Overview
Hepatic myelopathy, also known as portal-cavity shunt myelopathy, is a special type of neurological complication of liver disease, characterized by slowly progressive spastic paraparesis, with pathological changes of demyelination of lateral and posterior cords of the spinal cord. The disease most often occurs in the decompensated stage of cirrhosis, with prominent manifestations of hepatic decompensation and portal hypertension. Most patients have recurrent upper gastrointestinal bleeding, portal-body vein shunt and post-splenic renal vein anastomosis. Most often surgical or naturally occurring porto-caval shunts are seen. Most cases coexist with hepatic encephalopathy, and often spinal cord symptoms are masked by the consciousness and motor deficits of severe encephalopathy and the diagnosis cannot be made until demyelinating changes in the posterior and lateral cords of the spinal cord are detected on pathologic examination. In the absence of a history of surgery, there is often marked varicose veins of the abdominal wall, suggesting that a portal-body vein shunt has naturally developed.
Etiology
The cause of hepatic myelopathy is unknown. Usually, half of hepatic myelopathy is caused by portal cirrhosis, and 1/3 is caused by viral hepatitis. It is generally believed that it may be related to the dysfunction of hepatic detoxification and the metabolic disorders of brain tissue caused by the increase of blood ammonia. In addition, it is related to the formation of pseudo mediators with structural similarity to catecholamines during protein metabolism, which interferes with the normal transmission of mediators in the brainstem reticular formation upstream activation system. Hepatic myelopathy is most commonly seen in patients with multiple episodes of hepatic encephalopathy, portal shunt surgery and partial gastrectomy.
Symptoms
The disease occurs most often in the decompensated phase of cirrhosis, with prominent manifestations of hepatic decompensation and portal hypertension. Most patients have recurrent upper gastrointestinal bleeding, portal-body vein shunt and post-splenic renal vein anastomosis. Those without a history of surgery often have marked abdominal wall varices, suggesting that a portal-body vein shunt has naturally developed. The onset of symptoms of hepatic myelopathy usually occurs 4 months to 10 years after porto-corporeal vena cava anastomosis or after splenorenal venous anastomosis; in patients with natural shunts, the time between the onset of symptoms of liver damage, such as jaundice, ascites, and vomiting of blood, and the onset of symptoms of myelopathy ranges from 6 months to 8 years. There are also cases in which spinal cord symptoms appear directly without hepatic encephalopathy. There are even occasional cases of concurrent and prior neurologic symptoms followed by hepatic disease. The disease is divided into 3 stages:
1. Hepatic symptomatic stage (preneurological symptomatic stage)
It is mainly characterized by chronic liver damage, such as loss of appetite, abdominal distension, fatigue, hepatosplenomegaly, ascites, spider nevus, elevated alanine aminotransferase (ALT), decreased total serum protein, inverted A/G ratio, elevated blood ammonia, esophagogastric fundal varicose veins, abdominal wall varicose veins, and upper gastrointestinal hemorrhage, and so on.
2. Hepatic encephalopathy stage (spastic paraplegia stage)
Recurrent transient encephalopathic symptoms may appear, mainly including mood abnormalities such as euphoria, poor sleep, excitement or retardation; behavioral abnormalities such as unconscious hyperactivity and wandering; intellectual abnormalities such as memory and disorientation; mental abnormalities such as speech disorders, mania, and fuzzy consciousness; autonomic symptoms such as tachycardia, flushing of the skin of the face and forearm, and an abnormal feeling of coldness in the calves and feet, as well as other neurological symptoms such as fluttering tremor, dysarthria, and transient visual disturbances. other neurologic symptoms such as fluttering tremor, dysarthria, and transient visual disturbances. Dizziness, impaired ability to calculate, and still able to take care of themselves. However, some patients go directly from the hepatic phase to the spastic paraplegic phase.
3. Spinal cord stage
Spinal cord symptoms and encephalopathic symptoms do not grow in parallel, but the encephalopathic symptoms are characterized by recurrent transient episodes, while the spinal cord disease is slowly aggravating. The spinal cord lesion stage often occurs after the encephalopathy stage, but it can also occur before the encephalopathy stage, or even without the encephalopathy stage. It is characterized by a feeling of heaviness in both lower limbs, a feeling of effort in walking, muscle shivering in both lower limbs, and inflexibility in movement. It gradually develops into bilateral symmetrical spastic paraplegia, with early extensor spastic paraplegia, increased muscle tone, tonicity, knee and ankle extension, “folding knife phenomenon”, and walking with spastic gait and scissor gait. In the late stage, flexion spastic paraplegia occurs, and in a few cases, quadriplegia occurs, but the lower limbs are still the most important. On examination, it is found that the muscle strength of both lower limbs is reduced, muscle tension is increased, tendon reflex is hyperactive, ankle clonus and bin clonus are often positive, abdominal wall reflex and tibial reflex are disappeared, and cone beam sign is positive and other pathological signs. Limb symptoms were generally symmetrical, with more pronounced proximal than distal symptoms. Individual cases have lower limb muscular atrophy or both hands muscular atrophy, normal electromyography or neurogenic damage. In a few patients, peripheral neuropathy may be combined with bilateral symmetrical stocking-glove-like superficial hypesthesia. Occasionally, deep hyperalgesia is present. There is no sphincter dysfunction. In the presence of hepatic encephalopathy, individuals have urinary incontinence or retention.
Examination
1. Hepatic encephalopathy that progresses more rapidly is characterized by liver function abnormalities such as increased aminotransferases, decreased albumin, and increased globulin. Increased blood ammonia is an important laboratory characteristic of chronic onset, but the level of blood ammonia is not parallel to the severity of cerebral-spinal cord damage.
2. Cerebrospinal fluid is mostly normal, with some mildly or moderately elevated proteins.
3. Serum copper blue protein, vitamin B12, folic acid and syphilis serologic tests are normal.
4. In patients with hepatomegaly complicated with spastic paraplegia, abnormalities of copper metabolism such as corneal K-F pigment ring, decreased serum copper blue protein serum oxidase and serum total copper, increased serum direct response copper and 24-hour urinary excretion of copper can be seen under the slit-lamp or with the naked eye.
5. Electromyography shows upper motor neuron damage. Electroencephalogram shows mild to moderate diffuse abnormalities.
6. MRI of the spinal cord is helpful in ruling out other spinal cord pathologies.
Diagnosis
1. history of acute and chronic liver disease and cirrhosis.
2. Signs of liver disease such as portal-body vein anastomosis, TIPS, or extensive in vivo natural side branch formation.
3. Those with symptoms and signs of chronic encephalopathy and upper motor neuron damage, slow onset of disease in young adults, progressive aggravation of spastic paraplegia of both lower limbs, and recurrent transient consciousness and mental disorders should be highly suspected of hepatic myelopathy.
4. Significantly increased blood ammonia is an important basis for the diagnosis of this disease. Generally, there is no myasthenia, sensory impairment and sphincter dysfunction. Cerebrospinal fluid is normal, serum copper oxidase is normal, and there is no corneal pigment ring.
Questions you may be concerned about
What tests are needed for hepatic myelopathy?
Hepatic myelopathy requires blood tests, ultrasound, magnetic resonance imaging (MRI), electroencephalogram electromyography (EEGEM), and serum albumin on the advice of your doctor.
1. Blood test: Generally, patients with hepatic myelopathy have a history of chronic liver disease, and the first thing they need to do is to take blood tests to check their liver function.
2. Ultrasound: Ultrasound examination of the liver will reveal cirrhosis, especially when portal hypertension occurs.
3. Magnetic Resonance Imaging (MRI): MRI of the head and spinal cord can detect abnormalities in the head and spinal cord and distinguish them from other diseases.
4. Electroencephalogram (EEG) and electromyography (EMG): In patients who undergo EMG and EEG, abnormal changes with different manifestations can be seen.
5. Serum albumin: If the patient’s condition progresses rapidly, it will naturally lead to a rapid decline in albumin, a marked increase in transaminases, and likewise an abnormal elevation of globulin, all of which are manifestations of abnormal liver function.
There are more tests on hepatic myelopathy, and the specific tests need to be chosen according to the patient’s specific situation under the advice of the doctor.
Differential diagnosis
1. Hepatomegaly
Mostly seen in adolescents and with positive family history. The main manifestations are muscle ankylosis, limb tremor, mental disorders, speech disorders, corneal color hepatic myelopathy pigment ring. Serum copper and cuprocyanin are decreased, and urinary copper is increased. Liver biopsy liver tissue contains increased copper. Brain CT scan may show enlarged ventricles or soft foci of brain parenchyma.
2. Amyotrophic lateral sclerosis
Most of the disease develops after middle age and progresses slowly. It mostly manifests as upper and lower motor neuron paralysis of the limbs, and the atrophy of the hand muscles is more obvious, which is often accompanied by muscle tremors. The caudal motor nerves may also be involved, with dysphagia, dysarthria, and atrophy of the lingual and sternocleidomastoid muscles. There is no sensory impairment, and it is not associated with liver disease.
3. Hereditary spastic paraplegia
Spastic paraplegia of both lower limbs with scissor-like gait and mild ataxia is a slowly progressive disease that develops in childhood. The condition stabilizes or improves with age. There is a clear family history of the disease and no liver disease.
4. Subacute combined degeneration of the spinal cord
The disease starts in middle age, with subacute or chronic progression and long course. Clinical symptoms include anemia such as lethargy, fatigue, tongue inflammation, diarrhea and pale skin and mucous membranes, etc. Later, the posterior cord and lateral cords of the spinal cord may appear. Later, signs of damage to the posterior and lateral cords of the spinal cord and the pyramidal tracts appear. It may be accompanied by peripheral nerve damage with a spastic ataxic gait and positive eyes closed sign.
Complications
1. Hepatic encephalopathy
Hepatic encephalopathy is the most common cause of death. The main clinical manifestations are impaired consciousness, behavioral disorders and coma.
2. Upper gastrointestinal tract hemorrhage
Often manifested by vomiting blood and black feces. If the amount of bleeding is not large, only black feces may be present. Large amount of bleeding can lead to shock, and induce ascites and hepatic encephalopathy, or even death.
3. Infection.
4. Primary liver cancer.
5. Hepatorenal syndrome.
6. Portal vein thrombosis.
Treatment
At present, there is a lack of clear and effective treatment for hepatic myelopathy, which often involves active treatment of the primary disease. The principle of treatment is to protect the liver, lower blood ammonia and promote the recovery of spinal cord function. Because of the complex pathogenesis and multifactorial involvement, comprehensive measures need to be taken.
1. Reduce the production and absorption of intestinal toxins
(1) Diet and nutrition: Limit the intake of protein, supply a certain amount of calories and vitamins every day, and take sugar as the main food, and then gradually increase the amount according to the clinical symptoms and the measurement of blood ammonia until the patient can tolerate it. Plant protein is the best, plant protein contains less methionine, aromatic amino acids, but contains a lot of branched chain amino acids, and can increase fecal nitrogen excretion. In addition, plant proteins contain non-absorbable fiber, which is beneficial to the elimination of ammonia by intestinal fermentation and acid production, and is conducive to laxative.
(2) Enema or diarrhea to remove the intestinal accumulation of food, blood or other nitrogenous substances, can be used as saline or weakly acidic solution (such as dilute acetic acid solution) enema, or oral or nasal 33% magnesium sulfate 30 ~ 60ml diarrhea. Lactulose orally or by enema is preferred. Lactulose is decomposed into lactic acid and acetic acid by bacteria in the colon after oral administration, which makes the intestinal lumen acidic, thus reducing the formation and absorption of ammonia and promoting the growth of beneficial bacteria at the same time.
(3) Inhibit the growth of bacteria Oral neomycin, rifaximin, or norethindrone vancomycin are effective.
2. Promote the metabolic removal of toxic substances and correct the disorders of amino acid metabolism.
(1) Ammonia-lowering treatment Potassium/sodium glutamate, arginine, sodium benzoate, phenylacetic acid, ornithine-ɑ-ketoglutarate and ornithine, and mentholatum have significant ammonia-lowering effects.
(2) Branched-chain amino acids Oral or intravenous administration of amino acid mixtures based on branched-chain amino acids can theoretically correct imbalances in amino acid metabolism and inhibit the formation of pseudo-neurotransmitters in the brain, but their efficacy in poro-somatic shunt encephalopathy is controversial. For those who cannot tolerate protein foods, intake of a mixture rich in branched-chain amino acids in sufficient quantity is effective and safe in restoring positive nitrogen balance in patients.
(3) Artificial liver Hemoperfusion with activated charcoal and resin or hemodialysis with polyacrylonitrile can remove blood ammonia and other toxic substances.
3. Intrathecal dexamethasone injection for spinal cord disease
It can stop the demyelination of spinal cord pyramidal tracts, and the recent efficacy is moderate.
4. Liver transplantation
It is an effective treatment for all kinds of end-stage liver diseases, and all kinds of stubborn and serious complications can be significantly improved after transplantation. Liver transplantation can fundamentally remove the cause of hepatic myelopathy, which is favorable for prevention and treatment, but most scholars believe that it is unable to improve the neurological damage in patients who have already developed spastic paraplegia of the lower limbs.
5. Others
Acupuncture, physiotherapy, massage and traditional Chinese medicine can also improve the condition to different degrees.
Prognosis
The prognosis of this disease is poor and is highly dependent on the degree of cirrhosis. The spinal cord injury is often irreversible, and the spastic paraplegia is progressively aggravated. The main cause of death in this disease is liver failure and other serious complications.
Aggressive and effective treatment of the primary liver disease is the basis for prevention of the disease.