Paraneoplastic syndrome refers to the various clinical manifestations of the nervous system caused by the “indirect” or “distant” effects of malignant tumors or potential malignant tumors in various systems of the body. It does not include the symptoms caused by the direct spread, infiltration, compression and metastasis of malignant tumors; nor does it include the symptoms caused by the treatment of malignant tumors with radiotherapy, chemotherapy or anti-cancer drugs. Other symptoms such as opportunistic infections arising from long-term immunosuppressive treatment of malignant tumors, or systemic metabolic disorders arising from malignant tumors invading a certain organ are not included in paraneoplastic syndrome. It has been proved that the autoimmune reaction of the body’s nervous system to the underlying malignant tumor may be an important factor in the development of the syndrome. The antibodies detected in the serum and cerebrospinal fluid of patients with this syndrome can simultaneously react with their own neurological tissues and potential malignant tumors, and the level of antibodies in the cerebrospinal fluid can be higher than that in the serum. Symptoms and signs] Clinical manifestations may include symptoms of all systems of the body and local symptoms of the nervous system. The most common systemic symptoms are loss of appetite, fatigue, anemia and hypercoagulable state. Other symptoms may occur in the skin, connective tissue, blood vessels, gastrointestinal tract, kidney, skeletal system and endocrine system. Local symptoms of the nervous system may appear months or even years before the malignant tumor is detected. Some malignant tumors are so small that they are not detected until autopsy or under the microscope, making them more difficult to diagnose during life. In some cases, neurological symptoms do not appear until weeks, months, or even years after the appearance of the tumor. The appearance of symptoms in a very small number of patients may also be due to mere immune deficiency of the body and not necessarily to an underlying malignancy. Neurological related symptoms are classified into the following types according to the involved anatomical and functional sites: 1. Paraneoplastic syndrome of brain and spinal cord 1. Subacute cerebellar degeneration is the most common symptom of paraneoplastic syndrome invading brain tissue. It can be complicated by any malignant tumor, but the most common ones are small cell lung cancer, gynecologic malignancy and Hodgkin’s disease. The first symptom is gait instability, which later develops over weeks to months into symmetrical ataxia of the trunk and extremities with dysarthria and nystagmus. Sometimes vertigo and diplopia are present. Some cases have an acute onset, with symptoms peaking within hours to days; others progress slowly and may be combined with mild dementia. Other signs may include dysphagia, sensory abnormalities, and a positive extensor-plantar reflex. 2. Limbic encephalitis The lesions mainly invade the limbic system. It has a subacute onset and progresses over several weeks, or can be insidious. Early symptoms are often anxiety and depression, followed by severe near-memory loss. Other symptoms include irritability, confusion, hallucinations, partial or generalized seizures, and even sleepiness. In some cases, progressive dementia occurs, which may occasionally resolve spontaneously. 3. Brainstem inflammation The main lesions are located in the lower brainstem. Clinical symptoms include vertigo, vomiting, ataxia, nystagmus, oculomotor disorders, bulbar palsy and pathological reflexes. Less common symptoms include deafness, myoclonus, involuntary movements, and even Parkinson’s syndrome-like manifestations. 4, myelitis The prominent clinical manifestations are muscle atrophy and weakness of the limbs, accompanied by muscle bundle tremor, the upper limbs are often heavier than the lower limbs, suggesting that the cervical medulla is more damaged. Sometimes the cervical muscles and intercostal muscles are obviously involved and lead to cervical muscle weakness and respiratory difficulties. If the posterior horn is involved, the clinical manifestations are similar to spinal cavernous disease. 5. Necrotizing myelopathy is relatively rare. It is reported to be combined with lymphoma in 1/3, lung cancer in 1/3, and other types of tumors in 1/3. The first symptoms are asymmetric weakness of both lower extremities, which rise rapidly within a few days and eventually lead to limb weakness and death with respiratory distress. Paraneoplastic syndrome of peripheral nerves and muscles (including neuromuscular junction) 1.Sensory neuropathy is relatively rare. It is mostly associated with small cell lung cancer, followed by lymphoma. The average age of onset of the disease is 59 years, with slightly more women. The onset of the disease is subacute, but there are also acute onset cases. The typical clinical presentation is pain, numbness and abnormal sensation in the distal extremities, which gradually progresses to the proximal extremities and trunk, and rarely invades the face. Objective examination shows various sensory deficits in the distal extremities, with the lower extremities being more important than the upper extremities, resulting in sensory ataxia and pseudohypoparasitism due to severe deep sensory deficits. Tendon reflexes are diminished or absent, and muscle strength often remains normal. If there is significant muscle atrophy or muscle weakness then it often suggests spinal cord invasion involving the anterior horn cells and occasionally bladder dysfunction. Sensory-motor neuropathy is most often combined with lung cancer, followed by lymphoma, and also reported with malignant glioma in the brain. The onset of the disease can be acute, subacute, chronic and relapsing. In acute cases, the clinical presentation resembles “Green-Barre syndrome” with respiratory muscle paralysis and bulbar palsy, and this type is usually combined with lymphoma. In the subacute and chronic forms, the first symptoms are often sensory disturbances and weakness in the distal extremities, decreased tendon reflexes, and heavier lower extremities than upper extremities, with some involving the proximal extremities and occasional trigeminal nerve involvement. The remission and recurrence type can occur during the course of the disease, and the progression of the primary tumor may not be parallel. This type is less common in combination with lung cancer, but can be combined with tumors of the gastrointestinal tract and genital system. Lambert-Eaton syndrome, also known as myasthenia gravis syndrome, is often combined with small cell lung cancer in 70-80% of patients, with onset after 50 years of age, and is more common in men. The onset of the disease is subacute, with weakness and fatigue of the skeletal muscles of the proximal extremities and trunk as the main manifestation, and progressive aggravation. Occasionally, the extraocular muscles and the medullary muscles are affected, and the fatigue can be relieved after rest. Half of the patients may have a combination of autonomic dysfunction, such as reduced glandular secretion, impotence, postural hypotension, and most patients do not respond to anticholinesterase drugs. 4. Plant neuropathy is relatively rare. Mostly combined with lung cancer, especially small cell lung cancer. Clinical manifestations include subacute progressive gastrointestinal hypotonia, decreased peristalsis, bladder dysfunction, abnormal pupils, little or excessive sweating, impotence, and upright hypotension. Less common manifestations include peripheral neuropathy combined with plasmacytosis (see Crow-Fukase syndrome for details), myasthenia gravis, dermatomyositis and polymyositis, rigid man syndrome, motor neuron disease, etc., which can be detailed in the relevant chapters. The cerebrospinal fluid examination often shows an increase in the number of white blood cells, mainly lymphocytes. The protein content is also mildly to moderately elevated, IgG is increased, and oligoclonal bands may appear. In some diseases, specific antibodies can be measured in blood and cerebrospinal fluid. For example, anti-Yo antibodies can be measured in patients with subacute cerebellar degeneration; anti-Hu antibodies can be measured in patients with sensory neuropathy; anti-glutamic acid decarboxylase antibodies can be measured in patients with rigid man syndrome; and anti-Hu antibodies can be measured in patients with vegetative neuropathy. Patients with myopathy may find increased CK and its isoenzymes, EMG may have characteristic changes of myopathy, and the heavy frequency test shows decreasing (myasthenia gravis) or increasing (Lambert-Eaton syndrome) changes. The following information is helpful for the diagnosis of this syndrome: ① Most of the onset is subacute, and the symptoms tend to stabilize after a few days to weeks of progression. The symptoms are usually characteristic, for example, symptoms of subacute cerebellar degeneration often suggest the possibility of malignancy, and for example, 60% of Lambert-Eaton syndrome is often combined with small cell lung cancer. (3) Patients often show leukocytosis and increased protein content in the cerebrospinal fluid, especially increased IgG. ④The syndrome has a wide range of lesions and sometimes the clinical symptoms can overlap, with more prominent symptoms manifested in the more heavily involved areas. If specific autoantibodies can be measured in the serum and cerebrospinal fluid, it is valuable for diagnosis. ⑥EMG has some reference significance for the classification of patients with myopathy. Differential diagnosis】 It should exclude the direct invasion or metastasis of the tumor; or the systemic endocrine metabolic disorder caused by the organs and tissues where the tumor is located, or the neurological damage caused by radiotherapy or chemotherapy, etc., resulting in various clinical manifestations. [Treatment] Generally speaking, the progression of clinical symptoms of paraneoplastic syndrome and the development of malignant tumor are not necessarily parallel. Sometimes the malignant tumor has been removed, but the symptoms of the syndrome continue to progress; some tumors can be removed and the syndrome can stop developing or get remission. Some people advocate the application of hormones, immunosuppressants, plasma exchange and other treatments, but the effect is difficult to be sure. In conclusion, there is no specific treatment for this syndrome.