Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: a case report and review of imaging findings

Chong, Insun; Wang, Kevin Yuqi; Lincoln, Christie M.

doi:10.1016/j.clinimag.2018.11.005

Cited by 28 publications

(16 citation statements)

References 21 publications

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“…Rare but serious drug-related adverse events have emerged over time with the use of FTY in MS patients, including cases of cryptococcal meningitis, progressive multifocal leukoencephalopathy and immune thrombocytopenic purpura [7][8][9] . Biomarkers predicting such adverse events or distinguishing patients who respond particularly well or poorly to FTY would be of great clinical value but are yet to be discovered.…”

mentioning

confidence: 99%

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

Ghadiri

Rezk

et al. 2020

Sci Rep

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Bar-or 1,3* Biomarkers predicting fingolimod (FTY) treatment response in relapsing-remitting multiple sclerosis (RRMS) are lacking. Here, we performed extensive functional immunophenotyping using multiparametric flow cytometry to examine peripheral immune changes under FTY treatment and explore biomarkers of FTY treatment response. From among 135 RRMS patients who initiated FTY in a 2-year multicentre observational study, 36 were classified as 'Active' or 'Stable' based on clinical and/ or radiological activity on-treatment. Flow cytometric analysis of immune cell subsets was performed on pre-and on-treatment peripheral blood mononuclear cells (PBMC) samples. Decreased absolute counts of B cells and most T-cell subsets were seen on-treatment. Senescent CD8 + T cells, CD56 + t cells, CD56 dim natural killer cells, monocytes and dendritic cells were not reduced in number and hence relatively increased in frequency on-treatment. An unbiased multiparametric and traditional manual analysis of T-cell subsets suggested a higher pre-treatment frequency of CD4 + central memory T cells (TCM) in patients who were subsequently Active versus Stable on-treatment. Lower pre-treatment terminally differentiated effector memory (TEMRA) cell frequencies were also seen in the subsequently Active cohort. Together, our data highlight differential effects of FTY on peripheral immune cell subsets and suggest that pre-treatment T-cell subset frequencies may have value in predicting FTY treatment response.

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confidence: 99%

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

Ghadiri

Rezk

et al. 2020

Sci Rep

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“…C. neoformans has a special affinity to cross blood brain barrier (BBB), and many mechanisms have been proposed in this regard [ 4 ]. So far, eight cases of meningoencephalitis [ [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] ] have been reported, with 2 reported deaths [ 11 , 14 ] and significant long-term cognitive impairment in one case [ 9 ]. To the best of our knowledge, two cases of disseminated disease have been reported [ 17 , 18 ], with significant permanent neurological and cognitive impairment as sequelae in one patient [ 18 ].…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…MRI findings of the brain in Cryptococcus-related meningoencephalitis vary, mostly showing leptomeningeal and parenchymal enhancement [ 19 ], which was not present in our case. Additionally, the reported disseminated and meningoencephalitis cases [ [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ] showed baseline lesions of MS, with no new lesions and making the early diagnosis difficult. Hence, initial imaging including CT and MRI do not completely rule out the possibility of infection.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Increased risk of disseminated cryptococcal infection in a patient with multiple sclerosis on fingolimod

Kaur

Lewis

Basit

et al. 2020

IDCases

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Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS), with an estimated 2.3 million people being affected globally, and is a major cause of permanent disability. About 90 % of the affected patients with MS have relapsing-remitting type. Fingolimod became the first FDA approved oral drug in 2010 with an immunomodulating mechanism to control the relapse rates. However, since its introduction, increased cases of cryptococcal infections have been reported including meningoencephalitis and disseminated infections. Herein, we present the case of a 34-year-old-male with disseminated Cryptococcal and localized varicella zoster virus (VZV) coinfection to highlight the risk of opportunistic infections associated with the long-term use of fingolimod. The objective of this literature review is for clinicians to have a high index of suspicion for cryptococcal infections when dealing with MS patients on Fingolimod, especially those who present with neurological symptoms, as this mimics MS relapse.

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“…Chong et al reported a case of a MS patient on fingolimod therapy with imaging findings, including enhancement pattern and lesion location atypical for active demyelination seen in MS, that were ultimately discovered to be manifestations of cryptococcal meningitis. 11 Besides, Ward et al reported a case of cryptococcal meningitis diagnosed 6 months after fingolimod discontinuation. In this context, MRI findings of that study revealed new intraparenchymal and sulcal contrast enhancement in a basilar predominant distribution, most concerning for an infectious or inflammatory process and again not consistent with demyelinating lesions.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcal Meningoencephalitis Treated with Fingolimod in a Patient with Multiple Sclerosis

Kuruoğlu¹,

Deveci²,

Tanyel³

et al. 2019

Turkiye Klinikleri J Case Rep

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Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: a case report and review of imaging findings

Cited by 28 publications

References 21 publications

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

Increased risk of disseminated cryptococcal infection in a patient with multiple sclerosis on fingolimod

Cryptococcal Meningoencephalitis Treated with Fingolimod in a Patient with Multiple Sclerosis

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