Cerebrospinal Fluid Analysis (CSF)

History of the cerebrospinal fluid (CSF)

1. Cotugno recognized it in 1794; CSF is the third major body fluid.
2. CSF provides a physiologic system to supply nutrients to the nervous tissue.
3. It removes metabolic wastes.
4. It provides a cushion to the brain and spinal cord against trauma.
5. The brain and spinal cord are lined by meninges, which consist of:
   1. The Dura mater is the outer layer.
   2. The Arachnoid mater is in between the outer and inner layers.
   3. The Pia mater is the inner layer.
6. CSF flows through the arachnoidal space between the arachnoid and pia mater.
7. 20 mL of CSF is produced every hour in the choroid plexus and reabsorbed by the arachnoid villi to maintain a total volume of 140 to 170 mL in adults and 10 to 60 mL in neonates.

Definition of the cerebrospinal fluid (CSF)

1. It is a clear, colorless fluid similar to blood plasma and interstitial fluid.
2. Approximately 600 mL of CSF is produced daily.
3. Around 125 to 150 mL of CSF circulates in the ventricles and subarachnoid space.
4. The choroid plexus in the lateral, third, and fourth ventricles produce a major portion of the CSF.
5. CSF does not accumulate but is reabsorbed into venous circulation through arachnoid villi.
6. The blood forms CSF, and after circulating throughout the CNS, it returns to the blood.

CSF production:

1. CSF is secreted by the choroid plexus, around the cerebral vessels, and along the walls of the ventricles of the brain.
2. It fills:
   1. Ventricle and cisternae.
   2. Bath the spinal cord.
   3. It is reabsorbed into the blood through the arachnoid villi.
   4. CSF turnover is rapid, exchanging about four times/day.
   5. >80% of the CSF protein contents originate from plasma by ultrafiltration and pinocytosis.
   6. The rest is from the intrathecal synthesis.
   7. As the CSF passes down the lumbar region of the spinal space, the protein concentration increases.

Functions of Cerebrospinal Fluid (CSF):

1. The intracranial and the spinal cord float in the CSF and are protected from blows and jolts.
2. The buoyant properties of the CSF prevent the brain from tugging on meninges, Nerve roots, and blood vessels.
3. Its primary function is to protect the brain and spinal cord from injury.
4. It transports the substances through the central nervous system.
5. CSF is the ultrafiltrate of the plasma.

The appearance of CSF:

1. Normal CSF Is clear and colorless.
   1. This clear CSF circulates in the subarachnoid space.
   2. No clot is seen.

The pressure of CSF:

1. It is 70 to 180 mm H2O or 5 to 14 mm Hg (another reference = 100 to 200 mm H2O).
2. This pressure is when the person is lying down and doubles up when the person sits up.

Total cell count in CSF:

1. In adults, normal CSF contains 0 to 5 cells/cmm.
   1. These are mononuclear cells and lymphocytes.
   2. In newborns, the CSF cell count is 0 to 30/cmm, mostly neutrophils.
2. Infants are 0 to 20 cells/cmm.
3. No RBC is seen.

The glucose level of CSF:

1. It is 45 to 80 mg /dL . The reference value is 45 mg/dL (2.5 mmol/L) or higher.
   1. In a normal person, it is rare to find glucose below 45 mg/dL.
   2. CSF glucose is 20 mg /dL lower than the blood glucose level.
   3. CSF glucose level is around 60% of the serum glucose level.
   4. In newborns, the CSF glucose level is 80% of the serum glucose level.
   5. The CSF glucose decrease is important to diagnose the various types of meningitis.
2. Ventricular glucose is 5 to 10 mg higher than the lumbar CSF.

The protein level of CSF:

1. Normal CSF protein is 15 to 45 mg/dL in lumbar CSF.
2. It is 15 to 25 mg/dL in the cisternal fluid.
3. It is 5 to 15 mg/dL in the ventricular fluid.
4. In the newborn, the values are different and more uncertain.
   1. At the time of birth is 30 mg/dL and the range is 75 to 150 mg/dL.
   2. In infants from 30 days to 90 days, CSF protein is 20 to 100 mg/dL.
   3. The range from 90 days to 6 months is 15 to 50 mg/dL. The values slowly decline and reach the adult level by six months of age.

Age of the patient	Amount of total protein
Infants	30 to 200 mg/dL
Child	14 to 45 mg/dL
Adult	15 to 45 mg/dL
Elderly	15 to 60 mg/dL

Gamma globulin (CSF):

1. It is 3 to 12 % of the total protein.

Chloride (CSF):

1. It is from 120 to 130 meq/L.
2. It is 20 meq higher than the serum.

LDH (CSF):

1. It is 15 to 17 units/L

Bilirubin (CSF):

1. It is negative.

Normal Cerebrospinal Fluid Analysis (CSF) findings and normal range from various sources:

Lab findings	Source 2	Source 1	Source 4
Volume		Adult 90 to 150 mL Child = 60 to 100 mL
Pressure	<20 cm H2O	50 to 180  mm H2O If the pressure is >180 mm H2O. Then do not take more than 1 to 2 ml of CSF)	Adult = 90 to 180 mm H2O Child (<8 years) = 10 to 100 mm H2O
Appearance	Clear and colorless, no clot	Crystal clear and colorless	Clear and colorless
Blood	Nil	Negative	Nil
White cell count	Neonates = 0 to 30 cell/µL 1 to 5 years = 0 to 20 cells/ µL 6 to 18 years = 0 to 10 cells/  µL Adult = 0 to 5 cells/ µL	0 to 30 cells  0 to 5 cells	Adult = 0 to 5 WBC/µL Newborn = 0 to 30 WBC/µL Child = 0 to 15 WBC/µL
Differential count
Neutrophils	0 to 6%	Adult = 0 to 6% Newborn = 0 to 8%	Adult = 0 to 6% Newborn = 0 to 8%
Lymphocytes	40 to 80%	Adult = 40 to 80% Newborn = 5 to 35%	Adult = 40 to 80% Newborn = 5 to 35%
Monocytes	15 to 45%	Adult = 15 to 45% Newborn = 50 to 90%	Adult = 15 to 45% Newborn = 50 to 90%
Protein	15 to 45 mg/dL It is high in elders and children up to 70 mg/dL		Adult = 15 to 45 mg/dL = lumbar 15 to 25 mg/dL = Cisternal 5 to 15 mg/dL = Ventricular Neonates = 15 to 100 mg/dL Adults >60 years = 15 to 60 mg/dL
Lumbar  area		Adult = 15 to 45 mg/dL Neonates = 15 to 100 mg/dL >60 years = 15 to 60 mg/dL	Adult = 15 to 45 mg/dL
Cisternal area		15 to 25 mg/dL	Adult = 15 to 45 mg/dL = lumbar
Ventricular area		5 to 15 mg/dL	Adult = 5 to 15 mg/dL
Electrophoresis
Prealbumin	2 to 7%		2 to 7%
Albumin	56 to 76%	10 to 35 mg/dL	56 to 76%
Alpha1 globulin	2 to 7%		2 to 7%
Alpha2 globulin	4 to 12%		4 to 12%
Beta globulin	8 to 18%		8 to 18%
Gamma globulin	3 to 12%		3 to 12%
IgG	0 to 4.5 mg/dL		<4.0 mg/dL
Oligoclonal band	Negative		Negative
Biochemical estimation
Glucose	50 to 75 mg/dL (60 to 70% of blood glucose)	Infant, child = 60 to 80  mg/dL Adult = 40 to 70 mg?dL	Adult = 40 to 70 mg/dL Child = 60 to 80 mg/dL CSF/plasma glucose ratio = <0.5 CSF glucose levels are 60 to 70% of the blood
pH		Lumbar area= 7.28 to 7.32 Cisternal area = 7.32 to 7.34
Sodium		135 to 160 meq/L
Potassium		2.6 to 3.0 meq/L
Chloride	700 to 750 mg/dL	115 to 130 meq/L	Infant = 110 to 130 meq/L Adult = 118 to 132 meq/L
LDH	<2 to 7.2 units/mL	<20 U/L	Adult = <20 U/L (around 10% of serum)
Lactic acid	10 to 25 mg/dL	10 to 24 mg/dL	Adult = 10 to 22 mg/dL Newborn = 10 to 60 mg/dL
Glutamine	6 to 15 mg/dL	Neonates = 10.34 ± 3.6 mg/dL 3 months to 2 year = 7.27 ± 1.3 mg/dL 2 to 10 years = 6.76 ± 1.20 mg/dL Adult = 8.61 ± 0.50 mg/dL
Urea nitrogen		6 to 16 mg/dL
Phosphorus		1.2 to 2.0 mg/dL
Creatinine		0.5 to 1.2 mg/dL
Uric acid		0.5 to 4.5 mg/dL
Bilirubin		Negative
Ammonia		10 to 35 µg/dL
Syphilis serology	Negative	Negative	Negative
CSF cytology for malignancy	Negative	Negative	Negative

Normal CSF summary:

Characteristics	Normal values
Volume	Adult = 90 to 150 mL Neonates = 10 to 60 mL
Appearance	Clear, colorless, and no clot seen Xanthochromasia = Negative
Total cell count
Adult and children	0 to 6/cmm, all are mononuclear
Infants	<19 /cmm
Neonates	<30/cmm
Chemistry
Glucose (Lumbar area)	Lumbar area = 45 to 80 mg/dL (20 mg/dL < blood glucose) Ventricular area = 5 to 10 mg/dL>lumbar fluid
Total protein
Lumbar area	Neonates =≤150 mg/dL 2 to 3 weeks = 20 to 80 mg/dL 3 months to 60 years = 15 to 45 mg/dL >60 years  = 15 to 60 mg/dL
Ventricular area	5 to 15 mg/dL
Cisternal area	15 to 25 mg/dL
IgG	<4.0 mg/dL (<10% of total CSF proteins)
Chloride	120 to 130 m eq/L (20 meq/L > than serum value)
Sodium	142 to 150 meq/L
Potassium	2.2 to 3.3 meq/L
CO2	25 meq/L
pH	7.35 to 7.40
AST (SGOT)	7 to 49 units
Urea nitrogen	5 to 25 mg/dL
Bilirubin	Negative
Creatine kinase (CK)	0 to 5 IU/L
Lactate dehydrogenase (LDH)	∼10% of the serum level
CSF electrophoresis
Oligoclonal band	Negative
Proteins	Prealbumin = 2% to 7% Albumin = 56% to 76% Alpha-1- globulin = 2% to 7% Alpha-2- globulin = 4% to 12% Beta- globulin = 8% to 18% Gamma globulins = 3% to 12%
IgG	<4.0 mg/dL (<10% of the total CSF proteins)