You are on page 1of 28

C H A P T E R

6 0

Spinal Puncture and


Cerebrospinal Fluid
Examination

sophisticated bacteriologic, biochemical, cytologic, and serologic techniques were introduced. In 1919 Dandy reported on
replacing CSF with air to determine normal brain anatomy
and to identify pathologic changes.3 Water-soluble contrast
media have since been used to delineate the spinal subarachnoid space and cerebral cisterns. Other uses of spinal dural
puncture include drainage of fluids and injection of anesthetic
agents, chemotherapeutic agents, and antibiotics.

Brian D. Euerle

ANATOMY AND PHYSIOLOGY

erebrospinal fluid (CSF) examination is performed in the


emergency department (ED) to obtain information relevant to the diagnosis and treatment of specific disease entities.
Many urgent and life-threatening conditions require immediate and accurate knowledge of the nature of the CSF. However,
on rare occasions, certain harmful consequences may result
from a spinal puncture. Perform a careful neurologic examination before the procedure, and give special thought to the
risks and merits of the procedure in each situation.

HISTORICAL PERSPECTIVE
In 1885, Corning punctured the subarachnoid space to induce
cocaine anesthesia in a living patient.1 In 1891, Quincke first
removed CSF in a diagnostic study and introduced the use of
a stylet.2 He studied the cellular contents and measured
protein and glucose levels. Quincke was also the first to record
CSF pressure with a manometer. Subsequently, increasingly

In adults, CSF occupies approximately 140mL of the spinal


and cranial cavities, with approximately 30mL in the spinal
canal. This volume is the result of a balance between continuous secretion (primarily by the ventricular choroid plexus) and
absorption into the venous system (mainly by way of the
arachnoid villi). After formation, the fluid passes out of the
ventricles via the midline dorsal foramen of Luschka and
the lateral ventral foramina of Magendie. The fluid then flows
into the spinal subarachnoid space, the basilar cisterns, and
the cerebral subarachnoid space. The rate of production is
approximately 0.35mL/min, and ventricular production of
CSF is such that there is a net flow out of the ventricles of 50
to 100mL/day. The usual volume of CSF (15 to 20mL)
removed at lumbar puncture is commonly regenerated in
about 1 hour.
CSF may have an embryologic nutritive function; at maturity, CSF most likely acts as a mechanical barrier between the
soft brain and the rigid fibroosseous dura, skull, and vertebral
column. It also appears to support the weight of the brain.4
When buoyed by CSF, the functional weight of the brain is
reduced from 1400 to 50g. Contraction and expansion of
CSF accommodates changes in brain volume.

Spinal Puncture
Indications

Equipment

Suspected central nervous system infection (meningitis)


Suspected spontaneous subarachnoid hemorrhage
Suspected central nervous system syphilis
Suspected idiopathic intracranial hypertension

Lidocaine
Syringe

Contraindications
Absolute:
Presence of infection near the puncture site
Relative:
Coagulopathy
Presence of increased intracranial pressure caused by
a space-occupying lesion
Severe thrombocytopenia

Complications
Brain herniation
Cauda equina syndrome
Cranial nerve VI palsy
Epidermoid tumor
Epidural cerebrospinal fluid collection
Epidural hematoma

Meningitis
Minor backache
Postdural puncture headache
Retroperitoneal abscess
Subarachnoid hemorrhage
Subdural hematoma

Antiseptic
and applicator

3-way
stopcock

Spinal needles

Needles for
anesthetic

Sterile drape
Manometer

6-inch
extension
tubing
Collection tubes

The equipment for spinal puncture is most commonly found in a


prepackaged kit.

Review Box 60-1 Spinal puncture: indications, contraindications, complications, and equipment.

1218

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

INDICATIONS FOR SPINAL PUNCTURE


General Indications
The indications for spinal puncture have been reduced with
the introduction of noninvasive diagnostic procedures
magnetic resonance imaging (MRI) and computed tomography (CT). A few clinical situations require early or even
emergency spinal puncture. The primary indication for an
emergency spinal tap is the possibility of central nervous
system (CNS) infection (meningitis), with the exception of a
suspected brain abscess or a parameningeal process. The need
for early detection of meningitis results in the performance
of many more lumbar punctures than ultimate diagnoses of
infection.5 No other method can be used to completely
exclude meningitis.
The mere presence of a fever does not mandate lumbar
puncture. However, CSF should generally be examined for
evidence of infection in patients with a fever of unknown
origin, especially if consciousness is altered or the immune
system is impaired, even in the absence of meningeal irritation. Meningeal signs may not be present in patients who are
old, debilitated, or immunosuppressed; are receiving antiinflammatory drugs; or have had partial treatment with antibiotics.6,7 In a newborn, even a fever is not a dependable sign
because temperatures may be normal or even subnormal. For
infants younger than 1 year, a high index of suspicion is
required to make the diagnosis of meningitis.
Approximately 25% of infants with meningitis will not
have nuchal rigidity, but many appear toxic or moribund. A
tense and bulging fontanelle is somewhat more reliable,
although this sign may be absent in a dehydrated child. Neonatal meningitis occurs in 25% of sepsis cases. In addition,
15% to 20% of infants with meningitis have negative blood
cultures.8,9 In a child between the ages of 1 month and 3 years,
fever, irritability, and vomiting are the most common signs of
meningitis. Typically, handling is painful for the child, and the
child cannot be comforted. In addition, an older child may
complain of a headache. At all ages, patients generally appear
ill and drowsy with a dulled sensorium. Physical signs become
more useful in diagnosing meningitis in children older than
3 years10 and include nuchal rigidity, Kernigs sign (effort to
extend the knee is resisted), and Brudzinskis sign (passive
flexion of one hip causes the other leg to rise, and effort to
flex the neck makes the knees come up). The jolt accentuation
test is a more sensitive sign of meningeal irritation.11 This test
is considered positive when the patients pain is exacerbated
by lateral rotation of the head to either side. A petechial rash
in a febrile patient should also raise suspicion for Neisseria
meningitis.12 Previous use of antimicrobial agents may modify
the clinical and CSF findings; partially treated children are
less likely to be febrile or exhibit an altered mental status. In
addition, patients in the early stages of meningitis may lack
the classic features associated with advanced disease.
The second indication for emergency spinal puncture is
suspected spontaneous subarachnoid hemorrhage (SAH). The
diagnosis is usually made by imaging (head CT) or by the
direct finding of blood in CSF obtained by spinal puncture.13,14
The sensitivity of CT has been estimated to be as high as 95%
soon after hemorrhage, but it drops in patients evaluated later
than 24 hours after the event to 76% after 48 hours and to
about 50% at 1 week. Before a major hemorrhage, 20% to
60% of patients with aneurysmal SAH have had a sentinel

1219

thunderclap or warning leak headache (i.e., an unusual


sudden headache caused by a minor leak of blood from the
aneurysm). The headache may precede a major rupture by
hours to months. The goal of early clinical recognition is
surgical or other interventional therapy before a recurrent
major hemorrhage. After a warning leak, head CT is more
likely to be negative, thus giving added importance to the
performance of a lumbar puncture. Migraine or vascular
headache is a common misdiagnosis in patients with SAH who
initially have negative findings on head CT.
The usual clinical picture of SAH is an instantaneous
excruciating headache. Patients generally recall the exact
moment that the headache occurred. The location of the
headache is variable and does not necessarily indicate the
site of hemorrhage. Nausea, vomiting, and prostration are
common symptoms, with approximately one third of patients
becoming unconscious at the onset. Examination reveals an
acutely ill patient with irritability or overt altered mental
status. Meningeal signs are commonly present at the time of
initial examination and usually develop within 2 to 3 days.
The meningeal signs may become more severe during the first
week after hemorrhage and correspond to the breakdown of
blood in CSF. During the first week many patients are febrile,
a reflection of chemical hemic meningitis.15 Failure to detect
blood radiographically in an awake patient may indicate a
small hemorrhage or a predominant basal accumulation of
blood. If a patient is initially seen several days after the hemorrhage, the blood may have become isodense with brain
tissue and may no longer be visible on CT. The proper diagnosis would then require spinal puncture.
Newer CT scanners detect recent SAH quite accurately.16
However, because acute SAH is not detected by the initial CT
scan in at least 2% to 5% of all patients, lumbar puncture is
appropriate to rule out the diagnosis with certainty.17-19 If the
neurologic picture demonstrates localizing findings, the presence of a large intracranial hematoma should be suspected,
and spinal puncture is contraindicated until imaging studies
delineate the nature of the lesion.
Other nonemergent reasons for examination of CSF
include evaluation for CNS syphilis or unexplained seizures,
instillation of chemotherapy and contrast agents, assessment
for a suspected demyelinating or inflammatory CNS process,
and treatment of headache from SAH. Carcinomatous meningitis and suspected spinal cord compression from metastatic
disease may require spinal puncture for myelography and
cytologic examination. MRI is a suitable alternative for identifying compressive myelopathy and has largely replaced
contrast-enhanced myelography in developed countries.

IIH (Pseudotumor Cerebri)


Idiopathic intracranial hypertension (IIH) is a rare condition
of unclear etiology. Patients with IIH have a marked elevation
in intracranial pressure (ICP; usually to 250 to 450cm H2O)
without hydrocephalus or mass lesions in the setting of normal
CSF composition. Findings on neuroimaging studies are typically normal, and most cases are idiopathic. Because of the
nonspecific signs and symptoms, many cases initially escape
detection by clinicians. IIH has been associated with hypervitaminosis A, tetracycline, estrogen therapy, and a plethora
of other conditions such as sarcoidosis, tuberculosis, and carcinomatosis. Because of the nonspecific findings, many cases
initially escape detection by clinicians. IIH is most common

1220

SECTION

X NEUROLOGIC PROCEDURES

in obese adolescent girls and young women, but it can also


occur in children and men. Patients suffer from chronic headaches, typically worse with maneuvers that increase ICP (e.g.,
Valsalva maneuver, squatting, bending, coughing). Papilledema is frequently present. Cranial nerve palsies, particularly
of the sixth cranial nerve, are due to increased ICP alone and
may be falsely localizing.20
IIH may regress spontaneously after a few months. The
major concern is visual loss, which may be permanent. The
diagnosis can be made only by lumbar puncture performed
after neuroimaging. This condition underscores the need to
measure opening pressure during lumbar puncture whenever
possible. Many cases can be controlled with medication, but
occasionally, lumbar puncture is required to lower ICP. One
way to lower ICP in the ED is to drain CSF via lumbar puncture by removing 5- to 10-mL aliquots of CSF and checking
ICP after each removal until a pressure lower than 200mm
H2O is achieved. Herniation does not occur despite the elevated pressure in IIH, probably because ICP is uniform in all
CNS compartments. Since spinal fluid is regenerated rapidly,
the procedure may need to be repeated every few days to keep
CSF pressure at this level. Analysis of CSF should demonstrate all parameters to be normal. Drug therapy, in the form
of acetazolamide, glycerol, diuretics, or corticosteroids, has
been advocated and may negate the need for repeated lumbar
puncture. Resistant cases may require shunting procedures.

CONTRAINDICATIONS TO SPINAL PUNCTURE


Spinal puncture is absolutely contraindicated in patients with
infection in the tissues near the puncture site.4,21 Spinal puncture is relatively contraindicated in the presence of increased ICP
caused by a space-occupying lesion. Caution is particularly advised
when lateralizing signs (hemiparesis) or signs of uncal herniation (unilateral third-nerve palsy with an altered level of consciousness) are present. In such cases, a tentorial or cerebellar
pressure cone may be precipitated or aggravated by the spinal
puncture. Cardiorespiratory collapse, stupor, seizures, and
sudden death may occur when pressure is reduced in the
spinal canal.22
The risk for herniation seems to be particularly pronounced in patients with brain abscesses.23,24 Brain abscesses
are frequently manifested as expanding intracranial lesions
that induce headache, mental disturbances, and focal neurologic signs rather than as an infectious process with signs of
meningeal irritation. Fever is often absent. In 75% of cases,
a primary source of chronic suppuration is present. Common
predisposing factors for brain abscess include craniofacial
trauma; craniocerebral trauma; penetrating injuries that push
bone fragments into the brain; large animal bites of infants
skulls; neurosurgical procedures; cardiovascular disorders
treated with right-to-left shunts; bacterial endocarditis; gramnegative sepsis in neonates; dental infections; chronic sinusitis; otitis; mastoiditis; chronic abdominal, pulmonary, or
pelvic infection; bacterial meningitis; and immunosuppression. Abscesses may also develop in infarcted brain tissue in
septic patients if the blood-brain barrier is compromised.25
Although the CSF is usually abnormal (elevated pressure,
elevated white blood cell [WBC] count, and elevated protein
concentration), spinal puncture in patients with a known or
suspected abscess is contraindicated. Brain herniation markedly reduces the patients likelihood of survival. If the history

Figure 60-1 This computed tomography scan demonstrates a lowdensity mass lesion with an enhancing rim and surrounding edema
in an immunosuppressed patient with an Aspergillus abscess. Lumbar
puncture in such a patient would be contraindicated. (From Zitelli BJ
and Davis HW: Atlas of Pediatric Physical Diagnosis. 5th ed. Philadelphia: Saunders; 2007.)

suggests abscess, CT can rapidly diagnose and localize the


lesion (Fig. 60-1).26 Because the appearance of brain abscesses
on CT is similar to that of neoplastic and vascular lesions,
false-positive reports of brain abscess are possible.26
Spinal epidural hematomas are very rare but may occur in
certain subpopulations of patients undergoing lumbar puncture. Those most at risk are individuals with a bleeding diathesis, including those treated with anticoagulants either
before or immediately after lumbar puncture and those with
abnormal clotting mechanisms, especially thrombocytopenia.
The condition can rarely occur even with a nontraumatic tap
and in the absence of a coagulation defect.27 Spinal subdural
hematomas after lumbar puncture are even rarer.28,29 Lumbar
puncture can injure the dural or arachnoid vessels, which may
result in minor hemorrhage into the CSF. This is generally
of little consequence. However, the number of patients with
hemophilia and human immunodeficiency virus (HIV)
infection who require lumbar puncture has increased since
the late 1990s.
In a coagulopathic patient, attempt to correct the clotting
deficiency if clinically feasible and time permits. The procedure should be performed by experienced clinicians, who are
less likely to traumatize the dura. After the procedure, monitor
the patient carefully for progressive back pain, lower extremity motor and sensory deficits, and sphincter impairment.
Thoroughly investigate any complaints of motor weakness,
sensory loss, or incontinence after lumbar puncture. Lumbar
puncture may be performed in patients with a coagulation
defect if the procedure is expected to provide essential information such as in the diagnosis of meningitis and the pathogen responsible. In cases of severe thrombocytopenia, infusion
of platelets before the puncture may be desirable. Correct
warfarin-induced coagulopathy with fresh frozen plasma
(FFP) or prothrombin complex concentrate together with
vitamin K. However, the vitamin KFFP protocol may take

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

12 to 24 hours to totally reverse the effect of warfarin. Correct


the coagulopathy before a puncture if the clinical situation
permits such delay. Lumbar puncture can be performed safely
in patients with hemophilia A or B whose deficient clotting
factor is replenished before the procedure.30 Additional
replacement of the clotting factor after the procedure is of
unknown value.
Performance of lumbar puncture in patients with leukemia
and low platelet counts has also been studied. Howard and
coworkers reported on 5223 lumbar punctures performed on
958 children with newly diagnosed acute lymphoblastic leukemia.31 The platelet count was 10 109/L or lower in 29
children, 11 to 20 109/L in 170 children, and 21 to 50
109/L in 742 children. No serious complications were reported
in any group. The overall rate of traumatic taps was 10.5%,
but such taps were not associated with adverse sequelae. The
authors concluded that in children with acute lymphoblastic
leukemia, prophylactic platelet transfusion for lumbar puncture is not required if the platelet count is higher than 10
109/L. The number of patients with platelet counts lower than
10 109/L was too small to allow any conclusion about this
group. A more recent review concluded that in the absence
of additional risk factors, a platelet count of 40 109/L
is safe for lumbar puncture. Lower counts are probably
safe as well, but there was insufficient evidence to make
recommendations.32
Aspirin and nonsteroidal antiinflammatory agents have not
been shown to increase the risk for bleeding following lumbar
puncture. Subcutaneous heparin administration is not believed
to pose a substantial risk for bleeding after lumbar puncture
if the total daily dose is less than 10,000 units. The risk for
bleeding in patients taking clopidogrel, ticlopidine, or a glycoprotein (GP) IIb/IIIa receptor antagonist is not known but
is probably small; however, use of these agents should cause
the clinician to proceed with caution. In such cases, performing the procedure under fluoroscopy may be prudent if the
test is needed on an emergency basis. One scenario is the need
to diagnose meningitis because of an unusual or difficult-totreat pathogen. It is necessary to withhold clopidogrel and
ticlopidine 1 to 2 weeks before their anticoagulant effect has
fully dissipated, thus making the decision for emergency
lumbar puncture in such patients a risk-benefit scenario, with
no firm guidelines. Pharmacologic data suggest that cessation
of the GP IIb/IIIa receptor antagonist tirofiban may allow
lumbar puncture after 8 hours and cessation of abciximab
after 24 to 48 hours. Spinal hematoma may develop in 1% to
2% of patients who receive full anticoagulant therapy after
undergoing lumbar puncture.
The clinician should proceed with caution in a patient with
prior lumbar fusion or laminectomy. It is technically difficult
to enter the subarachnoid space in the presence of significant
postoperative changes. It would be acceptable to perform the
puncture in an applicable space above or below the surgical
scar; otherwise, opting for fluoroscopic guidance is prudent.
Some cases of bacterial meningitis have been related to
performing lumbar puncture in a bacteremic patient. Presumably, the procedure introduces bacteria into the CSF. This
phenomenon is rare, difficult to substantiate, and not supported by clinical data. Though of theoretical concern, bacteremia should not be used as a criterion to forego lumbar
puncture if meningitis is suspected.
If the history and physical examination suggest a treatable
illness such as meningitis or SAH, the clinician may perform

1221

a spinal puncture after careful consideration of the entire


clinical picture. In all cases, undertake the study after careful
thought regarding how the results will contribute to evaluation and treatment of the patient. It is unlikely that spinal
puncture will beneficially alter management in patients with
neoplastic disease, intracranial hematoma, abscess, a completed nonembolic infarction, or cranial trauma. Moreover,
even when acute life-threatening emergencies such as SAH
or meningitis are suspected, delaying CSF examination temporarily while empirical treatment proceeds is an important
management option when there are concerns about the safety
of the procedure.

EQUIPMENT
Assemble the standard equipment for a spinal puncture before
starting the procedure. Place it where the operator can easily
access it. A standard-point Quincke cutting needle is most
often used and supplied with the kit. Some operators prefer
to use a Sprotte needle (Havels, Inc., Cincinnati, OH)
or a Whitacre needle (Becton Dickinson and Company,
Rutherford, NJ) to minimize any dural injury associated
with passage of the needle (Fig. 60-2). These styletted needles
have a side port for withdrawal of fluid and, theoretically, are
more likely to separate than cut the dural tissue.
Although commercial kits provide most of the items
needed for lumbar puncture, the operator should bring
additional supplies, including supplemental spinal needles,
specimen tubes, gauze, antiseptic solution, additional local
anesthetic, needles and syringes, and extra sterile gloves of the
appropriate size (see Review Box 60-1).

PROCEDURE
Lumbar puncture is commonly carried out with the patient
in the lateral recumbent position (Fig. 60-3). A line connecting the posterior superior iliac crests intersects the midline at
approximately the L4 spinous process (Fig. 60-4). Spinal
needles entering the subarachnoid space at this point are well
below the termination of the spinal cord, and the only important neurologic structure is the cauda equina. Generally, the
needle pushes isolated nerves to the side during advancement.
The adjacent interspace above or below may be used, depending on which area appears to be most accessible to palpation.
The space between the lumbar vertebrae is relatively wide. In
the thoracic region, the spinous processes overlap and are
directed caudally; therefore, there is no midline area free of
overlying bone. In adults, the spinal cord extends to the lower
level of L1 or the body of L2 in 31% of persons, thus eliminating higher levels as sites for puncture. Puncture in adults
and older children may be performed from the L2-L3 interspace to the L5-S1 interspace.
Developmentally, the spinal canal and the spinal cord are
of equal length in the fetus. Growth of the cord does not
keep pace with the longitudinal growth of the spinal canal.
At birth, the cord ends at the level of the L3 vertebra.
Consequently, in infants the needle should be placed at the
L4-L5 or L5-S1 interspace. The subarachnoid space extends
to the S2 vertebral level; however, the overlying bony mass
prevents entry into this lowermost portion of the subarachnoid space.

1222

SECTION

X NEUROLOGIC PROCEDURES

Sprotte

Quincke

Whitacre

Standard point
(Quincke)

Pencil point
(Whitacre)

Figure 60-2 A, Various spinal needles. B, Penetration of the dura


by Whitacre (pencil-point) and Quincke (cutting) needles. The
Whitacre needle separates the fibers of the dura without cutting
them, whereas the Quincke needle cuts the fibers. The Quincke
needle leaves a hole in the dura through which cerebrospinal fluid
can leak until the hole heals several days or weeks later. Use of
the Whitacre needle has been associated with a lower incidence of
postlumbar puncture headache. (A, From Thomsen T, Setnik G, eds.
Procedures ConsultEmergency Medicine Module. Copyright
2008 Elsevier Inc. All rights reserved.)

When performed with parenteral sedation and proper local


anesthesia, a spinal tap is neither overly distressing nor very
painful to most patients. Almost all patients are likely to have
some anxiety about a spinal puncture for several reasons,
including the stories commonly told of severe complications.
Explain the procedure in advance and discuss each step during
the course of the test to reduce the patients anxiety. Inquire
about any history of allergies to local anesthetic agents and
topical antiseptics. Obtain written informed consent whenever
possible. In all cases, include a detailed procedural note that
documents the process of patient or guardian education
regarding the indications, procedural techniques, risks and
benefits, alternatives to the procedure, and the patients or
guardians consent for the procedure. Abridge this step when
the patient is critically ill or eliminate it when the patient is
mentally incapacitated and no guardian is present. Many

patients greatly fear lumbar puncture, and hence some clinicians provide routine preprocedure sedation or analgesia if not
clinically contraindicated. Intravenous midazolam and fentanyl are useful adjuncts, but practices vary and there is no
consensus on standards with regard to the use or nonuse of
preprocedure medications. In anxious patients it is reasonable
to give a benzodiazepine agent parenterally (e.g., midazolam,
0.1 to 2.5mg intravenously for a healthy adult younger than
60 years of age) to facilitate the procedure. Fentanyl at a dose
of 0.5 to 1.5g/kg (adults) is a reasonable alternative.
The next important step is positioning the patient. Generally, place older children and adults in the lateral decubitus
position for the procedure. Give the patient a pillow to keep
the head in line with the vertebral axis. Position the shoulders
and hips perpendicular to the stretcher or table. Use a firm
table or bed when available. Because flexion of the neck does
not facilitate the procedure to any great extent and severe
flexion may add to the patients discomfort, this step may be
omitted. Severe flexion of the neck in an infant may cause
airway compromise. Pull the knees up to the chest and arch
the lower part of the patients back toward the clinician by
having the patients knees drawn toward the chest.
Some clinicians place the patient in an upright sitting position because the midline is more easily identified. This position can be used in both adults and infants (Fig. 60-5). The
higher CSF hydrostatic pressure while sitting may aid flow of
CSF in a dehydrated patient. Observe caution regarding
orthostatic changes in blood pressure and airway maintenance. Generally, allow a sitting patient to lean onto a bedside
stand and use a pillow to rest the head and arms. Have an
assistant support the patient during the procedure. Radiographic studies by Fisher and colleagues have demonstrated
the advantages of hip flexion when the sitting position is
used.33 To accomplish hip flexion, use a stool to support the
patients feet, which pulls the knees up toward the chest. This
increases lumbar interspinous width, which may increase the
success and ease of needle passage.
Iatrogenic infection after lumbar puncture is extremely
rare. Use sterile gloves during the procedure, but the need for
face masks is debatable.34-36 Apply the same guidelines for
control of central line infection (caps, gowns, gloves, and
masks) to lumbar puncture.37 Wash the patients back with an
antiseptic solution applied in a circular motion and increase
the circumference of the cleansed area with each motion.
Place a sterile towel or drape between the patients hip and
the bed. Commercial trays have a second sterile drape with a
hole that may be centered over the site selected for the
procedure.
Infiltrate the skin and deeper subcutaneous tissue generously with local anesthetic. Buffered or warmed 1% lidocaine
is preferred. Warn the patient about transient discomfort
from the anesthetic. Anesthetizing the deeper subcutaneous
tissue significantly reduces procedural discomfort. Merely
raising a skin wheal is insufficient anesthesia. Some operators
not only anesthetize the interspinous ligament but also apply
local anesthetic in a vertically fanning distribution on both
sides of the spinous processes near the lamina. Such a field
block on each side of the spinous processes anesthetizes the
recurrent spinal nerves that innervate the interspinous ligaments and muscles.
While waiting for the anesthetic to take effect, connect the
stopcock and manometer and ensure that the valve is working.
Commonly, a 3.5-inch, 20-gauge needle is used in adults, and

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

1223

SPINAL PUNCTURE
1

Position the patient


in the bed. Generally,
the lateral decubitus
position is preferred.
Arch the patients
back towards you.

2
Level of
iliac crest
Anatomic
midline

Consider mild
sedation or analgesia
when clinically
appropriate.

Prepare the skin with


antiseptic solution.
Apply in a circular
motion with a gradually
increasing
circumference.

Create a wheal with


anesthetic in the skin
overlying the entry
site. Then, infiltrate
and anesthetize the
deeper tissues.

CSF will flow from


the needle hub
when the
subarachnoid space
has been penetrated.

Collect the CSF


sample in sequential,
numbered vials.

Identify and mark


anatomic landmarks.
The L4 spinous
process is at the level
of the posteriorsuperior iliac crests.

Apply a sterile drape.

Insert the needle in


the midline. Hold
the needle parallel
to the bed, and
advance it toward the
umbilicus. Remove
the stylet periodically
to check for CSF.

Attach the
manometer and
measure the
opening pressure.

10

Replace the stylet


before removing the
needle.

Figure 60-3 Spinal puncture. CSF, cerebrospinal fluid.

1224

SECTION

X NEUROLOGIC PROCEDURES

L3 L4 L5
Iliac crest

L3
L4
L5

Spinal cord
L5 L 4 L3 L2 L1

Cauda equina
Iliac crest

B
Figure 60-6 Various ways to hold the spinal needle.

Figure 60-4 The L4 spinous process is at the level of the posterior


superior iliac crest. The spinal cord ends approximately at the level
of L1 or L2 in adults; fibers of the cauda equina extend inferiorly
from there. When the patient is positioned correctly for lumbar
puncture, an imaginary line connecting the iliac crests will be exactly
perpendicular to the bed, and the spine will be parallel to the bed.

Iliac crest
L4-L5 landmark

B
Figure 60-5 A, Many clinicians prefer the sitting position for
lumbar puncture because of the ease of entering the dural space.
However, the opening pressure obtained in this position is not accurate. If possible, place the patient in the lateral decubitus position for
measurement of pressure, usually after fluid has been collected.
B, Upright positioning in an infant. (A, From Thomsen T, Setnik G,
eds. Procedures ConsultEmergency Medicine Module. Copyright
2008 Elsevier Inc. All rights reserved. B, from Dieckmann R, Selbst S,
eds. Pediatric Emergency and Critical Care Procedures. St. Louis:
Mosby; 1997.)

a 2.5-inch, 22-gauge needle is used in children (a 1.5-inch,


22-gauge needle is available for infants). Needles of these sizes
have enough rigidity to allow the procedure to be accomplished easily but make less of a dural tear than larger needles
do. Patients should be told to report any pain and be informed
that they will feel some pressure.
With the patient in the lateral decubitus position, place the
needle into the skin in the midline, parallel to the bed. Hold
the needle between both thumbs and index fingers (Fig. 60-6).
After the subcutaneous tissue has been penetrated, angle the
needle toward the umbilicus. The bevel of the needle should
be facing straight up toward the ceiling.
The supraspinal ligament connects the spinous processes,
and the interspinal ligaments join the inferior and superior
borders of adjacent spinous processes. The ligamentum
flavum is a strong, elastic membrane that may reach a thickness of 1cm in the lumbar region. The ligamentum flavum
covers the interlaminar space between the vertebrae and
assists the paraspinous muscles in maintaining an upright
posture (Fig. 60-7). The ligaments are stretched in a flexed
position and are more easily crossed by the needle. The ligaments offer resistance to the needle, and a pop is often felt
as they are penetrated. Hold the stylet in place during advancement but remove it frequently to see whether the subarachnoid space has been reached. The pop may not be felt with
the very sharp needles contained in disposable trays.
If bone is encountered, partially withdraw the needle to
subcutaneous tissue. Repalpate the back and ascertain that the
needle is in the midline. Directing the tip of the needle toward
the navel often enhances navigation of the interspinal space.
If bone is encountered again, slightly withdraw and reangle
the needle so that the point is placed at a more sharply cephalad angle (Fig. 60-8). This approach should avoid the inferior
spinous process.
Normal CSF is a clear fluid and will flow from the needle
when the subarachnoid space has been penetrated and the
stylet is removed. In normal patients, the dura will be penetrated when the needle is advanced about one half to three
fourths of its length. In obese patients, the entire length of the
needle may be required to reach the subdural space (Fig. 60-9).
If feasible, attach the manometer and record the opening
pressure (Fig. 60-10). This step is commonly omitted in critically ill patients. Pressure readings from a struggling patient
may be inaccurate. Readings are valid only if taken with the
patient relaxed and in the lateral decubitus position (not the
sitting position). A three-way stopcock, supplied in disposable

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

1225

Supraspinal
ligament
Filum
terminale

Body of L1

Interspinal
ligament

Conus
medullaris
Anulus
fibrosus
and
nucleus
pulposus of the
intervertebral
disk

Ligamentum
flavum
Cauda equina
in the subarachnoid
space
Spinous
process of L-4
Dura/arachnoid

Posterior
longitudinal
ligament

Epidural space

Termination of
the thecal sac

Figure 60-7 Midsagittal section through the lumbar spinal column


with a spinal puncture needle in place between the spinous processes
of L3 and L4. Note the slightly ascending direction of the needle.
The needle has pierced three ligaments and the dura/arachnoid and
is in the subarachnoid space. (From Lachman E. Anatomy as applied to
clinical medicine. New Physician. 1968;17:145.)

trays, allows both collection of CSF and measurement of


opening pressure with a single needle. Positioning of the
manometer is often more convenient if an extension tube
(provided with most disposable trays) connects the needle hub
to the stopcock, which in turn is attached to the manometer.
Position the manometer so that the zero mark is at the level
of the spinal needle. Then ask the patient to relax. Extending
the legs after needle placement does not meaningfully decrease
opening CSF pressure.38 The observation of phasic changes
in the fluid column with respirations and arterial pulsations
confirms needle placement in the subarachnoid space. If the
needle is against a nerve root or is only partially within the
dura, the pressure may be falsely low, and respiratory excursions will not be reflected in the manometer. Minor rotation
of the needle may solve these problems. Hyperventilation will
reduce the pressure readings because of hypocapnia and the
resultant cerebral vasoconstriction.
After measuring the pressure, turn the stopcock and collect
enough fluid to perform all the studies desired. The first
sample of fluid exits from the manometer if pressure has been
measured, and then additional fluid flows from the spinal
canal. Even if the pressure is elevated, remove sufficient fluid
for performance of all indicated studies because the risk associated with the procedure involves the dural rent, not only the
amount of fluid initially removed. Presumably, more fluid will
subsequently be lost through the hole in the dura. Replace
the stylet into the needle before withdrawing it.
Commercial trays generally supply four specimen tubes.
One tube is commonly used for determining protein and
glucose levels and for electrophoretic studies, another is used
for microbiologic and cytologic studies, and a third is used for
serologic tests. Cell counts should be performed in the first

B
Figure 60-8 A, This 22-gauge spinal needle has struck bone during
advancement (notice the bend in the needle) and needs to be repositioned. B, If bone is encountered, it is usually the inferior spinous
process (red spinal needle). The needle must be partially withdrawn
into subcutaneous tissue and then readvanced in a more cephalad
direction (green needle).

Figure 60-9 The spinal needle is usually advanced one half to three
fourths of its length before the spinal canal is reached. In this obese
patient, the needle was advanced all the way to the hub of the needle
before spinal fluid was returned.

and third tubes to help differentiate traumatic taps from true


SAH. Depending on the clinical scenario, additional tests may
be indicated. Use special stains, such as India ink for suspected
Cryptococcus infection in patients with acquired immuno
deficiency syndrome (AIDS), acid-fast stain in patients with
possible tuberculous meningitis, and viral studies in patients
with suspected encephalitis. The fourth tube can be stored
under refrigeration in the laboratory for any additional studies
that may be required after the initial assessment.

1226

SECTION

X NEUROLOGIC PROCEDURES

Traumatic taps are common and usually clinically inconsequential. Nevertheless, they can be minimized by proper
patient and needle positioning. A traumatic tap most commonly occurs when the subarachnoid space is transfixed at the
entrance of the ventral epidural space, where the venous
plexus is heavier. A plexus of veins forms a ring around the
cord, and these veins may be entered if the needle is advanced
too far ventrally or is directed laterally (Fig. 60-11). If
blood is encountered and the fluid does not clear, repeat the
procedure at a higher interspace with a fresh needle. A traumatic tap, per se, is not a particularly dangerous problem in
a patient with normal coagulation, and no specific precautions
are needed if blood-tinged fluid is obtained. However, observe
for signs of cord or spinal nerve compression from a hematoma developing within the first several hours in patients with
a coagulopathy.

Lateral Approach for Lumbar Puncture


The supraspinal ligament might be calcified in older persons,
thus making a midline perforation difficult. A calcified ligament may deflect the needle. In this case, use a slightly lateral
approach. Because the lower lamina rises upward from the
midline, direct the needle slightly cephalad to miss the lamina
and slightly medially to compensate for the lateral approach.
The needle passes through the skin, superficial fascia, fat, the
dense posterior layer of the thoracolumbar fascia, and the
erector spinae muscles. The needle then penetrates the ligamentum flavum (bypassing the supraspinal and interspinal
ligaments), the epidural space, and the dura before CSF is
obtained (Fig. 60-12). Lateral cervical puncture is an alternative approach that can be performed utilizing an insertion site
1cm inferior and 1cm dorsal to the mastoid process.39

Lumbar Puncture in Infants


Lumbar puncture in infants is usually performed to exclude
meningitis or encephalitis. The sitting position may allow the
midline to be identified more easily. Use of a needle without
a stylet has been suggested for small infants because this
device allows the pressure to be estimated as the needle

punctures the dura.40 However, failure to use a stylet may


cause the subsequent development of an intraspinal epidermoid tumor.41 Use of a butterfly infusion set needle simplifies
the procedure, which is helpful when managing a squirming
or hyperactive patient.40 In general, a stylet is recommended
primarily at the time of skin penetration and on needle withdrawal, although many operators use the stylet during any
advancement of the needle.

Internal
vertebral
plexus

External
vertebral
plexus

Nerve roots
forming
the cauda
equina

Radiculomedullary
vein
Arachnoid
Lumbar
vein

Dura
mater

L5 nerve root
Internal
vertebral
plexus

Spinal
needle

Figure 60-11 The spinal contents at L4 and L5 show the relationship of a lumbar puncture needle to the major vessels at this level.
The major radiculomedullary vein, shown accompanying the L5
nerve root, is situated far lateral to a needle correctly positioned in
the midline of the dural sac. Note the avascular subdural space. (From
Edelson RN, Chernik IVL, Rosner JB. Spinal subdural hematomas. Arch
Neurol. 1974;31:134. Illustration by Lynn McDowell. Reproduced by
permission. Copyright 1974, American Medical Association.)

Interspinal
ligament

Supraspinal
ligament

Ligamentum
flavum

Erector
spinae
muscle

Articular process

Epidural
space

Dura/arachnoid

Body of L3

Figure 60-10 To measure the opening pressure, attach the manometer to the needle hub with a 3-way stopcock. The zero mark of
the manometer should be level with the site of needle entry.

Subarachnoid space
containing the cauda
equina and lumbar
puncture needles

Figure 60-12 Horizontal section through the body of L3. Note the
two puncture needles in the subarachnoid space. The medial needle
is in the midline. The lateral needle exemplifies the lateral approach,
which avoids the occasionally calcified supraspinal ligament. Note
the lateral needle piercing the intrinsic musculature of the back and
only one ligament, the ligamentum flavum. (From Lachman E.
Anatomy as applied to clinical medicine. New Physician. 1968;17:745.)

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

If the childs neck is very tightly flexed, CSF might not be


obtained. However, if the head is held in midflexion, CSF
usually flows briskly. If CSF fails to flow, gently suction with
a 1.0-mL syringe to exclude a low-pressure syndrome. Because
pressure readings are inaccurate in a struggling child, measurement of pressure is not commonly attempted in infants
and young children.42
Avoid prolonged severe flexion of the neck in an infant because
it may produce dangerous airway obstruction. If the infant suddenly stops crying, check the airway immediately.43 Proper
positioning is best accomplished by an assistant, who maintains the spine maximally flexed by partially overlying the
child and using the chest and body weight to immobilize the
thorax and hips while holding the child behind the shoulders
and knees.44 Infants have poor neck control; therefore, the
assistant must also ensure that the child maintains an open
airway. Pay particular attention to avoiding marked neck and
trunk flexion. Incorrect positioning usually results in multiple
punctures and a bloody tap.
Newborn and preterm infants may experience significant
hypoxia and clinical deterioration during lumbar puncture; a
sitting position appears to be preferable.45 Lumbar puncture
in infants with respiratory distress syndrome may pose greater
risk than benefit.46 This is a problem primarily in neonates

ULTRASOUND: Lumbar Puncture 


When ultrasound is used to guide lumbar puncture, it is generally done
in a static manner: the ultrasound probe is used to determine the site
of skin entry, the skin is marked, and the probe is then set aside.
Equipment
A linear probe is preferred, although for patients with an extremely high
body mass index, a curvilinear probe may be required because of the
distance between the skin and the spine.

Figure 60-US1 Transverse image of the lumbar spine. The


crescent-shaped hyperechoic structure (arrow) is a spinous process.
Note the presence of posterior acoustic shadowing. Align the probe
so that the spinous process is directly centered in the image. The
general symmetry of the image provides additional assurance that
the probe is centered correctly.

1227

but may also apply to younger infants with sepsis. Closely


monitor all infants with serious cardiopulmonary disease
during the procedure. Preoxygenation with or without monitoring oxygen saturation may be used as a precaution.
Although local anesthesia or sedation has not been a
routine practice during lumbar puncture in an infant or child,
it is being reconsidered.47,48 Neonates perceive pain, and local
anesthesia neither produces physiologic instability nor makes
the procedure more difficult.49,50 The use of topically applied
EMLA (eutectic mixture of local anesthetics) (AstraZeneca)
reduces the pain associated with needle insertion in newborns.51 Sedation of an anxious child may be considered, but
sedatives are relatively contraindicated in an obtunded patient
without a protected airway and in the setting of hemodynamic
instability.

The Difficult Lumbar Puncture


The traditional approach to lumbar puncture depends on
palpation of bony landmarks to determine the correct location
for insertion of the needle. However, landmarks are difficult
to palpate in overweight and obese patients.52 When lumbar
puncture fails, the usual alternative has been fluoroscopic
guidance, which necessitates movement of the patient out of
by Christine Butts, MD
Image Interpretation
The bony spinous process will appear as a hyperechoic crescent-shaped
structure with posterior acoustic shadowing. In the transverse view, acquisition of a perfectly symmetric image will provide assurance that the
probe is in the anatomic midline (Fig. 60-US1). In the longitudinal view,
multiple spinous processes can be visualized, along with the interspaces
between them (Fig. 60-US2).

Figure 60-US2 Longitudinal image of the lumbar spine. Again


visible are the spinous processes (small arrows), which appear as
crescent-shaped hyperechoic structures with acoustic shadowing.
In between each spinous process is the interspinous space (large
arrow). Note how this space is bordered on either side by the
acoustic shadow of the spinous process. Note also how the probe
is centered directly over the interspace.
Continued

1228

SECTION

X NEUROLOGIC PROCEDURES

ULTRASOUND: Lumbar Puncture, contd

US probe,
transverse
orientation

Figure 60-US3 First use the ultrasound (US) probe in the transverse orientation at the level of the iliac crests, and obtain an image
with the shadow of the spinous process centered on the screen (as
in Fig. 60-US1). Mark the skin at the exact midpoint of the transducer. This represents the anatomic midline.

US probe,
longitudinal
orientation

Figure 60-US4 Rotate the ultrasound (US) probe 90 degrees and


obtain a midline longitudinal view. Position the probe so that the
interspace is centered on the screen (as in Fig. 60-US2). Mark the
skin at the midpoint of the transducer. This represents the level of
needle entry.

Procedure and Technique


To perform ultrasound-guided lumbar puncture, position the patient in
the usual manner. Place the ultrasound probe over the spine in a transverse orientation at the level of the iliac crests such that the shadow
caused by the spinous process is centered on the screen. Use a pen to
mark the skin on each side of the transducer, exactly at the midpoints
(Fig. 60-US3). These two marks can then be connected to mark the
midline of the spine. Next, rotate the transducer 90 degrees to obtain a
midline longitudinal view and position it until the gap between two spinal
processes is in the center of the screen. Mark the skin at the midpoint
of each side of the transducer and then connect the marks to form a
single line (Fig. 60-US4). The intersection of the two lines is the site for
entry of the needle (Fig. 60-US5). Cleanse the skin with antiseptic solution and perform the remainder of the procedure in the usual fashion.

Figure 60-US5 The intersection of the anatomic midline and the


level of the interspinous space is the site of needle entry.

the ED, as well as the availability of an appropriately trained


radiologist.52 Bedside ultrasound is increasing being used in
emergency and critical care medicine, and its scope of practice
has expanded to include guidance for a number of procedures,
including lumbar puncture (see Ultrasound Box).53-56 Ultrasound can be used in adults, as well as in neonates and infants.57

COMPLICATIONS
Headache after Lumbar Puncture
A number of complications from lumbar puncture have been
reported.58 One of the most common is headache, which

occurs after 1% to 70% of spinal taps.59-66 In general, the


development of postpuncture headache can be neither prognosticated nor prevented. The syndrome most commonly
starts within the first 48 hours after the procedure (although
a case occurring 12 days after the procedure has been
reported)67 and usually lasts for 1 to 2 days (occasionally as
long as 14 days). Cases lasting months have been described.
The headache usually begins within minutes after the patient
arises and characteristically ceases as soon as the patient lies
down. The pain is mild to incapacitating and is generally
cervical and suboccipital in location but might involve the
shoulders and the entire cranium. Exceptional cases include
nausea, vomiting, vertigo, blurred vision, ear pressure,

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

tinnitus, and stiff neck. The headache may change to a positional backache or neck ache.
The technique of spinal puncture probably has little to do
with the development of a postprocedure headache. The syndrome is widely thought to be caused by leakage of fluid
through the dural puncture site. This results in a reduction
in CSF volume below the cisterna magna and downward
movement of brain tissue, along with displacement and
stretching of pain-sensitive structures such as the meninges
and vessels, and causes a traction headache. The recumbent
position brings relief because the weight of the brain is shifted
cephalad. Another proposed mechanism is cerebral vasodilation. A more recent hypothesis suggests that the headache is
caused by an altered distribution of craniospinal elasticity and
acute intracranial venous dilation.68 Some authors have commented on the incidence and severity of postdural puncture
headache as being related to the orientation of the spinal
needle bevel and its type and size.69-79 It is clear that the incidence of postdural puncture headache is lower when the
bevel of the needle is oriented parallel to the longitudinal axis
of the spine. Until relatively recently the explanation for this
was that the parallel bevel would separate rather than cut the
longitudinal dural fibers and thus produce a smaller dural hole
and less CSF leakage. However, it is now known that the dural
fibers are oriented randomly, not longitudinally.80 Even with
random fiber orientation, back flexion is more likely to close
a dural hole in the longitudinal plane than a hole in the horizontal plane.
The two basic types of spinal needles are cutting (Quincke)
and noncutting or pencil point (Sprotte and Whitacre). Noncutting needles cause a lower incidence of headache after
dural puncture, perhaps because the tip of the needle tends
to separate rather than cut the dural fibers. It has traditionally
been thought that the dural hole resulting from puncture
with a noncutting needle is smaller than that created by puncture with a cutting needle; however, this may not be true.
The important difference may be that the cutting needle
causes a clean-cut opening in the dura whereas the noncutting needle produces a jagged opening with rough edges.81
The jagged opening may produce a more intense inflammatory response that results in edema and more complete
closure of the hole. The use of atraumatic spinal needles is
not routine.82 As more spinal kit manufacturers include them
in kits, their use might increase.83 A single-institution study
suggested that routine use of noncutting needles yields a
potential cost savings.84 However, in thick-skinned individuals, passage of a thin, noncutting needle may be technically
difficult. Making the initial pass with a thicker cutting needle
to the level of the interspinal ligament, followed by removal
and advancement of a noncutting needle in the same soft
tissue tract, can be helpful.
Use of a smaller-diameter needle is one intervention that
will probably cause a lower incidence of postpuncture headache because it creates a smaller dural hole. If diameter were
the only consideration, as small a needle as possible would be
used. However, a needle must provide adequate CSF flow
rates to allow timely CSF collection and pressure measurement. With a very small needle, a syringe may be needed to
withdraw fluid, and pressure cannot be recorded easily. In
addition, technically, a small needle such as a 26 gauge is difficult to place and manipulate into a position in which it does
not become intermittently obstructed by nerve roots. When
these characteristics are considered, a 20- to 22-gauge

1229

atraumatic needle seems to be the best overall choice for


diagnostic lumbar puncture.72
Despite common beliefs about techniques and postprocedure interventions, lumbar puncture headaches may not be
completely preventable. Studies of the influence of directives
such as strict bed rest on postpuncture headache have yielded
contradictory results, with no consensus on any specific preventive intervention forthcoming concerning the worsening
of, improvement in, or effect on the incidence. Brocker
reported a reduction in the incidence of headache from 36.5%
to 0.5% when patients lie prone instead of supine for 3 hours
after puncture with an 18-gauge needle.85 He postulated that
the prone position caused hyperextension of the spine and
disrupted alignment of the holes in the dura and the arachnoid, thus making leakage less likely. Thoennissen and
coworkers concluded that there was no evidence that longer
bed rest after lumbar puncture was better than immediate
mobilization or short bed rest in reducing the incidence of
headache.86 There appears to be no reason to enforce bed rest
following lumbar puncture.
Other factors that might influence the incidence of a post
spinal puncture headache were reviewed by Fishman and by
Lin and Giederman.21,87 The incidence is higher in young
patients than in older patients and is also increased in females
and individuals with a history of headache. Many medications
have been advocated for the treatment of headache after
lumbar puncture: barbiturates, codeine, neostigmine, ergots,
diphenhydramine (Benadryl), dimenhydrinate (Dramamine),
caffeine, amphetamine sulfate (Benzedrine), ephedrine, intravenous fluids (normal saline, lactated Ringers solution), magnesium sulfate, and vitamins.21,88-90
Caffeine is a traditional common initial intervention for
postpuncture headache, and it appears to be of benefit.90 Caffeine can be administered in the ED, and pain relief can be
seen within a few hours and is thought to result from caffeines
vasoconstrictive effect on the cerebral vasculature. One suggested regimen is 500mg of caffeine (sodium benzoate)
diluted in 1000mL of normal saline infused over a 1- to
2-hour period. A second dose can be given if the headache is
not relieved. If successful, consumption of caffeinated beverages may be continued as an outpatient.
Most postpuncture headaches can be managed by bed rest
with the head in the horizontal position. Avoid dehydration
because it lowers CSF pressure and might aggravate the headache. Although dehydration should be avoided, the role of
fluid supplementation in the prevention of postdural puncture headache remains uncertain.
Simple analgesics are commonly prescribed, but they have
no apparent advantage over bed rest and fluid intake. A patient
with a prolonged headache after spinal puncture should be
reassessed to rule out structural causes. Because a spinal headache has classic signs and symptoms, if the headache is not
postural, consider other causes.
In summary, because most postlumbar puncture headaches are mild and self-limited, conservative therapy for the
first 24 to 48 hours is recommended. Bed rest and oral analgesics, including opioids, are usually effective, as well as perhaps
oral caffeine drinks, but for those refractory to conservative
measures, an epidural blood patch is recommended.
For patients with a prolonged low-pressure headache,
placement of an epidural blood patch by experienced operators is highly successful and often provides dramatic relief.91-95
Consider a blood patch for all patients with seriously

1230

SECTION

X NEUROLOGIC PROCEDURES

symptomatic spinal headaches. Perform an epidural tap at the


level of the previous lumbar puncture. Use the loss-of-resistance technique with sterile saline to locate the epidural
space.96 Draw 10 to 20mL of autologous blood into a syringe
aseptically and slowly inject it (1 to 2mL every 10 seconds)
into the epidural space at the site of the dural puncture.97 Slow
or discontinue the injection if back pain or paresthesia develops. Keep the patient supine for 1 hour while hydration is
administered intravenously. Relief usually occurs within 20 to
30 minutes after the procedure. Epidural patches are less
likely to be effective if symptoms have been present for more
than 2 weeks. Pain is relieved when the blood patch forms a
gelatinous tamponade that stops the CSF leak and immediately elevates CSF pressure. Patch failures (15% to 20%) are
believed to be caused by improper needle placement, injection
of an inadequate quantity of blood (after which a second patch
is usually successful), or an incorrect diagnosis.
Complications reported after placement of an epidural
patch include back stiffness, paresthesia, radicular pain, subdural hematoma, adhesive arachnoiditis, and bacterial meningitis.98 The procedure should be used in patients with
refractory headaches that do not respond to conservative
therapy, and it should be performed by clinicians trained in
the procedure.

Infection
Spinal puncture is contraindicated in the presence of local
infection at the puncture site (cellulitis, suspected epidural
abscess, or furunculosis) because of the danger of inducing
meningitis. A large concentration of bacteria in the bloodstream at the time of CSF examination is associated with
meningitis. The meningitis could be coincidental (spontaneous) or could result from leakage of blood containing bacteria into the subarachnoid space after lumbar puncture
(induced). It is likely that many cases of puncture-induced
meningitis emerge after a cautious clinician performs a lumbar
puncture early in the course of meningitis, before the infection has had time to be reflected in CSF. A recent review
concluded that the majority of cases of postpuncture meningitis are probably caused by contamination of the site with
aerosolized bacteria from medical personnel, contamination
from skin flora, or least commonly, direct or hematogenous
spread from an endogenous infectious site.37 Suspected bacteremia is not a contraindication to lumbar puncture. Delay
in diagnosis because of concern regarding the risks associated
with lumbar puncture is probably more serious than the risk
of causing meningitis with the procedure.99,100

Herniation Syndromes after Lumbar


Puncture
Lumbar puncture is of value in confirming a diagnosis of
meningitis, encephalitis, or SAH. Generally, when the patient
has symptoms consistent with bacterial meningitis but not
increased ICP, it is safe to perform lumbar puncture before a
head CT scan. Lumbar puncture may also be the best initial
procedure to diagnose SAH, thus reducing the need for
routine CT scanning in certain low-risk patients with acute
sudden headache.101 However, in patients with focal findings,
papilledema, or a suspected intracranial mass lesion, one
should perform a CT scan before lumbar puncture. When
meningitis remains in the differential diagnosis, antibiotics

are best administered after blood is obtained for culture and


before the CT scan.
Particularly in patients with supratentorial masses, there
may be a large pressure gradient between the cranial and
lumbar compartments. When brain volume is increased
because of a mass or edema, rostrocaudal displacement may
occur after lumbar puncture if the skull is intact.
The question of whether lumbar puncture precipitates
brain herniation in cases in which herniation would not have
occurred spontaneously cannot be answered with certainty.
Controversy still exists regarding the risk for brain herniation
from lumbar puncture in patients with acute bacterial meningitis, and data continue to be sparse.102 Herniation may occur
in the absence of lumbar puncture in the setting of acute bacterial meningitis and has been temporally related to the procedure. Brain herniation occurs in about 5% of patients with
acute bacterial meningitis and accounts for about 30% of the
deaths associated with the disease.102 Although CT imaging
may reveal contraindications to lumbar puncture, normal findings on CT do not eliminate the risk for herniation and do not
necessarily mean that a lumbar puncture is safe.
Lowering pressure in the lumbar spinal canal by removing
CSF can increase the gradient between the cranial and lumbar
compartments and thereby theoretically promote both transtentorial and foramen magnum (cerebellar) herniation. The
frequency with which lumbar puncture causes or accelerates
transtentorial herniation is unknown because herniation
might have developed spontaneously in a seriously ill patient
without the procedure. With the current use of small-caliber
spinal needles, herniation appears to be extremely rare; nonetheless, it is fully predictable neither by CT nor by opening
CSF pressure readings.
A careful neurologic examination should precede all spinal
punctures. When the patient has a history of headache and
fever with progressive deterioration in mental status and
localizing neurologic signs, spinal puncture should not be
performed as the initial diagnostic procedure. Gopal and colleagues identified three statistically significant predictors of
new intracranial masses: papilledema, focal abnormalities on
neurologic examination, and altered mental status.103 Greig
and Goroszeniuk made similar recommendations.104 Hasbun
and associates demonstrated that in adults with suspected
meningitis, the presence of any of 13 clinical features is predictive of abnormal findings on CT (Box 60-1).105 Theoretically, the presence of abnormal findings on CT portends
potential herniation, with or without lumbar puncture. The
absence of abnormal findings suggests the patient is a good
candidate for immediate lumbar puncture because the risk
for brain herniation as a result of the procedure is low (see
Box 60-1). Joffe argues that clinical signs of impending herniation are the most appropriate criteria on which to base
decision making regarding the timing of lumbar puncture in
patients with acute bacterial meningitis.102 Such signs include
a significantly decreased level of consciousness (Glasgow
Coma Scale score 11), brainstem findings (pupillary changes,
posturing, irregular respirations), and a very recent seizure.102
It is recommended that these patients undergo neuroimaging
(CT or MRI) and receive antibiotics empirically while awaiting the results of imaging, which will help in assessment of
the safety of a subsequent lumbar puncture. Measures to
lower ICP before spinal puncture may also be considered.
Appropriate cultures of blood and more easily accessible body
fluids should be obtained before the administration of

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

BOX 60-1 Clinical Characteristics Associated

with Abnormal Findings on Head CT


in Adults with Suspected Meningitis
Age 60 years or older
Immunocompromised state*
History of central nervous system disease
Seizure within 1 week before initial evaluation
Abnormal level of consciousness
Inability to answer two questions correctly
Inability to follow two commands correctly
Gaze palsy
Abnormal visual fields
Facial palsy
Arm drift
Leg drift
Abnormal language
From Hasbun R, Abrahams J, Jekel J, etal. Computed tomography of the head
before lumbar puncture in adults with suspected meningitis. N Engl J Med.
2001;345:1727.
CT, computed tomography.
*Includes patients with human immunodeficiency virus infection or acquired
immunodeficiency syndrome, those receiving immunosuppressive therapy, and those
who have undergone transplantation.

Mass, stroke, or focal infection.

Aphasia, dysarthria, or extinction.

antibiotics. Blood cultures are positive in 80% of infants with


meningitis.
Critically ill patients with acute bacterial meningitis often
deteriorate rapidly and experience fatal brain herniation, both
shortly after lumbar puncture and in the absence of the
procedure. A direct cause-and-effect relationship between
lumbar puncture and brain herniation in the setting of suspected meningitis is obscure and probably cannot be defined
prospectively in the ED when clinical decisions must be made.
A recent review identified 22 case reports of rapid deterioration and herniation after lumbar puncture in adults and children with acute bacterial meningitis.102 The general consensus
is that less ill patients (clearly a subjective clinical judgment)
with a clinical scenario that includes meningitis as a possibility
can be evaluated safely with lumbar puncture. In critically ill
patients, especially those with localizing neurologic signs,
severely depressed level of consciousness, or papilledema,
diagnostic lumbar puncture may be delayed until the risk for
herniation is lower, and aggressive and empirical treatment
with meningitis doses of antibiotics should proceed.
Head CT can identify hemorrhagic lesions and most neoplasms. Its results should contribute to the decision regarding
the need for and the risk involved with spinal puncture. Head
CT can identify patients with unequal pressure between intracranial compartments, who are at greater risk for cerebral
herniation. Findings that suggest unequal pressure include (1)
lateral shift of midline structures, (2) loss of the suprachiasmatic and perimesencephalic cisterns, (3) shift or obliteration
of the fourth ventricle, and (4) failure to visualize the superior
cerebellar and quadrigeminal plate cisterns with sparing of the
ambient cisterns.106 The presence of a mass in the posterior
fossa is a strong contraindication to lumbar puncture. Unfortunately, because of bone and motion artifact, the posterior
fossa may be a difficult area to visualize on CT.

1231

Although there is no clear standard with respect to the use


of CT before lumbar puncture, a reasonable and logical
approach is to avoid initial lumbar puncture and first perform
head CT when a mass lesion is suspected or if the patient has
signs and symptoms of increased ICP (see Box 60-1). This
approach correlates with the clinical policy promulgated by
the American College of Emergency Physicians in 2002.107

Epidermoid Tumor
An epidermoid tumor or cyst is a mass of desquamated cells
containing keratin within a capsule of well-differentiated
stratified squamous epithelium. Congenital lesions arise from
epithelial tissue that becomes sequestered at the time of
closure of the neural groove between the third and the fifth
weeks of embryonic life, but such lesions are rare. Acquired
intraspinal epidermoid tumors result from the implantation
of epidermoid tissue into the spinal canal at the time of
lumbar puncture performed with needles without stylets or
with ill-fitting stylets. The clinical syndrome consists of pain
in the back and lower extremities developing years after
spinal puncture. Failure to use a stylet on needle withdrawal
might also result in aspiration of a nerve root into the epidural space.

Backache and Radicular Symptoms


Minor backache from the trauma of the spinal needle occurs
in 90% of patients. Frank disk herniation has been reported
from passage of the needle beyond the subarachnoid space
into the anulus fibrosus. Transient sensory symptoms from
irritation of the cauda equina are also common.
Other reported complications include transient unilateral
or bilateral sixth-nerve palsies caused by stretching or displacement of the abducens nerve as it crosses the petrous
ridge of the temporal bone, SAH, subdural and epidural
hematoma, epidural CSF collection, cauda equina syndrome,
anaphylactoid reactions to local anesthetics, settling of cord
tumors, and retroperitoneal abscess produced by laceration of
the dura in patients with meningitis.108-114 Most of these complications are rare and seldom encountered; however, they
should be considered if a patient returns after a lumbar puncture with worsening back pain or abnormal findings on
neurologic examination.
The complications associated with lateral cervical and cisternal puncture are similar to those encountered with lumbar
puncture. Perforation of a large vessel with resultant cisterna
magna hematoma or obstruction of vertebral artery flow has
been described. Puncture of the medulla oblongata may cause
vomiting or apnea, and puncture of the cord may be associated with pain. Long-lasting side effects of cord puncture
seem to be rare. A traumatic tap and postpuncture headache
may occur.

Spinal Epidural Hemorrhage


Rarely, serious bleeding leading to spinal hematoma secondary to lumbar puncture can produce spinal cord compromise
and permanent significant neurologic deficits, such as cauda
equina syndrome.27 This may occur more frequently in coagulopathic patients but can occur in those with a normal coagulation profile and a seemingly atraumatic tap. The bleeding is
concealed and may be suspected only by persistent severe

1232

SECTION

X NEUROLOGIC PROCEDURES

backache or neurologic findings. Weakness, numbness, and


incontinence after spinal puncture must be investigated,
usually with MRI for a possible spinal hematoma. Surgical
intervention, including laminectomy and evacuation of blood,
may be required and must occur in a timely manner to avoid
permanent loss of neurologic function. Those with mild
symptoms and progressive recovery may be managed conservatively with close monitoring.

INTERPRETATION
Pressure
CSF pressure is clinically important.115 Measure it accurately
whenever feasible. Unfortunately, in some cases it will be
logistically impossible to obtain. If the lumbar puncture is
being performed with the patient in a seated position, place
the patient in the lateral decubitus position before a measurement is obtained. This may be done initially, before fluid is
collected, or after fluid collection, in which case a closing
pressure is obtained. By repositioning the patient and measuring the pressure after fluid is collected, the likelihood of the
needle being displaced as a result of the repositioning is minimized.13,17 Accurate measurement depends on cooperation of
the patient. Measurements from struggling or agitated patients
will probably be inaccurate; in such cases, sedation may allow
more accurate readings to be obtained.
Normal CSF pressure is between 7 and 20cm H2O. Obese
patients may have a CSF pressure of up to 25cm H2O. Elevated pressure is abnormal. Opening pressure is taken
promptly, thereby avoiding falsely low values caused by
leakage through and around the needle. Herniating cerebellar
tonsils may occlude the foramen magnum and prevent
increased ICP from being reflected in the lumbar pressure
reading. Increased ICP can result from expansion of the brain
(edema, hemorrhage, or neoplasm), overproduction of CSF
(choroid plexus papilloma), a defect in absorption, or obstruction of flow of CSF through the ventricles. Cerebral edema
may be associated with meningitis, CO2 retention, SAH,
anoxia, congestive heart failure, or superior vena cava obstruction. Pressure may be falsely elevated in a tense patient when
the head is elevated above the plane of the needle and, possibly, in markedly obese patients and those experiencing
muscle contraction.21 Pressure is not usually measured in neonates because a struggling or crying child will have a falsely
elevated pressure. Avery and colleagues concluded that for
most children (1 to 18 years of age), an opening pressure
above 28cm H2O should be considered elevated.116
Low pressure suggests obstruction of the needle by the
meninges. Low pressure can also be seen with a spinal block.
Rarely, a primary low-pressure syndrome occurs in a setting
of trauma, after neurosurgical procedures, secondary to
subdural hematoma in elderly patients, with barbiturate
intoxication, and in cases of CSF leakage through holes in the
arachnoid.117,118
The Queckenstedt test is useful for demonstrating obstruction in the spinal subarachnoid space,4,21 but this test is seldom
performed today because myelographic techniques have been
refined and the availability of MRI has reduced the number
of myelograms and associated lumbar puncture studies.
However, because situations might arise when this simple and
reliable test is important diagnostically, the technique is
described here.

With the patient in the lateral recumbent position, compression of the jugular vein causes decreased venous return to
the heart. This distends the cerebral veins and causes a rise
in ICP, which is transmitted throughout the system and measured in the manometer. After 10 seconds of bilateral compression, CSF pressure usually rises to 15cm H2O over the
initial reading and returns to baseline 10 to 20 seconds after
release. If there is no change in lumbar pressure or if the rise
and fall are delayed, one may conclude that the spinal subarachnoid space does not communicate with the cranial subarachnoid space. In this situation, to facilitate subsequent
myelography, consider injecting Pantopaque before removing
the needle. This is necessary because the lumbar dural sac may
collapse and thus make it impossible to reenter the canal. If
cervical cord disease is suspected, repeat the test with the neck
in the neutral position, hyperextended, and flexed. When
lateral sinus obstruction is suspected, use unilateral jugular
venous compression (Tobey-Ayer test).

Appearance
If CSF is not crystal clear and colorless, a pathologic condition of the CNS should be suspected. The examiner should
compare the fluid with water and view down the long axis of
the tube or by holding both tubes against a white background.
A glass tube is preferred because plastic tubes are frequently
not clear. CSF will appear grossly bloody if more than 6000
red blood cells (RBCs)/L are present. Note that the fluid
may appear clear with as many as 400 RBCs/L and 200
WBCs/L.21 Xanthochromia, a yellow-orange discoloration
of the supernate of centrifuged CSF, is generally considered
to be the result of SAH of at least a few hours duration and
has been used to differentiate prior bleeding from a traumatic
tap. A traumatic tap does not usually exhibit xanthochromia
(see the later section The Traumatic Tap). Xanthochromia
is produced by red cell lysis and is caused by one or more
of the following pigments: oxyhemoglobin, bilirubin, or
methemoglobin
Traditionally, CSF samples have been assessed for xanthochromia by visual inspection by a laboratory technician after
centrifugation of a sample of CSF. Most hospitals still use this
method.119 Recently, spectrophotometry, designed to demonstrate both oxyhemoglobin and bilirubin, has been advocated
as a more precise way of determining xanthochromia. Oxyhemoglobin alone without bilirubin in a CSF sample is thought
to be artifactual (traumatic). Visually, bilirubin and oxyhemoglobin cannot be differentiated. Therefore, detection of bilirubin by spectrophotometry should define xanthochromia
and prompt additional investigation for SAH. Relying on
spectrophotometry to identify xanthochromia without
pigment differentiation will cause a high false-positive interpretation. The absence of both oxyhemoglobin and bilirubin
by spectrophotometry does not support the diagnosis of SAH.
Oxyhemoglobin causes red coloration; bilirubin, yellow; and
methemoglobin, brown. Oxyhemoglobin is seen within 2
hours after subarachnoid bleeding and red cell lysis, but it may
be detected immediately if the bleeding is profuse. Formation
of oxyhemoglobin peaks 24 to 48 hours after hemorrhage, and
the discoloration disappears in 3 to 30 days.4
Blood must be present in CSF (in vivo) for a number of
hours for bilirubin to appear; it will not appear spontaneously
once CSF is in the collection tube. The appearance of bilirubin in CSF involves the conversion of oxyhemoglobin by the

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

enzyme heme oxygenase. The enzyme is found in the choroid


plexus, the arachnoid, and the meninges. Enzyme activity
appears approximately 12 hours after the hemorrhage.4 Bilirubin may persist in CSF for 2 to 4 weeks. Moreover, bilirubin
in CSF caused by hepatic or hemolytic disease does not appear
until a serum level of 10 to 15mg of total bilirubin per
100mL is reached, unless underlying disease associated with
high CSF protein levels is present. Xanthochromia may also
be seen with CSF protein values above 150mg/dL. CSF may
clot in patients with a complete spinal block and very high
CSF protein.
Graves and Sidman noted that an RBC concentration of
5000/L, created by adding RBCs to acellular CSF, will
produce xanthochromia evident on spectrophotometry by 2
hours.120 The addition of RBCs to achieve RBC concentrations of 20,000/L and 30,000/L will produce xanthochromia by 1 hour or immediately, respectively. Therefore,
xanthochromia may occur with a traumatic tap and does not
always indicate SAH.
Methemoglobin is a reduction product of oxyhemoglobin
that is characteristically found in encapsulated subdural hematomas and in old intracerebral hematomas.

Cells
In adults, WBC counts higher than 5 cells/L indicate the
presence of a pathologic condition. A recent large study by
Kestenbaum and colleagues determined 95th percentile WBC
reference values in normal infants: 19 cells/L for infants 28
days of age or younger and 9 cells/L for those between the
ages of 29 and 56 days.121 A median CSF WBC count of 271
WBCs/L has been reported in infants with group B Streptococcus in the era of intrapartum antibiotic prophylaxis. The
CSF WBC count in infants is higher with gram-negative
meningitis than with gram-positive CNS infections. In
general, polymorphonuclear leukocytes are never seen in
normal adults. However, with use of the cytocentrifuge, an
occasional specimen from an otherwise normal individual may
show one to two neutrophils.122 More than three neutrophils
is always abnormal in an adult. Moreover, as many as 30% of
patients exhibit CSF pleocytosis after a generalized or focal
seizure. Nonetheless, such a finding should prompt culture of
CSF because the presence of neutrophilic pleocytosis is commonly associated with bacterial meningitis or the early stages
of viral or tuberculous meningitis. Small lymphocytes may be
seen in normal individuals. Small and large immunocompetent cells are found with a variety of bacterial, fungal, viral,
granulomatous, and spirochetal diseases.
Eosinophils always indicate an abnormal condition, most
commonly a parasitic infestation of the CNS. They may also
be seen after myelography and pneumoencephalography and,
to a minor degree, with other inflammatory diseases, including tuberculous meningitis and neurosyphilis. Normal CSF
RBC counts are lower than 10 cells/L. Herpes simplex virus
(HSV) encephalitis may elevate the RBC count. Finally,
myeloid and RBC precursors may contaminate CSF with
bone marrow cells from an adjacent vertebral body.123

Glucose
Glucose enters CSF by way of the choroid plexus, as well as by
transcapillary movement into the extracellular space of the
brain and the cord via carrier-mediated transport. It then

1233

BOX 60-2 Low CSF Glucose Syndromes


Bacterial meningitis
Tuberculous meningitis
Fungal meningitis
Sarcoidosis
Meningeal carcinomatosis
Amebic meningitis
Cysticercosis
Trichinosis
Syphilis
Chemical meningitis
Subarachnoid hemorrhage
Mumps meningitis
Herpes simplex encephalitis
Hypoglycemia
CSF, cerebrospinal fluid.

equilibrates freely within the CSF subarachnoid space. Once


in CSF, glucose undergoes glycolysis and there is an invariable
rise in CSF lactate levels. Glucose levels remain subnormal for
1 to 2 weeks after effective treatment of bacterial meningitis.
The normal range of CSF glucose is 50 to 80mg/dL,
which is 60% to 70% of the glucose concentration in blood.
Ventricular fluid glucose levels are 6 to 8mg/dL higher than
in lumbar fluid. A ratio of CSF glucose to blood glucose of
less than 0.5 or a CSF glucose level below 40mg/dL is invariably abnormal. The ratio is higher in infants, in whom a ratio
of less than 0.6 is considered abnormal. Hyperglycemia may
mask a depressed CSF glucose level; when present, the ratio
of CSF glucose to blood glucose should be measured routinely. With extreme hyperglycemia, a ratio of less than 0.3 is
abnormal.124 Between 90 and 120 minutes is required before
CSF glucose reaches a steady state with changes in blood
glucose (e.g., after an intravenous injection of glucose). When
CSF glucose is of diagnostic importance, obtain CSF and
blood samples, ideally after a 4-hour fast.
Low CSF glucose levels may be associated with several
diseases of the nervous system (Box 60-2). Only low concentrations of glucose are of diagnostic value; elevated CSF
glucose levels generally have little significance and usually
reflect hyperglycemia. A rapid estimate of the CSF glucose
level can be obtained by using bedside reagent strip testing
with a commercial autoanalyzer. Formal laboratory testing is
recommended for confirmation of the bedside levels.

Protein
The normal range of lumbar CSF protein is 15 to 45mg/dL.
Infants normally have a lower level than adults do, and protein
levels may drop after lumbar puncture. The concentration is
lower in the ventricles (5 to 15mg/dL) and the basilar cisterns
(10 to 25mg/dL) as a result of a gradient in the permeability
of capillary endothelial cells to proteins in blood. Levels of
CSF protein in premature infants and full-term neonates are
higher than in adults, with a mean of 90mg/dL; protein levels
decline by the age of 8 weeks because of maturation of the
blood-brain barrier.
Most of the proteins in CSF come from blood, which
normally has a protein concentration of up to 8000mg/dL.

1234

SECTION

X NEUROLOGIC PROCEDURES

Protein entry is determined by its molecular size and the relative impermeability of the blood-CSF barrier. A full range of
serum proteins is found in CSF at a several hundredfold
dilution.
An increase in the total CSF protein level is a nonspecific
abnormality associated with many disease states. Levels higher
than 500mg/dL are uncommon and seen mainly with meningitis, subarachnoid hemorrhage, and spinal tumors. The
high levels that occur with cord tumors result from an increase
in local capillary permeability. With high levels (generally
1000mg/dL), CSF may clot (Froins syndrome).
Hemorrhage into CSF or the introduction of blood by a
traumatic tap increases CSF protein levels. If the serum
protein concentration is normal, the CSF protein level should
theoretically rise by 1mg/dL for every 1000 RBCs, but this
relationship varies. The inflammatory effect of hemolyzed
RBCs may also significantly increase CSF protein.
Selective measurement of immunoglobulin fractions in
CSF has proved to be of diagnostic value in suspected cases
of multiple sclerosis. Elevated CSF immunoglobulin levels
may reflect disruption of the blood-brain barrier or a local
antibody response to a CNS immune response.125 Stimuli may
be infectious or antigenic and produce an inflammatory
response. Elevated immunoglobulin levels have been found in
many conditions, including syphilis, viral encephalitis, subacute sclerosing panencephalitis, progressive rubella encephalitis, tuberculous meningitis, sarcoidosis, cysticercosis, and
acute inflammatory demyelinating polyneuropathy (GuillainBarr syndrome).

The Traumatic Tap


The incidence of a traumatic tap is 10% to 30%, depending
on the criteria used to define the condition.126-128 Currently,
there is no consensus on what constitutes a traumatic tap.
Traditionally, the number of RBCs in CSF, the rate of clearance of RBCs from tube 1 to tube 3 or 4, and the presence
or absence of xanthochromia have guided clinicians in
attempts to define the need for further investigation for SAH
when blood is detected during lumbar puncture.
Absolute Number of RBCs
The current literature makes no firm recommendations
regarding the absolute CSF RBC count that can be used as a
cutoff to differentiate SAH from a traumatic tap. However,
SAH consistently produces more RBCs in CSF than a traumatic tap does. In tube 3 or 4, an absolute RBC value of 400
to 500 RBCs/L or less is very suggestive of a traumatic tap,
and this value has been traditionally used by clinicians.13 In a
retrospective study of 300 patients, Gorchynski and coworkers
reported a 100% negative predictive value for SAH with an
RBC count in tube 4 of 500 RBCs/L or less, with a sensitivity
of 100% for SAH.129 No radiographically normal subject had
an RBC count of greater than 10,000 RBCs/L, thus suggesting that results above this number are suspicious for radiographically detectable SAH. When the RBC count in tube 4
ranged between 500 and 10,000 RBCs/L, SAH could not be
ruled out without further study. Any attempt to define precisely how low an RBC count must be to eliminate the possibility of SAH would result in an arbitrary threshold. As the
foregoing discussion suggests, SAH is exceedingly unlikely
with RBC counts lower than 500 and becomes progressively
less likely as this number decreases.

RBC Clearance from First to Last Tubes


In traumatic punctures, the fluid generally clears of RBCs
between tubes 1 and tubes 3 or 4 as the needle is washed by
CSF. In fact, a decrease in the RBC count between the first
and last tubes of at least 25% to 30% has traditionally been
considered strong evidence of a traumatic tap.2,130 However,
it must be remembered that a traumatic tap may also occur
in a patient with true SAH. Thus, regardless of the change in
RBC count from the first to last tubes, SAH cannot be
excluded unless the RBC count approaches zero in either
tube. If this is not the case and xanthochromia is not present
(see below), it may be most prudent to repeat the puncture at
a different interspace or site. To help avoid this situation,
when a clinician encounters what is suspected to be a traumatic tap (e.g., a streak of blood flowing into an otherwise
clear-appearing stream of CSF), wasting the first 2 or 3mL
of CSF while positioning the needle to obtain the clearest
possible sample will increase the odds of an RBC count
approaching zero.
Xanthochromia
RBCs undergo hemolysis in CSF after a few hours and xanthochromia is produced. Xanthochromia persists for up to 4
weeks, depending on the number of RBCs originally present.
Xanthochromia is suggestive of but not pathognomonic for
SAH.131 An early CSF examination may show clear fluid
before the development of hemolysis, even after spontaneous
subarachnoid bleeding. However, xanthochromia may be
detected immediately after a traumatic tap if the RBC count
exceeds 30,000/L.120 The presence of a clot in one of the
tubes strongly favors a traumatic tap. With SAH, clotting
does not occur because blood is defibrinated at the site of the
hemorrhage. Lumbar puncture performed several days after
a traumatic tap may also yield stained fluid. Collection of clear
CSF from an immediately repeated puncture at a higher
interspace also indicates a traumatic tap. The fluid from a
traumatic tap should contain about 1 WBC per 700 RBCs if
the complete blood cell count is normal, but this ratio is
highly variable. All blood-contaminated CSF should be cultured, especially samples from uncooperative infants and children being evaluated for sepsis.
A D-dimer test on CSF can be used to determine SAH by
identifying local fibrinolysis.132 Other conditions such as disseminated intravascular coagulation, a previous traumatic tap,
or prior thrombolytic therapy may produce false-positive
results.
Fluoroscopically guided lumbar puncture in patients with
suspected SAH and negative findings on CT is another option
that may reduce the frequency of traumatic punctures, but it
requires specific expertise and is frequently performed in the
radiology suite.133

CSF Analysis with Infections


Bacterial Infections
The CSF findings are essential to establish a provisional diagnosis of acute bacterial meningitis.134 CSF analysis establishes
not only the diagnosis but also the causative organism and
therefore the choice of antibiotics (Table 60-1). CSF must be
transported to the laboratory immediately and be examined
at once. CSF cells begin to lyse within 1 hour after collection;
this process can be slowed by refrigeration. In cases of meningococcal infection, a delay in processing may cause the

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

1235

TABLE 60-1 CSF Analysis in Bacterial and Viral Meningitis*


BACTERIAL MENINGITIS

VIRAL MENINGITIS

Usually elevated

Usually normal

White blood cell count (per mm )

Elevated, 500-10,000+

Elevated, 6-1000

Differential count

Polymorphonuclear predominance

Lymphocytic predominance

Glucose level

Decreased, 0-40mg/dL

Usually normal

Protein level

Elevated, >50mg/dL

Normal or slightly elevated

Opening pressure
3

Adapted from Fong B, Van Bendegem J. Lumbar puncture. In: Reichman E, Simon R, eds. Emergency Medical Procedures. New York: McGraw-Hill; 2004:875.
CSF, cerebrospinal fluid.
*This is only a guide. Care must be taken when interpreting these parameters, especially early in the clinical course.

diagnosis to be missed because the organism tends to autolyze


rapidly. For other organisms, speed is somewhat less important but still warranted.
Gram stain is of great importance because the results direct
antibiotic therapy. Gram-negative intracellular or extracellular diplococci are indicative of Neisseria meningitidis. Small
gram-negative bacilli may indicate Haemophilus influenzae,
especially in children. The presence of gram-positive cocci
indicates Streptococcus pneumoniae, other Streptococcus species,
or Staphylococcus. Twenty percent of Gram stains are falsely
negative because too few organisms are present. The Gram
stain smear is more likely to be positive in patients who have
not received prior antibiotic therapy. Acridine orange stain
may improve the yield with gram-negative organisms.135
For culture, blood and chocolate agar are required. N.
meningitidis and H. influenzae grow best on chocolate agar.
The plates are incubated under 10% CO2. Thioglycolate
medium is used for possible anaerobic organisms. Cultures
are examined at 24 and 48 hours, but the plates should be kept
for at least 7 days. Large volumes of CSF may improve yields.
While the culture results are pending, bacterial infection
should be suspected in patients with an elevated opening pressure and marked pleocytosis ranging between 500 and 20,000
WBCs/L. The differential count with bacterial infections is
usually neutrophil predominant. A count higher than 1000
cells/L seldom occurs with viral infections. Occasionally,
acellular fluid may be collected from a severely immunosuppressed patient. Moreover, repeated lumbar puncture may be
required in febrile patients whose clinical features remain
compatible with meningitis.124,136,137 In such scenarios, broadspectrum empirical antibiotics should be continued until the
results of repeated testing or bacterial culture are available.
CSF glucose levels of 40mg/dL or lower or less than 50%
of a simultaneous blood glucose level should raise the question of bacterial meningitis, even in the presence of a negative
Gram stain and a low cell count. Glucose levels with bacterial
meningitis are occasionally below 10mg/dL but are normal
in a small percentage of patients.124 The CSF protein content
with bacterial meningitis ranges from 500 to 1500mg/dL and
usually returns to normal by the end of therapy. Of note,
previous antibiotic therapy may adversely affect the sensitivity
of cultures and Gram stain for bacterial meningitis but does
not significantly affect WBC counts, the ratio of CSF glucose
to blood glucose, or CSF protein values.138 Spanos and colleagues developed a useful nomogram to help distinguish
bacterial from viral infections139; however, no technique is

perfect in this regard, and in general the clinician should err


on the side of diagnosing bacterial meningitis until the results
of culture are available.
Microbial Antigens and PCR
In 50% to 80% of cases of bacterial meningitis, blood cultures
are positive for the etiologic agent.140 In addition to Gram
stain and cultures, several tests are available to establish a
bacterial cause of meningitis, including CSF counterimmunoelectrophoresis (CIE), CSF latex agglutination, and coagglutination CIE.6 In general, these ancillary tests have low
sensitivity for bacterial meningitis, thus limiting their use.
CIE uses wells in two rows of agarose gel. A different
antiserum is placed in each well. A current is passed through
the gel, which causes the reactants to move toward each other
by electrophoretic mobilization of the antigen. The appearance of a line of precipitation in 1 to 4 hours represents a
positive reaction between antiserum and antigen.141 Commercial kits are available to detect S. pneumoniae; Listeria
monocytogenes; H. influenzae; N. meningitidis A, B, C, and
W135; group B streptococci; K1 strains of Escherichia coli;
Klebsiella; and Pseudomonas species.142
Particle agglutination involves staphylococcal coagglutination and latex agglutination. Antibody on the surface of a
colloid combines with antigen-binding sites to cross-link the
colloid-forming antigen bridges. A matrix forms and appears
as a macroscopic agglutination. Agglutination tests can detect
levels of antigen that are approximately 10 times lower than
CIE is capable of detecting. False-positive results can occur
in the presence of rheumatoid factor, serum complement
components, and possibly other serum proteins. The technique may be used for infections with H. influenzae, S. pneumoniae, N. meningitidis, and group B streptococci.
Another technique that has some potential use for
identification of bacterial meningitis is the enzyme-linked
immunosorbent assay. This technique may detect levels of
antigen 100 to 1000 times lower than agglutination tests can
but is technically more difficult and requires 4 hours to
perform.
A positive CSF antigen test may be expected in 70% to
90% of patients with Neisseria meningitis. This compares with
a positive Gram stain in approximately 70% of patients. Positive latex antigen tests have been reported in approximately
60% of S. pneumoniae meningitis cases, with a positive Gram
stain in 80%. A positive latex test and Gram stain are reported
in approximately 85% of H. influenzae meningitis cases.140,141

1236

SECTION

X NEUROLOGIC PROCEDURES

Group B streptococci can be detected with 60% to 90%


sensitivity.
Bacterial antigens may persist in CSF for several days after
antibiotic therapy. With appropriate antimicrobial therapy,
25% to 33% of positive tests convert to negative per day. A
negative test, however, does not rule out bacterial meningitis.142 In addition, blood and urine can be examined for
antigen. Frequently, antigen is found only in urine. Urine
needs to be concentrated and may have the disadvantage of
reflecting urinary tract infections. Moreover, the particle
agglutination test for H. influenzae type B may be positive up
to 10 days after children have received H. influenzae polysaccharide vaccine. Antigen tests are not useful in diagnosing
gram-negative bacillary, staphylococcal, and Listeria meningitis. In addition, although antigen tests may identify the bacterial pathogen, they do not provide information about the
antibiotic susceptibility of the organism.
Polymerase chain reaction (PCR) may aid in the rapid
diagnosis of CNS infection when results of the aforementioned common techniques are suboptimal. PCR amplifies
target nucleic acid in CSF by the use of repeated cycles of
DNA synthesis. PCR requires the use of flanking DNA
sequences at the opposite ends of the target DNA. Synthetic
primers anneal to their respective recognition sequences at
the opposite end of the target sequence; they serve as primers
for new DNA synthesis. PCR allows detection and quantification of organisms whose genetic material is DNA or messenger RNA. PCR permits the diagnosis of infectious disease
with a high degree of sensitivity and specificity and allows
rapid reliable detection of microbes present in small numbers.
Nonetheless, false-negative and false-positive laboratory
results may occur.
Empirical Antibiotic Use before Lumbar Puncture
Many patients are transported within a facility or to a referral
center for a CT to rule out an intracranial mass after clinical
concern for meningitis is raised. In such instances, CSF examination might not be performed before transport because of
technical problems (an uncooperative or a large patient) or
concerns regarding the safety of lumbar puncture in an
obtunded patient with possible increased ICP.124,143 The initial
clinician may have to decide whether to initiate empirical
antibiotic therapy. Antibiotic administration could obscure
the bacterial source, whereas a delay in initiating therapy
increases morbidity and mortality. It may be difficult to identify individuals at risk for a fulminant course, and bacterial
meningitis cannot always be diagnosed with confidence;
some cases may be misdiagnosed as SAH or metabolic
encephalopathy.
After administration of parenteral antibiotics, CSF cultures are not adversely affected for 2 to 3 hours. Twenty-four
hours after treatment, as many as 38% of patients with meningitis may still have positive CSF cultures. Kanegaye and
associates demonstrated that CSF sterilization may depend on
the infecting organism.144 They reported CSF sterilization
after antibiotic administration within the following time
frames: meningococcal, less than 2 hours; pneumococcal,
less than 4.3 hours; and group B streptococcal, longer
than 8 hours.
Blood should be obtained for culture immediately before
the administration of antibiotics whenever possible. When
CSF is cultured more than a few hours after parenteral antibiotics are administered, antigen tests may be helpful.

Occasionally, lymphocytic pleocytosis may develop in response


to antibiotic therapy, but in most cases, the cell count, differential, and glucose and protein concentrations are
unchanged in the first 2 to 3 days of antibiotic therapy.124 It
is thus is reasonable to initiate therapy on the premise that a
delay might be deleterious. If a lumbar puncture cannot be
performed, consultation with clinicians at a referral center
seems appropriate. If a lumbar puncture is performed before
transfer, a portion of the CSF (chilled on ice) should be sent
with the patient or held in the referring hospital laboratory.
Bacterial meningitis in children younger than 10 years has
historically been caused by H. influenzae. Fortunately, this
organism is easy to grow in early postantibiotic cultures and
is likely to be associated with positive blood cultures and
antigen tests. In the pediatric population, a single dose of an
antibiotic before transport is unlikely to prevent identification
of bacteria. In neonates, adults, and immunosuppressed
patients, the sensitivity of blood cultures and immunologic
tests is less reliable. CSF examination as early as possible in
the course of treatment is preferred.
For suspected or confirmed cases of acute bacterial meningitis, antimicrobial therapy can be started and be based on
the most likely causative organism with respect to the age of
the subject, associated diseases, and renal function. Tables
60-2 through 60-4 offer guidelines for emergency antibiotic
therapy. For immunocompromised patients and after neurosurgery, a third-generation cephalosporin (cefotaxime, ceftizoxime, ceftazidime, or ceftriaxone) plus ampicillin and
vancomycin should be used for coverage against staphylococci, L. monocytogenes, and gram-negative organisms.6 The
third-generation cephalosporins are efficacious in many

TABLE 60-2 Empirical Therapy for Purulent


Meningitis*

PREDISPOSING FACTOR

Age
0-4wk
4-12wk
3mo-18yr
18-50yr
>50yr

ANTIMICROBIAL THERAPY

Ampicillin plus cefotaxime or


ampicillin plus an aminoglycoside
Ampicillin plus a third-generation
cephalosporin
Third-generation cephalosporin or
ampicillin plus chloramphenicol
Third-generation cephalosporin
Ampicillin plus a third-generation
cephalosporin

Immunocompromised
state

Vancomycin plus ampicillin plus


ceftazidime

Basilar skull fracture

Third-generation cephalosporin

Head trauma; post


neurosurgery

Vancomycin plus ceftazidime

Cerebrospinal fluid
shunt

Vancomycin plus ceftazidime

*Consider corticosteroids before administration of antibiotics (see text).

Vancomycin should be added to all empirical therapeutic regimens when strains


of Streptococcus pneumoniae that are highly resistant to penicillin or cephalosporin
are suspected.

Cefotaxime or ceftriaxone.

Add ampicillin if meningitis caused by Listeria monocytogenes is suspected.

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

empirical regimens or situations in which the organism is


known. Reliance on third-generation cephalosporins alone
for all cases of bacterial meningitis would result in treatment
failure for all Listeria species and increasing numbers of
Enterobacter, Serratia, and Pseudomonas groups.
Dexamethasone Therapy for Bacterial Meningitis
In acute bacterial meningitis, bacterial cell wall components,
including lipopolysaccharides and teichoic acid, initiate and
exacerbate the host response. These substances stimulate the
production of cytokines, including interleukin-1 and tumor
necrosis factor, from macrophages and monocytes. Cytokines
may injure vessels, diminish cerebral perfusion, and stimulate
cerebral swelling.143 The outcome of acute bacterial meningitis has been related to the severity of the inflammatory process
in the subarachnoid space.
Studies have suggested benefit from adjunctive dexamethasone therapy in reducing neurologic sequelae, especially
hearing loss, in children with H. influenzae meningitis and in
lowering the mortality rate and providing a better overall
outcome in adults with community-acquired acute bacterial
meningitis caused by S. pneumoniae.145 There appear to be few
adverse sequelae from steroid therapy. The adjunctive benefit
of corticosteroids during treatment of meningitis caused by
other viral, fungal, or parasitic organisms is unknown. A
recent Cochrane review concluded that the corticosteroid
dexamethasone leads to a major reduction in hearing loss and
death in both children and adults with bacterial meningitis,

1237

TABLE 60-3 Recommended TOTAL DAILY DOSE

(with Divided Dosing Intervals in Hours) of Antimicrobial


Agents for Meningitis in Adults with Normal Renal and
Hepatic Function*
ANTIMICROBIAL
AGENT

TOTAL DAILY DOSE


(INTRAVENOUS)

Ampicillin

12g/day

Cefotaxime

8-12g/day

Ceftazidime

6g/day

6g/day

12-24

Chloramphenicol

4g/day

Gentamicin

2mg/kg IV load,
then 1.7mg/kg q8h

Tobramycin

2mg/kg IV load,
then 1.7mg/kg IV q8h

Vancomycin

2-3g/day

Ceftriaxone

DOSING
INTERVAL (hr)

4
4-6

8-12

*Consider corticosteroids before the administration of antibiotics (see text).

High dose recommended for pneumococcal meningitis.

Peak and trough serum concentrations must be monitored.

TABLE 60-4 Recommended Total Daily Doses with Divided Dosing Intervals in Hours of Antimicrobial Agents
for Meningitis in Neonates, Infants, and Children with Normal Renal and Hepatic Function
ANTIMICROBIAL
AGENT*

NEONATES (0-7 DAYS)

NEONATES (8-28 DAYS)

INFANTS AND CHILDREN

Amikacin

15-20mg/kg/day
IV divided q12h

30mg/kg/day
IV divided q8h

15-22.5mg/kg/day IV divided
q8h (max dose 1.5g/day)

Ampicillin

200-300mg/kg/day
IV divided q8h

400mg/kg/day
IV divided q6h

300-400mg/kg/day IV divided
q3-4h (max dose 10-12g/day)

Cefotaxime

100-150mg/kg/day
IV divided q8-12h

200mg/kg/day
IV divided q6h

200-300mg/kg/day IV divided
q6-8h (max 12g/day)

Ceftazidime

100-150mg/kg/day
IV divided q8-12h

100mg/kg/day
IV divided q12h

150mg/kg/day IV divided
q8h (max 6g/day)

Ceftriaxone

100mg/kg/day IV divided q12h

Chloramphenicol

25mg/kg/day IV q24h (initial


loading 20mg/kg, then first
maintenance dose 12h later)

25-50mg/kg/day IV divided
q12-24h (initial loading
20mg/kg, then first
maintenance dose 12h later)

75-100mg/kg/day IV divided
q6h (max 2-4 g/day)

Gentamicin

2.5mg/kg/day IV divided
q8h*

4-5mg/kg/day IV divided
q12-48h*

7.5mg/kg/day IV divided q8h*

Tobramycin

4-5mg/kg/day q24-48h*

4-5mg/kg/day IV divided
q12-48h*

5-7.5mg/kg/day IV divided q8h*

Vancomycin

10-15mg/kg/day IV divided
q8-12h

45-60mg/kg/day IV divided
q8-12h

60mg/kg/day IV divided q8h

*Consider corticosteroids before the administration of antibiotics (see text).

Smaller dosages and longer intervals of administration may be advisable for very-low-birth-weight neonates (<2000g).

Peak and trough serum concentrations must be monitored.

1238

SECTION

X NEUROLOGIC PROCEDURES

without major adverse effects.146 Interestingly, in children in


low-income countries, the use of corticosteroids was associated with neither benefit nor harmful effects.
The dosage of dexamethasone is 0.15mg/kg (10mg
intravenously in adults) every 6 hours for 4 days. It is recommended that the corticosteroid be given before or simultaneously with antibiotic use, but the exact timing and specific
benefits are unclear. It has been suggested that caution be
exercised when administering corticosteroids to immunocompromised and leukopenic patients with bacterial meningitis,
but no specific recommendations have been published.
A moderate inflammatory response in the meninges is
required for penetration of the CNS by many antibiotics.
Reducing meningeal inflammation reduces the concentration
of antibiotics in CSF. Corticosteroids should be discontinued
after approximately 4 days of treatment, at which time the
meningeal inflammation should have been reduced.147,148
Neurosyphilis
The true incidence of neurosyphilis is unknown. Approximately 5000 new cases of this disease occur in the United
States each year.149 Its natural history and clinical manifestations have been modified in the antibiotic era. The widespread use of oral antibiotics has changed neurosyphilis into
chronic, partially treated meningitis. Partial therapy may clear
peripheral infection and attenuate the immune response.
Therapy may be sufficient to minimize symptoms but insufficient to eradicate organisms in the CNS and eye, which may
then multiply.
CSF findings suggestive of neurosyphilis include more
than 5 WBCs/L, an elevated protein concentration, an elevated -globulin concentration, and a positive serologic test
for syphilis. The glucose concentration is usually normal. Cell
and protein values are higher in early neurosyphilis than in
late neurosyphilis.
Diagnostic certainty remains difficult. The diagnostic criterion standard is darkfield microscopy to identify the morphology and flexing corkscrew motility of spirochetes.
Serologic tests for syphilis are either treponemal or nontreponemal. Nontreponemal tests detect a nonspecific globulin
complex called reagin. Reagin tests, such as the Venereal
Disease Research Laboratory (VDRL) flocculation test, lack
sensitivity and should not be used to exclude the diagnosis of
neurosyphilis. One third to one half of patients with neurosyphilis have a negative VDRL test on serum, and more than
one third have a negative VDRL test on CSF.149 CSF VDRL
is quite specific, with false-positive results seen primarily after
traumatic taps.
Treponemal tests provide evidence of a specific immune
response to Treponema pallidum. These tests include serum
fluorescent treponemal antibody absorption (FTA-ABS),
microhemagglutination tests for T. pallidum, and the T. pallidum hemagglutination assay. A positive serum treponemal test
indicates past infection with syphilis and may be reactive
indefinitely, even after treatment. Therefore, CSF is used as
a guide to the presence and activity of neurosyphilis. The
VDRL test is commonly used on CSF and, when positive, is
strong evidence of neurosyphilis. False-positive CSF VDRL
tests are rare. The FTA-ABS test can be used on CSF; the
false-positive rate is between 4% and 6% and is believed to
represent antibodies that have entered passively from serum.150
The FTA-ABS test measures immunoglobulin G (IgG) antibody and cannot differentiate active from past infection. The

CSF VDRL may be reactive as a result of contamination with


seropositive blood (traumatic tap, SAH) or because of entry
of serum reagin into CSF during meningitis. In summary,
CSF VDRL and CSF FTA-ABS are complementary tests in
the diagnosis of neurosyphilis; CSF VDRL is highly specific
but not sensitive, whereas CSF FTA-ABS is less specific but
more sensitive.
There is some concern that many patients with parenchymal neurosyphilis have normal CSF. This finding has led to
the recommendation that a patient with signs of progressive
neurosyphilis and a positive treponemal serologic test be
treated with antibiotics regardless of the CSF findings.
CSF pleocytosis may be provoked after 1 week of therapy
and may provide supportive evidence for a diagnosis of
neurosyphilis. PCR may have future applications for the
diagnosis of neurosyphilis (see Neurosyphilis in Patients
Infected with Human Immunodeficiency Virus later in this
chapter).
Viral Meningitis
The organisms most commonly isolated in viral meningitis
are the enteroviruses (coxsackieviruses, echoviruses) and
mumps virus. Enteroviruses are most commonly seen in the
summer and fall, and mumps appears most frequently in the
winter and spring. Viral cultures in most hospitals are not
available and play little role in acute decisions regarding diagnosis and treatment. A serial rise in CSF antibody titers may
be helpful but are difficult to obtain in patients who have
recovered clinically. Intrathecal production of organ-specific
antibodies (IgM, IgG, and IgA isotopes) may be diagnostic of
neurologic infection if there is no history of infection. Serum
and CSF antibody titers must be measured in a specialized
laboratory. Viral meningitis is diagnosed when bacterial
culture and Gram stain are negative. A tentative diagnosis
may be based on analysis of CSF.
The WBC count in viral meningitis and encephalitis is
characteristically 10 to 1000 cells/L. The differential cell
count is predominantly lymphocytic and mononuclear in
type. In the early stages of meningoencephalitis, however,
polymorphonuclear cells may predominate, thus making the
distinction between viral and bacterial infection difficult. In
such cases, a tap repeated in 12 to 24 hours will assist in clarifying the diagnosis. Protein levels are usually mildly elevated,
but normal levels may be seen. Antibiotic coverage pending
the results of culture may be reasonably initiated if the diagnosis of viral meningitis is in doubt.124 The CSF glucose
concentration is characteristically normal; notable exceptions
include some cases of mumps meningoencephalitis and HSV
encephalitis. CSF pleocytosis and elevated protein levels
have also been found in asymptomatic HIV-seropositive
individuals.151
If CSF cannot be delivered to the viral laboratory in 24 to
48 hours, it should be refrigerated at 4C. Members of the
enterovirus group are occasionally isolated from CSF. Herpesviruses and arboviruses are also found in CSF. PCR is the
diagnostic test of choice for HSV meningoencephalitis and
will be used increasingly for the diagnosis of other CNS viral
infections. Although the majority of cases of viral meningitis
are self-limited and have a good outcome, HSV encephalitis
is a rapidly progressive and life-threatening emergency that
responds to treatment with intravenous acyclovir. Thus, in an
acutely ill patient in whom the diagnosis of acute meningoencephalitis is being considered, a negative Gram stain and

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination

pleocytosis are sufficient grounds to initiate empirical acyclovir therapy until the results of more definitive diagnostic data
from PCR are available.152

CSF Analysis in Immunocompromised


Patients
The number of immunocompromised individuals is increasing because of the HIV epidemic and the increased survival
of patients with cancer and autoimmune disorders. The
nervous system is a major target of the HIV virus: neurologic
disease develops in 40% to 60% of infected individuals during
their lifetime. One third of HIV-infected patients have
neurologic complaints as the initial manifestations of AIDS,
and an even higher incidence of nervous system involvement
is found at autopsy.153 The risk for CNS infection depends
on the underlying disease, treatment, duration, and type of
immune abnormality. Abnormalities include defects in
T-lymphocyte and macrophage cellular immune function,
defects in humoral immunity, defects in the number and function of neutrophils, and loss of splenic function with an inability to remove encapsulated bacteria.154 The major neurologic
manifestations of HIV infection, including clinical characteristics, are summarized in Table 60-5.
Patients with defective cell-mediated immunity include
those with lymphoma, organ transplants recipients, those
taking corticosteroids daily, and patients with AIDS. These
individuals are vulnerable to infections with microorganisms
that are intracellular parasites. A common source of acute
bacterial meningitis in such patients is L. monocytogenes. Clinical findings include fever, headache, seizures, focal neurologic
deficits, and brainstem encephalitis.
Patients with defective humoral immunity include those
with chronic lymphocytic leukemia, multiple myeloma, and
Hodgkins disease after radiotherapy or chemotherapy. These
patients have difficulty controlling infection by encapsulated
bacteria. A fulminant meningitis caused by S. pneumoniae, H.
influenzae type B, or N. meningitidis may develop. After splenectomy, patients are at risk for the development of meningitis for the same reason. Neutropenic patients are at risk
for meningitis caused by Pseudomonas aeruginosa and the
Enterobacteriaceae.
Establishing a specific diagnosis in HIV and organ transplant patients may be difficult or impossible because of overlapping clinical and radiographic findings, the presence of
simultaneous infections with more than one organism, and
changes in CSF that may be nonspecific. The immune
response may be altered, with absence of the usual signs of
meningeal irritation. Patients may have diffuse encephalopathy or focal neurologic deficits. CSF is abnormal in 60% of
asymptomatic HIV-infected individuals, thus complicating
correlation of the CSF and clinical findings.153
Neurosyphilis in Patients Infected with HIV
Syphilis and HIV infection may both be transmitted sexually,
and patients with syphilis are at increased risk for HIV infection. CNS invasion is probably no more common in patients
with HIV than in those not infected with the virus.155 Both
diseases may cause an elevation in CSF WBC counts, protein
levels, and -globulin levels. The incidence of syphilitic meningitis, meningovascular syphilis, and ocular syphilis seems to
be increasing. HIV-infected patients treated for syphilis may
have viable organisms in CSF after therapy or have persistent

1239

CSF VDRL titers. Treatment failures are more likely to occur


with single-dose benzathine penicillin therapy.
Neurosyphilis may be more difficult to diagnose in HIVinfected patients. A small number of patients with secondary
or ocular syphilis have negative serum reagin tests. Positive
treponemal tests may revert to nonreactivity after treatment,
particularly in individuals with advanced symptomatic HIV
disease and a low VDRL titer at the time of diagnosis. CSF
pleocytosis and increased -globulin levels may not help distinguish between HIV infection and CNS syphilis.
HIV-infected patients should undergo serum treponemal
and nontreponemal tests early in their illness to minimize the
likelihood of false-negative results.155 Infected patients should
undergo a CSF examination. Previously treated patients who
did not have a CSF examination at the time of initial syphilis
treatment should undergo lumbar puncture because of a
probable increased risk for neurosyphilis even with a decline
in serum nontreponemal titers.
Cryptococcal Meningitis
The most common cause of CNS fungal infection is Cryptococcus neoformans. Infection with this fungus develops in approximately 5% of AIDS patients. Clinical findings in AIDS and
non-AIDS patients include nonspecific symptoms of headache and altered mental status with or without meningeal
signs. Most patients have increased ICP. Immunocompetent
patients show a lymphocytic pleocytosis with CSF WBC
counts lower than 500/L. Glucose levels are depressed, with
elevation of CSF protein. India ink preparations are positive
in 50% of cases. CSF is less likely to have abnormal cell counts
and chemistries in patients infected with HIV. However, CSF
cultures and cryptococcal polysaccharide capsular antigens
are almost always positive. False-positive antigen tests are rare
but may be seen in the presence of rheumatoid factor. Blood
cultures are frequently positive in AIDS patients. Cisternal
puncture for fluid analysis may be helpful in undiagnosed
cases of lymphocytic meningitis in which multiple lumbar
punctures have not established a diagnosis.153
Toxoplasmosis
Toxoplasma gondii, an intracellular protozoan, is associated with
CNS infection in up to 30% of AIDS patients who have antibodies to this organism. Most adults have antibodies against
this organism; infection is believed to represent reactivation of
latent primary infection. Toxoplasma encephalitis usually develops within the first 2 years after the diagnosis of AIDS. Cerebral toxoplasmosis is usually accompanied by the acute or
subacute development of focal disease, including seizures.
MRI or CT scanning often reveals multiple abscesses that may
represent multiple pathogens. Toxoplasmosis and lymphoma
may be difficult to distinguish clinically. Less commonly, the
manifestation is one of chronic meningitis with confusion,
memory loss, and lethargy similar to the AIDS-dementia
complex. CSF in these patients is nonspecific with increased
protein, mononuclear pleocytosis (<100 cells/L), and rarely,
a reduced glucose concentration. Serum and CSF serology
may be either positive or negative and does not help make a
diagnosis, although most patients with encephalitis have
detectable IgG antibodies. The diagnosis is usually based on
clinical and imaging responses to antibiotics (pyrimethamine
or sulfadiazine) or on brain biopsy. Treatment failures with
relapse occur in 50% of AIDS patients and in 15% to 25% of
non-AIDS patients and necessitate life-long treatment.

Memory loss, gait


disorder, behavioral
change
Headache, fever,
confusion, lethargy,
seizures
Headache, confusion,
lethargy, memory loss,
seizures
Lethargy, confusion,
weakness

Rapidly progressive
confusion, apathy,
weakness
Gait dysfunction, lower
extremity weakness
and stiffness, urinary
dysfunction
Fever, headache, neck
stiffness, memory loss

<200

<200

<100

<100

<50

<200

<200

Toxoplasma encephalitis

CNS lymphoma

Progressive multifocal
leukoencephalopathy

CMV encephalitis

Vacuolar myelopathy

Cryptococcus neoformans
meningitis

INITIAL SYMPTOMS

HIV dementia

CD4+ COUNT
(CELLS/mm3)

Lethargy, confusion,
meningeal signs, cranial
nerve palsies

Spastic paraparesis,
Babinskis signs, sensory
abnormalities

Dementia, cranial
neuropathies, spasticity

Hemiparesis, ataxia, visual


disturbance

Dementia, hemiparesis,
aphasia

Dementia, ataxia,
hemiparesis

Dementia, spasticity,
psychosis

NEUROLOGIC SIGNS

CSF India ink


Serum and CSF Cryptococcus
neoformans antigen and culture

MRI/CSF: normal or nonspecific


abnormalities

CT/MRI: periventricular and


meningeal abnormalities
CSF: CMV culture, PCR
Electrolyte abnormalities

CT/MRI: multiple hypodense,


nonenhancing white matter
lesions
Stereotactic biopsy

CT/MRI: enhancing lesions


(especially if single)
Stereotactic biopsy

Serum Toxoplasma antibodies


CT/MRI: multiple enhancing
lesions, edema

CT/MRI: brain atrophy, white


matter abnormalities
CSF: increased 2-microglobulin

DIAGNOSTIC STUDIES

Amphotericin B (plus or minus


flucytosine), fluconazole

Baclofen, physical therapy

Ganciclovir, foscarnet

High-dose zidovudine, ara-C


(IV, IT); clinical trial

Radiotherapy

Pyrimethamine, sulfadiazine,
clindamycin

High-dose zidovudine, clinical


trial

THERAPY

SECTION

TABLE 60-5 Major Neurologic Manifestations of HIV Infection

1240
X NEUROLOGIC PROCEDURES

Distal numbness,
paresthesias, pain

Progressive weakness,
paresthesias

Facial weakness,
footdrop, wristdrop
Lower extremity
weakness, paresthesias,
urinary dysfunction

<200

>500 (early),
<50 (late)

>500 (early),
<50 (late)

<50

Any

Distal symmetric
polyneuropathy

Inflammatory
demyelinating
polyneuropathy

Mononeuropathy
multiplex

Progressive
polyradiculopathy

Myopathy

Proximal muscle weakness

Flaccid paraparesis, saddle


anesthesia, decreased
reflexes, urinary retention

Multifocal cranial and


peripheral neuropathies

Weakness, areflexia, mild


sensory loss

Stocking-glove sensory loss,


decreased ankle reflexes

Dementia, stroke,
meningeal or
myelopathic signs, cranial
nerve palsies

Increased creatine kinase


EMG: irritative myopathy
Muscle biopsy: myofiber
degeneration, inflammation,
inclusions

CSF: increased leukocytes (PMNs),


CMV culture, PCR
EMG: polyradiculopathy

EMG: multifocal axonal neuropathy


Nerve biopsy: inflammation,
vasculitis, CMV inclusions

CSF: increased leukocyte count,


elevated protein
EMG: demyelination

EMG: distal axonopathy

CSF: increased leukocyte count,


increased protein
Serum and CSF VDRL

Zidovudine reduction or
withdrawal, corticosteroids

Ganciclovir, foscarnet

Early: none
Late: ganciclovir

Early (increased CD4+ count):


plasmapheresis, IVIG, steroids
Late (decreased CD4 count):
ganciclovir

Neurotoxin withdrawal,
analgesics, tricyclic
antidepressants,
anticonvulsants, capsaicin

Penicillin IV (plus probenecid)

CHAPTER

From Simpson DM, Tagliati M. Neurologic manifestations of HIV infection. Ann Intern Med. 1994;121:770.
CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EMG, electromyography; HIV, human immunodeficiency virus; IT, intrathecal; IV, intravenous; IVIG, intravenous
immunoglobulin; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PMNs, polymorphonuclear leukocytes; VDRL, Venereal Disease Research Laboratory.

Muscle weakness,
myalgia, weight loss

Headache, memory loss,


visual disturbances

Any

Neurosyphilis


60 Spinal Puncture and Cerebrospinal Fluid Examination
1241

1242

SECTION

X NEUROLOGIC PROCEDURES

Mycobacterial Tuberculosis
CNS mycobacterial infection is almost always the result of
infection with Mycobacterium tuberculosis. Infection typically
occurs in the setting of disseminated tuberculosis. Atypical
Mycobacterium infection in HIV-infected individuals uncommonly affects the CNS.
The clinical manifestation is meningitis (particularly meningitis involving the basal cisterns), encephalitis, or abscess
formation. If tuberculosis is suspected, a large volume of CSF
(10mL) is required for adequate culture. The cell count
varies from 100 to 400 cells/L, with a lymphocytic predominance; 30% may show predominantly neutrophils early in the
course of infection. Protein levels are elevated (100 to 500mg/
dL), and the CSF glucose level may be depressed. Acid-fast
stains should be examined by experienced technicians. Fluid
is inoculated onto Lwenstein-Jensen medium, and the
absence of visible growth on the medium should not be considered negative until 8 weeks has elapsed. CSF cultures are
more sensitive than stains.
Primary CNS Lymphoma
CNS lymphoma develops in 2% of AIDS patients. The signs
and symptoms resemble those of diffuse encephalopathy,
although focal neurologic deficits occur occasionally. Leptomeningeal spread of malignancy is reflected in a modest
lymphocytic pleocytosis with slightly elevated protein and
decreased glucose levels. Cytologic yield is improved by
repeated lumbar punctures and submitting large quantities of
CSF or fluid obtained by cisternal puncture.153

Progressive Multifocal Leukoencephalopathy


Progressive multifocal leukoencephalopathy is an uncommon
disorder in individuals with impaired cell-mediated immunity
and is caused by reactivation of JC papovavirus in the kidney.
Progressive demyelination is manifested as dementia, blindness, aphasia, hemiparesis, and seizures, which progress until
death. MRI and CT demonstrate nonenhancing white matter
lesions without a mass effect. Definitive diagnosis is made by
brain biopsy, but CSF may show the presence of myelin basic
protein, increased IgG, and an acellular or a mild CSF pleocytosis (<50 WBCs/L). Average survival is 4 months.154
Cytomegalovirus Infection
Cytomegalovirus is detected in the brains of 30% of HIVinfected persons at autopsy. A distinct CNS disorder has not
been defined. CSF pleocytosis may be minimal. Retinitis and
painful polyradiculopathies are recognized, with a prominent
CSF pleocytosis found in the latter condition.153

Acknowledgment
The editors and author acknowledge the contributions of Jon
Kooiker to this chapter in previous editions. The author
would like to thank Linda J. Kesselring, MS, ELS, for copyediting the manuscript and incorporating revisions into the
final document.
References are available at www.expertconsult.com

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination 1242.e1

References
1. Corning JL. Spinal anaesthesia and local medication of the cord. N Y State
Med J. 1885;42:483.
2. Quincke H. Die lumbar Punktur des Hydrocephalus. Klin Wochenschr.
1891;28:929.
3. Dandy WE. Experimental hydrocephalus. Ann Surg. 1919;70:129.
4. Tourtellotte WW, Shorr RJ. Cerebrospinal fluid. In: Youmans JP, ed. Neurological Surgery. Vol 1. Philadelphia: Saunders; 1982:423.
5. Practice parameters: lumbar puncture (summary statement). Report of the
Quality Standards Subcommittee of the American Academy of Neurology.
Neurology. 1993;43:625.
6. Martin JB, Tyler KL, Scheld WM. Bacterial meningitis. In: Tyler KL, Martin
JB, eds. Infectious Diseases of the Central Nervous System. Philadelphia: Davis;
1993:176.
7. Rothrock SG, Green SM, Wren J, et al. Pediatric bacterial meningitis: is prior
antibiotic therapy associated with an altered clinical presentation? Ann Emerg
Med. 1992;21:146.
8. Bell AH, Brown D, Halliday HL, et al. Meningitis in the newborna 14-year
review. Arch Dis Child. 1989;64:873.
9. Visser VE, Hill RT. Lumbar puncture in the evaluation of suspected neonatal
sepsis. J Pediatr. 1980;96:1063.
10. Walsh-Kelly C, Nelson DB, Smith DS, et al. Clinical predictors of bacterial
versus aseptic meningitis in childhood. Ann Emerg Med. 1992;21:910.
11. Uchihara T, Tsukagoshi H. Jolt accentuation of headache: the most sensitive
sign of CSF pleocytosis. Headache. 1991;31;167.
12. Geiseler PJ, Nelson KE. Bacterial meningitis without clinical signs of meningeal irritation. South Med J. 1982;75:448.
13. Shah KH, Edlow JA. Distinguishing traumatic lumbar puncture from true
subarachnoid hemorrhage. J Emerg Med. 2002;23:67.
14. Edlow JA. Diagnosis of subarachnoid hemorrhage in the emergency department. Emerg Med Clin North Am. 2003;21:73.
15. Sundt TM. Intracranial aneurysms and subarachnoid hemorrhage. In: Siekert
RG, ed. Cerebral Vascular Survey Report. Rochester, MN: Whiting; 1980:306.
16. Boesiger BM. Subarachnoid hemorrhage diagnosis by computed tomography
and lumbar puncture: are fifth generation CT scanners better at identifying
subarachnoid hemorrhage? J Emerg Med. 2005;29:23.
17. Sames TA, Storrow AB, Finkelstein JA, et al. Sensitivity of new-generation
computed tomography in subarachnoid hemorrhage. Acad Emerg Med.
1996;3:16.
18. Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis:
lumbar puncture is still needed when the computed tomography scan is
normal. Acad Emerg Med. 1996;3:827.
19. van der Wee N, Rinkel GJ, Hasan D, et al. Detection of subarachnoid hemorrhage on early CT: is lumbar puncture still needed after a negative scan?
J Neurol Neurosurg Psychiatry. 1995;58:357.
20. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial
hypertension. Neurology. 2002;59:1492.
21. Fishman RA. Cerebrospinal fluid. Diseases of the Nervous System. Philadelphia:
Saunders; 1992:349.
22. Duffy GP. Lumbar puncture in the presence of raised intracranial pressure.
Br Med J. 1969;1:407.
23. Brewer NS, MacCarty CS, Wellman WE. Brain abscess: a review of recent
experience. Ann Intern Med. 1975;82:571.
24. Samson DS, Clark K. A current review of brain abscess. Am J Med. 1973;54:201.
25. Seydoux C, Francioli P. Bacterial brain abscesses: factors influencing mortality
and sequelae. Clin Infect Dis. 1992;15:394.
26. Zimmerman RA, Bilaniuk LT, Shipkin PM, et al. Evolution of cerebral abscess:
correlation of clinical features with computed tomography: a case report.
Neurology. 1977;27:14.
27. Sinclair AJ, Carroll C, Davies B. Cauda equina syndrome following lumbar
puncture. Clin Neurosci. 2009;16:714.
28. Domenicucci M, Ramieri A, Ciappetta P, et al. Nontraumatic acute spinal
subdural hematoma. J Neurosurg. 1999;91:65.
29. Egede LE, Moses H, Wang H. Spinal subdural hematoma: a rare complication
of lumbar puncture. Md Med J. 1999;48:15.
30. Silverman R, Kwiatkowski T, Bernstein S, et al. Safety of lumbar puncture in
patients with hemophilia. Ann Emerg Med. 1993;22:1739.
31. Howard SC, Gajjar A, Ribeiro RC, et al. Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA.
2000;284:2222.
32. van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following
neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals.
Br J Haematol. 2010;148:15.
33. Fisher L, Lupu L, Gurevitz B, et al. Hip flexion and lumbar puncture: a
radiologic study. Anesthesia. 2001;56:262.
34. Baer ET. Iatrogenic meningitis: the case for face masks. Clin Infect Dis.
2000;31:519.
35. Black SR, Weinstein RA. The case for face masksZorro or zero? Clin Infect
Dis. 2000;31:522.
36. Yaniv LG, Potasman I. Iatrogenic meningitis: an increasing role for resistant
viridans streptococci? Case report and review of the last 20 years. Scand J Infect
Dis. 2000;32:693.
37. Baer ET. Postdural puncture bacterial meningitis. Anesthesiology. 2006;105:381.
38. Abbrescia KL, Brabson TA, Dalsy WC, et al. The effects of lower-extremity
position on cerebrospinal fluid pressure. Acad Emerg Med. 2001;8:8.

39. Zivin J. Lateral cervical puncture: an alternative to lumbar puncture. Neurology. 1978;28:616.
40. Greensher J, Mofenson HC, Borofsky LG, et al. Lumbar puncture in the
neonate: a simplified technique. J Pediatr. 1971;78:1034.
41. McDonald JV, Klump TE. Intraspinal epidermoid tumors caused by lumbar
puncture. Arch Neurol. 1986;43:936.
42. Oliver WJ, Shope TC, Kuhns LR. Fatal lumbar puncture: fact versus fiction
an approach to a clinical dilemma. Pediatrics. 2003;112:e174.
43. Fiser DH, Gober GA, Smith CE, et al. Prevention of hypoxemia during
lumbar puncture in infancy with preoxygenation. Pediatr Emerg Care.
1993;9:81.
44. Abo A, Chen L, Johnston P, et al. Positioning for lumbar puncture in children
evaluated by bedside ultrasound. Pediatrics. 2010;125:e1149.
45. Weisman LE, Merenstein GB, Steenbarger JR. The effect of lumbar puncture
position in sick neonates. Am J Dis Child. 1983;137:1077.
46. Eldadah M, Frenkel LD, Hiatt IM, et al. Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome. Pediatr Infect Dis
J. 1987;6:243.
47. Fein D, Avner JR, Khine H. Pattern of pain management during lumbar
puncture in children. Pediatr Emerg Care. 2010;26:357.
48. Hoyle JD Jr, Rogers AJ, Reischman DE, et al. Pain intervention for infant
lumbar puncture in the emergency department: physician practice and beliefs.
Acad Emerg Med. 2011;18:140.
49. Pinheiro JMB, Furdon S, Ochoa LF. Role of local anesthesia during lumbar
puncture in neonates. Pediatrics. 1993;91:379.
50. Porter FL, Miller JP, Cole S, et al. A controlled clinical trial of local anesthesia
for lumbar puncture in newborns. Pediatrics. 1991;88:663.
51. Kaur G, Gupta P, Kumar A. A randomized trial of eutectic mixture of local
anesthetics during lumbar puncture in newborns. Arch Pediatr Adolesc Med.
2003;157:1065.
52. Stiffler KA, Jwayyed S, Wilber ST, et al. The use of ultrasound to identify
pertinent landmarks for lumbar puncture. Am J Emerg Med. 2007;25:331.
53. Strony R. Ultrasound-assisted lumbar puncture in obese patients. Crit Care
Clin. 2010;26:661.
54. Nomura JT, Leech SJ, Shenbagamurthi S, et al. A randomized controlled trial
of ultrasound-assisted lumbar puncture. J Ultrasound Med. 2007;26:1341.
55. Cummings T, Jones JS. Towards evidence based emergency medicine: best
BETs from the Manchester Royal Infirmary. Use of ultrasonography for
lumbar puncture. Emerg Med J. 2007;24:492.
56. Ferre RM, Sweeney TW. Emergency physicians can easily obtain ultrasound
images of anatomical landmarks relevant to lumbar puncture. Am J Emerg
Med. 2007;25:291.
57. Coley BD, Shiels WE 2nd, Hogan MJ. Diagnostic and interventional ultrasonography in neonatal and infant lumbar puncture. Pediatr Radiol.
2001;31:399.
58. Williams J, Lye DC, Umapathi T. Diagnostic lumbar puncture: minimizing
complications. Intern Med J. 2008;38:587.
59. Evans RW. Complications of lumbar puncture. Neurol Clin. 1998;16:83.
60. Sudlow C, Warlow C. Epidural blood patching for preventing and treating
postdural puncture headaches. Cochrane Database Syst Rev. 2002;(2):CD001791.
61. Turnbull DK, Shepherd DB. Postdural puncture headache: pathogenesis,
prevention and treatment. Br J Anaesth. 2003;91:718.
62. Holdgate A, Cuthbert K. Perils and pitfalls of lumbar puncture in the emergency department. Emerg Med (Fremantle). 2001;13:351.
63. Janssens E, Aerssens P, Alliet P, et al. Postdural puncture headaches in children: a literature review. Eur J Pediatr. 2003;162:117.
64. Bezov D, Lipton RB, Ashina S. Postdural puncture headache: Part I.
Diagnosis, epidemiology, etiology, and pathophysiology. Headache. 2010;50:
1144.
65. Zetterberg H, Tullhog K, Hansson O, et al. Low incidence of postlumbar
puncture headache in 1,089 consecutive memory clinic patients. Eur Neurol.
2010;63:326.
66. Frank RL. Lumbar puncture and postdural puncture headaches: implications
for the emergency physician. J Emerg Med. 2008;35:149.
67. Reamy BV. Post-epidural headache: how late can it occur? J Am Board Fam
Med. 2009;22:202.
68. Levine DN, Rapalino O. The pathophysiology of lumbar puncture headache.
J Neurol Sci. 2001;192:1.
69. Flaatten H, Thorsen T, Askeland B, et al. Puncture technique and postural
postdural puncture headache: a randomized, double-blind study comparing
transverse and parallel puncture. Acta Anaesthesiol Scand. 1998;42:1209.
70. Zetlaoui PJ. Bevel orientation and postural puncture headache: a new possible
explanation? Acta Anaesthesiol Scand. 1999;43:967.
71. Aamodt A, Vedeler C. Complications after LP related to needle type: pencilpoint versus Quincke. Acta Neurol Scand. 2001;103:396.
72. Carson D, Serpell M. Choosing the best needle for diagnostic lumbar puncture. Neurology. 1996;47:33.
73. Eriksson AL, Hallen B, LagerKranser M, et al. Whitacre or Quincke needles
does it really matter? Acta Anaesthesiol Scand Suppl. 1998;113:17.
74. Flaatten H, Felthaus J, Kuwelker M, et al. Postural postdural puncture
headache: a prospective randomised study and a meta-analysis comparing two
different 0.40mm O.D. (27g) spinal needles. Acta Anaesthesiol Scand.
2000;44:643.
75. Kleyweg RP, Hertzberger LI, Carbaat PA. Significant reduction in post
lumbar puncture headache using an atraumatic needle: a double-blind, controlled clinical trial. Cephalalgia. 1998;18:635.

1242.e2

SECTION

X NEUROLOGIC PROCEDURES

76. Lierz P, Gustorff B, Felleiter P. First experiences with a new spinal needle. Reg
Anesth Pain Med. 2000;25:209.
77. Serpell MG, Rawal N. Headaches after diagnostic dural puncture. BMJ.
2000;321:973.
78. Thomas SR, Jamieson DR, Muir KW. Randomized controlled trial of atraumatic versus standard needles for diagnostic lumbar puncture. BMJ.
2000;321:986.
79. Vilming ST, Kloster R, Sandvik L. The importance of sex, age, needle size,
height and body mass index in postlumbar puncture headache. Cephalagia.
2000;21:738.
80. Reina MA, Dittman M, Lopez-Garcia A, et al. New perspectives in the microscopic structure of human dura matter in the dorsolumbar region. Reg Anesth.
1997;22:161.
81. Reina MA, deLeon-Casasola OA, Lopez A, et al. An in vitro study of dural
lesions produced by 25-gauge Quincke and Whitacre needles evaluated by
scanning election microscopy. Reg Anesth Pain Med. 2000;25:347.
82. Arendt K, Demaerschalk BM, Wingerchuk DM, et al. Atraumatic lumbar
puncture needles: after all these years, are we still missing the point? Neurologist. 2009;15:17.
83. Birnbach DJ, Kuroda MM, Sternman D, et al. Use of atraumatic spinal needles
among neurologists in the United States. Headache. 2001;41:385.
84. Dakka Y, Warra N, Albadareen RJ, et al. Headache rate and cost of care following lumbar puncture at a single tertiary care hospital. Neurology. 2011;77:71.
85. Brocker RJ. A technique to avoid post spinal-tap headache. JAMA.
1958;168:261.
86. Theonnissen J, Herkner H, Lang W, et al. Does bed rest after cervical or
lumbar puncture prevent headache? A systematic review and meta-analysis.
CMAJ. 2001;165:1311.
87. Lin W, Giederman J. Myth: fluids, bed rest, and caffeine are effective in
preventing and treating patients with postlumbar puncture headache. West J
Med. 2002;176:69.
88. Choi A, Laurito CE, Cunningham FE. Pharmacologic management of postdural puncture headache. Ann Pharmacother. 1996;30:831.
89. Vincent S, Aboff B. Use of caffeine in postdural puncture headache: a case
report. Del Med J. 2000;73:97.
90. Basurto Ona X, Martnez Garca L, Sol I, et al. Drug therapy for treating
post dural puncture headache. Cochrane Database Syst Rev. 2011;8:CD007887.
91. Klepstad P. Relief of postural postdural puncture headache by an epidural
blood patch 12 months after dural puncture. Acta Anaesthesiol Scand.
1999;43:964.
92. Olsen KS. Epidural blood patch in the treatment of postlumbar puncture
headache. Pain. 1987;30:293.
93. Vercauteren MP, Hoffman VH, Mertens E, et al. Seven-year review of requests
for epidural blood patches for headache after dural puncture: referral patterns
and the effectiveness of blood patches. Eur J Anaesthesiol. 1999;16:298.
94. Boonmak P, Boonmak S. Epidural blood patching for preventing and treating
postdural puncture headache. Cochrane Database Syst Rev. 2010;1:CD001791.
95. van Kooten F, Oedit R, Bakker SL, et al. Epidural blood patch in post dural
puncture headache: a randomised, observer-blind, controlled clinical trial.
J Neurol Neurosurg Psychiatry. 2008;79:553.
96. Safa-Tisseront V, Thormann F, Malassine P, et al. Effectiveness of epidural
blood patch in the management of postdural puncture headache. Anesthesiology. 2001;95:334.
97. Paech MJ, Doherty DA, Christmas T, et al. The volume of blood for epidural
blood patch in obstetrics: a randomized, blinded clinical trial. Anesth Analg.
2011;113:126.
98. Desai MJ, Dave AP, Martin MB. Delayed radicular pain following two large
volume epidural blood patches for postlumbar puncture headache: a case
report. Pain Phys. 2010;13:257.
99. Feder HM Jr, Adelman AM, Pugno PA, et al. Family practice grand rounds:
meningitis following normal lumbar punctures. J Fam Pract. 1985;20:437.
100. Krishna V, Liu V, Singleton AF. Should lumbar puncture be routinely performed in patients with suspected bacteremia? J Natl Med Assoc. 1983;75:1153.
101. Schull MJ. Lumbar puncture first: an alternative model for the investigation
of lone acute sudden headache. Acad Emerg Med. 1999;6:131.
102. Joffe AR. Lumbar puncture and brain herniation in acute bacterial meningitis:
a review. J Intensive Care Med. 2007;22:194.
103. Gopal AK, Whitehouse JD, Simel DL, et al. Cranial computed tomography
before lumbar puncture: a prospective clinical evaluation. Arch Intern Med.
1999;159:2681.
104. Greig PR, Goroszeniuk D. Role of computed tomography before lumbar
puncture: a survey of clinical practice. Postgrad Med J. 2006;82:162.
105. Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of the head
before lumbar puncture in adults with suspected meningitis. N Engl J Med.
2001;345:1727.
106. Gower DJ, Baker AL, Bell WO, et al. Contraindications to lumbar puncture
as defined by computed cranial tomography. J Neurol Neurosurg Psychiatry.
1987;50:1071.
107. Silvers SM, Simmons B, Wall S, et al. Clinical policy: critical issues in the
evaluation and management of patients presenting to the emergency department with acute headache. Ann Emerg Med. 2002;39:108.
108. Levine JF, Hiesiger EM, Whelan MP, et al. Pneumococcal meningitis associated with retroperitoneal abscess: a rare complication of lumbar puncture.
JAMA. 1982;248:2308.
109. Thomke F, Mika-Gruttner A, Visbeck A, et al. The risk of abducens palsy after
diagnostic lumbar puncture. Neurology. 2000;54:768.

110. Ng WH, Drake JM. Symptomatic spinal epidural CSF collection after lumbar
puncture in a young adult: case report and review of literature. Childs Nerv
Syst. 2010;26:259.
111. Aronson PL, Zonfrillo MR. Epidural cerebrospinal fluid collection after
lumbar puncture. Pediatr Emerg Care. 2009;25:467.
112. Sinclair AJ, Carroll C, Davies B. Cauda equina syndrome following a lumbar
puncture. J Clin Neurosci. 2009;16:714.
113. Lee SJ, Lin YY, Hsu CW, et al. Intraventricular hematoma, subarachnoid
hematoma and spinal epidural hematoma caused by lumbar puncture: an
unusual complication. Am J Med Sci. 2009;337:143.
114. Liu WH, Lin JH, Lin JC, et al. Severe intracranial and intraspinal subarachnoid hemorrhage after lumbar puncture: a rare case report. Am J Emerg Med.
2008;26:633.e1.
115. Hewett R, Counsell C. Documentation of cerebrospinal fluid opening pressure and other important aspects of lumbar puncture in acute headache. Int J
Clin Pract. 2010;64:930.
116. Avery RA, Shah SS, Licht DJ, et al. Reference range for cerebrospinal fluid
opening pressure in children. N Engl J Med. 2010;363:891.
117. Rando TA, Fishman RA. Spontaneous intracranial hypotension: report of two
cases and review of the literature. Neurology. 1992;42:481.
118. Shenkin HA, Finneson BE. Clinical significance of low cerebral spinal fluid
pressure. Neurology. 1958;8:157.
119. Arora S, Swadron SP, Dissanayake V. Evaluating the sensitivity of visual xanthochromia in patients with known subarachnoid hemorrhage. J Emerg Med.
2010;39:13-16.
120. Graves PF, Sidman RD. Xanthochromia is not pathognomic for subarachnoid
hemorrhage [abstract]. Acad Emerg Med. 2002;9:412.
121. Kestenbaum LA, Ebberson J, Zorc JJ, et al. Defining cerebrospinal fluid white
blood cell count reference values in neonates and young infants. Pediatrics.
2010;125:257.
122. Hayward RA, Oye RK. Are polymorphonuclear leukocytes an abnormal
finding in cerebrospinal fluid? Results from 225 normal cerebrospinal fluid
specimens. Arch Intern Med. 1988;148:1623.
123. Kruskall MS, Carter SR, Rtz LP. Contamination of cerebrospinal fluid by
vertebral bone-marrow cells during lumbar puncture. N Engl J Med.
1983;308:697.
124. Greenlee JE. Approach to diagnosis of meningitis: cerebrospinal fluid evaluation. Infect Dis Clin. 1990;4:583.
125. Whitaker JN, Beneveniste EN, Zhou SD. Cerebral spinal fluid. In: Cook SD,
ed. Handbook of Multiple Sclerosis. New York: Marcel Dekker; 1990:251.
126. Shah KH, Richard KM, Nicholas S, et al. Incidence of traumatic lumbar
puncture. Acad Emerg Med. 2003;10:151.
127. Yu SD, Chen MY, Johnson AJ. Factors associated with traumatic fluoroscopyguided lumbar punctures: a retrospective review. AJNR Am J Neuroradiol.
2009;30:512.
128. Shah KH, McGillicuddy D, Spear J, et al. Predicting difficult and traumatic
lumbar punctures. Am J Emerg Med. 2007;25:608.
129. Gorchynski J, Oman J, Newton T. Interpretation of traumatic lumbar puncture in the setting of possible subarachnoid hemorrhage: who can be safely
discharged? Calif J Emerg Med. 2007;8:3.
130. Rinkel GJ, van Gijn J, Wijdicks EF. Subarachnoid hemorrhage without detectable aneurysm: a review of causes. Stroke. 1993;24:1403.
131. Graves P, Sidman R. Xanthochromia is not pathognomonic for subarachnoid
hemorrhage. Acad Emerg Med. 2004;11:131.
132. Julia-Sanchis ML, Estela-Burriel PL, Liron-Hernandez FJ, et al. Rapid differential diagnosis between subarachnoid haemorrhage and traumatic lumbar
puncture by D-dimer assay. Clin Chem. 2007;53:993.
133. Eskey CJ, Ogilvy CS. Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and implications for the assessment of CT-negative
subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2001;22:571.
134. Welch H, Hasbun R. Lumbar puncture and cerebrospinal fluid analysis. Handb
Clin Neurol. 2010;96:31.
135. Kleiman MB, Reynolds JK, Watts NH, et al. Superiority of acridine orange
stain versus Gram stain in partially treated bacterial meningitis. J Pediatr.
1984;104:401.
136. Ris J, Mancebo J, Domingo P, et al. Bacterial meningitis despite normal CSF
findings. JAMA. 1985;254:2893.
137. Vorki AP, Puthuran P. Value of second lumbar puncture in confirming
a diagnosis of aseptic meningitis: a prospective study. Arch Neurol. 1979;36:
581.
138. Shohet I, Shahar E, Meyerovich J, et al. Diagnosis of bacterial meningitis in
previously treated children. South Med J. 1985;78:299.
139. Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis: an analysis of the predictive value of initial observations. JAMA.
1989;262:2700.
140. Talan DA, Hoffman JR, Yoshikawa TT, et al. Role of empiric parenteral
antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of
the art. Rev Infect Dis. 1988;10:365.
141. Edberg SC. Conventional and molecular techniques for the laboratory
diagnosis of infections of the central nervous system. Neurol Clin. 1986;
4:13.
142. Klein JO, Feigin RD, McCracken GH Jr. Report of the Task Force on Diagnosis and Management of Meningitis. Pediatrics. 1986;78:959.
143. Lipton JD, Schafermeyer RW. Evolving concepts in pediatric bacterial
meningitisPart I: pathophysiology and diagnosis; and Part II: current management and therapeutic research. Ann Emerg Med. 1993;22:1602.

CHAPTER

60 Spinal Puncture and Cerebrospinal Fluid Examination 1242.e3

144. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric


bacterial meningitis: defining the time interval for recovery of cerebral spinal
fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108:
1169.
145. de Gans J, Van de beek D. Dexamethasone in adults with bacterial meningitis.
N Engl J Med. 2002;347:1549.
146. van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial
meningitis. Cochrane Database Syst Rev. 2007;1:CD004405.
147. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.
N Engl J Med. 1991;324:1525.
148. Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992;327:864.
149. Hotson JR. Modern neurosyphilis: a partially treated chronic meningitis. West
J Med. 1981;135:191.
150. Jaffe HW. The laboratory diagnosis of syphilis: new concepts. Ann Intern Med.
1975;83:846.

151. Chalmers AC, Aprill BS, Shephard H. Cerebrospinal fluid and human immunodeficiency virus: findings in healthy, asymptomatic, seropositive men. Arch
Intern Med. 1990;150:1538.
152. Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the
emergency department to patients ultimately diagnosed with encephalitis. Ann
Emerg Med. 2006;47:100.
153. Levy RM, Berger JR. HIV and HTLV infections of the nervous system. In:
Tyler KL, Martin JB, eds. Infectious Diseases of the Central Nervous System.
Philadelphia: Davis; 1993:47.
154. Evans BK, Donley DK, Whitaker JN. Neurological manifestations of infection with the human immunodeficiency viruses. In: Scheld MW, Whitley RJ,
Durack DT, eds. Infections of the Central Nervous System. New York: Raven;
1991:201.
155. Marra C. Neurosyphilis. In: Infections of the Nervous System. Presented before
the Annual Meeting of the American Academy of Neurology, May 3, 1992,
San Diego, CA.