Paraneoplastic pseudo-obstruction,mononeuropathy multiplex,and sensory neuronopathy

A patient with mononeuropathy multiplex, sensory neuronopathy, and diffuse intestinal pseudo-obstruction consisting of gastroparesis and impaired small and large bowel motility was found to have a small cell carcinoma of the lung. The constellation of findings were indicative of paraneoplastic neuropathy, which was confirmed with the appropriate antibody studies demonstrating antineuronal nuclear antibodies. Identification of paraneoplastic neuropathy is important, since early treatment of the primary cancer, which is virtually always a small cell carcinoma of the lung, may halt the progression of the disorder. © 1994 John Wiley & Sons, Inc.     

AAEM case report #31: Paraneoplastic sensory neuronopathy

Sensory neuronopathy (SN) presents with sensory ataxia and no weakness. The site of pathology is in the dorsal root ganglia. Electrodiagnostic studies show absence of sensory nerve action potentials and preservation of motor nerve function. Elderly individuals with sensory ataxia and typical electrodiagnostic findings of SN should be evaluated for underlying carcinoma. © 1996 American Association of Electrodiagnostic Medicine. Published by John Wiley & Sons, Inc.     

Neuronal antinuclear antibody in sensory neuronopathy from lung cancer

We found an antinuclear antibody highly restricted to nuclei of neurons in two patients with subacute sensory neuronopathy complicating oat cell carcinoma of the lung. Serum was tested by indirect immunofluorescence and immunoperoxidase staining. At low concentrations of antibody, only the nuclei of the neurons were stained. At high concentrations, there was also staining of the nuclei of glial cells and fetal nonneural tissues. The cytoplasm of most neurons was stained with the immunoperoxidase method.     

Sensory neuronopathy and small cell lung cancer: antineuronal antibody reacting with neuroblastoma cells

The anti-Hu antibody is associated with a paraneoplastic subacute sensory neuronopathy (SSN) described in cases of small cell lung cancer (SCLC). The Hu antigen is a pan-neuronal nuclear antigen with a molecular weight of 35–40 kDa. In this study we demonstrated the presence of the paraneoplastic Hu antigen in different neuroblastoma cell lines. We showed that by indirect immunocytochemistry the serum of patients with SSN and SCLC reacts with the nuclei of neuroblastoma cell lines SKN-SH and LAN-1. Western blot analysis of nuclear extracts from neuroblastoma cell lines SKN-SH, IMR-32 and LAN-1 confirmed the presence of the Hu antigen in these neuroblastoma cell lines. By comparing the immunocytochemical method and the Western blot analysis we were able to determine that the Western blot analysis was a more sensitive test. Screening of the sera of a large population (a total of 122 patients with SCLC, 17 with paraneoplastic disorders as well as 121 controls with other neurological disorders) was performed and showed all 5 of the patients with SSN and SCLC to be positive for the anti-Hu antibody, whereas only 11 of the 122 SCLC patients and none of the controls were positive, thereby suggesting that this test has a very high degree of sensitivity.     

Acute motor and sensory neuronopathy associated with small‐cell lung cancer: A clinicopathological study

A 48‐year‐old Chinese woman developed ascending motor paralysis while visiting Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient’s course was complicated by anoxic encephalopathy. Nerve conduction studies revealed a severely decreased amplitude of compound muscle action potentials and a sural nerve biopsy specimen showed findings consistent with axonal‐form Guillain–Barré syndrome. An autopsy, excluding the brain, demonstrated small‐cell lung cancer that was not detected clinically, axonal‐dominant degeneration in the nerve roots and distal peripheral nerves, and the loss of both myelin and axons in the dorsal spinal column. The spinal anterior horn cells were severely decreased and were accompanied by astrocytic reaction in all spinal segments with lymphocytic infiltration. A limited examination of the dorsal root ganglia did not show Nageotte nodules, but the infiltration of T cells was observed. Although the clinical course mimicked axonal‐form Guillain–Barré syndrome, the autopsy demonstrated both sensory and motor neuronal involvement, as well as small‐cell lung cancer. Although anti‐Hu and antiganglioside antibodies were negative in the patient’s serum, the paraneoplastic mechanism might have damaged the anterior horn and dorsal root ganglia cells, which subsequently led to secondary axonal degeneration. There has been a report on a case of paraneoplastic subacute motor neuronopathy, but the acute course described here has not been reported before.     

Paraneoplastic pandysautonomia as a manifestation of non-small cell lung cancer

Pandysautonomia is a severe and rare clinical condition characterized by widespread sympathetic and parasympathetic dysfunction. Consideration of whether symptoms and presentation are acute, subacute, or chronic is often helpful in establishing a differential diagnosis. The underlying mechanisms leading to pure pandysautonomia are unclear; however, there is some evidence suggestive of an immune-mediated pathogenesis. Herein, we report a case with pandysautonomia as a paraneoplastic manifestation of non-small cell lung cancer that had an excellent response to symptomatic and supportive treatments, as well as IVIG therapy.     

Subacute sensory neuronopathy with signs of involvement of anterior horn cells in a patient with small cell lung carcinoma (case report)]

A 55 years old woman with small-cell lung carcinoma is described. Ten months after the diagnosis was established, subacute sensory neuronopathy with the signs of involvement of anterior horn cells (confirmed by EMG exam) occurred. Since neurological symptoms appeared at the time when anti-cancer treatment was ceased, the diagnosis of paraneoplastic lesion peripheral nervous system was established. Biopsy of sural nerve obtained 3 months after the onset of neurological signs showed nearly complete loss of normal looking myelinated fibers due to the process of axonal degeneration with relatively better preserved unmyelinated fibers. The patient died after 1 year and 2 months from the beginning of the disease because of metastatic tumours in the brain.     

Chorea,transverse myelitis,neuropathy and a distinctive MRI: Paraneoplastic manifestations of probable small cell lung cancer

Paraneoplastic chorea occurs most commonly in association with small cell lung cancer, often in combination with other paraneoplastic phenomena and sometimes with distinctive basal ganglia T2-weighted MRI hyperintensities. A case of acute-onset chorea is presented in which this phenomenon, combined with transverse myelitis, neuropathy and the described characteristic MRI changes prompted positron emission tomography scanning, in which evidence of probable small cell cancer was uncovered.     

Paraneoplastic optic neuropathy and cerebellar ataxia with small cell carcinoma of the lung.

Bilateral optic neuropathy and subacute cerebellar ataxia were manifestations of a paraneoplastic neurologic disorder in a woman found to have small cell carcinoma of the lung. Serologic tests revealed a neuronal autoantibody specific for CRMP-5, a 62-kd member of the collapsin response-mediating protein family. Unexplained optic neuropathy in the setting of subacute cerebellar ataxia should cause suspicion of a paraneoplastic disorder and prompt testing for this autoantibody, especially in patients at risk for lung carcinoma.     

Facial onset sensory and motor neuronopathy

Facial onset sensory and motor neuronopathy (FOSMN) is a recently defined slowly progressive motor neuron disorder. It is characterized by facial onset sensory abnormalities which may spread to the scalp, neck, upper trunk and extremities, followed by lower motor neuron deficits. Bulbar symptoms, such as dysarthria and dysphagia, muscle weakness, cramps and fasciculations, can present later in the course of the disease. We search the PubMed database for articles published in English from 2006 to 2016 using the term of “Facial onset sensory and motor neuronopathy”. Reference lists of the identified articles were selected and reviewed. Only 38 cases of FOSMN have been reported in the Pubmed database since it was first reported in 2006. Typically, FOSMN present with slowly evolving numbness of the face followed by neck and arm weakness. Reduced or absent of corneal reflexes and blink reflex is the main pathognomonic features of FOSMN. In this review, we summarize the epidemiology, clinical presentation, auxiliary examination, and treatment of all the reported cases of FOSMN. Moreover, we discuss the pathogenesis of this rare disorder. In addition, we propose diagnostic criteria for FOSMN.     

Electrodiagnostic evolution of carcinomatous sensory neuronopathy

Sensory neuronopathy is a well-recognized remote effect of carcinoma. We report the clinical and electrodiagnostic evolution of a sensory neuronopathy in a patient with carcinoma of the lung. Serial electrophysiologic studies suggest transformation from normal peripheral nerve function through early posterior root involvement to absent sensory nerve function. Diffuse motor conduction abnormalities occurred late in the disease, perhaps reflecting motor axon changes associated with disuse.     

感觉性神经元神经病的实验病理研究

目的:建立一成功率高,感觉症状确实的感觉性神经元神经病的动物模型。并同时观察不同剂量维生素 B6对于大鼠感觉性神经系统的作用。方法:50只雌性Wistar大鼠分别给予600mg／kg(1周或2周),400mg／kg(4周), 200mg／kg(4周或8周)与100mg／kg(4周或8周)维生素B6,腹腔注射,每天一次。取其后根神经节(DRG),周围神经及脊髓作光镜与电镜分析。染色方法有HE,Luxol Fast Blue,Masson三色与银浸染色。半薄切片用甲苯胺兰染色,超薄切片用醋酸双氧铀与枸橼酸铅染色。结果:腰段DRG受累最重,其次为颈段、胸段。大剂量组导致感觉性神经元神经病,动物步态不稳,甚至瘫痪。DRG细胞体体积减少或坏死,伴以轴突萎缩与崩解,并可见吞噬细胞吞噬现象。小剂量组动物无异常临床表现,DRG神经元病变轻微,但存在轴突萎缩与变性。电镜下发现近端突与胞体均有细胞骨架异常。脊髓后束中薄束比楔束病变重。结论:多种因素包括用药时间、用药剂量及不同亚群神经元的药物敏感性不同,均可影响维生素B6神经毒性的最终表现。     

Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited

High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3–8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3–10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable. Blood levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory polyneuropathy in two patients. Two years after vitamin discontinuation, all patients showed no significant improvement in the neuropathy and gait. In conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not be reversible.     

Cytotoxic T lymphocyte-mediated cell death in paraneoplastic sensory neuronopathy with anti-Hu antibody.

Paraneoplastic sensory neuronopathy (PSN) has been shown to harbor characteristic anti-neuronal autoantibody 'anti-Hu' in their sera and cerebrospinal fluid. Creation of animal models exhibiting clinical or pathological features seen in PSN by means of passive transfer of anti-Hu positive IgG has not been achieved. Although, anti-Hu antibody was shown to induce neuronal cell lysis in vitro, this result has not been reproduced so far. Since prominent T cell infiltration are seen in the central nervous system and posterior spinal ganglion of the patients with anti-Hu syndrome, we studied cytotoxic T cell (CTL) activity in peripheral mononuclear cells from a patient with PSN harboring anti-Hu antibody. The activated CD8+ T cells from the patient's venous blood were shown to lyse her own fibroblasts which were incubated with interferon-gamma to induce HLA class I molecules on their surface and the recombinant HuD protein was injected into the cells by microinjector. This is the first report showing the existence of CTL in a patient with PSN.