# Lumbar Puncture and CSF Analysis

## Introduction

Lumbar puncture (LP) is one of the most fundamental procedures in neurology, providing diagnostic information that cannot be obtained by any other means. Cerebrospinal fluid analysis is essential for diagnosing meningitis, encephalitis, subarachnoid hemorrhage, autoimmune neurological disorders, demyelinating diseases, and leptomeningeal malignancy. Every neurologist must be proficient in performing the procedure safely, interpreting results accurately, and managing complications.

## Indications

### Diagnostic

LP is indicated in suspected CNS infection (meningitis, encephalitis, neurosyphilis, tuberculous meningitis, fungal meningitis), suspected subarachnoid hemorrhage when CT head is negative but clinical suspicion remains high, suspected autoimmune or inflammatory CNS disease (multiple sclerosis, neuromyelitis optica, autoimmune encephalitis, neurosarcoidosis), suspected leptomeningeal carcinomatosis or CNS lymphoma, evaluation of idiopathic intracranial hypertension (IIH) for measuring opening pressure and excluding secondary causes, evaluation of normal pressure hydrocephalus (NPH) with a high-volume therapeutic tap and gait assessment before and after, suspected Guillain-Barre syndrome (to demonstrate albumino-cytological dissociation), and CSF biomarker testing for neurodegenerative disease (Alzheimer disease biomarkers, RT-QuIC for prion disease).

### Therapeutic

Therapeutic indications include CSF removal to lower ICP and relieve symptoms in idiopathic intracranial hypertension, serial therapeutic LPs to manage elevated ICP in cryptococcal meningitis, and intrathecal medication administration including chemotherapy, antibiotics, and baclofen pump trials.

## Contraindications

### Absolute

Absolute contraindications include skin infection at the LP site (cellulitis, abscess) and evidence of obstructive hydrocephalus, posterior fossa mass, or significant midline shift on imaging, which carry a risk of herniation.

### Relative

Relative contraindications include coagulopathy (INR greater than 1.5 or platelets less than 50,000/mcL, which should be corrected before proceeding), anticoagulant therapy (requiring appropriate timing relative to dosing per published guidelines), thrombocytopenia (requiring platelet transfusion if below 50,000/mcL for elective LP), elevated ICP from a mass lesion (obtain imaging first), and spinal epidural abscess at the intended level.

### When to Image Before LP

CT head should be obtained before LP in patients with altered level of consciousness, focal neurological deficits, new-onset seizures, papilledema, immunocompromised state, or a history of CNS mass lesion. A normal CT does not guarantee safety from herniation but significantly reduces risk. In suspected bacterial meningitis, antibiotics should never be delayed for LP; treatment should begin immediately, with blood cultures drawn first and LP performed as soon as safely possible thereafter.

## Procedure

### Patient Positioning

The lateral decubitus position is preferred for opening pressure measurement, with the patient lying on their side with knees drawn to the chest and neck flexed, keeping the spine perpendicular to the bed. The seated position, with the patient sitting upright and leaning forward over a bedside table, maximizes the interlaminar space but provides less reliable opening pressure measurement.

### Technique

The L3-L4 or L4-L5 interspace is identified using the iliac crest landmarks, which correspond approximately to L4. After sterile preparation, draping, and local anesthesia with 1-2% lidocaine injected subcutaneously and into deeper tissues, a 20- or 22-gauge atraumatic spinal needle (Sprotte or Whitacre) is inserted with the bevel oriented parallel to the longitudinal dural fibers to reduce post-LP headache risk. The needle is advanced with the stylet in place through the skin, subcutaneous tissue, supraspinous ligament, interspinous ligament, ligamentum flavum, epidural space, and dura-arachnoid. A "pop" or give is often felt upon entering the subarachnoid space. The stylet is removed to check for CSF flow; if there is no flow, the needle is rotated 90 degrees or advanced slightly.

### Opening Pressure

Opening pressure is measured with the patient in the lateral decubitus position and legs extended after initial positioning, using a manometer connected to the spinal needle via a three-way stopcock. Normal opening pressure in adults is 6-20 cm H2O, with up to 25 cm H2O potentially normal in obese patients. Elevated opening pressure (greater than 25 cm H2O) is seen in bacterial meningitis, cryptococcal meningitis, IIH, and venous sinus thrombosis. Low opening pressure (less than 6 cm H2O) suggests intracranial hypotension from a spontaneous or post-procedure CSF leak.

### Sample Collection

CSF is collected in sequentially numbered sterile tubes, typically four. Tube 1 is sent for cell count and differential. Tube 2 is for protein and glucose (with a concurrent serum glucose sent for ratio calculation). Tube 3 goes for microbiology (Gram stain, culture, PCR panels, AFB, and fungal culture as indicated). Tube 4 is sent for cell count and differential (for comparison with tube 1 to distinguish traumatic tap from true SAH) along with additional studies such as cytology, flow cytometry, oligoclonal bands, and special biomarkers. The total volume collected is typically 10-20 mL, with larger volumes needed for cytology or multiple specialized tests. The stylet should be replaced before withdrawing the needle, as this may reduce post-LP headache.

![Anatomical illustration of lumbar puncture technique showing needle trajectory through spinal structures](images/lumbar-puncture-technique.jpg)

## CSF Analysis

### Normal CSF Values

| Condition | WBC (cells/mcL) | Predominant Cell | Protein (mg/dL) | Glucose (CSF:serum) | Opening Pressure | Special Findings |
|---|---|---|---|---|---|---|
| Normal | 0-5 | Mononuclear | 15-45 | >0.6 | 6-20 cm H2O | Clear, colorless |
| Bacterial meningitis | 1,000-10,000+ | Neutrophils | 100-500+ | <0.4 | Elevated | Positive Gram stain/culture; lactate >35 |
| Viral meningitis | 10-500 | Lymphocytes | 50-100 | Normal (>0.6) | Normal/mildly elevated | PCR positive; early neutrophil predominance possible |
| TB meningitis | 50-500 | Lymphocytes | 100-500 | <0.4 | Elevated | AFB smear (low sensitivity); adenosine deaminase elevated |
| Fungal meningitis | 10-500 | Lymphocytes | 50-500 | <0.4 | Often markedly elevated | India ink (Crypto); antigen testing |
| MS | 0-50 | Lymphocytes | Normal or mildly elevated | Normal | Normal | Oligoclonal bands (>95%); elevated IgG index |
| GBS | 0-10 | — | Elevated (>45) | Normal | Normal | Albumino-cytological dissociation |
| SAH | Elevated RBCs | — | Elevated | Normal | Elevated | Xanthochromia (after 12 hours); consistent RBC count across tubes |
| Leptomeningeal carcinomatosis | 10-100+ | Lymphocytes/atypical cells | Elevated | Often <0.4 | Elevated | Positive cytology; flow cytometry |

Normal CSF is clear and colorless with an opening pressure of 6-20 cm H2O. The WBC count is 0-5 cells/mcL (all mononuclear) and the RBC count is 0 cells/mcL. Protein ranges from 15-45 mg/dL, and glucose from 50-80 mg/dL (with a CSF-to-serum ratio greater than 0.6). Gram stain should show no organisms, and culture should show no growth.

### Interpreting the Cell Count

Neutrophilic pleocytosis is the primary consideration for bacterial meningitis, but it can also be seen in early viral meningitis (first 24-48 hours) and early or severe fungal or tuberculous meningitis. Lymphocytic pleocytosis is seen in viral meningitis and encephalitis, tuberculous meningitis, fungal meningitis, neurosyphilis, Lyme disease, autoimmune encephalitis, leptomeningeal carcinomatosis, and neurosarcoidosis. Eosinophilic pleocytosis (greater than 10% eosinophils) suggests parasitic infections (cysticercosis, Angiostrongylus), fungal infections (Coccidioides), drug reaction, or malignancy.

### Traumatic Tap Versus Subarachnoid Hemorrhage

A traumatic tap shows a decreasing RBC count from tube 1 to tube 4, with clear supernatant and no xanthochromia. Subarachnoid hemorrhage produces a consistent RBC count across tubes, xanthochromia (yellow discoloration of the supernatant due to bilirubin from hemoglobin degradation, present 12 hours or more after hemorrhage), and elevated opening pressure. A rough correction factor for traumatic taps subtracts approximately 1 WBC for every 700-1000 RBCs in CSF, and 1 mg/dL protein for every 1000 RBCs.

### Protein Elevation

Mild elevation (45-100 mg/dL) occurs in many conditions including viral meningitis, MS, and diabetic neuropathy. Moderate elevation (100-500 mg/dL) is seen in bacterial meningitis, TB meningitis, GBS, and spinal block. Marked elevation (greater than 500 mg/dL) occurs in bacterial meningitis, spinal block (Froin syndrome), and tuberculous meningitis.

### Glucose

Low CSF glucose (hypoglycorrhachia, with a CSF-to-serum ratio less than 0.4) is found in bacterial meningitis, TB meningitis, fungal meningitis, leptomeningeal carcinomatosis, neurosarcoidosis, and chemical meningitis. Normal CSF glucose is maintained in viral meningitis, autoimmune encephalitis, MS, and usually in neurosyphilis.

### Special Studies

Oligoclonal bands (OCBs) present in CSF but not serum are found in more than 95% of MS patients; they also occur in neurosyphilis, SSPE, neurosarcoidosis, and other inflammatory conditions. The IgG index is elevated in MS and other states of intrathecal immunoglobulin production. Cytology and flow cytometry for leptomeningeal malignancy have improved sensitivity with larger volumes (at least 10 mL) and multiple LPs. CSF lactate greater than 35 mg/dL supports bacterial meningitis and is useful when the Gram stain is negative and antibiotics have already been started.

![Table summarizing CSF profiles in bacterial, viral, tuberculous, fungal meningitis, and subarachnoid hemorrhage](images/csf-profiles-table.jpg)

## Complications

### Post-Lumbar Puncture Headache (PLPH)

Post-LP headache is the most common complication, occurring in 10-30% of cases with cutting needles and 2-12% with atraumatic needles. It presents as a postural headache that is worse when upright and improved when supine, with onset within 24-48 hours of the procedure. Associated symptoms include nausea, neck stiffness, tinnitus, and photophobia. Prevention strategies include using atraumatic needles (Sprotte, Whitacre), smaller gauge needles, and replacing the stylet before withdrawal; bed rest has not been proven to prevent PLPH. Treatment begins with conservative measures including caffeine (300-500 mg orally or IV), hydration, and analgesics. For symptoms persisting beyond 24-48 hours, an epidural blood patch has a success rate greater than 85%.

### Other Complications

Infection (meningitis) is extremely rare with proper sterile technique. Bleeding, including epidural or subdural hematoma, has increased risk with coagulopathy. Nerve root irritation manifests as transient radiculopathy with sharp pain radiating to the leg during needle insertion, requiring repositioning of the needle. Cerebral herniation is rare but catastrophic and is avoided by appropriate pre-LP imaging. Back pain is common and usually self-limited, with local site tenderness persisting for 1-3 days.

![Algorithm for management of post-lumbar puncture headache](images/plph-management.jpg)

## Clinical Pearls

Atraumatic (non-cutting) spinal needles significantly reduce the risk of post-LP headache and should be used routinely; there is no evidence supporting bed rest after LP for headache prevention. A normal CT head does not completely eliminate the risk of herniation; clinical judgment remains essential, and LP should be deferred if there are signs of impending herniation regardless of CT findings. When evaluating for subarachnoid hemorrhage with LP, xanthochromia is the critical finding, and it takes at least 12 hours to develop after hemorrhage, so very early LPs may show RBCs without xanthochromia. In suspected bacterial meningitis, antibiotics should never be delayed for LP; blood cultures should be drawn, antibiotics started, and LP performed as soon as safely possible thereafter. CSF oligoclonal bands are found in more than 95% of MS patients and remain a key diagnostic criterion; their absence should prompt reconsideration of the diagnosis.

## References

1. Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. *Alzheimers Dement (Amst)*. 2017;8:111-126.
2. Arevalo-Rodriguez I, Ciapponi A, Roquei Figuls M, et al. Posture and fluids for preventing post-dural puncture headache. *Cochrane Database Syst Rev*. 2016;3(3):CD009199.
3. Nath S, Koziarz A, Badhiwala JH, et al. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. *Lancet*. 2018;391(10126):1197-1204.
4. Deisenhammer F, Bartos A, Egg R, et al. Guidelines on routine cerebrospinal fluid analysis: report from an EFNS task force. *Eur J Neurol*. 2006;13(9):913-922.