Hepatic myelopathy

　　1. Etiology

　　The etiology and pathogenesis of the disease are not fully understood at present. Most believe that it is mainly related to three factors: severe liver cirrhosis; the existence of abundant portosystemic blood shunting (including surgical shunting or extensive collateral circulation); long-term hyperammonemia. At the same time, it may be related to various factors such as protein metabolism disorders, malnutrition, vitamin B group deficiency, and the accumulation of toxic metabolic substances in the body.

　　2. Pathogenesis

　　Due to significant liver dysfunction during severe liver disease, especially after portocaval or splenic vein shunt surgery or the formation of natural portosystemic collateral circulation, many toxic substances from the intestines, including ammonia, mercaptans, short-chain fatty acids, and amino butyric acid, cannot be converted and cleared by the liver and directly enter the systemic circulation, causing chronic spinal cord poisoning and degeneration. Among them, increased blood ammonia is an important factor in hepatic myelopathy, as long-term high blood ammonia can affect the central nervous system's utilization of oxygen, causing neural system damage and functional decline.

　　Some believe that it may be related to an imbalance in amino acid metabolism: an abnormal ratio of branched-chain amino acids (BCAA) to aromatic amino acids (AAA), leading to spinal cord lesions; autoimmune injury: The hepatitis virus may activate the immune response of neural cells, causing autoimmune injury, damaging Schwann cells, and leading to the loss of myelin sheaths; Deficiency of vitamin B group: Affects the supply of neural energy and causes disorders in the production of myelin proteins. In addition, some people also believe that the disease may be related to abnormal metabolism of urea and glycine.

　　The basic pathological change of this disease is liver cirrhosis. The pathological changes in the central nervous system are most prominent in the demyelination of the pyramidal tract in the lateral cord of the spinal cord, accompanied by moderate axonal degeneration and gliosis. There may be slight degeneration in the anterior and posterior cerebellar peduncles in the lateral cord and the fasciculus gracilis in the posterior cord. There is a significant reduction in nerve cells, replaced by gliocytes. The pathological changes extend from the cervical cord downward through the entire spinal cord, but the degeneration in the thoracic and lumbar segments of the spinal cord is most prominent, and the pyramidal tract above the cervical cord is rarely involved. The pathological changes in the brain are basically consistent with those of hepatic encephalopathy, with widespread Alzheimer type II astrocytes in the deep cortex of the cerebral cortex, putamen, thalamus, substantia nigra, red nucleus, and cerebellar cortex. Diffuse lobar necrosis, degeneration of nerve cells, and myelin can also be seen in the cortex.

　　During the stage of hepatic encephalopathy, patients may experience transient visual impairment, dizziness, and decreased computational ability. During the stage of spinal cord disease, patients' lower limbs gradually develop into symmetrical spastic paraplegia, with a spastic gait and a scissors gait. Some cases have atrophy of the lower limbs or hands.

　　1, Hepatic encephalopathy is the most common cause of death. It is a comprehensive syndrome of central nervous system dysfunction based on metabolic disorders, with the main clinical manifestations being disturbance of consciousness, abnormal behavior, and coma.

　　2, Large-scale bleeding from the upper gastrointestinal tract often manifests as hematemesis and melena. If the amount of bleeding is not large, only melena may occur. Large-scale bleeding can lead to shock, trigger ascites and hepatic encephalopathy, and even death.

　　3, Infection;

　　4, Primary liver disease;

　　5, Liver-kidney syndrome, characterized by oliguria or anuria, azotemia, hyponatremia, and low urinary sodium.

　　6, Portal vein thrombosis.

　　This disease often occurs in the decompensated stage of liver cirrhosis, with prominent manifestations of decreased liver function and portal hypertension. Most patients have recurrent upper gastrointestinal bleeding, and those without surgical history after portosystemic shunt and splenorenal shunt operations often have obvious varicose veins on the abdominal wall, indicating that a natural portosystemic shunt has been formed.

　　The onset time of symptoms of hepatic myelopathy usually occurs 4 to 10 years after the portosystemic shunt or splenorenal shunt operation; for patients with natural分流, the time from the onset of symptoms of liver damage such as jaundice, ascites, hematemesis to the appearance of spinal cord symptoms is 6 to 8 years, and in some cases, the spinal cord symptoms appear directly without hepatic encephalopathy, and even occasionally, the symptoms of the nervous system appear before the manifestation of liver disease. Clinically, according to the symptoms, Chinese scholars divide this disease into 3 stages:

　　1, Stage of hepatic symptoms (pre-neurological symptoms):It is mainly the manifestation of chronic liver damage, such as anorexia, abdominal distension, fatigue, enlargement of the liver and spleen, ascites, spider angioma, increased ALT, decreased serum total protein, inverted A/G ratio, increased blood ammonia, varices of the esophageal and gastric fundus, varices of the abdominal wall, and upper gastrointestinal bleeding, etc.

　　2, Stage of hepatic encephalopathy (spastic paraplegia stage):Transient encephalopathy symptoms may occur repeatedly, mainly manifested as elation, poor sleep, excitement or dullness, and other emotional abnormalities; unconscious hyperactivity, disordered running, and other behavioral abnormalities; decreased memory and orientation, and other intellectual abnormalities; disordered speech, mania, confusion of consciousness, and other mental abnormalities; tachycardia, erythema of the skin on the face and anterior chest, abnormal cold sensation in the lower legs and feet, and other autonomic nervous symptoms, as well as flapping tremors, dysarthria, transient visual impairment, and other neurological symptoms, dizziness, decreased computational ability, and can still take care of oneself in daily life, but some patients lack the stage of encephalopathy and directly enter the stage of spastic paraplegia from the stage of hepatic symptoms.

　　3, Stage of myelopathy:The symptoms of myelopathy are not parallel to the symptoms of encephalopathy. The brain symptoms are characterized by recurrent transient attacks, while the myelopathy presents a gradual progressive worsening. The stage of myelopathy often occurs after the stage of encephalopathy, but it can also occur before the stage of encephalopathy, even without the stage of encephalopathy. It is characterized by a feeling of沉重 in the lower limbs, difficulty in walking, shivering of the muscles in the lower limbs, poor flexibility, and gradually developing into symmetrical spastic paraplegia. In the early stage, it presents as an extended spastic paraplegia with increased muscle tone, appearing rigid, with the knees and ankles extended, and the phenomenon of 'folding knife'. Walking is characterized by a spastic gait and a scissors gait. In the late stage, it presents as a flexion spastic paraplegia, with a few cases of quadriplegia, but still with a greater emphasis on the lower limbs. Examination reveals decreased muscle strength in the lower limbs, increased muscle tone, hyperreflexia of the tendons, and often positive ankle and patellar clonus. The abdominal wall reflex and cremasteric reflex disappear, and the positive signs of the pyramidal tract. The limb symptoms are generally symmetrical, with more obvious symptoms in the proximal part than in the distal part. Some cases have muscle atrophy in the lower limbs or hands, normal electromyography or neurogenic damage, and a few patients may have peripheral nerve lesions, presenting with symmetrical stocking-like hypoesthesia of the lower limbs, occasionally with decreased deep sensation. Bladder function is not impaired. In cases with hepatic encephalopathy, some individuals may have urinary incontinence or urinary retention.

　　1, According to traditional Chinese medicine, factors such as declining physical fitness, drinking, food accumulation, depression, overeating of fatty and sweet foods, and others may cause changes in the liver.

　　2, Vegetables are commonly used in people's lives, rich in nutrients, beneficial, and can be eaten regularly. Vegetables are not only rich in vitamins but also contain a large amount of fiber, lignin, organic acids, inorganic salts, and other substances, which are essential nutrients for the recovery process of liver patients.

　　Therapeutic diet for hepatic myelopathy:

　　1. Take 15 grams of trichosanthes root powder and 50 grams of glutinous rice, and cook them together into porridge. Suitable for those with lung heat and injury of body fluid.

　　2. Take 50 grams of fresh lily bulbs and 50 grams of glutinous rice, add an appropriate amount of sugar. Cook the rice until half-cooked, then add the lily bulbs and cook together until they are done, and then add the sugar and mix well. Suitable for those with lung heat and injury of body fluid.

　　3. Take 60 grams of yam and coix seed, and 24 grams of jujube frost cake. Boil the yam and coix seed until they are cooked, then add the broken jujube frost cake to the porridge and continue to cook until it is soft and ready. Suitable for those with lung heat and injury of body fluid.

　　4. Boil 50 grams of red bean and 200 grams of glutinous rice into porridge, add an appropriate amount of salt and a little monosodium glutamate, and it is ready. Suitable for those with damp-heat invasion.

　　First, treatment:

　　Currently, there is a lack of clear and effective treatment methods for hepatic myelopathy, and it is often active treatment of the primary disease. The treatment principle is to protect the liver, reduce blood ammonia, and promote the recovery of spinal cord function. Due to the complex pathogenesis and the involvement of multiple factors, comprehensive measures need to be taken.

　　1. Reduce the generation and absorption of toxic substances in the intestines:

　　(1) Diet and nutrition: Limit protein intake, provide 5.0-6.7kPa of calories and adequate vitamins daily, with carbohydrates as the main food. The intake can be gradually increased according to clinical symptoms and blood ammonia levels until the patient can tolerate it. Plant protein is best, as it contains less methionine and aromatic amino acids, but contains a large amount of branched-chain amino acids, and can increase fecal nitrogen excretion. In addition, plant protein contains non-absorbable fiber, which is fermented by intestinal enzymes to produce acid,有利于the elimination of ammonia and is conducive to defecation.

　　(2) Enema or catharsis: To clear intestinal food residue, blood, or other nitrogen-containing substances, use physiological saline or weak acidic solution (such as dilute acetic acid solution) for enema, or take 30-60ml of 33% magnesium sulfate orally or nasally. Lactulose is the preferred choice for both oral and enema administration. After oral administration, lactulose is decomposed by bacteria in the colon into lactic acid and acetic acid, making the intestinal lumen acidic and thus reducing the formation and absorption of ammonia. At the same time, it promotes the growth of beneficial bacteria.

　　(3) Inhibition of Bacterial Growth: Oral neomycin 2-4g/d or the selection of norfloxacin are both effective.

　　2. Promote the metabolism and clearance of toxic substances, correct the disorder of amino acid metabolism:

　　(1) Ammonia Reduction Therapy: Potassium or sodium glutamate, arginine, sodium benzoate, phenylacetic acid, ornithine-ketoglutarate, and ornithine, aspartate, all have significant ammonia-reducing effects.

　　(2) Branched-chain Amino Acids: Oral or intravenous injection of a mixture of amino acids mainly containing branched-chain amino acids can theoretically correct the imbalance of amino acid metabolism, inhibit the formation of false neurotransmitters in the brain, but the efficacy of portal-systemic shunt encephalopathy is still controversial. For patients who cannot tolerate protein food, intake of a sufficient amount of a mixture rich in branched-chain amino acids is effective and safe for restoring the patient's positive nitrogen balance.

　　(3) Artificial Liver: Hemoperfusion with activated carbon, resin, or hemodialysis with polyacrylonitrile can remove blood ammonia and other toxic substances.

　　3. Treatment of Spinal Cord DiseaseIntrathecal injection of dexamethasone can prevent demyelination of the spinal cord pyramidal tract, and the recent efficacy is still acceptable. On the basis of protecting the liver, combined with acupuncture, physical therapy, massage, and traditional Chinese medicine, there is also varying degrees of improvement. The combination of breviscapine intravenous infusion and acupoint injection.

　　4. Liver TransplantationIt is an effective method for treating various end-stage liver diseases, and various intractable and severe complications can be significantly improved after transplantation. Liver transplantation can fundamentally eliminate the causes of hepatic myelopathy, which is beneficial for prevention and treatment. However, for patients with lower limb spastic paraplegia, most scholars believe that it is impossible to improve the condition of neural injury. Weissnbom et al. recently reported that 3 patients had significant improvement in the symptoms of spinal cord disease after liver transplantation, and the degree of improvement was positively correlated with the time interval between the onset of spinal cord disease and liver transplantation. It is believed that early detection and diagnosis of the disease, and timely liver transplantation, are necessary.

　　II. Prognosis

　　The prognosis of this disease is poor and is closely related to the degree of liver cirrhosis. Spinal cord injury is often irreversible, and spastic paraplegia tends to worsen progressively. The main cause of death is liver failure and other serious complications.