The document discusses cerebrospinal fluid (CSF), including its production and pathways in the central nervous system. CSF acts as a cushion or buffer for the brain, is produced by the choroid plexus at a rate of around 500 ml per day, and circulates through the ventricular system and subarachnoid space. Analysis of CSF provides valuable information for diagnosing neurological conditions through examination of cells, proteins, glucose, and other analytes. Abnormal levels can indicate infections, inflammatory conditions, and other disorders.

1. CEREBROSPINAL FLUID DR.SRIRAMA A NJANEYULU

2. CSF Occupies the subarachnoid space and the ventricular system around and inside the brain. Occupies the space between the arachnoid mater and the pia mater. It constitutes the content of all ventricles, cisterns and sulci , as well as the central canal of the spinal cord. It acts as a "cushion" or buffer for the cortex, providing a basic mechanical and immunological protection to the brain inside the skull.

3. Definition Cerebrospinal fluid (CSF) is a biologic fluid, formed mainly in the ventricular choroid plexus, distributed within the ventricular system, basal cisterns, and subarachnoid space.

4. CSF PATH

6. Csf production secreted by the choroid plexus - 500 ml per day, 0.35 ml per minute, and a turnover of 14% per hour. The usual volume is 150 ml. Formation occurs as a result of a two-step process. Fluid is first filtered through the core capillaries of the choroid plexus into the extracellular space surrounding the choroidal cells. This fluid is a plasma ultrafiltrate. Then sodium is actively transported by sodium–potassium activated adenosine triphosphatase (ATPase) across the choroidal cells into the CSF; water follows down an osmotic: gradient. Cholinergic stimulation increases production and adrenergic stimulation decreases production. Drugs that inhibit sodium–potassium ATPase or carbonic anhydrase decrease production. Furosemide also slows CSF production due to its effect on chloride flux. Some CSF is apparently produced in the ependyma of the brain, in addition to the choroid plexus.

7. MAJOR TRANSPORT INTERFACES in CNSs

9. Schema of main CNS compartments and interfaces. The blood-brain andblood-CSF barriers are true barriers with tight junctions between endothelial and epithelial cells, respectively. The brain-CSFinterface, because of gap junctions between ependymal (or pia-glial) cells, is more permeable than brain or spinal cord capillariesand choroid plexus.

10. Blood-CSF barrier. CP is comprised of one cell layer of circumferentially arranged epithelial cells.Plexus capillaries, unlike counterparts in brain, are permeable to macromolecules.

11. Blood-brain barrier: Endothelial cells arelinked by tight junctions, conferring low paracellular permeability. Endothelial cell pinocytotic vesicle paucity reflects minimaltranscytosis.

12. Brain-CSF interface: Ependymal lining in lateral ventricles permits relatively free diffusion of solutes betweenbrain ISF and large-cavity CSF. Motile cilia at ependymal cell apex move CSF downstream to SAS.

13. contraindications Absolute Infection in the skin overlying the access site. Relative Papilledema . A bleeding diathesis . A platelet count of 50,000 or lower . Severe pulmonary disease or respiratory difficulty in the patient.

14. Normal Values for Adults(fishman) Opening pressure 50–200 mm H2O CSF Color Colorless Turbidity Crystal clear Mononuclear cells <5 per mm3 Pmn leukocytes 0 Total protein 22–38 mg/dl Glucose 60–80% of blood glucose

15. CSF AGE GROUPS

16. Average values of constituents of normal CSF and serum(fishman)

17. Indications for lp To obtain pressure measurements and procure a sample of the CSF for cellular, cytologic, chemical, and bacteriologic examination. To aid in therapy by the administration of spinal anesthetics and occasionally antibiotics or antitumor agents, or by reduction of CSF pressure. To inject a radiopaque substance, as in myelography, or a radioactiveagent, as in radionuclide cisternography.

18. complications Brain herniation, 1 to 15% (Fishman, 1980). Headache,10% . Tourtellotte and associates (1964). Diplopia due to unilateral or bilateral sixth nerve palsy. Subarachnoid hemorrhage, or a "traumatic" tap. spinal epidural hematoma or spinal subdural hematoma.

19. Studies indicated for evaluation of CSF. ( Shulman)

20. Analysis of Xanthochromic CSF Technique-Compare CSF with a similar volume of water in an identical tube; look down the longitudinal axis of the tube, against a white background. Pigments seen in subarachnoid hemorrhage (SAH) Oxyhemoglobin-Pink or orange color; released into CSF in 2 hours after SAH, due to RBC lysis; may be released within 30 minutes if RBC greater than 150,000/mm3; maximum color in 36 hours, disappears in 7 to 10 days; cerebrospinal fluid must be examined immediately after the LP, since oxyhemoglobin can be produced by lysis of RBC in the test tube. Bilirubin-Produces the yellow pigment, or xanthochromia of CSF; produced in vivo by the conversion of free hemoglobin by macrophages and other leptomeningeal cells; not seen for 10 to 12 hours after the hemorrhage; reaches a maximum in 48 hours, and persists 2 to 4 hours. Methemoglobin- brown,appears when blood is loculated or encysted and isolated from the flow of CSF Other causes of xanthochromia Protein-Protein over 150 mg/dl produces xanthochroma, the intensity paralleling the amount of protein Red blood cells-RBC over 100,000/mm3 produce xanthochromia as a result of serum brought with them Jaundice-Serum bilirubin of 15 mg/dl produces xanthochromia. Carotene-Hypercarotenemia in food faddists produces xanthochromia Miscellaneous-Subdural hematomas, trauma, and clots in other locations will produce xanthochromia White blood cells-The WBC/RBC ratio is similar to that of the plasma in traumatic taps and fresh SAH; SAH that is a few days old will produce a chemical meningitis, which elevates the number of WBC Protein-Each 1000 RBC min raises CSF protein 1.5 mg/dl Traumatic tap-Tubes 1 to 3 show decreasing RBC.

21. Cellularity No cells or 1-5 lympho’s. Neonate-<30 pmn. EXAMINATION OF CELL Diagnosis of inf. Follow up in course of illness Response to treatment FALSE LOW COUNT >60 Mts Settlement of cells Lysis of cells Adsorbs to wall of bottle

22. ELEVATED WBC COUNT INDICATES REACTIVE PROCESS >5/cmm-abnormal 5-10-slight pleocytosis 11-50-moderate ple. 50-200-severe pleo.

23. Neutrophilicpleocytosis Bacterial inf. Early viral inf. Early TB inf.

24. Lynphocyticpleocytosis Viral inf. TB inf. Fungal inf. CNS tumours. SAH.

25. EOSINOPHYLIC PLEOCYTOSIS PARASITIC INF. TB. SYPHYLIS. LCMV. SSPE. MALIGNANT LYMPHOMA. LEUKEMIA. GRANULOMATOUS MENNIGITIS. IDIOPATHIC EOSINOPHYLIC MENINGITIS. HODGKINS LYMPHOMA.

26. Noninfectious Causes of CSF Pleocytosis Chemical meningitis Myelography Spinal anesthesia Intrathecal medication Ingestion of mercury or arsenic Vasculitis Subarachnoid hemorrhage Behcet's syndrome Lead encephalopathy Sarcoid Tumor (leukemia most common; glucose can drop to zero) Seizure activity (must diagnose only if other possibilities are ruled out and if pleocytosis is minimal and rapidly clears)

27. Proteins In contrast to the high protein content of blood (5500 to 8000 mg/dL), that of the lumbar spinal fluid is 45 mg/dL or less in the adult. Basal cisterns is 10 to 25 mg/dL , ventricles is 5 to 15 mg/dL, Reflecting a ventricular–lumbar gradient in the permeability of capillary endothelial cells to protein (blood-CSF barrier) and a lesser degree of fluid circulation in the lumbosacral region. Children,the protein concentration is less than 20 mg/dl. Higher Level -a pathologic process in or near the ependyma or meninges—in either the brain, spinal cord, or nerve roots.

28. SAH-PROTEIN Bleeding into the ventricles or subarachnoid space results in spillage not only of RBC but of serum proteins. If the serum protein concentrations are normal, the CSF protein should increase by about 1 mg per 1000 RBC provided that the same tube of CSF is used in determining the cell count and protein content. The same holds for a traumatic puncture that allows seepage of venous blood into the CSF at the puncture site. However, in the case of subarachnoid hemorrhage, due to the irritating effect of hemolyzed RBC upon the leptomeninges, the CSF protein may be increased by many times this ratio.

29. PROTEIN In bacterial meningitis, in which choroidal and meningeal perfusion are increased, often reaches 500 mg/dL or more. Viral infections -less intense and mainly lymphocytic reaction and a lesser elevation of protein— usually 50 to 100 mg but sometimes up to 200 mg/dL. Paraventricular tumors, by reducing the blood-CSF barrier, often raise the total protein to over 100 mg/dL. 500 mg/dL or even higher are found in exceptional cases of the Guillain-Barre´ syndrome and chronic inflammatory demyelinatingpolyneuropathy. 1000 mg/dL or more- loculation of the lumbar CSF (CSF block); deeply yellow and clots readily because of the presence of fibrinogen;a combination called Froin syndrome. Partial CSF blocks by ruptured discs or tumor may elevate the protein to 100 to 200 mg/dL. Low CSF protein -meningismus (a febrile illness with signs of meningeal irritation but normal CSF), meningealhydrops , hyperthyroidism, or after a recent LP

30. Fractionation of CSF Protein The protein fractions that have been identified electrophoretically are prealbumin albumin alpha1, alpha2,beta1, beta2, and gamma globulin fraction. gamma globulin fraction is the major immunoglobulin in normal CSF is IgG.

31. PROTEINS CSF always contains a prealbumin fraction and the plasma does not. CSF beta2 or tau fraction (transferrin) is proportionally larger than that in the plasma and again higher in the ventricular than in the spinal fluid. The gamma globulin fraction in CSF is about 70 percent of that in serum.

32. IG-g IgG, which may exceed 12 percent of the total CSF protein in diseases such as multiple sclerosis, neurosyphilis, subacutesclerosingpanencephalitis, chronic viral meningoencephalitides. The serum IgG is not correspondingly increased,which means that this immune globulin originates in (or is preferentially transported into) the nervous system. However, an elevation of serum gamma globulin—as occurs in cirrhosis, sarcoidosis,myxedema, and multiple myeloma—will be accompanied by a rise in the CSF globulin.

33. Glucose 45 to 80 mg/dL, (0.6 to 0.7 of serum concentrations). Higher levels parallel the blood glucose;but with marked hyperglycemia, the ratio of CSF to blood glucose is reduced (0.5 to 0.6). With extremely low serum glucose, the ratio becomes higher, approximating 0.85. CSF values below 35 mg/dL are abnormal. After the I.V. injection of glucose, 2 to 4 h is required to reach equilibrium with the CSF; a similar delay follows the lowering of blood glucose. Low values of CSF glucose (hypoglycorrhachia) in the presence of pleocytosis usually indicate pyogenic, tuberculous, or fungal meningitis, although similar reductions are observed in some patients with widespread neoplastic infiltration of the meninges and occasionally with sarcoidosis and subarachnoid hemorrhage (usually in the first week).

34. Serologic and Virologic Tests cryptococcal surface antigen Venereal Disease Research Laboratories (VDRL) slide flocculation test and rapid plasma reagin (RPR) agglutination test polymerase chain reaction (PCR) herpesviruses and cytomegalovirus

35. ammonia hepatic encephalopathy, inherited hyperammonemias, Reye syndrome. concentration corresponds roughly with the severity of the encephalopathy.

36. uric acid 5 percent of that in serum High gout. Uremia. meningitis . low Wilson disease

37. Urea& amino acids The urea concentration in the CSF is slightly lower than that in the serum;in uremia, it rises in parallel with that in the blood. An intravenous injection of urea raises the blood level immediately and the CSF level more slowly, exerting an osmotic dehydrating effect on the central nervous tissues and CSF. The concentration of amino acids in the CSF is about one-third that in plasma. Elevations of glutamine are found in hepatic coma and the Reye syndrome and of phenylalanine, histidine, valine, leucine, isoleucine,tyrosine, and homocystine in the corresponding aminoacidurias.

38. ENJYMES ADA- TB meningitis Lymphoma with meningeal involvement SAH Sarcoidosis Lactic dehydrogenase, especially isoenzymes 4 and 5, which are derived from granulocytes elevated in bacterial meningitis but not in aseptic or viral meningitis. Lactic dehydrogenase is also elevated in cases of carcinomatous meningitis, as is carcinoembryonic antigen; CEA, however, is not elevated in bacterial, viral, or fungal meningitis.

39. catecholamines Homovanillic acid (HVA), the major catabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), the major catabolite of serotonin, are normally present in the spinal fluid; Both are five or six times higher in the ventricular than the lumbar CSF. The levels of both catabolites are reduced in patients with idiopathic and drug-induced parkinsonism

40. Dementia {Ann Neurol. 2005 May}

41. Dementia progression A study conducted by investigators at Washington University School of Medicine, in St. Louis, Missouri. Patients with very mild dementia of the Alzheimer's type (DAT), lower levels of the peptide amyloid beta 1-42 (Aβ42), high tau or phosphorylated tau at threonine 181 (ptau-181), or high tau-to-Aβ42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. {Arch Neurol. 2009;66:638-645}

42. ms mononuclear cell pleocytosis,increased level of intrathecally synthesized IgG. The total CSF protein is usually normal or slightly elevated. Various formulas distinguish intrathecally synthesized IgG from IgG that may have entered the CNS passively from the serum. One formula (the CSF IgG index) expresses the ratio of IgG to albumin in the CSF divided by the same ratio in the serum. The measurement of oligoclonal banding (OCB) in the CSF also assesses intrathecal production of IgG. detected by agarose gel electrophoresis. Two or more OCBs are found in 75 to 90% of patients with MS. OCBs may be absent at the onset of MS, and in individual patients the number of bands present may increase with time. It is important that paired serum samples be studied to exclude a peripheral (i.e., non-CNS) origin of any OCBs detected in the CSF. A mild CSF pleocytosis (5 cells/L) is present in25% of cases,usually in young patients with RRMS. A pleocytosis of 75 cells/L, the presence of polymorphonuclear leukocytes, or a protein concentration of 1.0 g/L (100 mg/dL) in CSF should raise concern that the patient may not have MS. oligoclonal band demonstration is the most useful single test in helping to establish the presence of multiple sclerosis; lgGquantitation is the least helpful. Myelin basic protein should be quantitated for following the activity of multiple sclerosis;

43. Clinical ImpressIons of Patients ConsidereD Not to Have MS but Positive Test Results{N=166}