Mental disorders associated with hepatolenticular degeneration
Introduction
Introduction to mental disorders associated with hepatolenticular degeneration Hepatolenticular degeneration (hepatolenticular degeneration) is an autosomal recessive hereditary disease caused by a decrease in the level of ceruloplasmin (a copper-binding enzyme) in plasma. Because it was first reported by Wilson in 1912, it is also known as Wilson's disease. This disease causes liver and brain diseases due to acetone metabolism disorder in the body. The clinical features are extrapyramidal symptoms, liver damage and characteristic corneal pigment ring. There are different levels of mental disorders, the age of onset varies from juvenile to strong, and about half of the patients are between 20 and 30 years old. Due to frequent mental symptoms, it is easily misdiagnosed as a primary mental disorder. Its condition continues to progress, and most of them have a poor prognosis. basic knowledge The proportion of illness: 0.005% Susceptible people: people who are 20 to 30 years old Mode of infection: non-infectious Complications: dysphagia, urinary tract infection, hemorrhoids, fracture, portal hypertension, hemorrhagic shock, upper gastrointestinal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, epilepsy
Cause
Causes of mental disorders associated with hepatolenticular degeneration
Genetic factors (40%):
The disease is an autosomal recessive monogenic genetic disease, with a positive family history of about 20% to 30%, most of the siblings of the first generation, it is found that at least 25 mutations in its gene, located on chromosome 13, as for its gene The defect is that the structural gene or control gene has not been determined, and some literature reports that the incidence of close relatives is higher, but it is still controversial.
Due to the lack of ceruloplasmin in patients, it cannot bind to copper, so that a large amount of copper is deposited in the liver, brain (the nucleus), cornea and kidney, leading to copper metabolism disorders and causing a series of visceral function and tissue damage; the most common The site of the brain is the basal ganglia, cerebellum, cerebral cortex, cornea, liver, kidney, etc. The pathological changes of this disease are mainly in the lenticular nucleus, and the cerebral cortex can also be damaged. The pathological sections can be seen in the nucleus and caudate nucleus. Or disappear, and replaced by astrocytes, if copper is deposited in the liver, there may be large liver, acute or chronic hepatitis and cirrhosis, liver atrophy.
Biliary tract copper barrier (15%):
After examination with 64Cu or 67Cu radionuclide, it was found that patients with this disease had reduced copper discharge in the hepatobiliary system, which caused copper to deposit in the liver or other organs and tissues. This is a more noticeable hypothesis.
The presence of abnormal proteins in the cell (10%):
The hypothesis believes that the mutant gene is an abnormal protein in the cell, or the abnormal enzyme causes the protein to be incompletely hydrolyzed to form an abnormal polypeptide. The abnormal protein or polypeptide mainly exists in liver, brain, kidney and other tissues. It has an unusually strong affinity for copper, which hinders the synthesis of ceruloplasmin and causes copper to deposit in the tissue.
Lysosomal defects (10%):
Hepatocyte lysosomal defects, in the early stage, can not concentrate copper to lysosomes, and later can not release copper into the bile and be discharged, resulting in a large amount of copper deposition in the liver or other tissues.
Ceruloalin synthesis barrier (15%):
Matsuda (1974) used radioimmunoassay to measure the normal ceruloplasmin content in the serum of patients, suggesting that the process of copper and proto-copper cytoprotein synthesis was blocked.
The pathological changes of the disease mainly occur in the lenticular nucleus, and the cerebral cortex can also be damaged. The shape of the brain is normal by the naked eye. The striatum is atrophied and brown in the cut surface, and the nucleus often has a cavity. The pathological biopsy shows the shell. The nuclear and caudate nucleus neurons degenerate or disappear, and are replaced by astrocytes, some form typical Alzheimer cells, and then degenerative changes, special staining can be found in the damaged area around the capillaries of copper deposition.
The disease is characterized by steatosis in the early stage of liver cirrhosis, hepatocyte necrosis in severe cases, liver volume reduction in the late stage of cirrhosis, lobular sclerosis, fine nodules on the surface, normal and degraded pathological sections, and irregular hepatocyte area Staggered distribution, and there is connective tissue and small bile duct proliferation.
Prevention
Prevention of mental disorders associated with hepatolenticular degeneration
In order to control and reduce the occurrence of hereditary diseases, it must be based on prevention. Although there is still controversy about the high incidence of close relatives of this disease, it is also necessary to vigorously advocate the avoidance of marriage by close relatives and the implementation of the eugenics protection law. Certainly, those who may or may have caused congenital diseases in future generations should avoid birth. At present, China is formulating a eugenics protection law, prohibiting the marriage of close relatives. "Pro-family-friendly" will increase the incidence of some genetic diseases. It is expressly forbidden to marry close relatives. In addition to receiving the above treatments, the confirmed patients should actively treat various chronic physical diseases and prevent various infectious diseases, and continuously improve their health. At the same time, because the children of the family have the same risk of disease, Easy early genetic counseling services.
In addition, a large number of clinical practice has shown that many patients with hepatolenticular degeneration have undergone regular copper-extraction, symptomatic treatment, clinical symptoms and signs have improved significantly, but after discharge, patients think that symptoms have disappeared, and no medication or less than prescribed The dose of the drug, and did not pay attention to avoid eating foods with high copper content. As a result, the patient was aggravated and re-admitted, and even died. Some patients or their families were superstitious about some qigong and unilaterally stopped taking copper-discharging drugs. The condition is aggravated, and even the patient's life is ruined, and the regrets are late! The patient and his family's compliance with the treatment is often relieved for a long time, has a good quality of life, and even has excellent academic and career achievements. Results.
Patients with hepatolenticular degeneration are more likely to have anxiety and depression. They are disappointed by the unclear speech, clumsy movements, impaired liver function, and disappointment; they feel guilty about the burden of family economy, manpower and material resources. , low mood, unwilling to cooperate with diagnosis and treatment, and even refuse treatment, individual patients resentful of parents due to the hereditary nature of the disease, temper, psychological counseling and treatment is very important, through psychological therapy that is compatible with the patient's psychological abnormalities, Correcting the psychological deviation or abnormal psychology, improving the patient's compliance with the diagnosis and treatment process, is conducive to improving the prognosis, and the social support for the patient also significantly affects the patient's efficacy, family, relatives, friends and other economics for the patient, Material and spiritual support and encouragement can often enhance the confidence of patients to overcome the disease; care and care for patients can often enhance the effectiveness of their treatment, schools, units, medical insurance and administrative departments, and even charities, Funding for patients and their families can solve some of their difficulties, reduce or remove Its worries also help patients get a good prognosis.
Complication
Complications of mental disorders associated with Wilson's disease Complications dysphagia urinary tract infection acne fracture portal hypertension hemorrhagic shock upper gastrointestinal bleeding hepatic encephalopathy hepatorenal syndrome epilepsy
Patients with hepatolenticular degeneration have low immune function, which can be secondary to various systemic infections, and often die from liver failure or concurrent infection. Some patients have symptoms of pseudobulbar paralysis, such as difficulty swallowing, returning to drinking water, etc., especially long-term. Patients in bed are more likely to develop hypostatic pneumonia, urinary tract infections and hemorrhoids, patients with extrapyramidal symptoms, difficulty walking, easy to fall and fractures, patients with Wilson's disease have portal hypertension during decompensated cirrhosis Patients with combined esophageal and gastric varices are prone to acute upper gastrointestinal hemorrhage and even hemorrhagic shock; a small number of livers have reduced detoxification ability, prone to hepatic encephalopathy, hepatorenal syndrome, etc.; some patients merge due to brain damage In seizures, the above-mentioned various complications often aggravate the condition, seriously affecting the treatment effect, and prolonging the hospitalization time of patients. If not timely and accurate treatment, the prognosis of some patients is worse than that of patients without complications.
Symptom
Symptoms of mental disorders associated with hepatolenticular degeneration Common symptoms Dysphagia, moodiness, liver and ascites, intelligent decline, mental retardation, suspicion, irritability, articulation, involuntary movement, mandatory crying
The vast majority of the disease is a slow onset. In the early stage, extrapyramidal symptoms such as limb tremor, swing, increased muscle tone, involuntary movement, etc., which account for about 20% of mental disorders, and children with mental disorders are the first. Symptoms, manifested as emotional abnormalities or decreased learning ability.
1. The majority of patients with onset are slow onset; a few are subacute, the disease progresses faster; the latter is more common in children or juvenile patients, the first symptom is more common with extrapyramidal symptoms, and the first symptom is mental disorder. About 20% of the children, the majority of children with mental symptoms onset, manifested as emotional abnormalities or decreased learning ability.
2. Psychiatric symptoms The symptoms of hepatolenticular degeneration are diversified. In the early stage, there are changes in mood abnormalities or personality traits. In the course of the disease, similar emotional psychotic symptoms or schizophrenia-like manifestations may occur, and in the later stages of the disease, intelligence is used. The decrease is more obvious, and the severe one is demented.
Clinically, most of the psychiatric symptoms occur about 1 year after the onset of neurological symptoms, but they can also behave earlier. The emotional disorders are mainly mandatory crying, emotional instability, moodiness, irritability, euphoria, or apathy, decreased interest, etc. Common (Ouyang Shan, 1990), can also be seen depression, anxiety symptoms, personality and behavioral disorders are characterized by dullness, childishness, ridicule, rash, arbitrariness, lying or stealing, etc., but impulsive behavior is not uncommon, logical thinking is also It can be obviously abnormal, and hallucinations and delusions are rare. As the disease progresses, the mental retardation becomes more and more obvious. In the later stage, there is a serious dementia state. Some patients may have auditory hallucinations and victimized delusions or schizophrenia-like manifestations. The brain parenchyma is severely damaged. At this time, the patient's daily life is completely incapable of self-care, and sexual performance can be manifested.
3. Neurological symptoms and signs The three main signs of this disease are extrapyramidal symptoms, cirrhosis and corneal pigment ring (Kayser-Fleischer ring). In the first symptom, extrapyramidal dyskinesia is very obvious, such as limb tremor, arm Large swings, increased muscle tone or rigidity, involuntary movements, ataxia, etc. are most common, and others such as unclear articulation, drooling and difficulty swallowing are not uncommon.
In most cases, there is a brown-green pigment ring (Kayser-Fleischer ring) on the outer edge of the cornea. Laboratory tests have reduced serum copper oxidase activity, and the detection rate of corneal pigment ring is over 90%. It has important diagnostic value. The ring is brown. Or gray-green, located at the edge of the cornea, easier to see under the slit lamp.
Liver damage is mainly caused by the liver, splenomegaly is the most common, and ascites and cirrhosis occur in the late stage.
The disease is a persistent progressive disease, and most of the prognosis is poor. From the onset of symptoms to death for about 7 to 15 years, it is mostly due to liver failure or concurrent infection.
Examine
Examination of mental disorders associated with hepatolenticular degeneration
1. Serum ceruloplasmin and serum copper decreased, urinary copper and liver copper increased, serum copper oxidase absorbance test in 90% of patients was lower than the normal value of the main biochemical abnormalities of hepatolenticular degeneration, serum ceruloplasmin determination Normal person is 200 ~ 400mg / L (or 0.25 ~ 0.49 OD); children are usually less than 200mg / L; 24h urinary copper output measured significantly increased in children, often up to 100 ~ 1000ug / 24h; cell copper content determination: Normal people are about 20ug/g (dry weight), and children can be as high as 200-3000ug/g.
2. Liver function tests showed alanine aminotransferase (SGPT) and thymol turbidity test (ZnTTT) increased.
3. Patients with very low blood levels are unfavorable factors for copper complexing therapy. If not treated in time, it is often difficult to adhere to copper-extracting treatment. Patients with severe liver and kidney function should also avoid using liver and kidney function. The damaged drug, liver fibrosis index can understand the severity of cirrhosis in patients, and provide objective observation indicators for anti-fibrosis treatment.
4. EEG examination is about 30% to 50% abnormal, mostly mild to moderate, but not specific.
5. The abnormal rate of brainstem auditory evoked potential is higher, up to 90%; the main manifestation is the prolongation of III-VIPL and the decrease of amplitude (Pan Yingfu, 1987), which may be the diffuse deposition of copper in the brain stem, causing brainstem auditory Systemic neuronal degeneration and demyelination changes.
6. Brain CT scans showed that 30% to 40% of patients showed bilateral basal ganglion symmetrical low-density lesions, cerebral cortex and brain stem atrophy can also be seen, as well as ventricular enlargement and lateral fissure widening, magnetic resonance imaging ( MRI) is more clear, showing a wider range of lesions than brain CT scans, not only the enlargement of the ventricles, but also the abnormal signals in the thalamus and brainstem (T1W low signal, T2W high signal).
Electroencephalogram, abnormal changes of EMG suggest brain and peripheral nerves, muscle damage, brain stem evoked potentials before and after treatment can be used to help determine the severity and efficacy of brain damage in patients, B-ultrasound can understand patients Imaging classification of the liver, degree of spleen enlargement, damage to the renal cortex, and presence or absence of cholelithiasis may be helpful in estimating the prognosis. Head CT or MRI, in addition to special lesions in the basal ganglia, may help the disease. In addition to the diagnosis of the cerebral cortex, if the cerebral cortex is atrophy, the frontotemporal softening lesions are formed, patients often have mental retardation, poor academic performance, and should be treated with corresponding brain resuscitation, so the auxiliary examination has important reference value for judging the treatment and prognosis of patients. .
Diagnosis
Diagnosis and diagnosis of mental disorders associated with hepatolenticular degeneration
Diagnostic criteria
Extrapyramidal symptoms, corneal pigment ring and serum copper oxidase decrease in absorbance are three important criteria for the diagnosis of this disease. In addition, liver disease or liver disease, increased urinary copper (>50g) is also diagnostic; and brain CT and MRI For auxiliary diagnostic reference.
1. Evidence of organic damage
(1) Brain lesions, liver lesions.
(2) Age of onset and clear genetic history.
(3) Increased muscle tone, tremor, corneal KF ring, etc.
2. Mental symptoms
(1) Intelligent damage is progressively aggravated.
(2) emotional disorders and personality changes.
3. Laboratory inspection
(1) serum ceruloplasmin and blood copper decreased, urinary copper, liver copper increased, serum copper hydrogenase decreased.
(2) liver function damage SGPT, ZnTTT and so on.
(3) Brain CT and MRI examination showed a low density change in the basal ganglia.
Extrapyramidal symptoms, corneal pigment ring and serum copper oxidase absorbance decreased by 3 items is the key basis for the diagnosis of this disease.
Differential diagnosis
In the differential diagnosis, it should be differentiated from brain diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of the emotional abnormality and the decline of internal driving force, it should be differentiated from schizophrenia and affective disorder. .
1. Different from other brain degenerative diseases, the disease has obvious corneal pigment ring, blood copper changes, CT, MRI examination can be seen that brain basal ganglia changes and clear liver symptoms can be identified.
2. Identification of functional psychosis The mental symptoms of this disease are mainly brain organic lesions, such as personality changes, dementia, etc.; extrapyramidal symptoms, characteristic KF ring laboratory examination can confirm the diagnosis.
Because the disease has three main characteristics, there will be no difficulty in identification.
