CASE REPORT article
Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1649779
A Fatal Case of CNS Actinomyces Mimicking Tolosa-Hunt Syndrome: Is it Time to Reevaluate Diagnostic Criteria?
Provisionally accepted
Natalie Bristol1
Courtney Venegas1*
Isha Snehal2Mathias Maisenbacher1Ryan Higgins1Thomas Auen1Catherine Cichon1Richard Hankins1*Christie Barnes1Sahara Cathcart1Ana Yuil-Valdes1Jie Chen1Cindy Schmidt1
Subin Mathew1*- 1University of Nebraska Medical Center, Omaha, United States
- 2Mayo Clinic Minnesota, Rochester, United States
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Background: Tolosa-Hunt Syndrome (THS) is a rare diagnosis characterized by headaches, painful ophthalmoplegia, and granulomatous inflammation of the cavernous sinus. It is a diagnosis of exclusion but can mimic many other conditions, including central nervous system (CNS) actinomycosis. This systematic review evaluated the frequency of CNS actinomycosis initially diagnosed as THS and evaluated lapses in the current diagnostic criteria which were related to poor outcomes. Case Report: We present a case of a 43-year-old man who was diagnosed with THS ten weeks prior to his final hospital presentation. Previous infectious work up was negative. He returned with altered mental status and was found to have leptomeningeal enhancement, vasculitis, and acute infarcts. He decompensated while on broad-spectrum antimicrobials. The patient was ultimately found to have CNS actinomycosis when next generation sequencing identified Actinomyces israelii. This diagnosis was confirmed by biopsy. Unfortunately, due to the extent of the infarcts, the patient passed away. Results: A total of 344 records were analyzed for title/abstract review and ultimately revealed Eight cases of CNS actinomycosis initially diagnosed as THS. 62.5% of cases had dental history prior to symptom onset. Cerebral spinal fluid cultures were obtained in 75% percent of cases, and all were negative for Actinomyces. 88% of cases were diagnosed by histopathology evaluation and 25% of cases were fatal. Conclusion: With the low reported prevalence of CNS actinomycosis, the inadequacy of current testing for Actinomyces, and the significant overlap of symptoms with THS, it is essential that clinicians are aware of CNS actinomycosis as a potential infectious etiology if early and potentially curative treatment is to be provided. The current definition of THS may encourage harmful practices and should be revised.
Keywords: Headaches, Painful ophthalmoplegia, non-specific granulomatous inflammation of the cavernous sinus, magnetic resonance imaging (MRI), soft tissue mass involving the cavernous sinus, Central nervous system (CNS) Actinomyces infection, serologic next-generation sequencing (NGS)
Received: 23 Jun 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Bristol, Venegas, Snehal, Maisenbacher, Higgins, Auen, Cichon, Hankins, Barnes, Cathcart, Yuil-Valdes, Chen, Schmidt and Mathew. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Courtney Venegas, University of Nebraska Medical Center, Omaha, United States
Richard Hankins, University of Nebraska Medical Center, Omaha, United States
Subin Mathew, University of Nebraska Medical Center, Omaha, United States
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