Østergaard et al.

BMC Clinical Pathology (2017) 17:15

DOI 10.1186/s12907-017-0053-0

RESEARCH ARTICLE Open Access

Cerebrospinal fluid pleocytosis level as a

diagnostic predictor? A cross-sectional
study
Anne Ahrens Østergaard1, Thomas Vognbjerg Sydenham2, Mads Nybo3,4 and Åse Bengård Andersen1,4,5*

Abstract
Background: Lumbar puncture with quantification of leukocytes and differential count of cellular subsets in the
cerebrospinal fluid is a standard procedure in cases of suspected neuroinfectious conditions. However, a number of
non-infectious causes may result in a low leukocyte number (0–1000 cells/ml). We wanted to assess the diagnostic
diversity of unselected adult patients with pleocytosis in the cerebrospinal fluid.
Methods: The study is based on data from cerebrospinal fluid (CSF) analyses of all adult patients (15 years or older)
admitted to a large university hospital in Denmark during a two-year period (2008–2009). Data from the local patient
administrative system supplied with data from patient charts were combined with laboratory data.
Results: A total of 5390 cerebrospinal fluid samples from 3290 patients were included. Pleocytosis >5 leucocytes/μl
was found in samples from 262 patients of which 106 (40.5%) were caused by infection of the central nervous system
(CNS), 20 (7.6%) by infection outside CNS, 79 (30.2%) due to non-infectious neurological diseases, 23 (8.8%) by malignancy,
and 34 (13.0%) caused by other conditions. Significantly higher mean CSF leukocytes was found in patients suffering from
CNS infection (mean 1135 cells/μl, p-value <0.0001).
Conclusions: CNS infection, non-infectious neurological disease, malignancy, and infection outside CNS can cause
pleocytosis of the cerebrospinal fluid. Leukocyte counts above 100/μl is mainly caused by CNS infection, whereas the
number of differential diagnoses is higher if the CSF leukocyte counts is below 50/μl. These conditions are most commonly
caused by non-infectious neurological diseases including seizures.
Keywords: Cerebrospinal fluid, CSF, Pleocytosis, Lumbar puncture, Central nervous system infection, CNS infection, Seizures

Background other medical conditions, e.g. neurological, rheumatic or

Migration of leukocytes to the cerebrospinal fluid (CSF) malignant disease [5, 6]. Some patients with pleocytosis
is a cardinal symptom of an infectious condition affect- in the CSF never obtain a final diagnosis and in many
ing the meninges or the cerebral parenchyma. Bacterial settings the proportion of patients with “suspected CNS
and viral meningitis cannot reliably be differentiated infection” is larger than that of patients with proven
clinically and requires lumbar puncture to analyse the aetiology [1].
CSF [1, 2]. Patients suffering from viral meningitis Apart from the issue of a large overlap in leukocyte
present CSF leukocyte concentrations varying from 10 concentrations caused by viral and bacterial infections,
to 1000/μl, but typically below 500 [3]. In bacterial men- the relative distributions of the non-infectious diagnoses
ingitis CSF leukocytes vary from below 100 to more than are not well described. One reason for this is the fact
10,000 leukocytes/μl, often between 1000 and 5000/μl that these patients are dealt with by different clinical
[4]. However, pleocytosis in the CSF may also occur in specialities.

* Correspondence: Aase.Bengaard.Andersen@regionh.dk Methods

1
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
4
University of Southern Denmark, Odense, Denmark This study aimed at obtaining an overview of the relative
Full list of author information is available at the end of the article contribution of the causes of cerebrospinal pleocytosis
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 2 of 8

by a comprehensive method including all adult patients

(regardless indication for lumbar puncture, requesting
department, and symptomatology of the patient) admit-
ted to a large university hospital in Denmark during a
two-year period.
Pleocytosis is defined as increased cell count. In the
following the term pleocytosis will be used to describe
>5 leucocytes/μl in CSF. The study was performed at
Odense University Hospital, a large regional hospital in
Denmark with 1038 beds serving as referral hospital for
1.8 million inhabitants and holding all medical special-
ities including neurology, neurosurgery, rheumatology,
oncology and haematology.
Data from CSF analyses performed at the Department
of Clinical Biochemistry and Pharmacology from January
1st 2008 to December 31th 2009 (sample date, CSF leu-
kocytes, CSF monocytes, CSF polymorphonuclear leuko-
cytes, CSF protein, CSF glucose and plasma glucose) and
data from the patient administration system of Funen
County (FPAS; Fyns Patient Administrative System)
(patient age, sex, hospital admission dates, discharge
dates and discharge diagnoses) from 1994 to 2012 was
retrieved. In addition, we obtained data from the elec-
tronic patient records on hospital admissions and CSF
sample reports.
Only the initial CSF analysis requested with pleocytosis
(>5 leukocytes/μl after correction for erythrocytes (1
leucocyte/1000 erythrocytes)) in hospitalized patients at
age of 15 years or older were included. Exclusion criteria
were: not the first CSF sample in the time period, wrong
social security number, if the sample was not cerebro-
spinal fluid, if the erythrocytes were in layers or too
numerous to quantify, if a sample was collected by a
method different from lumbar puncture, or if the patient
was transferred to another hospital with an uncertain
diagnosis. If a sample was analysed more than once, the Fig. 1 Flowchart of study inclusion
report given to the clinician was used (Fig. 1). Discharge
diagnoses (ICD-10) were used to categorise the cause of
pleocytosis. However, the cause of pleocytosis was ad- disorder” and the suspected disorder was CNS infection;
justed in the following circumstances: 1) Discharge the cause of pleocytosis was changed to CNS infection,
diagnosis was not verified para-clinically (magnetic 5) the patient received full treatment for a CNS infection
resonance imaging (MRI)/computed tomography (CT), but this was not included in discharge summary; the
microbiological analyses, flow-cytometry, or autopsy) cause of pleocytosis was changed to CNS infection. 6)
and the discharge summary mentioned a diagnosis in the discharge diagnosis did not coincide with the pa-
plain text not coded as a discharge diagnosis; the cause tient chart or discharge summary; the cause of pleo-
of pleocytosis was changed to this diagnosis. 2) a CNS cytosis was changed to the cause mentioned in the
infection was mentioned in the discharge summary but chart. 7) a clear diagnosis was not made at time of
not included as a discharge diagnosis; Cause of pleocyto- discharge but was verified within 3 months after
sis was changed to CNS infection. 3) a discharge diagno- discharge date; this diagnosis was used as cause of
sis was not verified nor was CNS infection but a pleocytosis.
secondary diagnosis was verified; the cause of pleocytosis The category CNS infection was further divided into 2
was changed to this diagnosis. 4) Discharge diagnosis groups: verified and probable. A discharge diagnosis was
was “Observation for other suspected diseases and con- considered verified if the diagnosis was verified by MRI,
ditions” or “Observation for suspected nervous system CT, microbiological analyses, or autopsy.
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 3 of 8

Charlson index score [7] was used to describe patients (14.9%), and the department of intensive care (7.3%)
comorbidity. Charlson score estimating risk of death were the main contributors to CSF analyses.
from comorbid disease in longitudinal studies by scoring Patients were divided into diagnosis categories of CNS
each comorbid disease a score of 1, 2, 3, or 6.22 comor- infection, Infection outside CNS, Non-infectious neuro-
bidity conditions are included. Calculation was based on logical diseases, Malignancy, Other, and subgroups
registered diagnoses in the patient administration system (Appendix A). CNS infection amounted to 40.5% of the
from years 1994 to 2009. causes of pleocytosis. Infection outside CNS to 7.6%,
Non-infectious neurological diseases to 30.2%, Malignancy
8.8%, and Other 13.0%.
Statistical analysis
There was no significant difference in distribution of
Data processing was performed in STATA version 13.1–
sex in any of the categories (Table 1). Significantly lower
14.0. Wilcoxon/Mann-Whitney (Mann-Whitney U/
mean age was found in the Non-infectious neurological
Wilcoxon rank sum) test was performed for data not
diseases category (mean age 46.1, p-value 0.0088). Mean
normally distributed (sex, Charlson score, CSF leuko-
Charlson score in the 262 patients was 0.9, range 0–11.
cytes, CSF protein, CSF monocyte proportion, and
Mean Charlson score was significantly lower in the
CSF polymorph nuclear leukocyte proportion). Student’s
Non-infectious neurological diseases category (mean 0.6,
t-test was used if data was normally distributed (age). All
p-value 0.0125), while it was significantly higher in the
p-values were comparisons between the marked category
Malignancy (mean 2.7, p-value <0.001) than in all other
and the other categories. Only significant p-values (≤0.05)
categories. In general, there was a tendency of high
were included.
mean Charlson score in the categories with high
mean age.
Results In 141 patients mean CSF/plasma glucose ratio was
Out of 5390 unselected cerebrospinal fluid samples, 262 0.6 (normal). Significantly lower CSF/plasma glucose
met the inclusion criteria (Fig. 1). The neurological de- ratio was found in the decreased interval (<0.46) for
partment (56.5%), department of emergency admission CNS infection (mean 0.2, p 0.0085). Significant higher

Table 1 Summery of baseline findings by diagnosis category

Diagnosis category
CNS infection Infection outside CNS Non-infectious neurological Malignancy, all foci Other (n = 34) Total (n = 262)
(n = 106) (n = 20) diseases (n = 79) (n = 23)
Sexa n (%) n (%) n (%) n (%) n (%) n (%)
Male 49 (46.2) 11 (55.0) 43 (54.4) 14 (60.9) 16 (47.1) 133 (50.8)
Female 57 (53.8) 9 (45.0) 36 (45.6) 9 (39.1) 18 (52.9) 129 (49.2)
b
Age n (%) n (%) n (%) n (%) n (%) n (%)
< 36 yrs 26 (24.5) 5 (25.0) 24 (30.6) 2 (8.7) 7 (20.6) 64 (24.4)
36-51 yrs 31 (29.3) 27 (34.2) 6 (26.1)* 7 (20.6) 71 (27.1)
52-64 yrs 20 (18.9) 4 (20.0) 14 (17.7) 9 (39.1) 13 (38.2) 60 (22.9)
≥ 65 yrs 29 (27.4) 11 (55.0) 14 (17.7) 6 (26.1) 7 (20.6) 67 (25.6)
Mean 50.4 58.5 46.1* 59.1 52.0 50.7
Range 15–88 17–91 20–89 28–81 17–95 15–95
Charlson scorea n (%) n (%) n (%) n (%) n (%) n (%)
0 66 (62.3) 9 (45.0) 52 (65.8) 1 (4.4) 19 (55.9) 147 (56.1)
1 25 (23.6) 3 (15.0) 18 (22.8) 1 (4.4) 9 (26.5) 56 (21.4)
2 7 (6.6) 5 (25.0) 5 (6.3) 14 (60.9) 6 (17.7) 37 (14.1)
3 2 (1.9) 2 (10.0) 2 (2.5) 3 (13.0) 9 (3.4)
≥4 6 (5.7) 1 (5.0) 2 (2.5) 4 (17.4) 13 (5.0)
Mean 0.7 1.2 0.6 2.7** 0.6 0.9
Range 0–6 0–4 0–7 0–11 0–2 0–11
a
Wilcoxon-Mann-Whitney test
b
p-values calculated by Student’s t-test
*p-value <0.01
**p-value <0.001
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 4 of 8

CSF/plasma glucose ratio was found in the decreased in patients with CSF leukocytes below 100/μl. Infection
interval (<0.46) for Non-infectious neurological dis- outside CNS occurred primarily when CSF leukocytes
eases (mean 0.4, p 0.0276). were below 50/μl. CNS infection was the only category
The mean concentration of CSF leukocytes was 494/μl present in all intervals.
(Table 2). Significantly higher concentrations of mean The mean CSF protein concentration in all patients
CSF leukocytes were found in patients with CNS infec- was 1.0 g/l (Table 2). CSF protein was normal (0.2–
tion (mean 1135, p-value <0.001). In the category CNS 0.4 g/l) or decreased in 32.4% of all patients. All patients
infection no distinction between viral and bacterial neu- with CNS infection had a significantly higher level of
roinfection was made. When only verified diagnoses protein in CSF (mean 1.4) (p-value <0.0001). CNS pro-
were included, a higher concentration of CSF leukocytes tein is known to be increased in meningitis, but also to
were found in the category Meningitis, acute bacterial be one of the least specific parameters in CSF [4].
(p-value = 0.0002) (Table 5) compared to the others in Of the 106 patients with CNS infection 59 (55.7%)
CNS infection. were paraclinically confirmed. For the categories of
The proportion of patients in the CNS infection cat- malignancy 20 (87.0%), other 15 (44.1%), non-infectious
egory increased with increasing CSF leukocyte concen- neurologically disease 37 (46.8%), and other infection 10
tration, and at leukocyte counts above 100/μl CNS (50.0%) were paraclinically confirmed. Table 3 shows
infection was the most frequent cause of pleocytosis that more diagnoses in the CNS infection category were
(Fig. 2). Eighty seven point three percent of the pa- paraclinically verified as cell count increases. Mean pro-
tients with more than 200 leukocytes were diagnosed tein level was higher in the verified CNS infections than
with CNS infection. in probable CNS infection. CSF/plasma glucose ratios
In CSF samples with leukocytes below 50/μl especially shows a tendency of being lower in total in the verified
non-infectious neurological diagnoses should be consid- category and are in both groups the lowest when cell
ered as differential diagnoses, since the proportion of count is high.
CNS infection increased with increasing CSF leukocytes For six patients, seizures, epilepsy or status epilepticus
(Fig. 3). The category of Other seemed to occur mainly was the cause of pleocytosis. Two patients had <10

Table 2 Summary of CSF findings by diagnosis category

Diagnosis category
CNS infection Infection outside Non-infectious Malignancy, all Other (n = 34) Total (n = 262)
(n = 106) CNS (n = 20) neurological foci (n = 23)
diseases (n = 79)
CSF leukocytes/μla n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean]
6–10 11 (10.4) 8.1 10 (50.0) 7.3 32 (40.5) 7.3 8 (34.8) 7.4 14 (41.2) 7.2 75 (28.6) 7.4
>10–50 23 (21.7) 29.3 9 (45.0) 22.9 34 (43.0) 20.2 11 (47.8) 21.9 14 (41.2) 20.1 91 (34.7) 23.0
>50–100 8 (7.6) 84.0 3 (3.8) 66 2 (8.7) 62.5 5 (14.7) 69.8 18 (6.9) 74.7
>100–200 17 (16.0) 135.0 6 (7.6) 138 1 (2.9) 159 24 (9.2) 136.8
>200–400 13 (12.3) 266.4 1 (5.0) 221 2 (2.5) 247.5 1 (4.4) 347 17 (6.5) 266.2
>400–600 12 (11.3) 524.6 1 (1.3) 537 13 (5.0) 525.5
>600–800 2 (1.9) 744 2 (0.8) 744
>800–1000 3 (2.8) 896 3 (1.2) 896
>1000 17 (16.0) 6041.2 1 (1.3) 2015 1 (4.4) 1980 19 (7.3) 5615.5
Total 106 (100.0) 1135.5** 20 (100.0) 25.0* 79 (100.0) 63.2** 23 (100.0) 119.7 34 (100.0) 26.2* 262 (100.0) 494.3
CSF protein g/la n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean] n (%) [mean]
<0.2 1 (1.3) 0.0 1 (2.9) 0.0 2 (0.8) 0.0
0.2–0.4 18 (17.0) 0.4 12 (60.0) 0.3 34 (43.0) 0.3 8 (34.8) 0.3 11 (32.4) 0.4 83 (31.7) 0.3
0.41–1.11 50 (47.2) 0.7 8 (40.0) 0.8 36 (45.6) 0.7 10 (43.5) 0.6 18 (52.9) 0.6 122 (46.6) 0.7
>1.11 38 (35.9) 2.8 8 (10.1) 2.5 5 (21.7) 2.9 4 (11.8) 2.6 55 (21.0) 2.8
Total 106 (100.0) 1.4** 20 (100.0) 0.5 79 (100.0) 0.7** 23 (100.0) 1.0 34 (100.0) 0.7 262 (100.0) 1.0
a
Wilcoxon-Mann-Whitney test
b
p-values by Student’s t-test
*p-value <0.01
**p-value <0.001
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 5 of 8

Fig. 2 Distribution of diagnose category per cell count. CNS infection is the only category present in all intervals. The category of Other occurs mainly
in patients with CSF leukocytes below 100/μl. Infection outside CNS occurs primarily when CSF leukocytes were below 50/μl

leukocytes/μl and four patiens had 10–50 leukocytes/μl patient chart review. We found it important to manually
(Table 4). Pleocytosis has previosly been found in review the charts as also suggested by others in retro-
patientes after seizures [8]. Higher concentrations of spective studies to secure that all relevant diagnoses
CSF leukocytes were found in Other neurological dis- were included [9, 10].
eases. One patient, who suffered from obstructive hydro- A wide span of diagnoses were included in the Others
cephalus, had >1000 leukocytes/μl in CSF (categorised category including neurosarcoidosis and rheumatic dis-
as Other neurological diseases) but did not suffer from eases, which are known causes of pleocytosis [6, 11–13].
neuroinfection. No distinction between viral and bacter- In the category Other, the mean CSF leukocyte concen-
ial meningitis was made. No patients had tuberculosis or tration was 26/μl (SD 32.6). The patients in this category
fungal CNS infection as shown in the Appendix. did not differ from the other patients in age, sex, or
Charlson score. It could be speculated that some of
Discussion these patients suffered from a benign viral infection
The discharge diagnoses were retrospectively adjusted either not detected by available diagnostic setups or
for 36 (13.7%) patients following discharge summary and not tested for.

Fig. 3 Distribution of diagnose category as a percentage per cell count. The proportion of patients in the CNS infection category increased with
increasing CSF leukocyte concentration, and at leukocyte counts above 100/μl CNS infection was the most frequent cause of pleocytosis
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 6 of 8

Table 3 CSF leukocyte count, mean protein and mean CSF/plasma glucose ratio in verified and probable CNS infection
CSF leukocytes CNS infection, Verified CNS infection, Probable Total
/μl a
n (% horizontal) Protein g/l Glucose ratio n (% horizontal) Protein g/l Glucose ratio n (% vertical) Protein g/l Glucose ratio
Mean (range) mean (range) mean (range) mean (range) mean (range) mean (range)
6–10 4 (36.4) 0.6 (0.4–0.9) - 7 (63.6) 0.7 (0.4–0.9) 0.7 (0.5–0.9) 11 (10.4) 0,6 (0.4–0.9) 0.7 (0.5–0.9)
>10–50 9 (39.1) 0.9 (0.3–2.2) 0,5 (0.4–0.7) 14 (60.9) 0.6 (0.3–2.2) 0.6 (0.3–1.0) 23 (21.7) 0.7 (0.2–2.2) 0.6 (0.3–1.0)
>50–100 5 (62.5) 1.0 (0.2–1.6) 0.6 (0.5–0.7) 3 (37.5) 0.6 (0.4–0.7) 0.4 (0.4–0.5) 8 (7.6) 0,8 (0.2–1.6) 0.5 (0.4–0.7)
>100–200 7 (41.2) 0.8 (0.3–1.3) 0.7 (0.5–0.7) 10 (58.8) 0.8 (0.4–1.7) 0.6 (0.6–0.8) 17 (16.0) 0.8 (0.3–1.7) 0.7 (0.6–1.0)
>200–400 8 (61.5) 1.3 (0.4–2.4) 0.5 (0.4–0.6) 5 (38.5) 0.9 (0.5–1.9) 0.6 (0.5–0.8) 13 (12.3) 1.1 (0.4–2.4) 0.6 (0.4–0.8)
>400–600 8 (66.7) 2.3 (0.7–6.8) 0.4 (0.0–0.6) 4 (33.3) 1.3 (0.6–2.8) 0.6 (0.4–0.9) 12 (11.3) 2.0 (0.6–6.8) 0.5 (0.0–0.9)
>600–800 2 (100.0) 1.4 (0.8–2) 0.5 (0.3–0.6) 2 (1.9) 1.4 (0.8–2.0) 0.5 (0.3–0.6)
>800–1000 2 (66.7) 1.2 (1.2–1.2) 0.7 (0.7–0.7) 1 (33.3) 1.4 0.4 3 (2.8) 1.3 (1.2–1.4) 0.5 (0.4–0.7)
>1000 14 (82.4) 4 (0.8–6.8) 0.1 (0.1–0.1) 3 (17.6) 4.4 (1.5–9.0) 0.2 (0.1–0.1) 17 (16.0) 3.6 (0.8–6.8) 0.2 (0.0–0.4)
Total 59 (55.7) 1.8 (0.2–6.8) 0.4 (0.0–1.0) 47 (44.3) 1.0 (0.2–9.0) 0.6 (0.1–1.0) 106 (100.0) 1.4 (0.2–9) 0.5 (0.0–1.0)
- missing data: CSV/plasma glucose ratio only available in 59 of 106 patients

In the Non-infectious neurological diseases category This explains the high mean cell count in the subgroup
five patients suffered from Migraine or Headache and Cancer, foci elsewhere (Table 5).
three patients from Paralysis/paresis of facial nerve.
These eight patients could have suffered from a mild Limitations
viral CNS infection or Lyme’s disease, since viral CNS The study was performed retrospectively, which means
infection can present with similar symptoms [14, 15]. that no actions of the treating staff or patients could in-
However, variation from the normal levels cannot be fluence the results. A limitation of the study is the fact
ruled out. that data only was available from registers and patient
Three patients in the Malignancy category suffered charts, which might have led to incorrect categorization
from lung or oropharyngeal cancer. Previously, it has of some of the patients. However, all patients charts have
been found that patients can develop chemical meningi- been reviewed and categorized as part of this study as
tis (sterile and inflammatory) due to concurrent systemic described in the methods section. Not all diagnoses were
and local chemotherapy [16]. This could explain pleocy- paraclinically confirmed. This could be due to adminis-
tosis in these patients. One patient in the Malignancy tration of antimicrobial therapy prior to lumbar punc-
category was found with 1980 cells in CSF and suffered ture or due to insufficient sensitivity of the available
from agranulocytosis secondary to cancer chemotherapy methods.
but was not found to suffer from a CNS infection
though the high cell count would suggest otherwise. Conclusions
Neither was the patient found to suffer from infection This study correlates CSF findings to final diagnosis.
else where and was therefore categorized as Malignancy. CNS infection, non-infectious neurological disease,

Table 4 CSF leukocyte count in non-infectious neurological diseases subgroups

Non-infectious neurological diseases CSF leukocytes/μl
subgroup
≤10 >10–50 >50–100 >100–200 >200–400 >400–600 >600 Total
n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%)
Encephalitis/myelitis, non-infectious 8 (66.7) 2 (16.7) 1 (8.3) 1 (8.3) 12 (100.0)
Seizures/epilepsy/status epilepticus 2 (33.3) 4 (66.7) 6 (100.0)
Ischemia/infarction/stroke 4 (36.3) 4 (36.6) 1 (9.1) 2 (18.2) 11 (100.0)
Intracranial haemorrhage 1 (50.0) 1 (50.0) 2 (100.0)
Multiple sclerosis 8 (53.3) 7 (46.7) 15 (100.0)
Demyelinating disease/polyneuropathy 2 (40.0) 3 (60.0) 5 (100.0)
Paralysis/palsy of cranial nerve 2 (66.7) 1 (33.3) 3 (100.0)
Headache/migraine 3 (60.0) 2 (40.0) 5 (100.0)
Other neurological 11 (55.0) 5 (25.0) 1 (5.0) 1 (5.0) 1 (5.0) 1 (5.0) 20 (100.0)
Total 32 (40.5) 34 (43.0) 3 (3.8) 6 (7.6) 2 (2.5) 1 (1.3) 1 (1.3) 79 (100.0)
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 7 of 8

malignancy, and infection outside CNS can cause Table 5 Summary of subgroups in the diagnosis categories
pleocytosis of the cerebrospinal fluid. Leukocyte (Continued)
counts above 100/μl are mainly caused by CNS in- (including: Acute transverse myelitis
fection, whereas the number of differential diagnoses in demyelinating disease of central
is higher when CSF leukocytes levels are below 50/μl. nervous system, Other extrapyramidal
and movement disorders, Ventriculitis
These conditions are most commonly caused by non- of the brain, unspecified, Sequelae of
infectious neurological diseases including seizures. inflammatory diseases of central
nervous system), Obstructive
hydrocephalus, Spinal stenosis,
Herniation of lumbar disc with
Appendix radiculopathy, Disorder of central
nervous system, unspecified, Symptom
of central nervous system unspecified)
Table 5 Summary of subgroups in the diagnosis categories Malignancy. all foci 23 8.8 119.7
Number Percent Mean CSF Lymphoma 9 39.13 20.7
leukocytes/μl
Leukaemia 3 13.04 16.3
CNS infection 106 40.5 1135.5
CNS cancer 5 21.74 30.6
Meningitis. viral/unknown agent 38 35.9 617.0
Cancer. foci elsewhere 4 17.39 500.5
Meningitis. acute bacterial 21 19.8 3591.3 (Including: Malignant neoplasm
Meningitis. borrelia/syphilis 25 23.6 150.6 of unspecified part of unspecified
bronchus or lung, Malignant
Encephalitis. infectious 11 10.4 295.3 neoplasm of oropharynx, unspecified,
CNS abscess 3 2.8 4654.3 Agranulocytosis secondary to cancer
chemotherapy)
Other CNS infection 8 7.6 66.0
(Including: Herpes zoster with Carcinomatosis 2 8.7 181.0
other complication in CNS, Other 34 13.0 26.2
Hydrocephalus caused by
infectious or parasitic disease Sarcoidosis 4 11.4 54.5
classified elsewhere, Rheumatologic 2 5.7 89.0
Meningoencephalitis due to
toxoplasmosis, Polyneuropathy Cardiologic. non-infectious 2 5.7 8.0
caused by infectious or parasitic Observation for suspected/other 8 22.9 25.9
disease classified elsewhere, or not specified findings
Viral infection of CNS unspecified)
Others 18 52.9 15.1
Infection outside CNS 20 7.6 25.0 (Including: Acute respiratory failure,
Endocarditis 2 9.5 113.5 Fever, unspecified, Hypokalemia,
Complications following infusion,
Sepsis 10 47.6 18.8 transfusion and therapeutic injection,
Other infection with foci outside CNS 8 40.0 10.6 Care involving use of rehabilitation
(including: Acute pharyngitis, procedure, unspecified, Unspecified
Acute sinusitis, Analabsces, Other multiple injuries, Hypopituitarism,
pneumonia due to other unspecified Benign paroxysmal vertigo)
microorganism, Oral candidiasis,
HIV with other infectious and parasitic
disease, Erysiphelas, unspecified, Appendix
Viralinfection, unspecified, Pilonidal
cyst with abscess) Abbreviations
Non-infectious neurological diseases 79 30.2 63.2 CNS: Central nervous system; CSF: Cerebrospinal fluid; CT: Computed tomography;
MRI: Magnetic resonance imaging; PCR: Polymerace chain reaction
Encephalitis/myelitis. Non-infectious 12 15.2 108.3
Seizures/epilepsy/status epilepticus 6 7.6 15.8 Acknowledgements
We thank Michael Due Larsen, Center for Clinical Epidemiology, Odense
Ischemia/infarction/stroke 11 13.9 38.9
University Hospital, for assisting the Charlson score calculations and Michala
Intracranial haemorrhage 2 2.5 85.0 Kehrer, Department of Infectious Diseases, Odense University Hospital, for
help with STATA calculations.
Multiple sclerosis 15 19.0 15.0
Demyelinating disease/ 5 6.3 10.8 Funding
polyneuropathy University of Southern Denmark Research Foundation (Syddansk Universitets
Paralysis/palsy of cranial nerve 3 3.8 29.7 Forskningsfond) sponsored the study.

Headache/migraine 5 6.3 10.2

Availability of data and materials
Other neurological 20 25.3 129.1 Anonymized dataset supporting the conclusions of this article can be handed
by request to the authors.
Østergaard et al. BMC Clinical Pathology (2017) 17:15 Page 8 of 8

Authors’ contributions 15. Bremell D, Hagberg L. Clinical characteristics and cerebrospinal fluid parameters in
ÅBA contributed with study design, interpretation, and supervised the study. patients with peripheral facial palsy caused by Lyme neuroborreliosis compared
TVS contributed with study design, acquisition, and analysis of the data. MN with facial palsy of unknown origin (Bell’s palsy). BMC Infect Dis. 2011;11:215.
contributed with acquisition of data. AAØ contributed with conception, 16. Chamberlain MC, Glantz MJ. Cerebrospinal fluid-disseminated meningioma.
acquisition and analysis of data. All authors participated in preparing the Cancer. 2005;103(7):1427–30.
manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study was approved by the Danish Data Protection Agency (case no. 13/
14900) including permission to use the data from the database. Due to
national law consent to participate is not required.

Consent for publication

Not applicable.

Competing interests
The authors declare that they have no competing interests.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.

Author details
1
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
2
Department of Clinical Microbiology, Odense University Hospital, Odense,
Denmark. 3Department of Clinical Biochemistry and Pharmacology, Odense
University Hospital, Odense, Denmark. 4University of Southern Denmark, Odense,
Denmark. 5Department of Infectious Diseases 8632, Copenhagen University
Hospital Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen OE, Denmark.

Received: 23 July 2016 Accepted: 17 August 2017

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