CSF Analysis: All You Need to Know

Introduction:

Cerebrospinal fluid is a transparent fluid that forms as an ultrafiltration of plasma. CSF can be found in both the intracranial and spinal compartments. It is constantly produced by the choroid plexus within the ventricles of the brain and circulates through the subarachnoid space of the brain and spinal cord through CSF routes. The entire amount of CSF in an adult is around 140 milliliters. CSF is formed at 0.2 to 0.7 milliliters per minute, equating to 500 to 700 milliliters daily. The primary purpose of CSF is to minimize brain buoyancy (the object's tendency to float in the liquid). It also provides nutrients and aids in the elimination of numerous things, such as amino acids, neurotransmitters, metabolic wastes, and cells. Several processes retain the composition of the CSF. Yet, in illness situations, the content and pressure of CSF might change. As a result, CSF examination using various methodologies will aid in diagnosis, prognosis, and treatment response. CSF analysis is critical in the identification of acute neurological disorders and the initiation of treatment therapies.

What Are the Characteristics of Normal CSF?

The following are the characteristics of normal CSF:

• Clear fluid.

• pH 7.4.

• Pressure during opening is 0 to 200 mm (millimeters of water column).

• Zero to five (up to 30 in neonates) white blood cell (WBC) counts.

• No RBC present.

• Lymphocytes are the type of WBC present.

• 15 to 40 mg/dL (milligrams per deciliter) CSF protein.

• One to three mmol/ L (millimoles per liter) CSF lactate.

• 50–80 mg/dL (two-thirds of blood glucose) CSF glucose.

• No microorganism present.

How Is the CSF Sample Collection Done?

• If the patient has coagulopathy or is receiving anticoagulants or antiplatelet medication, lumbar puncture (LP) must be performed based on the length of drug activity and ASRA (American Society of Regional Anesthesia) criteria.

• A fasting LP is performed for CSF investigation in individuals with seizures assumed to be caused by metabolic disease. In individuals with obtunded sensorium, a computerized tomography (CT) scan of the brain is required to rule out symptoms of elevated intracranial pressure (ICP) and mass lesions due to the possibility of brain herniation due to LP.

• Sedation may be necessary for uncooperative patients and children, and fasting recommendations must be followed to prevent aspiration.

• LP can be done using a lateral or sitting position. Generally, a 22-gauze to 24-gauze spinal needle is placed under aseptic conditions after locating the lumbar L2-3 or L3-4 spaces and local infiltration.

• After the spinal subarachnoid area has been located using a lack of resistance, the stylet is carefully removed to minimize excessive CSF leakage. If CSF opening pressure measurement is desired, a manometer can be attached.

• The color of the CSF is recorded, and if blood is stained because of a traumatic puncture, it may be necessary to wait for the blood to clear before collecting samples.

• For analysis, samples are typically collected in three to four test tubes, each of three to five milliliters for analysis of CSF. Without refrigeration, samples are transferred to the lab in biohazard bags.

What Are the Indications for Lumbar Puncture?

Diagnostic:

• Infections of the central nervous system (CNS).

• Autoimmune diseases of the CNS such as Guilliain Barrie syndrome.

• Vasculitis of the CNS.

• CT scan is negative, and there is no subarachnoid hemorrhage.

• Malignant cells are present in metastasis.

• For injection of dye, such as fluorescein, to locate the source of CSF leaks.

Therapeutic:

• Intracranial hypertension is benign.

• Acute communicable hydrocephalus.

• Meningitis caused by cryptococcal bacteria in HIV (human immunodeficiency virus) patients.

• In case of CSF leakage.

Administration of Intrathecal Drugs:

• Administration of antibiotics.

• Administration of antineoplastic drugs.

What Are the Contraindications for Lumbar Puncture?

Relative Contraindications:

• Platelet count of below 20000 to 40000 per cubic millimeter.

• Therapy using thienopyridines.

Absolute Contraindications:

• Obstructive hydrocephalus that does not communicate.

• Diathesis of uncorrected hemorrhage.

• Anticoagulant treatment (LP timing depends on stopping the anticoagulant drug).

• Platelet counts less than 20000 per cubic millimeter.

• Stenosis or compression of the spinal cord above the level of puncture.

• Skin infection locally at the site of lumbar puncture.

Method of Approach to CSF Analysis in Various Conditions?

1. Approach to CSF Analysis in Acute Brain Conditions:

• CSF In Subarachnoid Hemorrhage (SAH):

  • Subarachnoid Hemorrhage (SAH) is an emergency neurological disorder that requires the patient's admission to critical care. SAH can be caused by rupture of cerebral aneurysms, arteriovenous malformations (AVM), vasculitis, trauma, or idiopathic reasons.

  • Most patients approach with an acute onset severe headache that worsens within one hour of commencement and is frequently described as the worst headache they have ever had. Patients with severe instances may experience loss of consciousness (LOC), seizures, cranial nerve palsies, and various motor impairments.

  • Diagnosing the issue as soon as possible is critical since rebleeding from an aneurysmal origin might be fatal. Since headache is a common symptom of intracranial disorders, a high index of suspicion is required.

  • Before the introduction of CT scanners, LP was the primary diagnostic technique for SAH. The initial diagnostic modality is now a simple CT scan. Yet, despite clinical suspicion, a CT scan for SAH may be normal. CT is considered extremely sensitive up to five days after the SAH.

  • In these circumstances, lumbar puncture is a valuable diagnostic procedure generally performed 12 hours after the commencement of symptoms. LP is recommended if there is a significant clinical suspicion of SAH but a negative CT.

  • LP is usually completed within a few hours. SAH is confirmed by the presence of RBCs (more than 1000 cells/cu mm or cells per cubic millimeters) or xanthochromia (Level 2 evidence suggestion B). Traumatic LP, on the other hand, might complicate the RBC and result in false positives.

  • CSF is taken in three test tubes to differentiate between traumatic tap and SAH, and red cells in each tube are counted. A reduction in red cells is generally indicative of a traumatic tap. Another way is to centrifuge the CSF and examine the supernatant fluid for xanthochromia. Spectrophotometry is indicated for detecting xanthochromia.

  • As a result of the lysis of RBCs in CSF and the release of pigments such as oxyhemoglobin, methemoglobin, and bilirubin, xanthochromia can be noticed as quickly as 12 hours, nevertheless, because of the existence of pigments until three weeks after the first SAH, LP is ineffective in diagnosing rebleeding SAH.

• CSF Analysis in Meningitis or Meningoencephalitis:

  • Individuals suspected of meningitis are among the most common reasons for LP and CSF analysis. Meningitis can be obtained in the community or the hospital and is caused by various pathogens such as bacteria, viruses, fungi, protozoa, and others.

  • Aseptic meningitis must be recognized from other types of meningitis that need CSF investigation. Meningitis can present as an acute devastating sickness or persistent symptoms like TB.

  • Individuals with acute meningitis typically exhibit altered awareness, fever, and neck stiffness. Just 46 percent of patients have the traditional triad. In others, one or two of the triad indications may be present.

  • Patients may also experience nausea, vomiting, headaches, and photophobia. Other clinical indications of meningoencephalitis include altered sensorium, disorientation, behavioral abnormalities, seizures, and localized neurological impairments.

  • When there is a high index of suspicion of meningitis, a single antibiotic dosage is frequently given immediately once blood cultures are taken and without waiting for confirmation by LP. A CT scan may be recommended before LP if the patient has high intracranial pressure (ICP) or a mass lesion such as cerebral edema or herniation.

• CSF Analysis in Acute Demyelinating/Autoimmune Diseases:

  • Demyelinating disorders are a group of diseases in which the patient may arrive at the emergency department with an acute neurological state. CSF analysis can help diagnose certain disorders, the progression of the disease, and the prognosis following medication.

  • Multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica (NMO) are demyelinating illnesses. Along with these disorders, autoimmune diseases such as Guillain-Barre syndrome, transverse myelitis, and others can induce varied degrees of demyelination and degeneration. Because of significant inflammatory damage of Brain structures or consequences, these disorders may result in acute crises.

  • The appearance of localized collections of lymphocytes and monocytes with different degrees of demyelination, axonal damage, and activation of the astroglial and microglial are pathological findings in this category of conditions. In addition to complementing factor deposition, blood vessel vasculitis can be detected. Pathology is frequently the result of a post-infectious, post-vaccination, or systemic inflammatory reaction.

  • This results in an autoimmune or inflammatory response to CNS components. Because most illnesses respond to therapy, early diagnosis, and treatment enhance patient outcomes. CSF examination provides essential information about the disease's diagnosis, progression, or recurrence and treatment efficacy.

2. Brain and Spinal Cord Neoplasms:

CNS neoplasms that benefit from CSF analysis are often caused by primary CNS lymphoma or secondary leptomeningeal deposits. Patients may appear promptly with symptoms of increased intracranial pressure caused by mass effect, cerebral edema, or herniations. Radiological examinations will aid in the diagnosis. Yet, it can be challenging to discern between secondary and primary tumors or infections such as abscesses. A CSF analysis might be beneficial. Following the first CT scan or MRI (magnetic resonance imaging), centrifuged CSF can be utilized to determine the presence or absence of malignant cells and numerous tumor markers such as colon, lung, and prostate.

3. CSF Analysis in Spinal Cord Diseases:

• Guillain Barre Syndrome (GBS):

  • Albumino-Cytologic Dissociation: High CSF protein with average cell count is the typical immunologic CSF alteration (albuminocytologic dissociation). Pleocytosis can develop in uncommon cases.

  • Neurofilament Light (NFL) Protein Assay: NFL levels were linked with impairment during the acute phase of GBS and were substantially predictive of long-term disability. NFL levels in the control group were age-dependent, irrespective of gender, and linked with albuminocytologic dissociation, a measure of the blood-brain barrier integrity in patients.

• Amyotrophic Lateral Sclerosis (ALS):

  • Since miR-218 levels are largely preserved inside the surviving motor neurons, miR-218 depletion in ALS spinal cord tissue is probably related to losing motor neurons. MiR-218 expression is linked to the dysfunction of motor neurons and mortality in both animal and human models of motor neuron loss and disorder.

• Spinal Cord Ependymoma:

  • Tumor-derived cell-free DNA (cfDNA) can be discovered when the tumor is not enveloped by parenchyma or separated by arachnoid membranes. Six out of seven tumor patients had tumor-derived cfDNA in their CSF.

Conclusion:

CSF analysis is a critical examination of individuals with acute neurological disorders. While identifying microbiological organisms is not required for acute meningitis, it will aid in establishing a diagnosis and prognosis and evaluating the efficacy of various medicines to treat the patient's circumstances. CSF analysis has progressed from basic analysis to evaluating numerous biomarkers to assist clinicians. As a result, the physician must understand the reasons for these studies, as they are not commonly available and are costly.