P14.123 Neurological complications related to checkpoints inhibitors

Abstract BACKGROUND Currently, immunotherapy is part of the therapeutic arsenal for oncological treatment. Indeed, the need for new medications has led to the development of immune checkpoint inhibitors. Despite favourable oncological outcomes, these treatments have been associated with immune-related adverse events. Although infrequent, neurological toxicities have been reported. Early recognition is crucial for improvement of functional outcome and requires a multidisciplinary approach. OBJECTIVE To describe a case series of patients with neurological complications related to checkpoint inhibitors. PATIENTS AND METHODS We identified six oncological patients who presented immunomediated neurological complications, derived from the use of checkpoints inhibitors. Five cases were men. Ages ranged from 58 to 73 years. Nivolumab, alone or combined, was the most commonly associated drug (4/6). Underlying diseases included lung carcinoma (2/6), melanoma (2/6), renal carcinoma (1/6) and ovarian adenocarcinoma (1/6). An acute demyelinating sensory-motor polyneuropathy and an acute axonal sensory polyneuropathy were documented in two and one case, respectively. In these, the cerebrospinal fluid analysis revealed albuminocytologic dissociation. All three cases improved after treatment with intravenous immunoglobulins (0.4 g/Kg a day for five days). The latter and another case were diagnosed of aseptic meningitis after cerebrospinal fluid lymphocytic pleocytosis was found. High fever was also associated with lower extremities areflexia, weakness and ataxia. Methylprednisolone (1g/day for five days) was administered. One case of necrotizing inflammatory myositis with high levels of creatine kinasa, confirmed by muscular biopsy, involving cervical weakness and ptosis, was effectively treated with Methylprednisolone (1g/day for five days) follow by oral prednisone tapering. An anti-Yo related pancerebellar syndrome was the only case with a fatal outcome despite treatment. CONCLUSION The increasingly frequent use of immunotherapy in the treatment of cancer may lead to an increase in neurological complications. These include a broad spectrum of syndromes with peripheral nervous system predominantly susceptible. Early identification of these and appropriate management of drug-related toxicity are required. Immune-modulating therapies are particularly beneficial.

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032 Neurological sequelae of immune checkpoint inhibitors: a case series

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.31 ◽

2018 ◽

Vol 89 (6) ◽

pp. A13.3-A14 ◽

Cited By ~ 1

Author(s):

Matthew Silsby ◽

Stephen R Duma ◽

Neil Mahant ◽

Steve Vucic ◽

Andrew Henderson

Keyword(s):

T Cells ◽

Checkpoint Inhibitors ◽

Early Recognition ◽

Case Series ◽

Tumour Response ◽

Stage Iv ◽

High Dose ◽

Solid Organ ◽

Fisher Syndrome ◽

Neurological Sequelae

IntroductionMonoclonal antibodies directed against co-stimulatory molecules on T cells (checkpoint inhibitors, CIs) are used to treat solid organ malignancies. Neurological complications are an increasingly recognised consequence of their use. We present three patients referred to the Neurology service at Westmead Hospital in 2017 with new neurological complaints following CI therapy.CasesPatient 1, a 54 year old woman with stage IV non-small cell lung cancer treated with pembrolizumab (anti-PD-1), presented with cerebral vasculitis causing bilateral ACA territory cerebral infarction. Patient 2, a 59 year old woman with metastatic melanoma treated with ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1), presented with ataxia, diplopia and ptosis consistent with Miller Fisher syndrome. Patient 3, a 77 year old woman with metastatic colorectal adenocarcinoma treated with nivolumab (anti-PD-1), presented with ocular myasthenia manifesting as fatigable ptosis and complex ophthalmoplegia.The diagnoses were made by clinical assessment with imaging and neurophysiological investigations where possible. Antibodies relevant to the neurological condition were negative, in keeping with previous reports. CIs were discontinued in all patients. Treatment included intravenous pulsed methylprednisolone followed by high dose oral taper in all patients. Additionally, Patient 1 was treated with infliximab and rituximab; Patients 2 and 3 received intravenous immunoglobulin followed by monthly maintenance therapy; Patient 2 underwent plasma exchange. Patients 1 and 2 recovered independent ambulation. Patient 3 died two months after presentation due to underlying malignancy.ConclusionCheckpoint inhibitors block co-stimulatory molecules on T-cells, allowing the immune system to mount an anti-tumour response. The resulting immune dysregulation can also lead to organ-specific inflammatory and immune complications, of which neurological sequelae are increasingly recognised. The three reported patients highlight the spectrum of disease that can arise. Their occurrence within one year suggests an increasing incidence, and a need for increased vigilance. Early recognition is paramount as treatment with high dose corticosteroids, even in conditions that would not normally respond, is recommended.

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Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series

10.1101/2020.07.15.20126730 ◽

2020 ◽

Cited By ~ 2

Author(s):

Micheala McCuddy ◽

Praful Kelkar ◽

Yu Zhao ◽

David Wicklund

Keyword(s):

Early Recognition ◽

Ventilatory Support ◽

Case Series ◽

Corticosteroid Treatment ◽

Neurological Complications ◽

Plasma Therapy ◽

The North ◽

Immune Mediated ◽

Elevated Protein ◽

Acute Demyelinating Encephalomyelitis

AbstractObjectiveTo report three patients infected with COVID-19 with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM).MethodPatient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USAResultsThree patients (two men and one woman, aged 38 - 63) presented with fatigue, cough and fever leading to development of acute respiratory distress syndrome secondary to COVID-19 infection requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three of the patients received Convalescent plasma therapy for COVID-19. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement.ConclusionNeurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.

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Case Series Review of Neuroradiologic Changes Associated with Immune Checkpoint Inhibitor Therapy

Neuro-Oncology Practice ◽

10.1093/nop/npaa079 ◽

2020 ◽

Author(s):

Na Tosha N Gatson ◽

Mina Makary ◽

Shane P Bross ◽

Joseph Vadakara ◽

Tristan Maiers ◽

...

Keyword(s):

Immune Checkpoint ◽

Inflammatory Responses ◽

Checkpoint Inhibitors ◽

Case Series ◽

Neurological Complications ◽

Patient Treatment ◽

Cancer Therapies ◽

Treatment Regimens ◽

First Case ◽

Impact Patient Care

Abstract While immuno-oncotherapy (IO) has significantly improved outcomes in the treatment of systemic cancers, various neurological complications have accompanied these therapies. Treatment with immune checkpoint inhibitors (ICIs) risks multi-organ autoimmune inflammatory responses with gastrointestinal, dermatologic, and endocrine complications being the most common types of complications. Despite some evidence that these therapies are effective to treat central nervous system (CNS) tumors, there are a significant range of related neurological side effects due to ICIs. Neuroradiologic changes associated with ICIs are commonly misdiagnosed as progression and might limit treatment or otherwise impact patient care. Here, we provide a radiologic case series review restricted to neurological complications attributed to ICIs, anti-CTLA-4 and PD-L-1/PD-1 inhibitors. We report the first case series dedicated to the review of CNS/PNS radiologic changes secondary to ICI therapy in cancer patients. We provide a brief case synopsis with neuroimaging followed by an annotated review of the literature relevant to each case. We present a series of neuroradiologic findings including nonspecific parenchymal and encephalitic, hypophyseal, neural (cranial and peripheral), meningeal, cavity associated, and cranial osseous changes seen in association with use of ICIs. Misdiagnosis of radiologic abnormalities secondary to neurological irAEs can impact patient treatment regimens and clinical outcomes. Rapid recognition of various neuroradiologic changes associated with ICI therapy can improve patient tolerance and adherence to cancer therapies.

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Cerebrospinal fluid confirmed COVID-19-associated encephalitis treated successfully

BMJ Case Reports ◽

10.1136/bcr-2020-237378 ◽

2020 ◽

Vol 13 (9) ◽

pp. e237378 ◽

Cited By ~ 1

Author(s):

Yasmine Mohamed Kamal ◽

Yasmin Abdelmajid ◽

Abubaker Abdul Rahman Al Madani

Keyword(s):

Cerebrospinal Fluid ◽

Respiratory Symptoms ◽

Medical Literature ◽

Clinical Presentation ◽

Early Recognition ◽

Neurological Complications ◽

Red Flags ◽

Cerebrospinal Fluid Analysis ◽

Fluid Analysis ◽

The Brain

The COVID-19 pandemic that attracted global attention in December 2019 is well known for its clinical picture that is consistent with respiratory symptoms. Currently, the available medical literature describing the neurological complications of COVID-19 is gradually emerging. We hereby describe a case of a 31-year-old COVID-19-positive patient who was admitted on emergency basis. His clinical presentation was primarily neurological, rather than the COVID-19’s classical respiratory manifestations. He presented with acute behavioural changes, severe confusion and drowsiness. The cerebrospinal fluid analysis was consistent with COVID-19 encephalitis, as well as the brain imaging. This experience confirms that neurological manifestations might be expected in COVID-19 infections, despite the absence of significant respiratory symptoms. Whenever certain red flags are raised, physicians who are involved in the management of COVID-19 should promptly consider the possibility of encephalitis. Early recognition of COVID-19 encephalitis and timely management may lead to a better outcome.

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Atlantoaxial Stabilization by Posterior C1 and C2 Screw-Rod Fixation for Various Pathologies: Case Series and Comprehensive Review of Literature

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0041-1722838 ◽

2021 ◽

Author(s):

Chandramohan Unni ◽

Vijayan Pettakkandy ◽

Abdul Jaleel P. ◽

Subrat Kumar Soren ◽

Vineeth K. K.

Keyword(s):

Early Recognition ◽

Case Series ◽

Neurological Complications ◽

Os Odontoideum ◽

Atlantoaxial Joint ◽

Chronic Inflammatory Condition ◽

History Of ◽

Atlantoaxial Stabilization ◽

C2 Fixation ◽

Harms Technique

AbstractWe retrospectively analyzed atlantoaxial dislocation (AAD) of various pathologies, namely, rheumatoid arthritis (RA), os odontoideum, and trauma. Various techniques were discussed in relation to C1-C2 stabilization. The study aims to share our clinical experience in a series of six cases of C1-C2 instability that underwent posterior C1-C2 fusion, with free hand technique and limited fluoroscopy. The clinicoradiological presentation for each patient is described. We reviewed different literatures related to our case vividly and focused on the basic neuroanatomy involved in the atlantoaxial joint. All patients of AAD had evidence of severe canal compromise and chronic compressive spinal cord changes. In our study, the patients age ranged from 28 to 52 years. The study included four males and two females. Out of six patients of AAD, three had history of trauma, two had os odontoideum, and one had chronic inflammatory condition (RA). From our case series, we concluded that the Goel–Harms technique is the most versatile and surgeon friendly technique for C1-C2 fixation. Early recognition and surgical intervention of atlantoaxial joint instability is essential to prevent catastrophic neurological complications.

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BioGlue for prevention of postoperative cerebrospinal fluid leaks in transsphenoidal surgery: a case series

Yearbook of Neurology and Neurosurgery ◽

10.1016/s0513-5117(08)79179-8 ◽

2008 ◽

Vol 2008 ◽

pp. 234-235

Author(s):

D.H. Kim

Keyword(s):

Cerebrospinal Fluid ◽

Transsphenoidal Surgery ◽

Case Series ◽

Cerebrospinal Fluid Leaks

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A case series of endocrine immune-related adverse effects of checkpoint inhibitors

Endocrine Abstracts ◽

10.1530/endoabs.56.gp192 ◽

2018 ◽

Author(s):

Fotini Adamidou ◽

Thomas Georgiou ◽

Katerina Kafantari ◽

Paraskevi Komzia ◽

Anastasios Vagionas ◽

...

Keyword(s):

Adverse Effects ◽

Checkpoint Inhibitors ◽

Case Series

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Pulmonary Arterial Thrombosis Is a Novel and Underreported Feature in Severe COVID-19 with Fatal Outcome: Results from a Prospective Single-Centre Clinicopathological Case Series

SSRN Electronic Journal ◽

10.2139/ssrn.3586685 ◽

2020 ◽

Cited By ~ 2

Author(s):

Sigurd Lax ◽

Kristijan Skok ◽

Peter Zechner ◽

Harald Kessler ◽

Norbert Kaufmann ◽

...

Keyword(s):

Arterial Thrombosis ◽

Fatal Outcome ◽

Case Series ◽

Single Centre ◽

Pulmonary Arterial

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Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)

Journal of Neurology ◽

10.1007/s00415-021-10406-y ◽

2021 ◽

Author(s):

Biyan Nathanael Harapan ◽

Hyeon Joo Yoo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Case Reports ◽

Case Series ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Fisher Syndrome ◽

Novel Coronavirus ◽

The Impact

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

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