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Cerebrospinal fluid: Physiology and utility of an examination in

disease states
Authors: Kimberly S Johnson, MD, Daniel J Sexton, MD
Section Editor: Allan R Tunkel, MD, PhD, MACP
Deputy Editors: Meg Sullivan, MD, Janet L Wilterdink, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2019. | This topic last updated: May 28, 2019.

INTRODUCTION

Examination of the cerebrospinal fluid (CSF) may provide critically important diagnostic information
in a number of infectious and noninfectious medical conditions. Knowledge of the normal physiology
and pathophysiology of CSF production and flow is useful in interpreting such test results.

This topic will review the normal physiology and composition of CSF. The technique for obtaining CSF
via lumbar puncture and the complications and contraindications to this test are discussed
separately. (See "Lumbar puncture: Technique, indications, contraindications, and complications in
adults".)

CSF analysis in children is presented elsewhere. (See "Bacterial meningitis in children older than one
month: Clinical features and diagnosis", section on 'Interpretation of CSF'.)

PHYSIOLOGY OF CSF FORMATION AND FLOW

Cerebrospinal fluid (CSF) is produced by the choroid plexus in the lateral, third, and fourth ventricles
and circulates through the subarachnoid space between the arachnoid mater and the pia mater. The
choroid plexus consists of projections of vessels and pia mater that protrude into the ventricular
cavities as frond-like villi containing capillaries in loose connective stroma. A specialized layer of
ependymal cells called the choroidal epithelium overlies these villi (figure 1).

CSF is formed in the choroid plexus by both filtration and active transport. In normal adults, the CSF
volume is 125 to 150 mL; approximately 20 percent of the CSF is contained in the ventricles; the rest
is contained in the subarachnoid space in the cranium and spinal cord. The normal rate of CSF
production is approximately 20 mL per hour.

CSF circulates from the lateral ventricles into the third ventricle and then the fourth ventricle via the
cerebral aqueduct. Thereafter, CSF passes through apertures in the fourth ventricle into the
subarachnoid space at the base of the brain and then flows over the convexities of the brain and
down the length of the spinal cord. The CSF is propelled along the neuroaxis by a cranio-caudal
pulsatile wave induced by flow in the cerebral arteries and by the associated expansions of the
vascular compartment in the cranial vault.

CSF is reabsorbed in the arachnoid villi, located along the superior sagittal and intracranial venous
sinuses and around the spinal nerve roots. Each arachnoid villus functions as a one-way valve
permitting unidirectional flow of CSF into the blood. Arachnoid villi and venous sinuses are separated
by endothelial cells connected by tight junctions (figure 1). Arachnoid villi normally allow the passage
of particles less than 7.5 micron in diameter from the CSF into the blood.

Movement of CSF and cellular components across arachnoid villi occurs via transport within giant
vesicles. These vesicles may become obstructed by bacteria or cells as a result of an inflammatory
process or by red blood cells during subarachnoid hemorrhage.

Lipid-soluble molecules or drugs readily diffuse across the vascular endothelium and epithelium of
the choroid plexus into the interstitial fluid and CSF. In contrast, ionically charged molecules generally
require active transport for entry into the CSF. Drug entry also may be altered in patients with
meningitis by the accompanying inflammation, and this may subsequently rapidly change with
regression of this inflammation with therapy. (See 'CSF in CNS infection' below.)

In addition to these well-described transport mechanisms, newer studies have documented the
existence of other pathways involved in the movement of CSF and solutes throughout the central
nervous system (CNS) [1]. These include perivascular pathways within the CNS parenchyma that
support the clearance of solutes from the brain to the CSF and extra-axial meningeal lymphatic
vessels associated with the dural sinuses that facilitate the movement of solutes in the CSF into the
systemic vascular system. The finding of dura-associated lymphatic vessels is contrary to long-held
beliefs about the absence of meningeal lymphatics. The role of these lymphatic pathways, however,
in the clearance of interstitial and CSF solutes has not yet been elucidated.

CSF PRESSURE

Cerebrospinal fluid (CSF) secretion and reabsorption remain in balance in most healthy individuals to
maintain a CSF pressure less than 150 mm H20. The normal CSF pressure as measured with a
manometer in a patient lying flat in the lateral decubitus position with the legs extended is between
60 and 250 mm H20 [2]; however, some experts consider the upper limit of normal CSF pressure to be
200 mm H20 (figure 2) [3]. Although obese patients tend to have higher opening pressures than
nonobese patients, the correlation between opening pressure and body mass index was weak in a
study involving 242 outpatients with a variety of neurologic complaints and/or conditions that are not
associated with elevated CSF pressure [2]. Finally, it is important to note that a variety of factors, such
as the patient's position, the skill of the person performing the lumbar puncture, and the degree of
relaxation of the patient can affect the measurement of the opening pressure.

The differential diagnosis of an increase in CSF pressure includes both infectious and noninfectious
diseases and relates to disruptions in the normal physiology of CSF secretion and absorption and
whether or not compensatory mechanisms develop if secretion or absorption of CSF is altered.
Processes, such as infection, bleeding, or a tumor, can alter the balance between CSF secretion and
reabsorption and thus cause intracranial hypertension. However, slow-growing masses, such as
abscesses or tumors, may allow time for compensation between CSF secretion and absorption to
occur; thus, a rise in CSF pressure may not occur until the normal compliance of the intracranial
structures is overcome. In contrast, acute infections, such as meningitis, typically lead to rapid
increases in CSF pressure due to alterations in either production or reabsorption of CSF, or as a result
of cerebral edema. (See "Neurologic complications of bacterial meningitis in adults", section on
'Increased intracranial pressure' and "Bacterial meningitis in children: Neurologic complications",
section on 'Major neurologic complications'.)

Downward and backward shifting of the cerebrum and brainstem may occur when intracranial
hypertension develops, resulting in either respiratory depression and/or death due to herniation of the
cingulate gyrus, the uncus of the temporal lobe, or the cerebellar tonsils. (See "Evaluation and
management of elevated intracranial pressure in adults".)

THE BLOOD-BRAIN BARRIER

The term "blood-brain barrier" is used to describe barrier systems that separate the brain and the
cerebrospinal fluid (CSF) from the blood and prevent entry by simple diffusion of fluids, electrolytes,
and other substances from blood into the CSF or brain [4]. There are actually two barriers: a blood-
brain barrier and a blood-CSF barrier. Both barriers separate the central nervous system (CNS) from
systemic immune responses and affect the composition of the brain interstitial fluid and CSF. The
blood-brain and the blood-CSF barriers are not precisely equivalent [4].

Blood-brain barrier — The blood-brain barrier controls the content of brain interstitial fluid. It has a
5000-fold greater surface area than the blood-CSF barrier [4]. The anatomic basis for the blood-brain
barrier is a series of high-resistance, tight junctions between endothelial cells as well as astrocytes
with processes that terminate in overlapping fashion on capillary walls.

Lipid-soluble small molecules with a molecular mass less than 400 to 600 Da are transported readily
through the blood-brain barrier. In contrast, many drugs and other small molecules cannot cross this
barrier system [5].

Blood-CSF barrier — The blood-CSF barrier controls the composition of the CSF, which, as noted
above, is primarily dependent upon secretion in the choroid plexus. The blood-CSF barrier is formed
by tight junctions between choroid epithelial cells.

Both barrier systems are dynamic. Endothelial cells and astrocytes that compose the blood-brain
barrier and cells forming the blood-CSF barrier are capable of producing cytokines such as tumor
necrosis factor and interleukins. In addition, astrocytes can act as antigen-presenting cells that
modulate the immunologic response to CNS infections. Release of cytokines from endothelial cells
and astrocytes probably mediate or generate much of the CNS inflammatory response in infectious
and noninfectious conditions.

A brain-CSF barrier also exists in the pia mater. A continuous layer of astrocytes overlies the
basement membrane of cells in the pia mater. These astrocytes are separated by gap junctions that
affect the movement of constituents from the CSF into the brain.

Microbe entry in meningitis — The mechanism by which bacteria or other microbes traverse the
blood-brain barrier and enter the CNS remains poorly understood. A number of theories have been
advanced [6-10]. As examples:

● Microbes in the blood could traverse the blood-brain barrier via attachment of specific bacterial
surface constituents to endothelial cells. Such surface constituents include the capsular
polysaccharide present on many of the encapsulated bacteria that cause acute bacterial
meningitis. As an example, the phosphorylcholine moiety of the pneumococcal cell wall
lipoteichoic acid appears to utilize endogenous receptors for platelet activating factor to
facilitate attachment and transcellular migration across endothelium [7].

● Pili on gram-negative rods may facilitate bacterial entry into the brain or CSF. Such interactions
have been hypothesized to occur in children with Escherichia coli meningitis [8] and in patients
with meningitis due to certain strains of Neisseria meningitidis [6].

● Microbes can theoretically transverse the blood-brain barrier inside circulating cells such as
monocytes. This phenomenon has been described as a "Trojan horse mechanism."
A more detailed discussion of the pathogenesis of bacterial meningitis is presented in a separate
topic review. (See "Pathogenesis and pathophysiology of bacterial meningitis".)

COMPOSITION OF THE CSF

Xanthochromia — Normal cerebrospinal fluid (CSF) is clear and colorless. Both infectious and
noninfectious processes can alter the appearance of the CSF. As few as 200 white blood cells
(WBCs)/microL or 400 red blood cells (RBCs)/microL will cause CSF to appear turbid. CSF will appear
grossly bloody if ≥6000 RBCs/microL are present [3].

Red blood cells rapidly lyse after entry into CSF. The breakdown of hemoglobin first to oxyhemoglobin
(pink) and later to bilirubin (yellow) leads to a yellow or pink discoloration of the CSF known as
xanthochromia. Spectrophotometry can be used to analyze blood breakdown products as they
progress from oxyhemoglobin to methemoglobin and finally to bilirubin, thereby ruling out traumatic
blood [11-13]. Although xanthochromia is generally confirmed visually [14], laboratory confirmation
with spectrophotometry may be more sensitive and, if available, is recommended by some experts
[11,15,16].

Xanthochromia can be detected as soon as two to four hours after RBCs have entered the
subarachnoid space, and therefore this is often used in the diagnosis of subarachnoid hemorrhage
(SAH). Xanthochromia is present in over 90 percent of patients with a subarachnoid hemorrhage
within 12 hours of the onset of bleeding, and it may persist thereafter for two to four weeks [11,17-
19]. The use of xanthochromia and RBC count to distinguish SAH from traumatic tap is discussed
separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis",
section on 'Lumbar puncture'.)

Xanthochromia can also occur with increased CSF concentrations of protein (≥150 mg/dL) or
systemic hyperbilirubinemia (serum bilirubin >10 to 15 mg/dL) [3].

Cells

Normal findings — The CSF is normally acellular. However, up to 5 WBCs and 5 RBCs are
considered normal in adults when the CSF is sampled by lumbar puncture (LP). More than 3
polymorphonuclear leukocytes (PMNs)/microL are abnormal in adults. The CSF cell profiles in
neonates and children are discussed separately. (See "Bacterial meningitis in the neonate: Clinical
features and diagnosis", section on 'Cell count' and "Bacterial meningitis in children older than one
month: Clinical features and diagnosis", section on 'Cell count'.)

The CSF cell count determination should be performed promptly since the count may be falsely low if
measured more than 60 minutes after the LP is performed. This spuriously low cell count may be due
to settling of the cells in the CSF over time and/or adherence of RBCs or PMNs to plastic tubes.

Pleocytosis — An elevated CSF WBC concentration does not diagnose an infection, since
increases in the CSF WBC concentration can occur in a variety of both infectious and noninfectious
inflammatory states. The following truisms about the interpretation of CSF cell counts may be useful:

● The CSF cell count must always be correlated with clinical findings. PMNs, for example,
predominate in the CSF of as many as two-thirds of patients with meningitis due to
enteroviruses; a shift to lymphocytic predominance usually occurs within 12 to 24 hours [20,21].
On the other hand, lymphocytes rarely predominate in the early phases of bacterial meningitis.
(See "Aseptic meningitis in adults" and 'CSF in CNS infection' below.)

● The presence of eosinophils in the CSF has limited diagnostic utility. CSF eosinophilia may occur
in parasitic infestations but also in infections due to other microorganisms, including
Mycobacterium tuberculosis, Mycoplasma pneumoniae, Rickettsia rickettsii, some fungi, and in
noninfectious conditions, such as lymphomas, leukemias of various types, subarachnoid
hemorrhage, and obstructive hydrocephalus.

Predicted WBC count after traumatic tap — Accidental trauma to a capillary or venule may occur
during performance of an LP, increasing the number of both RBCs and WBCs in the CSF. If a traumatic
lumbar puncture is suspected and the peripheral WBC count is not abnormally low or high, a good
rule of thumb for estimating the adjusted WBC count is to subtract 1 WBC for every 500 to 1500 RBCs
measured in the CSF. The formula in the following Calculator can also be used to determine the
adjusted WBC count in the presence of CSF RBCs (calculator 1) [22,23]. The interpretation of CSF
pleocytosis in the setting of bacterial meningitis is discussed in detail separately. (See "Clinical
features and diagnosis of acute bacterial meningitis in adults", section on 'Pleocytosis'.)

The presence or absence of otherwise unexplained xanthochromia also may help distinguish a
traumatic tap from subarachnoid hemorrhage as long as the LP is performed at least six hours after
the onset of headache. (See 'Xanthochromia' above.)

Interpretation of traumatic LPs in children is discussed separately. (See "Bacterial meningitis in

children older than one month: Clinical features and diagnosis", section on 'Interpretation of CSF'.)

Chemical composition — Determination of CSF protein and glucose concentrations are routinely done
and may reveal useful clinical information.

Protein — Proteins are largely excluded from the CSF by the blood-CSF barrier. Proteins gaining
access to the CSF primarily reach the CSF by transport within pinocytotic vesicles traversing capillary
endothelial cells. The normal CSF protein concentration ranges from 23 to 38 mg/dL (0.23 to 0.38
g/L) in adults [3]; in one report, the extreme upper and lower CSF protein concentrations in normal
individuals were 58 and 9 mg/dL (0.58 and 0.09 g/L), respectively [19]. CSF protein concentrations in
premature and term neonates normally range between 20 and 170 mg/dL (0.2 and 1.7 g/L) [24]. The
CSF protein concentration may be mildly elevated in patients with diabetes mellitus.

CSF protein can also be elevated by a subarachnoid hemorrhage or a traumatic LP. The presence of
CSF bleeding results in approximately 1 mg of protein/dL per 1000 RBCs/microL. When assessing the
potential effect of CSF bleeding on an elevated CSF protein concentration, the CSF protein
concentration and RBC count should be performed on the same tube of CSF.

Elevations in the CSF protein concentration can occur in both infectious and noninfectious conditions,
including conditions associated with obstruction of CSF flow.

CSF protein elevations may persist for weeks or months following recovery from meningitis and have
little utility in assessing cure or the response to therapy [25]. (See 'CSF in CNS infection' below.)

Immunoglobulins and oligoclonal bands — Immunoglobulins are almost totally excluded from

the CSF in healthy individuals. The blood to CSF ratio of IgG is normally 500:1 or more. Elevations in
oligoclonally expanded immunoglobulin concentrations in the CSF, termed oligoclonal bands, may
occur in any disorder that disrupts the blood-brain barrier. Oligoclonal bands may also be caused by
intrathecal production of IgG, and the presence of such bands is a diagnostic criterion for multiple
sclerosis [26]. Examples of other diseases that can cause oligoclonal bands in the CSF include
infections (eg, nervous system Lyme disease), autoimmune diseases, brain tumors, and
lymphoproliferative diseases. Given how many diseases can result in oligoclonal bands in the CSF, the
diagnostic utility of this finding is limited. (See "Nervous system Lyme disease", section on 'CSF
antibodies' and "Evaluation and diagnosis of multiple sclerosis in adults", section on 'CSF analysis
and oligoclonal bands'.)

Glucose — Low CSF glucose concentration (hypoglycorrhachia) may occur in a variety of

infectious and noninfectious pathologic conditions. Elevated CSF glucose concentrations only occur
in the setting of hyperglycemia.

● CSF glucose concentrations less than 18 mg/dL (1.0 mmol/L) are strongly predictive of bacterial
meningitis [25]. Abnormally low CSF glucose concentrations can also occur in mycobacterial,
mycoplasmal (M. pneumoniae), treponemal, and fungal CNS infections (table 1). During recovery
from meningitis, CSF glucose concentration tends to normalize more rapidly than the CSF cell
count and protein concentration. (See 'CSF in CNS infection' below.)

In contrast, the CSF glucose concentration is typically normal during most viral CNS infections,
although low concentrations have been reported in patients with meningoencephalitis due to
 mumps, enteroviruses, lymphocytic choriomeningitis (LCM), herpes simplex, and herpes zoster
viruses.

● Low CSF glucose concentrations can also occur in noninfectious conditions; patients with
leptomeningeal carcinomatosis, leukemia, CNS lymphoma, severe subarachnoid hemorrhages, or
neurosarcoidosis may have hypoglycorrhachia because of cellular or inflammatory infiltrates that
disrupt the active transport of glucose into the CSF (table 1) [27]. Salicylate poisoning has been
reported to cause low CSF glucose concentration, but this has not been well-documented, and
this association is speculative [28-30].

Also, hypoglycemic patients who present with CNS symptoms may have low CSF glucose
concentrations (see "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations,
diagnosis, and causes").

In the setting of hyperglycemia, a low CSF glucose may not be recognized if only the absolute CSF
glucose concentration is considered. The normal CSF-to-serum glucose ratio is >0.6 [31,32]. Attempts
to "correct" the CSF glucose concentration for hyperglycemia should take into account the fact that it
takes several hours for the serum glucose to equilibrate with the CSF glucose; thus the timing of the
last meal and/or administration of insulin or oral hypoglycemic may be relevant [33]. Other
considerations include that CSF-to-serum glucose ratios in neonates are highly variable and also that
ventricular CSF glucose concentration is 6 to 18 mg/dL (0.33 to 1.0 mmol/L) higher than in the
lumbar CSF [34]. In addition, CSF glucose levels rarely exceed 300 mg/dL (16.7 mmol/L) even in
patients with severe hyperglycemia.

Lactate — Determination of the CSF lactate concentration has been suggested as a useful test to
differentiate bacterial from viral meningitis. Two meta-analyses that included 25 studies (1692
patients) and 31 studies (1885 patients) concluded that the diagnostic accuracy of CSF lactate was
superior to that of CSF white blood cell count, glucose, and protein concentration in differentiating
bacterial from aseptic meningitis [35,36], although sensitivity was lower in patients who received
antimicrobial treatment prior to lumbar puncture [36], and CSF lactate may be elevated in patients
with other CNS diseases.

Cytology — Cytology is occasionally useful for the diagnosis of malignancy involving the CNS [37]. In
such instances, at least 10 to 15 mL of fluid should be sent to the pathology laboratory for prompt
examination.

CSF IN CNS INFECTION

Chemical analysis and Gram stain of the cerebrospinal fluid (CSF) are an integral part of the
evaluation of patients with suspected meningitis or encephalitis. Although there is overlap, there are
broad general differences between the findings in bacterial and viral infections (table 2). (See "Clinical
features and diagnosis of acute bacterial meningitis in adults" and "Viral encephalitis in adults" and
"Aseptic meningitis in adults".)

Among patients with viral meningitis, the typical findings include:

● The CSF white blood cell (WBC) count is usually less than 250/microL and almost always less
than 2000/microL [25]. The differential typically shows a predominance of lymphocytes, although
early infection may reveal a predominance of neutrophils that, within the next 24 hours, generally
shows a shift from neutrophils to lymphocytes [21].

● The CSF protein concentration is typically less than 150 mg/dL; it has been estimated that CSF
protein concentrations greater than 220 mg/dL reduce the probability of viral infection to 1
percent or less [25].

● The CSF glucose concentration is usually more than 50 percent of serum concentration, but
moderately reduced values are occasionally seen with herpes simplex virus (HSV), mumps, some
enteroviruses, and lymphocytic choriomeningitis virus.

Among patients with bacterial meningitis, the classic findings are (table 2):

● A CSF WBC count above 1000/microL, usually with a neutrophilic predominance

● A CSF protein concentration above 250 mg/dL

● A CSF glucose concentration below 45 mg/dL (2.5 mmol/L)

However, the spectrum of CSF values in bacterial meningitis is so wide that there is substantial
overlap with the findings in viral infection (table 2). This was illustrated in a review of 296 episodes of
community-acquired bacterial meningitis: 50 percent had a CSF glucose above 40 mg/dL (2.2
mmol/L), 44 percent had a CSF protein below 200 mg/dL, and 13 percent had a CSF white cell count
below 100/microL [38]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults",
section on 'CSF analysis'.)

SUMMARY

● The normal cerebrospinal fluid (CSF) pressure is 60 to 200 mmH20; obese patients may have
CSF pressures up to 250 mmH20. (See 'Physiology of CSF formation and flow' above.)
● Infection, bleeding, or a tumor can alter the balance between CSF secretion and reabsorption,
resulting in intracranial hypertension. The normal CSF pressure as measured with a manometer
in a patient lying flat in the lateral decubitus position with the legs extended is between 60 and
250 mmH20; however, some experts consider the upper limit of normal CSF pressure to be 200
mmH20. (See 'Physiology of CSF formation and flow' above and 'CSF pressure' above.)

● The term "blood-brain barrier" is used to describe barrier systems that separate the brain and the
CSF from the blood and prevent entry by simple diffusion of fluids, electrolytes, and other
substances from blood into the CSF or brain. (See 'The blood-brain barrier' above.)

● The mechanism by which bacteria or other microbes traverse the blood-brain barrier and enter
the center nervous system (CNS) remains poorly understood. (See 'Microbe entry in meningitis'
above.)

● Xanthochromia, a yellow or pink discoloration of the CSF, represents most often the presence of
hemoglobin degradation products and indicates that blood has been in the CSF for at least two
hours (eg, subarachnoid hemorrhage). Other causes of xanthochromia include increased CSF
concentrations of protein (≥150 mg/dL), systemic hyperbilirubinemia (serum bilirubin >10 to 15
mg/dL), and occasionally in the setting of a traumatic lumbar puncture with more than 100,000
red blood cells/microL. (See 'Xanthochromia' above.)

● The CSF is normally acellular, although up to 5 white blood cells (WBCs) and 5 red blood cells
(RBCs) are considered normal in adults when the CSF is sampled by lumbar puncture (LP);
newborns, in contrast, may have up to 20 WBCs/microL in the CSF. (See 'Normal findings' above.)

● An elevated CSF WBC concentration does not diagnose an infection, since increases in the CSF
WBC concentration can occur in a variety of both infectious and noninfectious inflammatory
states. (See 'Pleocytosis' above.)

● The two major tests performed in the chemistry laboratory on CSF are determination of protein
and glucose concentrations. (See 'Chemical composition' above.)

● Chemical analysis and Gram stain of the CSF are an integral part of the evaluation of patients
with suspected meningitis or encephalitis. Although there is overlap, there are broad general
differences between the findings in bacterial and viral infections (table 2). (See 'CSF in CNS
infection' above.)

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Topic 1285 Version 29.0

GRAPHICS

Cerebrospinal fluid (CSF) formation and reabsorption

Graphic 57840 Version 4.0

Cerebrospinal fluid (CSF) manometry

Midsagittal section through lumbar spinal column showing positioning for measurement of CSF
opening pressure. The manometer is attached to the spinal needle hub with a three-way stop-
cock. CSF is permitted to enter the manometer; opening pressure is recorded at the highest level
attained by the CSF in the manometer column. Pressure measurements should be taken with the
patient recumbent.

Adapted from Dieckmann RA, Fiser DH, Selbst SM, (Eds). Illustrated Textbook of Pediatric Emergency and
Critical Care Procedures. Mosby, St. Louis, 1997.

Graphic 54738 Version 4.0

Common and uncommon etiologies of hypoglycorrhachia

Etiologies uncommonly associated with

Etiologies commonly associated with
hypoglycorrhachia
hypoglycorrhachia
(reported but not typical)

Infectious causes

Bacterial meningitis (including Nocardia and Brucella)* Syphilitic meningitis

Fungal meningitis* Lyme meningitis*
Mycobacterial (tuberculous) meningitis* Viral meningitis
Amebic meningoencephalitis Neurocysticercosis*
Cytomegalovirus-associated progressive polyradiculopathy CNS toxoplasmosis
or meningoencephalitis

Noninfectious causes

Carcinomatous meningitis* Cholesterol-induced leptomeningitis secondary to Currarino

Glucose transporter 1 deficiency syndrome*
Leukemia/lymphoma with CNS involvement* Neurosarcoidosis*
Subarachnoid hemorrhage* Rheumatoid meningitis
Systemic lupus erythematosus with CNS involvement
Neuro-Behçet's disease
Dermoid cyst*
Granulomatous angiitis of the central nervous system
Malignant atrophic papulosis
Salicylate toxicity (uncertain association)

CNS: central nervous system.

* Etiologies reported to cause severe hypoglycorrhachia, generally defined as cerebrospinal fluid glucose level ≤10 mg/dL.

Original figure modified for this publication. Chow E, Troy SB. The differential diagnosis of hypoglycorrhachia in adult patients. Am J Med Sci 2014;
348:186. Table used with the permission of Elsevier Inc. All rights reserved.

Graphic 107252 Version 3.0

Typical cerebrospinal fluid findings in central nervous system infections*

Total white blood cell count

Glucose (mg/dL) Protein (mg/dL)
  (cells/microL)

<10 ¶ 10 to 40 Δ 100 to 500 ◊ 50 to 300 § >1000 100 to 1000 5 to 100

More Bacterial Bacterial Bacterial Viral meningitis Bacterial Bacterial or Early bacterial
common meningitis meningitis meningitis Nervous system meningitis viral meningitis
Lyme disease meningitis Viral
(neuroborreliosis) TB meningitis meningitis
Encephalitis  Neurosyphilis
Neurosyphilis TB meningitis
¥
TB meningitis

Less TB meningitis Neurosyphilis     Some cases Encephalitis Encephalitis

common Fungal Some viral of mumps
meningitis infections and LCMV
(such as
mumps and
LCMV)

TB: tuberculosis; LCMV: lymphocytic choriomeningitis virus.

* It is important to note that the spectrum of cerebrospinal fluid values in bacterial meningitis is so wide that the absence of one or more of
these findings is of little value. Refer to the UpToDate topic reviews on bacterial meningitis for additional details.
¶ <0.6 mmol/L.
Δ 0.6 to 2.2 mmol/L.
◊ 1 to 5 g/L.
§ 0.5 to 3 g/L.
¥ Cerebrospinal fluid protein concentrations may be higher in some patients with tuberculous meningitis; concentrations >500 mg/dL are an
indication of blood-brain barrier disruption or increased intracerebral production of immunoglobulins, and extremely high concentrations, in the
range of 2 to 6 g/dL, may be found in association with subarachnoid block.

Graphic 76324 Version 10.0

Contributor Disclosures
Kimberly S Johnson, MD Nothing to disclose Daniel J Sexton, MD Grant/Research/Clinical Trial Support:
Centers for Disease Control and Prevention; National Institutes of Health [Healthcare epidemiology].
Consultant/Advisory Boards: Magnolia Medical Technologies [Medical diagnostics]; National Football League
[Infection prevention]; Johnson & Johnson [Mesh-related infections]. Equity Ownership/Stock Options: Magnolia
Medical Technologies [Medical diagnostics (Blood culture techniques)]. Allan R Tunkel, MD, PhD, MACP Nothing
to disclose Meg Sullivan, MD Grant/Research/Clinical Trial Support: Gilead Sciences [Pre-exposure prophylaxis
for contraception (Tenofovir)]. Consultant/Advisory Boards: Gilead Sciences [Pre-exposure prophylaxis for
contraception (Tenofovir)]. Janet L Wilterdink, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.

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