RESUMO
Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.
Assuntos
Síndrome de Isaacs , Mieloma Múltiplo , Polineuropatia Paraneoplásica , Doenças do Sistema Nervoso Periférico , Humanos , Polineuropatia Paraneoplásica/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Autoanticorpos , Nervos Periféricos , Imunoglobulina M , DorRESUMO
The authors describe a patient with a background of metastatic small cell prostate cancer who presented with a rapidly evolving sensorimotor neuropathy with bulbar features closely resembling Guillain-Barré syndrome, with a good initial response to intravenous immunoglobulins and platinum-based chemotherapy. This represented a likely paraneoplastic manifestation of the patient's urological malignancy.
Assuntos
Carcinoma de Células Pequenas , Síndrome de Guillain-Barré , Polineuropatia Paraneoplásica , Doenças do Sistema Nervoso Periférico , Neoplasias da Próstata , Masculino , Humanos , Polineuropatia Paraneoplásica/diagnóstico , Polineuropatia Paraneoplásica/etiologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/tratamento farmacológico , Síndrome de Guillain-Barré/tratamento farmacológico , Autoanticorpos , Imunoglobulinas Intravenosas/uso terapêutico , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVES: Pathologic descriptions of peripheral nerve involvement in paraneoplastic neuropathies are sparse, mostly from autopsies focusing on CNS and dorsal root ganglia tissues. Here, we describe the clinicopathologic features of peripheral nerve biopsies in patients with paraneoplastic neurologic syndromes to expand the currently limited knowledge. METHODS: Retrospective review of the Mayo Clinic electronic medical record from 1995 to 2022 for patients identified to have subacute onset neuropathy with paraneoplastic antibodies identified in our neuroimmunology laboratory having available nerve biopsies performed at the time of diagnosis. Patients with another cause of neuropathy not linked to their subacute onset were excluded. RESULTS: Nineteen patients met inclusion criteria: 4 with amphiphysin antibodies, 6 with antineuronal nuclear antibody (ANNA)-1 only, 3 with both ANNA-1 and collapsin response-mediator protein 5 (CRMP-5), 2 with ANNA-2, and 4 with CRMP-5 antibodies only. Fifteen biopsies had reduced the density of myelinated nerve fibers-4 with multifocality. Subperineurial edema was present in 17 biopsies. Prominent epineurial perivascular inflammation was present in 3 biopsies, all belonging to patients with a lumbosacral radiculoplexus neuropathy (LRPN) phenotype. DISCUSSION: Axonal loss, subperineurial edema, and an absence of prominent inflammation are the most common findings in nerve biopsies of patients with paraneoplastic antibodies strongly associated with cancer. The LRPN phenotype was the only subset with inflammatory collections. Paraneoplastic autoantibody testing should be considered in patients with subacute onset neuropathies, with or without interstitial inflammatory findings.
Assuntos
Neoplasias , Polineuropatia Paraneoplásica , Humanos , Neoplasias/complicações , Autoanticorpos , Inflamação , EdemaRESUMO
We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.
Assuntos
Neoplasias do Sistema Nervoso Central , Doenças do Nervo Facial , Linfoma , Neuropatia Ciática , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/imunologia , Doenças do Nervo Facial/etiologia , Doenças do Nervo Facial/imunologia , Doenças do Nervo Facial/terapia , Fluordesoxiglucose F18 , Imunoglobulina G/imunologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Receptores de GABA/metabolismo , Neuropatia Ciática/etiologia , Neuropatia Ciática/imunologia , Neuropatia Ciática/terapia , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Linfoma/complicações , Linfoma/diagnóstico por imagem , Linfoma/imunologia , Polineuropatia Paraneoplásica/etiologia , Polineuropatia Paraneoplásica/imunologia , Prednisona/uso terapêutico , Glucocorticoides/uso terapêutico , Troca Plasmática , Proteínas do Tecido Nervoso/imunologiaRESUMO
We describe the first case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma. Our patient presented with progressive unsteadiness and numbness involving bilateral upper and lower limbs. He had symmetrical length-dependent lower motor neuron pattern of weakness and numbness involving both small and large fibres with prominent sensory ataxia. An extended workup for the polyneuropathy involving a serum paraneoplastic antineuronal antibody panel showed a positive reaction for anti-CV2 antibody. CT scan of the thorax, abdomen and pelvis revealed a right upper lung nodule and histopathological examination of the nodule revealed lung adenocarcinoma. He was scheduled for chemotherapy following his discharge and there was improvement of his sensorimotor polyneuropathy following his chemotherapy.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Polineuropatia Paraneoplásica , Masculino , Humanos , Polineuropatia Paraneoplásica/etiologia , Hipestesia , Adenocarcinoma de Pulmão/complicações , Neurônios Motores/patologia , Neoplasias Pulmonares/patologia , AutoanticorposRESUMO
Introdução: Os avanços nas áreas da saúde e tecnologia favoreceram o processo de transição demográfica e o aumento da expectativa de vida. Consequentemente, o aumento da população idosa ocasiona um aumento das doenças crônicas não-transmissíveis, que incluem o câncer, considerado a segunda principal causa de morte em todo mundo. Dentre as diversas opções de tratamento do câncer destaca-se a quimioterapia, que durante seu uso o paciente pode apresentar diferentes eventos adversos. Um destes eventos é a neurotoxicidade, conhecida como neuropatia periférica induzida por quimioterápicos (NPIQ), que é caracterizada como uma lesão inflamatória ou degenerativa dos nervos periféricos. Manifesta-se por sintomas sensoriais típicos, como perda de sensibilidade nos membros e perda de reflexos, fraqueza em mãos e pés e disestesias, perda de discriminação entre o toque e temperatura (frio e calor), cujas manifestações clínicas incluem dor, formigamento, choque e queimação, e podem implicar em consequências negativas para a vida cotidiana e tornando-se mais vulnerável a ocorrências de quedas. Objetivos: Avaliar a ocorrência da NPIQ e o risco de queda em mulheres idosas com diagnóstico de câncer. Métodos: Estudo quantitativo, descritivo e transversal, desenvolvido com 60 mulheres idosas que realizavam o tratamento quimioterápico para qualquer tipo de câncer. Os dados coletados foram sócio-demográficos e sobre o câncer, e foram aplicados os instrumentos: Escala de Risco de Queda (Fall Risk Score), Escala de Fragilidade de Edmonton (Edmonton Frail Scale) e Ferramenta de Avaliação de Neuropatia Periférica Induzida por Quimioterapia (FANPIQ). Os dados foram digitados no Microsoft Excel, e analisado no Statistical Package for the Social Sciences - SPSS v. 22.0. Foram realizadas análises descritivas com média e desvio padrão, analítica e testes de regressão multivariada. Resultados: A média de idade das participantes foi 69,57 (DP±7,63) anos, 58,3% apresentava hipertensão arterial e 30% diabetes mellitus, 96,7% utilizavam algum tipo de medicação e 75% apresentavam câncer de mama. Quanto ao risco de queda, 36,7% das participantes afirmaram já ter apresentado algum tipo de queda nos últimos 12 meses, com ou sem lesão; entretanto somente 6,7% apresentaram algum déficit sensorial. Na avaliação da fragilidade, 58,3% das idosas não precisavam de auxílio para realizar atividades básicas da vida diária, e 48,3% das participantes foram aprovadas na cognição. Quanto aos sintomas neuropáticos que avaliou a ocorrência de dormência, formigamento, sensibilidade e neuralgia durante o tratamento quimioterápico, todos com influência em algumas atividades cotidianas das mulheres. De acordo com as análises de regressão, a dormência e formigamento nas mãos, neuralgia, dormência nos pés e sensibilidade ao frio foram itens com associação estatística na escala de fragilidade. Conclusão: Este estudo avaliou a ocorrência da NPIQ e o risco de queda em mulheres idosas com diagnóstico de câncer. Apesar de pouco descrito na literatura, foi possível identificar a influência da NPIQ nas atividades cotidianas, com a associação entre os sintomas e o risco de queda, bem como as limitações funcionais no cotidiano da mulher
Introduction: Advances in the areas of health and technology favored the process of demographic transition and increased life expectancy. Consequently, the increase in the elderly population causes an increase in non-communicable chronic diseases, which include cancer, considered the second leading cause of death worldwide. Among the various cancer treatment options, chemotherapy stands out, as during its use the patient may experience different adverse events. One of these events is neurotoxicity, known as chemotherapy-induced peripheral neuropathy (CIPN), which is characterized as an inflammatory or degenerative lesion of the peripheral nerves. It is manifested by typical sensory symptoms, such as loss of sensitivity in the limbs and loss of reflexes, weakness in the hands and feet and dysesthesias, loss of discrimination between touch and temperature (cold and heat), whose clinical manifestations include pain, tingling, shock and burning, and may result in negative consequences for everyday life and make them more vulnerable to falls. Objective: To assess the occurrence of CIPN and the risk of falling in elderly women diagnosed with cancer. Method: Quantitative, descriptive and cross-sectional study, developed with 60 elderly women who underwent chemotherapy treatment for any type of cancer. The data collected were socio-demographic and about cancer, and the following instruments were applied: Fall Risk Score, Edmonton Frail Scale, and the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (FANPIQ). Data were entered into Microsoft Excel, and analyzed using the Statistical Package for the Social Sciences - SPSS v. 22.0. Descriptive analyzes were performed with mean and standard deviation, analytical and multivariate regression tests. Results: The participants' mean age was 69.57 (SD±7.63) years, 58.3% had arterial hypertension and 30% had diabetes mellitus, 96.7% used some type of medication and 75% had breast cancer. As for the risk of falling, 36.7% of the participants stated that they had already had some type of fall in the last 12 months, with or without injury; however, only 6.7% had some sensory deficit. In the assessment of frailty, 58.3% of the elderly women did not need help to carry out basic activities of daily living, and 48.3% of the participants passed the cognition test. As for the neuropathic symptoms, it evaluated the occurrence of numbness, tingling, sensitivity and neuralgia during chemotherapy treatment, all of which influenced some of the women's daily activities. According to the regression analyses, numbness and tingling in the hands, neuralgia, numbness in the feet and sensitivity to cold were items with statistical association in the frailty scale. Conclusion: This study evaluated the occurrence of CIPN and the risk of falling in elderly women diagnosed with cancer. Although little described in the literature, it was possible to identify the influence of CIPN on daily activities, with the association between symptoms and the risk of falling, as well as functional limitations in women's daily lives
Assuntos
Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Acidentes por Quedas , Polineuropatia Paraneoplásica , Neoplasias , FragilidadeRESUMO
OBJECTIVE: To identify the autoantigen in 2 individuals with possible seronegative paraneoplastic neuropathy. METHODS: Serum and CSF were screened by tissue-based assay and panned for candidate autoantibodies by phage display immunoprecipitation sequencing (PhIP-Seq). The candidate antigen was validated by immunostaining knockout tissue and HEK 293T cell-based assay. RESULTS: Case 1 presented with gait instability, distal lower extremity numbness, and paresthesias after a recent diagnosis of serous uterine and fallopian carcinoma. Case 2 had a remote history of breast adenocarcinoma and presented with gait instability, distal lower extremity numbness, and paresthesias that progressed to generalized weakness. CSF and serum from both patients immunostained the axon initial segment (AIS) and node of Ranvier (NoR) of mice and enriched ßIV-spectrin by PhIP-Seq. Patient CSF and serum failed to immunostain NoRs in dorsal root sensory neurons from ßI/ßIV-deficient mice. ßIV-spectrin autoantibodies were confirmed by overexpression of AIS and nodal ßIV-spectrin isoforms Σ1 and Σ6 by a cell-based assay. ßIV-spectrin was not enriched in a combined 4,815 PhIP-Seq screens of healthy and other neurologic disease patients. DISCUSSION: Therefore, ßIV-spectrin autoantibodies may be a marker of paraneoplastic neuropathy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ßIV-spectrin antibodies are specific autoantibody biomarkers for paraneoplastic neuropathy.
Assuntos
Polineuropatia Paraneoplásica , Espectrina , Humanos , Autoanticorpos , Hipestesia , Parestesia , Animais , CamundongosRESUMO
A 49-year-old man presented with progressive asymmetric weakness and pain. Electrodiagnostic tests and nerve biopsy suggested chronic demyelinating polyneuropathy refractory to immune-modulating therapy. The patient's symptoms were aggravated, and he was finally diagnosed with T-cell lymphoma based on the findings of the second 18F-2 fluoro-2-deoxy-glucose positron emission tomography/CT performed 16 months after symptom onset. The patient received intravenous chemotherapy, but died 2 months later because of lymphoma progression. A clinical suspicion of neurolymphomatosis and early diagnosis are important for proper management.
Assuntos
Doença Enxerto-Hospedeiro , Linfoma de Células T , Neurolinfomatose , Polineuropatia Paraneoplásica , Doença Enxerto-Hospedeiro/complicações , Humanos , Linfoma de Células T/complicações , Masculino , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/diagnóstico , Polineuropatia Paraneoplásica/etiologia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/efeitos adversosRESUMO
Introdução: Síndrome POEMS trata de um raro evento paraneoplásico, sem relato atual na literatura sobre sua real prevalência. A maior parte dos casos ocorre em homens de meia idade; Relato do Caso: Relatamos o caso de um paciente masculino, 65 anos, admitido com queixa edema e parestesia em pernas que evoluiu para plegia, associada a hiporexia e fadiga. Investigação ambulatorial inicial evidenciou polirradiculoneuropatia inflamatória desmielinizante crônica (PIDC) de etiologia indefinida. Excluídos secundarismos para polirradiculoneuropatia inflamatória desmielinizante crônica, o paciente foi a seguir diagnosticado com hipotireoidismo primário, hipogonadismo severo, lesões hipercrômicas em pele, ascite, derrame pleural e trombocitose, além de gamopatia monoclonal IgA Lambda por imunofixação sérica. Sorologias para HIV, Sífilis e Hepatites todas negativas. Excluída a possibilidade de Mieloma Múltiplo e outras gamopatias, foi aventada a hipótese de Síndrome POEMS, sendo realizada dosagem de Fator de Crescimento Endotelial Vascular (VEGF) plasmática (425 pg/mL; VR = <96.2). O paciente passou então a preencher os critérios obrigatórios para diagnóstico, além de um maior (VEGF elevada) e vários outros menores. Trata-se de um caso atípico na medida em que, lesões ósseas, presentes em até 97% dos casos, não foram evidenciadas no paciente em questão, tornando desafiador o diagnóstico e sendo então necessário recorrer à dosagem de VEGF. O diagnóstico de síndromes raras, embora desafiante, traz ao clínico um olhar mais amplo do paciente na medida em que incrementa o raciocínio clínico. Difundir e explorar esse universo é cada vez mais necessário
Introduction: POEMS syndrome is a rare paraneoplastic event, with no current report in the literature about its real prevalence. Most cases occur in middle-aged men; Case Report: We report the case of a male patient, 65 years old, admitted with complaints of edema and paresthesia in the legs that progressed to plegia, associated with hyporexia and fatigue. Initial outpatient investigation revealed Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) of undefined etiology. Excluding secondaries for chronic inflammatory demyelinating polyradiculoneuropathy, the patient was subsequently diagnosed with primary hypothyroidism, severe hypogonadism, hyperchromic skin lesions, ascites, pleural effusion and thrombocytosis, in addition to monoclonal IgA Lambda gammopathy by serum immunofixation. All serologies for HIV, Hepatitis and syphilis were negative. Excluding the possibility of Multiple Myeloma and other gammopathies, the hypothesis of POEMS Syndrome was raised, and plasma Vascular Endotelial Growth Factor (VEGF) measurement was performed (425 pg/mL; RV = <96.2). The patient then started to fulfill the mandatory criteria for diagnosis, in addition to a major (elevated VEGF) and several other minors. This is an atypical case in that bone lesions, present in up to 97% of the cases, were not evidenced in the patient in question, making the diagnosis challenging and therefore requiring the use of VEGF dosage. The diagnosis of rare syndromes, although challenging, brings the clinician a broader view of the patient as it increases clinical reasoning. Spreading and exploring this universe is increasingly necessary
Assuntos
Humanos , Paraproteinemias , Síndrome POEMS/diagnóstico , Polineuropatia Paraneoplásica , Diagnóstico Diferencial , Doenças do Sistema EndócrinoRESUMO
BACKGROUND: Paraneoplastic neurologic syndromes (PNS) are rare, however, are important to recognize as oftentimes they precede the detection of an occult malignancy. Our case highlights a rare circumstance of paraneoplastic radiculoneuropathy and the importance of recognizing PNS in antibody negative disease, as is the case in up to 16% of sensory neuronopathies, and the process of excluding other etiologies. CASE PRESENTATION: We discuss a 51-year-old man who presented with asymmetric subacute sensorimotor deficits in the lower limbs. Initial clinical examination showed weakness throughout the right lower limb and normal strength on the left with objective numbness in a mixed dermatomal and stocking-glove distribution. Electrophysiology was consistent with axonal sensorimotor neuropathy. Cerebrospinal fluid showed pleocytosis and elevated protein. Intravenous immunoglobulin treatment was given with some improvement in pain symptoms but no measurable motor improvement. Following clinical and electrophysiologic deterioration the patient was transferred to a tertiary centre. Magnetic resonance imaging of the spine showed smooth enhancement of the ventral caudal nerve roots. Chest computed tomography revealed left lower vascular scarring. Further positron emission tomography scan imaging identified fluorodeoxyglucose avid right lung lymphadenopathy. Bronchoscopy-guided biopsy revealed small cell lung carcinoma. Onconeural and antiganglioside antibodies were negative. The patient was then transferred to a medical oncology ward where he underwent chemoradiotherapy and subsequently experienced improvement in his motor function, supporting that his neurological condition was indeed secondary to a paraneoplastic process. CONCLUSIONS: Onconeural negative paraneoplastic radiculoneuropathy can precede diagnosis of small cell lung carcinoma. If considered early and adequately investigated, it can allow earlier diagnosis and treatment of underlying malignancy, improving overall and neurological prognosis.
Assuntos
Cauda Equina , Neoplasias Pulmonares , Polineuropatia Paraneoplásica , Síndromes Paraneoplásicas do Sistema Nervoso , Carcinoma de Pequenas Células do Pulmão , Autoanticorpos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/diagnóstico por imagem , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico por imagem , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagemRESUMO
A 78-year-old woman experienced gait disturbance. She became unable to walk within a month. On admission, her cranial nerves were normal. She had motor weakness in the arms and legs, dysesthesia of the peripheral extremities, impaired deep sensation in the legs, and hyporeflexia in the arms and legs. She was initially diagnosed with Guillain-Barré syndrome; therefore, she was treated with intravenous immunoglobulin therapy and steroid mini-pulse therapy, however improvements of her neurological deficits were minimal. Anti-Hu antibody was positive in serum and gallbladder carcinoma was detected. She was treated with chemotherapy but neurological symptoms worsened progressively. Gallbladder carcinoma can rarely cause anti-Hu associated paraneoplastic sensorimotor neuropathy.
Assuntos
Anticorpos Antinucleares , Anticorpos Antineoplásicos , Neoplasias da Vesícula Biliar , Polineuropatia Paraneoplásica , Idoso , Feminino , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/terapia , Humanos , Polineuropatia Paraneoplásica/etiologiaAssuntos
Neoplasias Pulmonares/patologia , Melanoma/patologia , Polineuropatia Paraneoplásica/patologia , Síndromes Paraneoplásicas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Melanoma/diagnóstico , Melanoma/genética , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/diagnóstico , Polineuropatia Paraneoplásica/genética , Síndromes Paraneoplásicas/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
BACKGROUND AND AIMS: SOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. METHODS: We describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. RESULTS: Treatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. INTERPRETATION: Male breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.
Assuntos
Neoplasias da Mama Masculina/complicações , Carcinoma Ductal de Mama/complicações , Polineuropatia Paraneoplásica/tratamento farmacológico , Polineuropatia Paraneoplásica/etiologia , Fatores de Transcrição SOXB1/imunologia , Idoso , Autoanticorpos/imunologia , Autoantígenos/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Polineuropatia Paraneoplásica/imunologiaRESUMO
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patients' ability to walk and perform activities of daily living independently. With the lack of a diagnostic biomarker, the diagnosis relies on clinical suspicion, clinical findings, and the demonstration of demyelinating changes on electrodiagnostic (EDx) testing and nerve pathology. As a result, patients can often be misdiagnosed with CIDP and unnecessarily treated with immunotherapy. Interpreting the EDx testing and cerebrospinal fluid findings in light of the clinical phenotype, recognizing atypical forms of CIDP, and screening for CIDP mimickers are the mainstays of the approach to patients suspected of having CIDP, and are detailed in this review. We also review the currently available treatment options, including intravenous immunoglobulin (IVIg), corticosteroids (CCS), and plasma exchange (PE), and discuss how to approach treatment-refractory cases. Finally, we emphasize the need to adopt objective outcome measures to monitor treatment response.
Assuntos
Eletrodiagnóstico , Condução Nervosa , Nervos Periféricos/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Corticosteroides/uso terapêutico , Neuropatias Amiloides/diagnóstico , Líquido Cefalorraquidiano/química , Doença de Charcot-Marie-Tooth/diagnóstico , Diagnóstico Diferencial , Erros de Diagnóstico , Progressão da Doença , Humanos , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Infusões Subcutâneas , Uso Excessivo dos Serviços de Saúde , Avaliação de Resultados em Cuidados de Saúde , Síndrome POEMS/diagnóstico , Polineuropatia Paraneoplásica/diagnóstico , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Nervos Periféricos/patologia , Troca Plasmática/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapiaRESUMO
Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.
Assuntos
Neoplasias Pulmonares , Polineuropatia Paraneoplásica , Carcinoma de Pequenas Células do Pulmão , Autoanticorpos , Carboplatina/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Polineuropatia Paraneoplásica/induzido quimicamente , Polineuropatia Paraneoplásica/diagnóstico , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
OBJECTIVE: To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement. METHODS: Observational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity. RESULTS: Among 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27-84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody [ANNA] type 1 [anti-Hu], n = 5; collapsin response mediator protein 5 [CRMP5] [anti-CV2], n = 6; Purkinje cell cytoplasmic antibody type 1 [PCA1] [anti-Yo], n = 1; Purkinje cell cytoplasmic antibody type 2 [PCA2], n = 2; kelch-like protein 11 [KLHL11], n = 1; and combinations thereof: ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed in 25 cases (onconeural antibodies, n = 19; unclassified antibodies, n = 3; no antibodies, n = 3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%), sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pounds (63%). Neurologic examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally extensive (45%), tract-specific spinal cord T2 hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of 28 (36%) were unable to ambulate independently at last follow-up (median 24 months, range 5-133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin Scale scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1-4] vs 4 [range 2-6], p < 0.001). CONCLUSIONS: Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.
Assuntos
Autoanticorpos/sangue , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/sangue , Polineuropatia Paraneoplásica/diagnóstico , Polineuropatia Paraneoplásica/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Estudos RetrospectivosRESUMO
A 67-year-old woman with a history of smoking and cardiovascular risk factors was admitted to the emergency room for uncontrolled diabetes, loss of appetite, nausea, significant weight loss and asthenia. The initial investigation, including cerebral and gastrointestinal explorations, were normal. One month later, she started presenting severe asymmetric proprioceptive ataxia of the lower extremities. She also reported paresthesia and neuropathic pain in both feet and ankles. A positron emission tomography (PET)-scanner showed a hypermetabolic nodule in the right lung. The neurological symptoms were attributed to paraneoplastic sensory and dysautonomic neuropathy, even though the bronchoscopic biopsies came back negative at first. Anti-Hu, anti-CV2/CRMP5 and anti-SOX1 antibodies were documented. Due to the severity and rapid progression of symptoms (from the lower to the upper limbs), corticosteroids, intravenous immunoglobulins and immunosuppressants were introduced prior to biopsies revealing a small-cell lung cancer. Despite these treatments and antineoplastic chemotherapy, her status deteriorated rapidly.
Assuntos
Neoplasias Pulmonares , Polineuropatia Paraneoplásica , Carcinoma de Pequenas Células do Pulmão , Idoso , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Autoanticorpos/sangue , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Polineuropatia Paraneoplásica/diagnóstico , Polineuropatia Paraneoplásica/etiologia , Polineuropatia Paraneoplásica/terapia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
Peripheral neuropathy is common, but rarely due to vasculitis. This report is the case of a 74-year-old woman with systemic vasculitis who presented with progressive arm and leg weakness associated with numbness. Autopsy revealed a colon cancer, which may have triggered the vasculitis. This case illustrates the association between vasculitis and malignancy. The best treatment of vasculitis in patients with cancer-associated vasculitis is usually treatment of the cancer, which often yields remission of the vasculitis. This case also illustrates the difficulty of suspecting vasculitis since the symptoms and signs are nonspecific and protean. It is important not to miss a diagnosis of vasculitis. It is often life-threatening. It is treatable. The critical step in the diagnosis of vasculitis is to think of it.