Elsevier

World Neurosurgery

Volume 123, March 2019, Pages 425-434.e5
World Neurosurgery

Literature Review
Diagnosis and Treatment of Isolated Cerebral Mucormycosis: Patient-Level Data Meta-Analysis and Mayo Clinic Experience

Portions of the present study were presented in abstract form at the 47th Critical Care Congress, Society of Critical Care Medicine, San Antonio, Texas, February 25, 2018.
https://doi.org/10.1016/j.wneu.2018.10.218Get rights and content

Background

Isolated cerebral mucormycosis is a rare and serious infection associated with intravenous drug abuse.

Methods

We performed a comprehensive meta-analysis of cases reported in studies and have included an unreported case from our institution. We searched PubMed/Medline, EMBASE, Scopus, Cochrane Databases, and our institution’s electronic medical health records from inception through March 31, 2018. The cases were considered isolated (only affecting the cerebrum, cerebellum, or brainstem) if the absence of other primary sources of infection had been documented. Continuous variables were summarized using the median and interquartile range and categorical variables using frequencies and proportions. The relationships between variables were tested using the Wilcoxon rank sum and Pearson χ2 tests.

Results

A total of 130 studies (141 patients) met the eligibility requirements and were screened; 68 patients were included. The median age was 28 years (interquartile range, 24–38); 57% were men. Most patients had a history of intravenous drug abuse (82%), and 20% had positive human immunodeficiency virus findings. The lesion location was mostly supratentorial (91%), especially in the basal ganglia (71.2%). The cultures were positive in 38%, with Rhizopus the most common organism (59%). The mortality rate was 65%. The survivors were significantly more likely to have received amphotericin B (92% vs. 43%; P < 0.001) or to have undergone stereotactic aspiration (58% vs. 25%; P < 0.01).

Conclusions

Isolated cerebral mucormycosis has a pooled mortality rate of 65%. The presence of lesions in the basal ganglia, rapidly progressive symptoms, and a history of intravenous drug abuse should raise suspicion for the early initiation of amphotericin B and stereotactic aspiration.

Introduction

The first documented description of mucormycosis involving the central nervous system was published in 1885 by Paltauf,1 who coined the term “mycosis mucorina.” The nomenclature for these infections has varied and has included mucormycosis, zygomycosis, and phycomycosis.2 The causative fungi belong to the order Mucorales with the predominant genera being Rhizopus and Mucor, followed by Lichtheimia, Rhizomucor, Saksenaea, Cunninghamella, and Apophysomyces.3, 4, 5, 6, 7, 8 These organisms are found almost ubiquitously in soil and decomposing organic matter. The most important aspect of immune function in neutralizing spores or hyphae has been shown experimentally and clinically to be phagocytic activity.9 Patients with either severe neutropenia or severely inhibited neutrophil function are at greater risk of mucormycosis than patients with impaired T-cell immunity.10, 11

Rhinocerebral mucormycosis is a well-described entity that is typically characterized by gray and/or erythematous lesions with black eschars in the nasal and palatal region. The highly angioinvasive fungi can rapidly spread into the brain parenchyma, causing lesions primarily in the frontal and temporal lobes, and are associated with mortality rates as high as 96%.7, 12 However, isolated involvement of the brain is extremely rare, and only sporadic cases have been reported.7 Isolated cerebral infections have been hypothesized to be caused by direct inoculation of spores present either in drugs of abuse or in the cutting agents.13 The pathologic features pose substantial diagnostic challenges that hinder timely diagnosis and administration of therapy, increasing mortality dramatically.

Given the rarity of isolated cerebral mucormycosis, no established guidelines exist to assist clinicians with the best management approach. One solution would be pooling and analyzing data from all studies reported to date. Therefore, we reviewed the reported data and provide a comprehensive meta-analysis of individual-level data of all reported studies. We also report an unpublished case from our institution.

Section snippets

Search Strategy and Selection Criteria

A comprehensive search was conducted of the following databases from their inception through March 31, 2018: PubMed, Ovid MEDLINE Epub Ahead of Print, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search strategy was designed and the search was conducted by an experienced librarian with input from the present study's principal investigators

Results

For our present review, we followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Supplemental Figure 1). Our initial search yielded 2552 results spanning publication years 1885 through March 31, 2018, of which 130 reports (141 patients) met the eligibility criteria and were screened in full text for inclusion. Of the 141 total patients, 74 (52.5%) were excluded (Supplemental Table 3 and Supplemental References). A total of 56 studies with 67 patients

Discussion

Isolated cerebral mucormycosis is challenging to diagnose and to treat and, although rare, is estimated to account for ∼8% of all mucormycosis cases.7 To decrease the mortality associated with this potentially fatal disease, mucormycosis needs to be identified earlier and treated quickly with antifungal agents. From the present review of 68 cases, we found that amphotericin B and stereotactic aspiration use were associated with a significant decrease in patient mortality, and lesion location in

Conclusions

Isolated cerebral mucormycosis is a rare cause of intracranial abscess. The prognosis is grave, and ∼65% of patients will die. A high level of suspicion is needed for patients with a history of IVDA who have non–contrast-enhancing lesions in the basal ganglia and rapidly progressing symptoms, especially hemiparesis. Given the significant survival benefit for patients who receive amphotericin B, we suggest early stereotactic aspiration should be performed in such cases to obtain tissue for

Acknowledgments

The authors thank Larry J. Prokop, M.L.S., for his assistance with the electronic literature search. The authors also thank Leah Voit-Ostricki for her assistance in preparing the figures.

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    Conflict of interest statement: Funding for the present study was provided in part through a grant from Mayo Clinic Health System–Franciscan Healthcare Foundation and the Mayo Foundation of Mayo Clinic. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Dr. Watts is a consultant for Medtronic Spine and Biologics.

    Panagiotis Kerezoudis and Charles R. Watts contributed equally to this work and share first authorship.

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