multiple system atrophy
Introduction
Introduction to multi-system shrinkage Multiplesystematrophy (MSA) is a group of progressive neurological degenerative diseases of unexplained sporadic adult onset, first named by Graham and Oppenheimer in 1969, mainly involving the extrapyramidal, cerebellum, autonomic, and brainstem. And the spinal cord. The syndrome involves multiple systems, including the striatum nigral line and the olivine cerebral cerebellum, the spinal autonomic nerve center and even the anterior horn of the spinal cord, the lateral cord and the peripheral nervous system. The clinical manifestations are Parkinson's syndrome, cerebellum, autonomic nerve, Different combinations of dysfunction such as pyramidal tract, so it can be clinically classified into three syndromes: striatum substantia nigra degeneration (SND), which is mainly characterized by extrapyramidal dysfunction, mainly characterized by autonomic dysfunction Shy- Drager syndrome (SDS) and sporadic olive pons cerebellar atrophy (OPCA), which is mainly characterized by ataxia. In fact, it is often difficult to separate these diseases. Graham and Oppenheimer summarize the cases with similar clinical signs and symptoms in the literature, suggesting that these three syndromes are different authors' separate descriptions and nomenclatures of an independent degenerative disease of the nervous system. There are only affected parts and severity between them. Differences, clinical manifestations of a system of symptoms appear earlier, or severely affected, other systemic symptoms appear later, or the degree of involvement is relatively light. The results of neuropathological examination confirmed that the degree of involvement of each system was completely consistent with the characteristics of clinical manifestations. Currently, in the MEDLINE database, sporadic OPCA, SDS and SND are classified in MSA. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: syncope, depression, urinary tract infection
Cause
Multi-system atrophy etiology
Cause of the disease (70%):
The etiology is unclear, and inclusion bodies are found in cytoplasms such as glial cells, especially oligodendrocytes. Immunohistochemical studies have found that these inclusion bodies contain immunoreactive cell cycle-dependent kinases, mitogen-activated protein activating enzymes, etc. . The expression of -synuclein was found in the brainstem, spinal cord, cerebellum, and lower olive nucleus, suggesting an important role in the pathogenesis of this disease.
Pathogenesis (15%):
1. Oligodendrocyte cytoplasmic inclusion bodies
Oligodendroglial cytoplasmic inclusion is the histological feature of MSA. Oligodendrocytes play an important role in the pathogenesis. In the past, neuronal degeneration and loss were considered in the pathological changes of MSA. It is primary, which is the basis of pathological changes, and demyelination is secondary. Since the discovery of oligodendrocyte cytoplasmic inclusion bodies, some authors have put forward new views on the pathogenesis of MSA. Oligodendrocytes play an important role in neuronal degeneration in the pathogenesis, on the grounds that silver staining and immunohistochemistry show that intracellular abnormal changes in oligodendrocytes are more pronounced than changes in neurons themselves. Characteristics, Nakazato Yoichi et al. observed that the distribution and density of cytoplasmic inclusion bodies in oligodendrocytes are consistent with the severity of disease degeneration, but some authors believe that the number of cytoplasmic inclusions in oligodendrocytes is related to MSA. There was no significant correlation between the severity of the lesions. Papp et al observed that the higher oligodendrocyte density was in the primary motor cortex, the pyramidal and extrapyramidal system, and the cortical cerebellum. The main function of oligodendrocytes is to maintain the integrity of the myelinated myelin sheath. When the structure of oligodendrocytes is abnormal, its function is inevitably affected. This may be An important cause of myelin loss.
2. Neuronal apoptosis Some people believe that its pathogenesis is related to neuronal apoptosis. There are two types of neuronal death in the nervous system: necrosis and apoptosis. The cell membrane remains intact when apoptotic occurs. The cell volume is reduced, the organelle structure and morphology are present, the lysosomal components are preserved, the nuclear chromatin is concentrated, and the endogenous DNA endonuclease is activated to cause DNA degradation to produce DNA fragments and apoptotic bodies.
3. For abnormal enzyme metabolism, see the cerebellar atrophy of the olive pons.
4. Pathological changes of the gross specimen can be seen in the cerebellum, brainstem and spinal cord atrophy, thinning; microscopic degeneration of the specific parts of the above-mentioned nerve cells, gliosis and demyelination of myelinated fibers, the main site of pathological changes in the pons Cross-fiber, basal ganglia, medullary olive nucleus, vagus nerve dorsal nucleus, blue plaque, cerebellum, lower foot, cerebellar dentate nucleus and hemisphere, midbrain substantia nigra and basal nucleus globus pallidus, caudate nucleus, putamen, Neuronal loss and gliosis in the medial lateral column cells, anterior horn cells, etc.; degeneration of corticospinal tract, loss of sheath, peripheral nerves are mainly demyelinating lesions.
(1) nigrostriatal and blue-spotted lesions: the main cause of Parkinson's syndrome in patients, neuronal loss is 1/3 of the outer side of the substantia nigra pars compacta, and the nigral pigment cells disappear; early striate The body's neurons decreased, with the most severe 2/3 of the dorsal nucleus of the putamen; the globus pallidus was extensively affected, and the blue-spotted neurons were reduced; the above pathological changes were completely consistent with idiopathic Parkinson's disease.
(2) Bridge nucleus and cerebellar Purkinje cell lesions: clinically, OPCA is a prominent symptom. The prominent parts of neuron loss are bridge nuclei, cerebellar Purkinje cells and lower olive nucleus, in which cerebellar midfoot involvement is more obvious, but There are usually no significant changes in cerebellar granule cells, dentate nucleus and cerebellum.
(3) Autonomic neuropathy: The pathological changes of autonomic dysfunction are mainly located in the medial lateral cell column of the spinal cord and the dorsal nucleus of the vagus nerve. The lesions involve both the sympathetic and parasympathetic systems, and the other affected cells have a single ventral ventricle in the brainstem. Amineergic neurons and arcuate nucleus, the Onuf's nucleus in the ventral anterior horn cells of the 2,3 segments of the spinal cord, regulate the autonomic nerve center of the bladder and rectal sphincter, and also have significant damage, and mild neuron loss in the hypothalamus.
(4) oligodendrocyte cytoplasmic inclusions: the most common and characteristic pathological changes are Glyas staining and immunohistochemical staining or modified Bielschowsky silver staining in the white matter with extensive diffuse oligodendrocyte cytoplasm Inclusion body, also known as "oligodendroglial tangle-like inclusion", or "glial cytoplasmic inclusion (GCI)", "small spur An oligodendroglial microtubular tangle, mainly in the shape of a half moon/sickle around a small round nucleus, or a flame argyrophilic structure adjacent to the nucleus. These structures are mainly composed of altered microtubules. Under the electron microscope, the inclusion body is 10~25nm in diameter, and the pipe network structure composed of fine particle-like substances is mainly distributed in the white matter of the brainstem, basal ganglia, cerebellum and cerebral cortex. The number varies from person to person and application is multi-polymerized. Acrylamide gel electrophoresis can separate cytoplasmic inclusions from oligodendrocytes into a variety of protein bands, including -synuclein and B-crystal protein (B-crystal). Lin), tubulin (tubulin) and ubiquitin, these proteins are cytoskeletal proteins. Some authors believe that oligodendrocyte cytoplasmic inclusions may represent synchronous neuronal degeneration, or may be a neuron degeneration. This phenomenon can be used as a special marker for the pathology of MSA, because these inclusion bodies are found in almost all MSA patients diagnosed by pathology and do not appear in the control group. These structures support OPCA, SDS and SND are concepts of the same disease process variation. At present, most reports suggest that oligodendrocyte cytoplasmic inclusions are found only in the brain and spinal white matter of sporadic MSA cases, but not in the central nervous system white matter of simple or hereditary spinal cerebellar degeneration. Conducive to the identification of MSA and hereditary spinocerebellar degeneration, and some authors believe that oligodendrocyte cytoplasmic inclusions, like inclusions in other neurodegenerative diseases, are associated with alpha-synuclein gene mutations. Synucleinopathy leading to alpha-synuclein coding and structural neurobiochemical abnormalities.
Pathological diagnosis of MSA, including at least three lesions such as the putamen and substantia nigra, can be determined. SDS, SND and OPCA pathological changes often overlap each other. For example, SDS cases show significant loss of spinal horn cells, but the latter is clinically autonomous. Neurological dysfunction is not completely consistent, and some cases of OPCA have the same damage. The characteristic pathological manifestations of SND are loss of chitinuclear neurons and deposition of haematin and lipofuscin (1ipofuscin) and nigra degeneration. The lesions are cerebellar cortex and pons, the lower olive nucleus is atrophy, the neurons and transverse fibers are reduced, the olive nucleus has severe neuronal loss and significant gliosis, the cerebellar Purkinje cells are lost, and the granular layer is thinned, especially the ankle. .
Mcleod and Bennet reported that peripheral neuropathological changes were myelinated fibrosis, posterior root ganglion axis mutation, and no unmyelinated fiber changes were seen, but Guo Yuxi et al showed a sural nerve biopsy in 7 patients with MSA complicated with peripheral neuropathy. The myelin fibers are light and moderately lost. The morphology is mainly composed of myelin and thin myelin sheath. There are also hypertrophic nerve changes and regenerated fibers. No axonal degeneration is observed. Some cases of unmyelinated fibers are reduced under electron microscope, while Schwann cells And collagen fibrosis, and collagen sac formation, in line with chronic demyelinating lesions, failed to confirm the evidence of primary degeneration of MSA posterior root ganglion cells.
Prevention
Multiple system shrinkage prevention
1. Rehabilitation spirit, clear heart and soul: prevent multiple system shrinkage to maintain a happy and optimistic mood, avoid excessive mental stress, excessive thinking, should be clear-minded, ignorant, quiet, self-sustaining, open-minded, open-minded Don't care, don't be greedy, keep a quiet and peaceful attitude, especially for middle-aged and older people.
2. Drug conditioning, delaying aging: For those over 50 years old, especially those with a family history of multiple systemic atrophy, it is more necessary to choose to use anti-aging Chinese medicine conditioning at the age of 50 to improve brain cell aging. situation.
3. Balance nutrition, less sputum: adjust diet, diet should be light and rich in nutrition, eat less fat and nourishment products, mainly high protein and high vitamin diet, eat more vegetables and fruits and iodine-containing food, pay attention to Balanced nutrition, ban alcohol and quit smoking, and develop good eating habits. This is also a common way to prevent multiple system atrophy.
Complication
Multiple system atrophy complications Complications, syncope, depression, urinary tract infection
Symptoms of MSA patients are often syncope, complicated by head or systemic trauma, depression, abnormal mental behavior, varying degrees of dementia and seborrheic dermatitis.
In addition, attention should be paid to secondary lung infections, urinary tract infections, etc.
Symptom
Multiple system atrophy symptoms common symptoms cognitive dysfunction hypotension ataxia ataxia cerebellar ataxia
The age of onset of MSA is mostly in middle-aged or pre-senile (32-74 years old), 90% of which is significantly earlier than idiopathic Parkinson's disease in 40-64 years, with a course of 3 to 9 years.
There are three major clinical signs: cerebellar symptoms, extrapyramidal symptoms, autonomic symptoms, 89% of which appear Parkinson's syndrome; 78% have autonomic failure; 50% have cerebellar ataxia, the most common combination is Parkinson's syndrome with autonomic dysfunction or cerebellar ataxia and autonomic dysfunction, in addition, quite a part may have pyramidal tract signs, brain stem damage (extraocular tendon), cognitive dysfunction and so on.
The clinical features are:
1. Recessive onset, slow progress, and gradually worsened.
2. From a single system to multiple systems, the symptoms of each group can appear one after another, overlapping and combining with each other.
SND and OPCA are more likely to evolve into MSA. Xu Xiaoxiang reported that the clinical symptoms of other parts of the nervous system were observed after 3 years of initial symptoms. The degree of damage was compared: autonomic symptoms SDS>OPCA>SND, cerebellar symptoms OPPA>SDS> SND, extrapyramidal symptoms SND>SDS>OPCA, pyramidal tract sign SNDSDS>OPCA, brainstem damage OPCA>SDS.
3. The clinical manifestations are separated from the pathological findings. The pathological findings are often wider than those seen in the clinic. In addition to the complex compensatory mechanism, this separation may be related to clinical examination or clinical manifestations lag behind pathology. Damage related.
In a group of 188 patients with pathologically confirmed MSA, 28% of patients had cerebellum, extrapyramidal, autonomic nervous system and cone system. Another 29% had Parkinson's syndrome and impaired autonomic function. Three signs of cerebellar sign or pyramidal tract sign were recruited; 11% of patients had Parkinson's syndrome and autonomic nerve damage; 10% of patients showed only Parkinson's syndrome.
Sakakibara conducted a questionnaire survey of 121 patients with MSA (48 patients with OPCA, 7 patients with SND, and 56 patients with SDS). The results showed that urinary symptoms (96%) in MSA patients were significantly more common in orthostatic hypotension (43%) (P<0.01). In particular, OPCA and SND, 53 patients with urinary and orthostatic hypotension, the first symptom of the urinary system accounted for 48%, more common than the first symptom of orthostatic hypotension (29%), 23% The patient developed two symptoms at the same time, and the authors concluded that urinary dysfunction in MSA patients is more common than orthostatic hypotension and often occurs earlier.
Because the incidence and prevalence of the disease are low, the clinical manifestations of different parts of the nervous system in the course of the disease are the first symptoms, often with a systematic damage as a prominent manifestation, and the clinical symptoms of other systemic damage are relatively light. Or it will appear in the late stage, making early clinical diagnosis difficult.
Examine
Multi-system atrophy check
1. Upright experiment: The supine position, sitting position and upright blood pressure were measured separately. The blood pressure decreased by more than 30 mmHg within 2 to 3 minutes, the diastolic blood pressure was more than 20 mmHg, and the heart rate was unchanged.
2. Blood biochemical examination: Determination of plasma norepinephrine content, 24h urine catecholamine content determination was significantly reduced.
3. Cerebrospinal fluid examination: except for the individual reports of decreased acetylcholinesterase in cerebrospinal fluid, most patients have normal cerebrospinal fluid.
4. Electromyography: The fibrillation potential can occur in the muscle being examined.
5. EEG examination: the background is mostly slow wave rhythm.
6. Neuropsychological examination: mild cognitive dysfunction, increased depression and anxiety factors.
7. Imaging examination: CT and MRI examination showed cerebral bridge, cerebellar atrophy, manifested as cerebellar vermis, hemisphere and whole cerebellar atrophy, cerebellar sulcus deepened, increased, cerebellar upper pool, pons cerebellum angle pool, cerebellar medullary pool and The cerebellar subarachnoid space is enlarged, the midbrain atrophy, the cerebral pedicle is thinned, the quadrilateral pool, the ring pool and the basal pool are enlarged, the pons, the cerebellum atrophy, the fourth ventricle is enlarged, and the severe lateral ventricle may be bilateral. The third ventricle is enlarged, the lateral sulcus widens and the amount of the brain, and the cerebral hemisphere atrophy of the brain atrophy changes.
MRI is the most valuable diagnostic method. MRI T2-weighted images often show the presence of pathological iron deposits, which are characterized by a decrease in the posterolateral signal of the bilateral putamen and a narrowing of the high signal region normally present between the red and black matter. These changes are seen in all pathologically proven MSA patients. These changes can occur before the patient's symptoms appear, while those with Parkinson's disease do not. In addition, T1 weighted images show atrophy of the putamen signal, cerebellum and The brain stem is atrophied.
PET showed a decrease in basal metabolic rate and decreased fluorodopa uptake in the frontal lobe, striatum, cerebellum and brainstem; striatum uptake of 123I-3-iodo-6-methoxyformamide (123II-IBZM) reduced.
Diagnosis
Multi-system atrophy diagnosis
Diagnostic criteria
In 1999, Gilman et al. of the University of Michigan in the United States proposed four clinical characteristics and diagnostic criteria for MSA:
Clinical features
(1) autonomic failure and/or dysuria.
(2) Parkinson's syndrome.
(3) Cerebellar ataxia.
(4) Corticospinal dysfunction.
2. Diagnostic criteria
(1) Possible MSA: 1st clinical feature plus 2 other features.
(2) Probably MSA: 1 clinical feature plus Parkinson's syndrome or cerebellar ataxia that does not respond well to dopamine.
(3) Confirmed MSA: confirmed by neuropathological examination.
Differential diagnosis
If it is superimposed with other degenerative diseases, pay attention to identification.
1. Orthostatic hypotension When the human body is in a straight steric position, due to the neurological or cardiovascular system dysfunction that regulates and maintains normal blood pressure, the hypotensive state that occurs when the blood pressure changes with the body position cannot be made. Clinical features: blood pressure is erect Sudden decline within 7min, greater than 15mmHg, accompanied by symptoms of insufficient blood supply to the brain, the incidence of orthostatic hypotension accounted for 4% of the total population, 33% of elderly patients.
Mainly divided into: idiopathic (with autonomic nervous system symptoms); secondary (secondary neurological diseases); and postural dysregulation (vasopressor syncope), generally without bladder and rectal dysfunction.
2. Parkinson's disease combined with the results of past autopsy, 5.1% to 11% of patients with primary Parkinson's disease were confirmed to be MSA. In 1995, Wenning reported 370 cases of Parkinson's disease in the UK. In the brain specimens with clinical manifestations of Parkinson's syndrome, 35 patients with pathological diagnosis (9.5%) were diagnosed by neuropathology. The average age of onset of these patients was 55 years old, and they showed Parkinson's syndrome before birth. Affected persons accounted for 97%; cerebellar ataxia accounted for 34%; pyramidal signage accounted for 54%; average survival of 7.3 years (2.1 to 11.5 years), suggesting that patients with clinical diagnosis of idiopathic Parkinson's disease Among them, nearly 10% of patients with pathological findings confirmed that they met the diagnostic criteria of MSA.
3. Also pay attention to the identification of familial OPCA, progressive supranuclear palsy, cortical basal ganglia degeneration, and dementia with Lewy bodies.
