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• #1 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.

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

  https://www.uptodate.com/contents/overview-of-paraneoplastic-syndromes-of-the-nervous-system

  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. These syndromes may affect any part of the nervous system, from cerebral cortex to neuromuscular junction and muscle (table 1), either damaging one area or multiple areas. […] This topic provides an overview of the pathogenesis, diagnosis, and treatment of paraneoplastic neurologic disorders. Individual syndromes are discussed separately.

• #3 Chapter 79: Neurologic Paraneoplastic Syndromes | Harrison’s Manual of Medicine

  https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623219/all/Chapter_79:_Neurologic_Paraneoplastic_Syndromes

  Paraneoplastic neurologic disorders (PNDs) are cancer-related syndromes that can affect any part of the nervous system; caused by mechanisms other than metastasis or by complications of cancer such as coagulopathy, stroke, metabolic and nutritional conditions, infections, and side effects of cancer therapy. […] In 60% of pts the neurologic symptoms precede cancer diagnosis. […] PNDs occur in 0.51% of all cancer pts, but they occur in 23% of pts with neuroblastoma or small cell lung cancer (SCLC), and in 30-50% of pts with thymoma or sclerotic myeloma.

• #4 Mayo Clinic Health Library – Paraneoplastic syndromes of the nervous system | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20251949

  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.

• #5 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. […] The discovery of onconeural antibodies has led to the widely accepted nowadays hypothesis that PNS are immune-mediated disorders. […] PNS pathogenesis is currently related to an aberrant expression in the tumor of an antigen that is normally expressed only in the nervous system. […] However, the role of onconeural antibodies in neurological dysfunction is not clear. […] The role of VGCC-Ab has been demonstrated by the fact that the electrophysiologic abnormalities characteristic for LEMS can be reproduced when immunoglobulin G (IgG) from LEMS patients is given to experimental animals. […] Thus, these paraneoplastic antibodies seem to be only a marker of the autoimmunity and do not cause the disease. […] Recently, it has been suggested that cellular immune mechanisms play a critical role in the pathogenesis of PNS.

• #6 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 associated with antibodies against intracellular antigens, known as “high-risk” antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as “intermediate- or low-risk” antibodies, are less frequently associated with cancer. PNS of the central nervous system (CNS) exhibit a range of overlapping “high-risk” clinical syndromes, including but not limited to latent and overt rapidly progressive cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome, paraneoplastic (and limbic) encephalitis/encephalomyelitis, and stiff-person spectrum disorders. 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. Antibodies directed against intracellular (e.g., cytoplasmic, nuclear, or synaptic) neuronal antigens are traditionally named “onconeural” antibodies and are associated with cytotoxic T cells (which are thought to exert a pathogenic role). 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. Accordingly, the previously-named “onconeural antibodies” (e.g., intracellular antibodies) are now called “high-risk antibodies” (e.g., associated with cancer in >70% of cases), and the NSA-Ab are now considered “intermediate-risk antibodies” (e.g., associated with cancer in 30–70% of cases) or “low-risk antibodies” (e.g., associated with cancer in <30% of cases). The panel also identified recommendations for PNS triggered by immune-checkpoint inhibitors (ICIs), a treatment class currently used to treat cancers. This classification helps clinician in having an immediate evaluation of risk of underlying oncological conditions, treatment response, and prognosis for patients with PNS.

• #7 Paraneoplastic Syndromes: Symptoms, Types & Treatment

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

  Some cancerous tumors secrete substances, like hormones or proteins, that cause certain organs in your body to work atypically. As a result, you may experience symptoms that wouldn’t occur without the tumor. […] Often, paraneoplastic syndromes occur because your body’s immune system mistakenly harms healthy tissue. Your immune system makes a substance called antibodies. Antibodies protect you from disease by identifying and destroying abnormal cells, like cancer cells. Sometimes, the signals get crossed, and antibodies attack healthy cells and tissue instead, causing symptoms associated with a paraneoplastic syndrome. […] 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.

• #8 Paraneoplastic syndromes of the nervous system | PPT

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

  Paraneoplastic syndromes of the nervous system are disorders that accompany benign or malignant tumors but are not directly caused by tumor invasion or mass effects. […] Immunological factors are believed to be responsible for paraneoplastic syndromes. The immunologic response is directed against shared antigens that are ectopically expressed by the tumor, but otherwise exclusively expressed by the nervous system, or rarely by the nervous system and testes. […] 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 and antibodies directed against neuronal cell surface or synaptic proteins. […] One or more paraneoplastic neurologic disorder is present in up to 9% of patients with small cell lung cancer (SCLC).

• #9 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.

• #10 Paraneoplastic neurological syndromes: a practical approach to diagnosis and management | Practical Neurology

  https://pn.bmj.com/content/22/1/19

  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. […] A key feature of PNS is that the cancer triggers the immune response, and so it should express the autoantigen to which the immune response (including an autoantibody) is directed: this ensures a direct biological link between the cancer and PNS. […] Among other benefits, these observed relationships avoid the spurious attribution of common cancers to neurological presentations with an alternative explanation, and hence encourage accurate diagnosis and prognostication. […] The likely origin of immunisation is the tumour itself, given immunohistochemical evidence of relevant antigen expression in cancers including SCLC, testicular seminoma and ovarian carcinoma.

• #11 Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and muscle – UpToDate

  https://www.uptodate.com/contents/paraneoplastic-syndromes-affecting-spinal-cord-peripheral-nerve-and-muscle

  Paraneoplastic neurologic syndromes are a heterogeneous group of neurologic disorders associated with systemic cancer and caused by mechanisms other than metastases, metabolic and nutritional deficits, infections, coagulopathy, or side effects of cancer treatment. […] Paraneoplastic syndromes affecting the spinal cord, dorsal root ganglia, peripheral nerve, neuromuscular junction, and muscle will be reviewed here. […] The usual culprit is small cell lung cancer (SCLC). […] In a case series of 31 patients with an isolated progressive paraneoplastic myelopathy, the most common coexisting cancers were lung and breast; kidney cancer, thyroid cancer, gynecologic cancers, and melanomas were also present in a few patients. […] The study suggests that in patients with new-onset progressive myelopathy of unknown cause, the presence of symmetric, longitudinally extensive tract or gray matter-specific changes on spinal MRI should raise suspicion for a paraneoplastic etiology.

• #12 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. […] PNS may be the first presentation of the underlying neoplasm (often tumor is unknown). Neurological involvement in PNS often produces rapid and severe deficits in short period of time. Prompt tumor control improves neurological outcome. […] 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.

• #13 Paraneoplastic syndromes of the nervous system – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/paraneoplastic-syndromes-of-the-nervous-system/

  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. […] 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. […] 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. […] Any cancer may be associated with a paraneoplastic syndrome of the nervous system. However, it occurs more often in people with cancers of the lung, ovary, breast, testis or lymphatic system.

• #14 Paraneoplastic Syndromes – StatPearls – NCBI Bookshelf

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

  Paraneoplastic syndromes are secondary to an occult malignancy, but the exact mechanism remains unclear. […] These syndromes commonly manifest in patients with lung cancer, breast cancer, hematological malignancies, medullary thyroid cancer, gynecological malignancies, and prostate cancer.

• #15

  https://homeopathyaajtak.com/diseases/all/paraneoplastic-syndromes-of-the-nervous-system-451

  Paraneoplastic syndromes of the nervous system are a group of uncommon disorders 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. […] Paraneoplastic syndromes are not caused by cancer cells directly disrupting nerve function, by the cancer spreading (metastasis), or by other complications such as infections or treatment side effects. Instead, they occur alongside the cancer as a result of the activation of your immune system. […] Researchers believe paraneoplastic syndromes are caused by cancer-fighting abilities of the immune system, particularly antibodies and certain white blood cells, known as T cells. Instead of attacking only the cancer cells, these immune system agents also attack the normal cells of the nervous system and cause neurological disorders. […] Any cancer may be associated with a paraneoplastic syndrome of the nervous system. However, the disorders occur more often in people with cancers of the lung, ovary, breast, testis or lymphatic system.

• #16 Paraneoplastic syndromes | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/paraneoplastic-syndromes

  Paraneoplastic syndromes occur secondary to the indirect effects of a malignancy and occur remotely to the primary malignancy. Symptoms are mediated by cytokines, hormones or immune cross-reactivity. These syndromes can cause a diverse range of symptoms and can affect multiple systems. […] Paraneoplastic syndromes arise most commonly with small cell lung cancer as well as gynecological and hematological malignancies. […] Paraneoplastic syndromes can affect multiple systems and have a diverse presentation.

• #17 Paraneoplastic Syndromes

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

  Paraneoplastic syndromes are a group of rare disorders that are triggered by an abnormal immune system response to a cancerous tumor known as a „neoplasm.” […] 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. […] These disorders typically affect middle-aged to older people and are most common in individuals with lung, ovarian, lymphatic, or breast cancer. […] 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.

• #18 Paraneoplastic Syndromes: Causes, Symptoms and Treatment

  https://www.rupahealth.com/post/paraneoplastic-syndromes-causes-symptoms-and-treatment

  Commonly associated cancers include small cell lung cancer, breast cancer, ovarian cancer, and Hodgkin lymphoma. […] Diagnosing paraneoplastic syndromes can be challenging because their symptoms overlap with many other neurological, autoimmune, and infectious diseases. […] Effective treatment focuses on managing the underlying cancer and controlling immune-related symptoms using immunotherapy, steroids, or plasmapheresis. […] Long-term outcomes vary; some patients recover fully, while others may have persistent symptoms requiring ongoing care and rehabilitation. […] Global disparities exist in diagnosis and treatment due to differences in healthcare systems, access to specialists, and availability of advanced diagnostic tools.

• #19 Paraneoplastic Syndromes Affecting the Nervous System | Neupsy Key

  https://neupsykey.com/paraneoplastic-syndromes-affecting-the-nervous-system/

  Exceptions include Lambert-Eaton myasthenic syndrome (LEMS), which affects about 3 percent of patients with small-cell lung cancer (SCLC). […] The hypothesis is that patients develop neurologic symptoms because the tumor expresses onconeural antigens that cause a cellular and/or humoral response; this then cross-reacts with specific antigens in varied regions of the nervous system. […] Between 40 and 60 percent of patients with LEMS harbor a malignancy, and, as in the other PNS, neurologic symptoms often precede tumor diagnosis. […] The most common malignancy associated with LEMS is SCLC. […] PCD may occur in isolation but may be associated with other PNS, including LE and LEMS. […] PCD is most commonly associated with SCLC, gynecologic cancers, and Hodgkins lymphoma. […] Several paraneoplastic antibodies have been identified in patients with PCD.

• #20 Paraneoplastic syndromes of the nervous system | PPT

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

  Paraneoplastic peripheral neuropathy affects 5-15% of patients with plasma cell dyscrasias associated with malignant monoclonal gammopathies. […] Diagnostic criteria for paraneoplastic syndromes include definite and possible categories, with specific criteria for each. […] Treatment approaches for paraneoplastic syndromes focus on the removal of the antigen source by treating the underlying tumor or suppression of the immune response. […] Testing for paraneoplastic antibodies can facilitate recognition of simultaneous occurrence of two or more paraneoplastic syndromes in one patient.

• #21 Paraneoplastic syndrome: Connection to small cell lung cancer

  https://www.medicalnewstoday.com/articles/small-cell-lung-cancer-paraneoplastic

  There is a strong association between limbic encephalitis (LE) and SCLC, with SCLC being present in 40% of LE cases. […] Cerebella degeneration occurs when SCLC triggers the production of antibodies that attack brain cells called Purkinje cells. […] The exact cause of rheumatologic syndromes is still not known. […] The NORD states there is currently no consensus on the most effective treatment for paraneoplastic syndrome. […] According to the NORD, older adults are more likely than others to develop paraneoplastic syndrome. […] Research has shown that the condition can occur in up to 10% of all lung cancer cases, including those living with SCLC. […] The best way to prevent paraneoplastic syndrome is to take steps to limit the likelihood of developing SCLC or other lung cancers. […] Paraneoplastic syndrome is a rare group of disorders that causes neurological damage to the brain, nerves, spinal cord, or muscles. […] The condition occurs due to the presence of a malignant tumor, such as small cell lung cancer.

• #22 Paraneoplastic Syndromes: Symptoms, Types & Treatment

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

  Paraneoplastic syndromes are rare conditions that can occur alongside cancerous tumors. Sometimes, tumors release substances that cause your body’s organs and body systems to behave abnormally. Or your body’s attempt to destroy a tumor can cause unintended damage to healthy tissue. The damage can cause the symptoms of a paraneoplastic syndrome. […] A paraneoplastic syndrome is a set of signs and symptoms that can occur when you have cancer. The symptoms develop when a malignant tumor causes changes in your body that aren’t directly caused by the cancer itself. The tumor may secrete a hormone or protein that affects a particular body system. […] Paraneoplastic syndromes can affect multiple body systems and organs, including your nervous system, endocrine system (hormones), kidneys, bones, joints, skin and blood, etc.

• #23 What Is Paraneoplastic Syndrome?

  https://www.icliniq.com/articles/cancer/paraneoplastic-syndrome

  Paraneoplastic syndromes are rare disorders that can occur simultaneously with cancerous tumors. […] Paraneoplastic syndromes can affect multiple body systems and organs, including the nervous system, endocrine system (hormones), kidneys, bones, joints, skin, and blood. […] Approximately eight to 20 percent of cancer patients develop paraneoplastic syndromes. […] Anyone with a cancerous tumor can develop paraneoplastic syndrome. […] Some cancerous tumors secrete substances, such as hormones and proteins, that cause problems with the function of certain organs in the body. […] Paraneoplastic syndromes often occur because the body’s immune system mistakenly damages healthy tissue. […] The immune system produces substances called antibodies. […] Signals cross, and antibodies instead attack healthy cells and tissues, sometimes causing symptoms associated with paraneoplastic syndromes.

• #24 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 causes of the paraneoplastic syndromes associated with underlying cancers are not well known. Only a few cases clearly demonstrate an etiologic and a pathogenetic factor. […] Fever is thought to result from the release of endogenous pyrogens (ie, lymphokines or tissue pyrogenes). […] Cachexia is thought to be caused by bioactive molecules produced by the tumor, such as alpha-lymphotoxin (tumor necrosis factor [TNF] alpha), peptides, and nucleotides, which are able to affect metabolism. […] The causes of hypertrophic osteoarthropathy remain unknown, although several hypotheses have been developed (eg, estrogen or growth hormone [GH] production by the tumor, vagal hyperactivity).

• #25 Paraneoplastic syndromes – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/paraneoplastic-syndromes/

  Paraneoplastic syndromes are a set of clinical features that are caused by either an altered immune response to a systemic malignancy or because of substances (e.g., hormones, cellular proteins) produced by tumors. […] They are caused neither by the local mass effect nor by metastasis of the associated cancer. […] Some paraneoplasias are associated with many different malignancies, such as tumor-induced hypercalcemia, which is caused by parathyroid hormone-related protein (PTHrP) produced from tumor cells. […] A general overview of the most common paraneoplastic syndromes and their associations is presented here. […] Common paraneoplastic manifestations are cachexia, hyperthermia, and increased risk of thrombosis. […] Paraneoplastic syndromes present with a wide range of findings and are most commonly associated with lung, ovarian, lymphatic, and breast cancers.

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

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

  The autoimmune basis of polymyositis and dermatomyositis is confirmed by the presence of a lymphoplasma cellular infiltrate of the muscular interstices and by the presence of muscle necrosis, which is revealed by increased serum levels of creatine kinase and lactate dehydrogenase (LDH) and an elevated erythrocyte sedimentation rate (ESR). […] The pathogenesis of paraneoplastic endocrine syndromes results from aberrant production by tumors of protein hormones, hormone precursors, or hormonelike substances. […] 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.

• #27 Paraneoplastic syndromes – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/paraneoplastic-syndromes/

  Small cell lung cancer is especially notorious for its numerous and distinct paraneoplastic syndromes. […] Hypercalcemia of malignancy is caused by PTHrP secretion by the tumor. […] Cushing syndrome is caused by neoplastic tissue producing ectopic ACTH. […] Syndrome of inappropriate ADH secretion is caused by neoplastic tissue producing ectopic ADH.

• #28 Paraneoplastic syndromes in lung cancer and their management

  https://atm.amegroups.org/article/view/26458/html

  Paraneoplastic syndromes refer to the remote effects associated with malignancy which are unrelated to direct tumor invasion or metastases (1). These may occur before the cancer is diagnosed and can be independent in their severity to the stage of the primary tumor. Paraneoplastic syndromes are most commonly associated with lung cancer, reported in approximately 10% of cases (1). […] Endocrine syndromes, particularly syndrome of inappropriate ADH secretion (SIADH) and humoral hypercalcemia of malignancy (HHM) are the most common paraneoplastic syndromes seen in lung cancer and are related to the histologic type of cancer (1). […] HHM is typically found in advanced disease and is associated with a poor prognosis (7). […] SIADH represents a state of euvolemic, hypoosmolar hyponatremia, which, in the case of lung cancer is secondary to ectopic ADH production; 10-45% of small cell lung cancer (compared to 1% of non-small lung cancers) can produce ectopic ADH (10,11) resulting in excessive urinary sodium excretion.

• #29 Paraneoplastic syndromes in lung cancer and their management

  https://atm.amegroups.org/article/view/26458/html

  The symptoms of SIADH depend on the degree and acuity of the hyponatremia. Non-specific symptoms such as headache and fatigue might be the initial presentation of paraneoplastic SIADH. […] The manifestations of ECS result from the unregulated production of adrenocorticotropic hormone (ACTH) from malignant cells (4). Elevated ACTH levels may be detectable in up to 50% of patients with lung cancer (13,14). […] Ectopic ACTH secretion is almost always associated with SCLC (14) or less commonly bronchial carcinoids. […] Ectopic growth hormone releasing hormone (GHRH) secretion from malignant cells can manifest as acromegaly (24); in the case of lung cancer, bronchial carcinoids (25) and epidermoid carcinomas (26) have been implicated; SCLC have been reported less frequently (27,28). […] Paraneoplastic neurological syndromes (PNSs) are autoimmune in nature; unlike most paraneoplastic syndromes, they are independent of local tumor or metastatic effects (35).

• #30 Paraneoplastic Syndromes of the Nervous System: Understanding the Causes, Symptoms, and Treatment Options

  https://www.doctorshubnepal.com/diseases-conditions/paraneoplastic-syndromes-of-the-nervous-system-1

  Paraneoplastic syndromes of the nervous system are a group of rare conditions that develop in some people who have cancer. […] The exact cause of paraneoplastic syndromes of the nervous system is not fully understood. However, it is thought that the immune system’s attack on the tumor cells can also trigger an attack on normal cells in the nervous system. […] Several factors can increase the risk of developing paraneoplastic syndromes of the nervous system: Having a diagnosis of cancer can increase the risk of developing paraneoplastic syndromes. […] Certain genetic mutations can increase the risk of developing paraneoplastic syndromes.

• #31 Paraneoplastic Syndromes: Causes, Symptoms and Treatment

  https://www.rupahealth.com/post/paraneoplastic-syndromes-causes-symptoms-and-treatment

  Paraneoplastic syndromes are rare but serious conditions that can develop in people with cancer. […] Paraneoplastic syndromes are a group of rare disorders that occur when the immune system reacts abnormally to a cancerous tumor. […] These syndromes are not directly caused by the cancer cells themselves but rather by substances secreted by the tumor (e.g., autoantibodies, cytokines, hormones, peptides) that can impact multiple organ systems. […] While the exact cause of paraneoplastic syndromes varies, they are often associated with specific types of cancer. […] Some people may be genetically predisposed to developing paraneoplastic syndromes, while environmental factors such as smoking or exposure to toxins may also play a role. […] Paraneoplastic syndromes may involve several organ systems:

• #32 Paraneoplastic Syndromes: Symptoms, Types & Treatment

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

  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.

• #33 Paraneoplastic Syndromes and MPNs | myMPNteam

  https://www.mympnteam.com/resources/paraneoplastic-syndromes-and-mpns

  Paraneoplastic disorders of the nervous system (brain, spinal cord, and nerves) include: Lambert-Eaton myasthenic syndrome, Stiff-person syndrome, Encephalitis, Myasthenia gravis, Cerebellar degeneration, Limbic or brain stem encephalitis, Neuromyotonia, Opsoclonus, Sensory neuropathy. […] Paraneoplastic syndromes can be a clue to physicians to check the bone marrow for signs of MPNs or to look for another cancer in the body. […] Because these syndromes are related to inflammation and the autoimmune system, treatment options can include corticosteroids to reduce inflammation, intravenous immunoglobulins to boost healthy antibodies, immunosuppressants to help manage the immune system’s response, plasmapheresis to reduce the amount of antibodies in the blood. […] Ultimately, the presence of paraneoplastic syndromes can make the prognosis of the underlying cancer worse.

• #34 Paraneoplastic Syndromes and Lymphoma | MyLymphomaTeam

  https://www.mylymphomateam.com/resources/paraneoplastic-syndromes-and-lymphoma

  Other paraneoplastic syndromes have also been observed in people with lymphoma. […] Autoimmune cytopenias are a common paraneoplastic syndrome in lymphomas. […] Many other paraneoplastic syndromes have also been observed in the context of lymphoma. […] This syndrome affects the nervous system and involves rapid, multidirectional eye movements (opsoclonus), quick, involuntary muscle jerks (myoclonus), uncoordinated movement (ataxia), irritability, and sleep disturbance. […] Prompt and effective diagnosis and treatment of paraneoplastic syndromes is important because these syndromes can affect outcomes related to lymphoma. […] Because the presence of paraneoplastic syndromes can make the prognosis of underlying cancer worse, it is important to recognize paraneoplastic syndromes when they occur.

• #35 Paraneoplastic syndromes in lung cancer and their management

  https://atm.amegroups.org/article/view/26458/html

  Onconeural antibodies appear to be central to the pathogenesis, though their absence does not preclude a diagnosis of PNS (36). […] In cases of possible or definite PNS all other possible causes of neurological causes should be excluded like brain or leptomeningeal metastasis, nerve root or spinal cord invasion or compression, electrolyte disturbances, hyperglycemia, or adverse effects to irradiation or chemotherapy. […] The hallmark of LEMS is proximal muscle weakness, predominantly affecting the lower extremities (starting from the pelvic girdle) (39). […] Paraneoplastic SCD is rare and most commonly associated with SCLC. […] Paraneoplastic SSN is a constellation of neurologic symptoms beginning with the loss of vibratory and joint sense and progressing, usually within 12 weeks, to impaired temperature sensation and pain.

• #36 Paraneoplastic Syndromes – Cancer – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/cancer/overview-of-cancer/paraneoplastic-syndromes

  Paraneoplastic (associated with cancer) syndromes occur when a cancer causes unusual symptoms due to substances that circulate in the bloodstream. […] About 20% of people with cancer develop a paraneoplastic syndrome. […] Diagnosis of the paraneoplastic syndrome often includes testing for the substance circulating in the bloodstream that causes the paraneoplastic syndrome. […] Eventually, treating the underlying cancer is the best way to control a paraneoplastic syndrome. […] Polyneuropathy is a dysfunction of peripheral nerves (nerves outside the brain and spinal cord), resulting in weakness, loss of sensation, and reduced reflexes. […] Subacute sensory neuropathy is a rare form of polyneuropathy that sometimes develops before the cancer is diagnosed. […] A variety of unusual symptoms may result from antibodies directed against the tumor that also interact with brain tissue to cause a change in mental function, disorientation, vision changes, and muscle weakness. […] Eaton-Lambert syndrome occurs in some people with small cell carcinoma of the lung. […] Subacute necrotizing myelopathy is a rare syndrome in which rapid loss of neurons in the spinal cord leads to paralysis.

• #37 Paraneoplastic Syndromes | Encyclopedia.com

  https://www.encyclopedia.com/medicine/diseases-and-conditions/pathology/paraneoplastic-syndromes

  Paraneoplastic syndromes (PS) are rare disorders triggered by the immune system’s response to cancer cells, or by remote effects of tumor-derived factors. […] These syndromes are believed to occur when cancer-fighting anti-bodies or white blood cells, known as T-cells, mistakenly attack normal body cells. […] Paraneoplastic syndromes are defined as clinical syndromes involving non-cancerous effects in the body that accompany malignant disease, and can affect any part of the nervous system from the cerebral cortex to peripheral nerves and muscles. […] In general (although not always), PS develops in an acute or subacute fashion, over days or weeks. […] Most or all paraneoplastic syndromes are activated by the body’s immune system. […] Paraneoplastic syndromes occur when the primary or original tumor secretes substances such as hormones, proteins, growth factors, cytokines, and antibodies.

• #38 Paraneoplastic Syndrome Lung Cancer: Symptoms, Causes, Treatment

  https://www.healthline.com/health/lung-cancer/paraneoplastic-syndrome-lung-cancer

  Paraneoplastic syndromes are rare groups of symptoms that affect some people with cancer. These symptoms arent directly caused by the spread of cancer but by: […] It’s thought that the two main causes are the production of hormones or other signaling molecules by cancer cells and a misdirected autoimmune response. […] Damage caused to your nervous system by your immune system can far exceed the damage caused by cancer. […] In a 2019 study, researchers found that lung cancer was the most common type of cancer that lead to paraneoplastic syndromes. […] The two main categories of lung cancer are: […] In a 2017 study, researchers found that paraneoplastic syndromes were nearly 5 times more common in people with NSCLC and 8 times higher in SCLC compared with the general population. […] In about 60 percent of people, paraneoplastic syndrome symptoms start before cancer is diagnosed.

• #39 Paraneoplastic Syndromes and Ovarian Cancer | MyOvarianCancerTeam

  https://www.myovariancancerteam.com/resources/paraneoplastic-syndromes-and-ovarian-cancer

  Middle-aged people who have ovarian cancer as well as those with lung, breast, or lymphatic cancer are thought to be most at risk for paraneoplastic syndromes. […] Sometimes, people may notice the symptoms of paraneoplastic syndrome before they notice any symptoms from underlying cancer. […] Prompt diagnosis and treatment of paraneoplastic syndromes are important because these syndromes can affect the outcomes related to cancer. […] If someone has paraneoplastic syndromes, they can be treated in many different ways. […] Generally, first-line treatment for paraneoplastic syndromes focuses on treating the underlying cancer. […] Because the conditions can vary greatly, the treatment of paraneoplastic symptoms also varies, depending on what part of the body is being attacked. […] The paraneoplastic syndrome may make it difficult for you to receive the recommended treatment for ovarian cancer. […] Paraneoplastic syndromes can also make the prognosis of the underlying cancer worse, so it is important to recognize paraneoplastic syndromes when they occur.

• #40 Paraneoplastic Neurologic Syndromes | Oncohema Key

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

  For example, the likelihood that LEMS or subacute cerebellar degeneration in a middle-aged or elderly patient is paraneoplastic is probably greater than 50%. […] In contrast, subacute sensory neuropathy or dermatomyositis probably is paraneoplastic in origin in less than 20% of patients. […] In most paraneoplastic syndromes, symptoms develop acutely or subacutely and may resemble a viral process. […] Symptoms evolve over weeks or months and then stabilize, differentiating them from the more chronic and progressive degenerative diseases of middle age and adulthood. […] The diagnosis of a paraneoplastic neurologic syndrome is relatively straightforward for patients who experience symptoms of a well-defined syndrome that typically is associated with cancer. […] The specificity of some paraneoplastic antineuronal antibodies for paraneoplastic neurologic syndromes or some types of cancer makes them useful diagnostic tools.

• #41 Paraneoplastic Neurologic Syndromes | Oncohema Key

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

  In patients with a history of cancer or who have recently gone into tumor remission, the development of a paraneoplastic neurologic syndrome frequently heralds tumor recurrence. […] The best approach to treating paraneoplastic neurologic syndromes is to discover and treat the tumor promptly and provide supportive care for the neurologic deficits with symptomatic treatment and physical therapy.

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

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

  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 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. […] 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. […] PNS are usually 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.

• #43 Diagnostic Approach to a Patient With Paraneoplastic Neurological Syndrome | Mahta | World Journal of Oncology

  https://wjon.org/index.php/wjon/article/view/571/407

  Paraneoplastic neurological syndromes (PNS) are defined as any neurological dysfunction in a cancer patient in the absence of direct mass effect of the primary tumor or metastatic involvement of the central nervous system and it is caused by mechanisms other than metabolic or nutritional deficits, infections or coagulopathy or side effects of cancer treatment. […] These paraneoplastic neurological syndromes are heterogeneous and caused by an immune response to an underlying malignancy in less than 1% of cancer patients. […] This immune response is mediated by onconeural antibodies produced by tumor cells with some cross reactivity with components of the nervous system. […] Small cell lung cancer has been notorious for causing PNS. The most common syndromes associated with small cell lung cancer include subacute cerebellar degeneration, brain stem and limbic encephalitides, opsoclonus-myoclonus syndrome, myelopathy, acquired neuromyotonia and Eaton-Lambert syndrome.

• #44 Diagnostic Approach to a Patient With Paraneoplastic Neurological Syndrome | Mahta | World Journal of Oncology

  https://wjon.org/index.php/wjon/article/view/571/407

  The first step in diagnosis of PNS is to rule out other etiologies including infections, connective tissue disorders, metabolic causes or even drug side effects. […] If there is an evidence of cancer and the neurological syndrome is typical, the diagnosis is highly suggestive of PNS and further testing for onconeuronal antibodies can be helpful but is not necessary. […] Chemotherapy plus an immunosuppressive therapy and/or plasmapheresis should be initiated as soon as the diagnosis is established, however; the neurologic symptoms may or may not improve after treatment.

• #45 Paraneoplastic Neurologic Syndromes | Oncohema Key

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

  In the right clinical context, the detection of a paraneoplastic antibody in the serum or cerebrospinal fluid (CSF) helps establish the diagnosis and focus the search of the neoplasm. […] If the detected antibody usually does not associate with the patients neurologic syndrome, other etiologies for the neurologic dysfunction should be considered. […] Similarly, if the detected cancer is not the histologic type typically found in association with the patients antibody, the presence of a second neoplasm should be suspected. […] If paraneoplastic antibodies are present but a cancer is not discovered, the patient should be assumed to harbor an occult neoplasm unless proven otherwise. […] Whole-body positron emission tomographic (PET) scans may detect tumors that escape detection by other standard imaging methods.

• #46 Paraneoplastic Neurologic Syndromes | Oncohema Key

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

  The paraneoplastic neurologic syndromes include an extensive group of disorders that can affect any part of the central or peripheral nervous system. […] Evidence indicates that many of these syndromes have an immunopathogenesis. […] Patients with paraneoplastic neurologic syndromes may have serum and cerebrospinal fluid antibodies that are highly specific for the presence of a cancer. […] The detection of these antibodies serves as a marker of paraneoplasia. […] Other antibodies associate with specific neurologic syndromes that occur with or without cancer. […] In these cases, the antibodies serve as markers for the neurologic syndrome but do not distinguish between a paraneoplastic or nonparaneoplastic etiology. […] Antibodies directly mediate some disorders such as the Lambert-Eaton myasthenic syndrome, myasthenia gravis, and neuromyotonia and likely mediate other disorders such as anti-N-methyl-d-aspartate receptor encephalitis.

• #47 Paraneoplastic Neurologic Syndrome: Types, Causes & Treatment

  https://www.ganeshdiagnostic.com/blog/paraneoplastic-neurologic-syndrome-types-causes-and-treatment

  Rare conditions known as paraneoplastic neurological syndromes (PNS) are linked to cancer but are not brought on by the disease itself, metastasis, or side effects of treatment. Often, they are autoimmune. […] Most PNS are autoimmune. The body starts an immune response when attempting to remove tumour cells, and this reaction may target healthy neurological structures. […] The specificity for paraneoplastic syndromes is quite high when antibodies against onconeural antigens, such as Hu, CV2/CRMP5, Yo, and amphiphysin, are detected alongside a compatible neurological condition. […] These illnesses’ precise incidence and prevalence are unclear. PNS is a clinically uncommon condition. […] The first neurological condition to be recognised and documented with a known malignant aetiology was limbic encephalitis (LE).

• #48 Paraneoplastic syndromes of the nervous system | PPT

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

  Paraneoplastic peripheral neuropathy affects 5-15% of patients with plasma cell dyscrasias associated with malignant monoclonal gammopathies. […] Diagnostic criteria for paraneoplastic syndromes include definite and possible categories, with specific criteria for each. […] Treatment approaches for paraneoplastic syndromes focus on the removal of the antigen source by treating the underlying tumor or suppression of the immune response. […] Testing for paraneoplastic antibodies can facilitate recognition of simultaneous occurrence of two or more paraneoplastic syndromes in one patient.

• #49 A Rare Case of Paraneoplastic Syndrome | 2023, Volume 29 – Issue 1 | Turkish Journal of Neurology

  https://tjn.org.tr/full-text/62/eng

  Paraneoplastic neurological syndromes affect different parts of the nervous system and may present as limbic encephalitis, subacute cerebellar degeneration, and neuronopathies. […] Paraneoplastic syndromes may occur in patients diagnosed with cancer or as the first finding in patients not yet diagnosed with cancer. […] To diagnose paraneoplastic and autoimmune encephalitis, infections, metastasis, vascular causes, and the toxic effects of cancer treatment drugs should be excluded. […] However, while Zic4 antibodies in the Zic family have been reported as being mostly associated with small cell lung cancer, they might also be associated with other malignancies, such as B-cell lymphoma and neuroblastoma. […] Malignancy should be investigated in patients with rapidly developing cognitive problems, and the necessary tests and treatments should be planned with paraneoplastic syndromes in mind. All other etiological causes should be excluded before diagnosing paraneoplastic and autoimmune encephalitis.

• #50 Paraneoplastic Syndrome: Causes, Symptoms, Diagnosis and Treatment

  https://www.prepladder.com/neet-pg-study-material/medicine/paraneoplastic-syndrome-causes-symptoms-diagnosis-and-treatment

  Paraneoplastic syndrome symptoms are typically the first signs of malignancy. […] A paraneoplastic syndrome can appear in any patient with a malignant tumour. The following cancers are most frequently linked to paraneoplastic syndromes: Ovarian cancer, Stomach cancer, Leukaemia, Lymphoma, Small-cell lung cancer, Breast cancer, Carcinoma of the pancreas, Renal cancer, Testicular cancer.

• #51 Paraneoplastic syndromes CNS manifestations | PPT

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

  Paraneoplastic syndromes are rare disorders triggered by an altered immune response to cancer. They involve non-metastatic systemic effects that accompany malignant disease. Common paraneoplastic syndromes affect the endocrine, neurologic, dermatologic, and rheumatologic systems. Timely recognition of paraneoplastic syndromes is important as it may lead to early cancer detection and treatment. […] Paraneoplastic syndromes are clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. They can affect systems in the body in endocrine, neuromuscular, musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, or renal ways. The mechanisms are not fully understood but may involve cross-reacting antibodies, production of physiologically active substances, interference with metabolic pathways, or unknown causes.

• #52 Paraneoplastic Syndromes | Encyclopedia.com

  https://www.encyclopedia.com/medicine/diseases-and-conditions/pathology/paraneoplastic-syndromes

  The substances are referred to as mediators. […] Mediators interfere with communication between cells in the body. […] Paraneoplastic syndromes can occur with any type of malignancy. […] However, they occur most frequently with lung cancer, specifically small-cell lung carcinoma. […] The presence of the syndrome may be the only indication that a patient has a malignancy or that a malignancy has recurred. […] Paraneoplastic syndromes may be useful as clinical indicators to evaluate the response of the primary cancer to the treatment. […] Resolution of the paraneoplastic syndrome can be correlated with tumor response to treatment. […] SIADH results from numerous different types of cancer. […] The malignancies known to cause SIADH include lung cancer, small cell type, gastrointestinal cancers, genitourinary cancer, lymphoma, head and neck cancers, thymoma, brain and central nervous system tumors, breast cancer, and melanoma. […] Certain cancers produce and secrete ADH themselves. […] Of all the types of cancer that produce ADH themselves, small cell lung cancer is by far the most common.

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

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

  Paraneoplastic autonomic dysfunction is a secondary effect of cancer. Small-cell lung cancer is particularly likely to cause paraneoplastic syndromes, but many types of malignancy can cause these types of syndromes, including teratoma, neuroblastoma, retinoblastoma, oligodendroglioma, melanoma, leiomyosarcoma, hematological tumors, and cancers of the thymus, gastrointestinal tract, rectum, prostate, breast, fallopian tubes, uterus, bladder, kidney, pancreas, testicles, malignancies and ovary. […] Exactly how cancers result in paraneoplastic neurological symptoms is incompletely understood. The development of these syndromes are not due to direct tumor invasion. Expression of onconeural antigens by the cancer cells resulting in autoimmunity appears to be the mechanism. […] 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.

• #54 Paraneoplastic Syndromes in Small-Cell Lung Cancer

  https://www.webmd.com/lung-cancer/paraneoplastic-syndromes-small-cell-lung-cancer

  Paraneoplastic syndromes are a group of symptoms that happen in some people who have small-cell lung cancer (SCLC). Some paraneoplastic syndromes affect your nervous system, including your brain, spinal cord, and nerves. Others affect your endocrine system (your hormone system). […] Neurologic and endocrine paraneoplastic syndromes have different causes. In paraneoplastic neurologic syndrome, white cells and antibodies that normally fight cancer attack healthy nerve cells by mistake. This is called an autoimmune response. That means your symptoms aren’t caused by SCLC, but by your body’s immune system. This immune response may damage your nervous system more than it harms the tumor. […] In paraneoplastic endocrine syndrome, tumors start to make their own hormones. Your body already makes these hormones, usually in the exact amount you need. This sometimes makes your cancer harder to diagnose and treat. Symptoms depend on the type of hormone, but most can have serious effects on your body.

• #55 Paraneoplastic Neurologic Syndromes | Oncohema Key

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

  For paraneoplastic neurologic syndromes in which T-cell mechanisms are predominant, the associated antibodies target intracellular neuronal proteins. […] The response to therapy is, in general, disappointing. […] The physicians main concern should be to rule out other diagnostic entities and to uncover the presence of the associated neoplasm. […] For these syndromes the treatment approach should be aimed at the tumor, because stabilization and, less often, improvement of neurologic symptoms after tumor treatment have been reported for almost all syndromes. […] In a few cases, depending on the syndrome and whether the patient is in the early stages of the neurologic disease, treatment with immunosuppression may have some effect on the paraneoplastic neurologic syndrome. […] Most paraneoplastic neurologic syndromes are thought to have an immunopathogenesis.

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