olivopontocerebellar atrophy
Introduction
Introduction to the cerebral atrophy of the pons Olivopontorerebellaratrophy (OPCA) is a chronic degeneration of the central nervous system with cerebellar ataxia and brain stem damage as the main clinical manifestations. In 1891, Menzel first reported two patients with clinical manifestations of Parkinson's syndrome, autonomic failure, and pyramidal tract lesions, consistent with current clinical and pathological changes in multiple systemic atrophy (MSA). In 1900, Dejerine and Thomas named the patient with this group of clinical manifestations as OPCA. Later neurological and pathological studies found that many patients with OPCA have a family-genetic tendency to express autosomal dominant or recessive inheritance. SCA-1 in the class of hereditary spinocerebellar ataxia. Some sporadic cases of OPCA mainly manifested as mild cerebellar ataxia. On this basis, drinking water cough and dysphagia gradually appeared. The course of the disease often combined with obvious symptoms of Parkinson's syndrome and autonomic failure, and a few others. The patient may have one or more of bilateral pyramidal tract signs, limb muscle atrophy, nystagmus or extraocular tendon symptoms. It is currently believed that only patients with sporadic hair are classified as MSA. basic knowledge The proportion of illness: 0.003% Susceptible population: the disease starts in middle age or early age (23 to 63 years old) Mode of infection: non-infectious Complications: syncope, urinary tract infection
Cause
Causes of cerebral atrophy of olivoponics
Biochemical abnormalities (30%):
The biochemical changes of OPCA involve amino acid neurotransmitters and related enzymes, acetylcholine and its enzymatic activity, monoamine neurotransmitters, quinolinic acid-related enzymes, and guanidine, glycerol phosphate ethanolamine, thiamine, etc., especially for these biochemical changes. Further research on amino acid transmitters is of great significance for revealing the etiology and pathogenesis of this disease.
(1) Changes in amino acid neurotransmitters and related enzymes: Some authors found that N-methyl-D-aspartate (NMDA) decreased in the cerebellar cortex of patients, and taurine increased. The former is the excitatory transmitter of olive-centiary fiber, and the latter is the inhibitory transmitter. It is speculated that some factors may cause metabolic disorders, which may cause some neurons to be sensitive to the excitotoxic damage of amino acid neurotransmitters, while the amino acid content is reduced. May be the result of this metabolic disorder, and animal experiments have shown that most of the toxicity of glutamate is mediated by NMDA. Experiments by Bebin et al. show that there is a correlation between decreased brain amino acid levels and neuronal loss. The pathogenesis of OPCA is related to the excitotoxicity of excitatory amino acids.
Some people have measured the amino acid content in the cerebrospinal fluid of patients with OPCA, and found that the level of glutamate is significantly decreased, while the concentrations of alanine, glycine, methionine (methionine) and proline are elevated, and methionine participates in various biochemical processes in the brain. Its pathophysiological role in OPCA needs further study. As an inhibitory neurotransmitter, glycine may act as a glutamate receptor agonist, so it may be related to glutamate metabolism in adult type OPCA. It plays a pathophysiological role.
Some authors have measured glutamate dehydrogenase (GDH) to 1/3 of normal people in white blood cells of patients with OPCA. Most studies have shown that GDH and malate dehydrogenase activity in brain tissue of OPCA patients are normal. However, it was found that the activities of various enzymes such as GDH in peripheral blood leukocytes, lymphocytes and platelets were decreased. Iwatsuji et al found that the total GDH activity and the thermostable GDH activity of blood lymphocytes in OPCA patients were significantly decreased, and lymphocyte GDH activity and glutamate activity were considered. Neuron metabolism, Sorbi et al. measured 7 mitochondrial enzyme activities in platelets of OPCA patients, and found that only 6 patients with dominant hereditary OPCA had only decreased GDH activity, and 8 patients with non-dominant genetic OPCA had GDH and pyruvate dehydrogenation. The activities of the enzyme complex, proline dehydrogenase, succinate dehydrogenase and citrate synthase decreased, which showed that there was no significant change in enzyme activity in brain tissue, but decreased in peripheral blood. Some authors believe that peripheral GDH activity defects do not appear to indicate defects in brain GDH, but some authors indicate that brain changes in pathological examination of patients with OPCA with GDH activity defects are It is selectively affected by neurons that are glutamate-dominated.
(2) Changes in acetylcholine and its enzymatic activity: Xiao Changgu Zhengming et al. measured the activity of acetylcholinesterase (AchE) in cerebrospinal fluid of 16 patients with OPCA by Ellman method, and found that the activity of AchE in cerebrospinal fluid decreased and the bottom of cerebral bridge of Mm, atrophy of cerebellar vermis The degree is positively correlated, and it is believed that the changes in cerebrospinal fluid AchE activity reflect the activity of cerebral cerebellar cholinergic neurons compared with other degenerative diseases.
(3) Changes in monoamine neurotransmitters: changes in the levels of monoamine neurotransmitters suggest that OPCA neuropathy may involve the basal ganglia.
(4) Changes in quinolinic acid-related enzymes: Kish et al. Determination of two metabolic enzymes of quinolinic acid by radiochemical methods in 11 cases of OPCA necropsy: 3-hydroxyanthranilic acid oxidase (3HAO) and quinolinic acid phosphate The activity of ribosyltransferase (QPRT) showed that 3HAO activity in the cerebellar cortex was normal, QPRT activity was significantly increased, and there was no significant change in the activity of the occipital cortex. In this group of patients, the Purkinje cells in the cerebellar cortex were severely lost, and the granulosa cells were Relatively retained, quinolinic acid has much stronger excitotoxicity than glutamate. QPRT is a quinolinic acid catabolic enzyme with increased activity, which may be a protective mechanism for quinolinic acid-sensitive granulosa cells.
(5) Others: Abnormal metabolism of sputum, abnormal metabolism of membrane phospholipids, changes in thiamine may also be involved in the disease. Pedraza et al studied the blood and thiamine levels in cerebrospinal fluid of 29 patients with OPCA, and found no significant change in thiamine levels in the blood. The level of cerebrospinal fluid was significantly decreased. The authors believe that this result can be explained by the severe cerebellar atrophy in patients with OPCA.
In addition, there are reports related to vitamin E deficiency. It is difficult to judge which of these abnormalities are key biochemical changes. In-depth study of amino acid neurotransmitter changes may be important to reveal the etiology and pathogenesis of this disease.
Virus infection (30%):
It has been speculated that an unknown pathogenic factor (probably a lentivirus) may act on the nucleic acid of the neuron. Some scholars have found the viral shell nucleus from the cerebellar cortex of the patient and believe that the occurrence of the disease is related to the viral infection. Dennis passed Electron microscopic observation of two cerebellar biopsy tissues revealed that the cerebellar cortex axons had crystal-like inclusion bodies and braided tubes arranged in a matrix, which resembled some paramyxovirus nucleocapsids and some nuclear inclusion structures of virus infection. It is believed that viral infection may be involved in the pathogenesis of this disease.
Certain viruses are known to cause chromosomal abnormalities and can also be embedded in the host's genome, disrupting the integrity of the nucleic acid, so these viruses may cause cellular protein or enzyme synthesis disorders like an abnormal gene.
Gene defects (15%):
In addition, due to gene mutation, in addition, patients with sporadic OPCA and hereditary OPCA patients are very similar in clinical and pathological manner. Therefore, further research is needed in molecular biology. Eadie pointed out that defective genes affect the chemical structure of Essik embryonic cells. Onset.
Prevention
Olive pons cerebellar atrophy prevention
Prevention of olivopontocerebellar atrophy, should actively prevent and cure certain systemic diseases, especially diseases affecting vascular health, such as hypertension, diabetes, hyperlipidemia, arteriosclerosis, etc., to achieve early detection, early diagnosis, early treatment, This will delay and control the development of the disease. Lightly adjust the lifestyle, improve the nutritional structure, correct bad habits; focus on drugs to control, of course, medication should be gradual and perseverance.
Complication
Oval pons cerebellar atrophy complications Complications, syncope, urinary tract infection
With the development of the disease, the complications of this disease are common with syncope, mental decline, slow thinking, low cognitive ability, decreased ability to use and acquire knowledge, apathy or depression, and secondary lung infections and urinary tract infections. Wait.
Symptom
Olivine pons cerebellar atrophy symptoms common symptoms slow thinking fatigue dysphagia smart decline dizziness urinary incontinence paralysis gait instability muscle atrophy ataxia
Clinically, the disease starts in middle age or early senile (23-63 years old), the average age of onset is (49.22±1.64) years old, male: female is 1:1, insidious onset, slow progress.
Cerebellar ataxia
Cerebellar dysfunction is the most prominent symptom of this disease, accounting for 73%, showing progressive cerebellar ataxia, many early appearances, Dai Zhihua reported the first symptoms with lower limb weakness and ataxia (88%), first performance In the lower limbs, the lower limbs are often soft, fatigued, easy to fall and seek medical treatment, spontaneous activity is slow and inflexible, gait is unstable, balance obstacles, basement widens, and the two upper limbs are unable to move finely, and the movements are clumsy and unstable. Symptoms of cranial nerve damage due to cerebellar dysfunction are dizziness, dysarthria, intermittent language, difficulty swallowing, water cough, nystagmus, intentional tremor, and some cases may have fasciculation of the lingual and facial muscles. There may be facial nerve spasms.
2. Eye movement disorder
It resembles supranuclear ophthalmoplegia (ie, difficulty in upper vision, high muscle tone in the extremities, hyperreflexia, positive or negative pathological signs), which can be manifested as condiction disorders and extraocular muscle dyskinesia (about 60% each), slow eyeballs Slow eye movement or slowing of saccade movement may be a characteristic clinical marker of OPCA. The mechanism is unknown. The astigmatic electroencephalogram shows horizontal gaze nystagmus (about 80%), smooth tracking (ETT) abnormality, and optokinetics. Ocular nystagmus (OKN) abnormalities and cold temperature experimental visual inhibition (VS) failure, may have optic atrophy.
3. Autonomic dysfunction
Such as orthostatic hypotension, flaccid bladder (urinary incontinence or retention), sexual dysfunction and sweating disorders.
4. Pyramid bundle sign
Some authors report that sputum hyperreflexia or extensor sacral reflexes can sometimes be found when examining patients, but the clinical manifestations of pyramidal tract symptoms are mild.
5. Extrapyramidal system symptoms
Some patients have symptoms and signs of extrapyramidal system disease in the late stage. It is reported in the literature that 33% to 50% of patients have Parkinson's syndrome in the late stage, and 8.2% of patients have Parkinson's syndrome as the first symptom. In some cases, limb involuntary movement occurs. Hands and feet move.
Some cases are often accompanied by lightning-like lower extremity pain and deep sensory disturbances; in rare cases, muscle atrophy, scoliosis, high arch and other deformities may be associated.
In this disease, some patients in the late stage showed different degrees of dementia, accounting for 11.11%, and the characteristics of dementia were subcortical. The mechanism is not very clear. Some authors believe that the lesions affect some cell nuclei of the brain stem (red nucleus, Substantia nigra and lower olive nucleus, cerebellum can cause subcortical dementia, clinical manifestations of memory loss, retrospective memory impairment, mental decline, slow thinking, low cognitive ability, decreased ability to use and acquire knowledge, apathy or depression.
Physical examination showed that the patient's speech was vague, nystagmus, dysarthria, difficulty swallowing, eye muscles and hemifacial spasm, occasionally "soft tremor tremor", head and trunk sway, muscle tension decreased, increased or normal, sputum reflex Or disappear, generally can not lead to the pyramidal tract sign, with cerebellar ataxia signs, such as involving the basal ganglia, then the body gear-like rigidity, mask face, static tremor.
Peng Jianping reported MRI findings in 48 patients with OPCA, the main signs:
(1) The shape of the brain stem is thinner, especially the anterior and posterior diameter of the pons is more pronounced. This sign shows the best in the sagittal position of the MR.
(2) The cerebellar volume is symmetrical and small, the cerebellar lobes are widened and deepened, and the hemispherical lobes become thin and straight, showing a dry dendritic shape. This sign shows better in the MR axial or sagittal position.
(3) The cerebral cistern and ventricle are enlarged, and the widening of the anterior pool is most obvious. The cerebellum and brain stem atrophy are often obvious.
(4) Other manifestations: a few may have atrophy of the cerebral cortex.
Examine
Examination of cerebellar atrophy in olive pons
1. Cerebrospinal fluid is normal (individual reports of decreased cerebrospinal fluid acetylcholinesterase).
2. Blood biochemical examination
Determination of plasma norepinephrine content, 24h urine catecholamine content determination can be significantly reduced.
3. Cranial CT showed cerebellum and brain stem atrophy, but CT negative can not rule out the diagnosis of this disease. Some authors believe that CT examination of OPCA patients should include the following two or more signs:
(1) Cerebellar sulcus enlargement > 1.0 mm.
(2) Cerebellar pons pool expansion >1.5mm.
(3) The fourth ventricle is enlarged by >4 mm.
(4) The cerebellum is enlarged on the pool.
(5) The expansion of the anterior chamber and the expansion of the anterior chamber of the medulla are >3.5 mm.
4. Head MRI shows brain stem, cerebellar atrophy, and clear cerebellar sacral atrophy. Some studies have pointed out that in addition to cerebellum and brain stem atrophy, OPCA is often accompanied by a decrease in the signal of the substantia nigra, and less signal reduction of the shell nucleus. The OPCA is distinguished from the SDS and SND. The latter two often have a putamen, especially the posterior part of the putamen. The MRI can clearly show the anatomy of the posterior fossa, which is considered to be the best neuroimaging method for the diagnosis of OPCA. Savoiardo et al. pointed out that the morphological changes of OPCA showed the best on T1WI images, especially the median sagittal image, which was very clear on the display of brain stem and cerebellar atrophy.
5. Brainstem auditory evoked potentials I, II, III wave latency is prolonged.
6. Ocular electrogram
(1) Horizontal gaze nystagmus occurs.
(2) The slow phase velocity of the optokinetic nystagmus is reduced.
(3) The eye tracking experiment is a stepped curve.
(4) The cold temperature experiment sees the failure of inhibition.
Diagnosis
Diagnosis and diagnosis of cerebral pons cerebellar atrophy
Diagnostic criteria
The diagnosis of this disease currently lacks a specific laboratory diagnosis method, mainly relying on clinical manifestations, CT, MRI scan to see the degree of cerebellum and brain stem atrophy, and exclude other diseases.
Diagnostic points:
1. The onset of the disease is in the middle of the middle age, sporadic, and more than 50 years old.
2. Chronic progressive cerebellar ataxia as a prominent clinical manifestation.
3. In addition to cerebellar symptoms, there are multiple systemic manifestations, such as brain stem involvement manifested as supranuclear dyskinesia, slow eye movement; may also involve extrapyramidal system, cone system and autonomic nervous system.
4. Can show progressive decline in intelligence.
5. CT or MRI shows brainstem/brain atrophy.
6. Standard
Because of the clinical symptoms of this disease and multiple system degeneration, SND, SDS has many overlaps, in order to facilitate clinical diagnosis, some authors propose the following diagnostic criteria as a reference:
(1) Chronic progressive cerebellar ataxia with sporadic adult latent onset.
(2) CT or MRI showed brainstem/cerebellar atrophy and excluding cerebrovascular disease, occupying lesions, inflammation and other organic diseases.
(3) supranuclear dyskinesia.
(4) Extrapyramidal involvement.
(5) autonomic dysfunction.
(6) Progressive mental decline.
(7) There is a pathological sign of pyramidal involvement or hyperreflexia; the sense of vibration is reduced.
One or two of the above 7 items are mandatory standards; two of the 3 to 7 items can be used for clinical diagnosis of OPCA, and the scattered OPA and genetic type OPA are difficult to identify. The former has a greater onset age and a faster progression. Spinal cord symptoms.
Differential diagnosis
The diseases that need to be identified are mainly SDS, SND, Parkinson's disease and spinocerebellar ataxia.
