CEREBRO SPINAL FLUID

ANALYSIS

Dr Anvesh Narimeti

Unit 1

HISTORY

The technique for needle lumbar puncture was introduced

by the German physician Heinrich Quincke

• He was perhaps the first to

recognise angioedema whic

h is often referred to as

"Quincke's edema

"Quincke's pulse“ in AR

CSF PRODUCTION AND CIRCULATION

1. Normal blood brain barrier is important for the normal chemistry results of CSF

2. Mechanism of formation:

1. Selective ultrafiltration of plasma

2. Active secretion by epithelial membrane

PRESSURE OF CSF DEPENDS ON DRAINAGE SYSTEM

TOTAL PRODUCTION OF CSF PER DAY=500-600 ml per day

TOTAL VOLUME OF CSF IN ADULT IS = 140 ml

THE RATE OF ABSORPTION CORRELATES WITH THE CSF PRESSURE

LUMBAR PUNCTURElumbar puncture should be carried out if some specific piece of information is likely to come from csf examination that would substantially contribute towards

Diagnosis

Treatment

Assesment of progress of disease

WE PERFORM CT SCAN IN SUSPECTED MENINGITIS BEFORE LP IF ONE OR MORE RISK FACTORS ARE PRESENT

ALTERED MENTATION

FOCAL NEUROLOGICAL SIGNS

PAPILLEDEMA

SEIZURES WITH IN PREVIOUS WEEK

IMPAIRED CELLULAR IMMUNITY

CONTRAINDICATIONS

ABSOLUTE

• LOCAL SEPSIS

• SPACE OCCUPYING LESION WITH RAISED ICT

RELATIVE

• PAPILLEDEMA

• BLEEDING DIATHESIS PLATELTS LESS THAN 50000

SEVERE PULMONARY AND RESPIRATORY DIFFICULTY

TECHNIQUE OF LUMBAR PUNCTURE

COMPLICATIONS OF LP POST LP HEAD ACHE

INFECTION

BLEEDING

CEREBRAL HERNIATION

MINOR NEUROLOGICAL SYMPTOMS LIKE RADICULAR PAIN AND NUMBNESS

BACK PAIN

DIPLOPIA

SUSPECT HERNIATION?

DETERIORATION OF CONSCIOUSNESS IMMEDIATELY OR WITH IN 12 HRS

NECK STIFFNESS

DILATED PUPILS

BRADYCARDIA

NORMAL VALUES OF ADULT CSFOpening pressure 50–200 mm H2O CSF (range in

literature)

Color Colorless

Turbidity Crystal clear

Mononuclear cells Less than 5 per mm3

Polymorpho nuclear cells 0

Total protein

Glucose

22–38 mg/dL

60–80% of blood glucose

Measuring intracranial pressure

Connect to manometer after successful tap rapidly in order to

avoid significant fluid loss that can falsly lower csf pressure

If opening pressure is above normal; rule out causes for falsely

elevated pressure.

abdominal compression either due to position or anxiety with a

consequent tensing of the abdominal musculature.

Gently straighten the legs. In majority, the pressure will

decrease to normal. If it does not, then distract the patient

A pressure upto 230 may be found in normal obese patients.

Pressure cannot be assessed by simply observing the speed with

which the csf drips out of the needle.manometer must always

be used.

High pressure csf

Intra cranial neoplasms

Meningitis

Sub arachanoid haemorrhage

Low pressure csf

• Faulty placement of needle in which abdominal

compression cause no rise

• Below the level of complete spinal block

Examination of fluid

Hold the container first upto the light and then

against a white surface.

Normal CSF: Clear & colorless Viscosity : Equal to water

Turbid CSF- Bacteria, WBCs cells or pus cells: suggestive of a CNS infection (menigitis or encephalitis)

Blood : suggestive of hemorrhage: subarachnoid or artifactual traumatic tap: DIFFERNTIATE?

Yellow colour 1- Jaundice (bilirubin in CSF)

2- Xanthochromia: CSF suggests that a subarachnoid hemorrhage has recently occurred (at least within 6hours prior to tapping).The yellow color is due to bilirubin generated in the CNS by the breakdown of hemoglobin released from RBC's. (so jaundice should be excluded).3- rarely highly proteinaceous fluid

Cells An infection of the nervous system produces three basic CSF types

Type A

• WBC-500–20,000,90% neutrophils,

• low CSF sugar,

• protein elevated to 100–500 mg/dL.

Type B

• 25–500 WBC,mononuclear cells (but may be PMLs early in the course of disease)

• low or occasionally normal CSF sugar

• protein of 50–500 mg/dL,characteristic of tuberculosis and other granulomatous meningitides

Type C

• 5–1,000 WBC/mm3,mononuclear pleocytosis (may be PMLs early)

• normal glucose(rarely quite low)

• protein less than 100 mg/dL.

Type A

Bacterial meningitis

Primary amoebic meningoencephalitis: rare

condition caused by free-living amebas. The classic

epidemiology,absence of organisms on gram stain and eventually

on culture, hemorrhagic component to the fluid should promptly

suggest the diagnosis, which can be confirmed by wet mounts of

the CSF revealing motile trophozoites

Ruptured brain abscess : diagnosed by a gram stain

showing

multiple types of organisms, an extremely high protein

level

and isolation of multiple organisms including

anaerobes.

TYPE B

Tuberculosis

Fungal meningitis: produced by a variety of fungi; the

most common are cryptococci, histoplasma, coccidioides and

candida.seen in immuno-suppressed

Sarcoidosis :often has meningeal involvement. Te

characteristic picture is a mild to moderate pleocytosis that is

almost mononuclear, in the range of 10–300 WBC/mm3, mild

to moderate protein elevation (between 50 mg/dL and 200

Meningeal carcinomatosis : crux of the diagnosis is the

demonstration of neoplastic cells in the CSF. Te most common

primary tumors reported to cause meningeal carcinomatosis are

breast carcinoma, lymphomas, lung carcinoma and pancreatic carcinoma.

Csf protein is markedly elevated.

Type c fluid

Parameningeal infections

Listeria monocytogenes meningitis is peculiar gram-positive

rod with characteristic “tumbling motility”

Secondary syphilis

Toxoplasmosis

Herpes simplex virus 1 (HSV-1) meningoencephalitis,

Viral meningitis enteroviruses account for over 50% of

cases. Other agents include flaviviruses, mumps, herpes

simplex, lymphocytic choriomeningitis (LCM) and the

human immunodeficiency virus (HIV).

Human immunodeficiency virus

CSF Glucose

- Normal CSF glucose: 50-80 mg/dl

- The actual CSF glucose concentration may be:1- Falsely low in the presence of hypoglycemia 2- Incorrectly interpreted as normal when the patient is hyperglycemic

-Accordingly, CSF glucose should always be compared with a simultaneous plasma glucose that is drawn prior to lumbar puncture.

Normal CSF glucose/ plasma glucose ratio is approximately 0.6-0.7(N.B. Ratio is decreased if plasma glucose is more than 500 mg/dl

due to saturation of the glucose carrier system to CSF

Elevated CSF / plasma glucose ratio (more than 0.7)has no CSF diagnostic significance (occurs with hyperglycemia)

Decreased CSF / plasma glucose ratio(hypoglycorrhachia):1- CNS septic (pyogenic) infections

Due to increased glycolysis by leukocytes and bacteria (with increase CSF lactate)2- Brain tumors

due to increased metabolism of glucose by CNS

3- TB meningitis & sarcoidosisDue to inhibition of glucose entry into the subarachnoid

space

N.B. in viral CNS infections, CSF glucose is usually normal

CSF PROTEINS

Cerebrospinal fluid proteins are derived from serum proteins with the exception of trace proteins and some beta globulins.

Certain proteins arise within the intrathecalcompartment:

1- Immunoglobulins produced by CNS lymphocytes2- Transthyretin (produced by choroid plexus)3- Various structural proteins found in brain tissue

Three conditions can cause abnormalities of

the CSF proteins:

Increased entry of plasma proteins due to

increased permeability of blood-brain

barrier

Local synthesis of proteins within the CNS

Impaired resorption of CSF proteins.

Decreased CSF protein:

Leak of CSF from a tear in the dura due to severe trauma

Otorrohea: leak of CSF from ear

Rhinorrohea: leak of CSF from nose

Increased CSF protein:

Lysis of contaminant blood from traumatic tap (each 1,000 rbc/mm3 raise the csf protein 1.5mg/dl)

Increased permeability of epithelial membrane (blood-brain barrier)

- CNS bacterial or fungal infections

- Cerebral hemorrhages

Increased production by CNS tissue as in cases of:

- Multiple sclerosis (MS)

- Subacute sclerosing panencephalitis (SSPE)

Obstruction as in cases of :

- Tumors or abscess

Analysis of protein fractions: (Albumin & IgG)

1- Albumin of CSF

is obtained from blood by means of blood-brain barrier (as it is

produced solely by the liver)

In cases of increased permeability of BBB, albumin is increased in

CSF

2- IgG of CSF can be obtained:

from blood (By BBB) : increase in cases of increase permeability of BBB

& by local synthesis from plasma cells within CSF (increased in cases of MS)

So, it is essential to determine the source of IgG

FIRST: CHECK INTEGRITY OF BLOOD BRAIN BARRIER (BBB)

BY CSF / serum albumin index calculation

CSF serum albumin index = CSF albumin (mg/dl) / serum albumin (g/dl)

Index less than 9 indicates intact BBB (no increased permeability of BBB)

SECOND: CSF IgG INDEX IS CALCULATED

CSF IgG / Serum IgG

CSF IgG index = ---------------------------------------

CSF albumin / serum albumin

Normal : less than 0.7

Increased in cases of demylineating diseases of CNS as : Multiple sclerosis (MS)

CSF Immunoglobulin

CSF IgG can arise:

1)from plasma cells within CSF

2) from the blood through BBB

↑CSF [IgG] without concomitant ↑ in CSF [Alb] suggests local production of IgG:

multiple sclerosis (MS)

subacute sclerosing panencephalitis (SPEE)

CSF IgG/Serum IgG

CSF serum /Albumin index

CSF IgG index:

Normally: < 0.7=

CSF Electrophoresis: Oligoclonal Banding

CSF lactate

CSF lactate is increased in cases of bacterial

meningitis (due to increased glycolysis by bacteria &

inflamatory cells)

The level of CSF glutamine reflects level of ammonia in that is normally removed in the CNS by formation of glutamine (amino acid glutamate + ammonia).

Glutamine synthesis helps to protect the CNS from the toxic effects of increased ammonia.

Ammonia production is increase dramatically in patients with liver failure.

Accordingly, CSF glutamine production is increased in cases of hepatic encephalopathy

CSF glutamine

Enzymes in the CSF

CSF lactate dehydrogenase (LDH) may be elevated in bacterial meningitis.

CSF adenosine deaminase (ADA) elevations can occur in tuberculousmeningitis.

Other Chemical Components of

CSF

CSF [Calcium], [Potassium] & [Phosphates] are lower than their levels in the blood

CSF [Chloride] & [Magnesium] are higher than their levels in the blood

Abnormal CSF [Chloride]

marked in acute bacterial meningitis

slight in viral meningitis & brain tumors

Interpretations of Results of CSF

Chemical Analysis

Bacterial Meningitis

Viral Meningitis

TuberculousMeningitis

Brain Tumor

Protein

Increased Normal Increased Increased

Glucose DecreasedNormal

orslightly

affected

Decreased Decreased

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