Aseptic Meningoencephalitis after Iohexol CT Myelography

SUMMARY: We describe the case of a patient with aseptic meningoencephalitis after intrathecal iohexol injection for myelography and review the previous literature on similar cases of contrast-induced neurotoxicity.


Discussion
Intrathecal injection of ionic, water-soluble contrast agents, first used in the United States in 1931, was associated with significant meningeal irritation and therefore was never popularized. 1 Metrizamide, developed in the late 1960s, was the first of a newer generation of nonionic, water-soluble contrast agents that were better tolerated. 2 Aseptic meningitis was still reported in approximately 5% of these myelograms. 3 Newer agents such as iohexol and iopamidol replaced metrizamide, as comparative trials showed a decreased incidence of severe adverse neurologic effects with these agents. 4,5 Iohexol is a popular nonionic, water-soluble, radiographic contrast medium for myelography with an iodine content of 46.36%. Omnipaque 240, 300, and 350 contain 240 mg, 300 mg, and 350 mg of organic iodine per milliliter, respectively. The osmolarity of Omnipaque 240, 300, and 350 is 391 mOsm/L, 465 mOsm/L, and 541 mOsm/L, respectively, compared with 285 mOsm/L of plasma and 301 mOsm/L of CSF.
The most common minor adverse effects after iohexol myelography are headache (11% to 21%), 5,6 nausea (10%), vomiting (3%), and dizziness (3%). 5 Mild neckache and backache are also not unusual. Complications of myelography include seizure, aseptic meningitis, 7-10 meningoencephalitis, 11-13 bacterial meningitis, 14 intracranial hemorrhage, 15 spinal hematoma, 16 encephalopathy, 17 transient confusion, 18,19 and paraplegia. 20 Aseptic meningitis or meningoencephalitis after iohexol myelography is very rare. In a 1986 review of the literature by Elkin et al, 4 they found no cases of serious neurologic adverse effects (defined as mental status changes or seizure) in 248 patients who underwent myelography with iohexol. In 1988, Nestvold and Sortland 21 also found no severe neurologic complications in the 331 patients reviewed who underwent iohexol myelography. Also in 1988, Skalpe and Nakstad 22 reported a study of 1000 iohexol myelographies with no serious neurologic adverse effects. To our knowledge, there are only 2 case reports of aseptic meningitis 9,10 and 1 case of aseptic meningoencephalitis 13 after iohexol myelography. In the case of meningoencephalitis, the patient received 18 mL of iohexol 180. The patient's mental status improved 72 hours after the myelogram, and his fever resolved by 120 hours. Two cases of aseptic meningitis with iotrolan myelography 7,8 and 2 cases of aseptic meningoencephalitis with iopamidol myelography 11,12 have also been described.
Previous reports of patients with chemical aseptic meningoencephalitis from myelography describe headaches, nausea, fevers, and mental status changes within 24 hours of the my-elogram. Serum leukocytosis and CSF pleocytosis (with polymorphonuclear cell predominance) may be seen. Negative results on CSF cultures are a requisite. Bender et al 7 proposed measuring serum procalcitonin levels as a guide to help differentiate between bacterial and aseptic chemical meningitis because procalcitonin levels are higher in bacterial infections.
Iomeprol is a newer agent that also seems to have a safety profile similar to that of iohexol, iotrolan, and iopamidol. 23 It is a nonionic iodinated contrast medium that has a lower osmolarity and higher water solubility than older agents. 24 It is also the first contrast medium to be formulated without edetic acid. 23 These factors may reduce its potential to cause adverse events, 23 and comparative studies with iohexol and iomeprol with regard to neurologic complications may be useful.
The pathophysiology and predisposing factors for the development of aseptic meningitis or meningoencephalitis after intrathecal injection of these mentioned contrast agents are not well understood. The neurotoxicity of contrast agents has been linked to the osmolarity, presence of sodium ions, and lipid solubility of the agent. 25 Some authors hypothesize that osmolarity disturbances 17 or direct toxicity 11 cause meningeal irritation. In addition, an immune-mediated cause has not been excluded. If immune related, steroids could play a role in early treatment and possibly hasten recovery. However, most reported patients experienced no serious sequelae without steroid treatment.

Conclusions
In general, iohexol is a safe and effective contrast agent for CT myelography. Clinicians should be aware of the rare occurrence of aseptic meningoencephalitis related to myelography. The clinical symptoms, timeline, and CSF analysis are helpful to differentiate aseptic meningoencephalitis from other complications of myelography.