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INNOSC Theranostics and
            Pharmacological Sciences                                        Fungal markers in intracranial fungal infections



            sinuses (PNSs), orbit, and cranial areas – are the primary   to early diagnostic tools in resource-limited low-  and
            disease sites.  Disease progression in these regions is   middle-income countries such as Pakistan.
                      5
            accompanied by pain, fever, ophthalmic complications,
            epistaxis, and cough.  The symptoms progress gradually and   2. Case series
                            6
            often include proptosis, monocular blindness, congestion,   We retrospectively reviewed the medical records of
            classic meningitis symptoms, and hemorrhage.  Owing   patients with clinically suspected IFI. Only patients with
                                                   7
            to its angioinvasive properties,  Aspergillus can affect   fungal assay data (GM and BDG levels), neuroimaging
            the branches  of the internal carotid artery (ICA) in the   studies (computed tomography [CT] of the PNS and
            ethmoidal or orbital regions, leading to microaneurysms   magnetic resonance imaging [MRI]), and CSF analysis
            and cerebral emboli.  Furthermore, bone destruction is   results were included in this study. We solely focused on
                             8
            observed in 30 – 50% of patients with sinus infections. 9  the diagnostic approach for suspected cases of IFI from a
              The European Organization for Research and Treatment   single center and did not address the treatment regimens
            of Cancer and the Mycoses Study Group have included   or management outcomes. The interpretation of the BDG
            galactomannan (GM) and 1,3-β-d-glucan (BDG) assays as   and GM index values is provided in Table 1.
            microbiological criteria for diagnosing fungal infections.    2.1. Case 1
                                                         10
            GM, a polysaccharide antigen primarily found in the cell
            walls of Aspergillus spp., can be detected using the Platelia   A 48-year-old man presented with headaches, vertigo,
            Aspergillus enzyme immunoassay (Bio-Rad Laboratories,   left-sided visual  loss,  and hearing loss 2  months  after
            Inc., headquartered in Hercules, California, USA). This   surgical excision of a parasellar space-occupying lesion.
            method utilizes serum or bronchoalveolar lavage fluid   CSF analysis revealed an elevated protein level, a decreased
            samples. However, cerebrospinal fluid (CSF) can be used   glucose level, and  an increased white blood cell  (WBC)
            to treat cerebral aspergillosis. 10-12             count  (lymphocytes,  95%).  The  serum  was  positive  for
                                                               BDG, whereas Gram and acid–fast bacteria staining
              BDG, a cell wall component of most fungi (excluding   yielded negative results.
            Cryptococci,  Zygomycetes, and  Blastomyces dermatitidis),
            is a panfungal serological marker. Although BDG is   Contrast-enhanced MRI of the brain revealed an
            not specific to IA, it can be used to diagnose invasive   intracranial extra-axial mass in the right parasellar region.
            candidiasis. 10-12  Of the four available BDG detection assays   The  mass  extended  into  both  cavernous  sinuses  and
            (Fungitell, Wako, Fungitec-G, and Maruha), only Fungitell   involved the right supraclinoid ICA, cerebellar peduncle,
            (Associates of Cape Cod, Inc., 124 Bernard E. Saint Jean   and brainstem.
            Drive,  East  Falmouth,  Massachusetts  02536-4445,  USA)   2.2. Case 2
            has been FDA-approved for use with serum. 10
                                                               A 51-year-old man with fungal sinusitis presented with
              Pakistan faces unique challenges because of its humid
            climate, which fosters fungal growth and widespread   swelling in the left maxillary region 8  months after a
                                                               craniotomy. GM and BDG fungal biomarker  assays were
            immunosuppressive therapy use. Furthermore, owing to   positive. Contrast-enhanced MRI of the brain revealed
            limited data on intracranial fungal infections (IFIs) and   changes in the left maxillary sinus with ipsilateral intraorbital
            restricted availability and affordability of neuroimaging   and intracranial extensions. The CT PNS confirmed the
            or CSF analysis, diagnoses are delayed or missed.   findings of chronic left maxillary sinusitis with osteomyelitis.
            Consequently, the timely detection of fungal infections
            must be improved by assessing specific diagnostic   2.3. Case 3
            parameters  such  as GM  and  BDG assays,  which  can
            enhance the diagnostic accuracy and facilitate prompt   A 61-year-old man with hepatitis C and uncontrolled type-2
            treatment. Given the low socioeconomic status of patients   diabetes presented with proptosis, pain, lacrimation, and
            in our setup, we must focus on targeted diagnostic   Table 1. Cutoffs for the serum fungal diagnostic assays and
            markers to streamline patient and healthcare provider   their interpretation
            processes.
                                                               Tests                Cutoff         Interpretation
              This study contributes to the existing literature on   β-d-glucan    <60 pg/mL       Negative
            IFIs by presenting a case series of patients with IFIs who
            were admitted to the Jinnah Postgraduate Medical Center,              60–80 pg/dL      Intermediate*
            a tertiary care hospital in Karachi, Pakistan, between                 >80 pg/dL       Positive
            November 2022 and May 2023. We aimed to evaluate the   Galactomannan     <0.5          Negative
            potential role of serum fungal biomarkers as an adjunct   Notes: *Repeat test-recommended; **GMI >0.5 in two consecutive samples.


             Volume 8 Issue 2 (2025)                        97                               doi: 10.36922/itps.4528
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