
==== Front
Clin Case Rep
Clin Case Rep
10.1002/(ISSN)2050-0904
CCR3
Clinical Case Reports
2050-0904
John Wiley and Sons Inc. Hoboken

10.1002/ccr3.9123
CCR39123
CCR3-2024-05-1318
Neurology
Neurosurgery
Veterinary Medicine
Case Report
Case Report
Gliosarcoma associated with bilateral hippocampal sclerosis in a cat presenting complex partial seizures with orofacial involvement: A case report
Martinez et al.
Martinez Ana https://orcid.org/0000-0002-9104-6260
1
Binks Sophie 2
Pumarola Martí 3
Hardas Alexandros 4
Easton Alistair 5
Campo Leticia 5
Browne Molly 5
Martins Susana 5
Garosi Laurent S. 6
Di Dona Francesco 7
Tauro Anna https://orcid.org/0000-0003-0606-7831
8 9 anna.tauro@yahoo.co.uk

1 Queen's Veterinary School University of Cambridge Cambridge UK
2 Oxford Autoimmune Neurology Group University of Oxford Oxford UK
3 Mouse and Comparative Pathology Unit, Department of Animal Medicine and Surgery, Veterinary Faculty, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN), Campus UAB Universitat Autònoma de Barcelona Barcelona Spain
4 Department of Pathobiology and Population Sciences The Royal Veterinary College Hatfield UK
5 Translational Histopathology Laboratory, Department of Oncology University of Oxford Oxford UK
6 Vet Oracle Teleradiology, CVS Limited Norfolk UK
7 Freelance Consultant Naples Italy
8 Chestergates Veterinary Specialists, Units E&F Chester UK
9 College of Veterinary Medicine North Carolina State University Raleigh North Carolina USA
* Correspondence
Anna Tauro, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Email: anna.tauro@yahoo.co.uk

09 9 2024
9 2024
12 9 10.1002/ccr3.v12.9 e912308 5 2024
11 6 2024
© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Key Clinical Message

Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis.

Abstract

A 16‐year‐old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill‐defined, round, intra‐axial mass in the right piriform lobe, showing hyperintensity on T2W, T2‐FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2‐FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1‐antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody‐associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1‐antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high‐grade glioma.

case report
complex partial seizures
gliosarcoma
hippocampal sclerosis
MRI scans
voltage‐gated potassium channels
source-schema-version-number2.0
cover-dateSeptember 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:09.09.2024
Martinez A , Binks S , Pumarola M , et al. Gliosarcoma associated with bilateral hippocampal sclerosis in a cat presenting complex partial seizures with orofacial involvement: A case report. Clin Case Rep. 2024;12 :e9123. doi:10.1002/ccr3.9123
==== Body
pmc1 INTRODUCTION

Gliosarcoma is a rare histopathological subtype of glioblastoma characterized by a combination of glial and mesenchymal components. 1 , 2

Hippocampal necrosis (HN) and/or sclerosis (HS) evidence has been described in a feline form of limbic encephalitis (LE) called feline complex partial cluster seizures with orofacial involvement (FePSO), typically in the absence of an underlying tumor. 3 , 4 Meningiomas and oligodendrogliomas have been associated with alterations in hippocampal magnetic resonance (MR) signals in feline epileptic patients, albeit without definitive confirmation of FePSO. 5

We present a case of a cat with complex partial seizures and orofacial involvement resembling LE in humans and cats. In this instance, the condition is associated with a cerebral gliosarcoma and accompanied by MR and histopathological evidence of bilateral hippocampal changes. The report delves into clinical presentation, imaging results, histopathological examination, and immunohistochemistry findings.

2 CASE PRESENTATION

A 16‐year‐old neutered female domestic shorthair cat was referred for evaluation due to the sudden onset of signs including inappetence, ataxia, disorientation, and vacant staring.

Upon physical examination, the urinary bladder was found to be excessively distended and resistant to manual expression. Neurological examination revealed signs of ataxia, lethargy, and disorientation. The cat exhibited an absence of left menace response and reduced nasal sensation on the left side, while the remainder of the neurological examination showed no noteworthy findings. The cat displayed focal seizures characterized by a rightward head turn and circling, accompanied by orofacial automatisms such as facial twitching, lip‐smacking, salivation, and mydriasis. These episodes were brief, lasting roughly 30 s, and repeating multiple times throughout the day. They often ended with a single vocalization. In between these episodes, the patient would stare vacantly into space. These findings indicated dysfunction of the right forebrain with involvement of the limbic system.

A mild, non‐regenerative anemia was detected during complete blood count analysis, while serum biochemistry analysis yielded normal results. The total T4 level was low (9.4 nmol/L; reference interval: 10.0–60.0). Serial blood pressure measurements fell within normal ranges. The results of the rapid immunoassay, designed for simultaneous detection of feline leukemia virus (FeLV) antigen and feline immunodeficiency virus (FIV) antibodies, were negative.

Thoracic and abdominal radiography revealed unremarkable findings.

Brain MRI was performed using a Siemens Magnetom Essenza™ 1.5 T scanner. The MRI signal intensities are compared to gray matter. The MRI study revealed an ill‐defined intra‐axial mass in the right piriform lobe that extended into the right internal capsule. The mass appeared round in shape, exhibiting hypointensity on T1‐weighted (T1W) images, mild heterogeneous hyperintensity on T2‐weighted (T2W), T2‐weighted fluid‐attenuated inversion recovery (T2‐FLAIR), and diffusion weighted (DW) images, and homogeneous hyperintensity on T2* weighted (T2*W) images. No evidence of restricted diffusion was observed on apparent diffusion coefficient (ADC) map. The mass was surrounded by extensive perilesional edema, manifesting as a markedly hyperintense rim encircling the mass on T2W and T2‐FLAIR images. Upon administration of gadoteric acid (0.1 mmol/kg intravenously; Gadovist™, Bayer Schering Pharma), a well‐defined, marked, and homogeneous contrast enhancement was evident at the center of the mass. This lesion induced a slight mass effect, leading to a midline shift of the falx cerebri to the left and resulting in the effacement of the third ventricle as well as partial compression of the right lateral ventricle. Additionally, a moderate and bilateral swelling of the hippocampus was noted, characterized by heterogeneous hyperintensity on T2W, T2‐FLAIR, and DW images, accompanied by marked contrast enhancement (Figure 1). No evidence of restricted diffusion was observed on ADC map. Despite the presence of a space‐occupying lesion, the collection of cerebrospinal fluid (CSF) was not contraindicated, as the patient did not exhibit overt clinical or radiological signs of increased intracranial pressure. Cisternal CSF analysis revealed an elevated protein concentration (75 mg/dL; reference interval <25 mg/L), indicative of albuminocytologic dissociation in the absence of concurrent increased nucleated cellularity. Serological testing for Toxoplasma gondii returned negative results. While a preliminary diagnosis of glioma associated with moderate post‐ictal hippocampal changes was established, the potential presence of concurrent LE could not be entirely ruled out.

FIGURE 1 T2W midsagittal (A and B) and T2W (A1 and B1), T2‐FLAIR (A2 and B2), and T1W (A3 and B3) and T1W post‐contrast (A4 and B4) transverse MR images at the level of piriform lobe (As images) and hippocampus (Bs images). The images show an ill‐defined intra‐axial mass lesion in the right piriform lobe (white arrowheads), hyperintense on T2W and T2‐FLAIR images, and isointense on T1W transverse MR image. The mass shows a well‐defined and homogeneous contrast enhancement. There is moderate swelling in the hippocampus (blue stars), which is hyperintense on T2W and T2‐FLAIR images, and isointense on T1W transverse image, and associated with heterogeneous contrast enhancement.

Under general anesthesia, the urinary bladder was easily expressed, providing support for the suspicion of neurogenic urinary retention. The cat recovered well from the procedure, and his neurological status remained unchanged. We initiated the administration of levetiracetam (20 mg/kg iv every 8 h; Desitrend™, Desitin Pharma Ltd.) and phenobarbital (3 mg/kg iv every 12 h; Phenobarbital Sodium™, Martindale Pharma) were administered. The intravenous route was chosen due to the severe disorientation, inappetence, and recurrent epileptic seizures, which made oral drug administration challenging. While contemplating the placement of an esophageal feeding tube to aid feeding and drug delivery, as well as considering the use of an anti‐inflammatory dosage of corticosteroid drug to address the perilesional edema, the owner elected for euthanasia 24 h after treatment initiation, due to the poor long‐term prognosis.

The cat's brain was collected and preserved for histological examination within a few hours after euthanasia. Upon gross examination, a poorly defined, whitish space‐occupying lesion was evident in the right piriform lobe. Subsequent histological examination disclosed a neoplasm characterized by an infiltrative and vascularized nature. The tumor consisted of a pleomorphic spindle cell population arranged in irregular fascicles interspersed with numerous reactive astrocytes. Predominantly composed of spindle cells, these cells displayed elongated, fusiform, or ovoid nuclei with lax chromatin and prominent multiple nucleoli. Their cytoplasm was scarce, making cell margins difficult to discern. Notably, there was a marked anisocariosis, and frequent mitotic figures were observed (1–2/40× field). Stellated‐like cells were also present. Immunohistochemical analysis revealed that a majority of the neoplastic cells were positive for vimentin, indicative of mesenchymal origin, consistent with sarcoma. However, some cells also exhibited positivity for glial fibrillary acidic protein (GFAP) and S‐100 protein, suggesting a neuroectodermal origin, specifically astrocytic. Negative staining for Sox10 and Desmin excluded neural crest‐derived cell (such as Schwann cells and melanocytes) and smooth muscle cells neoplasms, respectively (Figure 2). Moreover, substantial loss of pyramidal neurons was evident, accompanied by fibrotic changes in the neuropil of both hippocampal Ammon's horns. Numerous mononuclear perivascular cuffs were observed in the medulla oblongata. The overall findings were consistent with a diagnosis of cerebral gliosarcoma concurrent with HS.

FIGURE 2 Photomicrograph of section stained in H&E of the cerebral gliosarcoma of a cat, illustrating a highly infiltrative and vascularized neoplasm made by a pleomorphic spindle cell population organized in irregular fascicles (A). On immunohistochemical analysis, most neoplastic cells are positive to vimentin (D), supporting the presence of sarcoma and some of the cells also show positivity to glial fibrillary acidic protein (B) and S‐100 protein (C), indicating astrocytic origin of the neoplastic cells (Scale bar = 1 mm). The black arrows highlight the areas with the strongest immune‐positive staining.

Unfortunately, feline leucine‐rich glioma‐inactivated 1 (LGI1)‐antibody testing in serum or CSF was not performed, and the possibility of retrospective testing on brain tissue was considered but ultimately proved unfeasible. Additional immunostaining on the tumor histology blocks was performed, revealing scattered positivity for CD3 (T‐cell marker) and CD20 (B‐cell marker) in association with blood vessels (Figure 3). Unfortunately, no hippocampal sections were available for immunohistological staining.

FIGURE 3 Photomicrograph of section stained in H&E (A and inset scale bars 1 mm and 100 μm, respectively) and CD3 (B), CD20 (C), and MHC (D) (all 100 μm) of the cerebral gliosarcoma of a cat. The arrowheads on H&E point to the tumor.

3 DIAGNOSIS

The patient was diagnosed with bilateral HS concurrent with gliosarcoma in the right piriform lobe. Although we couldn't determine the exact nature of the hippocampal changes due to insufficient biomaterial, the patient's prognosis was considered poor due to the presence of a high‐grade glioma. It is recommended to conduct feline LGI1‐antibody testing along with brain MRI to rule out FePSO.

4 DISCUSSION

We presented an uncommon case where bilateral HS was associated with gliosarcoma located in the right piriform lobe of a feline patient.

In both human and veterinary medicine, gliosarcoma is a rare primary neoplasm of the central nervous system. 1 According to the classification by the World Health Organization, 6 gliosarcoma is categorized as a subtype of glioblastoma grade IV astrocytoma. It is considered a malignant and rapidly growing tumor characterized by the presence of two distinct populations of cells: anaplastic astrocytic neoplastic cells and cells with sarcomatous differentiation. This bimorphic nature of gliosarcoma sets it apart from other types of gliomas and contributes to its aggressive behavior. 1

In human medicine, the approach to treatment typically involves a combination of resection, radiotherapy, and chemotherapy based on temozolomide. 7 However, the prognosis for gliosarcoma patients remains poor, with survival durations spanning from 4 to 18.5 months. 7

In feline literature, there exists solely a single case report of gliosarcoma. 2 This case featured a mass situated in the rostrotentorial region. Despite the cat having exhibited facial twitches and abnormal behavior for 18 months, no concurrent changes were observed in the hippocampus. The prognosis for this case was unfavorable, leading to euthanasia just 2 weeks after palliative corticosteroid treatment was administered.

In human patients, changes in hippocampal MR signals have been associated with both gliomas resulting from neoplastic cell infiltration, and LE. 8 , 9 LE is a non‐infectious cause of encephalitis and is being increasingly recognized as a cause of temporal lobe epilepsy (TLE), leading to HS and potentially drug‐resistant seizures. 9 LE can be associated with various antineuronal autoantibodies found in serum and/or CSF. 10 These antibodies target intracellular antigens in paraneoplastic LE cases or cell surface antigens like the voltage‐gated potassium channel (VGKC)‐associated proteins LGI1 and contactin‐associated protein 2 (CASPR2), expressed in the neuropil of the hippocampus and cerebellum. 11 Notably, the latter category of antibodies has generally shown a good response to immunomodulatory therapy. 11 In contrast, gliomas mimicking LE demonstrate poor response to immunotherapy. 8 Differential diagnosis between hippocampal changes due to glial cell infiltration and LE often necessitates biopsy or repeated MRI. 8

Among feline patients, changes in hippocampal MR signals have been associated with HS or HN. These changes are primarily connected to a feline form of LE known as FePSO. Frequently, these cases show positive antibody testing in serum LGI1 protein, which supports the diagnosis. 3 , 4 , 5 , 12 However, surface neuronal antibodies were identified in approximately 80% of feline cases in a cohort study, indicating the potential existence of other entities in seronegative cats. 3 While most cases demonstrated a positive response to antiepileptic treatment, 13 unlike human cases of LE, there is no definitive consensus regarding the utility and efficacy of steroid therapy in feline cases. 3

Some cases have exhibited a positive response to immunosuppressive prednisolone dose and antiepileptic treatment, although the efficacy of corticosteroids in larger observational cohorts is still under investigation. 13

HS or HN was found in six cats associated with other types of intracranial neoplasms, comprising three meningiomas and three oligodendrogliomas. 5 , 14 Interestingly, two of the meningiomas exhibited inflammatory infiltrates, resembling human LE. However, no antibody testing was carried out in these cases, hence a definitive confirmation of FePSO could not be established. 5 , 14

In our case, there was no evidence of neoplastic cell infiltration within the hippocampal region. However, we did observe numerous mononuclear perivascular cuffs in the histopathological section of the medulla oblongata. Immunostaining on the tumor histology blocks revealed scattered CD3 and CD20 positivity in connection with blood vessels (Figure 3). Regrettably, hippocampal sections were no longer available for immunohistological staining, preventing confirmation of hippocampal inflammation. Additionally, antibody testing could not be conducted due to insufficient biomaterial, which prevented us from confirming the presence of FePSO. The mononuclear perivascular cuffs might also suggest an immune response associated with gliosarcoma. 15

In humans experiencing generalized tonic–clonic seizure or status epilepticus, peri‐ictal changes may lead to transient modifications the hippocampal MR signals, even without a prior history of epilepsy. 16

Among feline patients, a report suggests potential post‐ictal changes affecting the hippocampus. 17 However, the author labels these findings as suspected HN. The diagnosis in this report lacks support from both antibody testing and histopathological analysis. Currently, no definitive proof of post‐ictal changes unrelated to FePSO exists in feline literature.

Recently, bilateral HN has been reported in a cat with a new‐onset of convulsive cluster seizures and status epilepticus. 18 Serum immunological analysis yielded negative results for LGI1 autoantibodies but revealed antibodies against DCC (deleted in colorectal carcinoma) also known as netrin‐1 receptor. While in humans, anti‐DCC autoantibodies are more associated with thymoma and myasthenia gravis than LE, 19 the author speculated on the potential presence of a feline form of paraneoplastic LE in this case. Unfortunately, only a brain necropsy was conducted, restricting the ability to confirm this speculation. This case demonstrated a transient remission for a month with anti‐seizure medication and an anti‐inflammatory dose of corticosteroids before progressing to status epilepticus and renal failure, necessitating euthanasia. It is worth noting that in human paraneoplastic LE cases, tumor treatment has shown to have a more significant impact on neurological outcomes than immune modulation or antiepileptic drugs. 18 , 20

In our case, thoracic and abdominal radiography did not reveal any significant findings, and there were no indications of neoplasia. As a result, it is improbable that the hippocampal changes are linked to a paraneoplastic process. Sadly, the rapid deterioration of the patient's condition hampered the evaluation of treatment options. Nevertheless, it is important to note that the prognosis associated with gliosarcoma is generally poor. 2 , 21

The limitations of this study include the absence of the feline LGI1‐antibody testing and immunostaining of hippocampal sections for immune mediators, primarily due to insufficient biomaterial. Unfortunately, this prevented us from attributing the histologically presence of inflammatory cells definitively to LE or confirming them as an immune response associated with gliosarcoma. Furthermore, although post‐ictal changes have been described but not confirmed in cats, 17 the observed hippocampal changes may also be considered attributable to cluster seizures.

5 CONCLUSION

Our report highlights a rare case of gliosarcoma in a cat, presenting a unique association with bilateral HS. For feline cases showing complex partial seizures with orofacial involvement, it is recommended to perform feline LGI1‐antibody testing in conjunction with brain MRI to exclude FePSO mediated by these entities. It is also advisable to perform thoracic and abdominal imaging to verify the absence of neoplasia in other regions of the body. Unfortunately, our case's prognosis remained poor due to the presence of a high‐grade glioma.

AUTHOR CONTRIBUTIONS

Ana Martinez: Writing – original draft; writing – review and editing. Sophie Binks: Investigation; writing – review and editing. Martí Pumarola: Investigation; writing – review and editing. Alexandros Hardas: Investigation; writing – review and editing. Alistair Easton: Investigation; writing – review and editing. Leticia Campo: Investigation; writing – review and editing. Molly Browne: Investigation; writing – review and editing. Susana Martins: Investigation; writing – review and editing. Laurent S. Garosi: Investigation; writing – review and editing. Francesco Di Dona: Investigation; writing – review and editing. Anna Tauro: Conceptualization; data curation; formal analysis; investigation; methodology; supervision; validation; writing – original draft; writing – review and editing.

FUNDING INFORMATION

The authors received no financial support for the research, authorship, and/or publication of this article.

CONFLICT OF INTEREST STATEMENT

The authors do not report any conflict of interest.

ETHICS STATEMENT

No ethical approval has been required for this study as it was not experimental. A written informed consent has been taken beforehand from the owners.

CONSENT

The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a review article with no original research data. The procedure was carried out as part of high‐standard veterinary care, and informed (written) client consent had been obtained beforehand. Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

ACKNOWLEDGMENTS

The authors thank Ester Blasco and Tamara Rivero Balsera for the technical assistance.

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
==== Refs
REFERENCES

1 Lutterbach J , Guttenberger R , Pagenstecher A . Gliosarcoma: a clinical study. Radiother Oncol. 2001;61 (1 ):57‐64. doi:10.1016/S0167-8140(01)00415-7 11578729
2 Álvarez P , Wessmann A , Pascual M , Comas O , Dolors P , Pumarola M . Cerebral gliosarcoma with perivascular involvement in a cat. JFMS Open Rep. 2019;5 (2 ):2055116919879783. doi:10.1177/2055116919879783 31636916
3 Glantschnigg‐Eisl U , Klang A , Kneissl S , et al. A feline model of spontaneously occurring autoimmune limbic encephalitis. Vet J. 2023;296‐297 :105974. doi:10.1016/j.tvjl.2023.105974
4 Klang A , Schmidt P , Kneissl S , et al. IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage‐gated Potassium Channel complex antibodies. J Neuropathol Exp Neurol. 2014;73 :403‐413. doi:10.1097/NEN.0000000000000063 24709680
5 Klang A , Högler S , Nedorost N , et al. Hippocampal necrosis and sclerosis in cats: a retrospective study of 35 cases. Acta Vet Hung. 2018;66 (2 ):269‐280. doi:10.1556/004.2018.025 29958521
6 Louis D , Perry A , Reifenberger G , et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131 :803‐820. doi:10.1007/s00401-016-1545-1 27157931
7 Huo Z , Yang D , Shen J , et al. Primary gliosarcoma with long‐survival: report of two cases and review of literature. Int J Clin Exp Pathol. 2014;7 (9 ):6323‐6332.25337286
8 Zoccarato M , Valeggia S , Zuliani L , et al. Conventional brain MRI features distinguishing limbic encephalitis from mesial temporal glioma. Neuroradiology. 2019;61 (8 ):853‐860. doi:10.1007/s00234-019-02212-1 31028423
9 Rácz A , Hummel C , Becker A , et al. Histopathologic characterization and neurodegenerative markers in patients with limbic encephalitis undergoing epilepsy surgery. Front Neurol. 2022;15 (13 ):859868. doi:10.3389/fneur.2022.859868
10 Graus F , Titulaer M , Balu R , et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15 (4 ):391‐404. doi:10.1016/S1474-4422(15)00401-9 26906964
11 Sharma A , Dubey D , Sawhney A , Janga K . GAD65 positive autoimmune limbic encephalitis: a case report and review of literature. J Clin Med Res. 2012;4 (6 ):424‐428. doi:10.4021/jocmr1080w 23226176
12 Pakozdy A , Halasz P , Klang A , et al. Suspected limbic encephalitis and seizure in cats associated with voltage‐gated potassium channel (VGKC) complex antibody. J Vet Intern Med. 2013;27 (1 ):212‐214. doi:10.1111/jvim.12026 23278981
13 Fors S , Van Meervenne S , Jeserevics J , Rakauskas M , Cizinauskas S . Feline hippocampal and piriform lobe necrosis as a consequence of severe cluster seizures in two cats in Finland. Acta Vet Scand. 2015;57 (1 ):41. doi:10.1186/s13028-015-0127-x 26215252
14 Vanhaesebrouck A , Posch B , Baker S , Plessas I , Palmer A , Constantino‐Casas F . Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis. J Feline Med Surg. 2012;14 (12 ):932‐937. doi:10.1177/1098612X12454419 22791561
15 Chen H , Li M , Guo Y , et al. Immune response in glioma's microenvironment. Innov Surg Sci. 2021;5 (3–4 ):20190001. doi:10.1515/iss-2019-0001 33511267
16 Kim J , Chung J , Yoon P , et al. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion‐weighted imaging. AJNR Am J Neuroradiol. 2001;22 (6 ):1149‐1160.11415912
17 Raimondi F , Shihab N , Gutierrez‐Quintana R , et al. Magnetic resonance imaging findings in epileptic cats with a normal interictal neurological examination: 188 cases. Vet Rec. 2017;180 (25 ):610. doi:10.1136/vr.104142 28386032
18 Hasegawa D , Ohnishi Y , Koyama E , et al. Deleted in colorectal cancer (netrin‐1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis. J Vet Intern Med. 2019;33 (3 ):1440‐1445. doi:10.1111/jvim.15492 30942925
19 Torres‐Vega E , Mancheño N , Cebrián‐Silla A , et al. Netrin‐1 receptor antibodies in thymoma‐associated neuromyotonia with myasthenia gravis. Neurology. 2017;88 (13 ):1235‐1242. doi:10.1212/WNL.0000000000003778 28251919
20 Gultekin S , Rosenfeld M , Voltz R , Eichen J , Posner J , Dalmau J . Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123 (Pt 7 ):1481‐1494. doi:10.1093/brain/123.7.1481 10869059
21 Amer A , Khose S , Alhasan H , et al. Clinical and survival characteristics of primary and secondary gliosarcoma patients. Clin Neurol Neurosurg. 2022;214 :107146. doi:10.1016/j.clineuro.2022.107146 35101778
