Cerebrospinal Fluid Leak Imaging
- Author: Hugh J F Robertson, MD, DMR, FRCPC, FRCR, FACR; Chief Editor: L Gill Naul, MD more...
Cerebrospinal fluid (CSF) leak may occur from the nose (rhinorrhea), from the external auditory canal (otorrhea), or from a traumatic or operative defect in the skull or spine. The fluid leak is a result of meningeal dural and arachnoid laceration with fistula formation. Blunt trauma is the most common cause. See the images below.
A suggested algorithm for the diagnosis of a CSF fistula follows.
Fluid leaking from the nose or external auditory canal must first be positively identified as CSF. Drops of fluid from a CSF leak placed on absorbent filter paper may result in the double-ring sign, a central circle of blood and an outer clear ring of CSF. Serum glucose, chloride, and total protein tests of the fluid are not specific or conclusive for CSF.
Confirm or exclude the presence of CSF in leaking fluid by means of an immunoelectrophoretic study of the fluid for beta-2 transferrin (B2Tr) or, where available, beta-trace protein.
For this specialized laboratory study, 0.5-1.0 mL of the fluid may be required. An absorptive sponge pad placed at or near the presumed site of fluid leak can facilitate the collection of the fluid. The enzyme B2Tr is produced in the brain by neuraminidase activity and is present in CSF, perilymph, and ocular aqueous humor but not in sinonasal mucous secretions and tears. This feature is the basis for a specific test for CSF based on immunoelectrophoresis. B2Tr may be found in blood serum in liver disease, such as in chronic alcoholism and in patients with inborn errors of glycoprotein metabolism or genetic variants of transferrin.
Beta-trace protein is prostaglandin D2 synthase. It is produced in epithelial cells of the choroid plexus and meninges and is found in CSF, perilymph, seminal fluid, and urine. It is approximately 35 times more concentrated in CSF than in blood serum. Immunoelectrophoretic assay of beta-trace protein has been reported to have high specificity and sensitivity for CSF detection.
Perform magnetic resonance (MR) cisternography. This study may also be useful for detecting inactive fistulas.
CT cisternography or radionuclide cisternography may be useful if CT and MR cisternography do not show the CSF fistula. Radionuclide cisternography may be useful to detect an intermittently active CSF fistula. Cisternography with an intrathecal injection of radioisotope or nonionic iodinated myelographic contrast medium or magnetic resonance imaging (MRI) cisternography usually localizes the CSF leak.
Brain and spinal MRI is useful in demonstrating meningocele and meningoencephalocele when associated with CSF leak, as well as for examining patients with spontaneous intracranial hypotension syndrome.[5, 6, 7]
On occasion, the methods listed above do not localize the CSF fistula, and surgical exploration may be necessary.
All methods of cisternography—radionuclide, CT, and MR—provide improved or optimal CSF fistula detection when the fistula is active and when a Valsalva maneuver or jugular venous compression is added to the imaging protocol. CSF fistula can usually be demonstrated by using some method of cisternography. Localization of the leak to the right or left nasal cavity may be difficult because of the tendency of the fluid to cross sides and flow from both nostrils. In a study of 4 patients who underwent radionuclide cisternography, as well as MRI and/or CT, for suspected CSF leaks, Thomas et al found that radionuclide cisternography accurately detected and localized the leaks in all patients. Each patient subsequently underwent a procedure for an epidural blood patch, and all patients experienced symptomatic relief.[8, 9, 2, 4, 10]
Methods for detecting CSF fistulas with intrathecal injections of dye pose a risk of chemical meningitis. Methylene blue, indigo carmine, and phenolsulfonphthalein (PSP) dyes are no longer in use. Some otolaryngologists use a dilute solution of fluorescein to localize CSF fistulas both preoperatively and during surgery. Typically, 0.5 mL of a 10% fluorescein solution is injected into the lumbar subarachnoid space over more than 1 minute. Cotton pledgets are placed in the nose, as for radionuclide cisternography. The dye reaches the skull base in 6 hours and is present over the cerebral convexities in 24 hours. The pledgets are examined for green fluorescence in a dark room with ultraviolet light 6 hours after the intrathecal PSP injection.
Skull radiographs are of limited diagnostic use in cerebrospinal fluid (CSF) leaks, but they may show a relevant skull fracture or the presence of empty sella.
CT findings associated with cerebrospinal fluid leaks include fractures or other bone defects; meningocele; focal fluid accumulation in the ethmoid air cells; frontal, sphenoid, or maxillary sinuses or mastoid air cells; and, sometimes, pneumocephalus. See images below.
CT cranial cisternography is performed with injection of 5-7 mL of nonionic myelographic contrast medium into the lumbar subarachnoid space. The patient is maintained in the prone position until a CT scan is performed. Ideally, the contrast medium is concentrated in the intracranial anterior and posterior skull base regions under fluoroscopic guidance by tilting the prone patient head downward on a fluoroscopic tilt table. Alternatively, with the patient lying prone on a stretcher, the patient's hips can be raised above the level of the head for 1-2 minutes to concentrate the contrast medium over the anterior and posterior regions of the skull base. Coronal CT images of 2-3 mm thickness are then obtained through the face and cranium, including all of the paranasal sinuses and the mastoid air cells.
CT myelography is used in the detection of spinal CSF leak. Slow CSF leaks may be detected by postmyelogram CT scan in which there is a time delay between the contrast medium intrathecal injection in the fluoroscopic room and subsequent transfer to the CT scan room. Fast CSF leaks have rapid contrast diffusion and may not be localized to a 2-vertebral segment of the spinal canal (suitable for local treatment by extradural blood patch or alternate therapy) by routine postmyelogram CT spine scan. A high percentage of fast leaks have spinal extradural fluid collections on preliminary MRI spine scans. Dynamic CT myelography is recommended in these patients, with the injection of the iodinated contrast medium intrathecal on the CT scan table with immediate spine CT scan.
CT cisternographic findings in CSF leak include the concentration of contrast medium in portions of a paranasal sinus or within ethmoid or mastoid air cells. Occasionally, a stream of contrast medium is demonstrated at the fistula site.
Digital subtraction radiographic cisternography can be similarly performed with a spinal subarachnoid injection of nonionic iodinated contrast medium. The images may demonstrate a CSF fistula, but this technique is used less frequently than other cisternographic methods.
Degree of confidence
The incidence of cerebrospinal fluid (CSF) fistula detection varies from 22-100% in clinical studies. The fistula detection rate is lowest for intermittent CSF leaks. The accuracy of active fistula detection with CT cisternography is 65-85%. In one study of 45 patients, CT of the skull and facial bones with high-resolution, thin-section axial and coronal images had an accuracy of 92%, a sensitivity of 92%, and a specificity of 100% in depicting the presence or absence of CSF fistula. Contemporary computer-reconstructed coronal images are usually of diagnostic quality, and direct CT coronal images may not be necessary.
Magnetic Resonance Imaging
Brain tissue herniation is best seen on MRI. Herniation of the inferior frontal gyrus may occur in frontal head injuries or in ethmoid developmental defects of the cribriform plate. Temporal lobe gyral herniation may occur through a petrous temporal bone tegmen tympani defect.[14, 15] See images below.
In spontaneous intracranial hypotension syndrome (SIHS), brain MRI shows thickening and contrast enhancement in the cranial pachymeninges. Subdural hygroma or hematoma on the cerebral convexities is common. The brain is noted to sink downward in the cranium with development of a pseudo-Chiari I malformation. The cerebral dural venous sinuses may be engorged. The cerebral ventricles may be reduced in size, and the pituitary gland may appear enlarged. There may be apparent downward displacement of the optic chiasm. The upper cervical epidural veins are congested. All of these changes are reversible with ablation of the cause of CSF leak, which is usually in the spine.
Spinal MRI in patients with SIHS may show some irregularity of the thecal sac due to partial dural collapse. Extradural fluid collections are common in spinal cerebrospinal fluid (CSF) leak. Intense extradural contrast enhancement is noted in congested epidural veins. One or more CSF fistulas may originate from spinal nerve root sleeves in the case of spontaneous spinal CSF leak.
The localization of one or multiple leaks can make possible and facilitate therapeutic CT-guided epidural blood patching.
A variety of cisternographic studies may be necessary to localize some spinal CSF fistulas. Spinal MRI findings are also potentially reversible after successful ablation of a CSF fistula.
MR cisternography and myelography
MR cisternography and myelography can accurately localize CSF leaks in the cranium and spine.[17, 18, 19, 20] This technique is based on the intrinsic T2 contrast between CSF and adjacent structures. A positive diagnosis of CSF fistula is made by finding direct continuity of the CSF fistula with the subarachnoid space. Coronal and sagittal imaging is necessary. See images below.
The high T2 signal from CSF fistula may be difficult to differentiate from that of sinusitis on axial images. A high rate of fistula detection may be possible with imaging in the prone position, but this may be uncomfortable for the patient. Therefore, imaging is usually done with the patient in the supine position. Rapid echo-planar imaging with the patient in the prone position and performing a Valsalva maneuver may allow for limited coronal imaging and increase the accuracy of MR cisternography.
MR cisternography is performed with heavily T2-weighted, fast spin-echo, fat-saturated sequences with thin sections and minimal or no gap. Typical imaging parameters include a repetition time of 10,000 ms, an effective echo time of 200 ms, 4 signals acquired, an echo train length of 16, a matrix of 512 X 192, no phase-wrap option, 3-mm sections interleaved contiguously (0-mm gap), and a 16-cm field of view.
A short repetition time can be used to achieve a result similar to that of the technique above, with slightly faster imaging times. The gray scale is reversed for optimal viewing. With one method, the average total time for coronal and sagittal imaging is 48 minutes. Most MRI machines offer fat suppression and image gray-scale reversal. Additional hardware or software is not required to perform MR myelography or cisternography.
MR cisternography may demonstrate inactive CSF fistulas. MR T2 myelography may demonstrate spinal CSF fistulas (see the images below). The intrathecal injection of 0.5 mL of gadopentetate dimeglumine diluted in 3-5 mL of CSF for MR cisternography has been reported to have high sensitivity and specificity for detection of active CSF fistula, exceeding the rate of fistula demonstration by CT, nuclear medicine, or noncontrasted MR cisternography.
Small series of patients had no apparent adverse effect from the gadolinium contrast medium.[19, 22] Gadolinium-based contrast media are approved for intravenous injection for MRI but have not been approved for intrathecal use in humans by the Food and Drug Administration (FDA). The intrathecal injection of gadolinium-based contrast media has been shown in several off-label studies to be effective and safe in selected patients in whom other cisternographic or myelographic studies have failed to demonstrate the CSF leak site.[23, 24] Severe brain injury has been reported in a patient who received erroneously 30 times the intended dose of gadolinium in an MRI myelogram.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], and gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Systemic Fibrosis.
NSF/NFD has occurred in patients with moderate to end-stage renal disease who have been given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the sclera of the eyes; joint stiffness with difficulty moving or straightening the arms, hands, legs, or feet; pain deep in the hips or ribs; and muscle weakness. For more information, see Medscape.
Degree of confidence
In one study, the detection of cerebrospinal fluid (CSF) fistula by MR cisternography had an accuracy of 89%, a sensitivity of 87%, and a specificity of 100%.
A study of 50 patients without a cerebrospinal fluid (CSF) leak who had an MRI brain scan showed a 42% false-positive rate for cribriform plate fistula, which was likely related to high T2 signal in ethmoid air cells from associated sinusitis or apparent defects in dura or bone from irregular superior ethmoid bone surfaces.
Diagnostic ultrasound has not been useful in cranial cerebrospinal fluid (CSF) leak. Paraspinal fluid collections can be localized for needle aspiration with ultrasound guidance.
Radionuclide cisternography is currently performed by administering a lumbar subarachnoid intrathecal injection of indium, Indium-111 (111 In) diethylenetriamine pentaacetic acid (DTPA), in a 500 µCi dose.111 In has minimal background activity and does not accumulate in the brain. Technetium as 99m Tc DTPA is a less frequently used isotope. See images below.
Head images are acquired 2, 6, 12, and 24 hours after injection of the isotope. Follow-up 48- or 72-hour scans are possible with111 In and may be useful in the detection of intermittent cerebrospinal fluid (CSF) fluid leaks.
The entire spine is scanned up to 24 hours in cases of spontaneous intracranial hypotension, spinal trauma, or postoperative CSF leaks. Cotton pledgets labeled for the placement site are positioned in the nose before the lumbar subarachnoid space injection of the isotope. Pledgets are placed close to the cribriform plate, in the middle meatus, and in the sphenoethmoidal recess of the right and left nasal cavities. A control pledget for lacrimal secretions is placed under one inferior nasal turbinate.
Pledgets are scanned in a glass tube at intervals of 2-24 hours with the highest count rate indicating a possible leak site. Alternatively, radioactivity of the nasal pledgets is compared with that of known plasma radioactivity.
For otorrhea, 1 cotton pledget is placed in each external auditory canal.
Degree of confidence
The sensitivity for cerebrospinal fluid (CSF) leaks is in the range of 50-100%. The specificity is almost 100% for contemporary radionuclide cisternography.
Cerebral arteriography is not used in the diagnostic imaging workup to localize the site of a cerebrospinal fluid (CSF) leak. Arterial injury may occur with skull trauma that causes CSF leakage. CTA, MRA, or digital subtraction cerebral and cervical arteriography may then be necessary.
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