Infections of the Central Nervous System

MLAB 2434 – Microbiology Keri Brophy-Martinez

General Concepts

Infections of the CNS are of critical concern and positive laboratory findings are “critical values”

Infections may be caused by bacteria, fungi, viruses or parasites

Anatomy of CNS

Brain, Spinal Cord and Cranial Nerves Meninges

Dura mater Pia arachnoid Pia mater

Subarachnoid space between pia arachnoid and pia mater; CSF

CSF

Unique body fluid produced by filtration and secretion from specialized capillary tufts of the four ventricles of the brain

Circulates around brain and spinal cord under pressure

Serves as cushion for brain and spinal cord

CSF Characteristics

CSF is a clear and colorless sterile fluid Adults

• Protein 15-45 mg/dL• Glucose 40-80 mg/dL• WBC 0-5 mm3

Newborns• Higher levels of protein & glucose

Infections indicated by increased cell counts and alterations in protein and glucose

Portals of entry for bacteriaRespiratory (most common route

of community-acquired infections)

AuditoryBloodstreamNeural routesContiguous sites

CNS Infections

Types of CNS Infections

Meningitis Also called “leptomeningitis” (pia

mater & arachnoid) Inflammation around blood vessels

within the subarachnoid space Classifications

• Acute• Chronic• Aseptic

Bacterial CNS Infections

Acute Bacterial MeningitisPeaks in winter & early springSymptoms include photophobia,

headache, nausea, vomiting, and stiff neck or Brundzinski sign

In infants, only symptoms may be irritability, poor feeding, and restlessness

Bacterial CNS Infections (cont’d) Acute Bacterial Meningitis (cont’d)

Infants• Group B Strep• L. monocytogenes• H. influenzae• S. pneumoniae• E. coli

Children• N. meningitidis• S. pneumoniae• H. influenzae

Bacterial CNS Infections (cont’d) Acute Bacterial Meningitis (cont’d)

Adolescents• N. meningitidis• S. pneumoniae

Adults• N. meningitidis• S. pneumoniae

Elderly• Gram-negative bacilli• N. meningitidis• S. pneumoniae

Bacterial CNS Infections (cont’d) Acute Bacterial Meningitis

(cont’d)Lab findings

• Leukocytosis with left shift and toxic changes, such as toxic granulation & Dohle bodies

• Increased CSF protein• Decreased CSF glucose

Increased intracranial pressure

Types of CNS Infections (cont’d)

“Aseptic Meningitis”CSF shows predominance of

lymphocytes with no organisms on direct examination

Commonly caused by viruses• Enterovirus• Arbovirus• Mumps virus• Herpes Simplex Virus

Types of CNS Infections (cont’d) Encephalitis/ Meningoencephalitis

Diffuse inflammation of the cerebral cortex

Observe mental changes or neurologic signs

Common in viral infections

Types of CNS Infections (cont’d)

Brain Abscesses Areas of tissue destruction containing

organisms and inflammatory cells Occur as spread from other body sites

or trauma to skull; infecting organism depends on predisposing conditions

Non-traumatic abscesses mostly are aerobic and anaerobic streptococci, Staphylococcus aureus, anaerobic GNR

Bacterial CNS Infections (cont’d) Mycobacterial Infection

Most commonly M. tuberculosis Enters by respiratory route and spread

via bloodstream CSF cells are mostly lymphocytes and

monocytes Mycobacteria are few and CSF should

be centrifuged to concentrate before culturing/gram staining

Bacterial CNS Infections (cont’d) Spirochetal Infections

Lyme Disease Neurosyphilis

Viral Infections Enterovirus Arboviruses Herpes Virus

Parasitic Infections Toxoplasma gondii Naegleria fowleri

Fungal Infections Crytococcus neoformans Candida species

Laboratory Diagnosis of CNS Infections CSF Collection

Lumbar puncture in lower back 3 to 4 tubes collected

• 1st = chemistries• 2nd = microbiology• 3rd = cell counts• 4th = special procedures (if collected)

Process ASAP

Laboratory Diagnosis of CNS Infections (cont’d) CSF Analysis

Acute Bacterial Meningitis• CSF turbid or cloudy• WBC increased with predominance of neutrophils• Increased CSF protein• Decreased CSF glucose

Centrifugation concentrates organisms Should be plated on at least BAP, CA and

broth; MAC if Gram-negative bacilli are expected

Bacterial Antigen Testing • Current literature indicates routine bacterial

antigen testing is of limited value

Laboratory Diagnosis of CNS Infections (cont’d) CSF Analysis

Viral Meningitis• Number of lymphocytes increased• Diagnosis based on PCR or EIA

Fungal Meningitis• Gram stain or India ink• Culture held for 4-6 weeks

Laboratory Diagnosis of CNS Infections (cont’d) CSF Analysis

Tuberculous meningitis• Increase in lymphocytes• Increase in protein• Decrease in glucose• AFB stain & culture • PCR can be used; however, false

positives common

Characteristic Findings in Meningitis

Bacterial Fungal Tuberculous Viral Syphilitic Parasitic

Organisms seen in CSF

See notes See notes See notes None None See notes

Cell count

(leukocytes/mL)

100-100,000

Neutrophils predominate

Normal- 500

Lymphocytes

predominate

50-500

Lymphocytes

predominate

Normal-200

Lymphocytes

predominate

100-750

Lymphocytes

predominate

Normal-200

Lymphocytes/

Eosinophils

predominate

Protein (mg/dL) 100-500 Normal- 250 Normal- 150 Frequently normal

50- 250 Usually increased

Glucose (mg/dL) <30 Normal- decreased

<45 Normal Normal Normal- decreased

References

Kiser, K. M., Payne, W. C., & Taff, T. A. (2011). Clinical Laboratory Microbiology: A Practical Approach . Upper Saddle River, NJ: Pearson Education.

Mahon, C. R., Lehman, D. C., & Manuselis, G. (2011). Textbook of Diagnostic Microbiology (4th ed.). Maryland Heights, MO: Saunders.