CSF Leaks

Kevin C. Welch, MD

Introduction
A disruption (a hole or tear) in the brain lining (called the dura) and the bone separating the brain and the sinuses will result in the drainage of fluid that normally surrounds the brain into the sinuses. This fluid is known as cerebrospinal fluid or "CSF." Drainage of CSF into the sinuses can result in a multitude of problems, not to mention the often times annoying constancy of nasal dripping.

This article discusses current concepts in the causes and diagnosis as well as treatment of CSF leaks.

Anatomy and Physiology
Cerebrospinal fluid consists of a mixture of water, electrolytes, glucose, amino acids and various proteins. Cerebrospinal fluid is colorless, clear, and usually does not contain any cells. The primary site of CSF production is the choroid plexus (an area within the brain), which is responsible for 50-80% of its daily production.

All these sites produce CSF at a rate of approximately 20 mL/hr for a total of approximately 500 mL daily. At any given time, there is approximately 90-150 mL of CSF circulating throughout the central nervous system (CNS, which includes the brain and spinal cord). Cerebrospinal fluid circulates around the brain and spinal cord within the subarachnoid space.


causes
In the adult patient, it is helpful to broadly classify CSF leaks into two categories: spontaneous CSF leaks and CSF leaks that are caused by injury to the bone separating the brain and the sinuses (known as the skull base: you can read the Patient Education topic Skull Base Anatomy for more information about this region). These include CSF leaks that are traumatic, caused by surgery (a.k.a. iatrogenic), and by tumors.

Accidental Trauma: Penetrating and closed-head trauma cause 90% of all cases of CSF leaks. Cerebrospinal fluid rhinorrhea (CSF leaking out of the nose) following a traumatic injury is classified as immediate (within 48 hours) or delayed. Of patients with delayed CSF leaks, 95% present within 3 months after the injury. Most patients with an injury causing CSF leaks are identified within 48 hours.

Surgical Trauma: Surgical trauma can occur during endoscopic sinus surgery or during neurosurgical procedures. These injuries occur along the bone separating the sinuses from the brain, or skull base and through the lining of the brain. Skull base injuries vary from simple cracks in the bone to large holes with potential injury to the brain.

Tumor-related CSF Rhinorrhea: It is uncommon for the growth of benign tumors to result in CSF rhinorrhea. However, aggressive benign tumors (such as inverted papilloma) and cancers can either erode or invade the bone of the skull base. The breakdown or destruction of the bone results in disruption of these barriers. If a leak is not present before surgery, very frequently the removal of these tumors results in an immediate CSF leak that is typically repaired at the time of the surgery.

Spontaneous CSF Rhinorrhea: Spontaneous CSF leaks occur in patients without any of the previous causes discussed. Recent evidence has led us to realize that spontaneous CSF leaks are probably due to elevated intracranial pressure (ICP). Intracranial pressure is a different pressure from blood pressure, which most patients are familiar with, and is measured in a completely different way. The causes of elevated ICP can be multiple; nevertheless, once elevated ICP develops, the pressure exerted on areas of the anterior skull base result in thinning of the bone. Ultimately, the bone is weakened until a defect (hole) is formed and a leak begins. The dura (brain lining) or a part of the brain may actually protrude through the weakened part of the bone (this is known as an encephalocele).

Clinical
History: A thorough history is the first step toward accurate diagnosis. The presentation of a CSF leak is typical: Clear, watery discharge that often occurs only on one side of the nose. Often the discharge is continuous, but it may be sporadic and related to certain activities. This drainage may be reproducible by bending over or by straining. Patients may report a metallic or salty taste. Many patients with spontaneous leaks often are diagnosed with allergies or sinus infections and are unsuccessfully treated, often for many months, with antihistamines, nose sprays, and antibiotics.

Patients with recurrent meningitis (multiple episodes), especially pneumococcal meningitis, should be evaluated for a CSF leak, regardless of the presence of active clear nasal discharge.

A history of headaches, ringing in the ears and blurry vision may suggest increased intracranial pressure. In these patients, MRI and CT may reveal signs of increased intracranial pressure, such as empty sella syndrome or arachnoid pits, radiologic findings which can be shown and described to you by your surgeon.

Physical Exam: Physical examination includes a complete head and neck examination. Nasal endoscopy (looking into the deeper portion of the nose and sinuses with an endoscope) is very helpful, especially in a patient who has undergone sinus surgery. Examination may reveal clear discharge, a skull base defect (if traumatic or surgically caused) or a mass, such as a tumor or encephalocele. In many cases, however, physical examination and nasal endoscopy are normal and the physician must base his or her decisions on history alone.

In patients with head trauma, the mixture of blood and CSF may make the diagnosis difficult. Cerebrospinal mixed with blood forms a "halo sign" when dripped on filter paper. However, the presence of a halo sign is not exclusive to CSF and can lead to false-positive results. The clinical findings most frequently associated with CSF rhinorrhea are meningitis (30%) and pneumocephalus (30%).

WORKUP
There are a number of laboratory and imaging studies that can be ordered to confirm the presence of a CSF leak. The ones listed here are the most common.

  1. Lab Studies
    1. Beta-2 transferrin
      1. Beta2-transferrin is a protein found nearly exclusively in CSF and can be identified in the nasal drainage.
      2. Beta-2 transferrin is stable at room temperature for approximately 4 hours; therefore, patients must store the collected fluid in a refrigerator immediately. Specimens should not be frozen.
      3. Beta-2 transferrin is the single best lab test for identifying the presence of CSF in nasal fluid.
  2. Imaging Studies
    1. Computed Tomography (CAT) scanning
      1. High-resolution CAT scanning is the best form of diagnostic imaging for identifying a CSF leak.
      2. CAT scans may demonstrate skull base defects resulting from accidental or iatrogenic trauma, an underlying anatomic or developmental abnormality, or a tumor.
    2. Magnetic Resonance Imaging (MRI)
      1. Unlike CAT scanning, MRI does not show bone well; therefore, it is difficult to see cracks in the skull base bone.
      2. MRI typically is not recommended as a first line imaging method in the evaluation of CSF leaks unless a tumor or a mass such as an encephalocele is seen on exam or suspected.
    3. CT Cisternography
      1. The diagnostic yield of CAT scan can be improved by injecting contrast into the spinal canal (this is called a cisternogram).
      2. CT cisternography can show the precise location of a CSF leak in most patients who have active clear nasal drainage.
      3. The disadvantages of CT cisternography include the fact that patients with intermittent CSF leaks may have false negative (may not show a problem when  a patient actually has it) studies and patients need to have a spinal tap in order to have the procedure.
    4. Nuclear Medicine Studies
      1. Nuclear isotopes (types of substances in the body we can trace) are injected into the spinal canal. When these isotopes circulate around the brain, they may leak into the nose or sinuses and collect on cotton pads inserted into the nose. After a number of hours, these pads are removed and analyzed for the presence of these nuclear isotopes.
      2. This study is safe, but it cannot precisely identify the location of the leak. The isotope is also absorbed into the circulatory system and can leak into the nose and sinus via the normal blood stream. Lastly, the study is incorrectly positive for a CSF leak in as many as 33% patients, so this procedure is no longer commonly used.
Diagnostic Procedures
The injection of a dye known as fluorescein (which shows up as a bright fluorescent greenish yellow color) into the spinal canal has been used to diagnose and localize the site(s) of CSF leaks.
  1. The US Food and Drug Administration has not approved the use of fluorescein for the diagnosis or treatment of CSF leaks; however, when used properly, it is safe.
  2. A small volume of the patient's own CSF is collected and a very small amount of fluorescein is mixed into this CSF and placed back into the patient. The fluorescein can also be mixed with sterile, preservative-free saline (salt water) and used in this way as well.
  3. Nasal endoscopy is performed approximately 30 minutes after the fluorescein/CSF mixture or fluorescein/saline mixture is injected.
  4. In most instances, fluorescein is directly observable within the nose and sinuses during nasal endoscopy and it appears as a bright neon green-yellow liquid. However, very small defects may leak only a very small amount of fluorescein, and this may be difficult to observe.

Treatment
Please see the following article for treatment of CSF leaks. There are many treatments for CSF leaks, and you should discuss the most appropriate work-up and treatment with your rhinologist.

Conclusion
Cerebrospinal fluid leaks, regardless of cause, are conditions that should be addressed by a rhinologist as soon as identified in order to avoid long-term complications such as meningitis, brain abscess (pus in the brain), and other infectious complications.


Revised 01/20/2015
©American Rhinologic Society