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Cerebrosipnal Fluid

(CSF)
Ruland D.N.Pakasi

Coverage Topics

Laboratory

Procedure
Laboratory Examinations
Lab. Findings in selected disorders/
diseases
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Specimen collection

CSF obtianable by
1.
2.
3.

4.

Lumbar puncture
Cisternal puncture
Lateral cervical
puncture
Ventricular cannulas

Operator:
Neurologist/
Neuropsichyartist
. Certified doctors
.

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Specimen collection & Opening


pressure

A manometer is attachedrecord opening


pressure (OP)
Normal OP:
90-180 mmH2O
Lateral decubitus position

slightly:
Sit up
Obese
Vary up to 10 mmH2O with respiration

OP > 200 mmH2O no 2 ml should be drawn

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Specimen collection & Opening


pressure
OP

seen with/ in:

Patient tension or straining


Congestive Heart Failure, Meningitis, Superior
Vena Cava Syndrome, thrombosis of venous
sinuses, cerebral edema, mass lesions,
hypoosmolality, and condition inhibiting CSF
absorption

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Specimen collection & Opening


pressure
OP

seen in:

Spinal-subarachnoid block
Circulatory collaps
Dehydration
CSF leakage

Dramatic

pressure drop after removal 1-2


mlsuggest herniation or spinal
blockno further withdrawing

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Specimen collection
Up to 20 ml may normally removed
Divided into 3 sterile tubes

1.
2.
3.

Chemistry & Immunologic studies


Microbiological examination
Cell count & differential

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Indication of Lumbar Puncture


Diagnpsis: 4 categories of disease

1.
2.
3.
4.

Meningeal infection
Subarachnoid hemorrhage
CNS malignancy
Demyelinating disease

Therapeutic

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Diseases detected by Laboratory


examination of CSF
High Sensitivity, High Specificity
Bacterial,

tuberculous, and fungal meningits

High Sensitivity, Moderate Specificity


Viral

menigitis
Subarachnoid hemorrhage
Multiple sclerosis

CNS

syphilis
Infectious polyneuritis
Paraspinal abscess

Moderate Sensitivity, High Specificity


Meningeal

malignancy

Moderate Sensitivty, Moderate Specificity


Intracranial

hemorrhage
Viral encepahlitis
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Subdural

hematome
9

Gross Examination

Procedure: conducted by competent, licenced


physician
To be observed

Normal CSF
Clear & colorless, viscocity similar to water

Turbidity or cloudness
WBC > 200 cells/L or
RBC > 400 cells/L

Clot formation
Traumatic tap
Complete spinal block (Froin Syndrome)
Suppurative, tuberculous meningitis

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Gross Examination

Viscous CSF
Metastatic mucin-producing adenocarcinomas
Cryptococcal meningitis

Pink-red
Usually: presence of blood
Grossly bloody: >6000 RBC/L, originate from

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subarachnoid hemorrhage
intracerebral hemorrhage
infarct of traumatic tap

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Gross Examination

Xanthochromia
Pink, orange or yellow due to RBC lysis & Hgb
breakdown
Other causes
1. Artefactual RBC lysis due to detergent
contamination or specimen delay without
refrigeration
2.
3.

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Bilirubin (bilirhachia): jaundiced patients


Protein > 150 mg/dL: traumatic tap + rbc
>100.000 cell/L, Complete spinal block,
Polyneuritis, Meningitis
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Gross Examination

Xanthochromia
Pink, orange or yellow due to RBC lysis & Hgb
breakdown
Other causes
4.
Carotinoids (orange): dietary
hypercarotenemia
5.

6.

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Melanin (brownish): meningeal metastatic


melanoma
Rifampicin Rx (red-orange)

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Gross Examination: Diff diagnosis


Bloody CSF
Traumatic Tap
Color

Clear

between 1st and 3rd

tube
Subarach.hemorrrelative
uniform
Erythrophagocy
tosis
Latex
agglutination
immunoassay
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Pathologic
hemorrhage
Relative uniform

Yes

No

Negative

Positive

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Microscopic examination
Total Cell Count

1.

Undiluted manual counting chamber

2.

Fuchs Rosenthal chamber


Neubauer hemocytometer

Differential count

Mononcl & PMN


unsatisfactoryimprecise
Wright-stained,air-dried cytocentrifuge
preparation is recommended

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Microscopic examination
.

RBC Count:

Limited diagnostic value


In traumatic punctureapproximation of true
total WBC or Total Protein
Corrected WBC Count
WBCcorr = WBCobs WBCadded
WBCadded = WBCbld x WBCCSF/WBCbld

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Microscopic examination
Reference interval for CSF Diff Counts by
Cytocentrifuge
Adults (%)

Neonates (%)

Lymphocytes

62 34

20 18

Monocytes

36 20

72 22

Neutrophils (PMN)

25

35

Histocytes

Rare

54

Ependymal cells

Rare

Rare

Eosinophils

Rare

Rare

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Cell Counter Chamber

Improved Neubauer

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Fuchs Rosenthal
18

Microscopic examination
Increased Neutrophils

1.
1.
2.
3.
4.
5.
6.
7.

8.

Meningitis
Other infections
Following seizures
Following CNS hemorrage
Following CNS Infarct
Reaction to repeated lumbar puncture
Injection of foreign materials into subarachnoid
space
Metastatic tumor in contact with CSF

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Microscopic examination
2.

Increased Lymphocytes
A.

Meningitis
1. Viral-, tuberculous-, Fungal-, Leptospiral
Meningitis
2. Bacterial meningitis due to unusual organism
(Listeria monocytogenes)
3. Parasitic infections: cysticercosis, trichinosis,
toxoplasmosis
4. Aseptic meningitis: septic focus adjecent to
meninges

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Microscopic examination
2.

Increased Lymphocytes
B.

Degenerative disorders
1.
2.
3.
4.
5.

C.

Subacute sclerosing panencephalitis


Multiple sclerosis
Encephalopathy due to drug abuse
Guilain-Barre syndrome
Acute disseminated encephalomyelitis

Other conditions
1.

Polyneuritis, Sarcoidosis of meninges, etc

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Microscopic examination
3.

Eosiniphilic pleocytosis
A.

Commonly associated with


1.
2.
3.
4.
5.

Parasitic infections
Fungal infections
Reaction to foreign material in CSF: drugs
Acute polyneuritis
Idiopathic hypereosinophilic syndrome

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Microscopic examination
3.

Eosinophilic pleocytosis
A.

Infrequently associated with


1.
2.
3.
4.
5.
6.
7.
8.

Bacterial meningitis
Tuberculous meningoencepahlitis
Viral mengitis
Leukemia, lymphoma
Ricketsial infection
Myeloproliferative disorders
Primary brain tumors
Neurosarcoidosis

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Chemical Analysis
1.
2.
3.
4.
5.
6.
7.
8.

Total protein
Other CSF proteins
Glucose
Lactate
Enzymes
Ammonia & Amines
Electrolyte & Acid-base Balance
Tumor markers

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Chemical Analysis - Total Protein


Normal range: 15-45 mg/dL
Methods

Colorimetry
Turbididimetric
Conventional: Precipitation by TCA
Simple, cheap

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Chemical Analysis - Total Protein


.
.

Useful but not specific indicator of disease


in :
1.
2.
3.
4.
5.

Traumatic spinal tap


Blood-CSF permeability
CSF circulation defects
Increased IgG synthesis
Increased IgG synthesis & Blood-CSF
permeability

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Chemical Analysis Total Protein


.

in :
2. Blood-CSF permeability

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Arachnoiditis (Rx MTX)


Meningitis (bacterial, fungal, tbc, etc)
Subarachnoidal intracerebral hemorrhage
Endocrine/ metabolic disorders
Diabetic neuropathy, Milk-Alkali
Syndrome,herediatry neuropathies & mielopathies,
etc
Drug toxicity: Ethanol, Phenytoin, phenothiazine

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Chemical Analysis Total Protein


3. CSF circulation defects

Mechanical obstruction: tumor, abscess, herniated disk


Loculated CSF effusion

4. Increased IgG synthesis

Neurosyphilis
Multiple sclerosis

5. Increased IgG synthesis & Blood-CSF


permeability

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Guillain-Barre syndrome
Collagen vascular disease
Chronic inflammatory demyelinating polyradiculopathy

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Chemical Analysis - Other Proteins


2-Macroglobulin (AMG)

.
.

Small amount transported


Significant means subdural hemorrhage or
BBB breakdown (bacterial meningitis

2Microglobulin

Significant level (>1.8 mg/dL) associated


with

Leptomeningel leukemia
Lymphoma
Viral infection (inc HIV-1)
Malignancies

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Chemical Analysis - Other CSF proteins


C-Reactive Protein (CRP)
To differentiate Bacterial from Viral meningitis
(esp.in children)

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Chemical Analysis - Glucose


Normal range: 50-80 mg/dL (fasting)

60 % of plasma value
CSF/Plasma Ratio: 0.3-0.9

Hypoglycorrhacia

< 40 mg/dL or ratio < 0.3


Characteristic in bacterial, tuberculous and fungal
infections
Results from
utilization by brain tissue & WBC (anaerobic
glycolysis)
Impaired transport into CSF

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Chemical Analysis - LD
Ref interval: 9.0-26.0 mg/dL
As adjunctive test in differentiating viral from
bacterial, mycoplasma, fungal and tuberculous
meningitis

.
.
.

Viral meningtis: us.<25 mg/dL


Bacterial meningitis: us.> 35 mg/dL
Others meningitis: intermediate level, overlap each
other

Persistent elevated levelspoor prognosis

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Chemical Analysis - LD
Havent proven to be practical in clinical lab
diagnosis
Lactate dehydrogenase (LD)

.
.

Normal upper limit 70 U/L


Help differentiate traumatic tap (tt) from intracranial
hemorrhage (ih)
tt: intact RBC do not significantly elevate LD
ih: LD

Lactate + LD
LD in bacterial meningitis

in aseptic meningitis

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Chemical Analysis - CK

Creatine kinase (CK)

< 5 U/L
Predominant CK-BB than CK-MB & CK-MM
: demyelinating diseases, seizures, stroke,
malignant tumors, meningitis, and head
injury

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Chemical Analysis
Ammonia & Amines

6.
.
.

1-1 blood values


Difficult to quantitate
-Ketoglutarate + brain-ammoniaglutamin
Glutamin protects CSF from ammonia toxicity
Glutamin levels reflects brain ammonia
.
.

SEPTEMBER 2013

Normal upper limit: 20 mg/dL


> 35 mg/dLhepatic encephalopathy

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Chemical Analysis
Electrolyte & Acid-base Balance

7.
.

No clinically useful indications to measure


Na, K, Cl, Ca or Mg
pH, PCO2, and bicarbonate are not practical
for patient care

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Chemical Analysis
Tumor markers

8.

The values in routine tests is not established


CEA: in metastatic carcinoma of
leptomeninges
hCG: choriocarcinoma
-Fetoprotein: germ cell tumor
CNS ferritin: CNS malignancy

Low sensitivity, low specificity

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Microbial Examination
Visit

Dept of Microbiology home page

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Cerebrospinal Fluid Abnormalities in


Various Disorders
Condition Pressure
Normal
Acute
bacterial
meningitis
Subacute
meningitis
(TB,
Cryptococ
cus
infection,
sarcoidosi
s,
leukemia,

Wbc/L

Predomin
ant Cell
Glucose
Type

Protein

100200
mm H2O

03

50100
mg/dL

2045
mg/dL

100
10,000

PMN

> 100
mg/dL

N or

100700

Cerebrospinal Fluid Abnormalities in


Various Disorders
Condition Pressure

Wbc/L

Predomin
ant Cell
Type

Acute
syphilitic
meningitis

N or

252000

Paretic
neurosyph
ilis

N or

152000

Lyme
disease of
CNS

N or

0500

N or

Glucose

Protein

Cerebrospinal Fluid Abnormalities in


Various Disorders
Condition Pressure

Wbc/L

Predomin
ant Cell
Type

Glucose

Protein

Brain
abscess or
tumor

N or

01000

Viral
infections

N or

1002000

N or

Cerebral
hemorrha
ge

Bloody

RBCs

Cerebral
thrombosi
s

N or

0100

N or

Cerebrospinal Fluid Abnormalities in


Various Disorders
Wbc/L

Predomina
nt Cell
Type

Glucose

Protein

050

N or

GuillainBarr
syndrome

0100

> 100
mg/dL

Lead
encephalopa
thy

0500

Pseudotumor
cerebri

Condition

Pressu
re

Spinal cord
tumor

Ruland D.N Pakasi

LAB.FINDINGS
IN SELECTED DISEASE/DISORDERS

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III. LAB.TESTS IN
CERTAIN NEUROLOGIC
DISORDERS

1.Brain Abscess

Intracranial abscess:
life-threatneing disease
Includes subdural % extradural empyema

Origin:
infection of contagious structures
Hematogenous spread from remote site (cyanotic
congenital heart
Skull trauma/ surgery
Meningitis
Unidentified source (15%)

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III. LAB.TESTS IN
CERTAIN NEUROLOGIC
DISORDERS

1.Brain Abscess

Lab Studies

Routine tests
CBC & Differential count
Moderate leucocytosis

Platelet count may be H or N

ESR (~60%)
CRP
Serologic
Available for some pathogens (e.g.IgG)
PCR for toxoplasmosis

Blood culture
At least 2, preferably before antibiotic
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III. LAB.TESTS IN
CERTAIN NEUROLOGIC
DISORDERS

1.Brain Abscess

Lab Studies

CSF
WBC ,
When abscess ruptures: 100.000/L RBC
Lactic acid > 500 mg/dL

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III. LAB.TESTS IN
2.Acute Bacterial
CERTAIN NEUROLOGIC
Meningitis
DISORDERS
WBC: increased with a shift to
the left.
CRP (C-Reactive Protein)
increases markedly
Appearance: opalescent to
purulent, slightly yellow, and
might have a coarse clot.
WBC countL <5 to >100 with
neutrophilic dominance (>80%);
as the disease progresses there
is a gradual increase in
Blood
lymphoctes and large monoclear
cells. Cell counts above
Cerebrospinal Fluid
50.000/l raise the possibility
that a brain abscess has
SEPTEMBER
2013 into the
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ruptured
subarachnoid

47

III. LAB.TESTS IN
CERTAIN NEUROLOGIC
DISORDERS

2.Acute Bacterial
Meningitis

Cerebrospinal Fluid

Gram-stained smear: positive in 60-90% patients.


Culture: positive in 65 to 90% patients. Prior
antibiotic treatment decrease the frequency of
positive cultures.
Protein > 50 mg/dl..
Glucose < 40 mg/dl (0-40 mg/dl; < 30% of blood
level)

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III. LAB.TESTS IN
2Acute
CERTAIN NEUROLOGIC
DISORDERS

Bacterial Meningitis

Cerebrospinal Fluid

LDH (esp. LDH4 and LDH5) increase (this


derived from granulocytes).
Bacterial antigens:

50% to 100% sensitivity.


This test is of great help for rapid diagnosis after
treatment has been started and the smears and
culture are negative.

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III. Lab.Tests in
Certain Neurologic
Disorders

3.Tuberculous Meningitis
Serum

sodium: decreased

Appearance:

Blood
Liquor
Cerebrospinal
Fluid:
SEPTEMBER 2013

opalascent, slightly
yellow; a delicate clot may be seen.
Glucose 10 mg/dl 40 mg/dl
Protein 45 mg/dl 500 mg/dl
(usually 100-200 mg/dl)
WBC: Lymphycytes 25/l 500 /l;
early in the infection, neutrophils
may equal lymphocytes.
Acid-fast (or Auramine-rhodomine)
stained smear of the fibrin clot or50
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III. Lab.Tests in
Certain Neurologic
Disorders

Basic
Coagulation
Panel

Abnormal PT, aPTT, Platelet


Count.

Electrolyte abnormalities
Hyponatremia can
potentiate brain edema and
cause seizures.

CT
MRI

Electrolyte

Imaging
Studies
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4.Subdural Hematoma

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III. Lab.Tests in
Certain Neurologic
Disorders

5.Epidural Hematoma
To

1.CBC

+ Platelet

monitor for infection and assess


hematocrit and platelets for further
hemorrhagic risk

Prothrombin
2. PT+aPTT

3.Electrolyte+

BUN+Ceatinin
+Glucose
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time (PT)/activated
partial thromboplastin time (aPTT)
- To identify bleeding diathesis

Serum

chemistries, to characterize
metabolic derangements that may
complicate clinical course

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5.Epidural Hematoma

III. Lab.Tests in
Certain Neurologic
Disorders
1.

Toxicology
screen +
Alkohol

2.

Blood typing

3.

Imaging
studies
SEPTEMBER 2013

Toxicology screen and serum


alcohol level - To identify
associated causes of head
trauma and establish need for
surveillance with regard to
withdrawal symptoms

Type and hold an appropriate


amount of blood - To prepare for
necessary transfusions needed
because of blood loss or anemia

Consult Dept of Radiology

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Lab
Studies

6.Spinal Muscular Atrophy

Laboratory testing
The creatine kinase (CK) level is

typically normal in SMA type I and


normal or slightly elevated in the
other types.
CSF findings are normal.

1.Lab

Tests

2.Genetic

test

SEPTEMBER 2013

Genetic testing
Both prenatal and postnatal tests are

now commercially available.


Tests for chromosome arm 5q should
be performed.
Caution should be exercised when
prenatal prediction is done in the
presence of atypical features because
these clinical variations may represent
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54

Lab
Studies

6.Spinal Muscular Atrophy

3.

Other tests
Most cases spare the cardiac
system, and ECGs are normal.
Electrophysiologic studies are
useful in differentiating the SMAs
from other neurogenic and
myopathic diseases
(Hausmanowa-Petrusewicz, 1986;
Krivickas, 1998).

others
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MYASTHENIA GRAVIS

Anti-acetylcholine receptor antibody

reliable for diagnosing autoimmune MG.


is positive in 74% of patients.

Results are positive in about 80% of patients with


generalized myasthenia and in 50% of those with
pure ocular myasthenia.

False-positive anti-AChR Ab test results have


been reported in cases of:

thymoma without MG and in patients with


Lambert-Eaton myasthenic syndrome, small cell
lung cancer, rheumatoid arthritis treated with
penicillamine, and in 1-3% of the population older
than 70 years.

MYASTHENIA GRAVIS

Antistriated muscle (anti-SM) Ab


is

another important test in patients with MG.


It is present in about 84% of patients with
thymoma who are younger than 40 years and
less often in patients without thymoma.
Thus its presence should prompt a search for
thymoma in patients younger than 40 years.
In individuals older than 40 years, anti-SM Ab
can be present without thymoma.

MYASTHENIA GRAVIS

Thyroid function tests

should be done to evaluate for coexistent thyroid


disease.

Anti-MuSK antibody

About half of the patients who are AChR-ab negative


(seronegative MG) may be positive for antimusclespecific kinase (MuSK) antibodies.

They may represent a distinct group of


autoimmune myasthenia gravis, as they show
some characteristics as a group that are
different from AChR-positive patients.

MYASTHENIA GRAVIS

Antistriational antibodies
Serum from some patients with myasthenia gravis
possesses antibodies that bind in a cross-striational
pattern to skeletal and heart muscle tissue sections. These
antibodies react with epitopes on the muscle protein titin
and ryanodine receptors (RyR). Almost all patients with
thymoma and myasthenia gravis and half of the late-onset
MG patients (onset > 50 y) exhibit an antibody profile with
a broad striational antibody response. Striational
antibodies are rarely found in AChR Ab negative patients.
These antibodies can be used as prognostic determinants
in MG; as in all subgroups of MG, higher titers of these
antibodies are associated with more severe disease.
As it is often associated with thymoma in young patients
with MG, the presence of titin/RyR antibodies should
arouse strong suspicion of thymoma in a young patient
with MG.

Guillain-Barre
Syndrome

Lab Studies

The diagnosis of Guillain-Barr


syndrome (GBS)
istypicallymade by the
presence of a progressive
ascending weakness with
areflexia. An LP,
electrodiagnostic studies, or
occasionally MRI findings can
give support for this diagnosis.
Typically, the LP is suggestive
of demyelination (ie, increased
protein >45 mg/dL within 3 wk
of onset) without evidence of
active infection (lack of CSF
pleocytosis), as originally

Guillain-Barre
Syndrome

Lab Studies

The CSF fi ndings may be normal


within the fi rst 48 hours of
symptoms, and occasionally the
protein may not rise for a week.
Serial spinal taps are sometimes
often warranted if early studies
are normal. Usually by 10 days of
symptoms, elevated CSF protein
fi ndings will be most prominent.

Most patients have fewer than 10


leukocytes per milliliter, but
occasionally a mild elevation (ie,
10-50 cells/mL) is seen. Greater
than 50 mononuclear cells/mL of
CSF casts some doubt on the
diagnosis of GBS.

STROKE, HEMORRHAGIC
Lab

Studies

Complete

blood count
Coagulation profile
Electrolytes
Serum glucose
Blood type and screen

STROKE, ISCHEMIC
Lab

Studies

CBC,

basic chemistry panel, coagulation studies, and cardiac


biomarkers should be obtained in most patients.

CBC serves as a baseline study and may reveal a


cause for the stroke (eg, polycythemia, thrombocytosis,
thrombocytopenia, leukemia) or provide evidence of
concurrent illness (eg, anemia).
Chemistry panel serves as a baseline study and may
reveal a stroke mimic (eg, hypoglycemia,
hyponatremia) or provide evidence of concurrent
illness (eg, diabetes, renal insufficiency).
Coagulation studies may reveal a coagulopathy and
are useful when thrombolytics or anticoagulants are
to be used.

STROKE, ISCHEMIC
Lab

Studies.

Cardiac biomarkers are important


because of the association of cerebral
vascular disease and coronary artery
disease.
Additionally, several studies have
indicated a link between elevations of
cardiac enzyme levels and poor outcome
in ischemic stroke.
Toxicology screening may be useful in
selected patients.

SUBARACHNOID HEMORRHAGE
(SAH)

Lab Studies
Serum

chemistry panel
CBC count
Prothrombin time (PT) and activated partial
thromboplastin time (aPTT) tests
Blood typing/screening tests
CSF findings suggesting subarachnoid hemorrhage
include numerous RBCs, xanthochromia, and
increased pressure.
About 6 h or more after a subarachnoid hemorrhage,
RBCs become crenated and lyse, resulting in a
xanthochromic CSF supernatant and visible crenated
RBCs (noted during microscopic CSF examination)

Bell's Palsy
Lab

Studies

In areas where Lyme disease is endemic, Lyme titers


(IgM and IgG) should be obtained.
Blood glucose or hemoglobin A1c may be obtained to
determine if the patient has undiagnosed diabetes.
Serum titres(IgM and IgA) forMycoplasma
pneumoniae may be obtained.A study in
Germanymeasured titres in patients with Bell palsy
and found that several patients had elevated titres
toM pneumoniae, and only 2 of those who tested
positive had respiratory symptoms.3
Serum titers for HSV may be obtained, but this is
usually not helpful owing to the ubiquitous nature of
this virus.
Lyme disease is a tick-transmitted infection caused by Borrelia burgdorferi.
Symptoms include an erythema migrans rash, which may be followed weeks to
months later by neurologic, cardiac, or joint abnormalities.

Lab.Tests in
Psychiatric
subjcts

Next time better

AlcoholRelated
Psychosis

SEPTEMB ER 20 13

is a 2 d a r y psychosis with predominant


hallucinations occurring in many alcoholrelated conditions, including acute
intoxication, withdrawal, after a major
decrease in alcohol consumption, and
alcohol idiosyncratic intoxication.

Alcohol is a neurotoxin that aff ects the


brain in a complex manner through
prolonged exposure and repeated
withdrawal, resulting in signifi cant
morbidity and mortality.

Alcohol-related psychosis is often an


indication of chronic alcoholism; thus, it is
associated with medical, neurological, and
psychosocial complications.

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68

AlcoholRelated
Psychosis

Finger-stick blood glucose test for


rapid determination of hypoglycemia
or hyperglycemia in a patient with
diabetes

Complete blood cell count to rule out


blood dyscrasias, infection, and
anemia

Electrolytes with magnesium, amylase,


albumin, total protein, uric acid, BUN,
alkaline phosphatase, and bilirubin

Electrolytes

Urinalysis to determine the presence


of a urinary tract infection and
determine renal function

Urinalysis

Stat urine or serum drug screen to


determine if illicit drugs are
contributing to psychosis and change
in mental status

Laboratory Studies

Glucose

CBC

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AlcoholRelated
Psychosis

Stat urine or serum


toxicology screen for levels
of acetaminophen, tricyclic
antidepressants, aspirin,
and other potential toxins
from either an accidental or
deliberate overdose

Prothrombin time

Stool for occult blood

BAL measurement (although


a patient may appear
intoxicated, clinical
intoxication can be
determined only by BAL)

Laboratory Studies

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A m p h e t a mi n e R e la t e d
Psy c h ia t r ic
D i so rd e rs

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The purpose of the workup is to


exclude complications of
amphetamine abuse and other causes
of psychosis and altered mental
status.

Laboratory evaluation should include


the following tests:

Finger-stick blood glucose test

CBC determination

Determination of electrolyte levels,


including magnesium, amylase,
albumin, total protein, uric acid,
BUN, alkaline phosphatase, and
bilirubin levels

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A m p h e t a mi n e R e la t e d
Psy c h ia t r ic
D i so rd e rs

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Urinalysis

Stat urine or serum toxicology


screening to exclude acetaminophen,
tricyclic antidepressants, aspirin, and
other potential toxins: Individuals who
abuse drugs may ingest a substance
called Urine Luck, or pyridinium
chlorochromate (PCC), to produce
invalid results on urine drug screens.
PCC alters the results for cannabis and
opiates but elevates levels of
amphetamines.

Blood test for an alcohol level if the


patient appears intoxicated

HIV and rapid plasma reagin (RPR)


tests

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72

Caff eineRelated
Psychiatric
Disorders

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A urine drug screen


helps exclude
symptoms due to
illicit drug use.
Thyroid studies are
also useful.

Caffeine blood
levels can be
obtained, but their
practical use as a
screening tool is
limited.
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73

CocaineRelated
Psychiatric
Disorders

Laboratory Studies

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When caring for patients with


suspected cocaine-induced
psychiatric disorders, a
number of laboratory studies
may be considered. For
example, a patient with
marked agitation with or
without psychotic features
may have complications from
cocaine intoxication, such as
rhabdomyolysis, myocardial
infarction, or renal failure.
The need for specifi c
laboratory and ancillary tests
noted below will vary
depending on the clinical
scenario.
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74

CocaineRelated
Psychiatric
Disorders

Electrolytes

Typically, hypokalemia occurs in acute


cocaine intoxication from intracellular
shifts of potassium ions. This corrects as
the intoxication resolves. In severe
cocaine toxicity, hyperkalemia may
develop and lead to cardiac dysrhythmias.
The exact etiology of this is unclear, but
rhabdomyolysis may be a contributing
factor.

Metabolic acidosis (a decreased serum


bicarbonate level) also may be observed
in acute cocaine intoxication. This also
corrects as the toxicity resolves. A
progressively worsening metabolic
acidosis associated with progressive
altered mental status is a poor prognostic
sign. Closely monitor these patients.

Laboratory Studies

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75

CocaineRelated
Psychiatric
Disorders

Laboratory Studies

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Glucose: In any patient


presenting with altered mental
status, obtain a rapid glucose
determination to rule out
hypoglycemia.

Renal function tests: Renal


failure due to rhabdomyolysis
and renal artery thrombosis has
been reported with cocaine
abuse.

Creatine kinase: This test may


help diagnose rhabdomyolysis

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76

CocaineRelated
Psychiatric
Disorders
Urinalysis: If an agitated patient shows a
urine-dip test result that is positive for
blood but microscopic analysis reveals no
red blood cells, consider urine myoglobin
Laboratory Studies and rhabdomyolysis as the cause.

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Pregnancy test: All women of childbearing


age should receive a pregnancy test.

Liver function tests: Hepatic damage may


occur in the acutely intoxicated patient. In
addition, patients who use cocaine are at
risk for infectious hepatitis, which also
may result in acute mental status changes.

Complete blood cell count: Anemia,


leukocytosis, and leukopenia all may lead
the clinician to consider other disease
entities.

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77

CocaineRelated
Psychiatric
Disorders

Toxicology

Urine drug screens: Benzoylecgonine, a


metabolite of cocaine, may be present
in the urine for 60 hours after a single
use of cocaine. In heavy cocaine use, it
has been found in the urine as much as
22 days after cessation of cocaine use.
Positive screen results are typically
verifi ed with gas chromatography with
mass spectrometry.

Plasma cocaine levels: Because cocaine


has a short half-life of 30-45 minutes
and the metabolites are present in the
urine for a much longer period, plasma
cocaine levels typically are not as
helpful as the tests that analyze for
cocaine metabolites in the urine.

Laboratory Studies

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78

CocaineRelated
Psychiatric
Disorders

Laboratory Studies

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Cardiac enzymes: Because


of the significant
prevalence of myocardial
infarction associated with
cocaine use, patients
presenting with chest pain
and cocaine abuse should
be considered candidates
for cardiac enzyme
monitoring.

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79

CocaineRelated
Psychiatric
Disorders
Other Tests

Laboratory Studies

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Arterial blood gas determ ination: This test may be u seful in


patien ts with either m arked tach ypn ea or a decreased seru m
bicarbon ate level to f urther delin eate the etiology.
ECG: An ECG sho uld be obtained if an individual w ho abu ses
cocain e reports chest pain, shortness of breath , syn cope, or
palpitations. Cocaine-indu ced m yocardial isch em ia, infarction,
and dysrhyth mias have been repo rted.

C o c ain e is a kn o w n fa st so d iu m c h an n el b lo c ke r o f c a rd ia c
m y oc y tes. T h is c a n lea d to a d e lay in th e u p stro ke o f p h a se 1 o f
d ep ola riz atio n an d su b se q u e n t w id en in g o f t h e Q R S d u r atio n .

C o c ain e c an c a u se eith e r m y o c ar d ial isc h e m ia or in f arc tion . T h is


c a n su b seq u en t ly le ad to S T d e p r essio n o r elev atio n d e p en d in g o n
t h e isc h e m ia /in fa rc t re g io n . H ow e v er, m an y y o u n g p atie n ts w h o
a b u s e c o c a in e h av e a b ase lin e J- p oin t e lev a tio n th at m ay b e
d iffi c u lt to d iff er en tia te fr o m a n in fa rc t p a tte rn . I n a d d ition ,
n or m al EC G fi n d in g s d o n ot r u le ou t th e p oss ib ility o f m y o c ar d ial
in ju r y in a p at ien t w h o ab u ses c o c a in e w h o h as c h e st p a in .

A c u te c o ca in e to xic ity also m ay re su lt in h y p e rka le m ia . T h is c a n


le a d t o a d iff u se p e a kin g of T wa v es, w id en in g o f t h e QR S , lo ss o f
P w av e s, o r, in th e m ost sev e re c ase s, a sin u so id al w av e p a tte rn .

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80

Opioid Abuse

Laboratory Studies

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Abuse and dependence

Urine drug screen

Detection of drugs in sweat


and hair is a recent addition to
drug abuse detection
technology. However, it is not
used widely.

Withdrawal

Electrolytes

CBC count

Urine drug screen is rarely


useful.

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81

Opioid Abuse

Intoxication

Comprehensive urine drug testing is


performed when the drug abuse habit of
the patient is unknown but suspected.
Some labs use the inexpensive thin-layer
chromatography (TLC) procedure. This
test has low sensitivity for commonly used
drugs. TLC cannot detect fentanyl.

Enzyme immunoassay and


radioimmunoassay are more sensitive than
TLC, but they are less specifi c because
molecules with similar functional groups
cross-react with antibodies. These are
relatively inexpensive tests.

Gas-liquid chromatography (GLC) and gas


chromatography-mass spectrometry (GC MS) are very sensitive and specifi c tests,
but they are time consuming, labor
intensive, and expensive.

Laboratory Studies

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82

Opioid Abuse

Intoxication

In drug abuse detection, knowing the halflife of the drug, the biotransformation of
the drug, and the excretion route of the
drug are important.

Screening and confi rmation cut-off


concentration for heroin, methadone,
morphine, and codeine is 300 ng/mL and
are detected in urine within 1-4 days.

False-negative results occur more easily


than false positives, simply because once
a test is screened negative, it is not
tested further. The federal government
requires that the results of the drug
testing programs go directly to medical
review offi ces to prevent improper
interpretation of drug testing data.

Blood alcohol levels also may be tested.

Laboratory Studies

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83

Thank you

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84

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