Paraneoplastic neuropathies and peripheral nerve hyperexcitability disorders.

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.

Acute sensorimotor paraneoplastic neuropathy in a patient with small cell prostate cancer.

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.

Clinicopathologic Findings in Patients With Paraneoplastic Neuropathies and Antibodies Strongly Associated With Cancer.

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.

Amphiphysin-IgG autoimmune sciatic neuropathy and facial neuropathy related to primary central nervous system lymphoma: A case report.

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.

Rare case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma.

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.

Neuropatía periférica, onicólisis y calidad de vida en mujeres con cáncer de mama en tratamiento con taxanos. Estudio longitudinal prospectivo / Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study

FUNDAMENTOS: La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. MÉTODOS: Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel y/o paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2 ®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. RESULTADOS: Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ2 =11,3; p<0,001 / χ2 =13,0; p<0,001), y el 38,1% una calidad de vida restringida a actividad exagerada (χ2 =10,3; p=0,001). En la valoración postratamiento, el 20,9% presentó neuropatía motora y el 32,6% neuropatía sensitiva (χ2 =3,57; p=0,059 / χ2 =6,23; p=0,013), el 86% onicólisis en extremidades superiores y el 90,7% en inferiores (χ2 =6,07; p=0,048 / χ2 =10,1; p=0,006) y el 58,5% al menos una calidad de vida restringida a actividad exagerada(χ2=8,47; p=0,014). A los seis meses no se recuperaron los valores iniciales...(AU)

BACKGROUND: Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS: Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2® . For the relationship of the qualitative variables, the chi-square, Fisher’s exact test, Mc’s test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS: 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2 =11.3; p<0.001 / χ2 =13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2 =10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2 =3.57; p=0.059 / χ2 =6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2 =6.07; p=0.048 / χ2 =10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2 =8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS: Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.(AU)

Pessoa com neuropatia periférica induzida pela quimioterapia: Da avaliação aos registos de enfermagem / Person with chemotherapy-induced peripheral neuropathy: From assessment to nursing records

A Neuropatia Periférica Induzida pela Quimioterapia (NPIQ) é a toxicidade neurológica mais frequente no tratamento do cancro. É causada pela deterioração do sistema nervoso periférico. O quadro clínico e a gravidade desta toxicidade podem manifestar-se de semanas a meses após o início da quimioterapia (QT), com maior ou menor grau de reversibilidade/cronicidade, condicionando o autocuidado, a autonomia e o bem-estar da pessoa. A sua prevenção, diagnóstico e tratamento são um desafio constante para os profissionais de saúde, particularmente para os enfermeiros, agentes no diagnóstico, avaliação, prevenção e reabilitação desta condição. Este estudo objetiva identificar e compreender como os enfermeiros avaliam e registam os efeitos da NPIQ, na pessoa, numa unidade ambulatória de Oncologia Médica. Desenvolveu-se um estudo de caso, com abordagem mista, repartido em duas fases, realizando-se, previamente, uma síntese da evidência, que identificou e mapeou os instrumentos utilizados por enfermeiros na avaliação da pessoa com NPIQ. Na primeira fase, quantitativa, procedeu-se à análise do padrão documental dos enfermeiros. Tal foi organizado numa base de dados, através de um formulário no Google Docs ®, suportado por uma grelha de extração de dados. Na segunda fase, qualitativa desenvolveu-se um focus group com a equipa de enfermagem, para explorar e refletir sobre a análise documental. Simultaneamente realizou-se a audiogravação, guiada por três investigadores. Após a transcrição, procedeu-se à organização e análise do conteúdo, através das orientações de Bardin. Cumpriram-se todos os procedimentos éticos e legais exigidos. Dos 278 registos de enfermagem analisados, apenas 2,2% apresentam o diagnóstico de NPIQ. E 0,4% apresenta a avaliação do seu grau. Nenhum identificou as alterações nas Atividades de Vida Diárias (AVD) nem ensinos realizados acerca das intervenções desenvolvidas. O focus group realizado permitiu verificar que os registos não ilustram a perceção, avaliação e intervenção dos enfermeiros, neste domínio, tendo imergido estas três categorias e várias subcategorias. Conscientes de que boas práticas resultam do desenvolvimento de um sistema complexo de intervenções, este estudo conduziu à sensibilização e mobilização de conhecimentos da equipa de enfermagem, com intenção de implementação de um instrumento de avaliação da NPIQ, e desenvolvimento de intervenções promotoras de diagnóstico e reabilitação da condição.

ßIV-Spectrin Autoantibodies in 2 Individuals With Neuropathy of Possible Paraneoplastic Origin: A Case Series.

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.

Chronic demyelinating polyneuropathy preceding T-cell lymphoma: differentiation between primary neurolymphomatosis and paraneoplastic neuropathy.

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.

Polineuropatía periférica sensitivo-motora paraneoplásica asociada a anti-Ri: a propósito de un caso / Paraneoplastic sensory-motor peripheral polyneuropathy associated with anti-Ri: A case report

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Síndrome POEMS: desafios no diagnóstico de um caso atípico / POEMS syndrome: challenges in the diagnosis of an atypical case

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

Paraneoplastic sensorimotor neuropathy and ventral cauda equina nerve root enhancement as initial presentation of small cell lung carcinoma: a case study.

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.

[Paraneoplastic sensorimotor neuropathy with anti-Hu antibody associated with gallbladder carcinoma].

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.

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma.

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.

Chronic inflammatory demyelinating polyradiculoneuropathy-Diagnostic pitfalls and treatment approach.

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.

Paraneoplastic Myeloneuropathies: Clinical, Oncologic, and Serologic Accompaniments.

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.

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer.

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.

Paraneoplastic subacute sensory neuropathy with triple positive antineuronal antibodies associated with small-cell lung cancer.

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.