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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
<issn pub-type="epub">1664-3224</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fimmu.2024.1375497</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Immunology</subject>
<subj-group>
<subject>Case Report</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Facial palsy after administration of immune checkpoint inhibitors: case report, literature review and clinical care management</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Mezni</surname>
<given-names>Essia</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2667367"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Corazza</surname>
<given-names>Giovanni</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2667334"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mari</surname>
<given-names>Roxane</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1894420"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Coze</surname>
<given-names>Stephanie</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Charrier</surname>
<given-names>Nathalie</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Chanez</surname>
<given-names>Brice</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1197496"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chretien</surname>
<given-names>Anne Sophie</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/143521"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
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<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Rochigneux</surname>
<given-names>Philippe</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/142963"/>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Medical Oncology Department, Paoli-Calmettes Institute</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Neurology Department, Assitance Publique H&#xf4;pitaux de Marseille, Aix-Marseille University</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Referral Centre for Neuromuscular Diseases and Amyotrophic Lateral Sclerosis (ALS), H&#xf4;pital La Timone</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Radiology Department, Assitance Publique H&#xf4;pitaux de Marseille, Aix-Marseille University</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<aff id="aff5">
<sup>5</sup>
<institution>Nuclear Medicine Department, Paoli-Calmettes Institut</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<aff id="aff6">
<sup>6</sup>
<institution>Team Immunity and Cancer, Centre de Recherche en Cance&#xed;rologie de Marseille (CRCM), Inserm, U1068, Centre national de la recherche scientifique (CNRS), Unit&#xe9; Mixte de Recherche 7258 (UMR7258), Paoli-Calmettes Institute, Aix-Marseille University</institution>, <addr-line>Marseille</addr-line>, <country>France</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Jonathan Pol, Institut National de la Sant&#xe9; et de la Recherche M&#xe9;dicale (INSERM), France</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Shigeaki Suzuki, Keio University, Japan</p>
<p>Jun Sawada, Asahikawa Medical University, Japan</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Philippe Rochigneux, <email xlink:href="mailto:rochigneuxp@ipc.unicancer.fr">rochigneuxp@ipc.unicancer.fr</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>22</day>
<month>03</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1375497</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>01</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>03</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Mezni, Corazza, Mari, Coze, Charrier, Chanez, Chretien and Rochigneux</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Mezni, Corazza, Mari, Coze, Charrier, Chanez, Chretien and Rochigneux</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>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) and the copyright owner(s) 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.</p>
</license>
</permissions>
<abstract>
<p>Neurological immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI) are rare complications of immunotherapy, particularly dreadful for patients and clinical teams. Indeed, neurological irAEs are potentially severe and their diagnosis require prompt recognition and treatment. Additionally, the spectrum of neurological irAEs is broad, affecting either neuromuscular junction, peripheral or central nervous system. Here, we described the case of a 55-year man with metastatic melanoma, facing a brutal right peripheral cerebral palsy after his third ipilimumab/nivolumab infusion. After the case presentation, we reviewed the literature about this rare complication of immunotherapy, and described its diagnosis work-up and clinical management.</p>
</abstract>
<kwd-group>
<kwd>cerebral palsy</kwd>
<kwd>immune checkpoint inhibitors</kwd>
<kwd>immune toxicity</kwd>
<kwd>neurological toxicity</kwd>
<kwd>nivolumab</kwd>
<kwd>ipilimumab</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="34"/>
<page-count count="9"/>
<word-count count="3124"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Cancer Immunity and Immunotherapy</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<title>Introduction</title>
<p>Immune checkpoint inhibitors (ICI) reinvigorate patient&#x2019;s own immune system to recognize and destroy tumor cells (<xref ref-type="bibr" rid="B1">1</xref>). These treatments, notably the CTLA-4 inhibitor ipilimumab (Ipi) and the PD-1 inhibitor nivolumab (Nivo), revolutionized the treatment of advanced solid tumors (<xref ref-type="bibr" rid="B2">2</xref>). Indeed, in metastatic melanoma, a first-line combination of Ipi and Nivo lead to an impressive 5-year overall survival of 52% (<xref ref-type="bibr" rid="B3">3</xref>). However, these efficient treatments have numerous immune-related adverse events (irAEs), with a broad spectrum of severity, that potentially affect every organ of the patient (<xref ref-type="bibr" rid="B4">4</xref>). If the onset of irAES are frequently associated with increased efficacy of ICI (<xref ref-type="bibr" rid="B5">5</xref>), their management in routine clinical practice remain challenging, as each of them requires specific diagnostic procedure and sometimes specific treatments (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>Among every irAES, neurological irAES (N-irAES) are particularly difficult to manage, for several reasons: i) contrary to frequent irAES, like thyroid dysfunction or cutaneous toxicity, neurological complications might be life-threatening; ii) neurological complications are highly polymorphic as they might affect central nervous system (encephalitis, meningitis), peripheral nervous system (peripheral neuropathy, Guillain-Barre syndrome) or neuromuscular junction (myositis, myasthenic syndromes) (<xref ref-type="bibr" rid="B7">7</xref>); iii) the differential diagnoses are numerous (cancer progression, paraneoplastic syndrome, stroke&#x2026;) and iv) the radiological and biological work-up necessary to diagnose N-irAES are frequently highly technologic (brain MRI, specific autoantibodies) or invasive (lumbar punction). Consequently, medical oncologists need clear knowledge to face neurological irAES and case descriptions are helpful in clinical practice.</p>
<p>Here, we report the case of a patient with metastatic melanoma experiencing a brutal facial palsy after three infusions of ipilimumab/nivolumab.</p>
</sec>
<sec id="s2">
<title>Case presentation</title>
<p>A 55 year-old man, ECOG-PS 0, with a medical history of dyslipidemia and non-severe malaria presented a right inguinal adenopathy, gradually increasing in volume, associated with a black skin lesion of the right thigh, surrounded with a perilesional vitiligo. In July 2022 (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>: patient&#x2019;s timeline), he consulted in our center (Paoli-Calmettes Institute, Cancer Center in Marseille, France) and beneficiated from a right inguinal lymph node biopsy (July 22, 2022). The histology revealed a malignant melanoma, PS100<sup>+</sup>, HMB 45<sup>+</sup> and MelanA<sup>+</sup>. The PET-CT confirmed a hypermetabolic skin lesion with large right inguinal adenopathies, without distant metastasis and the cerebral MRI was normal. The next generation sequencing (in-house panel of 96 genes) revealed a BRAF mutation in exon 15, V600D (p.(Val600Asp), a punctual variation of TERT promotor (c.-146C&gt;T) and focal homozygous deletions of genomic regions containing the loci CDKN2A and CDKN2B and TERT.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Patient&#x2019;s timeline.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1375497-g001.tif"/>
</fig>
<p>In August 2022, the patient had surgical excision of the skin lesion and a right inguinal lymph node dissection. As recommended in tumor board, the patient started adjuvant PD-1 inhibitor (pembrolizumab 200 mg/3 weeks), with C1D1 in October 2, 2022. Unfortunately, in April 2023, after only 6 months of adjuvant pembrolizumab the patient relapsed with multiple metastatic liver lesions and multiple sub-diaphragmatic lymph nodes, particularly in the right iliopelvic region (PET-CT of April 27, 2023: <xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2A</bold>
</xref>). The new tumor board recommended either the inclusion in a clinical trial (investigating Ipi/Nivo +/- anti IL-8) or the Ipi/Nivo combination in routine clinic that the patient preferred. The first three infusions of Ipi/Nivo were well tolerated [C1: May 24, 2023 (Day 1)/C2: June 13, 2023/C3: July 04, 2023], with only a grade 1 dermatitis with pruritus.</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>PET-CT at baseline <bold>(A)</bold>, after 3 Ipilimumab/Nivolumab combinations <bold>(B)</bold> and after 3 Nivolumab maintenance <bold>(C)</bold>.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1375497-g002.tif"/>
</fig>
<p>However, on July 22, 2023 (Day 59), the patient presented with acute peripheral left facial palsy (grade 3 on CTCAE v5.0), with retro-auricular pain and numbness of the face. He consulted the emergency department in a local hospital. The clinical examination did not show any associated neurological signs (motor or sensitive deficit of the limb, cognitive impairment, additional cranial nerve injury) and the biological tests were normal. The cerebral CT scanner was normal. A diagnosis of Bell&#x2019;s palsy was suspected: lumbar puncture was not performed and a treatment of oral prednisolone 1 mg/kg (80 mg) was started, together with ocular protection. The cerebral MRI in August 1, 2023 revealed no secondary localization, no signs suggestive of a stroke, but inflammation of the right facial nerve, suggestive of facial nerve neuritis (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>). HIV, VZV, HSV and Lyme (<italic>Borrelia burgdorferi</italic>) serology were negative, glycemia and TSH were normal. Altogether, the concertation between oncologists and neurologists adopted the probable diagnosis of an immune-related facial palsy caused by ipilimumab/nivolumab combination. Consequently, we decided to stop ipilimumab/nivolumab combination.</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>Cerebral MRI, Coronal <bold>(A)</bold> and axial <bold>(B)</bold> 3DT1MPRAGE sequences after gadolinium reconstruction showing contrast of the fundus of the internal auditory meatus and of the right geniculate ganglion attesting to right facial neuritis. Hypophisitis is shown in the sagittal sequence <bold>(C)</bold>.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1375497-g003.tif"/>
</fig>
<p>The clinical evolution was favorable: after 10 days of prednisolone, the facial palsy improved and the patients began to close his upper right eyelid. The prednisolone was decreased by 10 mg every week (until 10 mg, then 5 mg and stop) and in September 2023, the patient did not present any sign of cerebral palsy, nor ocular complication. Interestingly, two other irAEs were observed: i) an hypophysitis revealed by the brain MRI of August 1, 2023 (diffusely enlarged pituitary gland, not shown) and a corticotropic deficiency (8&#xa0;a.m. blood level cortisol: 2 nmol/l; blood level ACTH: 0.7 pmol/l); ii) a vitiligo around 20% of body surface starting in September 2023.</p>
<p>Concerning efficacy, the PET-CT after three infusions of Ipi/Nivo (August 9, 2023) revealed a very good metabolic partial response (liver metastases of segment I and IV, right external iliac adenopathy) and a complete response on other liver metastases and other sub-diaphragmatic lymph nodes (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2B</bold>
</xref>). We canceled the fourth and last ipilimumab/nivolumab combination and started the maintenance therapy by nivolumab monotherapy 480 mg q4w in September 13, 2023. PET-CT after three nivolumab maintenance (December 20, 2023) revealed a metabolic complete response in liver and lymph nodes (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2C</bold>
</xref>). At the date of redaction of this case report, the patient was ECOG-PS 0, maintained an intense professional activity without any clinical sequelae of the metastastic melanoma or the former facial palsy.</p>
</sec>
<sec id="s3">
<title>Literature review and discussion</title>
<p>Here, we report the case of a patient presenting a facial palsy after 3 infusions of ipilimumab/nivolumab. As ICI-induced facial palsy might be challenging for oncologists, we will discuss the literature and the clinical management of this rare neurological irAE.</p>
<sec id="s3_1">
<title>ICI-induced facial palsy: literature review</title>
<p>The first case of ICI-induced facial palsy was reported in 2015 by Altman et&#xa0;al. (<xref ref-type="bibr" rid="B8">8</xref>). The physiopathological mechanism of this neurological adverse event remains unknown to date, even if an immune tolerance breakdown is the most probable (<xref ref-type="bibr" rid="B9">9</xref>). Although rare, facial palsy has been reported in the literature with different ICIs agents and combinations: ipilimumab (<xref ref-type="bibr" rid="B10">10</xref>) pembrolizumab (<xref ref-type="bibr" rid="B11">11</xref>), atezolizumab (<xref ref-type="bibr" rid="B12">12</xref>), nivolumab (<xref ref-type="bibr" rid="B13">13</xref>), ipilimumab plus nivolumab (<xref ref-type="bibr" rid="B14">14</xref>), ipilimumab plus pembrolizumab (<xref ref-type="bibr" rid="B10">10</xref>), tremelimumab plus durvalumab (<xref ref-type="bibr" rid="B15">15</xref>). The <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref> summarizes the main reported cases of facial palsy induced by ICIs reported in the literature. Interestingly, brain MRI was normal in approximately 50% of the cases and an additional irAE was observed in approximately 30% of the cases. In our patient, whereas ICI monotherapy by pembrolizumab was not associated with irAEs and let to tumor progression, Ipi/Nivo combination led to three irAEs (notably facial palsy) and a metabolic complete response at 7 months.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Published cases of patients with checkpoint inhibitor-induced facial palsy (literature review).</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="center">Authors</th>
<th valign="top" align="center">Diagnosis</th>
<th valign="top" align="center">Gender</th>
<th valign="top" align="center">Age<break/>(years)</th>
<th valign="top" align="center">Treatment</th>
<th valign="top" align="center">Cycles before irAEs</th>
<th valign="top" align="center">Clinical presentation</th>
<th valign="top" align="center">MRI</th>
<th valign="top" align="center">Management</th>
<th valign="top" align="center">Duration of symptoms</th>
<th valign="top" align="center">outcome</th>
<th valign="top" align="center">ICIs discontinuation</th>
<th valign="top" align="center">Other immune toxicity</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="center">Zecchini et&#xa0;al. (<xref ref-type="bibr" rid="B14">14</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">45</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">valacyclovir<break/>+<break/>prednisone</td>
<td valign="top" align="center">13 days</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Permanent discontinuation of ipi<break/>+<break/>continuation of nivo monotherapy</td>
<td valign="top" align="center">skin toxicity</td>
</tr>
<tr>
<td valign="top" rowspan="5" align="center">Yuen C,et al (<xref ref-type="bibr" rid="B10">10</xref>).</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">F</td>
<td valign="top" align="center">49</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">Linear enhancement<break/>of the facial nerves</td>
<td valign="top" align="center">Dexamethasone</td>
<td valign="top" align="center">1 weak</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Autoimmune<break/>hemolytic<break/>anemia</td>
</tr>
<tr>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">68</td>
<td valign="top" align="center">ipi + pembro</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">Diffuse left facial nerve enhancement</td>
<td valign="top" align="center">Acyclovir</td>
<td valign="top" align="center">23 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">54</td>
<td valign="top" align="center">ipi</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">Enhancement of the right facial nerve</td>
<td valign="top" align="center">Prednisone<break/>+<break/>valacyclovir</td>
<td valign="top" align="center">4 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Neuropathy (GBS like syndrome)<break/>+<break/>autoimmune<break/>thyroiditis</td>
</tr>
<tr>
<td valign="top" align="center">bladder cancer</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">65</td>
<td valign="top" align="center">atezo</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">3 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center"/>
<td valign="top" align="center">Polyradiculopathy +<break/>neuropathy</td>
</tr>
<tr>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">39</td>
<td valign="top" align="center">ipi+ nivo</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">Enhancement of the right facial, bilateral oculomotor and the V2 segments of trigeminal nerves</td>
<td valign="top" align="center">Prednisone<break/>+<break/>valacyclovir</td>
<td valign="top" align="center">8 weeks</td>
<td valign="top" align="center">PR</td>
<td valign="top" align="center">Permanent discontinuation of atezo</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">Bruno, et&#xa0;al. (<xref ref-type="bibr" rid="B11">11</xref>)</td>
<td valign="top" align="center">adenocarcinoma of the lung</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">72</td>
<td valign="top" align="center">pembro</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">bilateral facial palsy + bilateral ptosis and ophthalmoplegia +<break/>dysphonia + dysphagia.</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">IV immunoglobulins</td>
<td valign="top" align="center"/>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">NM</td>
</tr>
<tr>
<td valign="top" align="center">Yost et&#xa0;al. (<xref ref-type="bibr" rid="B16">16</xref>).</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">64</td>
<td valign="top" align="center">pembro</td>
<td valign="top" align="center">3 months after 14 months of ICI</td>
<td valign="top" align="center">Bilateral facial + diffuse areflexia + flaccid dysarthria (bifacial weakness variant of Guillain-Barre syndrome)</td>
<td valign="top" align="center">subtle enhancement of the facial nerves bilaterally</td>
<td valign="top" align="center">Intravenous immunoglobulin<break/>+<break/>prednisone</td>
<td valign="top" align="center">2 weeks</td>
<td valign="top" align="center"/>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Autoimmune hepatitis</td>
</tr>
<tr>
<td valign="top" align="center">Vogrig et&#xa0;al. (<xref ref-type="bibr" rid="B17">17</xref>).</td>
<td valign="top" align="center">kidney cancer</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">51</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">unilateral facial palsy</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">corticosteroids</td>
<td valign="top" align="center">3 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">discontinuation of ipi</td>
<td valign="top" align="center">NM</td>
</tr>
<tr>
<td valign="top" align="center">Beninato, et&#xa0;al. (<xref ref-type="bibr" rid="B18">18</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">48</td>
<td valign="top" align="center">ipi</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">86 days</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Permanent discontinuation of ipi</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">Altman et&#xa0;al. (<xref ref-type="bibr" rid="B8">8</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">32</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">Unilateral facial palsy<break/>Bilateral facial palsy after C3 ipi+nivo</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">8 weeks</td>
<td valign="top" align="center">PR</td>
<td valign="top" align="center">Permanent discontinuation of ipi after C3</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">Yan et&#xa0;al. (<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">74</td>
<td valign="top" align="center">nivo</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Oral steroid</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="left">Takemura et&#xa0;al. (<xref ref-type="bibr" rid="B20">20</xref>)</td>
<td valign="top" align="center">kidney cancer</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">nivo</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">enhancement of the left facial nerve</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">8 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Permanent discontinuation of nivo</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">Kichloo et&#xa0;al. (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top" align="center">small cell lung cancer</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">68</td>
<td valign="top" align="center">atezo</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">4 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Temporary discontinuation</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="center">Zieman et&#xa0;al. (<xref ref-type="bibr" rid="B21">21</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">F</td>
<td valign="top" align="center">51</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Prednisone<break/>+<break/>valacyclovir</td>
<td valign="top" align="center">3 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Permanent discontinuation of ipi<break/>+<break/>continuation of nivo monotherapy</td>
<td valign="top" align="center">no</td>
</tr>
<tr>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">F</td>
<td valign="top" align="center">68</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Prednisone<break/>+<break/>valacyclovir</td>
<td valign="top" align="center">3 weeks</td>
<td valign="top" align="center">CR</td>
<td valign="top" align="center">Permanent discontinuation of ipi<break/>+<break/>continuation of nivo monotherapy</td>
<td valign="top" align="center">Autoimmune hepatitis<break/>+<break/>autoimmune colitis</td>
</tr>
<tr>
<td valign="top" align="center">Numata et&#xa0;al. (<xref ref-type="bibr" rid="B22">22</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">46</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">Unilateral facial palsy</td>
<td valign="top" align="center">normal</td>
<td valign="top" align="center">hydrocortisone</td>
<td valign="top" align="center">2 weeks</td>
<td valign="top" align="center">PR</td>
<td valign="top" align="center">Temporary discontinuation of ipi</td>
<td valign="top" align="center">Bilateral anterior uveitis + vitiligo</td>
</tr>
<tr>
<td valign="top" align="center">Altman et&#xa0;al. (<xref ref-type="bibr" rid="B8">8</xref>)</td>
<td valign="top" align="center">melanoma</td>
<td valign="top" align="center">M</td>
<td valign="top" align="center">32</td>
<td valign="top" align="center">ipi + nivo</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">Bilateral facial palsy</td>
<td valign="top" align="center">NM</td>
<td valign="top" align="center">Prednisone</td>
<td valign="top" align="center">8 weeks</td>
<td valign="top" align="center">PR</td>
<td valign="top" align="center">Permanent discontinuation after 3 cycles of ipi</td>
<td valign="top" align="center">no</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Ipi, ipilumumab; nivo, nivolumab; pembro, pembrolizumab; atezo, atezoluzumab; NM, not mentioned; CR, complete resolution; PR, Partial resolution; IV, Intravenous.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>A systematic analysis published in 2023 assessed the risk of facial palsy associated with ICIs based on data from 21 randomized trials including 10,779 patients treated with ICIs (<xref ref-type="bibr" rid="B15">15</xref>). Patients were treated for several primary cancers: melanoma, gastro-esophageal cancer, renal or urothelial cancer and malignant mesothelioma. An increased risk of facial palsy associated with ICIs was reported in 23 cases with OR 3.07 (95% CI: 1.4&#x2013;6.5) compared to control treatment. Results of subgroup analysis indicated that OR of ICI-related FP did not vary significantly by tumor type, ICIs treatment schedule, case of events, study design, median PFS and publication status. In the same analysis, the FDA Adverse Event Reporting System database was retrospectively reviewed between 2011 and 2022. In total, 274 cases were identified. Most patients presenting facial palsy were treated with ICI only (82.1%) rather than with combination of ICI with other drug (17.9%). The median onset time of facial palsy was 5.5 weeks in this review and 15 weeks in another case series (<xref ref-type="bibr" rid="B18">18</xref>). In most of the cases, drug interruption was performed (78%) and clinical outcome was favorable (71.7%).</p>
</sec>
<sec id="s3_2">
<title>Neurological irAEs and ICI-induced facial palsy: epidemiology</title>
<p>Neurological irAEs (N-irAEs) are relatively rare with an estimated prevalence of 1-4% of ICI-treated patients (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>). Yet, with cardiological irAEs, neurological adverse events are among the most serious irAEs (<xref ref-type="bibr" rid="B25">25</xref>), with mortality rate of 28% for myasthenic syndrome and 21% for encephalitis. Thus, early detection, diagnosis and management of N-irAEs is a major issue. N-irAEs involving peripheral nervous system are twice more frequent than central nervous system (CNS) toxicity (<xref ref-type="bibr" rid="B7">7</xref>), and clinical as well as paraclinical characteristics of ICI-induced neuropathies differ from chemotherapy-induced neuropathies (<xref ref-type="bibr" rid="B26">26</xref>). Among N-irAEs, occurrence of facial palsy is particularly rare, with an incidence around 0.2% in the ICI-treated population (23 cases/10.779 patients) in the largest reported study (<xref ref-type="bibr" rid="B15">15</xref>). Furthermore, a recent study showed that combination of CTLA-4 and PD(L)-1 inhibitors is a risk factor of developing cranial neuropathies, including facial palsy (<xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>Melanoma may have a potential risk of neurological irAE compared to other cancers. Indeed, in the literature described in <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>, 12/18 patients presenting ICI-induced facial palsy are melanoma patients. This might be due to the early onset of ICI in melanoma patients since 2010 (which might increase the reported cases) and the high frequency of ICI combination, notably Ipi/Nivo which increase irAEs. However, a meta-analysis of 694 articles (<xref ref-type="bibr" rid="B7">7</xref>), melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p = 0.003) and less common in encephalitis (19/56, 34%; p = 0.001).</p>
</sec>
<sec id="s3_3">
<title>ICI-induced facial palsy: diagnosis</title>
<p>The diagnosis of facial palsy is primarily clinical. Physicians need to eliminate central facial paralysis that would lead to look for CNS involvement with simple neurological examination. Then, associated neurological symptoms, notably for immune-related myasthenia gravis, must be carefully searched to adapt patient&#x2019;s further exams and surveillance (<xref ref-type="bibr" rid="B28">28</xref>). It is mandatory to exclude differential diagnoses such as stroke or toxic, metabolic, infectious and endocrine neuropathies. Nevertheless, the main goal is to eliminate a carcinologic progression such as brain or leptomeningeal metastases (<xref ref-type="bibr" rid="B17">17</xref>, <xref ref-type="bibr" rid="B28">28</xref>). Differentiating immune-related from <italic>a frigore</italic> facial palsy (Bell&#x2019;s palsy) can be difficult. The delay between ICI introduction and the occurrence of firsts symptoms is estimated to 2 months (0.5-17.0 months) and might help ICI imputability (<xref ref-type="bibr" rid="B17">17</xref>).</p>
<p>Even if some of them are missing in our report, biological exams are important to eliminate other etiologies of reversible neuropathies: HbA1c, vitamin B12, TSH, vitamin B6, folate, serum protein electrophoresis, immunofixation and CPK. Other exams might be done depending on the context: ANA, ESR, CRP, ANCA, anti&#x2013;smooth muscle, SSA/SSB, RNP, anti-dsDNA, ganglioside antibodies, anti-MAG, anti-Hu (ANNA-1 ab), thiamine, Lyme, hepatitis B or C, and HIV. Thus, to our knowledge, anti-onconeural antibodies has always been reported as negative when reported in isolated ICI-related facial palsy (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B10">10</xref>).</p>
<p>Lumbar puncture aims to seek for carcinomatous cells. CSF analysis may show a pleiocytosis (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B17">17</xref>), but may also be normal (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B14">14</xref>). Nerve conduction study shows a reduced amplitude in the facial nerve and an altered blink reflex (<xref ref-type="bibr" rid="B11">11</xref>). Brain MRI may reveal an ipsilateral facial nerve enhancement after gadolinium infusion, or be normal (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B17">17</xref>).</p>
<p>In the case of our patient, due to the presence of hypophysitis, sarcoidosis diagnosis should be considered, but the patient did not present symptoms in the organs classically touched in this pathology (lungs, lymph nodes, joints, skin, eyes, heart, kidneys, etc.). Additionally, even if our patient did not complain of other symptoms and tendinous reflexes where present, electromyography could have been performed in this patient to increase diagnostic sensitivity (<xref ref-type="bibr" rid="B29">29</xref>).</p>
</sec>
<sec id="s3_4">
<title>ICI-induced facial palsy: clinical management ant treatment</title>
<p>N-irAEs management first relies on ICI discontinuation. In some reported cases of combined ICI treatment, only one of them was discontinued (<xref ref-type="bibr" rid="B17">17</xref>). Oral corticosteroids (1-2 mg/kg/d) may be introduced, and slowly tapered within 4 to 6 weeks (<xref ref-type="bibr" rid="B27">27</xref>). Some authors have used intravenous immunoglobulin (IVIG) instead or with corticosteroids (<xref ref-type="bibr" rid="B17">17</xref>). It is mandatory to assess the disease course with early and repeated neurological examination to adapt patient&#x2019;s management. In case of facial palsy being the inaugural symptom of a Guillain-Barre syndrome or a more diffuse neuropathy, further therapies might be considered such as plasma exchange (<xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>The prognosis of isolated facial palsy is good with 70% of complete recovery, within a median of 41 days (<xref ref-type="bibr" rid="B18">18</xref>). However, recovery can be partial with persistent sequelae in approximately one patient out of four (<xref ref-type="bibr" rid="B17">17</xref>). In this context, rehabilitation strategies for facial nerve injuries is crucial and several techniques are available, including exercise, electrical stimulation, biofeedback, and facial neuromuscular retraining (<xref ref-type="bibr" rid="B30">30</xref>). In case of full recovery, reintroduction of ICI might be considered in case of absence of alternative therapy. Indeed, disease progression has been shown to be the main cause of death in patients with irAEs (<xref ref-type="bibr" rid="B24">24</xref>). To switch ICI subtype (from CTLA-4 to PD-1 inhibitors) in non-neurological irAEs has been associated to a lower risk of relapse (<xref ref-type="bibr" rid="B31">31</xref>), but evidence are lacking in N-irAEs. Yet, no clear guideline is currently available, and this attitude should be a case-by-case evaluation.</p>
</sec>
<sec id="s3_5">
<title>Oncological perspective: quick and multi-disciplinary management</title>
<p>In conclusion, ICI-induced facial palsy is a rare complication that a medical oncologist rarely sees in his routine practice. The key in the management of these rare N-irAEs is the multi-disciplinary network between oncologists and neurologists or internists (<xref ref-type="bibr" rid="B32">32</xref>). This essential collaboration can take various forms, such as external consultants, immuno-toxicity meetings, mailing lists, messaging applications (<xref ref-type="bibr" rid="B33">33</xref>). Quick clinical evaluation, quick imaging and lab tests are essential to eliminate differential diagnoses and start early corticosteroid treatment, effective in 70-80% of cases (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B34">34</xref>). Building a strong network to deal with rare and life-threatening irAEs is one of the new challenge of medical oncology, a medical specialty where multi-disciplinary care has always been highly estimated.</p>
</sec>
</sec>
<sec id="s4" sec-type="data-availability">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.</p>
</sec>
<sec id="s5" sec-type="ethics-statement">
<title>Ethics statement</title>
<p>The studies involving humans were approved by Institut Paoli Calmettes institutional review board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec id="s6" sec-type="author-contributions">
<title>Author contributions</title>
<p>EM: Writing &#x2013; review &amp; editing, Writing &#x2013; original draft, Formal analysis, Data curation. GC: Writing &#x2013; review &amp; editing, Writing &#x2013; original draft. RM: Writing &#x2013; review &amp; editing, Investigation. SC: Writing &#x2013; review &amp; editing, Visualization. NC: Writing &#x2013; review &amp; editing, Visualization. BC: Writing &#x2013; review &amp; editing, Supervision. AC: Writing &#x2013; review &amp; editing, Supervision, Conceptualization. PR: Writing &#x2013; review &amp; editing, Writing &#x2013; original draft, Supervision, Methodology, Investigation, Data curation, Conceptualization.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the&#xa0;research, authorship, and/or publication of this article. Our&#xa0;work is supported by Paoli-Calmettes Institute and Aix-Marseille University.</p>
</sec>
<sec id="s8" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s9" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<fn-group>
<title>Abbreviations</title>
<fn fn-type="abbr">
<p>AE, Adverse Events; CNS, Central Nervous System ; CTLA-4, Cytotoxic T-lymphocyte-associated protein 4; ECOG-PS, Eastern Cooperative Oncology Group - Performance Status; IC, Immune Checkpoint Inhibitors; irAEs, Immune-Related Adverse Events; Ipi, Ipilimumab; MRI, Magnetic Resonance Imaging; Nivo, Nivolumab; N-irAEs, Neurological irAEs; PD-1/PD-L1, Programmed cell Death protein 1/Programmed cell Death-Ligand 1; PET-CT, Positron Emission Tomography Computed Tomodensitometry Scanner.</p>
</fn>
</fn-group>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Couzin-Frankel</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Breakthrough of the year 2013</article-title>. <source>Cancer Immunother Sci</source>. (<year>2013</year>) <volume>342</volume>:<page-range>1432&#x2013;3</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1126/science.342.6165.1432</pub-id>
</citation>
</ref>
<ref id="B2">
<label>2</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wolchok</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Putting the immunologic brakes on cancer</article-title>. <source>Cell</source>. (<year>2018</year>) <volume>175</volume>:<page-range>1452&#x2013;4</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.cell.2018.11.006</pub-id>
</citation>
</ref>
<ref id="B3">
<label>3</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wolchok</surname> <given-names>JD</given-names>
</name>
<name>
<surname>Chiarion-Sileni</surname> <given-names>V</given-names>
</name>
<name>
<surname>Gonzalez</surname> <given-names>R</given-names>
</name>
<name>
<surname>Grob</surname> <given-names>J-J</given-names>
</name>
<name>
<surname>Rutkowski</surname> <given-names>P</given-names>
</name>
<name>
<surname>Lao</surname> <given-names>CD</given-names>
</name>
<etal/>
</person-group>. <article-title>Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma</article-title>. <source>J Clin Oncol</source>. (<year>2021</year>) <volume>40</volume>:<page-range>127&#x2013;37</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1200/JCO.21.02229</pub-id>
</citation>
</ref>
<ref id="B4">
<label>4</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Champiat</surname> <given-names>S</given-names>
</name>
<name>
<surname>Lambotte</surname> <given-names>O</given-names>
</name>
<name>
<surname>Barreau</surname> <given-names>E</given-names>
</name>
<name>
<surname>Belkhir</surname> <given-names>R</given-names>
</name>
<name>
<surname>Berdelou</surname> <given-names>A</given-names>
</name>
<name>
<surname>Carbonnel</surname> <given-names>F</given-names>
</name>
<etal/>
</person-group>. <article-title>Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper</article-title>. <source>Ann Oncol Off J Eur Soc Med Oncol</source>. (<year>2016</year>) <volume>27</volume>:<page-range>559&#x2013;74</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/annonc/mdv623</pub-id>
</citation>
</ref>
<ref id="B5">
<label>5</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Beaufils</surname> <given-names>M</given-names>
</name>
<name>
<surname>Amodru</surname> <given-names>V</given-names>
</name>
<name>
<surname>Tejeda</surname> <given-names>M</given-names>
</name>
<name>
<surname>Boher</surname> <given-names>JM</given-names>
</name>
<name>
<surname>Zemmour</surname> <given-names>C</given-names>
</name>
<name>
<surname>Chanez</surname> <given-names>B</given-names>
</name>
<etal/>
</person-group>. <article-title>Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records</article-title>. <source>J Immunother Cancer</source>. (<year>2023</year>) <volume>11</volume>:<elocation-id>e006786</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1136/jitc-2023-006786</pub-id>
</citation>
</ref>
<ref id="B6">
<label>6</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Haanen</surname> <given-names>J</given-names>
</name>
<name>
<surname>Obeid</surname> <given-names>M</given-names>
</name>
<name>
<surname>Spain</surname> <given-names>L</given-names>
</name>
<name>
<surname>Carbonnel</surname> <given-names>F</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Robert</surname> <given-names>C</given-names>
</name>
<etal/>
</person-group>. <article-title>Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up</article-title>. <source>Ann Oncol</source>. (<year>2022</year>) <volume>33</volume>:<page-range>1217&#x2013;38</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.annonc.2022.10.001</pub-id>
</citation>
</ref>
<ref id="B7">
<label>7</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Marini</surname> <given-names>A</given-names>
</name>
<name>
<surname>Bernardini</surname> <given-names>A</given-names>
</name>
<name>
<surname>Gigli</surname> <given-names>GL</given-names>
</name>
<name>
<surname>Valente</surname> <given-names>M</given-names>
</name>
<name>
<surname>Mu&#xf1;iz-Castrillo</surname> <given-names>S</given-names>
</name>
<name>
<surname>Honnorat</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>Neurologic adverse events of immune checkpoint inhibitors: A systematic review</article-title>. <source>Neurology</source>. (<year>2021</year>) <volume>96</volume>:<page-range>754&#x2013;66</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1212/WNL.0000000000011795</pub-id>
</citation>
</ref>
<ref id="B8">
<label>8</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Altman</surname> <given-names>AL</given-names>
</name>
<name>
<surname>Golub</surname> <given-names>JS</given-names>
</name>
<name>
<surname>Pensak</surname> <given-names>ML</given-names>
</name>
<name>
<surname>Samy</surname> <given-names>RN</given-names>
</name>
</person-group>. <article-title>Bilateral facial palsy following ipilimumab infusion for melanoma</article-title>. <source>Otolaryngol Neck Surg</source>. (<year>2015</year>) <volume>153</volume>:<page-range>894&#x2013;5</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1177/0194599815606701</pub-id>
</citation>
</ref>
<ref id="B9">
<label>9</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Vogrig</surname> <given-names>A</given-names>
</name>
<name>
<surname>Mu&#xf1;iz-Castrillo</surname> <given-names>S</given-names>
</name>
<name>
<surname>Desestret</surname> <given-names>V</given-names>
</name>
<name>
<surname>Joubert</surname> <given-names>B</given-names>
</name>
<name>
<surname>Honnorat</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors</article-title>. <source>Ther Adv Neurol Disord</source>. (<year>2020</year>) <volume>13</volume>:<elocation-id>1756286420932797</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1177/1756286420932797</pub-id>
</citation>
</ref>
<ref id="B10">
<label>10</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yuen</surname> <given-names>C</given-names>
</name>
<name>
<surname>Reid</surname> <given-names>P</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Soliven</surname> <given-names>B</given-names>
</name>
<name>
<surname>Luke</surname> <given-names>JJ</given-names>
</name>
<name>
<surname>Rezania</surname> <given-names>K</given-names>
</name>
</person-group>. <article-title>Facial palsy induced by checkpoint blockade: A single center retrospective study</article-title>. <source>J Immunother Hagerstown Md 1997</source>. (<year>2019</year>) <volume>42</volume>:<page-range>94&#x2013;6</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CJI.0000000000000254</pub-id>
</citation>
</ref>
<ref id="B11">
<label>11</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bruno</surname> <given-names>F</given-names>
</name>
<name>
<surname>Palmiero</surname> <given-names>RA</given-names>
</name>
<name>
<surname>Ferrero</surname> <given-names>B</given-names>
</name>
<name>
<surname>Franchino</surname> <given-names>F</given-names>
</name>
<name>
<surname>Pellerino</surname> <given-names>A</given-names>
</name>
<name>
<surname>Milanesi</surname> <given-names>E</given-names>
</name>
<etal/>
</person-group>. <article-title>Pembrolizumab-induced isolated cranial neuropathy: A rare case report and review of literature</article-title>. <source>Front Neurol</source>. (<year>2021</year>) <volume>12</volume>:<elocation-id>669493</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fneur.2021.669493</pub-id>
</citation>
</ref>
<ref id="B12">
<label>12</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kichloo</surname> <given-names>A</given-names>
</name>
<name>
<surname>Albosta</surname> <given-names>MS</given-names>
</name>
<name>
<surname>Jamal</surname> <given-names>SM</given-names>
</name>
<name>
<surname>Aljadah</surname> <given-names>M</given-names>
</name>
<name>
<surname>Wani</surname> <given-names>F</given-names>
</name>
<name>
<surname>Selene</surname> <given-names>I</given-names>
</name>
<etal/>
</person-group>. <article-title>Atezolizumab-induced bell&#x2019;s palsy in a patient with small cell lung cancer</article-title>. <source>J Investig Med High Impact Case Rep</source>. (<year>2020</year>) <volume>8</volume>:<elocation-id>2324709620965010</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1177/2324709620965010</pub-id>
</citation>
</ref>
<ref id="B13">
<label>13</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sakoh</surname> <given-names>T</given-names>
</name>
<name>
<surname>Kanzaki</surname> <given-names>M</given-names>
</name>
<name>
<surname>Miyamoto</surname> <given-names>A</given-names>
</name>
<name>
<surname>Mochizuki</surname> <given-names>S</given-names>
</name>
<name>
<surname>Kakumoto</surname> <given-names>T</given-names>
</name>
<name>
<surname>Sato</surname> <given-names>K</given-names>
</name>
<etal/>
</person-group>. <article-title>Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report</article-title>. <source>BMC Cancer</source>. (<year>2019</year>) <volume>19</volume>:<fpage>1220</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12885-019-6444-0</pub-id>
</citation>
</ref>
<ref id="B14">
<label>14</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zecchini</surname> <given-names>JM</given-names>
</name>
<name>
<surname>Kim</surname> <given-names>S</given-names>
</name>
<name>
<surname>Yum</surname> <given-names>K</given-names>
</name>
<name>
<surname>Friedlander</surname> <given-names>P</given-names>
</name>
</person-group>. <article-title>Development of bell&#x2019;s palsy after treatment with ipilimumab and nivolumab for metastatic melanoma: A case report</article-title>. <source>J Immunother</source>. (<year>2018</year>) <volume>41</volume>:<fpage>39</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CJI.0000000000000184</pub-id>
</citation>
</ref>
<ref id="B15">
<label>15</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Li</surname> <given-names>J</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>S</given-names>
</name>
<name>
<surname>He</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Qiu</surname> <given-names>K</given-names>
</name>
<etal/>
</person-group>. <article-title>Facial palsy induced by immune checkpoint blockade: A systematic analysis of clinical trials and a pharmacovigilance study of postmarketing data</article-title>. <source>Int Immunopharmacol</source>. (<year>2023</year>) <volume>125</volume>:<elocation-id>111184</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.intimp.2023.111184</pub-id>
</citation>
</ref>
<ref id="B16">
<label>16</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yost</surname> <given-names>MD</given-names>
</name>
<name>
<surname>Chou</surname> <given-names>CZ</given-names>
</name>
<name>
<surname>Botha</surname> <given-names>H</given-names>
</name>
<name>
<surname>Block</surname> <given-names>MS</given-names>
</name>
<name>
<surname>Liewluck</surname> <given-names>T</given-names>
</name>
</person-group>. <article-title>Facial diplegia after pembrolizumab treatment</article-title>. <source>Muscle Nerve</source>. (<year>2017</year>) <volume>56</volume>:<page-range>E20&#x2013;1</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/mus.25663</pub-id>
</citation>
</ref>
<ref id="B17">
<label>17</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Vogrig</surname> <given-names>A</given-names>
</name>
<name>
<surname>Mu&#xf1;iz-Castrillo</surname> <given-names>S</given-names>
</name>
<name>
<surname>Joubert</surname> <given-names>B</given-names>
</name>
<name>
<surname>Picard</surname> <given-names>G</given-names>
</name>
<name>
<surname>Rogemond</surname> <given-names>V</given-names>
</name>
<name>
<surname>Skowron</surname> <given-names>F</given-names>
</name>
<etal/>
</person-group>. <article-title>Cranial nerve disorders associated with immune checkpoint inhibitors</article-title>. <source>Neurology</source>. (<year>2021</year>) <volume>96</volume>:<page-range>e866&#x2013;75</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1212/WNL.0000000000011340</pub-id>
</citation>
</ref>
<ref id="B18">
<label>18</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Beninato</surname> <given-names>T</given-names>
</name>
<name>
<surname>Fuc&#xe0;</surname> <given-names>G</given-names>
</name>
<name>
<surname>Di Guardo</surname> <given-names>L</given-names>
</name>
<name>
<surname>Vetrano</surname> <given-names>I</given-names>
</name>
<name>
<surname>Valeri</surname> <given-names>B</given-names>
</name>
<name>
<surname>Nesa</surname> <given-names>F</given-names>
</name>
<etal/>
</person-group>. <article-title>Immune-related Bell&#x2019;s palsy in melanoma patients treated with immune checkpoint inhibitors</article-title>. <source>Melanoma Res</source>. (<year>2021</year>) <volume>31</volume>:<page-range>178&#x2013;80</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CMR.0000000000000715</pub-id>
</citation>
</ref>
<ref id="B19">
<label>19</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yan</surname> <given-names>C</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>M</given-names>
</name>
<name>
<surname>Swetlik</surname> <given-names>C</given-names>
</name>
<name>
<surname>Toljan</surname> <given-names>K</given-names>
</name>
<name>
<surname>Mahadeen</surname> <given-names>AZ</given-names>
</name>
<name>
<surname>Bena</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality</article-title>. <source>Eur J Neurol</source>. (<year>2023</year>) <volume>30</volume>:<page-range>3221&#x2013;7</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/ene.15942</pub-id>
</citation>
</ref>
<ref id="B20">
<label>20</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Takemura</surname> <given-names>K</given-names>
</name>
<name>
<surname>Yamanaka</surname> <given-names>T</given-names>
</name>
<name>
<surname>Hayashida</surname> <given-names>M</given-names>
</name>
<name>
<surname>Kizawa</surname> <given-names>R</given-names>
</name>
<name>
<surname>Yamaguchi</surname> <given-names>T</given-names>
</name>
<name>
<surname>Tanabe</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Bell&#x2019;s palsy during rechallenge of immune checkpoint inhibitor</article-title>. <source>IJU Case Rep</source>. (<year>2023</year>) <volume>6</volume>:<page-range>144&#x2013;6</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/iju5.12572</pub-id>
</citation>
</ref>
<ref id="B21">
<label>21</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zieman</surname> <given-names>D</given-names>
</name>
<name>
<surname>Frankel</surname> <given-names>AE</given-names>
</name>
</person-group>. <article-title>Autoimmune bell&#x2019;s palsy following immunotherapy for metastatic melanoma: A report of 2 cases</article-title>. <source>J Immunother</source>. (<year>2019</year>) <volume>42</volume>:<fpage>318</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CJI.0000000000000291</pub-id>
</citation>
</ref>
<ref id="B22">
<label>22</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Numata</surname> <given-names>S</given-names>
</name>
<name>
<surname>Iwata</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Okumura</surname> <given-names>R</given-names>
</name>
<name>
<surname>Arima</surname> <given-names>M</given-names>
</name>
<name>
<surname>Kobayashi</surname> <given-names>T</given-names>
</name>
<name>
<surname>Watanabe</surname> <given-names>S</given-names>
</name>
<etal/>
</person-group>. <article-title>Bilateral anterior uveitis and unilateral facial palsy due to ipilimumab for metastatic melanoma in an individual with human leukocyte antigen DR4: A case report</article-title>. <source>J Dermatol</source>. (<year>2018</year>) <volume>45</volume>:<page-range>113&#x2013;4</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/1346-8138.13779</pub-id>
</citation>
</ref>
<ref id="B23">
<label>23</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cuzzubbo</surname> <given-names>S</given-names>
</name>
<name>
<surname>Javeri</surname> <given-names>F</given-names>
</name>
<name>
<surname>Tissier</surname> <given-names>M</given-names>
</name>
<name>
<surname>Roumi</surname> <given-names>A</given-names>
</name>
<name>
<surname>Barlog</surname> <given-names>C</given-names>
</name>
<name>
<surname>Doridam</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature</article-title>. <source>Eur J Cancer Oxf Engl 1990</source>. (<year>2017</year>) <volume>73</volume>:<fpage>1</fpage>&#x2013;<lpage>8</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ejca.2016.12.001</pub-id>
</citation>
</ref>
<ref id="B24">
<label>24</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sechi</surname> <given-names>E</given-names>
</name>
<name>
<surname>Markovic</surname> <given-names>SN</given-names>
</name>
<name>
<surname>McKeon</surname> <given-names>A</given-names>
</name>
<name>
<surname>Dubey</surname> <given-names>D</given-names>
</name>
<name>
<surname>Liewluck</surname> <given-names>T</given-names>
</name>
<name>
<surname>Lennon</surname> <given-names>VA</given-names>
</name>
<etal/>
</person-group>. <article-title>Neurologic autoimmunity and immune checkpoint inhibitors</article-title>. <source>Neurology</source>. (<year>2020</year>) <volume>95</volume>:<page-range>e2442&#x2013;52</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1212/WNL.0000000000010632</pub-id>
</citation>
</ref>
<ref id="B25">
<label>25</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>DY</given-names>
</name>
<name>
<surname>Salem</surname> <given-names>J-E</given-names>
</name>
<name>
<surname>Cohen</surname> <given-names>JV</given-names>
</name>
<name>
<surname>Chandra</surname> <given-names>S</given-names>
</name>
<name>
<surname>Menzer</surname> <given-names>C</given-names>
</name>
<name>
<surname>Ye</surname> <given-names>F</given-names>
</name>
<etal/>
</person-group>. <article-title>Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis</article-title>. <source>JAMA Oncol</source>. (<year>2018</year>) <volume>4</volume>:<page-range>1721&#x2013;8</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1001/jamaoncol.2018.3923</pub-id>
</citation>
</ref>
<ref id="B26">
<label>26</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Schneider</surname> <given-names>BJ</given-names>
</name>
<name>
<surname>Naidoo</surname> <given-names>J</given-names>
</name>
<name>
<surname>Santomasso</surname> <given-names>BD</given-names>
</name>
<name>
<surname>Lacchetti</surname> <given-names>C</given-names>
</name>
<name>
<surname>Adkins</surname> <given-names>S</given-names>
</name>
<name>
<surname>Anadkat</surname> <given-names>M</given-names>
</name>
<etal/>
</person-group>. <article-title>Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update</article-title>. <source>J Clin Oncol</source>. (<year>2021</year>) <volume>39</volume>:<page-range>4073&#x2013;126</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1200/JCO.21.01440</pub-id>
</citation>
</ref>
<ref id="B27">
<label>27</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Farina</surname> <given-names>A</given-names>
</name>
<name>
<surname>Villagr&#xe1;n-Garc&#xed;a</surname> <given-names>M</given-names>
</name>
<name>
<surname>Honnorat</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Neurological adverse events of immune checkpoint inhibitors: An update of clinical presentations, diagnosis, and management</article-title>. <source>Rev Neurol (Paris)</source>. (<year>2023</year>) <volume>179</volume>:<page-range>506&#x2013;15</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.neurol.2023.03.003</pub-id>
</citation>
</ref>
<ref id="B28">
<label>28</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Psimaras</surname> <given-names>D</given-names>
</name>
<name>
<surname>Velasco</surname> <given-names>R</given-names>
</name>
<name>
<surname>Birzu</surname> <given-names>C</given-names>
</name>
<name>
<surname>Tamburin</surname> <given-names>S</given-names>
</name>
<name>
<surname>Lustberg</surname> <given-names>M</given-names>
</name>
<name>
<surname>Bruna</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>Immune checkpoint inhibitors-induced neuromuscular toxicity: From pathogenesis to treatment</article-title>. <source>J Peripher Nerv Syst</source>. (<year>2019</year>) <volume>24</volume>:<page-range>S74&#x2013;85</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/jns.12339</pub-id>
</citation>
</ref>
<ref id="B29">
<label>29</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Leonhard</surname> <given-names>SE</given-names>
</name>
<name>
<surname>Mandarakas</surname> <given-names>MR</given-names>
</name>
<name>
<surname>Gondim</surname> <given-names>FAA</given-names>
</name>
<name>
<surname>Bateman</surname> <given-names>K</given-names>
</name>
<name>
<surname>Ferreira</surname> <given-names>MLB</given-names>
</name>
<name>
<surname>Cornblath</surname> <given-names>DR</given-names>
</name>
<etal/>
</person-group>. <article-title>Diagnosis and management of Guillain&#x2013;Barr&#xe9; syndrome in ten steps</article-title>. <source>Nat Rev Neurol</source>. (<year>2019</year>) <volume>15</volume>:<page-range>671&#x2013;83</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41582-019-0250-9</pub-id>
</citation>
</ref>
<ref id="B30">
<label>30</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Novak</surname> <given-names>CB</given-names>
</name>
</person-group>. <article-title>Rehabilitation strategies for facial nerve injuries</article-title>. <source>Semin Plast Surg</source>. (<year>2004</year>) <volume>18</volume>:<fpage>47</fpage>&#x2013;<lpage>52</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1055/s-2004-823123</pub-id>
</citation>
</ref>
<ref id="B31">
<label>31</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Villagr&#xe1;n-Garc&#xed;a</surname> <given-names>M</given-names>
</name>
<name>
<surname>Velasco</surname> <given-names>R</given-names>
</name>
</person-group>. <article-title>Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice</article-title>. <source>Neurol Sci</source>. (<year>2022</year>) <volume>43</volume>:<page-range>2339&#x2013;61</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s10072-022-05920-4</pub-id>
</citation>
</ref>
<ref id="B32">
<label>32</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Pensato</surname> <given-names>U</given-names>
</name>
<name>
<surname>Guarino</surname> <given-names>M</given-names>
</name>
<name>
<surname>Muccioli</surname> <given-names>L</given-names>
</name>
</person-group>. <article-title>The role of neurologists in the era of cancer immunotherapy: Focus on CAR T-cell therapy and immune checkpoint inhibitors</article-title>. <source>Front Neurol</source>. (<year>2022</year>) <volume>13</volume>:<elocation-id>936141</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fneur.2022.936141</pub-id>
</citation>
</ref>
<ref id="B33">
<label>33</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ruste</surname> <given-names>V</given-names>
</name>
<name>
<surname>Goldschmidt</surname> <given-names>V</given-names>
</name>
<name>
<surname>Laparra</surname> <given-names>A</given-names>
</name>
<name>
<surname>Messayke</surname> <given-names>S</given-names>
</name>
<name>
<surname>Danlos</surname> <given-names>F-X</given-names>
</name>
<name>
<surname>Romano-Martin</surname> <given-names>P</given-names>
</name>
<etal/>
</person-group>. <article-title>The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: A prospective study of the French REISAMIC registry</article-title>. <source>Eur J Cancer</source>. (<year>2021</year>) <volume>158</volume>:<page-range>217&#x2013;24</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ejca.2021.08.048</pub-id>
</citation>
</ref>
<ref id="B34">
<label>34</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Pla&#xe7;ais</surname> <given-names>L</given-names>
</name>
<name>
<surname>Michot</surname> <given-names>J-M</given-names>
</name>
<name>
<surname>Champiat</surname> <given-names>S</given-names>
</name>
<name>
<surname>Romano-Martin</surname> <given-names>P</given-names>
</name>
<name>
<surname>Baldini</surname> <given-names>C</given-names>
</name>
<name>
<surname>Joao</surname> <given-names>MS</given-names>
</name>
<etal/>
</person-group>. <article-title>Neurological complications induced by anti-PD-1 or anti-PD-L1: prevalence, clinical description and treatment: 5-years experience of a national network</article-title>. (<year>2019</year>). doi:&#xa0;<pub-id pub-id-type="doi">10.2139/ssrn.3502375</pub-id>
</citation>
</ref>
</ref-list>
</back>
</article>