Lambert-Eaton Myasthenic Syndrome Caused by Atezolizumab in a Patient with Small-cell Lung Cancer

We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.     

Two Lambert-Eaton Myasthenic Syndrome Patients with Ameliorated Activities of Daily Living Due to Cholinesterase Inhibitors

We herein report two P/Q-type voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS) patients who responded dramatically to cholinesterase inhibitors. Patient 1, a 76-year-old man, had small-cell lung cancer and developed LEMS during chemotherapy. When symptomatic treatment was started with pyridostigmine, gait disturbance was ameliorated, and his modified Rankin scale decreased from 4 points to 3 points. Patient 2, a 68-year-old man, had cancer-free LEMS. Distigmine bromide was very effective and ameliorated not only his gait disturbance but also autonomic symptoms, and his modified Rankin scale decreased from 2 points to 1 point. Cholinesterase inhibitors alone may be effective in a small portion of LEMS patients.     

Remission by Chemotherapy of the Eaton-Lambert Myasthenic Syndrome in a Patient with Small Cell Bronchogenic Carcinoma

ABSTRACT. A 70-year-old man developed symptoms compatible with the Eaton-Lambert syndrome, and a small cell bronchogenic carcinoma was diagnosed. During treatment with cytostatics his muscular strength was restored and the lung tumour as well as the electrophysiologic findings characteristic of the Eaton-Lambert syndrome disappeared. To our knowledge, it has not been reported before that chemotherapy alone of a small cell bronchogenic carcinoma has resulted in clinical, roentgenologic, and electrophysiologic remission of the Eaton-Lambert syndrome.     

Paraneoplastic Opsoclonus-myoclonus Syndrome with Anti-Hu and Anti-SOX-1 Antibodies after Immune-checkpoint Inhibitor Treatment Combined with Chemotherapy in a Patient with Small-cell Lung Cancer

A 69-year-old man with advanced small-cell lung cancer achieved partial remission after 3 courses of immunochemotherapy that included atezolizumab. Ten days after the last treatment, he developed paraneoplastic opsoclonus-myoclonus syndrome and required mechanical ventilation. Serology testing detected anti-Hu and anti-SOX-1 antibodies. Despite steroid pulse therapy, various anticonvulsants, continuous intravenous sedation, and a fourth course of chemotherapy without atezolizumab, his condition failed to improve. Paraneoplastic opsoclonus-myoclonus syndrome with autoantibodies after immune-checkpoint inhibitor treatment has not been reported previously. Although a causal relationship between immune-checkpoint inhibitors and paraneoplastic syndromes has been suggested, the mechanism remains unknown.     

以Lambert-Eaton肌无力综合征为首发症状的肝细胞癌1例报告

正1病例资料患者女性,56岁,因眼睑下垂3个月就诊于当地医院神经内科,行肌电图提示Lambert-Eaton肌无力综合征(LambertEaton myasthenic syndrome,LEMS)可能性大。遂行头部核磁共振检查未见异常。肺部增强CT未见明显异常。肝胆三期增强CT示(图1):肝硬化、脾大、肝左叶外侧段异常强化影,考虑原发性肝癌可能性大,为求手术治疗入本院。既往史:患者     

Pleomorphic Carcinoma with Exophthalmos and a Subsequent Diagnosis of Paraneoplastic Syndrome

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.     

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.     

CV2/CRMP5-antibody-related Paraneoplastic Neurologic Syndrome Associated with Gastrointestinal Stromal Tumor

Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of neurological disorders caused by immune-mediated inflammatory mechanisms. We herein report a 77-year-old man with CV2/CRMP5-antibody-related PNS associated with a gastrointestinal stromal tumor (GIST). He was admitted for forgetfulness and delusional behavior. His neurological symptoms were subacute, and a whole-body examination revealed a gastric GIST. Serology showed CV2/collapsin response mediator protein (CRMP)-5 antibodies. Partial gastrectomy was performed for the GIST, and the neurological symptoms and serum CV2/CRMP5 antibodies disappeared. No relapse has occurred since the surgery. PNS should be considered in patients with subacute neurological disorders.     

Paraneoplastic polyarteritis nodosa with cerebral masses: case report and literature review

Polyarteritis nodosa (PAN) as a paraneoplastic vasculitis is rarely described, especially in association with squamous cell carcinoma (SCC). Furthermore, only 5% of all PAN patients have central nervous system (CNS) involvement, almost exclusively in the form of cerebral infarction or intracerebral haemorrhage. We report the first case of PAN with multiple immunosuppressant‐responsive, cerebral vasculitic lesions in association with metastatic SCC.     

Paraneoplastic Polymyositis Due to Renal Cell Carcinoma in a Patient with Autosomal Dominant Polycystic Kidney Disease

We herein report a 70-year-old man with malaise and muscle weakness that had developed within a month. The patient also had abdominal fullness due to polycystic kidney disease. Severe proximal skeletal muscle weakness and mild elevation of creatinine kinase to 301 IU/L were noted. A muscle biopsy of the right bicep showed polymyositis. Computed tomography showed a right renal mass, and an analysis after right nephrectomy identified clear cell carcinoma. The muscle weakness subsided one month after nephrectomy and intravenous immunoglobulin therapy. Therefore, we suspect that the development of polymyositis in this patient was closely related to renal cell carcinoma.     

Palmar Fasciitis and Polyarthritis Syndrome Associated with Lung Adenocarcinoma

Palmar fasciitis and polyarthritis syndrome (PFPAS) is a rare paraneoplastic rheumatic disease with characteristic features. We herein report a 77-year-old man with lung adenocarcinoma and contralateral pulmonary metastasis receiving chemotherapy who presented with progressive symmetrical flexion contractures associated with palmar fascial thickening and arthritis of both hands and shoulders. He was diagnosed with PFPAS as paraneoplastic manifestations. Salazosulfapyridine was not effective, but 15 mg/day of oral prednisolone improved his symptoms. Physicians should consider PFPAS and rule out malignancy in patients with arthritis in the extremities and flexion contractures associated with palmar fascial thickening.     

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs'' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs'' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs'' syndrome, suggesting that immunotherapy should be considered for Isaacs'' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.     

Spontaneous Regression of Small Cell Lung Carcinoma and Associated Hemichorea

The spontaneous regression (SR) of cancer is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and this phenomenon is rare in the case of small cell lung carcinoma (SCLC). We herein report an 83-year-old woman who presented with left-sided hemichorea associated with anti-SOX1 (SOX1-Ab) and -CV2/CRMP5 (CV2/CRMP5-Ab) antibodies with SR following a 7-year interval free of disease progression of SCLC. Hemichorea can present with the coexistence of anti-SOX1 and CV2/CRMP5-Ab with SR after a long interval free of SCLC. The immune response associated with these onco-neural antibodies may become independent of the original tumor trigger and remain active for many years.     

hnRNP A2/B1、LN-R在非小细胞肺癌的表达及临床意义

目的　探讨异质性细胞核核糖蛋白 A2 / B1 ( hn RNP A2 / B1 )、层粘连蛋白受体 ( L N- R)表达对非小细胞肺癌 ( NSCL C)的诊断价值及与 NSCL C临床病期、淋巴结转移的关系。方法　采用免疫组织化学方法检测 83例原发性 NSCL C、 32例肺良性肿瘤及 2 0例正常肺组织的 hn RNP A2 / B1 、 L N- R表达。结果　 NSCL C组 hn-RNP A2 / B1 、L N- R表达阳性率分别为 79.5 % ( 6 6 / 83)和 6 7.5 % ( 5 6 / 83) ,明显高于肺良性肿瘤组及正常肺组 (P <0 .0 5 ) ,肺良性肿瘤组阳性率与正常肺组无差异 ( P >0 .0 5 )。有淋巴结转移者 hn RNP A2 / B1 、 L N- R阳性率分别为 88.0 %和 76 .0 % ,明显高于无淋巴结转移者 ( 6 6 .7%、 5 4 .5 % ) ( P <0 .0 5 ) ; ～ 期 hn RNP A2 / B1 、 L N-R阳性率 ( 89.1%、 80 .4 % )明显高于 ～ 期患者阳性率 ( 6 7.6 %、 5 1.4 % ) ,P <0 .0 5。结论　hn RNP A2 / B1 、L N- R表达对 NSCL C诊断、预测病情及判断淋巴结转移均具有重要的临床价值。     

抗C1q抗体与系统性红斑狼疮疾病活动及狼疮肾炎的关系

目的研究抗C1q抗体与系统性红斑狼疮（systemic lupus erythematosus,SLE）疾病活动及肾损害的相关性。方法使用ELISA法测定93例初诊SLE患者和69例其他风湿性疾病患者及32名健康对照者血清中抗C1q抗体的浓度。同时记录SLE疾病活动指数（systemic lupus erythematosus Disease Activity Index,SLEDAI）、自身抗体和相关实验室指标。结果血清抗C1q抗体、抗dsDNA抗体、抗核小体抗体（anti-nucleosome antibodies,AnuA）,SLE组的阳性率分别为40.9%、62.4%和62.8%。血清抗C1q抗体阳性组患者的肾损害发生率（84.2%）明显高于阴性组（23.6%）。狼疮肾炎（lupus nephritis,LN）患者血清抗C1q抗体浓度（55.36±51.96）RU/ml及阳性率（71.1%）显著高于无肾炎表现的狼疮对照组（12.09±14.46）RU/ml,12.5%。无论患者有无肾损害,狼疮疾病活动患者抗C1q抗体浓度（62.46±50.29）RU/ml及阳性率（85.7%）显著高于疾病稳定的狼疮对照组（8.79±6.42）RU/ml,3.9%。而AnuA和抗dsDNA抗体只在伴有狼疮肾损害的疾病活动组即活动LN的阳性率（87.9%与50.0%）显著高于非活动LN对照组（66.7%与33.3%）。LN组抗C1q抗体、AnuA、抗dsDNA和抗Sm（Smith）抗体阳性率显著高于非LN组（71.1%与12.5%）,（77.8%与47.9%）,（57.8%与25.0%）,（31.1%与10.4%）。SLE疾病活动组抗C1q抗体、AnuA、抗dsDNA阳性率显著高于疾病稳定组（85.7%与3.9%）,（88.1%与41.2%）,（61.9%与17.6%）。活动LN抗C1q抗体、AnuA、抗dsDNA阳性率显著高于非活动LN（93.9%与8.3%）,（87.9%与50.0%）,（66.7%与33.3%）。活动LN组抗C1q抗体、AnuA、抗dsDNA及抗中性粒细胞胞质抗体（ANCA）阳性率显著高于其他SLE组（93.9%与13.1%）,（87.9%与48.3%）,（66.7%与26.7%）,（43.5%与8.5%）。结论血清抗C1q抗体能够反映SLE的疾病活动,并与SLE肾损害相关,是对活动性LN敏感的自身抗体。     

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.     

原发-转移病灶的RRM1和ERCC1表达差异性与非小细胞肺癌化疗疗效的相关性研究

目的探讨癌组织及转移淋巴结内RRM1和ERCC1蛋白表达与非小细胞肺癌(non-small cell lung cancer,NSCLC)患者以铂类药物为基础化疗方案疗效的相关性。方法收集出现淋巴结转移的非小细胞肺癌术后患者临床资料100例,并用免疫组化检测癌组织、转移淋巴结标本及其相应的癌旁正常肺组织中的RRM1和ERCC1蛋白表达水平,并分析其与铂类药物为基础化疗方案敏感性的相关性。结果 (1)RRM1在癌组织(T)和转移淋巴结组织(N)中表达阳性率分别为58%和33%,ERCC1在癌组织(T)和转移淋巴结组织(N)中表达阳性率分别为56%和29%,差异均有统计学意义(P0.05);(2)RRM1蛋白T(+)N(+)组化疗的有效率为13.3%(4/30),明显低于T(+)N(-)组的46.6%(13/28)以及T(-)N(-)组61.9%(26/42),差异具有统计学意义(P0.05);ERCC1蛋白T(+)N(+)组化疗的有效率为17.2%(5/2 9),明显低于T(+)N(-)组的44.4%(12/27)以及T(-)N(-)组的61.4%(27/44),差异有统计学意义(P0.05)。结论非小细胞肺癌患者RRM1和ERCC1在原发病灶与转移淋巴结表达的差异性是化疗方案中铂类药物敏感性差别的重要因素,可为非小细胞肺癌术后患者化疗方案选择提供参考