Overview
Although the mental disorders associated with leukemia may vary depending on the primary disease, the mental symptoms are different, but they all have a common feature: the non-specificity of mental symptoms. In general, acute organic mental disorders (disorders of consciousness syndrome) dominate the acute onset of the disease, mostly occurring at the peak of the somatic disease; chronic onset and early disease and recovery tend to be dominated by cerebral debilitating syndromes; in the late stages of the disease, chronic organic mental disorders can occur, characterized by personality changes or intellectual disability. Mental disorders and primary physical illnesses are often parallel in degree, and their clinical manifestations change with the severity of physical illnesses, from one state to another. Various types of mental disorders are often recurrent, intertwined and complex. Symptoms are characterized by lightness of day and heaviness of night.
Etiology
The cause of leukemia-associated mental disorders is still unclear, in which leukemia is the main causative factor of mental disorders, but not the only cause. Biopsychosocial and qualitative factors such as personality traits, age, genetic predisposition and differences in individual nervous system function and body reactivity are all related to the occurrence of mental disorders. The appearance of psychiatric symptoms associated with leukemia is not always proportional to the severity of leukemia. Possible factors of leukemia causing psychiatric disorders are:
1. Central nervous system hemorrhage
Leukemic cerebral hemorrhage is the most common type of neurological damage associated with leukemia, and there is a tendency for it to increase gradually in recent years, accounting for about 32% of the neurological damage caused by leukemia according to some statistics. This may be the main cause of psychoneurological disorders.
2. Leukemia cell proliferation and infiltration
Because most of the anti-leukemia drugs cannot pass the blood-brain barrier, leukemia cells can multiply in the central nervous system and neuropsychiatric disorders occur.
3. CNS infection
Leukemia patients due to normal mature granulocyte reduction and qualitative defects, and anti-leukemia drugs can promote granulocyte reduction, inhibit the cellular and humoral immunity, at the same time a large number of adrenocorticotropic hormone application, can make the body resistance decline, in the prevention and treatment of infections and often the application of a large number of antibiotics, so that some of the flora are inhibited, and prompted the other flora can be a large number of reproduction, constituting a bacterial, viral, fungal infections of the CNS, increasing the number of bacterial, viral, and fungal infections. This increases the chances of neuropsychiatric disorders.
4. Insufficient energy supply
The common pathophysiological change of leukemia associated with mental disorders is the change of diffuse brain energy demand. Due to the metabolic disorders caused by leukemia, the energy supply is insufficient. The brain is very sensitive to energy requirements, and when leukemia, the brain’s demand for energy increases, at this time, the body has a conflict between energy supply and demand, resulting in disruption of normal physiological functions of the brain. This is the main mechanism for the occurrence of such mental disorders.
5. Cerebral hypoxia
Leukemia, especially cardiovascular, pulmonary and cerebral involvement, can lead to insufficient oxygen-carrying capacity, or microcirculation disorders under the influence of harmful factors, etc., which can lead to insufficient cerebral blood supply and oxygenation and impaired cerebral function, which is also an important mechanism for the occurrence of mental disorders.
6. Role of biological toxins
In leukemia, if exogenous substances such as bacteria, viruses, parasites, chemical substances, harmful gases, etc. invade into the body, their toxins or intermediate metabolites directly act on the brain cells, causing damage to the brain cells and brain dysfunction leading to mental disorder.
7. Metabolic disorders
When leukemia occurs, disorders of fluid metabolism and acid-base balance as well as insufficiency of certain vitamins can lead to metabolic enzyme activity disorders, thus affecting metabolism and making energy supply insufficient, which will inevitably affect the brain function and lead to neuropsychiatric disorders.
8. Stress reaction
In leukemia, exogenous harmful factors, including biological stressors and psychological stressors, act on the body and produce a series of physiological and biochemical reactions through neurophysiological, neurobiochemical, neuroendocrine and immune mechanisms. In these reactions, the brain is either directly involved or indirectly affected, resulting in its normal physiological functions being affected, leading to the occurrence of mental disorders.
9. Individual susceptibility
Only a small number of patients with leukemia have leukemia associated mental disorders, suggesting that this may be related to genetic factors and individual qualities or character defects, such as mental disorders caused by physical diseases with a family history of 2% to 8%, higher than the general population; introverted, impatient, stubborn, capricious people are prone to mental disorders in physical diseases; poor stability of brain function, such as the elderly and children are prone to delirium in physical diseases. Delirium occurs.
Symptoms
1. Disorders of consciousness
The most common, accounting for 77% of the acute stage of leukemia, is the main manifestation of brain damage, the initial state of drowsiness, later can develop into lethargy, delirium and coma.
(1) Excited state, patients may be restless.
(2) Hallucination or delusional state, there are obvious hallucinations, hallucinations, delusions of being victimized, relationships mostly.
(3) Depressive state, in addition to emotional pessimism, sometimes with suicidal tendency.
2. Mental disorders have the following characteristics
In acute leukemia, the mental disorder associated with neutrophilic leukemia is the most common and the symptoms are more serious, and the mental symptoms are mainly consciousness disorder. In chronic leukemia, the incidence of mental disorders is lower, the symptoms are milder, and other mental disorders predominate. The relationship between psychiatric disorders and blood picture is not parallel, some patients’ psychiatric symptoms even appear when the blood picture improves, but it is closely related to brain damage. Most cases with neurologic symptoms are accompanied by mental disorders.
Examination
1. Acute leukemia
(1) Blood picture: hemoglobin and platelet decrease progressively, white blood cell count can be increased or decreased, and primitive or naive cells can be seen in classification.
(2) Bone marrow image: active to extremely active proliferation, which may be accompanied by myelofibrosis or myeloid necrosis. According to the different series of proliferating cells, it is classified as acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Their bone marrow characteristics are as follows:
(1) ANLL: ① M1 type (undifferentiated type of acute granulocytic leukemia): ≥90% of the progranulocytes (non-red lineage cells), early granulocytes are rare, and the stages below the mesophilic granulocytes are missing or rare; Auer vesicles can be seen. Auer bodies can be seen. Proliferation of the erythroid and megakaryocytic lineages is suppressed. M2 type (partially differentiated acute granulocytic leukemia): granulocyte lineage is obviously proliferated, Auer vesicles can be seen; erythroid lineage and megakaryocyte lineage proliferation is suppressed. According to the different degree of differentiation of granulocytes is divided into: M2a type: 30% to 90% of the primary granulocytes (non-erythroid cells), 10% monocytes. M2b type: the original and early increase in the number of young granulocytes, but the proliferation of abnormal neutrophilic granulocytes is predominantly, and the nucleus often has a nucleolus, and there is an obvious imbalance in the development of the nucleus and pulp, such cells > 30%. M3 type (acute granulomatous promyelocytic leukemia): predominantly granulomatous proliferation of abnormal promyelocytes, with >30% of such cells (non-erythroid cells); Auer vesicles are easy to be seen; the proliferation of the erythroid and megakaryocytic lineages is suppressed. According to the degree of differentiation of granulocytes, they are divided into: M3a type (coarse granular type): Aniline blue granules are coarse, dense or fused; M3b type (fine granular type): Aniline blue granules are dense and fine. M4 (acute granulocytic leukemia): proliferation of granulocyte and monocyte lineages, and suppressed proliferation of erythroid and megakaryocyte lineages. According to the different morphology of granulocyte and monocyte lineage, there are four types: M4a: primitive and early juvenile granulocyte hyperplasia is dominant, monocyte lineage is ≥20% (non-erythroid cells); M4b: proliferation of primary and juvenile monocytes is dominant, and >20% of the primary and early juvenile granulocytes are non-erythroid cells; M4c: the primitive cells with granulocyte lineage and the morphology of the monocyte lineage is >30% (non-erythroid cells); M4Eo: except for granulocyte lineage with the morphological characteristics of the monocyte lineage, >30% (non-erythroid cells). M4Eo: In addition to the above features, there are thick and round acidophilic granules and darker colored basophilic granules, accounting for 5% to 30% (non-erythroid cells). ⑤ M5 (acute monocytic leukemia): monocyte lineage hyperplasia, with tiny Auer vesicles; erythroid, granulocytic, and megakaryocytic lineage hyperplasia is suppressed. According to the different degree of differentiation of monocytes, it is divided into: M5a (undifferentiated): ≥80% of primitive monocytes (non-red lineage cells); M5b (partially differentiated): >30% of primitive and naïve monocytes, <80% of primitive monocytes (non-red lineage cells); M5b (partially differentiated): >30% of primitive and naïve monocytes, <80% of primitive monocytes.
(6) M6 (erythroleukemia): erythroid lineage >50% with morphological abnormalities, non-erythroid progranulocytes (or primitive + naïve monocytes >30% (non-erythroid cells); if pro-granulocytes or pro-monocytes >5% in blood film, pro-granulocytes or primitive + naïve monocytes in bone marrow non-erythroid cells >20%. Megakaryocytopenia. (vii) M7 (acute megakaryocytic leukemia): >30% pro-macrocytes. Relative inhibition of erythroid and granulocytic proliferation.
(2) ALL: ①L1 type: obvious proliferation of primitive and naïve lymphocytes, with a higher proportion of predominantly small lymphocytes; rounded nuclei, occasional depressions and folds, coarse chromatin, consistent structure, few nucleoli, unclear; little cytoplasm, mildly or moderately alkalophilic. L2 type: primitive and naive lymphocytes are obviously proliferated, with increased proportion, lymphocytes of different sizes, mainly large cells; irregular nuclear shape, depression and folding are easy to see, loose chromatin, inconsistent structure, clear nucleoli, one or more; more cytoplasm, mildly or moderately alkalophilic. (iii) L3 type: primitive and naïve lymphocytes are obviously proliferated, with an increased proportion, but the cell size is more consistent, with large cells predominating; the nuclear shape is more regular, the chromatin is uniformly finely dotted, the nucleolus is clearer in one or more, more obvious, and in the form of vesicles; the amount of cytoplasm is large, dark blue, and the vacuoles are often obvious and in the form of a honeycomb.
(3) Cytochemical staining
(1) Peroxidase and Sudan black staining: acute gonorrhea cells were negative (<3% positive); acute granulocytes were strongly positive; acute monocytes were positive or weakly positive.
(2) Glycogen staining: acute gonorrhea cells were positive (coarse granules or coarse lumps, often concentrated on one side of the cytoplasm); acute granulocytes and acute monocytes were weakly positive (diffuse fine granules); erythroleukemia: young erythrocytes were strongly positive.
(3) Non-specific esterase staining: acute monocytes were strongly positive, and could be significantly inhibited by sodium fluoride (>50%); acute granulocytes were positive or weakly positive, and were mildly inhibited by sodium fluoride (<50%); acute lymphocytes were generally negative.
(4) Neutrophil alkaline phosphatase staining: acute lymphoid leukemia points increased or normal; acute granulomatous leukemia significantly reduced; acute monocytic leukemia may be increased or reduced.
Immunology, cytogenetics and genotyping should be done when available.
2.Mental disorder related examination
Diagnosis
The following points must be present for the diagnosis to be established:
1. a diagnostic basis for leukemia.
2. The appearance of psychiatric symptoms is temporally related to the progression of leukemia. Usually the leukemia comes first and the psychiatric symptoms occur later.
3. Psychiatric symptoms often improve with the remission of leukemia or worsen with its exacerbation.
4. The psychiatric symptoms cannot be attributed to other psychiatric disorders.
5. The severity is such that ① the ability to test reality is diminished; ② social functioning is diminished.
Treatment
1. Symptomatic treatment
Since the existence of mental disorders will affect the treatment of physical diseases, and the improvement of physical diseases needs a process, it is necessary to apply appropriate psychotropic drugs for symptomatic treatment at the beginning of treatment. The principle of psychotropic drug treatment is different from that of functional mental diseases, ① the dose should be small. Hallucinations, delusions, excitement, agitation can be used when the appropriate antipsychotic drugs, but the dose should be small. ② fully consider the side effects and contraindications of the drug, the choice of similar drugs with fewer side effects. Antipsychotics should be used with caution in the case of impaired consciousness. ③The drug should be stopped when the mental symptoms are relieved.
2. Supportive therapy
If consciousness disorder is the main cause, supportive therapy should be implemented at the same time, including energy supply, maintaining water and electrolyte balance and vitamin supplementation.
3. Psychotherapy
Psychotherapy should be carried out on the basis of the above treatments, but it should be carried out after the acute phase has been relieved or after the recovery of the impaired consciousness, when the patient is able to accept it. The means of psychotherapy depends on the type of mental disorder, such as depression, anxiety, fear, etc., verbal explanation is the main; for patients with hallucinations and delusions, the interpretation of symptoms need to be reviewed, and often need to wait for the drugs to take effect, or the patient in a slightly acceptable conditions, or else cause aversion or resistance and refusal of treatment, and the result will be counterproductive; for psychomotor inhibition or reticence, stiffness, loneliness, withdrawal, to strengthen the behavioral training; for those remaining dementia, the treatment should be carried out in the same time. Behavioral training; for those with residual dementia, personality changes psychotherapy often has little effect. However, psychotherapy can reduce the incidence of mental retardation and personality change when used in combination at an early stage.