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Cerebrospinal fluid analysis

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Lumbar puncture is frequently performed in primary care. Properly interpreted tests can make cerebrospinal fluid (CSF) a key tool in the diagnosis of a variety of diseases. Proper evaluation of CSF depends on knowing which tests to order, normal ranges for the patient's age, and the test's limitations. Protein level, opening pressure, and CSF-to-serum glucose ratio vary with age. Xanthochromia is most often caused by the presence of blood, but several other conditions should be considered. The presence of blood can be a reliable predictor of subarachnoid hemorrhage but takes several hours to develop. The three-tube method, commonly used to rule out a central nervous system hemorrhage after a "traumatic tap," is not completely reliable. Red blood cells in CSF caused by a traumatic tap or a subarachnoid hemorrhage artificially increase the white blood cell count and protein level, thereby confounding the diagnosis. Diagnostic uncertainty can be decreased by using accepted corrective formulas. White blood cell differential may be misleading early in the course of meningitis, because more than 10 percent of cases with bacterial infection will have an initial lymphocytic predominance and viral meningitis may initially be dominated by neutrophils. Culture is the gold standard for determining the causative organism in meningitis. However, polymerase chain reaction is much faster and more sensitive in some circumstances. Latex agglutination, with high sensitivity but low specificity, may have a role in managing partially treated meningitis. To prove herpetic, cryptococcal, or tubercular infection, special staining techniques or collection methods may be required.
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SEPTEMBER 15, 2003 / VOLUME 68, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1103
pressure, and cautioned not to hyperventilate,
because hyperventilating will lower the open-
ing pressure.
Normal opening pressure ranges from 10 to
100 mm H
2
0 in young children, 60 to 200 mm
H
2
0 after eight years of age, and up to 250 mm
H
2
0 in obese patients.
2
Intracranial hypoten-
sion is defined as an opening pressure of less
than 60 mm H
2
0. This finding is rare except in
patients with a history of trauma causing a
CSF leak, or whenever the patient has had a
previous lumbar puncture.
3
Opening pressures above 250 mm H
2
0 are
diagnostic of intracranial hypertension. Ele-
vated intracranial pressure is present in many
pathologic states, including meningitis,
intracranial hemorrhage, and tumors. Idio-
pathic intracranial hypertension is a condition
most commonly seen in obese women during
their childbearing years. When an elevated
opening pressure is discovered, CSF should be
removed slowly and the pressure monitored
during the procedure. No additional CSF
should be removed once the pressure reaches
50 percent of the opening pressure.
4
P
rimary care physicians frequently
perform lumbar puncture, be-
cause cerebrospinal fluid (CSF) is
an invaluable diagnostic window
to the central nervous system
(CNS). Commonly performed tests on CSF
include protein and glucose levels, cell counts
and differential, microscopic examination,
and culture. Additional tests such as opening
pressure, supernatant color, latex agglutina-
tion, and polymerase chain reaction also may
be performed. Knowing which tests to order
and how to interpret them allows physicians
to use CSF as a key diagnostic tool in a vari-
ety of diseases.
Opening Pressure
To measure CSF opening pressure, the
patient must be in the lateral decubitus posi-
tion with the legs and neck in a neutral posi-
tion. The meniscus will fluctuate between 2
and 5 mm with the patient’s pulse and
between 4 and 10 mm with respirations.
1
The
patient should be advised not to strain,
because straining can increase the opening
Lumbar puncture is frequently performed in primary care. Properly interpreted tests can
make cerebrospinal fluid (CSF) a key tool in the diagnosis of a variety of diseases. Proper eval-
uation of CSF depends on knowing which tests to order, normal ranges for the patient’s age,
and the test’s limitations. Protein level, opening pressure, and CSF-to-serum glucose ratio
vary with age. Xanthochromia is most often caused by the presence of blood, but several
other conditions should be considered. The presence of blood can be a reliable predictor of
subarachnoid hemorrhage but takes several hours to develop. The three-tube method, com-
monly used to rule out a central nervous system hemorrhage after a “traumatic tap,” is not
completely reliable. Red blood cells in CSF caused by a traumatic tap or a subarachnoid hem-
orrhage artificially increase the white blood cell count and protein level, thereby confound-
ing the diagnosis. Diagnostic uncertainty can be decreased by using accepted corrective for-
mulas. White blood cell differential may be misleading early in the course of meningitis,
because more than 10 percent of cases with bacterial infection will have an initial lympho-
cytic predominance and viral meningitis may initially be dominated by neutrophils. Culture is
the gold standard for determining the causative organism in meningitis. However, poly-
merase chain reaction is much faster and more sensitive in some circumstances. Latex agglu-
tination, with high sensitivity but low specificity, may have a role in managing partially
treated meningitis. To prove herpetic, cryptococcal, or tubercular infection, special staining
techniques or collection methods may be required. (Am Fam Physician 2003;68:1103-8. Copy-
right© 2003 American Academy of Family Physicians.)
Cerebrospinal Fluid Analysis
DEAN A. SEEHUSEN, M.D., MARK M. REEVES, M.D., and DEMITRI A. FOMIN, M.D.
Tr ipler Army Medical Center, Honolulu, Hawaii
See page 1039 for
definitions of strength-
of-evidence levels.
Supernatant Color
Normal CSF is crystal clear. However, as few
as 200 white blood cells (WBCs) per mm
3
or
400 red blood cells (RBCs) per mm
3
will cause
CSF to appear turbid. Xanthochromia is a yel-
low, orange, or pink discoloration of the CSF,
most often caused by the lysis of RBCs result-
ing in hemoglobin breakdown to oxyhemo-
globin, methemoglobin, and bilirubin. Discol-
oration begins after RBCs have been in spinal
fluid for about two hours, and remains for two
to four weeks.
5
Xanthochromia is present in
more than 90 percent of patients within
12 hours of subarachnoid hemorrhage onset
2
and in patients with serum bilirubin levels
between 10 to 15 mg per dL (171 to 256.5
µmol per L). CSF protein levels of at least 150
mg per dL (1.5 g per L)—as seen in many
infectious and inflammatory conditions, or as
a result of a traumatic tap that contains more
than 100,000 RBCs per mm
3
—also will result
in xanthochromia.
2
Newborn CSF is often
xanthochromic because of the frequent eleva-
tion of bilirubin and protein levels in this age
group. Table 1 lists CSF colors associated with
various conditions.
Cell Count
Normal CSF may contain up to 5 WBCs per
mm
3
in adults and 20 WBCs per mm
3
in new-
borns.
6
Eighty-seven percent of patients with
bacterial meningitis will have a WBC count
higher than 1,000 per mm,
3
while 99 percent
will have more than 100 per mm
3
.Having less
than 100 WBCs per mm
3
is more common in
patients with viral meningitis.
2
Elevated WBC counts also may occur after a
seizure,
7
in intracerebral hemorrhage, with
malignancy, and in a variety of inflammatory
conditions. Tab l e 2 lists common CSF findings
in various types of meningitis.
Peripheral blood in the CSF after a “trau-
matic tap will result in an artificial increase
in WBCs by one WBC for every 500 to
1,000 RBCs in the CSF. This correction factor
is accurate as long as the peripheral WBC
count is not extremely high or low.
A traumatic tap occurs in approximately
20 percent of lumbar punctures. Common
practice is to measure cell counts in three
consecutive tubes of CSF. If the number of
RBCs is relatively constant, then it is assumed
that the blood is caused by an intracranial
1104 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 68, NUMBER 6 / SEPTEMBER 15, 2003
TABLE 1
Cerebrospinal Fluid Supernatant Colors
and Associated Conditions or Causes
Color of CSF
supernatant Conditions or causes
Yellow Blood breakdown products
Hyperbilirubinemia
CSF protein 150 mg per dL
(1.5 g per L)
>100,000 red blood cells per mm
3
Orange Blood breakdown products
High carotenoid ingestion
Pink Blood breakdown products
Green Hyperbilirubinemia
Purulent CSF
Brown Meningeal melanomatosis
CSF = cerebrospinal fluid.
Information from references 2, 4, and 5.
The Authors
DEAN A. SEEHUSEN, M.D., is a faculty development fellow in the Department of Fam-
ily Practice at Madigan Army Medical Center, Tacoma, Wash. He formerly was a staff
physician in the Department of Family Practice and Emergency Medical Services at
Tripler Army Medical Center, Honolulu. He earned his medical degree from the Uni-
versity of Iowa College of Medicine, Iowa City, and completed a residency in family
practice at Tripler Army Medical Center.
MARK M. REEVES, M.D., is director of the family practice residency program at Tripler
Army Medical Center. He earned his medical degree from the Uniformed Services Uni-
versity of the Health Sciences, Bethesda, Md., and completed a residency in family
practice at Dwight D. Eisenhower Army Medical Center, Augusta, Ga.
DEMITRI A. FOMIN, M.D., is a staff neurologist in the Department of Medicine, neu-
rology service, at Tripler Army Medical Center. He earned his medical degree from the
Uniformed Services University of the Health Sciences and completed a residency in
neurology at Walter Reed Army Medical Center, Washington, D.C.
Address correspondence to Dean A. Seehusen, M.D., 5803 152nd Ave. Ct. E, Sumner,
WA 98390 (e-mail: dseehusen@msn.com). Reprints are not available from the authors.
Xanthochromia is present in more than 90 percent of
patients within 12 hours of subarachnoid hemorrhage onset.
hemorrhage. A falling count is attributed to a
traumatic tap. The three-tube method, how-
ever, is not always reliable.
8
Xanthochromia is a more reliable predictor
of hemorrhage. If a traumatic tap occurs
within 12 hours of a suspected subarachnoid
hemorrhage, it is reasonable to repeat the
lumbar puncture one interspace up to try and
obtain clear CSF.
9
Cell Differential
The WBC count seen in normal adult CSF is
comprised of approximately 70 percent lym-
phocytes and 30 percent monocytes. Occa-
sionally, a solitary eosinophil or polymor-
phonucleocyte (PMN) will be seen in normal
CSF.
2
Several PMNs in a neonatal patient’s CSF
is not unusual.
6
The majority of patients with Guillain-
Barré syndrome will have 10 or fewer mono-
cytes per mm
3
and a minority of patients will
have 11 to 50 monocytes per mm
3
.Up to
50 monocytes per mm
3
are seen in about
25 percent of patients with multiple sclerosis.
2
The cell differential alone cannot differentiate
between bacterial and nonbacterial meningi-
tis. Lymphocytosis is seen in viral, fungal, and
tuberculous infections of the CNS, although a
predominance of PMNs may be present in the
early stages of these infections. CSF in bacter-
ial meningitis is typically dominated by the
presence of PMNs. However, more than
10 percent of bacterial meningitis cases will
show a lymphocytic predominance, especially
early in the clinical course and when there are
fewer than 1,000 WBCs per mm
3
(Table 2).
10
Eosinophilic meningitis is defined as more
than 10 eosinophils per mm
3
or a total CSF
cell count made up of more than 10 percent
eosinophils. Parasitic infection should be sus-
pected in this situation. Other possible causes
may include viral, fungal, or rickettsial menin-
gitis; having ventriculoperitoneal shunts with
or without coexisting infection; malignancy;
and adverse drug reactions.
11
Microscopic Examination
Gram stain is positive in 60 to 80 percent of
untreated cases of bacterial meningitis and in
40 to 60 percent of partially treated cases. The
sensitivity according to the causative organism
ranges from 90 percent in pneumococcal or
CSF Analysis
SEPTEMBER 15, 2003 / VOLUME 68, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1105
TABLE 2
Typical Cerebrospinal Fluid Findings in Various Types of Meningitis
Test Bacterial Viral Fungal Tubercular
Opening pressure Elevated Usually normal Variable Variable
White blood cell count 1,000 per mm
3
<100 per mm
3
Variable Variable
Cell differential Predominance of Predominance of Predominance Predominance
PMNs* lymphocytes of lymphocytes of lymphocytes
Protein Mild to marked Normal to elevated Elevated Elevated
elevation
CSF-to-serum glucose Normal to marked Usually normal Low Low
ratio decrease
CSF = cerebrospinal fluid; PMNs = polymorphonucleocytes.
*—Lymphocytosis present 10 percent of the time.
†—PMNs may predominate early in the course.
Information from references 2, 10, 17, and 20.
staphylococcal meningitis to less than 50 per-
cent in Listeria meningitis. Hyphae can occa-
sionally be seen in Candida or other fungal
meningitis cases.
Several factors influence the sensitivity of
Gram stain. Laboratory techniques used to
concentrate and stain CSF can greatly influ-
ence reliability. Cytocentrifugation increases
the ability to detect bacteria.
12
Greater num-
bers of colony-forming units (CFU) per mm
3
of CSF increase the likelihood of a positive
result. Staining will be positive in 25 percent of
cases if fewer than 1,000 CFU per mm
3
are
present, and in 75 percent of cases if more
than 100,000 CFU per mm
3
are present.
1
Lastly, the experience of laboratory personnel
is very important. Up to 10 percent of initial
Gram stains are misread.
13
Acid-fast staining should be done if tuber-
culosis is clinically suspected. Only 37 per-
cent of initial smears will be positive for acid-
fast bacilli. This result can be increased to
87 percent if four smears are done.
14
Sensi-
tivity also can be increased by examining the
CSF sediment.
15
Other stains should be performed if indi-
cated by the situation. Cryptococcus may be
identified up to 50 percent of the time on an
India ink preparation. A tap-water control
should always be done to ensure that the India
ink is not contaminated.
16
Toxoplasmosis can be diagnosed with
Wright or Giemsa stain. A simple wet prepa-
ration of CSF under a cover slip can yield pos-
itive results in a variety of protozoan and
helminthic infections.
14
Protein Level
CSF protein concentration is one of the
most sensitive indicators of pathology within
the CNS. Newborn patients have up to 150 mg
per dL (1.5 g per L) of protein.
2
The adult
range of 18 to 58 mg per dL (0.18 to 0.58 g per
L) is reached between six and 12 months of
age.
4
The physician should know what the
normal reference range is for his or her labo-
ratory,because the measurement is somewhat
technique-dependent.
Elevated CSF protein is seen in infections,
intracranial hemorrhages, multiple sclerosis,
Guillain Barré syndrome, malignancies, some
endocrine abnormalities, certain medication
use, and a variety of inflammatory conditions
(Table 3).Protein concentration is falsely ele-
vated by the presence of RBCs in a traumatic
tap situation. This can be corrected by sub-
tracting 1 mg per dL (0.01 g per L) of protein
for every 1,000 RBCs per mm
3
.
5
[Evidence
level B: observational study] This correction is
only accurate if the same tube is used for the
protein and cell counts.
Low CSF protein levels can occur in condi-
tions such as repeated lumbar puncture or a
chronic leak, in which CSF is lost at a higher
than normal rate.
5
Low CSF protein levels also
are seen in some children between the ages of
six months and two years, in acute water intox-
ication, and in a minority of patients with idio-
pathic intracranial hypertension. CSF protein
levels do not fall in hypoproteinemia.
2
Glucose Level
A true normal range cannot be given for
CSF glucose. As a general rule, CSF glucose is
1106
AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 68, NUMBER 6 / SEPTEMBER 15, 2003
TABLE 3
Average and Range of Cerebrospinal Fluid Protein
Average: mg
Condition per dL (g per L) Range: mg per dL (g per L)
Bacterial meningitis 418 (4.18) 21 to 2220 (0.21 to 22.2)
Brain tumor 115 (1.15) 15 to 1920 (0.15 to 19.2)
Brain abscess 69 (0.69) 16 to 288 (0.16 to 2.88)
Aseptic meningitis 77 (0.77) 11 to 400 (0.11 to 4.0)
Multiple sclerosis 43 (0.43) 13 to 133 (0.13 to 1.33)
Cerebral hemorrhage 270 (2.7) 19 to 2110 (0.19 to 21.1)
Epilepsy 31 (0.31) 7 to 200 (0.07 to 2.0)
Acute alcoholism 32 (0.32) 13 to 88 (0.13 to 0.88)
Neurosyphilis 68 (0.68) 15 to 4200 (0.15 to 42.0)
Adapted with permission from Fishman RA. Cerebrospinal fluid in diseases of the
nervous system. 2d ed. Philadelphia: Saunders, 1992.
about two thirds of the serum glucose mea-
sured during the preceding two to four hours
in a normal adult. This ratio decreases with
increasing serum glucose levels. CSF glucose
levels generally do not go above 300 mg per dL
(16.7 mmol per L) regardless of serum levels.
5
Glucose in the CSF of neonates varies much
more than in adults, and the CSF-to-serum
ratio is generally higher than in adults.
4
CNS infections can cause lowered CSF glu-
cose levels, although glucose levels are usually
normal in viral infections (Table 2).
14
Normal
glucose levels do not rule out infection,
because up to 50 percent of patients who have
bacterial meningitis will have normal CSF
glucose levels.
5
Chemical meningitis, inflammatory condi-
tions, subarachnoid hemorrhage, and hypo-
glycemia also cause hypoglycorrhachia (low
glucose level in CSF). Elevated levels of glu-
cose in the blood is the only cause of having an
elevated CSF glucose level. There is no patho-
logic process that causes CSF glucose levels to
be elevated.
Culture
Cultures done on 5 percent sheep blood
agar and enriched chocolate agar remain the
gold standards for diagnosing bacterial
meningitis.
12
Antibiotic treatment prior to
lumbar puncture can decrease the sensitivity
of culture, especially when given intra-
venously or intramuscularly.
17
Enterovirus, the leading cause of viral
meningitis, can be recovered in 40 to 80 per-
cent of cases. Culture for herpes simplex virus
is 80 to 90 percent sensitive but can take five to
seven days to become positive.
18
Results of
viral cultures rarely change the initial manage-
ment of meningitis.
19
Mycobacterium tuberculosis is best grown
using multiple large volume samples of CSF.
At least 15 mL and preferably 40 to 50 mL of
CSF are recommended. Culture is positive
56 percent of the time on the first sample,
and improved to 83 percent of the time if
four separate samples are cultured. These
cultures often take up to six weeks for posi-
tive identification.
20
Fungal cultures are positive in more than
95 percent of Cryptococcus neoformans cases
and in 66 percent of candidal meningitis
cases. Other fungi are less likely to be culture
positive.
9
Similar to tuberculous meningitis,
culture yield in fungal meningitis can be
increased by obtaining large volumes of CSF
via repeated lumbar punctures.
15
Latex Agglutination
Latex agglutination (LA) allows rapid de-
tection of bacterial antigens in CSF. Sensitivity
varies greatly between bacteria. LA for
Haemophilus influenzae has a sensitivity of 60
to 100 percent, but is much lower for other
bacteria. The specificity for LA is very low.
5
However, LA can be useful in partially treated
meningitis cases where cultures may not yield
an organism.
13
Because false positives lead to
unnecessary treatment, LA is not routinely
used today. Some experts suggest using LA in
cases of suspected bacterial meningitis if the
initial Gram stain and bacterial culture are
negative after 48 hours.
12
Polymerase Chain Reaction
Polymerase chain reaction (PCR) has been
a great advance in the diagnosis of meningitis.
PCR has high sensitivity and specificity for
many infections of the CNS, is fast, and can be
done with small volumes of CSF. Although
testing is expensive, there is a potential for cost
savings by decreasing overall diagnostic test-
ing and intervention.
21
PCR has been especially useful in the diag-
nosis of viral meningitis. PCR of the CSF has
a sensitivity of 95 to 100 percent, and a sensi-
tivity of 100 percent for herpes simplex virus
type 1, Epstein-Barr virus, and enterovirus.
14
CSF Analysis
SEPTEMBER 15, 2003 / VOLUME 68, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1107
Cultures of cerebrospinal fluid are still the gold standard for
confirming the diagnosis of bacterial meningitis.
PCR is faster and more sensitive than culture
for enterovirus meningitis.
22
When PCR is
positive for enterovirus, it allows earlier hospi-
tal discharge and less intervention.
23
[Evi-
dence level B: retrospective chart review]
PCR is the most sensitive means of diag-
nosing CMV infections of the CNS,
21
and it
has been suggested that PCR should replace
brain biopsy as the gold standard for herpes
encephalitis.
24
PCR has a sensitivity of 54 to 100 percent
and a specificity of 94 to 100 percent for
tuberculous meningitis, and could replace
acid-fast bacillus smear and culture as the test
of choice.
25
PCR is sensitive for acute neu-
rosyphilis but not for more chronic forms.
21
PCR also is being studied as a diagnostic tool
for bacterial meningitis and other infections
of the CNS.
12
The opinions and assertions contained herein are
the private views of the authors and are not to be
construed as official or as reflecting the views of the
U.S. Army Medical Corps or the U.S. Army at large.
The authors indicate that they do not have any con-
flicts of interest. Sources of funding: none reported.
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1108 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 68, NUMBER 6 / SEPTEMBER 15, 2003
Polymerase chain reaction testing has proved to be especially
useful in the diagnosis of viral meningitis.
CSF Analysis
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A pyogenic infection-induced brain abscess is rare, and usually affects immunocompromised people. Brain imaging and bacterial culture from the infection site are used to diagnose a brain abscess. An effective treatment method is surgical resection combined with antibiotic treatment with bacteria-sensitive antibiotics for a sufficient period of time. Presentation of the Case: A 16-year-old boy was confirmed to have Sphenoidal Sinusitis. The patient had been diagnosed with dengue fever three weeks ago and corona infection four months ago. And finally, he was diagnosed with Sphenoidal Sinusitis which manifested as severe headache, vomiting, and fever. He underwent bilateral Functional Endoscopy Sinus Surgery (FESS), sphenoidotomy and also temporal craniotomy and evacuation of abscess. Conclusion: The treatment of a brain abscess requires early diagnosis, appropriate surgical treatment, and adequate duration of therapy with effective antibiotics. Case Study Arthanareeswaran et al.; JPRI, 34(26A): 32-36, 2022; Article no.JPRI.84950 33
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Background Currently no reliable tools are available for predicting the risk of central nervous system (CNS) infections in patients with intracerebral hemorrhage after undergoing ventriculostomy drainage. The current study sought to develop and validate a nomogram to identify high-risk factors of CNS infection after ventriculomegaly drain placement for intracerebral hemorrhage. Methods A total of 185 patients with intracerebral hemorrhage who underwent ventriculoperitoneal drainage were enrolled to the current study. Patients were divided into a CNS infection group (20 patients) and a non-CNS infection group (165 patients). The baseline data from both groups was used to develop and evaluate a model for predicting the likelihood of developing CNS infection after ventriculoperitoneal drain placement for intracerebral hemorrhage. Results The finding showed that operative time, intraventricular drainage duration, postoperative temperature, white blood cell count in cerebrospinal fluid (CSF), neutrophils ratio in CSF, Red blood cell count in CSF, and glucose content in CSF were correlated with CNS infection. A nomogram for predicting the risk of CNS infection was constructed based on these variables. The c-index and the AUC of the ROC curve was 0.961, showing good discrimination. Clinical decision curve analysis indicated that the nomogram clinical application ranged between 1 and 100%. The clinical impact curve was generated to set with a threshold probability of 0.5. Conclusion The nomogram reported in the current study can be used by clinicians to identify patients likely to have secondary CNS infections, so that clinicians can better treat these patients at earlier stages.
Article
Background Neuroinflammation has been linked to depression; however, neuroinflammatory biomarkers in the cerebrospinal fluid (CSF) have not previously been thoroughly investigated in a large group of patients with recent onset depression compared to healthy controls. Methods Individually matched case-control study comparing patients with recent onset depression (ICD-10: F32) to controls. Primary outcomes: CSF white cell count (WCC), CSF/serum albumin ratio, CSF total protein and immunoglobulin G (IgG) index. Secondary outcomes: CSF WCC differential count, CSF neutrophil/lymphocyte, CSF/serum IgG and CSF/plasma glucose ratios. Linear models adjusting for sex and age were applied. Results We included 106 patients with recent onset depression (84.0% outpatients) and 106 healthy controls. Patients had 18% higher CSF WCC relative to controls (Relative Mean Difference [MD]: 1.18; 95% confidence interval [CI]: 1.02-1.40; p=0.025). CSF WCC differed with depression symptomatology (p=0.034), and patients with severe depression (n=29) had 43% higher CSF WCC relative to controls (MD: 1.43; 95% CI: 1.13-1.80, p=0.003). Two (1.9%) patients and no controls (0.0%) had CSF WCC above normal range (>5x10⁶/L). No significant differences between groups were observed regarding CSF/serum albumin ratio (MD: 1.07; 95% CI: 0.97-1.18; p=0.191), CSF total protein (MD: 1.01; 95% CI: 0.94-1.09; p=0.775) or IgG Index (MD: 1.05; 95% CI: 0.97-1.15; p=0.235). Regarding secondary outcomes, the proportion of CSF neutrophils was lower among patients (MD: 0.22; 95% CI: 0.08-0.59; p=0.003) relative to controls; whereas, the remaining outcomes were not significantly different (all p>0.06). Conclusion Patients had higher CSF WCC relative to controls, indicating increased neuroimmunological activation, particularly for severe depression.
Article
Cerebrospinal fluid (CSF) is a clear fluid coursing in the intracranial and spinal compartments. By estimating the levels of various CSF components utilizing relevant techniques, diagnosis, severity and prognostication of neurological conditions like infections, subarachnoid hemorrhage, demyelinating conditions, tumor like conditions, etc. can be done. Cerebrospinal fluid (CSF) provides an extremely valuable matrix for biomarker research for several purposes such as diagnosis, prognosis monitoring and identification of prominent leads in pathways of neurological disease.
Article
This study examined whether gene polymorphisms for toll-like receptor 10 (TLR10) associated with the susceptibility to and outcomes of bacterial meningitis (BM) in Angolan children. The study cohort consisted of 190 BM patients and the determination of ten single-nucleotide polymorphisms (SNPs) by Sanger sequencing. Patients with BM caused by S. pneumoniae who carried the following variants of TLR10 SNPs exhibited an increased risk of coexisting pneumonia: rs10004195 (T>A) (p = 0.025), rs10856837 (G>A) (p = 0.018) or rs11096956 (G>T) (p = 0.010). Yet, TLR10 SNPs rs11466652 (A>G), rs10856837 (G>A) and rs11096956 (G>T) influenced the protein levels in the cerebrospinal fluid (CSF). Moreover, compared with the wild type, patients with pneumococcal meningitis carrying a variant genotype of TLR10 SNP rs11466648 (A>G) exhibited an increased risk of developing blindness (p = 0.025), whereas patients with TLR10 SNP rs10004195 (T>A) exhibited a lower risk of convulsions at admission (p = 0.039) and a lower risk of altered consciousness (p = 0.029). This study suggests a relationship exists between coexisting pneumonia, protein levels in CSF, blindness, convulsions and an altered consciousness with genetic variations of TLR10 in BM in Angolan children.
Article
Background: Enlarged vertebral venous plexus (EVVP) was often observed in patients with bilateral transverse sinus stenosis (BTSS). The purpose of this study was to investigate the physiological role of EVVP in BTSS patients. Methods: Forty-five BTSS patients and 92 normal controls were prospectively recruited from January 2014 to December 2019. The index of transverse sinus stenosis (ITSS) was used for the assessment of BTSS severity. Subjects underwent a standard lumbar puncture to measure the intracranial pressure (ICP). Papilledema and tinnitus were evaluated by using Frisén's grade and questionnaires for Tinnitus Handicap Inventory (THI), respectively. The intensity and impact of headache were assessed by using 10-point Numeric Pain Rating Scale and six-item Headache Impact Test, respectively. Results: The BTSS group had more subjects with intracranial hypertension (IH) and less subjects with normal ICP than normal controls (p < 0.01; p < 0.01). BTSS patients had higher ICP than normal controls (p < 0.01). ICP was significantly lower in BTSS patients with EVVP than in those without EVVP (p < 0.01). No significant difference in ICP was found between normal controls with EVVP and those without EVVP (p = 0.99). A similar incidence of EVVP in BTSS patients and normal controls was found (p = 0.86). BTSS patients with IH exhibited a lower incidence of EVVP than those with normal ICP and overlapping ICP (p < 0.01; p < 0.01). The incidence of EVVP was not correlated with ITSS (p = 0.81). EVVP, rather than ITSS, correlated with ICP (p = 0.01). Furthermore, EVVP alleviated papilledema evaluated by Frisén's grade and tinnitus evaluated by the THI score in BTSS patients (p = 004; p = 0.02). Conclusions: EVVP in normal controls is a congenital phenomenon that exerts no impact on ICP. However, the presence of EVVP reduces ICP and alleviates IH-related papilledema and tinnitus in BTSS patients.
Article
Purpose A non-invasive magnetization transfer indirect spin labeling (MISL) MRI method is developed to quantify the water exchange between cerebrospinal fluid (CSF) and other tissues in the brain and to examine the age-dependence of water exchange. Method In the pulsed MISL, we implemented a short selective pulse followed by a post-labeling delay before an MRI acquisition with a long echo time; in the continuous MISL, a train of saturation pulses was applied. MISL signal (∆Z) was obtained by the subtraction of the label MRI at −3.5 ppm from the control MRI at 200 ppm. CSF was extracted from the mouse ventricles for the MISL optimization and validation. Comparison between wild type (WT) and aquaporin-4 knockout (AQP4−/−) mice was performed to examine the contributions of CSF water exchange, whereas its age-dependence was investigated by comparing the adult and young WT mice. Results The pulsed MISL method observed that the MISL signal reached the maximum at 1.5 s. The continuous MISL method showed the highest MISL signal in the fourth ventricle (∆Z = 13.5% ± 1.4%), whereas the third ventricle and the lateral ventricles had similar MISL ∆Z values (∆Z = 12.0% ± 1.8%). Additionally, significantly lower ∆Z (9.3%–18.7% reduction) was found in all ventricles for the adult mice than those of the young mice (p < 0.02). For the AQP4−/− mice, the ∆Z values were 5.9%–8.3% smaller than those of the age-matched WT mice in the lateral and fourth ventricles, but were not significant. Conclusion The MISL method has a great potential to study CSF water exchange with the surrounding tissues in brain.
Article
Rationale and Objectives Accurate cerebrospinal fluid (CSF) pressure measurements are critical for diagnosis and treatment of pathologic processes involving the central nervous system. Measuring opening CSF pressure using an analog device takes several minutes, which can be burdensome in a busy practice. The purpose of this study was to compare accuracy of a digital pressure measurement device with analog manometry, the reference gold standard. Secondary purpose included an assessment of possible time savings. Materials and Methods This study was a retrospective, cross-sectional investigation of 71 patients who underwent image-guided lumbar puncture (LP) with opening CSF pressure measurement at a single institution from June 2019 to September 2019. Exclusion criteria were examinations without complete data for both the digital and analog measurements or without recorded needle gauge. All included LPs and CSF pressures were measured with the patient in the left lateral decubitus position, legs extended. Acquired data included (1) digital and analog CSF pressures and (2) time required to measure CSF pressure. Results A total of 56 procedures were analyzed in 55 patients. There was no significant difference in mean CSF pressures between devices: 22.5 cm H2O digitally vs 23.1 analog ( p = .7). Use of the digital manometer resulted in a time savings of 6 min (438 s analog vs 78 s digital, p < .001). Conclusion Cerebrospinal fluid pressure measurements obtained with digital manometry demonstrate comparable accuracy to the reference standard of analog manometry, with an average time savings of approximately 6 min per case.
Article
CSF analysis is valuable in the investigation of many neurological disorders, including inflammatory, infectious and degenerative diseases of the CNS. Because CSF is in direct communication with the extracellular space of the brain and spinal cord, pathological changes in the CNS are often reflected in the CSF. In addition, studies of CSF proteins often provide crucial information about CNS disorders.
Article
Epidemiologic trends causing infections of the nervous system remain a significant source of morbidity and mortality one half-century after the introduction of penicillin. This article outlines common causes of bacterial meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord syndromes, and cranial and peripheral nerve problems. Recommendations for diagnostic evaluation and both empiric and definitive antimicrobial therapy are offered; controversial management issues are also discussed. The protean manifestations of varicella-zoster virus and Lyme diseases are outlined. In addition, special considerations in the immunocompromised host, including organ transplant recipients, cancer patients, and HIV-positive persons are explained, and antimicrobial therapy is discussed.
Article
Increased intracranial pressure can result in irreversible injury to the central nervous system. Among the many functions of the cerebrospinal fluid, it provides protection against acute changes in venous and arterial blood pressure or impact pressure. Nevertheless, trauma, tumors, infections, neurosurgical procedures, and other factors can cause increased intracranial pressure. Both surgical and nonsurgical therapeutic modalities can be used in the management of increased intracranial pressure attributable to traumatic and nontraumatic causes. In patients with cerebral injury and increased intracranial pressure, monitoring of the intracranial pressure can provide an objective measure of the response to therapy and the pressure dynamics. Intraventricular, intraparenchymal, subarachnoid, and epidural sites can be used for monitoring, and the advantages and disadvantages of the various devices available are discussed. With the proper understanding of the physiologic features of the cerebrospinal fluid, the physician can apply the management principles reviewed herein to minimize damage from intracranial hypertension.
Article
This article reviews the microbiology, pathogenesis, epidemiology, clinical manifestations, diagnostic tests, and recent advances in the therapy of protozoan and helminthic infections of the central nervous system, with more emphasis given to protozoan than to helminthic infections.
Article
Fungal meningitis tends to be a subacute or chronic process; however, it may be just as lethal as bacterial meningitis if untreated. There are many similarities between the pathogenic fungi. Most of the fungi are aerosolized and inhaled, and initiate a primary pulmonary infection which is usually self-limited. Hematogenous dissemination may follow the initial infection, with subsequent involvement of the CNS. Rarely, trauma or local extension provides the route to CNS infection. The host is frequently, although not always, immunosuppressed. The hyphae of molds generally cause focal disease with hemorrhagic necrosis secondary to vascular thrombosis. The yeasts tend to cause a more diffuse process with the base of the brain being primarily affected, such that hydrocephalus is seen as a frequent complication of chronic disease. Diagnosis may be difficult, as the CSF may be normal, with negative smears and sterile cultures, although more often there is at least one abnormality indicating disease. Serologies (if available, depending on the fungus) may point towards the proper diagnosis, as may a careful travel history. Currently, amphotericin B is still the drug of choice in most situations; however, the newer azole antifungal agents offer great promise, especially in the treatment of cryptococcal meningitis. The precise role of such agents will remain unclear until appropriate large-scale studies of their effectiveness have been completed. The treatment of the unusual CNS mycoses will continue to be based on clinical experience, and reports of the use of new azoles in these diseases need to be critically evaluated.
Article
Tuberculous meningitis is an uncommon but potentially devastating form of tuberculosis. Current antituberculous drugs are highly effective when treatment is initiated early, before the onset of altered mentation or focal neurologic deficits. Because the clinical outcome depends greatly on the stage at which therapy is initiated, early recognition is of paramount importance. Patients with the meningoencephalitis syndrome and CSF findings of low glucose levels, elevated protein levels, and pleocytosis should be treated immediately if there is evidence of TB elsewhere in the body, or if prompt evaluation fails to establish an alternative diagnosis. Examination of CSF is the best diagnostic approach; with sufficient diligence, serial AFB smears and cultures will usually yield positive results, even days after therapy has been started. The CT scan is an important and highly effective tool for the diagnosis and management of patients with TBM. In a patient with compatible clinical features, the combination of basilar meningeal enhancement and any degree of hydrocephalus is strongly suggestive of the diagnosis of TBM. Serial evaluation by CT scanning is useful for following the course of hydrocephalus and tuberculoma, particularly in reference to the need for, or response to, adjunctive therapy with corticosteroids and surgery. The decision to administer corticosteroids should be based on careful correlation of the clinical and radiographic features of the case. Surgical shunting should be considered early in the patient with hydrocephalus and symptoms of raised intracranial pressure. Tuberculomas are best treated medically, often in conjunction with corticosteroids where cerebral edema is believed to contribute to neurologic decline. The recommended chemotherapy regimen is isoniazid and rifampin in all patients, together with pyrazinamide for the first 2 months.
Article
CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis. Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy. Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture. In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis. Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40—50 mL) should be obtained for culture. If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered. Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers. Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation. Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension. Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure.