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

CNS Infections Portals of entry for bacteria Respiratory (most common route of community-acquired infections) Auditory Bloodstream Neural routes Contiguous sites

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 Meningitis Peaks in winter & early spring Symptoms 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

Bacterial CNS Infections (cont’d) Acute Bacterial Meningitis (cont’d) Adolescents N. meningitidis S. pneumoniae Adults Elderly Gram-negative bacilli

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 None Cell count (leukocytes/mL) 100-100,000 Neutrophils predominate Normal- 500 Lymphocytes predominate 50-500 Normal-200 100-750 Lymphocytes/ Eosinophils Protein (mg/dL) 100-500 Normal- 250 Normal- 150 Frequently normal 50- 250 Usually increased Glucose (mg/dL) <30 Normal- decreased <45 Normal

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.