Cerebrospinal fluid (CSF)
- Cerebrospinal fluid physico-chemical properties:
- Microscopic examination (cytology, hematology):
Cerebrospinal fluid physico-chemical properties
The relative density (specific gravity) of lumbar CSF is 1,005-1,009, suboccipital – 1,003-1,007, ventricular – 1,002-1,004.
Increasing the relative density of cerebrospinal fluid is observed in meningitis, uremia, diabetes, etc., decrease – in hydrocephalus.
Normal CSF is clear like distilled water, consists of water for 98.9-99.0% and 1.0 to 1.1% of dry residue.
Clouding liquor depends on the significantly increasing the amount of cell components (erythrocytes, leukocytes, tissue cellular elements), bacteria, fungi and increase the protein content.
The clouding caused by the cells and fungi, decreases or disappears after centrifugation, in contrast to the clouding caused by bacteria. While increased fibrinogen in the CSF also has been a change in transparency in the form of a light opalescence.
The degree of opacity of liquor is determined by comparing it with distilled water, poured into the same test tube, in transmitted daylight on a black background.
Fibrin (fibrinous) film
Normal CSF does not contain fibrinogen. The appearance of fibrinogen in the CSF caused by diseases of the central nervous system, causing impaired blood-brain barrier (BBB) – purulent and serous meningitis, CNS tumors, cerebral hemorrhage, compression, etc.
Normal cerebrospinal fluid is colorless, as distilled water. The coloration usually indicates a pathological process in the CNS. To determine the coloring of the cerebrospinal fluid compared to distilled water, poured into the same test tube.
Red blood cells (RBCs), erythrocytearchia (eritroarchia)
The presence of blood in the cerebrospinal fluid can detect macro- and microscopically. Distinguish traumatic tap (artifact) and true erythrocytearchia.
Traumatic tap erythrocytearchia is caused by ingress of blood into the CSF upon injury of blood vessels during the execution of the lumbar puncture.
True erythrocytearchia occurs due to cerebral hemorrhage in CSF spaces due to rupture of blood vessels in hemorrhagic stroke, brain tumors, traumatic brain injuries.
The amount of blood trapped in the CSF space, may vary from 0.01 to 90 ml. When the content of red blood cells less 0,1-0,15*109/L cerebrospinal fluid is colorless. A positive reaction in diagnostic zone of the test strip to the blood and the detection of red blood cells on microscopic examination of native preparation of liquor allow you to diagnose hidden erythrocytearchia.
When the concentration of erythrocyte 0,6-1,0*109/L liquor becomes grayish-pink color, with 2-50*109/L – pinkish-red, with 51-150*109/L – the color of fresh meat, with >150*109/L – bloody.
Erythrocytearchia indicates intracranial bleeding resulting from brain vessels aneurysm rupture, hemorrhagic stroke, hemorrhage in the brain tissue, hemorrhagic encephalitis, traumatic brain injury. Subarachnoid hemorrhage may occur as a result of paralysis of vasomotor nerves, and is accompanied by vasodilatation, stasis of blood in the capillaries and diapedesis of red blood cells.
Red blood cells disappear from the CSF at 5-10 days in mild traumatic brain injury and the exclusion of bleeding, in hemorrhagic stroke and severe head injury – at 10-20 a days, aneurysm rupture – at 40-80 days.
Pink, orange, yellow, and brown coloration of CSF caused by the decay products of blood — hemoglobin and bilirubin and is called xantochromia. Distinguish hemorrhagic and congestive xantochromia, which can be divided depending on the decay products of blood on the hemoglobin-archia (pink color) and xantochromia (yellow color).
Hemorrhagic xantochromia (bilirubinarchia) caused by ingress in a CSF space of blood, the decay of which leads to staining of the liquor in the pink, then orange and yellow. In hemorrhagic stroke, aneurysm rupture or craniocerebral trauma accompanied by massive hemorrhage, xantochromia appears in 1 days, with subarachnoid hemorrhage increases its intensity in 2-4 days.
The decrease in xantochromia (bilirubinarchia) and her disappearance are directly dependent on the etiology of the hemorrhage. Thus, rupture of the aneurysm xantochromia (bilirubinarchia) lasts 1-1. 5 months, as in stroke and TBI, not accompanied by bleeding, is 10-14 days.
Congestive xantochromia (bilirubinarchia) is the result of slow blood flow in the vessels of the brain. The hemodynamic instability leads to increased permeability of the vessel walls and the colored in yellow (bilirubin) blood plasma flow to the cerebrospinal fluid. This xantochromia (bilirubinarchia) is constant and is accompanied by hyperproteinemia.
Congestive xantochromia (bilirubinarchia) occurs in vascularized tumors of the central nervous system, directly connected to the CSF spaces in the blockade of the subarachnoid space, compression, meningitis (mainly for tuberculosis), arachnoiditis, etc.
Physiological xantochromia (bilirubinarchia) is common in infants and almost all premature. This phenomenon can be explained by increased permeability of the blood-brain barrier for bilirubin in blood plasma.
False xantochromia (bilirubinarchia) is caused by penetration into the cerebrospinal fluid of lipochromes or drugs, for example penicillin.
Green color of the liquor is observed in severe xantochromia (bilirubinarchia) in the oxidation of bilirubin to biliverdin. Green color also gives the admixture of pus, cerebrospinal fluid is cloudy. Such green color CSF gets in purulent meningitis, the breakthrough of a brain abscess into the subarachnoid space or into the ventricles.
pH is one of relatively stable biochemical parameters of cerebrospinal fluid. In healthy people the pH of lumbar CSF is 7.28-7.32. The pH change in the cerebrospinal fluid affects alveolar ventilation, cerebral circulation and consciousness.
Metabolic acidosis occurs most often in uremia, diabetic ketoacidosis, or alcohol intoxication. Cerebrospinal fluid pH stays in the normal range or only slightly reduced.
Metabolic alkalosis is observed in liver disease, prolonged vomiting, intake of alkaline substances. And the cerebrospinal fluid pH may be reduced paradoxically to 7.27.
In respiratory acidosis due to pulmonary insufficiency, CSF pH will decrease slightly.
Respiratory alkalosis caused by injuries, poisoning (especially salicylates), liver disease, does not significantly affect the CSF pH.
Primary CSF acidosis manifested in diseases of the nervous system: severe subarachnoid and cerebral hemorrhage, head injury, cerebral infarction, purulent meningitis, status epilepticus, brain metastases, etc.
Protein concentration in the lumbar cerebrospinal fluid is 0.22-0,33 g/L. Value 0.33 g/L is considered as a value of bordering to pathology, and the value 0.22 g/L - as a hydrocephalic lumbar cerebrospinal fluid.
Low protein concentration in CSF (hypoproteinarchia) is the reduction in the protein content of lumbar cerebrospinal fluid below 0.2 g/L, is considered as hydrocephalic CSF.
Low protein concentration in CSF (hypoproteinarchia) may occur:
- as a result of reducing the income of whey protein in cerebrospinal fluid
- when increasing the speed of metabolism of CSF
- when removing a large amount of spinal fluid over of hydrocephalus
- during pneumoencephalography (PEG)
- in patients with benign intracranial hypertension, hyperthyroidism, some leukemias
High protein concentration in CSF (hyperproteinarchia) is the increase in protein content in the cerebrospinal fluid, possible due to:
- subarachnoid hemorrhages
- brain tumors
- hypertensive encephalopathy
- acute and chronic inflammatory processes in CNS of various etiologies (arachnoiditis, arachno-encephalitis, encephalitis, meningitis, etc.)
- brain abscess
- cerebral cysticercosis
- in traumatic brain injury (TBI)
In healthy adults approximately 83% of the proteins of cerebrospinal fluid accounts for the proteins of the blood serum, however, 17% is of intrathecal origin (prealbumin, prostaglandin-D-synthase, the neuron-specific enolase, S100 protein, etc.).
The main mass of the total CSF protein is albumin, which has exclusively serum origin. In the normal CSF albumin content varies from 0.07 to 0.36 g/Ll and above. Almost any breach of the blood-brain barrier (BBB) leading to an increase in the absolute concentration of albumin in CSF and increase in the ratio of the concentration of CSF albumin/serum albumin. The ratio of albumin/globulin in the CSF regulates the osmotic pressure in the CNS.
At normal blood glucose level in lumbar cerebrospinal fluid glucose concentration is approximately 60% of the level in plasma. If hyperglycemia is the difference between CSF and blood increases significantly, in the CSF glucose reaches only 30-35% of the plasma level. The level of glucose in CSF is one of the important indicators of function of blood-brain barrier (BBB).
Hypoglycarchia is the reduction of glucose below 2,2 mmol/l or a ratio of blood glucose/cerebrospinal fluid glucose less than 0.3. Observed at:
- bacterial, tuberculous, amebic, or fungal meningitis
- cysticercosis and echinococcosis (50% of patients)
- primary and metastatic tumors of the brain membranes (gliomas, sarcomas, lymphomas, neuro-leukemia, melanoma, metastatic carcinoma from lung, stomach, etc.)
- the first day after subarachnoid hemorrhage
Hyperglycarchia — the increase of glucose level of CSF is rare, not typical even for diabetes. Observed at:
- during sleep (due to the slowing of blood circulation and reduce overall brain metabolism)
- brain injury and some types of meningoencephalitis
- in patients with ischemic disorders of cerebral circulation
Normally, ketones in the cerebrospinal fluid are not detected. Ketonearchia develops after:
- operations on the brain membranes
- craniocerebral trauma (TBI)
- subarachnoid hemorrhages
- intense excitation and CNS stimulation
Ketonearchia explained by the collapse of the protein and impaired utilization of ketone bodies, that normally are substrates for cells of the central nervous system.
Nitrites – is a waste product of many bacteria. Thus, a positive reaction to nitrites talking about bacterial meningitis. At the same time it must be remembered that this test will be negative in tuberculous and staphylococcal meningitis, as these agents do not restore the nitrate to nitrite.
Microscopic examination (cytology, hematology)
In normal cerebrospinal fluid of an adult is practically no cellular elements: in ventricular CSF – 0-1 cells/µl, suboccipital CSF – 2-3 cells/μl in lumbar CSF – 3-5 cells/μl.
The increase in the number of cells in the cerebrospinal fluid (pleocytosis) is considered as a symptom of organic lesions of the central nervous system. Pleocytosis divided on:
- light – 6-70*106cells/L
- moderate – 70-250*106cells/L
- expressed – 250-1000*106cells/L
- sharply expressed – >1000*106cells/L
- massive – >10*109cells/L
Modern methods of cytological studies indicate hematogenous origin of the liquor cells, except arachno-endothelial and ependymal cells.
CSF formula of healthy individuals are mostly represented by lymphocytes (70%) and monocytes (30%). In the cerebrospinal fluid of newborn also present neutrophilic granulocytes, whose content ranges from 6 to 50%.
Lymphocytes in the amount of 2-4 cells/µl are part of the normal cell count of the cerebrospinal fluid. Normal CSF contains only small lymphocytes.
Conditions accompanied by lymphocyte pleocytosis:
- Meningitis (viral, tuberculous, mycotic)
- Amebic encephalomyelitis
- Syphilitic meningoencephalitis
- Parasitic CNS infections (cysticercosis, toxoplasmosis)
- Degenerative diseases (subacute sclerosing panencephalitis, multiple sclerosis, drug encephalopathy, acute disseminated encephalomyelitis)
- Other pathology (sarcoidosis, polyneuritis, periarteritis involving brain vessels)
Monocytes – this is the second main cell population in normal CSF, normal value 1-3 cells/mm. Increasing the number of monocytes in the CSF formula indicated for chronic smoldering inflammation in the central nervous system:
- tuberculous meningitis
- viral meningitis
- multiple sclerosis
- hyperkinetic progressive panencephalitis
- ischemic diseases and brain tumors
Macrophages belong to the mononuclear phagocyte system in the normal cerebrospinal fluid does not occur. Availability 1-2 macrophages cells/L at normocytosis – a sign of the former bleeding or inflammation of the central nervous system.
Macrophages always found in the cerebrospinal fluid of patients with brain tumors growing in the lumen of the ventricles. A large number of macrophages in the postoperative period, testifies of of active CSF sanation.
Neutrophils in the cerebrospinal fluid of a healthy person almost never occur. This cell of haematogenous origin. Conditions associated with neutrophilic pleocytosis:
- Meningitis (exudative phase of bacterial meningitis, the early stage of viral meningitis, an acute phase of tuberculous meningitis, mycotic initial stage of meningitis, amebic meningoencephalitis)
- Brain abscess
- Cerebral and spinal syphilis
- Subdural empyema
- Hemorrhagic and ischemic stroke
- Subarachnoid hemorrhage at 1-3 day
- The response to the first and repeated lumbar punctures
- Drugs injection into the subarachnoid space
- Metastases of malignant neoplasms in the CNS
Eosinophils in the cerebrospinal fluid of healthy persons do not occur. Their appearance is regarded as a special reaction of the connective tissue vessels in the subarachnoid space on foreign proteins.
Eosinophils in the cerebrospinal fluid play the function of phagocytosis, absorbing bacteria, fungal spores and complexes antigen-antibody, especially with immunoglobulins and components of complement.
Eosinophilia in the cerebrospinal fluid is not accompanied by eosinophilia in the blood and Vice versa. Cerebrospinal fluid eosinophilia can be observed at normocytosis and pleocytosis. Eosinophils may flow into the CSF under special stimulation from the mesenchyme of pia mater, or directly from the blood.
Conditions associated with appearance of eosinophils in the cerebrospinal fluid (CSF):
- Parasitic infections (cysticercosis, echinococcosis)
- Meningitis (eosinophilic, bacterial, tuberculous, toxic, epidemic, syphilitic, viral)
- Fungal infections
- Administration of drugs or contrast agents in CNS
- Acute polyneuritis
- Idiopathic hypereosinophilic syndrome
- Brain cyst
- Ischemic and hemorrhagic stroke
- Brain tumors (meningioma, neuroblastoma, eosinophilic adenoma)
- Leukemias, neurosarcoidosis
- Condition after surgery on the meninges
Basophils in normal cerebrospinal fluid does not occur. They are involved in inflammatory processes of allergic origin, are found in the cerebrospinal fluid in severe neuroinfections occurring, especially in children.
Plasma cells are found in the cerebrospinal fluid only in pathological processes. Plasma cells are formed from B-lymphocytes in the follicles of the cortical areas of lymph nodes and marginal zone of white pulp of the spleen, where when meeting with antigen, they undergo antigen-dependent stage of differentiation. The main function of plasma cells is the synthesis and secretion of antibodies.
Conditions associated with appearance of plasma cells in the cerebrospinal fluid (CSF):
- Long lingering inflammation of the brain and meninges (chronic encephalitis, meningitis of various etiologies, arachnoiditis)
- Multiple sclerosis
- Hyperkinetic progressive panencephalitis
- Neurosyphilis (in combination with normocytosis or a slight pleocytosis)
- Some tumors of the central nervous system
- Tuberculous meningitis
- Collagenoses with involvement of the CNS
- Subarachnoid hemorrhage
Immature white blood cells (blasts)
In leukemia patients with involvement of the meninges occurs leukemic meningitis - neuroleukemia. Neuroleukemia more likely to develop in acute leukemia. Usually the number of cells in the cerebrospinal fluid ranging from 100 to 300*106/L, is not excluded higher pleocytosis constituting 5.2*109/L or more.
Malignant lymphoma in patients on the background of the use of chemotherapy and immunosuppressive therapy may develop cryptococcosis, coccidiomycosis, candidomycosis or blastomycotic meningitis, encephalitis or meningoencephalitis.
Arachnoendothelial cells is a single layer of epithelium of ependymal origin, morphologically similar to the mesothelium that covers all the spaces of the CNS filled with CSF, with the exception of the brain ventricles.
Arachnoendothelial cells found in the cerebrospinal fluid of patients with brain tumor, head injury and after operations on the meninges.
Brain and other organs and tissues tumor cells found in the study of cerebrospinal fluid in patients with primary and metastatic CNS tumors. Tumor cells enter into the cerebrospinal fluid as a result of exclusion from the tumor tissue adjacent to CSF spaces, as well as during germination the wall of the brain ventricles or meninges in leptomeningeal carcinomatosis (leptomeningeal metastasis of carcinoma, lymphoma, glioma, melanoma, or sarcoma).
- Complete blood count (CBC):
- Cerebrospinal fluid (CSF) analysis
- Biochemical markers of bone remodeling and diseases
- Markers of autoimmune connective tissue diseases (CTDs)
- Antiphospholipid syndrome (APS)
- Lipoprotein(a), Lp(a)
- Semen analysis (sperm count test)
- Tumor markers tests (cancer biomarkers):
- β-2 microglobulin (beta-2)
- Alpha-fetoprotein (AFP)
- Squamous cell carcinoma antigen (SCC)
- S100 protein tumormarker
- Mucin-like carcinoma-associated antigen (MCA)
- Neuron-specific enolase (NSE)
- Prostate-specific antigen (PSA) test
- Cancer associated antigen 549 (CA 549)
- CA 19-9, CA 72-4, CA 50, CA 15-3 and CA 125 tumor markers (cancer antigens)
- Carcinoembryonic antigen (CEA)
- Thyroglobulin (Tg)
- Tissue polypeptide antigens (ТРА, TPS)
- Cytokeratin-19 fragment (CYFRA 21-1)
- Human chorionic gonadotrophin (hCG)