Cerebrospinal fluid evaluation

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Chapter 8 CEREBROSPINAL FLUID EVALUATION

Theodore X. O’Connell

General Discussion

Lumbar puncture (LP) is a commonly performed procedure in pediatrics, used most commonly to evaluate for the presence of meningitis. Commonly performed tests on cerebrospinal fluid (CSF) include protein and glucose levels, cell counts and differential, microscopic examination, and culture. Additional tests—such as opening pressure, supernatant color, latex agglutination, and polymerase chain reaction—also may be performed.

Protein concentrations usually are elevated in patients with bacterial meningitis. Values less than 40 mg/dL are considered normal in infants and children. The CSF protein may be elevated in many processes, including infectious, immunologic, vascular, and degenerative diseases as well as tumors of the brain and spinal cord. The CSF protein may be increased after a bloody tap by approximately 1 mg/dL for every 1000 mm3. Values greater than 100 mg/dL suggest that bacterial infection is present. However, protein concentrations of more than 100 to 120 mg/dL commonly are observed in healthy, uninfected newborn infants, especially premature infants.

In most patients with bacterial meningitis, the CSF glucose concentration is low as a result of increased metabolic demands. A CSF glucose concentration that is less than half the simultaneously obtained blood glucose concentration usually is considered abnormal.

Normal white blood cell (WBC) count values depend on the patient’s age. In patients with acute bacterial meningitis, the cell count can be extremely variable, but it is usually in the range of 1000 to 5000 leukocytes/mm3. However, very early in the illness, the cell count may be normal despite a positive CSF culture. Polymorphonuclear (PMN) cells are always abnormal in a child, but 1 to 2/mm3 may be present in a normal neonate. An elevated PMN count suggests bacterial meningitis or the early phase of an aseptic meningitis. CSF lymphocytes indicates aseptic, tuberculous, or fungal meningitis; demyelinating diseases; brain or spinal cord tumor; immunologic disorders (including collagen vascular diseases); and chemical irritation (post myelogram, intrathecal methotrexate).

Normal CSF contains no red blood cells (RBCs). The presence of RBCs indicates a traumatic tap or a subarachnoid hemorrhage. Progressive clearing of blood CSF is noted during collection of the fluid in the case of a traumatic lumbar puncture.

The probability of seeing bacteria on a Gram-stained CSF preparation is dependent on the number of organisms present. The sensitivity is approximately 80% in a properly prepared smear but is lower when Listeria monocytogenes is the cause of meningitis.

Culture should be performed routinely on all spinal fluid specimens, even those that are grossly normal or have normal leukocyte count. The yield of CSF culture is lower in patients previously treated with antibiotics.

The mean opening lumbar CSF pressure is variable, depending on the age of the child. These pressures are outlined in Table 8-1. Opening pressures may exceed 150 to 200 mm H20 when bacterial meningitis is present.

Table 8-1 Evaluation of Cerebrospinal Fluid

  WBC Count Mean % PMNs
Preterm 0-25 WBCs/mm3 57%
Term 0-22 WBCs/mm3 61%
Child 0-7 WBCs/mm3 5%
Glucose    
   Preterm 24-63 mg/dL 1.3-3.5 mmol/L
   Term 34-119 mg/dL 1.9-6.6 mmol/L
   Child 40-80 mg/dL 2.2-4.4 mmol/L
CSF Glucose/Blood Glucose    
   Preterm 55%-105%  
   Term 44%-128%  
   Child 50%  
Lactic Acid Dehydrogenase    
   Normal range 5-30 U/L (or about 10% of serum value)  
Myelin Basic Protein <4 ng/mL  
Opening Pressure    
    (Lateral recumbent)    
   Newborn 8-11 cmH2O  
   Infant/Child <20 cmH2O  
   Respiratory Variations 0.5-1 cmH2O  
Protein    
   Preterm 65-150 mg/dL 0.65-1.5 g/L
   Term 20-170 mg/dL 0.20-1.7 g/L
   Child 5-40 mg/dL 0.05-0.40 g/L

CSF, cerebrospinal fluid; PMNs, polymorphonuclear lymphocytes; WBC, white blood cell.

Modified from Oski FA: Principles and Practice of Pediatrics, 3rd ed. Philadelphia: JB Lippincott, 1999 insert page number(s).

Latex agglutination allows rapid detection of bacterial antigens in CSF. Because false positives lead to unnecessary treatment, latex agglutination is not routinely used today. A positive antigen test result is usually meaningful, but a negative test result is unreliable for excluding a diagnosis of bacterial meningitis. Latex agglutination can be useful in partially treated meningitis cases where cultures might not yield an organism. Latex agglutination also may be helpful in cases of suspected bacterial meningitis if the initial Gram stain and bacterial culture are negative after 48 hours.

Polymerase chain reaction (PCR) has been especially useful in the diagnosis of viral meningitis. PCR can be used to diagnose infection with enteroviruses, herpes simplex virus, varicella zoster virus, human herpes virus-6, Epstein-Barr virus, cytomegalovirus, arboviruses (California encephalitis group, Japanese encephalitis, West Nile virus, dengue fever virus types 1 to 4, and yellow fever virus).

Contraindications for performing an LP include (1) elevated intracranial pressure due to a suspected mass lesion of the brain or spinal cord, (2) symptoms and signs of pending cerebral herniation in a child with probable meningitis, (3) critical illness (on rare occasions), (4) skin infection at the site of the LP, and (5) thrombocytopenia.

Examination of the cerebrospinal fluid of a patient with acute bacterial meningitis characteristically reveals the following: (1) a cloudy appearance, (2) an increased WBC count with a polymorphonuclear predominance, (3) a low glucose concentration in relation to the serum glucose concentration, (4) an elevated protein concentration, (5) a smear and culture positive for the causative microorganism, and (6) a high monometric pressure. Table 8-2 shows the CSF findings in patients with bacterial meningitis.

The spinal fluid in children with aseptic or proven viral meningitis characteristically shows an increase in lymphocytes and a normal or slightly decreased glucose concentration with a slightly elevated protein concentration. If the CSF is obtained early in the disease process, a large number of PMN cells may be present. A repeat lumbar puncture 24 to 48 hours later can demonstrate the typical lymphocyte predominance. PCR can provide a specific diagnosis within hours, especially for herpes virus and enteroviruses.

Tuberculous meningitis can be clinically indistinguishable from acute bacterial meningitis. The diagnosis of tuberculous meningitis can be established by (1) an increase in the number of CSF leukocytes, usually from 50 to 500 cells/mm3, with a lymphocyte predominance, low glucose concentration, very elevated protein concentration, and a culture negative for the usual pathogenic organisms but subsequently positive for tubercle bacilli; (2) a positive tuberculin skin test; (3) chest radiographs showing evidence of a tuberculous lesion; and (4) a positive history of contact with an active case of tuberculosis.

Most infectious causes of chronic meningitis elicit similar CSF abnormalities: a mildly elevated protein concentration, a normal glucose level, and fewer than 500 WBCs/mm3 with lymphocyte predominance. Table 8-3 outlines distinctive patterns of leukocyte predominance that may aid diagnosis.

Suggested Work-up

CSF evaluation:

See preceding text Blood culture Should be performed if meningitis is suspected, especially if antibiotics will be started empirically before examination of CSF

Additional Work-up

CSF opening pressure See preceding text
CSF latex agglutination See preceding text
CSF PCR:

As clinically indicated (see preceding text)   CSF oligocolonal bands If multiple sclerosis is suspected CSF lactate, amino acids, and endolase If metabolic diseases are suspected