CNS Infections Margrit Carlson, M.D. November 2003
Dec 28, 2015
CNS Infections
Margrit Carlson, M.D.
November 2003
How are infections in the CNS different?
Separated by the blood brain barrier
Immunologically distinct
Unique anatomic considerations dictate the spread of infection within the CNS
Closed space
Limited capacity for regeneration or compensation for injury
Blood Brain Barrier
Between blood and brain formed by the tight junctions of the cerebral capillary endothelium
Between blood and CSF formed by the tight junctions of the choroid plexus epithelium
Immune Response in the CNS
Access of immune effector cells to CNS is limited by the BBB
T lymphocytes can enter and exit the CNS in small numbers
Low expression of MHC molecules limits antigen presentation
Entry into the CNS
Bypassing the blood brain barrier direct extension from a local focus,
sinuses
middle ear or mastoid
dental source foreign body trauma
Entry through the BBB
direct penetration of the choroid plexus epithelium into the CSF (meningitis)
direct penetration of the capillary endothelium into the brain parenchyma (encephalitis)
disruption of the tight junctions
transportation across the barrier inside leukocytes
Types of infections
Meningitis- subarachnoid Encephalitis-brain parenchyma Abscess
subdural
brain
epidural
Cerebrospinal Fluid in Meningitis
Pressure Glucose Protein WBCNormal 180mm 2/3 of serum up to50 0-5
Bacterial I <40 50-1500 50-5000P
Viral N N N <100L
Chronic I 10-45 45-500 25-1000L
I=Increased N =Normal
P=polymorphonuclear leukocytes L=Lymphocyte
CSF Parameters
Pressure Glucose Protein WBCNormal 180mm 2/3 of serum 50 0-5
Abscess I N 30-20010-500 L
Encephalitis N N 20-125 20-200 L
I=Increased N =Normal
P=polymorphonuclear leukocytes L=Lymphocyte
Acute Meningitis
19 yo student is seen for sore throat x2 days. His symptoms worsen and he develops a terrible headache and photophobia. He is brought to the ER the next morning by his roommate. In the ER he is hypotensive, confused, complaining of headache and photophobia. He has a seizure.
He is given antibiotics and taken for a CT scan which is unremarkable.
CSF RBC 10 WBC 1230 93% PMNs glucose 33protein 276
Acute meningitis
Meningeal signs and symptoms worsen over a few days
symptoms: headache, fever, neck stiffness, photophobia and vomiting.
signs: nuchal rigidity, altered level of consciousness, seizures and cranial nerve palsies(sensorineural hearing loss)
Bacterial Meningitis 0-4 weeks Streptococcus agalactiae, E.
coli, Listeria monocytogenes
4-12 weeks H. influenzae, E. coli, L. monocytogenes, S.agalactiae,
3mo-18 years H. influenzae, N. meningiditis, S. pneumoniae
18-50 years S. pneumoniae, N. meningiditis
36 YO G3P2, 33 week IUP brought in by her sister for chest pain and confusion increasing over the last 3 days.
PE: temp was 38.5, she had photophobia but no nuccal rigidity. A vesicular rash was seen on her L chest
CSF: 320 RBC, 460 WBC, 50% lymphs and 34% monos
protein 623, glucose 91
Her MRI had diffuse meningeal enhancement
Meningitis in the Immunocompromised Host
Bacterial Syphilis, Listeria, Nocardia
Viral VZV, HSV
Fungal cryptococcus, coccidioidomycosis, histoplasmosis
Mycobacterial tuberculosis
44 yo construction worker had upper respiratory symptoms 1 month ago. He has had worsening fevers, a constant headache and photophobia for a month. His thinking has been slowed and he had an episode of aphasia lasting 1 day.
CSF: glucose 27protein 203RBC <1WBC 203
45%lymphs/40% mono/5% eos MRI: enhancement of the basal
cisterns, along the midbrain, pons, right optic tract, and the right caudate head.
Chronic meningitis
Gradual onset and progression
Focal symptoms
Increased intracranial pressure
History of exposure
Immunocompromised ?
Symptoms of Increased Intracranial Pressure
headache nausea, vomiting altered mental status ataxia incontinence papilledema 3rd or 6th nerve palsy
Infectious causes of chronic meningitis
Coccidioidomycosis, Cryptococcus, Histoplasmosis, Sporotrichosis
Tuberculosis
Syphilis, Lyme Disease
HIV, Enterovirus
Non-infectious causes of Chronic Meningitis
Behcet’s disease
Systemic lupus erythematosis
Sarcoidosis
Carcinomatous or lymphomatous meningitis
Granulomatous angiitis
Complications of Chronic Meningitis
hydrocephalus
vasculitis, cerebrovascular occlusion
cranial nerve palsies
32 yo Hispanic man has new onset confusion developing over 24 hours, aphasia, hallucinations and seizures following a bone marrow transplant for CML. He has no known ill contacts. He has had mucositis
Putting it all together
Sudden or gradual onset? Meningeal symptoms, encephalopathy? Focal findings? Fever ? Predisposing conditions and exposures Imaging LP results
CSF: glucose 67
protein 158RBC 179WBC 124 25% P /74% L
His MRI shows diffuse periventricular white matter disease and enhancement in the temporal lobes.
Acute Encephalitis
Fever Headache Altered level of consciousness: lethargy,
confusion, stupor, coma Seizures Hypothalamic or pituitary dysfunction
Causes of Acute Encephalitis
Herpes simplex, Varicella zoster
California, St Louis, Japanese, Western and Eastern equine encephalitis viruses
Enteroviruses (coxsackie, echo and enteroviruses)
Post measles, post influenza encephalomyelitis
HSV Pathogenesis
Retrograde transport of virus from mucous membranes to the sensory ganglia and rarely to the CNS
Anterograde transport from the sensory ganglia to the periphery during cutaneous exacerbations
33 yo with AIDS,CD4 cells 5, brought in by his partner who has noticed he has become more forgetful and withdrawn over the last 3-6 months.
He’s had no fevers or headache. No recent infections. He has been off antiretrovirals because of side effects.
MRI showed diffuse atrophy
CSF glucose 88protein 78RBC <1WBC 12 74% lymphs
26% monos
Chronic Encephalitis
Predominantly viral
Non-viral: Neurosyphilis, Lyme disease,
Neurotropic viruses:
Retroviruses: HTLV I and II, HIV
Herpes viruses: HSV, VZV and CMV
Chronic Encephalitis
Other:
JC virus: Progressive multifocal leukoencephalopathy
Subacute Sclerosing panencephalitis (Measles)
Rubella
Creutzfeldt-Jakob
HIV EncephalopathyAIDS Dementia Complex
7-27% of persons with CD4<200 have some impairment including:
decreased attention and concentration psychomotor slowing personality change, loss of initiative, drive,
animation hyperreflexia, ataxia, frontal release signs
Pathogenesis of ADC
HIV is present in the CSF and brain in primary infection.
HIV infects cells of monocyte lineage (macrophages, microglia, multinucleated giant cells).
Viral burden (HIV qPCR) in CSF or brain correlates with neurologic disease.
Pathogenesis of ADC
Release of neurotoxins from macrophages (nitric oxide, arachidonic acid, quinolinic acid).
Cytokine mediated release of neurotoxins.
Direct toxicity of viral proteins, i.e. gp120.
73 yo man with a fever who is brought in by his wife because he is confused and unable to move his right side.
He was complaining of a headache for a few days. He started vomiting this morning and was bumping into the wall on his way to the bathroom.
Brain Abscess
hematogenous spread through the blood brain barrier
direct extension via the the emissary veins into the cerebral venous circulation
Development of an abscess
Local area of cerebritis, inflammation and edema (1-3 days)
Expansion and development of a necrotic center (4-9 days)
Formation of a ring enhancing capsule by gliosis and fibrosis (14 days)
Clinical Presentation
Headache with gradual worsening Fever <50% Focal neurologic signs Seizures CSF: elevated protein, normal glucose
and mild leukocytosis Increased ICP: Nausea,vomiting, lethargy
Brain Abscess
Location
Source
Organism
Treatment
Brain Abscess
Paranasal Sinuses Frontal lobe
Otogenic Infection Temporal lobe, cerebellum
Hematogenous spread Multiple lesions MCA distribution
Post traumatic Site of wound
Post operative Site of surgery
Pathogens
Sinuses Streptococci, Haemophilus, Bacteroides, Fusobacterium
Otogenic as above, and Pseudomonas
Endocarditis Staphylococcus, Viridans streptococci
Lung abscess Streptococci, anaerobes, Actinomyces
Trauma Staph aureus
A 28 YO father of 3 develops worsening sinus headaches and is seen repeatedly at an outside ER. He has low grade fevers. His headache becomes excruciating and he subsequently becomes unresponsive during his evaluation.
Brain Abscess in the Immunocompromised
AIDS
Toxoplasmosis, Tuberculoma, Cryptococcoma, Coccidiodomycosis, Blastomycosis
Transplant
Aspergillus, Nocardia, Candida, Zygomycetes in addition to the above
35 YO man with 2 weeks of worsening headache, low grade fever and rash. He also has had myalgias and L knee pain and swelling.
He has no recent travel or outdoor activities, not sexually active x 6 months
CT Scan is unremarkable
CSF: 2 RBC, 25 WBC;20%segs, 60% lymphs, 20% monocytes, glucose 64, protein 45.
Fever, Headache,Rash and mild CSF pleocytosis
Enterovirus
Primary HIV
Epstein Barr
Secondary syphilis
Mycoplasma
Drug Reaction
Neurosyphilis
Primary, chancre 10-90 days Secondary,rash 4-10 weeks later (up to
6 months after initial infection Meningeal within 1st year after infection Meningovascular 4-7 years later Parenchymal disease decades later
Syphilis 50-75% of exposed partners were
infected. 30-70% of those with secondary syphilis
have CSF mononuclear pleocytosis, elevated protein or + RPR in CSF
25% untreated patients have recurrances 1/3 of untreated patients develop late
sequelae