Intrathecal Gadolinium-Enhanced MR Cisternography in the Evaluation of CSF Leakage

Discussion

Radiologic identification of the site of CSF leakage is important for presurgical planning, because accurate localization of the CSF leak increases the surgical success rate. Diagnostic methods used in the evaluation of CSF leakage have evolved during the past several decades. HRCT with direct coronal and/or axial sections has a sensitivity of 84%–95%^12,21; however, this technique relies on indirect signs (eg, fractures of the skull base, bony lesions or defects, mucosa swelling, fluid levels in the paranasal sinus, pneumoencephalos, and meningoencephalocele) to detect the site of the leak. Therefore, the question arises as to whether a defect depicted by HRCT is truly correlated with the site of the CSF fistula. Wenzel and Leppien²² reported a case of CSF rhinorrhea following posterior fossa surgery due to an acoustic schwannoma; in this patient, HRCT suggested a CSF leak laterally into the mastoid, whereas Gd-MRC clearly showed communication into the petrous pyramid adjacent to the internal auditory canal. In cases with multiple defects or fractures of the skull base, it may not be possible to determine the precise localization of the leak via HRCT.

MR imaging provides excellent anatomic depiction of the CSF spaces and surrounding tissues. However, in cases of suspected CSF leakage, further imaging evaluation may be required. Previous studies have indicated that unenhanced coronal T2-weighted MR imaging has the capability of demonstrating CSF fistulas; however, there is a relatively high incidence of false-positive findings (42%), especially in the presence of paranasal sinus disease.^21,23,24 False-negative findings have also been reported on nonenhanced MR images from patients who subsequently exhibited skull base fractures and frank CSF leaks during surgery.²³ Therefore, T2-weighted images were not included in our imaging protocol due to the high rate of false-negative and false-positive findings.

CTC is accepted as the most accurate method for the investigation of active cranial CSF leakage, but it has a number of disadvantages. The sensitivity of CTC ranges between 72% and 81%,^3,25 and CTC may have problems in detecting low-flow fistulas or fistulas with only hairlike communications. This is because iodinated contrast media do not distribute freely in the CSF spaces due to their tendency to form sediment or because the tiny amount of dilute contrast medium that leaks through a fistula cannot be distinguished from the surrounding bone. Wenzel and Leppien²² presented a case in which a CSF fistula was detected only by contrast-enhanced MR cisternography, whereas CTC did not show abnormal CSF communication. In these cases, Gd-DTPA may have certain advantages because it is distributed freely in the subarachnoid space and MR imaging offers much higher contrast resolution. To further increase sensitivity, one could examine patients in the prone position or apply the Valsalva maneuver; however, the Valsalva maneuver remains controversial and is not widely used.^11,12

The Biologic Effects of Ionizing Radiation VII report²⁶ published in 2005 by the National Academy of Sciences suggested significant increased risk of developing cancer from a single radiation exposure of 10 mSv. The authors recommended that care should be exercised in the use of CT in adults ≤40 years of age. It is obvious that the dose in CTC is also high with multisection CT when both HRCT and CTC images are obtained. Additional delayed scans are frequently required in slow-flow fistulas, and CT fluoroscopy is required to construct cine images for high-volume fistulas. Considering the high doses of radiation and the lack of criterion-standard sensitivity of the CTC, it is logical that safer and more reliable techniques are required to detect CSF leakage.²⁷

Many studies have supported the safety of intravenously administered Gd-DTPA. Although some potential adverse systemic effects have been reported, the incidences of these side effects are low.^28–33 Nausea or vomiting and headache are the most common side effects, with frequencies ranging from 0.26% to 0.42%.²⁸ Other rare reactions reported after the intravenous administration of Gd products include paresthesia, dizziness, focal convulsions, urticaria, cardiovascular reactions (eg, tachycardia and arrhythmia), laryngospasm, and anaphylactic shock.^28–31 In addition, nephrogenic systemic fibrosis characterized by skin thickening resembling scleroderma has been recently described as one of the adverse effects following Gd administration in patients with renal failure.³²

Animal studies have demonstrated the practical applicability of Gd-MRC in detecting the sites of surgically induced nasoethmoidal CSF fistulas.^34–36

In 2 previous reports, the behavioral and neurologic alterations were observed only after the intraventricular injection of relatively high doses of Gd; no such behavioral or morphologic changes were observed in the same studies when the total dose was limited to <3.3 μmol/g brain in 15 μL.^37,38 However, several recent studies reported intrathecal Gd-induced encephalopathy in humans after the accidental intrathecal injection of a high dose of Gd.^39,40 In these cases, the patients developed severe neurologic symptoms, such as dysarthria, blurred vision, nystagmus, ataxia, and somnolence, followed by behavioral disturbances and psychotic symptoms.

Intrathecal Gd-DTPA is currently used to identify potential CSF fistulas in patients with rhinorrhea. In the first prospective human trial, no significant gross neurologic abnormalities, CSF changes, electroencephalographic alterations, MR morphologic evidence, or MR signal intensity changes were observed during the initial examination or during follow-up clinicoradiologic studies.⁴¹ With a total volume of 0.5–1.0 mL, the estimated intrathecal dose per gram of brain in this trial was much lower than the dose used in animal experiments (0.07–0.36 versus 2.5–15 μmol/g brain).^37,38,42,43 Reiche et al⁴⁴ and Aydin et al⁴⁵ used the same technique to evaluate CSF fistulas, and a multicenter human study performed by Tali et al⁴³ evaluated the safety and clinical response to Gd-DTPA in 95 patients who presented clinically with a variety of cranial or spinal signs and symptoms. A recent study demonstrated the safety of low-dose intrathecal Gd application in pediatric patients.⁴⁶ In addition, a large case series published by Aydin et al⁴⁷ demonstrated the relative safety and tolerability of low-dose (0.5 mL) intrathecal Gd administration in the evaluation of CSF fistulas. However, the long-term effects of intrathecal Gd in large numbers of patients are not known.

In our series, CSF fistulas were not observed in 21 patients (25%), mostly in groups 3 and 4. One possible explanation is that the patients included in the study were clinically suspected of having CSF leakage, but their symptoms were, in fact, related to other causes. In addition, 10 of these patients showed no rhinorrhea during imaging, so there was probably no leakage during that period. Negative findings may also have been related to slow-flow fistulas. Thus, rhinorrhea must be present at the time of imaging to obtain good results. The patients without demonstrable CSF fistulas showed no persistent symptoms, and during the follow-up period, they showed no fistula complications.

Furthermore, we encountered an interesting case in which the patient developed a leak from a defect in the medial wall of the middle cranial fossa into the infratemporal fossa following trauma; to our knowledge, no such case has been reported in previous series. In addition, leakage into the middle ear cavity from a defect in the mastoid bone was detected in 6 patients with otorrhea following trauma. Finally, leakage into the sphenoid sinus was demonstrated in 8 patients who had undergone sellar surgery.

Dural repair was performed in 64 patients diagnosed with CSF leakage. Probable rhinorrhea occurred in only 1 patient approximately 1 week after treatment. Control MR cisternography was performed in this patient, and images obtained in the first hour showed probable leakage, which became obvious in images from the third and fifth hours. These observations emphasize the importance of late control images. In patients with strongly suspected leakage, combining early images with the late images increases the diagnostic value of the procedure.

As in previous studies, no early or late complications due to the intrathecal administration of Gd were observed in the present study. However, 5 patients experiencing postprocedural postural headache lasting <24 hours were treated with conservative measures. The mean incidence for postural headache reported here (8%) falls within the lower range of values reported in previous studies (4%–49%).⁴⁸ Furthermore, the cases of postprocedural headache encountered here were consistent in type and frequency with those observed after either water-soluble iodinated contrast material−enhanced myelographic procedures or simple diagnostic lumbar puncture. Thus, this subjective complaint is likely due to the lumbar tap (ie, iatrogenic CSF space postural hypotension associated with needle puncture−related transient CSF leakage) and not Gd-MRC.

In conclusion, MRC after the intrathecal administration of Gd-DTPA represents an effective and minimally invasive method for evaluating suspected CSF fistulas along the skull base. It provides multiplanar capabilities without risk of radiation exposure and an excellent approach to depict the anatomy of CSF spaces and CSF fistulas.