brain parenchyma
• 1/100,000
• Risk factors
- Otitis media/mastoiditis/paranasal sinusitis
- Chest infections
- Penetrating head trauma/neurosurgery
- Dental infections
Term
Brain Abscess: Pathophysiology
Definition
- Days 1-3 early cerebritis
• Perivascular infiltration of inflammatory cells • Central core necrosis
• Edema
- Days 4-9 late cerebritis
• Pus, macrophages/fibroblasts
- Days 10-13 early capsule formation • Ring-enhancing
- Days 14+ late capsule formation • Necrotic center with capsule
Term
Brain Abscess: Causes
Definition
- Otitis media/mastoiditis
• Streptococci
• Bacteroides spp.
• P. aeruginosa
Enterobacteriaceae
- Paranasal Sinusitis
• Streptococci
• Haemophilus spp. • Bacteroides spp.
• Pseudomonas spp. • S. aureus
- Endocarditis
• Viridans Streptococci or
S. aureus
- Lung
• Streptococci
• Staphylococci
• Bacteroides
• Fusobacterium spp.
- Urine
• Enterobacteriaceae or P. aeruginosa
Term
Brain Abscess: Causes
Definition
- Head Trauma/Neurosurgery
• Staphylococci
• Enterobacteriaceae
• Pseudomonas spp.
Term
Brain Abscess: Signs and Symptoms
Definition
• Headache-constant, dull, aching • Fever
• Seizure
• Focal neuro deficit
- Hemiparesis
- Aphasia
- Visual field defects
• Increased ICP
• Deficits depend on part of brain affected • No meningismus
Term
Brain Abscess: Evaluation
Definition
• MRI, CT
• Needle aspiration-gram stain/cx results
• Blood cx
• Blood work
Term
Brain Abscess: Treatment
Definition
• Treatment-drainage
- Antibiotics 6-8 weeks and serial MRI/CT
• Community Acquired
- 3rd generation cephalosporin
- Metronidazole
• Head trauma/neurosurgery
- Ceftazidime-Pseudomonas spp.
- Vanco-staphylococci
• AEDs
Term
Brain Abscess: Complications
Definition
• Seizures
• Persistent weakness • Aphasia
• Mental impairment
• Mortality <15%
Term
SUBDURAL EMPYEMA Epidemiology, Risk Factors, Causes
Definition
• Rare-15-20% of focal suppurative CNS infections
• Sinusitis
• Head trauma/
neurosurgery
• Males>females 3:1
• 20s-30s

• Etiology
• Streptococci
• Staphlococci
• Enterobacteriaceae • Anaerobic bacteria
Term
SUBDURAL EMPYEMA Pathophysiology
Definition
• Thrombophlebitis of veins draining sinuses
• Osteomyelitis
• Neurosurgery
Term
SUBDURAL EMPYEMA Signs and Symptoms
Definition
• Fever
•HA
• Sinusitis
• Neuro deficits-weakness
• Seizures
• Nuchal rigidity
• Increased ICP
• Decreased level of consciousness
Term
SUBDURAL EMPYEMA Evolution and Treatment
Definition
• DX-MRI/CT
• Treatment- a medical emergency!
- Requires drainage-burr holes vs craniotomy
- Empiric therapy-min 4w
• 3rd generation
cephalosporin
• Vancomycin
• Metronidazole
• Narrow coverage with gram stain/cx results
Term
SUBDURAL EMPYEMA complications/prognosis
Definition
• Seizures/hemiparesis
• Prognosis depends upon-
- PE at time of presentation
- Size of collection
- Time elapsed until drainage
Term
EPIDURAL ABSCESS

Epidemiology
Definition
• Between skull and dura
• Average age >50 years old
• Account for <2% of focal suppurative CNS infections
• Prognosis
- Mortality <5%
- Likely full recovery
Term
EPIDURAL ABSCESS risk factors
Definition
• Diabetes mellitus
• Spinal trauma/surgery
• IV drug abuse
• Alcoholism
• Renal insufficiency
• Immunosuppression
- Chronic steroids, cirrhosis, cancer, infection
• Pregnancy
Term
EPIDURAL ABSCESS pathophys
Definition
• Direct extension (10-30%)
- Osteomyelitis, soft tissue
• Hematogenous spread (50%)
• Instrumentation (15-20%)
- Surgery, epidural injection
• Unknown (~30%)
Term
EPIDURAL ABSCESS causes
Definition
- Sources
• Surgery-
osteomyelitis
• Fracture
• Sinusitis, mastoiditis, otitis media
• Venous transmission
Term
EPIDURAL ABSCESS Signs and Symptoms
Definition
• Fever
• HA
• Nuchal rigidity
• Seizures
• Focal neuro deficits
• Change in mental status
• Wound infection-post-op
• Early presentation maybe non-specific

• Stage 1
• Severe back pain and
fever
• Stage 2
• Spinal irritation and
radicular pain
• Stage 3
• Fecal and urinary
incontinence
• Stage 4
• Paralysis
Term
EPIDURAL ABSCESS Evaluation and Treatment
Definition
- Physical exam
• Spinal- tenderness
• Neurologic exam- complete
• Rectal exam
- Evaluation
• CBC
• Sed rate/CRP
• Blood cultures
• MRI/CT • MRI best
• Drainage
• Empiric therapy
- 3rd gen. cephalosporin, nafcillin, or vancomycin and metronidazole
- 3 week treatment minimum after drainage
- Narrow antibiotic treatment after culture results obtained
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