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1.
Handb Clin Neurol ; 200: 11-32, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494272

RESUMO

Paraneoplastic neurologic syndromes are a group of rare disorders that have fascinated neurologists for more than a century. The discovery in the 1980s that many of these disorders occurred in association with antibodies against neuronal proteins revived the interest for these diseases. This chapter first traces the history of the paraneoplastic neurologic syndromes during the era that preceded the discovery of immune mechanisms and then reviews the immunologic period during which many of these syndromes were found to be associated with antibodies against intracellular onconeuronal proteins and pathogenic cytotoxic T-cell mechanisms. Alongside these developments, investigations on the antibody-mediated disorders of the peripheral nervous system, such as the myasthenic syndromes or neuromyotonia, provided suggestions for the study of the central nervous system (CNS) syndromes. These converging areas of research culminated with the groundbreaking discovery of a new category of CNS disorders mediated by antibodies against neuronal surface proteins or receptors. These disorders are not always paraneoplastic, and the understanding of these syndromes and mechanisms has changed the landscape of neurology and neurosciences.


Assuntos
Doenças do Sistema Nervoso Central , Neoplasias , Neurologia , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Autoanticorpos , Neoplasias/complicações , Doenças do Sistema Nervoso Central/complicações
2.
Handb Clin Neurol ; 200: 275-282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494282

RESUMO

A number of the well-recognized autoimmune and paraneoplastic neurologic syndromes commonly involve the autonomic nervous system. In some cases, the autonomic nerves or ganglia are primary targets of neurologic autoimmunity, as in immune-mediated autonomic ganglionopathies. In other disorders such as encephalitis, autonomic centers in the brain may be affected. The presence of autonomic dysfunction (especially gastrointestinal dysmotility) is sometimes overlooked even though this may contribute significantly to the symptom burden in these paraneoplastic disorders. Additionally, recognition of autonomic features as part of the clinical syndrome can help point the diagnostic evaluation toward autoimmune and paraneoplastic etiologies. As with other paraneoplastic disorders, the clinical syndrome and the presence and type of neurologic autoantibodies help to secure the diagnosis and direct the most appropriate investigation for malignancy. Optimal management for these conditions typically includes aggressive treatment of the neoplasm, immunomodulatory therapy, and symptomatic treatments for orthostatic hypotension and gastrointestinal dysmotility.


Assuntos
Doenças do Sistema Nervoso Autônomo , Neoplasias , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Autoanticorpos , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Neoplasias/complicações , Sistema Nervoso Autônomo
3.
Handb Clin Neurol ; 200: 33-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494287

RESUMO

Paraneoplastic neurologic syndromes (PNS) represent a rare group of immune-mediated complications associated with an underlying tumor. Ectopic protein expression in neoplastic cells or an aberrant immune regulation in the course of hematooncologic diseases or thymomas trigger an autoimmune response that may affect any part of the central and/or peripheral nervous system. Recent advances in drug therapies as well as novel animal models and neuropathologic studies have led to further insights on the immune pathomechanisms of PNS. Although the syndromes share common paths in pathogenesis, they may differ in the disease course, prognosis, and therapy targets, depending on the localization and type of antibody epitope. Neuropathologic hallmarks of PNS associated with antibodies directed against intracellular epitopes are characterized by T cell-dominated inflammation, reactive gliosis including microglial nodules, and neuronal degeneration. By contrast, the neuropathology of cell surface antibody-mediated PNS strongly depends on the targeted antigen and varies from B cell/plasma cell-dominated inflammation and well-preserved neurons together with a reduced expression of the target antigen in anti-NMDAR encephalitis to irreversible Purkinje cell loss in anti-P/Q-type VGCC antibody-associated paraneoplastic cerebellar degeneration. The understanding of different pathomechanisms in PNS is important because they strongly correspond with therapy response and prognosis, and should guide treatment decisions.


Assuntos
Neoplasias , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Animais , Humanos , Autoanticorpos , Doenças do Sistema Nervoso/complicações , Neoplasias/complicações , Inflamação
4.
Handb Clin Neurol ; 200: 347-364, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494289

RESUMO

Among patients with paraneoplastic neurologic syndromes (PNS), emphasis has historically been placed on neural antibodies against intracellular proteins that have a strong association with malignancy. Because of the intracellular location of their antigenic targets, these antibodies are typically considered to be non-pathogenic surrogate markers of immune cell-mediated neural injury. Unfortunately, patients with these antibodies often have suboptimal response to immunotherapy and poor prognosis. Over the last two decades, however, dramatic advancements have been made in the discovery and clinical characterization of neural antibodies against extracellular targets. These antibodies are generally considered to be pathogenic, given their potential to directly alter antigen structure or function, and patients with these antibodies often respond favorably to prompt immunotherapy. These antibodies also associate with tumors and may thus occur as PNS, albeit more variably than neural antibodies against intracellular targets. The updated 2021 PNS diagnostic criteria, which classifies antibodies as high-risk, intermediate-risk, or lower-risk for an associated cancer, better clarifies how neural antibodies against extracellular targets relate to PNS. Using this recently created framework, the clinical presentations, ancillary test findings, oncologic associations, and treatment responses of syndromes associated with these antibodies are discussed.


Assuntos
Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Anticorpos/metabolismo , Neoplasias/complicações , Biomarcadores , Autoanticorpos
5.
Handb Clin Neurol ; 200: 335-346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494288

RESUMO

Although they are relatively rare, the diagnosis of paraneoplastic neurologic syndromes (PNS) can be aided by the identification of neural autoantibodies in patients' serum and cerebrospinal fluid (CSF). They often clinically manifest as characteristic syndromes, including limbic encephalitis, opsoclonus-myoclonus syndrome, paraneoplastic cerebellar degeneration, and paraneoplastic encephalomyelitis. The antibodies are directed either toward intracellular targets, or epitopes on the cell surface. As compared to cell surface antibodies, intracellular paraneoplastic autoantibodies are more classically associated with cancer, most often lung, breast, thymoma, gynecologic, testicular, and/or neuroendocrine cancers. The malignancies themselves tend to be small and regionally contained, attesting to the strength of the immune system in cancer immunosurveillance. Typically, the intracellular antibodies are not directly pathogenic and tend to be associated with PNS that are poorly responsive to treatment. With some notable exceptions, including patients with PNS associated with testicular cancer, patients with intracellular antibodies are typically older individuals, in their 7th decade of life and beyond. Many of them are current or former smokers. Treatment strategies include tumor removal as well as immunotherapy to treat the concomitant PNS. Newer technologies and the ever-broadening use of cancer immunotherapies are contributing to the continued identification of novel intracellularly targeted autoantibodies.


Assuntos
Encefalite Límbica , Síndromes Paraneoplásicas do Sistema Nervoso , Neoplasias Testiculares , Masculino , Humanos , Feminino , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Autoanticorpos , Imunoterapia
6.
Handb Clin Neurol ; 200: 419-429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494294

RESUMO

Paraneoplastic neurologic syndromes are rarely associated with hematologic malignancies. In their rarity, lymphomas are the diseases with more frequent paraneoplastic neurologic syndrome. High-risk antibodies are absent in most lymphoma-associated paraneoplastic neurologic syndromes, with the exception of antibodies to Tr/DNER in paraneoplastic cerebellar degeneration, mGluR5 in limbic encephalitis, and mGluR1 in some cerebellar ataxias. Peripheral nervous system paraneoplastic neurologic syndromes are rare and heterogeneous, with a prevalence of demyelinating polyradiculoneuropathy in non-Hodgkin lymphoma. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) is a rare, paraneoplastic syndrome due to an underlying plasma cell disorder. The diagnosis is based on defined criteria, and vascular endothelial growth factor (VEGF), not an antibody, is considered a reliable diagnostic marker that also mirrors therapy response. As with the paraneoplastic neurologic syndromes in solid tumors, therapies rely on cancer treatment associated with immunomodulatory treatment with better response in PNS with antibodies to surface antigens. The best outcome is generally present in Ophelia syndrome/limbic encephalitis with anti-mGluR5 antibodies, with frequent complete recovery. Besides patients with isolated osteosclerotic lesions (where radiotherapy is indicated), hematopoietic stem-cell transplantation is the therapy of choice in patients with POEMS syndrome. In the paraneoplastic neurologic syndromes secondary to immune checkpoint inhibitors, discontinuation of the drug together with immunomodulatory treatment is recommended.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Encefalite Límbica , Linfoma , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia
7.
Handb Clin Neurol ; 200: 397-407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494292

RESUMO

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from the transformation of neuroendocrine cells in several organs, most notably the gastro-entero-pancreatic system and respiratory tract. The classification was recently revised in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. NENs can rarely spread to the central or peripheral nervous systems. Neurologic involvement is determined by the rare development of paraneoplastic syndromes, which are remote effects of cancer. Mechanisms depend on immunologic response to a tumor, leading to the immune attack on the nervous system or the production of biologically active ("functioning") substances, which can determine humoral (endocrine) effects with neurologic manifestations. Paraneoplastic neurologic syndromes (PNS) are immunologically mediated and frequently detected in small cell lung cancer but rarely seen in other forms of NEN. PNS and Merkel cell carcinoma is increasingly reported, especially with Lambert Eaton myasthenic syndrome. Endocrine manifestations are found in a wide spectrum of NENs. They can develop at any stage of the diseases and determine neurologic manifestations. Patient outcomes are influenced by tumor prognosis, neurologic complications, and the severity of endocrine effects.


Assuntos
Síndrome Miastênica de Lambert-Eaton , Doenças do Sistema Nervoso , Tumores Neuroendócrinos , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Humanos , Tumores Neuroendócrinos/complicações , Síndromes Paraneoplásicas/complicações , Síndrome Miastênica de Lambert-Eaton/etiologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Autoanticorpos
8.
Handb Clin Neurol ; 200: 79-96, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494298

RESUMO

The correct diagnosis of a paraneoplastic neurologic syndrome (PNS) first requires the identification of the syndrome as one of those defined as high-risk (previously called classical) or intermediate-risk for cancer in the 2021 PNS diagnostic criteria. Testing for neuronal antibodies should be restricted to these syndromes as indiscriminate request decreases the diagnostic value of the antibodies. Identifying onconeural (high-risk for cancer) or intermediate-risk for cancer antibodies supports the paraneoplastic diagnosis and mandates the search for an underlying cancer. Tumor screening must follow the published guidelines. Repeated screening is indicated in neurologic syndromes with onconeural antibodies and patients with high-risk for cancer neurologic syndromes unless they present neuronal antibodies which are not associated with cancer. Neuronal antibodies should be screened by immunohistochemistry and confirmed by immunoblot (intracellular antigens) or cell-based assay (CBA) (surface antigens). Positive results only by immunoblot or CBA should be taken with caution. Although the 2021 diagnostic criteria for PNS do not capture all PNS, as they do not allow to diagnose definite PNS neurologic syndromes without neuronal antibodies, the updated criteria represent a step forward to differentiate true PNS from neurologic syndromes that coincide in time with cancer diagnosis without having a pathogenic link.


Assuntos
Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Autoanticorpos , Neurônios , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico
9.
Handb Clin Neurol ; 200: 57-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494297

RESUMO

Paraneoplastic neurologic syndromes (PNS), initially depicted as seemingly cryptic remote manifestations of malignancy, were first described clinically in the early 20th century, with pathophysiologic correlates becoming better elucidated in the latter half of the century. There remain many questions not only about the pathophysiology but also regarding the epidemiology of these conditions. The continuous discovery of novel autoantigens and related neurologic disease has broadened the association in classical PNS to include conditions such as paraneoplastic cerebellar degeneration. It has also brought into focus several other neurologic syndromes with a putative neoplastic association. These conditions are overall rare, making it difficult to capture large numbers of patients to study, and raising the question of whether incidence is increasing over time or improved identification is driving the increased numbers of cases. With the rise and increasing use of immunotherapy for cancer treatment, the incidence of these conditions is additionally expected to rise and may present with various clinical symptoms. As we enter an era of clinical trial intervention in these conditions, much work is needed to capture more granular data on population groups defined by socioeconomic characteristics such as age, ethnicity, economic resources, and gender to optimize care and clinical trial planning.


Assuntos
Neoplasias , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/epidemiologia , Neoplasias/epidemiologia , Neoplasias/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/complicações , Imunoterapia
10.
Handb Clin Neurol ; 200: 431-445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494295

RESUMO

Paraneoplastic neurologic syndromes (PNSs) are a group of diseases affecting the central and/or peripheral nervous system caused by immune-mediated processes directed toward antigens with shared expression in tumor and neural tissue. Germ cell tumors (GCTs) are associated with PNSs with varied clinical phenotypes. Early diagnosis of PNS is vital to potentially uncover and treat underlying tumors, improving the chances of recovery, and preventing permanent neurologic complications. In this chapter, we outline the pathophysiology and epidemiology of PNS. We briefly provide a summary of GCTs in males and females. We review the neural-specific autoantibodies and PNSs associated with GCTs and their clinical and radiologic accompaniments. We also provide an overview of the treatment and prognosis of these disorders.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Masculino , Feminino , Humanos , Autoanticorpos , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/complicações , Prognóstico , Neoplasias Embrionárias de Células Germinativas/complicações
11.
Pol Merkur Lekarski ; 52(1): 5-9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518226

RESUMO

OBJECTIVE: Aim: To analyse onconeural antibodies in the blood serum of breast cancer patients without neurological symptoms.. PATIENTS AND METHODS: Materials and Methods: The study included 48 women with breast cancer. Paraneoplastic Neurologic Syndromes 12 Ag (IgG) Euroline by EUROIMMUN test was used to determine onconeural antibodies: anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-Ma/anti-Ta, anti-amphiphysin, anti-recoverin, anti-SOX1, anti-tytin, anti-zic4, anti-GAD65 and anti-Tr (DNER). RESULTS: Results: The conducted analysis revealed the presence of onconeural antibodies such as: anti-recoverin, anti-CV2, anti-Zic4, anti-SOX1, anti-MA2/Ta and antititin in blood serum of women with breast cancer. CONCLUSION: Conclusions: Further analysis may allow the assessment of the possible clinical usefulness of these determinations.


Assuntos
Neoplasias da Mama , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Feminino , Prevalência , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Autoanticorpos
12.
Cell ; 187(4): 831-845.e19, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38301645

RESUMO

The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.


Assuntos
Antígenos de Neoplasias , Neoplasias , Proteínas do Tecido Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Animais , Humanos , Camundongos , Autoanticorpos , Capsídeo/metabolismo , Epitopos , Neoplasias/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Antígenos de Neoplasias/metabolismo , Proteínas do Tecido Nervoso/metabolismo
13.
Curr Treat Options Oncol ; 25(1): 42-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38198120

RESUMO

OPINION STATEMENT: Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed.


Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Humanos , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Fatores Imunológicos
14.
Semin Neurol ; 44(1): 36-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183975

RESUMO

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.


Assuntos
Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Humanos , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Autoanticorpos , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/terapia , Neurônios/patologia , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/terapia
16.
Wien Med Wochenschr ; 174(1-2): 16-21, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36867318

RESUMO

OBJECTIVE: Paraneoplastic neurological syndromes (PNS) are rare disorders associated with various onconeuronal antibodies. Anti-Ri antibodies (ANNA-2) are typically found in patients with opsoclonus myoclonus syndrome (OMS) and ataxia. CASE REPORT: We present an anti-Ri antibody-positive 77-year-old woman with subacute progressive bilateral cranial nerve VI palsy, gait disturbance and jaw dystonia. MRI of the brain showed hyperintense signals on T2 bitemporal without contrast enhancement. Cerebrospinal fluid (CSF) examination exhibited mild pleocytosis of 13 cells/µl and positive oligoclonal bands. CSF was overall inconspicuous for a malignant or inflammatory etiology. Immunofluorescence analysis revealed anti-Ri antibodies in both serum and CSF. Subsequent diagnostic work up resulted in a newly diagnosed ductal carcinoma of the right breast. PNS in this case partially responded to the anti-tumor therapy. CONCLUSION: This case shows similarities with recently published anti-Ri syndromes, which might form a distinct triad within the anti-Ri spectrum.


Assuntos
Doenças do Nervo Abducente , Distonia , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Feminino , Humanos , Idoso , Distonia/diagnóstico , Distonia/tratamento farmacológico , Distonia/etiologia , Síndromes Paraneoplásicas/patologia , Anticorpos Antineoplásicos/análise , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Autoanticorpos
17.
Rev Neurol (Paris) ; 180(1-2): 107-116, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38142198

RESUMO

In autoimmune neurological diseases, the autonomic nervous system can be the primary target of autoimmunity (e.g. autoimmune autonomic ganglionopathy), or, more frequently, be damaged together with other areas of the nervous system (e.g. Guillain-Barré syndrome). Patients with autoimmune encephalitis and paraneoplastic neurological syndromes (PNS) often develop dysautonomia; however, the frequency and spectrum of autonomic signs and symptoms remain ill defined except for those scenarios in which dysautonomia is a core feature of the disease. Such is the case of Lambert-Eaton myasthenic syndrome, Morvan syndrome or anti-NMDAR encephalitis; in the latter, patients with dysautonomia have been reported to carry a more severe disease and to retain higher disability than those without autonomic dysfunction. Likewise, the presence of autonomic involvement indicates a higher risk of death due to neurological cause in patients with anti-Hu PNS. However, in anti-Hu and other PNS, as well as in the context of immune checkpoint inhibitors' toxicities, the characterization of autonomic involvement is frequently overshadowed by the severity of other neurological symptoms and signs. When evaluated with tests specific for autonomic function, patients with autoimmune encephalitis or PNS usually show a more widespread autonomic involvement than clinically suggested, which may reflect a potential gap of care when it comes to diagnosing dysautonomia. This review aims to revise the autonomic involvement in patients with autoimmune encephalitis and PNS, using for that purpose an antibody-based approach. We also discuss and provide general recommendations for the evaluation and management of dysautonomia in these patients.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Doenças do Sistema Nervoso Autônomo , Encefalite , Doença de Hashimoto , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças Autoimunes do Sistema Nervoso/complicações , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Sistema Nervoso Autônomo , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Autoanticorpos
18.
Lancet Neurol ; 23(1): 81-94, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101905

RESUMO

Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets.


Assuntos
Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Humanos , Inibidores de Checkpoint Imunológico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Autoanticorpos
19.
Continuum (Minneap Minn) ; 29(6): 1779-1808, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085898

RESUMO

OBJECTIVE: Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. LATEST DEVELOPMENTS: Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. ESSENTIAL POINTS: All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.


Assuntos
Encefalite , Epilepsia , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , N-Metilaspartato , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Encefalite/complicações , Encefalite/diagnóstico , Encefalite/terapia , Autoanticorpos , Receptores de N-Metil-D-Aspartato
20.
J Neurol Sci ; 454: 120830, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37856996

RESUMO

INTRODUCTION: Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical manifestations and imaging patterns need further elucidation. OBJECTIVE/AIMS: To investigate the clinical profiles, antibody associations, neuroimaging patterns, treatments, and outcomes of PNS and AIE. METHODS: A systematic review of 379 articles published between 2014 and 2023 was conducted. Of the 55 studies screened, 333 patients were diagnosed with either PNS or AIE and tested positive for novel antibodies. Data on demographics, symptoms, imaging, antibodies, cancer associations, treatment, and outcomes were extracted. RESULTS: The study included 333 patients (mean age 54 years, 67% males) with PNS and AIE positive for various novel antibodies. 84% had central nervous system issues like cognitive impairment (53%), rhombencephalitis (17%), and cerebellar disorders (24%). Neuroimaging revealed distinct patterns with high-risk antibodies associated with brainstem lesions in 98%, cerebellar in 91%, hippocampal in 98%, basal ganglia in 75%, and spinal cord in 91%, while low/intermediate-risk antibodies were associated with medial temporal lobe lesions in 71% and other cortical/subcortical lesions in 55%. High-risk antibodies were associated with younger males, deep brain lesions, and increased mortality of 61%, while low/intermediate-risk antibodies were associated with females, cortical/subcortical lesions, and better outcomes with 39% mortality. Associated cancers included seminomas (23%), lung (19%), ovarian (2%), and breast (2%). Treatments included IVIG, chemotherapy, and plasmapheresis. Overall mortality was 25% in this cohort. CONCLUSION: PNS and AIE have distinct clinical and radiological patterns based on antibody profiles. High-risk antibodies are associated with increased mortality while low/intermediate-risk antibodies are associated with improved outcomes. Appropriate imaging and antibody testing are critical for accurate diagnosis.


Assuntos
Neoplasias , Doenças do Sistema Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico por imagem , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Autoanticorpos , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neuroimagem
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