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Months After Outbreak, MRI Identifies Fungal Infections Without Obvious Symptoms



(A) SAGITTAL T1 postcontrast image of the cervical spine shows thin linear dorsal epidural enhancement at the C5-C6 level (arrowhead). (B) Follow-up imaging performed 19 days later shows thickening of the area of enhancement (arrowheads). The patient had become increasingly symptomatic with neck pain at the cervical injection site prior to the second magnetic resonance imaging. Subsequent biopsy showed evidence of fungal hyphae and cultures grew Exserohilum species.

A study using MRI found that some patients who received contaminated steroid injections had fungal infections without worsening baseline pain or new neuropathic symptoms.

Patients who received contaminated steroid injections may have a fungal infection at the injection site but not realize they have a problem, according to a study that used MRI to screen for cases that may have gone unrecognized.

The study, which included screening results on 172 people, found some fungal infections even in patients who had no worsening of their baseline pain or new neuropathic symptoms. More than one in five patients screened with MRI showed evidence of spinal or paraspinal infection.

The findings suggest that perhaps there should be more aggressive MRI screening of patients who received injections of contaminated methylprednisolone acetate distributed by the New England Compounding Center, even if patients appear to be fine.

The findings also indicate that while the worst of the unprecedented outbreak of meningitis linked to contaminated lots of the steroid is over, spinal and paraspinal infections continue to be a concern more than half a year after cases first surfaced in October 2012.

“A proactive outreach to patients receiving injections from a highly contaminated lot, especially lot No. [email protected], is needed,” the research team based at St. Joseph Mercy Ann Arbor hospital in Michigan, reported in the June 19 edition of the Journal of the American Medical Association. “Magnetic resonance imaging may detect infection earlier in some patients, leading to more efficacious medical and surgical treatment and improved outcomes.”

According to the Centers for Disease Control and Prevention's (CDC) most recent count, 745 patients in 20 states have been diagnosed with meningitis, spinal or paraspinal infection, or joint infection and 58 have died as a result of contaminated injections.

Michigan was one of the epicenters of the outbreak of meningitis, and many patients who had received contaminated injections from a local pain clinic went to St. Joseph Mercy Ann Arbor hospital for treatment. While meningitis initially was the biggest worry related to the outbreak of Exserohilum rostratum fungal infections, cases of localized spinal and paraspinal infections began to be identified. — some with little to no change in chronic pain.

Anurag Malani, MD, the hospital's medical director for infection prevention and antimicrobial stewardship and the study's lead author, told Neurology Today that the observation prompted the hospital to conduct an outreach effort to patients in the area who were identified as having received injections from a contaminated lot but who had not come to the hospital for treatment. MRI screening on those patients was conducted between November 9, 2012 and April 30 of this year.

Of 172 patients screened, MRI was abnormal in 36 patients (21 percent), showing “epidural or paraspinal abscess or phlegmon, arachnoiditis, spinal osteomyelitis or diskitis, or moderate to severe epidural, paraspinal, or intradural enhancement,” according to the JAMA report. Patients were asked about new or worsening back or neck pain, lower extremity weakness and radiculopathy symptoms. Thirty-five of the 36 patients with abnormal MRI findings met the CDC's case definition for probable (17 patients) or confirmed (18 patients) fungal spinal or paraspinal infection.

The 35 patients were treated with antifungal drugs (voriconazole with or without liposomal amphotericin B). In addition, 24 of the patients required surgical debridement, and 17 of those patients (71 percent) had laboratory evidence of fungal infection, including five patients who reported having no symptoms, the report said.


DR. ANURAG MALANI: “Fungal infections can be difficult to treat. You dont want patients to progress to the point where it becomes much more difficult.”

Dr. Malani said the results underscore the importance of health care providers and public health officials doing “proactive outreach.”

“Fungal infections can be difficult to treat,” Dr. Malani said. “You don't want patients to progress to the point where it becomes much more difficult.”


But he and his coauthors stopped short of recommending universal screening of all patients who were exposed to potentially contaminated steroid injections.

“Our findings support obtaining contrast-enhanced MRI of the injection site in patients with persistent back pain even when their pain disorder has not worsened,” they wrote, especially those exposed to a highly contaminated lot, such as No. [email protected]

The CDC recommends MRI screening in specific circumstances. “CDC's guidance already addresses the concerns about obtaining an MRI on patients with baseline or mild symptoms to some degree,” Benjamin J Park, MD, who leads the epidemiology team in CDC's Mycotic Diseases branch, said in an e-mail response sent to Neurology Today. “At this point, CDC does not recommend obtaining MRIs on all 13,500 exposed persons, but we do recommend for clinicians to consider obtaining one.”

Dr. Park reiterated that the CDC recommends MRI screening in the following circumstances:

  • In patients with new or worsening symptoms at or near the injection site, physicians should obtain an MRI with contrast of the symptomatic area, if not contraindicated. The recommendation also applies to patients being treated for meningitis. In some cases, radiologic evidence of abscess or phlegmon has become apparent on repeat MRI studies performed after a normal scan. Clinicians should have a low threshold for repeat MRI studies in patients who continue to have symptoms related to the site of injection, even after a normal study. However, the optimal duration between MRI studies is unknown.
  • Clinicians should consider obtaining an MRI with contrast of the symptomatic area(s) in patients with persistent but baseline symptoms, because the presentation of spinal and paraspinal infections can be subtle and difficult to distinguish from a patient's baseline chronic pain.
  • In patients being treated for meningitis, clinicians should strongly consider obtaining an MRI of the injection site approximately two to three weeks after diagnosis of meningitis, even in the absence of new or worsening symptoms at or near the injection site.


William Schaffner, MD, an infectious disease specialist who serves as chair of preventive medicine at Vanderbilt University, said the new study on MRI screening is a good example of how a variety of tactics, from old-fashioned epidemiological tracking to high-tech tools, can be used to tackle a disease outbreak.

“Who would have thought we would be using MRI as a screening device to examine patients at risk, to document illness and to determine who needs treatment?” he told Neurology Today. But he noted that “on occasion, highly expensive, elaborate technology needs to be used in a fashion such as this. No doubt this was a unique infection which was introduced in a unique way.”

Dr. Schaffner, who is a consultant to the Tennessee health department, said that continued vigilance for signs of fungal infection is warranted. His state was one of the hotspots for cases.

“It is clear that some people who have these spinal and paraspinal infections can go on to develop meningitis and we know that is life threatening,” he said. “There is no evidence these infections will clear on their own.”

The researchers acknowledged that MRI screening was often repeated because some initial scans yielded equivocal results. They noted there was a learning curve to interpeting MRI results related to the infection, but said physicians got better at making diagnoses as they got more experienced with evaluating patients.

An editorial accompanying the JAMA study cautioned against universal MRI screening of patients potentially exposed to the contaminated steroid, though it said that “the number needed to screen was low (approximately 1 in 5 had MRI abnormalities) and thus was likely a cost-effective intervention.”

“Still, a cautious approach to widespread implementation of this practice is warranted,” the editorial said.

Dr. Malani said he and other doctors at his hospital are continuing to follow patients and to provide follow-up MRIs. “All will need regular follow-up for a long time,” he said.


•. Malani AN, Vandenberg DM, Singal B, et al. Magnetic resonance imaging screening to identify spinal and paraspinal infections associated with injections of contaminated methylprednisolone acetate. JAMA 2013;309(23):2465–2472.
    •. Thompson GR, Kontoyiannis DP, Patterson TF, et al. Editorial: Real-world experience in the midst of an Exserohilum meningitis outbreak. JAMA 2013:309(23):2493–2495.
      •. Centers for Disease Control and Prevention (CDC). Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a a single compounding pharmacy — United States, 2012. MMWR Morb Mortal Wkly Rep 2012;61(41): 839-842.
        •. CDC Info on the multistate fungal meningitis outbreak investigation:
          •. Neurology Today archive on fungal meningitis: