Lung Cancer and Paraneoplastic Neurologic Syndromes. Case Report and Review of the Literature (original) (raw)
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BMJ Case Reports, 2020
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 biopsie...
Paraneoplastic neurologic disorders in small cell lung carcinoma
Neurology, 2015
Objective: To determine the frequency and range of paraneoplastic neurologic disorders (PNDs) and neuronal antibodies in small cell lung carcinoma (SCLC). Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies. Thirty-eight healthy controls were analyzed in parallel. Results: PNDs were quite prevalent (n 5 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all ,5%]). Conclusions: The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC. Neurology ® 2015;85:235-239 GLOSSARY HC 5 healthy control; LE 5 limbic encephalitis; LEMS 5 Lambert-Eaton myasthenic syndrome; PCD 5 paraneoplastic cerebellar degeneration; PEM 5 paraneoplastic encephalomyelitis; PND 5 paraneoplastic neurologic disorder; SCLC 5 small cell lung carcinoma; SN 5 sensory neuronopathy.
Paraneoplastic neurologic syndrome: A practical approach
Annals of Indian Academy of Neurology, 2012
The first description of PNS was in the 19 th century by a French physician M Auche` who described the peripheral nervous system involvement in cancer patients in 1890. [3] The first antibody described was PCA-1 (Purkinje Cell Antibody 1), by Greenlee and Brashear in 1983, in two patients with ovarian carcinoma and paraneoplastic cerebellar degeneration. [4] More syndromes and antibodies have been subsequently described and the list of the syndromes and antibodies continue to increase day by day. Pathophysiology PNS are mainly autoimmune. [1] When the body tries to eliminate tumor cells, it launches an immune response, and this response can target normal neural tissues. [5] This could be mediated by antibodies or by T-cells. Thus, most of the PNS reflect a nervous system-specific autoimmune attack initiated by onconeural antigens released to the peripheral lymphoid tissue from an unsuspected primary or recurrent neoplasm. [2] Frequently, a cerebrospinal fluid (CSF) study in these patients reveals lymphocytic pleocytosis, elevated protein, increased IgG synthesis and oligoclonal bands, supporting the immunological pathology. In a recent European study, abnormal CSF was
What a Clinician Must Know Regarding Diagnosis of Paraneoplastic Neurological Syndromes
2012
About 3–5 % of patients with small-cell lung cancer and 15– 20 % of patients with thymoma develop paraneoplastic neurological syndromes (PNS). Less than 1 % of patients with other types of tumours develop paraneoplastic neurological symptoms [1]. As PNS are also associated with some benign tumours, eg, teratoma and thymoma, malignant properties are not a necessary component of the tumour, but expression of a relevant protein is necessary for the development of a PNS. Tumours in patients with PNS express proteins that are normally only expressed in the nervous system. The tumour protein is identical to the neuronal protein, but is identified as foreign or non-self by the immune system when expressed by the tumour cell. The body produces antibodies and activates T-cells to these proteins as part of the anti-tumour immune response. The antibodies and T-cells cross the blood-brain or blood-nerve barriers and cross-react with proteins in the nervous system. This cross-reaction leads to l...
Paraneoplastic Neurologic Syndromes - An Update on Current Understanding and Future Perspectives
European Neurological Review, 2010
Paraneoplastic neurological syndromes (PNS) are remote effects of tumours on the nervous system. They can strike at single or at multiple sites of the central nervous system (CNS) and the peripheral nervous system, and often appear before the detection of cancer. PNS can be disabling and debilitating and may be either an additional burden to cancer or the cause of death. The PNS Euronetwork group has collected a series of approximately 1,000 patients in several European centres. This study is the largest systematic series of patients with PNS and, for the first time, can answer questions about the most frequent PNS, their detailed symptoms, associated antibodies and the types of underlying tumours. The clinical course and laboratory findings for many PNS suggest an autoimmune pathogenesis; however research into this heterogeneous immunological relationship has been evolving over recent decades. The classical syndromes are antigen-target-oriented syndromes such as myasthenia gravis (...
Paraneoplastic neurological syndromes
Orphanet Journal of Rare Diseases, 2007
Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small cell lung cancer. PNS can affect any part of the central and peripheral nervous system, the neuromuscular junction, and muscle. They can be isolated or occur in association. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. PNS are usually severely disabling. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancerassociated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis. PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized antionconeural protein antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible. Unfortunately, about one-third of patients do not have detectable antibodies and 5% to 10% have an atypical antibody that is not well-characterized. As PNS are believed to be immune-mediated, suppression of the immune response represents another treatment approach.
Immunological Features of Paraneoplastic Neurological Syndromes
International Journal of Immunopathology and Pharmacology, 2004
Paraneoplastic neurological syndromes are a rare group of disorders that occur in 1 – 2 % of people with malignancy. They are usually caused by an immune response, triggered by and directed against a tumour, that cross-reacts with protein expressed by the peripheral or central nervous system. Any part of the nervous system can be affected and patients often develop severe and permanent disability. Diagnosis can be difficult as in two-thirds of patients the neurological problems appear up to 5 years before the tumour manifests. However, certain of these syndromes are often associated with specific serum autoantibodies that can be useful both in diagnosis of the neurological syndrome and in focusing the search for a particular tumour. Thus, these antibodies can allow earlier identification and treatment of cancer and, potentially, a reduction in morbidity and mortality. It was only in the 1980s that the first onconeural autoantibodies were characterized and their associations with cli...
Paraneoplastic Syndromes Affecting the Nervous System
Seminars in Oncology, 2006
Paraneoplastic syndromes can affect virtually any portion of the nervous system. Most paraneoplastic syndromes are believed to be caused by an autoimmune reaction to an "onconeural" antigen shared by the cancer and the nervous system. The immune reaction may retard growth of the cancer, but it also damages the nervous system. Specific autoantibodies found in some individual paraneoplastic syndromes are usually associated with specific tumors. Neurological disorders, clinically and pathologically identical to paraneoplastic syndromes, may occur in some patients without cancer, but paraneoplastic antibodies are not found in these patients. The diagnosis of a paraneoplastic syndrome is based on its increased incidence in patients with cancer, the occasional response of the neurological syndrome to treatment of the underlying cancer, or the presence of specific autoantibodies. Some paraneoplastic syndromes respond to treatment of the underlying cancer or to immunosuppression but, for most syndromes, no effective treatment exists.
Paraneoplastic neurological syndromes: a practical approach to diagnosis and management
Practical Neurology, 2021
Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised ‘onconeuronal’ antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient help to determine the clinical relevance of the syndrome and hence gu...