Case report

Fat droplets in the cerebrospinal fluid (CSF) spaces of the brain

  • Received: 22 May 2024 Revised: 27 October 2024 Accepted: 15 November 2024 Published: 27 November 2024
  • It is rare to find free floating fat droplets in the cerebral spinal fluid (CSF) spaces of the brain. When fat droplets are seen in the CSF spaces, the most common cause is the rupture of a dermoid cyst. Dermoid cysts are congenital inclusion cysts that form during the neural tube closure between the third and fifth weeks of embryogenesis. In this case report, we describe a case of a 74-year-old, right-handed female who presented with an acute onset of visual disturbances and left-hand numbness. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed hypodense “lesions” in the lateral ventricles and basal cisterns. The CT Hounsfield unit was between −41 to −83 Hounsfield Units, which is compatible with fat rather than air. The T1 weighted and FLAIR MRI showed hyperintense lesions “floating” on top of the CSF in the lateral ventricles, which is typical for fat droplets, presumably caused by a ruptured dermoid cyst. This case emphasizes the importance of analyzing Hounsfield Units to distinguish lesions by density, where fat ranges from −50 to −150 Hounsfield Units and air is −1000 Hounsfield Units. Pneumocephalus is the presence of air in the epidural, subdural, or subarachnoid space and can cause confusion, nausea, seizures and focal neurological symptoms. A careful analysis of the neuroimaging findings in the CT with or without MRI is important in making a correct diagnosis of a ruptured dermoid cyst versus pneumocephalus.

    Citation: Mark Reed, Christopher Miller, Cortney Connor, Jason S. Chang, Forshing Lui. Fat droplets in the cerebrospinal fluid (CSF) spaces of the brain[J]. AIMS Neuroscience, 2024, 11(4): 484-489. doi: 10.3934/Neuroscience.2024029

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  • It is rare to find free floating fat droplets in the cerebral spinal fluid (CSF) spaces of the brain. When fat droplets are seen in the CSF spaces, the most common cause is the rupture of a dermoid cyst. Dermoid cysts are congenital inclusion cysts that form during the neural tube closure between the third and fifth weeks of embryogenesis. In this case report, we describe a case of a 74-year-old, right-handed female who presented with an acute onset of visual disturbances and left-hand numbness. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed hypodense “lesions” in the lateral ventricles and basal cisterns. The CT Hounsfield unit was between −41 to −83 Hounsfield Units, which is compatible with fat rather than air. The T1 weighted and FLAIR MRI showed hyperintense lesions “floating” on top of the CSF in the lateral ventricles, which is typical for fat droplets, presumably caused by a ruptured dermoid cyst. This case emphasizes the importance of analyzing Hounsfield Units to distinguish lesions by density, where fat ranges from −50 to −150 Hounsfield Units and air is −1000 Hounsfield Units. Pneumocephalus is the presence of air in the epidural, subdural, or subarachnoid space and can cause confusion, nausea, seizures and focal neurological symptoms. A careful analysis of the neuroimaging findings in the CT with or without MRI is important in making a correct diagnosis of a ruptured dermoid cyst versus pneumocephalus.


    Abbreviations

    HU:

    Hounsfield Units; 

    CT:

    Computed Tomography; 

    MRI:

    Magnetic Resonance Image; 

    FLAIR:

    Fluid Attenuated Inversion Recovery; 

    CSF:

    Cerebrospinal Fluid

    Despite decades of research, no drug has so far been fully effective against HIV. Although currently available antiretroviral therapy (ART) can effectively suppress HIV replication by acting at different levels of the HIV life cycle, it does not completely eradicate infected cells but instead converts them into latent viral reservoirs which upon non-adherence to treatment leads to viral rebound. Moreover, ART presents many challenges in terms of long-term drug toxicities and side effects [1]. It has therefore become crucial to seek novel ways of approaching HIV cure. Immunotherapy seems to have paved the way for this. Importantly, NK cell-based immunotherapy has gained ground in cancer treatment with promising results [2]. NK cells are well known for their anti-tumor and antiviral activity, and they do not require prior antigenic stimuation for activation [3]. Therefore, NK-based immunotherapies against HIV are currently under consideration and are being tested in clinical trials. Some of those include CAR-NK cell therapy, toll-like receptor (TLR) agonists, broadly neutralizing Abs (bNAbs), bi- and tri-specific killer engagers (BiKEs & TriKEs), facilitating antibody-dependent cellular cytotoxicity (ADCC), blocking inhibitory NK receptors during infection, IL-15 and IL-15 superagonists (eg: ALT-803), etc. [4] (Figure 1).

    Figure 1.  NK-based immunotherapies available against HIV-infection. (a) TLR 3, 7, 8, and 9 found within endosomes are targeted by their respective agonists, leading to a signalling cascade that causes the release of cytokines to enhance the recruitment of anti-HIV responses. (b) Killer Engagers and bNAbs work by enhancing ADCC. (c) IL-15 superagonist ALT-803 and the IL-15 component of the TriKE binds to IL-15Rα to improve NK cell function, persistence, and expansion. (d) Chimeric antigen receptor with the red arrow pointing to the universal CAR-NK cell consisting of the anti-DNP CAR (e) Monalizumab blocks NKG2A whereas IPH2102/Lirilumab blocks KIR. Blocking of either KIR or NKG2A, both of which are inhibitory NK receptors results in relieving the inhibition exerted on the ADCC pathway. Created using biorender.com and adapted from one of our manuscripts submitted for publication.

    A major cause of frustration and a fact that is immensely challenging in HIV drug development attempts is overcoming HIV diversity. In fact, previous studies on multi-specific bNAbs have shown that focusing on two or three epitopes are inadequate to cover all HIV-1 variants. However, we recently came across an interesting article by Lim et al. where they have introduced for the first time in history, a universal CAR-NK cell approach providing an effective solution to counteract this HIV variability [5]. In contrast to currently available CARs which target a single epitope of HIV envelope glycoprotein gp160 (a complex between gp120 and gp41) and thus have failed to address this issue, the universal CAR model developed by Lim et al. indirectly targets different gp160 epitope variants. Their CAR-NK cell has been designed to recognize 2,4-dinitrophenyl (2,4-DNP) tagged to gp160 specific Abs, given that anti-gp160 Abs with different specificities are readily available. See Figure 1d [5]. This kind of approach has several potential advantages. Firstly, it is compatible with all types of Abs including those which are not effective in inducing ADCC. Also, it has higher specificity and can be considered safer as ADCC will not be induced by naturally produced serum Abs. Furthermore, they do not impair the primary NK cell response against gp160+ HIV-infected cells [5] As a solution to the competition exerted by natural anti-2,4-DNP Abs that exist in minor proportions in serum (≈1%), Lim et al. have suggested increasing the affinity of their universal CAR for DNP [6]. Compared to the use of T cell-based approaches, allogeneic NK cells are a better alternative since it is linked to a lower risk of inducing GvHD [7]. Their approach will be further evaluated through mouse models in future studies.

    Thus, we conclude that in order to tackle the tremendous diversity of HIV epitopes similar cost-effective and flexible universal strategies will be necessary. Furthermore, under the current situation, this approach alone will not be sufficient since the latent HIV reservoir will have to be reactivated and thus combination therapy with LRAs (latency reversing agents) and possibly other agents such as antiretroviral combinations seem essential as under pressure HIV is known to generate escape mutants or lead to selection [8],[9].


    Acknowledgments



    The authors report no targeted funding.

    Conflict of interest



    All authors declare no conflicts of interest in this paper.

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    [2] Ray M, Barnett D, Snipes G, et al. (2012) Ruptured intracranial dermoid cyst. Baylor University Medical Center Proceedings 25: 23-25. https://doi.org/10.1080/08998280.2012.11928775
    [3] Delgado-Muñoz P, Oliver-Ricart M, Labat-Alvarez E (2022) A Rare Case of an Intracranial Dermoid Cyst with Atypical Appearance on Computed Tomography and Magnetic Resonance Imaging. Am J Case Rep 23: e935115. https://doi.org/10.12659/AJCR.935115
    [4] Zhang MH, Feng Q, Zhu HL, et al. (2021) Asymptomatic traumatic rupture of an intracranial dermoid cyst: A case report. World J Clin Cases 9: 4046-4051. https://doi.org/10.12998/wjcc.v9.i16.4046
    [5] Zimny A, Zinskia L, Bladowska J, et al. (2013) Intracranial lesions with high signal intensity on T1-weighted MR images - review of pathologies. Pol J Radiol 78: 36-46. https://doi.org/10.12659/PJR.889663
    [6] Gorissen Z, Hakvoort K, Boogaart M, et al. (2019) Pneumocephalus: a rare and life-threatening, but reversible, complication after penetrating lumbar injury. Acta Neurochir 161: 361-365. https://doi.org/10.1007/s00701-018-03796-y
    [7] DenOtter T, Schubert J (2023) Hounsfield Unit. StatPearls . Treasure Island: StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547721/
    [8] Sood S, Gupta R (2014) Susceptibility Artifacts in Ruptured Intracranial Dermoid Cysts: A Poorly Understood but Important Phenomenon. Neuroradiol J 27: 677-684. https://doi.org/10.15274/NRJ-2014-10090
    [9] Picardo M, Ottaviani M, Camera E, et al. (2009) Sebaceous gland lipids. Dermato-Endocrinology 1: 68-71. https://doi.org/10.4161/derm.1.2.8472
    [10] Osborn A, Preece M (2006) Intracranial Cysts: Radiologic-Pathologic Correlation and Imaging Approach. Radiology 239: 650-664. https://doi.org/10.1148/radiol.2393050823
    [11] Mikami T, Maeda C, Aoki F, et al. (2021) A dermoid cyst misdiagnosed as a lipoma due to atypical magnetic resonance images: a case report. J Med Case Rep 15: 99. https://doi.org/10.1186/s13256-020-02584-6
    [12] El-Bahy K, Kotb A, Galal A, et al. (2006) Ruptured intracranial dermoid cysts. Acta Neurochir 148: 457-462. https://doi.org/10.1007/s00701-005-0722-0
    [13] Das J, Bajaj J (2024) Pneumocephalus. StatPearls . Treasure Island: StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535412/
    [14] Ray M, Barnett D, Snipes G, et al. (2012) Ruptured intracranial dermoid cyst. Baylor University Medical Center Proceedings 1: 23-25. https://doi.org/10.1080/08998280.2012.11928775
    [15] Blitz SE, Bernstock JD, Dmytriw AA, et al. (2021) Ruptured suprasellar dermoid cyst treated with lumbar drain to prevent postoperative hydrocephalus: Case report and Focused Review of Literature. Front Surg 8. https://doi.org/10.3389/fsurg.2021.714771
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