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1.
Handb Clin Neurol ; 165: 269-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727217

RESUMO

Brain tumors and paraneoplastic syndromes can cause various neuropsychiatric symptoms. Rarely, psychiatric symptoms may be the initial presentation of the underlying neurologic lesion. Brain imaging studies are crucial in the diagnosis of brain tumors. Paraneoplastic syndromes are mostly immune-mediated, and antineuronal antibodies may be detected in the blood or cerebrospinal fluid. Clinical suspicion is very important in assisting the diagnostic workup. Treatment of the psychiatric symptoms depends on the nature of the symptoms. Selection of the psychotropic agent has to be done carefully to minimize complications such as seizures and delirium secondary to anticholinergic toxicity. With advances in targeted therapies, immunology, and genetics, the future appears more promising.


Assuntos
Autoanticorpos/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/tratamento farmacológico , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Síndromes Paraneoplásicas do Sistema Nervoso/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Encefalite Límbica/sangue , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/psicologia , Síndromes Paraneoplásicas do Sistema Nervoso/psicologia , Psicofarmacologia , Psicotrópicos/uso terapêutico
3.
Continuum (Minneap Minn) ; 25(5): 1401-1421, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31584543

RESUMO

PURPOSE OF REVIEW: This article discusses the varied types of paraneoplastic syndromes that commonly have neuro-ophthalmologic manifestations. Diagnostic considerations and therapeutic options for individual diseases are also discussed. RECENT FINDINGS: Paraneoplastic syndromes can affect the afferent and efferent visual systems. Paraneoplastic syndromes may result in reduced visual acuity from retinal degeneration, alterations in melanocyte proliferation and uveal thickening, or acquired nystagmus. Ocular motor abnormalities related to paraneoplastic syndromes may present with symptoms from opsoclonus or from neuromuscular junction disease. Diagnosis remains challenging, but serologic identification of some specific antibodies may be helpful or confirmatory. Treatment, in addition to directed therapies against the underlying cancer, often requires systemic corticosteroids, plasma exchange, or immunosuppression, but some specific syndromes improve with use of targeted pharmacologic therapy. SUMMARY: Diagnosis and therapy of paraneoplastic syndromes presenting with neuro-ophthalmic symptoms remain a challenge, but strategies are evolving and new approaches are on the horizon.


Assuntos
Transtornos da Motilidade Ocular/etiologia , Doenças do Nervo Óptico/etiologia , Síndrome POEMS/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas Oculares/complicações , Doenças Retinianas/etiologia , Transtornos da Visão/etiologia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Síndrome POEMS/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas Oculares/diagnóstico , Doenças Retinianas/diagnóstico , Transtornos da Visão/diagnóstico
6.
Curr Oncol ; 26(4): e458-e465, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31548813

RESUMO

Objective: Paraneoplastic neurologic syndrome (pns) is a rare condition indirectly caused by an underlying malignancy. In many cases, the malignancy is occult at the time of the pns diagnosis, and the optimal diagnostic modality to detect the underlying tumour is unclear. In the present study, we aimed to assess the utility of 18F-fluorodeoxyglucose positron-emission tomography (fdg-pet) or pet integrated with computed tomography (pet/ct) in the investigation of these patients. Methods: We retrospectively analyzed data from the PET Access Program (pap) database in the province of Ontario to identify patients who underwent fdg-pet/ct imaging as part of a workup for pns. In all patients, prior conventional imaging was negative or indeterminate. To determine the diagnostic accuracy of fdg-pet/ct, data about demographics, presenting symptoms, and biochemical and radiologic workup, including fdg-pet/ct imaging results, were compared with data collected by the Ontario Cancer Registry (ocr). A systematic review of the literature and meta-analysis using our study inclusion criteria were performed for studies of fdg-pet accuracy. Results: Of 29 patients identified in the pap database, 9 had fdg-pet/ct results suspicious for malignancy. When correlated with data from the ocr, 5 fdg-pet/ct results were informative, resulting in a detection rate of 17%. Local sensitivity and specificity were 0.83 and 0.83 respectively. Two studies meeting our criteria were identified in the literature. The pooled sensitivity and specificity from the literature and local data were 0.88 and 0.90 respectively. Conclusions: When investigating for underlying malignancy in patients with suspected pns and negative conventional imaging, pet has high sensitivity and specificity.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
7.
Magy Onkol ; 63(3): 261-267, 2019 09 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533147

RESUMO

Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AE) are rare neurological disorders, which have similar symptoms, but vary in outcome and treatment strategy. In our retrospective statistical study we evaluated the autoantibody test results of serum and CSF from 2362 patients with suspected PNS and 1034 patients with suspected AE. For autoantibody testing, immunoblot assay (PNS) and cell-based indirect immunofluorescence assay (AE) were used. Autoantibodies were present in 8% of patients with suspected PNS: anti-Yo > anti-Hu > anti-Ma2 > anti-CV2 > anti-titin > anti-Zic4 > anti-amphiphysin > anti-Ri > anti-GAD65 > anti-Sox1 > anti-recoverin. Mostly elderly women were affected. Autoantibodies were present in 5.8% of patients with suspected AE: anti-NMDAR (young women) > anti-LGI1 (middle-aged men) > anti-GABABR (elderly men) > anti-Caspr2 (adult men). Our results correspond to the data described in the literature. The number of patients with suspected PNS and AE shows an increasing tendency, where the autoantibody testing with modern laboratory diagnostic methods helps in the early introduction of the appropriate therapy.


Assuntos
Encefalite/diagnóstico , Encefalite/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/imunologia , Encefalite/terapia , Feminino , Doença de Hashimoto/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Estudos Retrospectivos
8.
Pain Physician ; 22(5): 433-445, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31561645

RESUMO

BACKGROUND: This comprehensive review of pain in paraneoplastic neurological syndromes focuses on current mechanisms that lead to pain, including autoimmune processes as well as the systemic secretion of factors that sensitize nociceptive nerves. Systemic secretion of functional molecules is a well-recognized phenomenon in endocrine paraneoplastic syndromes; however, cancer pain research has predominantly focused on cytokine-nerve interactions in the tumor microenvironment, and few groups have applied the molecular mechanisms of local pain to study widespread neuropathic pain resulting from systemic secretion. We present a novel perspective in the field of pain research by converging data from clinical oncology with recent molecular pain research on cytokine-mediated sensitization of nociceptive nerves. OBJECTIVE: Our objective was to conduct a review of paraneoplastic neurological syndromes and provide updates on therapeutic recommendations. STUDY DESIGN: We used a narrative review design. METHODS: This review was done using searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles from inception to the present date. Other data sources included hand searches of publications driven by manuscript authors. Search terms included concepts of paraneoplastic syndrome and chronic pain with emphasis on both preclinical and clinical studies. RESULTS: Articles were screened by title, abstract, and full article review. They were then analyzed by specific clinical indications and appropriate data was presented based on critical analysis of those articles. LIMITATIONS: More studies that distinguish autoimmune paraneoplastic pain syndromes from those related to systemic cytokine secretion are required. CONCLUSION: By providing a unified review across disciplines, we illustrate that neuropathic pain related to the systemic secretion of cytokines may represent another category of paraneoplastic neurological syndromes distinct from the well-known autoimmune neuronopathies. In addition, we discuss the clinical significance of distinguishing autoimmune paraneoplastic pain syndromes from those related to systemic cytokine secretion and highlight the need for further research at the intersection of these fields. This review takes a look at both past and current literature with a critical analysis of findings and respective recommendations. In addition, based on review of the literature we provide updated therapeutic recommendations for the consideration of pain practitioners when dealing with this patient population. KEY WORDS: Paraneoplastic neurologic syndromes, chronic pain, neuropathic pain, treatment guidelines, cytokines.


Assuntos
Citocinas , Neuralgia , Síndromes Paraneoplásicas do Sistema Nervoso , Dor Crônica/terapia , Humanos , Neuralgia/etiologia
9.
N Engl J Med ; 381(1): 47-54, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269365

RESUMO

A 37-year-old man with a history of seminoma presented with vertigo, ataxia, and diplopia. An autoantibody specific for kelch-like protein 11 (KLHL11) was identified with the use of programmable phage display. Immunoassays were used to identify KLHL11 IgG in 12 other men with similar neurologic features and testicular disease. Immunostaining of the patient's IgG on mouse brain tissue showed sparse but distinctive points of staining in multiple brain regions, with enrichment in perivascular and perimeningeal tissues. The onset of the neurologic syndrome preceded the diagnosis of seminoma in 9 of the 13 patients. An age-adjusted estimate of the prevalence of autoimmune KLHL11 encephalitis in Olmsted County, Minnesota, was 2.79 cases per 100,000 men. (Funded by the Rochester Epidemiology Project and others.).


Assuntos
Autoanticorpos/análise , Encéfalo/imunologia , Proteínas de Transporte/imunologia , Técnicas de Visualização da Superfície Celular , Encefalite/imunologia , Doença de Hashimoto/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Seminoma/complicações , Neoplasias Testiculares/complicações , Adulto , Idoso , Encefalite/epidemiologia , Doença de Hashimoto/epidemiologia , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência
11.
J Obstet Gynaecol Res ; 45(9): 1948-1951, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270892

RESUMO

The present report describes a case of anti-Hu antibody-mediated encephalopathy associated with ovarian cancer. The patient developed paraneoplastic neurologic syndromes (PNS) during the course of ovarian cancer and showed a symptom of jargon aphasia; diagnosis of PNS was made on the basis of serological and cerebrospinal examination, electroencephalogram (EEG), and magnetic resonance images. EEG initially indicated a condition of non-convulsive status epilepticus; however, levetiracetam administration facilitated complete recovery of this condition. Furthermore, immunotherapy and steroid therapy were very effective and significant improvement was achieved. PNS usually occur before the cancer is identified; however, the possibility of PNS should be considered when neurologic symptoms are noted during the course of oncologic diseases, including ovarian cancer.


Assuntos
Autoanticorpos/imunologia , Encefalopatias/imunologia , Proteínas ELAV/imunologia , Neoplasias Ovarianas/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Idoso , Feminino , Humanos
12.
Semin Diagn Pathol ; 36(4): 279-292, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31253539

RESUMO

Paraneoplastic neurological syndromes (PNS) constitute a heterogeneous group of cancer-related disorders that can affect any level of the central and peripheral nervous system. There is compelling evidence that PNS are caused by an immune response directed against neural antigens that are abnormally expressed by the tumour. PNS are frequently associated with neural-specific autoantibodies whose characterization has direct implications for diagnostic workup, treatment and outcome. The last decade has seen a dramatic rise in the discovery of novel autoantibodies associated with PNS, which has led to more accurate diagnoses and earlier treatments, potentially resulting in better outcomes. The latest advancements in the field of autoimmune neurology have paved the way to a more comprehensive understanding of PNS; yet, many aspects of their immunopathogenesis remain to be elucidated and patient-tailored treatment strategies still need to be optimized.


Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Neoplasias/complicações , Neoplasias/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia
13.
Eur J Paediatr Neurol ; 23(4): 662-667, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31105004

RESUMO

Acquired polyneuropathies (PN) are rare in childhood and adolescent. We report on a 15-year-old male patient who presented with progressive gait instability, ataxia, neuropathic pain, distal muscle weakness and progressive loss of ambulation. Nerve conduction studies (NCS) revealed a progressive demyelinating sensorimotor polyneuropathy predominantly of the lower limbs. Cerebrospinal fluid (CSF) analyses revealed a cytoalbuminologic dissociation. Extensive diagnostic workup for autoantibodies and inflammatory markers was inconclusive. Corticosteroids and intravenous immunoglobulins did not affect. Cranial MRI revealed leptomeningeal enhancement of the cerebellum and the brainstem. Brain biopsy of the cerebellar lesions revealed an unclassifiable sarcoma. The patient was treated according to the CWS guidance study resulting in a decrease in enhanced lesion size. After two years NCS still revealed a demyelinating sensorimotor PN. This case report describes for the first time the clinical course of a chronic PN, putative paraneoplastic, associated with isolated unclassifiable CNS-sarcoma in an adolescent patient. Paraneoplastic pathogenesis should be considered in an unusual sequence of subacute progressive neurological symptoms even in children and adolescents.


Assuntos
Neoplasias Encefálicas/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Polineuropatias/etiologia , Sarcoma/complicações , Adolescente , Humanos , Masculino
14.
Bull Cancer ; 106(6): 590-603, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31072598

RESUMO

Paraneoplastic syndromes are signs or symptoms that result from tissue damage at locations remote from tumour sites. Paraneoplastic syndromes associated with cancer of unknown primary (CUP) are not well recognized as they are rarely reported. These syndromes can impair various organ functions and include endocrine, neurologic, dermatologic, rheumatologic, hematologic and several other system alterations. To our knowledge, the association between the histological CUP type and the paraneoplastic syndrome has never been assessed. In some instances, paraneoplastic syndromes can become the major clinical problems determining survival. However, they can also herald earlier the occurrence of CUP in patients with asymptomatic tumors. In this article, we review the available literature of CUP patients presenting paraneoplastic syndromes by trying to collect all available published cases during the last three decades. One additional goal of this article is to make practicing oncologists aware of the coexistence of paraneoplastic syndromes in patients with CUP.


Assuntos
Neoplasias Primárias Desconhecidas/complicações , Síndromes Paraneoplásicas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/etiologia , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Especificidade de Órgãos , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/classificação , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/etiologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia
15.
Neuron ; 102(2): 294-320, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30998900

RESUMO

RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA splicing, transport, and stability. Disruption of RNA binding proteins and widespread RNA processing defects are increasingly recognized as critical determinants of neurological diseases. Here, we describe distinct mechanisms by which the homeostasis of RNA binding proteins is compromised in neurological disorders through their reduced expression level, increased propensity to aggregate or sequestration by abnormal RNAs. These mechanisms all converge toward altered neuronal function highlighting the susceptibility of neurons to deleterious changes in RNA expression and the central role of RNA binding proteins in preserving neuronal integrity. Emerging therapeutic approaches to mitigate or reverse alterations of RNA binding proteins in neurological diseases are discussed.


Assuntos
Doenças do Sistema Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Animais , Autofagia , Sistemas CRISPR-Cas , Terapia Genética , Vetores Genéticos , Homeostase , Humanos , Terapia de Alvo Molecular , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/terapia , Oligorribonucleotídeos Antissenso/uso terapêutico , Síndromes Paraneoplásicas do Sistema Nervoso/genética , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Processamento Pós-Transcricional do RNA , Processamento de RNA , Estabilidade de RNA , Transporte de RNA
16.
Nat Rev Clin Oncol ; 16(9): 535-548, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30867573

RESUMO

Paraneoplastic neurological syndromes (PNSs) comprise a group of disorders that can affect any part of the nervous system in patients with cancer and frequently result from autoimmune responses triggered by the ectopic expression of neuronal proteins in cancer cells. These disorders are rare, although the introduction of immune-checkpoint inhibitors (ICIs) into cancer treatment algorithms has renewed interest in PNSs. ICIs are associated with a considerably increased incidence of immunological toxicities compared with traditional anticancer therapies, including neurological immune-related adverse effects (nirAEs) that can manifest as PNSs. Theoretically, the use of ICIs might increase the risk of PNSs, in particular, in patients with the types of cancer that are most frequently associated with these disorders (such as small-cell lung cancer), emphasizing the importance of their prompt diagnosis and treatment to prevent irreversible neurological deficits. To facilitate the recognition of these disorders in the context of immune-checkpoint inhibition, we provide an overview of PNSs, including the main syndromes, types of neuronal autoantibodies and associated immunological mechanisms. We also review the scenarios in which nirAEs fulfil the criteria for PNSs and examine their frequency and clinical presentations. Finally, we provide recommendations for the prevention and management of PNSs that can occur during ICI therapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Síndromes Paraneoplásicas do Sistema Nervoso/induzido quimicamente , Humanos , Imunoterapia/métodos
17.
J Neuroimmunol ; 330: 136-142, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878696

RESUMO

Paraneoplastic myelopathy is rare paraneoplastic neurological syndromes. We reviewed patients through medical records system and screened patients who presented with myelopathy, and/or coexisting cancer, and/or onconeural antibodies. Nine patients were identified as paraneoplastic myelopathy presenting with progressive subacute (2/9) or insidious (7/9) myelopathy. CSF abnormalities included elevated protein, 5; pleocytosis, 4; excess oligoclonal bands, 6. Seven patients had onconeural antibody. Cancer was confirmed histopathologically in 6 and diagnosed by PET-CT in 1. Four patients had symmetric, longitudinally extensive grey matter or tract-specific changes on spinal cord MRI. It was associated with significant morbidity and had poor response to treatment.


Assuntos
Imunoterapia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico por imagem , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico por imagem , Idoso , Feminino , Seguimentos , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas do Sistema Nervoso/tratamento farmacológico , Estudos Retrospectivos , Doenças da Medula Espinal/tratamento farmacológico
18.
Neurol Sci ; 40(7): 1461-1463, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30843116

RESUMO

INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission. CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.


Assuntos
Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/complicações , Neoplasias Pulmonares/complicações , Doença dos Neurônios Motores/complicações , Síndromes Paraneoplásicas do Sistema Nervoso , Carcinoma de Pequenas Células do Pulmão/complicações , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/patologia , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Doença dos Neurônios Motores/etiologia , Doença dos Neurônios Motores/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia
20.
Thorac Cancer ; 10(4): 1001-1004, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30810271

RESUMO

Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC-predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti-neuronal nuclear antibody-type 1, voltage-gated calcium channel (VGCC)-N-type, VGCC-P/Q-type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle-AChR, and VGCC-P/Q-type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody-positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited-stage disease at diagnosis.


Assuntos
Autoanticorpos/sangue , Neoplasias Pulmonares/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Carcinoma de Pequenas Células do Pulmão/imunologia , Análise de Sobrevida
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