Neurology 101: CSF profiling

Before the lumbar puncture, fluid from the nervous system was extracted via surgical means–often at great risk to the patient, and often with little benefit. When Heinrich Quincke finally described a dramatically safer technique of CSF sampling from the lumbar cistern, the world caught on. 20 years later… In this week’s BrainWaves episode, Mike Rubenstein and I go over the fundamentals of CSF, from production to diagnostic utility. It’s a longer episode, but one worth getting into.

First we discuss intracranial pressure (ICP). A normal ICP is less than 10 cm of water in infants, less than about 15 cm water in children, and less than 20 cm water in adults. When you see elevated ICP, you should be thinking of meningitis, tumors, intracranial hemorrhage, venous sinus thrombosis, pseudotumor cerebri, and a long list of other conditions.

 

What should cerebrospinal fluid look like? It should be clear, a lot like tap water. And if it’s not, you better put your thinking cap on. It can be red or pink from accidental perforation of a vessel (“traumatic tap”), or from subarachnoid hemorrhage. We talk about how to distinguish these in detail because it’s critical to differentiate this on a lumbar puncture. Besides the presence of red blood cells, elevated white blood cells (WBCs) indicates inflammation in the central nervous system.

  • 1,000 WBCs per HPF is bacterial meningitis until proven otherwise
  • 100-1000 WBCs = viral or fungal causes of meningitis, encephalitis, or myelitis
  • <100 WBCs = demyelinating, autoimmune, and other inflammatory disorders

Protein often follows suit with the WBCs. But sometimes it can be high in non-inflammatory situations. The CSF protein may also be falsely elevated in patients with subarachnoid blood or a traumatic tap, and can be corrected by 1mg/dL for every 1,000 RBCs. If the protein is elevated out of proportion to WBCs, or there are no WBCs, this albuminocytologic dissociation is very typical of Guillain-Barre Syndrome and CIDP. However, in the first week or so of GBS, protein levels may still be normal, and a repeat tap could be helpful. Protein can be falsely elevated in healthy patients under the following circumstances:

  • Neonates (protein up to 150 mg/dL is ok. By 6-12 months, the range of 15-50 mg/dL becomes the norm.)
  • Bedridden patients
  • Obese patients
  • Diabetics
  • Renal disease
  • Hypothyroidism
  • Spinal stenosis/Spinal block
  • Tobacco, alcohol users

More specific than just the total protein (which reflects CSF albumin), are the particular proteins you can quantitate. Like antibodies and oligoclonal bands (OCBs). Just look at the table below for conditions where you can find OCBs besides in demyelinating disease.

Our last chapter of the episode features a discussion on CSF analysis at pertains to neuroinfectious disease. Almost every aspect of basic CSF chemistry can lead you to finding an infectious cause: for bacterial meningitis, elevated opening pressure, extremely high WBC count, extremely high protein, and low glucose, but the gold standard remains the culture. Gram stain can give you some insight into which bacterial pathogen may be likely, and usually these patients will already be on broad-spectrum antibiotics, but the culture is still required. Cultures for typical bacterial pathogens, depending on the lab, may return within hours or a few days, but cultures for acid fast bacilli—things like tuberculosis—could take up to 2 weeks and often require a large volume of CSF. We also used to culture for viruses to grow the virus, but now real-time PCR can amplify specific viruses much more rapidly.

Additionally, there is a whole host of other, ancillary diagnostic testing you could consider, but we are running short on time. For instance, CSF lactate is one of the common indicators of mitochondrial disease, but it can also be high infectious disease and seizures. Unfortunately, we’re quite out of time here. So tap into the episode for more info.

 

[Jim Siegler]


The content in this episode was vetted and approved by Mike Rubenstein.

REFERENCES

Frederiks JA and Koehler PJ. The first lumbar puncture. J Hist Neurosci. 1997;6:147-53.

Seehusen DA, Reeves MM and Fomin DA. Cerebrospinal fluid analysis. Am Fam Physician. 2003;68:1103-8.

Shah KH and Edlow JA. Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage. J Emerg Med. 2002;23:67-74.

Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, Sellebjerg F and Force ET. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2006;13:913-22.

Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, Greenberg B, Russman AN, Katzan I, Gardner CJ, Hausler M, Nau R, Saraya T, Wada H, Goto H, de Martino M, Ueno M, Brown WD, Terborg C and Gilden DH. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70:853-60.

Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL and Dominguez SR. Acute flaccid myelitis: A clinical review of US cases 2012-2015. Annals of neurology. 2016;80:326-38.

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