Myelopathy is a common clinical condition that is an important cause of physical disability. Early detection and prevention are extremely important to improve the prognosis. Common causes of myelopathy include tumors, degenerative disc disease, compression injury due to acute spinal cord trauma, multiple sclerosis, optic nerve myelitis, and idiopathic transverse myelitis. The paper discusses the multiple metabolic-nutritional and toxic factors that lead to myelopathy, as well as the clinical manifestations, specific diagnostic and therapeutic approaches to such diseases. Metabolic nutrient deficiencies Copper deficiency Copper is an essential trace element in the body and is mainly found in the muscles, liver, brain and heart. Copper is involved in the synthesis of many enzymes, such as dopamine beta hydroxylase, which catalyzes the conversion of dopamine into norepinephrine, and superoxide dismutase, which scavenges superoxide from the body, are copper-containing enzymes. Copper is an important dietary nutrient with a very low daily requirement, mostly absorbed via the duodenum and to a lesser extent via the stomach. The hematological manifestations of copper deficiency are well known and include megaloblastic anemia similar to that seen in pernicious anemia. Whereas there are multiple causes of copper deficiency in neurological diseases, particularly spinal cord diseases, the most common cause of copper deficiency is abnormal copper absorption. Many patients with copper deficiency have a history of gastric surgery, particularly bariatric surgery for the treatment of morbid obesity. Impaired copper absorption secondary to celiac disease may also lead to copper deficiency. Another etiology of copper deficiency is related to excessive zinc intake. Zinc causes high expression of chelators and metallothioneins, but copper has a stronger affinity for metallothioneins than zinc, and copper competes with zinc to bind metallothioneins, and the binders remain in the intestinal wall cells and are excreted via the feces as the intestinal wall cells are shed, decreasing copper absorption. Zinc is included as an over-the-counter dietary supplement in a variety of over-the-counter cold and flu medications, and is also used as a denture adhesive. Excessive intake of zinc has been reported to lead to zinc toxicity, which can cause copper deficiency, and most zinc-containing products today have instructions on their packaging regarding zinc overdose. Gao Lixia et al. reported 7 cases of copper deficiency myelopathy with a mean age of 54.5 years (39-72 years), 3 cases with anemia and a slowly progressive course; 5 cases with numbness in hands and feet, 1 case with unsteadiness in walking, and 1 case with weakness in both lower extremities; all 7 cases had loss of vibration and position sensation in both lower extremities and positive cone bundle signs, suggesting damage to the lateral and posterior columns of the spinal cord; 2 cases had T2-weighted high signal in the posterior column of the thoracic medulla on MRI of the spinal cord; 7 cases serum copper was lower than normal, and serum zinc was increased in one case. Treatment with copper gluconate 2mg/d improved in only 3 cases. The clinical manifestations of copper deficiency were mainly spastic paraplegia and sensory ataxia (similar to subacute combined degeneration). Other forms include central nervous system demyelination, peripheral neuropathy and optic neuritis. The neurological manifestations of copper deficiency are very similar to those of vitamin B12 deficiency. Also, clinical cases of copper and vitamin B12 deficiency do occur together. Copper deficiency can have both anemia and neurological damage, or only neurological damage without hematologic damage such as anemia. MRI shows a T2-weighted high signal in the middle cervical medulla and posterior column of the thoracic medulla. The abnormal signal may disappear after treatment with copper agents. Vitamin B12 deficiency Vitamin B12, also known as cobalamin, is one of the important coenzymes in human metabolism and is involved in metabolic processes such as molecular rearrangement, methyl transfer, DNA and methionine synthesis. Vitamin B12 has a role in promoting the maturation of red blood cells and maintaining the normal function of the nervous system, and deficiency can lead to pernicious anemia and neurological damage. The human body can not synthesize vitamin B12 itself, the main source is animal food, especially liver. During the absorption process, vitamin B12 needs to form a complex with the internal factors secreted by the gastric mucosa in order to be absorbed by the intestine. There are 3 steps in the diagnosis of vitamin B12 deficiency: (i) determination of total serum vitamin B12 amount; (ii) determination of methylmalonic acid and homocysteine as functional defects of vitamin B12; (iii) determination of the full vitamin B12 functional transporters (vitamin B12 transporters II and I), and making disease diagnosis according to their abnormal combinations, respectively. Methylcobalamin (same role as vitamin B12), in intracellular methylcobalamin cobalt is III-valent drill, it must be converted to I-valent cobalt cobalamin to play a physiological role. When its conversion process is impaired, it causes cobalamin A disease, or B disease, or C disease, or D disease, or E disease, or F disease, or H disease, etc. In the mitochondria, impaired metabolism of adenocobalamin causes methylmalonic aciduria. Methylmalonic aciduria can cause psychotic symptoms, delusions, bipolar affective psychosis, and bilateral lower extremity upper motor neuron palsy. Defects such as impaired methylcobalamin uptake and cobalamin transporter II in cobalamin C disease and cobalamin D disease can cause subacute combined degeneration. Folate deficiency Folate is used in the body as a coenzyme of the carbon unit transferase system in the form of tetrahydrofolate, which is involved in the metabolism of nucleotides, amino acids and other substances. Nucleotides are the material basis for DNA and RNA synthesis, and folic acid deficiency leads to impairment of both synthesis thereby affecting cell formation and leading to anemia. In 1967, Ungar reported a case of megaloblastic anemia and neuropathy resembling subacute combined degeneration (SCD) of the spinal cord in a patient on long-term oral antiepileptic drugs, who was examined and found to have normal serum vitamin B12 levels, and after treatment with vitamin B12 was ineffective and folic acid was added, his blood and The neurological symptoms improved significantly after the addition of folic acid after the ineffective treatment with vitamin B12. Pincus et al. (1973) reported a case of SCD in which treatment with vitamin B12 alone was ineffective and the symptoms improved after switching to folic acid. Thus, folic acid deficiency is considered to be one of the causes of myelopathy. Folic acid deficiency myelopathy alone is less common than vitamin B12 deficiency myelopathy and is often combined with other types of nutritional deficiencies. Folic acid deficiency is associated with gastrointestinal disorders, alcohol abuse and long-term use of drugs such as methotrexate and methotrexate. Vitamin E deficiency Vitamin E is an important antioxidant that is absorbed in the intestine and binds to the alpha-tocopherol transporter protein to prevent excessive oxidation of unsaturated fatty acids contained in biofilms. Vitamin E deficiency results in the oxidation of unsaturated fatty acids in biofilms by peroxides such as free radicals to form oxidized lipids, leading to cellular degeneration and loss of normal physiological functions. In 1987, Sitrin et al. reported two patients with cystic fibrosis who presented with vitamin E deficiency and neurological lesions, including abnormal gait, walking impairment, decreased position and vibration sensation, and positive Romberg’s sign on examination, and the patients’ neurological symptoms improved after vitamin E treatment. It is evident that vitamin E deficiency can lead to spinal cord lesions. Vitamin E deficiency is usually associated with impaired absorption syndromes, including digestive tract disease, cystic fibrosis, cholestasis, and a variety of other intestinal dysfunctions. Vitamin E deficiency can also result from β-lipoprotein-free disorders and genetic defects in celiac synthesis and secretion. Food, Drug, and Chemical Ingredient Poisoning of Sallow Sallow is one of the oldest known foods with neurotoxic properties. Beta-oxalamino-L-alanine extracted from sallow can cause damage to motor neurons in the upper spinal cord. Bell extracted beta-N-methylamino-L-alanine in sulforaphane powder, causing amyotrophic lateral sclerosis. These foods have been consumed for a long time among the indigenous people of Guam. Konzo Konzo is a disease of spastic paraplegia or quadriplegia caused by food poisoning. It is caused by the patient’s consumption of cassava containing cyanide, etc., in the absence of protein in the diet. It starts acutely with weakness of the extremities or lower limbs. On examination, there is only damage to the pyramidal fasciculus, increased muscle tone, hyperactive tendon reflexes, and positive pyramidal fasciculus signs. There is no sensory impairment. Chloriodoquinoline, a drug used to treat intestinal parasitic diseases, can cause subacute spinal-optic neuropathy. it was seen in Japan from 1955 to 1970. The mechanism by which chloriodoquinoline causes neuropathy is not known, and as a copper chelator, its pathogenic mechanism may be similar to that of copper deficiency myelopathy. Chemotherapeutic agents Many chemotherapeutic agents are known to cause the appearance of myelopathy. These include cisplatin, doxorubicin, vincristine, cytarabine, and intrathecal methotrexate. Intrathecal injection of chemotherapeutic drugs may increase the probability of myelopathy by increasing the amount of the drug component itself or the preservatives and retardants within the component in the cerebrospinal fluid. Radiation Radiation myelopathy is considered a type of toxic myelopathy, and patients may develop spinal cord lesions months to years after receiving radiation. Organophosphorus poisoning Organophosphorus is a common pesticide ingredient and organophosphorus poisoning is also a cause of myelopathy. One of the main chemical components that causes myelopathy is trimethoate phosphate. This compound is incorporated in a variety of edible oils and is one of the main causes of ginger toxic neuropathy in Jamaica, a disease that was prevalent decades ago. Heroin addiction Heroin addiction is also associated with myelopathy, and either inhaled or intravenous injection of heroin can produce MRI features similar to those of transverse myelitis. Other causes of myelopathy and spinal neuropathy From 1992 to 1993, Cuba experienced a rare pandemic of optic neuropathy in which more than 50,000 people were infected. Approximately 1/3 of these patients developed peripheral neuropathy, ataxia, hearing loss, and dorsal myelopathy. The cause of the epidemic is malnutrition; in addition, smoking, alcohol abuse and sugar overconsumption are considered risk factors for the onset of the disease. Many patients are given cobalamin, folic acid and other B vitamin complexes for symptomatic relief. Hepatic myelopathy is relatively rare and is characterized by spastic lower extremity paraplegia with occasional sensory disturbances, mostly in patients with portal shunts (resulting from surgery or developing spontaneously). The pathophysiological mechanism is unclear and may be related to ammonia or other hepatic metabolites, or to increased levels of manganese. Myelin deficiency within the lateral columns of the spinal cord was found by pathological examination. Although some patients have experienced symptomatic relief after liver transplantation, there is no particularly effective treatment available.