Correction of Cerebrospinal Fluid Protein for the Presence of Red Blood
Cells in Children with a Traumatic Lumbar Puncture
Lise E. Nigrovic, MD, MPH, Samir S. Shah, MD, MSCE, and Mark I. Neuman, MD, MPH
We sought to determine the relationship between cerebrospinal fluid (CSF) protein and CSF red blood cells in chil-
dren with traumatic lumbar punctures. For every 1000 cell increase in CSF red blood cells per mm3, CSF protein
increases by 1.1 mg/dL (95% CI, 0.9-1.1 mg/dL). (J Pediatr 2011;-:---)
A
traumatic lumbar puncture (LP) occurs when the
needle used to perform the procedure unintentionally
causes bleeding in the subarachnoid space. In chil-
dren, rates of traumatic LPs may be as high as 30% depending
on clinical setting, patient age, and red blood cell (RBC)
threshold used.1,2 The introduction of peripheral blood
into the cerebrospinal fluid (CSF) complicates the interpreta-
tion of CSF results by increasing both CSF white blood cells
(WBCs) and CSF protein (because of both the higher protein
concentration in plasma compared with CSF and the release
of proteins from lysed RBCs). Therefore, the interpretation of
CSF protein may be obscured in cases in which the CSF RBC
count is elevated. Because bacterial meningitis may be more
difficult to exclude on the basis of CSF test results, children
with a traumatic LP may be unnecessarily hospitalized and
given parenteral antibiotics.
Although investigators have studied methods of correcting
observed CSF WBCs for the presence of CSF RBCs,3,4
approaches to correct CSF protein have not been based on
rigorous studies.5,6 Therefore, we sought to further explore
the relationship between CSF RBC and CSF protein in a large
prospective cohort of children who had an LP performed in
the emergency department (ED) of a single children’s hospital.
Methods
We performed a secondary analysis of a prospective cohort
study of children undergoing a LP in the ED at a single tertiary
care children’s hospital between July 2003 and January 2005.
The study was approved by the institutional review board, and
study methods have been described in detail previously.1 Spe-
cific methods pertinent to this subanalysis are provided.
Physicians performing an LP in the ED completed a brief
study form at the time of the procedure. For this analysis, we
only included children who had both CSF cell count and chem-
istry results available. We excluded patients with conditions
known to elevate CSF protein, including bacterial meningitis,
aseptic meningitis (with positive enteroviral polymerase chain
CSF Cerebrospinal fluid
ED Emergency department
LP Lumbar puncture
RBC Red blood cell
WBC White blood cell
reaction or herpes simplex virus polymerase chain reaction test-
ing or Lyme serology when performed), demyelinating condi-
tions, recent neurosurgery, or presence of a ventricular shunt.
We reviewed the electronic medical record to evaluate
eligibility criteria and to abstract laboratory data. We defined
a traumatic LP as CSF RBC $1000 cells/mm3.
The c2 test was used to compare proportions and linear
regression to measure the association between CSF RBC
and CSF protein (with R2 as a measure of model fit). We
analyzed these 4 groups of children: (1) all eligible patients;
(2) patients without CSF pleocytosis (defined as CSF WBC
<10 cells/mm3) corrected for the presence of CSF RBCs
with a ratio of 500 CSF RBCs to 1 CSF WBC),3,7 because cen-
tral nervous infections typically increase both CSF WBC and
CSF protein; (3) patients #90 days of age; and (4) patients
with traumatic LPs (CSF RBCs $1000 cells/mm3) in whom
the impact of CSF RBCs on CSF protein is likely to be greatest.
For all analyses, we used Statistical Program for the Social
Sciences version 18.0.0 (SPSS, Somers, New York).
Results
A total of 1474 eligible LPs were performed in the ED during
the study period, and 1459 patients (99% of eligible patients)
were enrolled in the study. Of those patients, 1354 (93% of en-
rolled patients) had CSF cell counts and chemistry analysis
available. We excluded 56 patients for these reasons: bacterial
meningitis (n = 10), aseptic meningitis (n = 40; enterovirus
[n = 29], herpes simplex virus [n = 3], and Lyme meningitis
[n = 8]), demyelinating conditions (n = 2), recent neurosur-
gery (n = 1), and presence of a ventricular shunt (n = 3). The
remaining 1298 children were included in our study.
The median age of study patients was 3 months (range,
0 days to 23 years) and 706 patients (54%) were male. Most
patients (75%) had LP performed to evaluate for central
From the Division of Emergency Medicine, Department of Pediatrics, Children’s
Hospital Boston and Harvard Medical School, Boston, MA (L.N., M.N.); and Division
of Infectious Diseases, The Children’s Hospital of Philadelphia and the Departments
of Pediatrics and Biostatistics and Epidemiology, University of Pennsylvania School
of Medicine, Philadelphia, PA (S.S.)
Supported by National Research Service Award (Research Training Grant in Pedi-
atric Emergency Medicine T32 HD40128-01). The authors declare no conflicts of
interest.
0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2011.02.038
1
THE JOURNAL OF PEDIATRICS  www.jpeds.com
Figure. Scatter plot of CSF RBC (cells/mm3) versus CSF
protein level (mg/dL; n = 1298).
nervous system infection. Of the 1298 study patients, 189
(15%) had a traumatic LP. Hospitalization was more com-
mon for patients with traumatic LP (65%) than non-
traumatic LP (47%; P < .001).
CSF protein increased linearly with increasing CSF RBCs
(Figure). Overall, CSF protein increased by 1.1 mg/dL for
every 1000 cell increase in CSR RBCs. The relationship was
similar for all 4 groups of study patients (Table).
Discussion
Unintentional introduction of peripheral blood into the CSF
can complicate interpretation of LP results. Traumatic LPs
were common in our prospective ED study. For children
with a traumatic LP, CSF protein levels should be corrected
for the presence of CSF RBCs by subtracting 1.1 mg/dL pro-
tein per 1000 RBCs cells/mm3.
Elevated CSF protein levels is a nonspecific indicator of CSF
inflammation or infection. CSF protein has been used in sev-
eral clinical decision rules to distinguish bacterial from aseptic
meningitis.8-10 The bacterial meningitis score, which has been
validated in a variety of settings,10,11 includes CSF protein
level $80 mg/dL as a high-risk predictor of bacterial menin-
gitis. In children with a traumatic LP, CSF should be inter-
preted only after correction for the presence of CSF RBCs.
Table. The relationship between cerebrospinal fluid red
blood cell and cerebrospinal fluid protein
Patient group Number of patients ß-coefficient 95% CI
All eligible 1298 1.1
No CSF pleocytosis* 1097 1.1
Age #90 days of age 667 1.0
Traumatic LP† 189 0.9
*Defined as CSF WBC <10 cells/mm3 corrected for the presence of CSF RBCs by using ratio of
500 CSF RBCs to 1 CSF WBC.
†
Defined as CSF RBC $1000 cells/mm3.
2 Nigrovic, Shah, and Neuman
Vol. -, No. -
A child with a traumatic LP may still be considered at very
low risk of having bacterial meningitis if the corrected CSF
protein is <80 mg/dL and no other risk factor is present.10
Our study has some limitations. First, our analysis was lim-
ited to enrolled patients. However, this limitation is unlikely to
substantially affect our findings because 99% of potentially el-
igible patients were included. Second, there was a relatively
small number of patients with traumatic LPs, which limited
our ability to perform important subgroup analyses. Lastly, it
is possible that we included patients with meningitis, in
whom the etiologic agent was not identified (ie, viral meningi-
tis in the child for whom viral testing was not performed). This
latter limitation might cause us to overestimate the magnitude
of the correction factor, but such overestimation is less likely
because the results were similar in the subanalysis restricted
to children without CSF pleocytosis. Although we did not spe-
cifically study the relationship between CSF RBCs and CSF
WBCs, we corrected CSF WBC for CSF RBC for the subanalysis
of children without pleocytosis. This 500 RBC for 1 WBC
correction factor has been sought in the literature.12 n
Submitted for publication Nov 23, 2010; last revision received Feb 3, 2011;
accepted Feb 28, 2011.
Reprint requests: Lise E. Nigrovic, MD, MPH, Division of Emergency Medicine,
Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115. E-mail:
lise.nigrovic@childrens.harvard.edu
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