Materiały źródłowe

• #1 Overview of paraneoplastic syndromes of the nervous system – UpToDate

  https://www.uptodate.com/contents/5188/print

  Paraneoplastic neurologic syndromes are a heterogeneous group of neurologic disorders caused by mechanisms other than metastases, metabolic and nutritional deficits, infections, coagulopathy, or side effects of cancer treatment. […] This topic provides an overview of the pathogenesis, diagnosis, and treatment of paraneoplastic neurologic disorders.

• #2 Paraneoplastic neurological syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-22

  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 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. […] PNS pathogenesis is currently related to an aberrant expression in the tumor of an antigen that is normally expressed only in the nervous system. […] Even if the antigens in the tumor are identical in structure to the neural antigens, they could be recognized as foreign, leading to an immune attack directed against both the tumor and the nervous system. […] However, only few onconeural antibodies have been shown to play a direct role in the pathogenesis of the neurological symptoms. […] Recently, it has been suggested that cellular immune mechanisms play a critical role in the pathogenesis of PNS.

• #3 Paraneoplastic Syndromes – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507890/

  Paraneoplastic syndromes are rare disorders with complex systemic clinical manifestations due to underlying malignancy. […] In paraneoplastic syndromes, the malignant cells do not directly cause symptoms related to metastasis; rather, they generate autoantibodies, cytokines, hormones, or peptides that affect multiple organ systems. […] Paraneoplastic syndromes are secondary to an occult malignancy, but the exact mechanism remains unclear. […] Tumor cells are immunogenic and lead to the activation of both cell-mediated and humoral immune systems. […] Most cases exhibit paraneoplastic syndrome with immunologic mechanisms; however, there are non-immunologic mechanisms of paraneoplastic syndrome. […] Paraneoplastic syndromes may evolve from immunologic or non-immunologic mechanisms.

• #4

  https://journals.lww.com/co-oncology/abstract/1996/05000/paraneoplastic_nervous_system_syndromes.6.aspx

  Recent progress in the understanding of the paraneoplastic neurologic syndromes has included further deliniation of the clinical syndromes and their treatment, attempts at standardization of the diagnostic nomenclature, investigations of pathogenetic mechanisms, and molecular characterization of the paraneoplastic antigens with implications as to their biologic relevance. […] Despite more than 30 years of investigation, the pathogenesis of these presumably autoimmune conditions remains unclear. […] Future investigations must focus on the disrupted genetic regulatory events involved in generation and propagation of the autoimmune response, antigen presentation and processing; target cell destruction, and consideration of alternative pathologic causes. […] Effective management strategies are most likely to develop from a better understanding of the disease pathogenesis, the development of animal model systems, and a creative look beyond the usual therapies employed in autoimmune conditions.

• #5 Synapse – Paraneoplastic syndromes

  https://synapse.mskcc.org/synapse/works/67843

  Paraneoplastic syndromes affecting the nervous system are rare but devastating complications of systemic cancer. The pathogenesis of paraneoplastic syndromes involving the nervous system is believed to be immune-mediated: the current hypothesis is that antigens usually expressed only in neurons are expressed in a cancer; the immune system recognizes the antigen in the cancer as foreign and mounts an immune response that slows the growth of the tumor but damages the nervous system. The diagnosis of a paraneoplastic syndrome is made either by identifying a small cancer in a patient with a neurologic disorder of unknown etiology or by identifying paraneoplastic autoantibodies in the serum of patients. The treatment involves identification and treatment of the causal cancer and immunosuppression to suppress both the humoral and cellular immune response.

• #6 Paraneoplastic Syndromes of the Nervous System

  https://www.degruyter.com/document/doi/10.1515/CCLM.2000.018/html?lang=en

  Paraneoplastic syndromes affecting the nervous system are unique among immune-mediated disorders in that the trigger of the immune response is known: tumor expression of proteins normally restricted to neurons (or other immunoprivileged sites, such as testis) but ectopically expressed in some cancers results in an immunological response characterized by high titers of antibodies targeting the onconeuronal antigen. […] A T-cell response is also elicited in some paraneoplastic syndromes and may be the cause of neuronal destruction. […] In some instances genes that code for the antigens recognized by the autoantibodies have been identified, cloned and sequenced. […] Some of the proteins so identified are RNA binding proteins but their specific function has not been identified. […] In some individuals with cancer but no paraneoplastic syndrome, low titers of antibody can be identified in the serum. […] Low titers of antibody are associated with a better prognosis of the cancer. […] Experimental animals immunized against a paraneoplastic antigen are partially protected against tumors that express that antigen.

• #7 Paraneoplastic Neurological Syndromes of the Central Nervous System: Pathophysiology, Diagnosis, and Treatment

  https://www.mdpi.com/2227-9059/11/5/1406

  Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. […] PNS are thought to arise from an immune response directed against common antigens/epitopes shared by tumor cells and normal healthy cells within the CNS. […] At the cellular level, PNS-associated cancers may harbor gene variants coding for onconeural proteins, particularly highly immunogenic antigens that are also expressed by CNS cells and which activate the immune system. […] The distinction between onconeural and NSA-Abs has therapeutic implications: immune treatments can be highly effective for PNS associated with NSA-Abs, while they are less effective in PNS associated with onconeural antibodies. […] The neural substrates of the pathophysiology of these disorders are still largely unclear.

• #8 Paraneoplastic Neurological Syndromes | SpringerLink

  https://link.springer.com/10.1007/978-3-031-24297-7_14-1

  Paraneoplastic neurological syndromes (PNS) are immune-mediated disorders triggered by cancer that may affect any level of the nervous system and often associated with autoantibodies targeting either intracellular or extracellular neural antigens. […] PNS physiopathology is so far poorly understood, but novel findings in certain types of PNS support that genetic alterations in the tumors may play an important role, leading to an abnormal expression of neural antigens followed by a crossed immune reaction between the nervous system and cancer. […] This hypothesis is further suggested by the development of PNS-like complications after the use of immune-checkpoint inhibitors as enhancers of the anti-tumor immune response during cancer treatment.

• #9 PARANEOPLASTIC DISORDERS OF THE NERVOUS SYSTEM | Neupsy Key

  https://neupsykey.com/paraneoplastic-disorders-of-the-nervous-system/

  Paraneoplastic neurological disorders (PNDs) are an extensive group of syndromes that can affect any part of the nervous system by mechanisms that are mostly immune mediated. […] In 60% of patients with PND, symptoms develop before the presence of a tumor is known; the majority of these patients are seen by neurologists, who should be aware that prompt diagnosis and treatment of the tumor along with immunotherapy may stabilize or improve the PND. […] Many of these disorders occur in association with immune responses against intraneuronal antigens expressed by the underlying cancer (paraneoplastic or onconeuronal antigens). These immune responses are characterized by the presence of antibodies and cytotoxic T cell responses against the onconeuronal antigens. […] Overall, these studies suggest that both antibody and cytotoxic T cell responses are probably necessary to cause neuronal injury. This concept is important not only for modeling the disease but also for the development of treatment strategies for PNDs of the central nervous system (CNS).

• #10 Paraneoplastic syndromes of the nervous system – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/paraneoplastic-syndromes/symptoms-causes/syc-20355687

  Paraneoplastic syndromes of the nervous system are a group of rare conditions that develop in some people who have cancer. […] Paraneoplastic syndromes of the nervous system occur when cancer-fighting agents of the immune system also attack parts of the brain, spinal cord, peripheral nerves or muscle. […] Researchers believe that paraneoplastic syndromes of the nervous system are caused by cancer-fighting abilities of the immune system. In particular, antibodies and certain white blood cells, known as T cells, are thought to be involved. Instead of attacking only the cancer cells, these immune system agents also attack the healthy cells of the nervous system. […] Paraneoplastic syndromes of the nervous system are not caused by cancer cells directly or by the cancer spreading, known as metastasis. They’re also not caused by other complications, such as infections or treatment side effects. Instead, the syndromes occur alongside the cancer as a result of the activation of your immune system.

• #11 Paraneoplastic Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/280744-overview

  Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. […] The pathophysiology of paraneoplastic syndromes is complex and intriguing. When a tumor arises, the body may produce antibodies to fight it by binding to and destroying tumor cells. Unfortunately, in some cases these antibodies cross-react with normal tissues and destroy them, which may result in a paraneoplastic disorder. […] In other cases, paraneoplastic syndromes result from the production and release of physiologically active substances by the tumor. Tumors may produce hormones, hormone precursors, a variety of enzymes, or cytokines. […] The pathogenesis of neuromuscular paraneoplastic disorders is unknown, but they probably are multifactorial, correlated with a virus becoming virulent, autoantibody formation, or production of substances that alter nervous functions.

• #12 Paraneoplastic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Paraneoplastic_syndrome

  The mechanism for a paraneoplastic syndrome varies from case to case. However, pathophysiological outcomes usually arise when a tumor does. Paraneoplastic syndrome often occurs alongside associated cancers as a result of an activated immune system. In this scenario, the body may produce antibodies to fight off the tumor by directly binding and destroying the tumor cell. Paraneoplastic disorders may arise in that antibodies would cross-react with normal tissues and destroy them. […] A specifically devastating form of (neurological) paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders (PNDs). These PNDs affect the central or peripheral nervous system; some are degenerative, though others (such as LEMS) may improve with treatment of the condition or the tumor. Symptoms of PNDs may include difficulty with walking and balance, dizziness, rapid uncontrolled eye movements, difficulty swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, and sensory loss in the limbs.

• #13 Paraneoplastic Neurological Disorders | PM&R KnowledgeNow

  https://now.aapmr.org/neuromuscular-manifestations-of-neoplasms-and-paraneoplastic-syndromes/

  Paraneoplastic neurological syndromes (PNS) are a group of neurological disorders resulting from an immune response triggered by an underlying tumor that affects the central and/or peripheral nervous systems, directed originally against the tumor itself. […] Although the pathogenesis of paraneoplastic neurologic syndromes is not fully understood, many of the syndromes are thought to be immune mediated. The mechanism entails ectopic expression by a tumor of an antigen that normally is expressed exclusively in the nervous system. […] Numerous antibodies have been identified in association with specific PNS. Antibodies targeting intracellular neuronal antigens (released after tumor-cell death) as in Classic PNS have been shown to display a cytotoxic T-lymphocyte-mediated pathogenesis. Conversely, antibodies associated with cell surfaces and synaptic proteins (Encephalitis types) display an antibody-mediated pathogenesis. […] The different subtypes of PNS are defined by the presence or the absence of paraneoplastic antibodies and the type of antibodies. Management and treatment should be tailored to each subtype. […] The hypothesis that PNS are immune mediated remains to be proven.

• #14 Paraneoplastic syndromes of the nervous system | PPT

  https://www.slideshare.net/slideshow/paraneoplastic-syndromes-of-the-nervous-system/235904940

  Antibodies that occur in paraneoplastic disorders have been divided into two categories depending on the location of the antigen. […] Antibodies directed against intracellular neuronal proteins (called classical paraneoplastic or well-characterized antibodies) and antibodies directed against neuronal cell surface or synaptic proteins. […] The identification of these antibodies in a patient with cerebellar dysfunction indicates paraneoplasia, almost always associated with an SCLC. […] Testing for paraneoplastic antibodies can facilitate recognition of simultaneous occurrence of 2 or more or even 3 paraneoplastic syndromes in 1 patient.

• #15 Paraneoplastic syndromes | MedLink Neurology

  https://www.medlink.com/articles/paraneoplastic-syndromes

  The neuronal molecular targets of most autoantibodies have been characterized. […] Many of the initially discovered onconeural antibodies (eg, anti-Hu and anti-Yo) react with intracellular neuronal protein antigens. […] Many of the protein antigens reacting with antineuronal antibodies are known to be expressed by the tumors from affected patients, providing circumstantial evidence supporting the general theory of an autoimmune response arising against shared „onconeural” antigens. […] The proven or postulated immunopathogenic mechanisms for neurologic paraneoplastic disorders fall into four main categories: (1) Autoantibodies against shared onconeural antigens directly cause neurologic disease. […] (2) A cellular immune reaction against onconeural antigens is the main cause of neuronal injury. […] (3) Neoplastic plasma cells produce monoclonal paraproteins (immunoglobulins), which react with peripheral nerve antigens and cause neuropathy. […] (4) Disorders that arise from other or poorly understood immune mechanisms.

• #16 (PDF) Paraneoplastic Syndromes Affecting the Nervous System

  https://www.academia.edu/16888074/Paraneoplastic_Syndromes_Affecting_the_Nervous_System

  Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death.

• #17 Paraneoplastic Neurologic Syndromes . | Oncohema Key

  https://oncohemakey.com/paraneoplastic-neurologic-syndromes-3/

  Paraneoplastic neurologic syndromes are heterogenous disorders that can occur in the setting of various types of cancer. Paraneoplastic neurologic disorders are commonly caused by immune-mediated mechanisms triggered by an underlying tumor and have to be distinguished from neurological symptoms related to direct tumor invasion, infection, vasculopathy, ischemia, metabolic disturbances, or treatment-related toxicities. […] While the detailed pathomechanism of most paraneoplastic syndromes remains elusive, production of antibodies directed against antigens expressed by both tumors and nervous system tissues have been described as a key mechanism in some distinct types of paraneoplastic syndromes. Antibodies can be directed against cytoplasmic antigens (e.g., Purkinje cells and anterior horn cells) or cell surface proteins (e.g., voltage gated potassium and calcium channels). Immune mechanisms may involve both humoral and T-cell-mediated responses, although the exact contribution of cellular and antibody-mediated mechanisms to the disease manifestation remains controversial.

• #18 Paraneoplastic syndromes in small cell lung cancer – Soomro – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/38423/html

  The mechanisms for the development of these paraneoplastic syndromes are not well understood, but they are known to be caused by an autoimmune-mediated disease process. […] These antibodies, often known as onconeural antibodies are frequently detected in the serum and cerebrospinal fluid and are characteristic of PNS. […] The formation of antibodies specific to intracellular neuronal antigens is thought to involve cell-mediated immune mechanisms. […] Onconeural antibodies bind to antigens on normal host neuronal tissues that share epitopes with the tumor antigens. […] The specific constellation of each PNS depends on the site, extent, and duration of disease involvement. […] The most common PNS found in patients with SCLC is LEMS. […] The pathophysiology of LEMS involves the binding of these antibodies to (P/Q) type voltage-gated calcium channels.

• #19 Paraneoplastic syndromes CNS manifestations | PPT

  https://www.slideshare.net/slideshow/paraneoplastic-syndromes-cns-manifestations-232575140/232575140

  Paraneoplastic syndrome (PNS) is the term used to refer to the disorders that accompany the benign or the malignant tumors and are not caused by mass effect or invasion / metastasis. These disorders are triggered by an immune system response to neuronal proteins expressed by the tumor(onconeural proteins). These PNS also occur due to substances secreted by the neoplasm itself. […] Most PNS are mediated by immune responses triggered by neuronal proteins (onconeural antigens) expressed by tumors. Both humoral (antibodies) and cell mediated immunity (CD4 CD8) are activated. Subsequently microglial activation leads to gliosis and neuronal loss. These Immune responses have complex mechanism hence these PNS are resistant to therapy. […] Cell mediated immunity acts against intracellular antigens and is less responsive to therapy than antibody mediated. Antibody mediated acts primarily at the neuronal surface antigens and neuromuscular junctions. Classic PNS occur with cancer association. Non classical PNS may or may not occur with cancer association and they are commonly seen in children.

• #20

  https://link.springer.com/article/10.1007/s11940-996-0005-y

  Several neurologic paraneoplastic disorders are believed to be caused by an autoimmune reaction against an antigen or antigens coexpressed by tumor cells and neurons. Of the paraneoplastic syndromes, the Lambert-Eaton myasthenic syndrome (LEMS) in which autoantibodies downregulate voltage-gated calcium channels at the presynaptic nerve terminal is associated with the strongest evidence of an autoimmune cause. […] For the other syndromes, including cerebellar degeneration, multifocal encephalomyelitis, sensory neuronopathy, limbic encephalitis, opsoclonus-myoclonus, and retinal degeneration, an autoimmune cause is indicated by the presence of specific antineuronal antibodies. […] These antibodies serve as a useful diagnostic tool, but their actual role in causing neuronal injury and clinical disease remains unclear.

• #21 Paraneoplastic Autonomic Neuropathy: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1156808-overview

  In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against P/Q type voltage-gated calcium channels (VGCC) are present. These antibodies lead to impaired presynaptic calcium release at the neuromuscular junction, resulting in predominantly proximal muscle weakness. […] The autoimmunity in paraneoplastic neurological syndromes does appear to confer some degree of antitumor effect. Inflammation similar to what is seen in the nervous system also affects the tumor.

• #22 Paraneoplastic syndromes in small cell lung cancer – Soomro – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/38423/html

  The motor weakness of LEMS can be improved with 3,4-diaminopyridine, cholinesterase inhibitors, and immunosuppressive therapy including glucocorticoids, intravenous immunoglobulin (IVIG), and plasma exchange. […] Myasthenia gravis is a PNS that is found in association with SCLC and thymoma in approximately 15% of patients. […] The disease process is characterized and caused by the presence of the onconeural antibodies, anti-acetylcholine antibodies (anti-Ach) that act at the level of the neuromuscular junction. […] The presence of anti-Hu antibodies is a very strong indication of the presence of an SSN. […] Cerebellar degeneration associated with neoplasia, referred to as paraneoplastic cerebellar degeneration, was first described in the literature in 1965 and is characterized by the subacute onset of cerebellar dysfunction. […] The use of steroids, intravenous immunoglobulin, and plasma exchange as treatments have rarely been successful at improving the neurological outcome. […] Despite this, the earliest possible removal and treatment of the cancer remains the mainstay of management in these cases.

• #23 Paraneoplastic cerebellar degeneration (PCD) – Autoimmune Association

  https://autoimmune.org/disease-information/paraneoplastic-cerebellar-degeneration-pcd/

  Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. Paraneoplastic syndromes are a group of rare disorders that are triggered by an abnormal immune system response to an underlying (usually undetected) malignant tumor. […] Paraneoplastic syndromes are thought to result from an abnormal immune response to an underlying (and often undetected) malignant tumor. PCD is typically thought to be caused by antibodies generated against tumor cells. Instead of just attacking the cancer cells, the cancer-fighting antibodies also attack normal cells in the cerebellum. […] PCD occurs most often in individuals with the following cancers: ovarian cancer, cancer of the uterus, breast cancer, small-cell lung cancer, and Hodgkin lymphoma.

• #24 Paraneoplastic Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/280744-overview

  The muscular system is involved in myasthenic phenomena (on a toxic and metabolic basis) that can be either simple (affecting the pelvic girdle) or part of Eaton-Lambert myasthenic syndrome (ELMS). […] Autoantibodies directed against the central neurons and brain often are present in the serum and cerebrospinal fluid (CSF) of patients with sensory and mixed neuropathies. […] Patients with cerebellar paraneoplastic disorders usually have degenerative loss of the molecular, granular, and Purkinje layers of the cerebellar cortex. […] Individuals with paraneoplastic encephalitis commonly have lymphocytic infiltration of the medial sections of the temporal lobes, with a loss of neurons.

• #25

  https://journals.lww.com/annalsofian/fulltext/2021/24010/editorial_commentary__paraneoplastic_syndromes.3.aspx

  The CSF in PNS of the central nervous system suggests an inflammatory process increased protein concentration with pleocytosis. Importantly the glucose content is normal. […] The diagnosis of PNS is classified as definite or possible based on the syndrome (classical or non-classical), Anti-bodies (present/absent, well/partially characterized) and tumor (present/absent). […] Although any tumour can produce a PNS, the most common tumors are small-cell lung cancer (SCLC), cancers of the breast and ovaries, thymomas, neuroblastomas, and plasma-cell tumors.

• #25

  https://journals.lww.com/annalsofian/fulltext/2021/24010/editorial_commentary__paraneoplastic_syndromes.3.aspx

  Paraneoplastic syndromes (PNS) are a group of clinically heterogenous neurological syndromes which share a common pathogenesis of immune-mediated neuronal degeneration triggered by distal neoplasm. […] In the majority of cases, antibodies (Ab) against intracellular antigen (Ag) are expressed by the tumour and central nervous system (CNS) onco-neural Ab and are detected in the serum and cerebrospinal fluid (CSF). […] As mentioned earlier, the classical syndromes have a high likelihood of paraneoplastic etiology with an underlying cancer, whereas non-classical syndromes are rarely associated with cancer. […] Hence, quoting Rosenfeld and Dalmau, in the right clinical context, the detection of paraneoplastic Abs in the serum and CSF helps to diagnose the PNS and focuses the search for the neoplasm.

• #26 Paraneoplastic syndromes CNS manifestations | PPT

  https://www.slideshare.net/slideshow/paraneoplastic-syndromes-cns-manifestations-232575140/232575140

  Paraneoplastic cerebellar degeneration (PCD) is characterized by symptoms such as dizziness, oscillopsia, blurry or double vision, nausea, and vomiting. Most commonly develops in women. […] Paraneoplastic encephalomyelitis / sensory neuronopathy (PEM/PSN) is most commonly associated with lung cancer. Onset of symptoms precedes diagnosis of cancer. […] Opsoclonus is a disorder of eye movement characterized by involuntary, chaotic saccades that occur in all directions of gaze; it is frequently associated with myoclonus and ataxia. Rarely they present with laryngeal spasms and autonomic dysfunctions. In adults, most commonly associated with Small cell lung cancer and Breast cancer. […] Lambert-Eaton myasthenic syndrome (LEMS) occurs much less frequently than myasthenia gravis. 50% of LEMS associated with a malignancy (small cell lung cancer (SCLC)). Antibodies directed against the voltage-gated calcium channel (VGCC) interfere with the normal pre-synaptic calcium influx required for Ach release.

• #27 PARANEOPLASTIC DISORDERS OF THE NERVOUS SYSTEM | Neupsy Key

  https://neupsykey.com/paraneoplastic-disorders-of-the-nervous-system/

  For many PNDs of the peripheral nerve and muscle, the evidence of immune-mediated mechanisms is also abundant, but the target antigens are less well defined than in PNDs of the CNS. […] It has been suggested that paraneoplastic immunity is clinically effective in controlling tumor growth, accounting for the small size and limited metastatic burden of tumors associated with PNDs. However, despite the demonstration that some patients with PNDs develop cytotoxic T cell responses to tumor antigens, the oncological outcomes in studies of hundreds of patients with antibody-associated PND do not significantly differ from those of patients without PNDs. […] The diagnosis of PNDs is usually based on (1) the recognition of the neurological syndrome, (2) the demonstration of the associated cancer, and (3) the detection of serum and CSF paraneoplastic antibodies.

• #28

  https://link.springer.com/article/10.1007/s11940-996-0005-y

  A small percentage of patients with paraneoplastic disorders shows major neurologic improvement after successful treatment of the associated tumor. […] The response to immunosuppression among patients with paraneoplastic central nervous system (CNS) dysfunction is much less favorable. […] Although exceptions clearly exist, most patients with CNS paraneoplastic disorders do not improve despite tumor treatment and immunosuppressive therapy. […] It is likely that many patients already have irreversible neuronal injury at the time of diagnosis. […] The decision to attempt immunosuppressive treatment must be made on an individual basis.

• #29 Paraneoplastic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Paraneoplastic_syndrome

  A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one). It is specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells. […] Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (e.g., neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective in suppressing tumor growth and symptoms. Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that (e.g., neuronal) protein.

• #30 Triggering factors and immunopathogenesis of paraneoplastic neurological syndromes – TEL – Thèses en ligne

  https://theses.hal.science/tel-03917161v1

  It has been recently demonstrated in both experimental and clinical settings that cancer immunotherapy using immune checkpoint inhibitors (ICI) can trigger neurological disorders similar to PNS. […] The present PhD project supports the view that the association between cancer and PNS is causal, and not merely temporal, as highlighted in the updated diagnostic criteria. Specific genetic signatures of cancer are likely responsible for triggering the immune response, which can in turn results in an efficient immune attack against the tumour.

• #30 Triggering factors and immunopathogenesis of paraneoplastic neurological syndromes – TEL – Thèses en ligne

  https://theses.hal.science/tel-03917161v1

  Paraneoplastic neurological syndromes (PNS) are rare immune-mediated conditions triggered by the presence of cancer and associated with specific neuronal antibodies. PNS occur at the intersection between immune system, tumor, and nervous system, where a combination of host characteristics, cancer-related specificities, and environmental factors may play a role. […] Despite many recent advances in the clinical and antibody characterization, the pathogenesis of PNS still remains largely obscure. The main hypothesis is that an aberrant immune response is directed towards neuronal antigens that are physiologically expressed by the nervous system and ectopically by cancer cells, however the exact mechanisms of this cross-immune reaction are totally unknown. […] In this regard, the analysis of triggering and predisposing factors of PNS can provide important clues into the immunopathogenesis of these neurological conditions.

• #31 Paraneoplastic Neurologic Syndromes

  https://www.jstage.jst.go.jp/article/internalmedicine1992/35/12/35_12_925/_article/-char/en

  Paraneoplastic neurologic syndromes are degenerative diseases of the central or peripheral nervous system that develop in association with a systemic neoplasm without a direct invasion by tumor. […] The pathogenesis of this disorder has been hypothesized in the past, and now there is increasing evidence that autoimmune processes triggered by the underlying neoplasm play a major role in the pathophysiology, as documented by many reports of identification of autoantibodies that react with both the target neural tissue and the underlying neoplasm, as evidenced by the extensive application of molecular biology techniques. […] The presence of antibodies in serum or CSF of some patients with this disorder now accurately identifies the subgroup of the disorders related to specific neoplasms. […] The trend of recent studies on the pathogenesis of this disease may in the future lead to a new era to clarify the pathogenesis.

• #32 Paraneoplastic Neurological Syndromes of the Central Nervous System: Pathophysiology, Diagnosis, and Treatment

  https://www.mdpi.com/2227-9059/11/5/1406

  The traditional classification of PNS and related antibodies has been recently revised by a panel of experts which developed a new set of diagnostic criteria with the aim of improving the clinical management of these conditions. […] One of the most challenging aspects of PNS of the CNS, is that they can manifest as different and frequently overlapping clinical syndromes that are often difficult to promptly diagnose or to easily categorize. […] The potential and the advance of this review consists on a broad description on how the field of PNS of the CNS is constantly expanding with newly discovered antibodies and syndromes. […] Standardized diagnostic criteria and disease biomarkers are fundamental to quickly recognize PNS to allow prompt treatment initiation, thus improving the long-term outcome of these conditions.

• #33 Paraneoplastic Neurologic Syndromes . | Oncohema Key

  https://oncohemakey.com/paraneoplastic-neurologic-syndromes-3/

  The most important management goals in patients with paraneoplastic neurologic syndromes are identification and treatment of an underlying cancer. In general, antibody-mediated neurologic disorders affecting the peripheral nervous system will have a higher likelihood of response to treatment and symptom improvement.

• #34 Treatment Recommendations of a Rare Neurological Paraneoplastic Syndrome Caused by Small Cell Lung Cancer: A Case Report

  https://www.anncaserep.com/full-text/accr-v2-id1283.php

  Now there is no randomised control trial data for the treatment for PNS. But the main treatments For PNS include: (1) anti-cancer treatments of surgery, radiotherapy, chemotherapy to control disease progression; (2) the immunosuppressive therapy, such as hormones, cyclophosphamide, plasma exchange and the treatment of the humoral immune method. […] The mechanism may be that the secretion of abnormal hormone of tumor cells and specific antigen of the nerve reduce, which weakens the ability of the body’s immune response of neural tissue. Therefore the whole body numbness symptoms were alleviated, avoiding the emergence of permanent neurological damage, improving the quality of life and prolonging survival.

• #35 Paraneoplastic Syndromes

  https://www.brainfacts.org/diseases-and-disorders/neurological-disorders-az/diseases-a-to-z-from-ninds/paraneoplastic-syndromes

  Paraneoplastic syndromes are thought to happen when cancer-fighting antibodies or white blood cells (known as T cells) mistakenly attack normal cells in the nervous system. […] Neurologic symptoms generally develop over a period of days to weeks and usually occur prior to the tumor being discovered. […] Research on paraneoplastic syndromes is aimed at enhancing scientific understanding and evaluating new therapeutic interventions. Researchers seek to learn what causes the autoimmune response in these disorders.

• #36 Paraneoplastic syndromes in small cell lung cancer – Soomro – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/38423/html

  Paraneoplastic syndromes can commonly occur due to lung cancer, especially small cell lung cancer. […] This review focuses on the epidemiology, pathogenesis, clinical features, and current management of the most common paraneoplastic syndromes encountered in patients with small cell lung cancer. […] Recent advances have allowed for greater understanding of these syndromes and for the development of improved diagnostic as well as therapeutic tools. […] Paraneoplastic syndromes are now understood to be a heterogeneous group of clinical syndromes characterized by a recognizable constellation of signs and symptoms in a patient that occurs in association with neoplastic disease processes. […] Generally, the pathophysiology that causes the paraneoplastic syndromes involves the ectopic production of biologically active hormones or peptides by the primary tumor, or alternatively by immune-mediated processes, including antibody and cell-mediated mechanisms.

• #37 Paraneoplastic Syndromes: Symptoms, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/17938-paraneoplastic-syndromes

  Paraneoplastic syndromes affecting your central nervous system (brain, spinal cord) and your peripheral nervous system (nerves outside of your brain and spinal cord) may cause: Dizziness. Double vision. Speech difficulty. Memory loss. Seizures. Muscle weakness. Reduced reflexes, sensation or coordination. Loss of feeling in your arms and legs. […] There are several paraneoplastic syndromes, including those that affect your nervous system, endocrine system, joints, blood, skin, kidneys, etc. […] Examples include: Cerebellar degeneration. Dysautonomia. Encephalitis. Encephalomyelitis. Lambert-Eaton myasthenic syndrome (LEMS). Myasthenia gravis (MG). Myelopathy. Neuromyotonia. Opsoclonus-myoclonus syndrome. Neuropathy (peripheral neuropathy). Stiff-person syndrome. […] Your healthcare provider will treat the underlying cancer thats causing your symptoms. Theyll also work to manage your symptoms to decrease any damage to your bodys organs or systems. […] Your prognosis mostly depends on your cancer. In some instances, paraneoplastic syndromes cause mild, temporary symptoms. In others, paraneoplastic syndromes cause severe symptoms that must be managed long-term.

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