Multiple system atrophy is a progressive degenerative pathology of the brain with a predominant lesion of the glial cells of the basal ganglia, cerebellum, and vegetative centers. Clinically manifested by a combination of Parkinsonism with cerebellar, vegetative and pyramidal insufficiency. It is diagnosed mainly according to clinical data, cerebral MRI, orthostatic test, EMG of sphincters are additionally performed. Therapy of multiple system atrophy is symptomatic (vascular, neurometabolic), most cases are resistant to treatment with levodopa drugs.
General information
The term multiple systemic atrophy (MSA) was introduced in 1969. In 1989, cytoplasmic inclusions pathognomonic for MSA were found in oligodendrogliocytes. The concept of multiple system atrophy combines three pathomorphologically similar nosologies, clinically representing a combination of Parkinsonian syndrome, autonomic dysfunction, cerebellar ataxia and pyramidal insufficiency. Previously, specialists in the field of neurology attributed these diseases to the group “parkinsonism-plus”. ISA accounts for 10-12% of parkinsonism cases. The incidence of pathology is 20 times less than Parkinson’s disease. The incidence is 3 cases per 100 thousand population. The debut of clinical manifestations occurs at the age of 50-60 years. The rapid progression of symptoms is characteristic.
Causes
The hereditary nature of MSA is not traceable, current observations do not detect family cases of the disease. However, many researchers assume the genetic determinacy of pathology as a predisposition to the development of MSA when exposed to adverse factors. Some scientists associate the increased risk of MCA with polymorphism in the alpha-synuclein gene. The etiofactors provoking the disease are not precisely defined. One of the conducted studies revealed indications of contact with toxic substances (pesticides, organic solvents) in the anamnesis of 11% of patients with MSA.
Pathogenesis
The mechanism of development is unknown. A feature of degenerative changes is the predominant lesion of glial cells with the accumulation of alpha-synuclein, tau protein and a number of other neural proteins. Pathological inclusions are found in oligodendrogliocytes of suprasegmental motor structures (pyramidal, extrapyramidal system, motor cortex, cerebellum) and autonomic centers of the central nervous system. Along with the defeat of the substantia nigra, the degeneration of the dopamine receptors of the shell occurs, causing the development of “postsynaptic” Parkinsonism resistant to dopaminergic therapy. The morphological picture is characterized by asymmetric atrophic changes in white matter, predominance of oligodendrogliocyte lesions, less pronounced damage to neurons. Multisystem degeneration affects strictly defined brain structures. Each clinical form has its own typical localization of the degenerative process.
Classification
In accordance with modern views on the problems of multiple system atrophy includes three nosological forms. The systematization is based on the clinical features of the disease. Depending on the prevailing syndrome, the following variants are distinguished:
- Striatonigral degeneration (SND). Degenerative changes are most pronounced in the striatum and the substantia nigra. The leading clinical syndrome is Parkinsonism.
- Olivopontocerebellar atrophy (OPCA). Multisystem degeneration extends to the cerebellum, lower olives and bridge. The clinical picture is dominated by cerebellar syndrome. MCA includes only sporadic cases of OPCA.
- Shai-Dreijer syndrome. Progressive vegetative insufficiency with pronounced orthostatic hypotension prevails. A number of authors suggest not to single out the Shay-Dreijger syndrome as the third variant of pathology, since the vegetative symptoms typical for it are observed to one degree or another in all forms of MSA.
Symptoms
The manifestation falls on the age period of 45-60 years. In 60% of patients, MSA starts with motor disorders, in 40% with vegetative symptoms. In the initial period, symptoms of parkinsonism are observed in 60% of cases: bradykinesia, slowness of movement, shuffling gait, hypomimia, monotony of voice. Their distinctive feature is the initial symmetry of manifestations. 30% of patients have cerebellar disorders: postural disorders, dysmetria, adiadochokinesis, intentional tremor. In 10% of cases, cerebellar ataxia is combined with parkinsonism.
Expanded multiple system atrophy occurs with Parkinsonian syndrome in 90% of patients. Cerebellar disorders are poorly manifested due to pronounced rigidity. Their presence is evidenced by the wide setting of the feet when walking, the chanted type of speech, increased tremor in the hand when approaching the goal (for example, when trying to take a cup). Mixed cerebellar-parkinsonian speech disorder in MSA, called dysarthrophonia, is a cerebellar dysarthria combined with monotony and muffled speech. Pyramidal symptoms are characterized by an increase in tendon reflexes and the appearance of stop signs, there are no classic spastic paresis.
The tremor is postural-kinetic in nature, it occurs as a result of a combination of tremulous hyperkinesis and small myoclonic twitches. Possible dystonic manifestations (spastic torticollis, facial hemispasm, focal limb dystonia), in some cases observed already in the onset of the disease. Vegetative insufficiency is manifested by anhidrosis, disorder of pelvic functions, orthostatic collapse with fainting, sometimes – Gorner’s triad, Raynaud’s syndrome. Pronounced cognitive impairments are uncharacteristic.
Complications
Pelvic disorders are complicated by the addition of a secondary infection with the occurrence of ascending inflammation of the urinary system: urethritis, cystitis, pyelonephritis. In the absence of timely treatment, the penetration of infectious agents into the blood with the development of sepsis is possible. Involvement of cranial nerves in the pathological process leads to progressive bulbar paralysis with dysphagia characteristic of it. The latter can be complicated by the ingress of food into the respiratory tract, followed by aspiration pneumonia. Bulbar paralysis of the vocal cords is dangerous by the appearance of asphyxia, which can cause sudden death.
Diagnostics
Multiple system atrophy is diagnosed on the basis of clinical data, the collection of which often requires observation of the patient in dynamics. The diagnosis of probable MSA is established when vegetative insufficiency is combined with at least one of the following syndromes: levodopa-resistant parkinsonism, cerebellar dysfunction. The diagnosis of MSA is opposed by the onset of the disease before the age of 30, a family history, a cognitive disorder (dementia), the presence of another disease that causes similar symptoms. Reliable diagnosis is possible only as a result of pathomorphological examination. In order to confirm the diagnosis, the following studies are necessary:
- Examination by a neurologist. In the neurological status, parkinsonism-plus is revealed — a combination of signs of parkinsonism with additional symptoms (pyramidal, vegetative, cerebellar). Cognitive disorders, signs of focal cortical lesions (agnosia, apraxia) are not determined.
- MRI of the brain. In the initial stage, it may correspond to the norm. Subsequently, atrophic changes of the brain are detected, most pronounced in the cerebellum and subcortical ganglia. MRI allows you to exclude multiple sclerosis, encephalitis, tumor processes.
- Study of the autonomic system. An orthostatic test is performed, confirming a pronounced drop in blood pressure when moving to a horizontal position. To diagnose pelvic disorders, electromyography of the sphincter apparatus is performed.
Multiple system atrophy is differentiated with Parkinson’s disease, vascular parkinsonism, spinocerebellar ataxia. The main difference between MCA and classical Parkinson’s disease is the presence of additional symptoms that go beyond the disorders of the extrapyramidal system, weak effectiveness of dopaminergic therapy. Vascular parkinsonism is characterized by concomitant cognitive impairment. Spinocerebellar ataxias are hereditary in nature, in complex diagnostic cases they are excluded with the help of DNA diagnostics.
Treatment
Since the etiopathogenesis remains unclear, treatment is carried out within the framework of symptomatic therapy. At the initial stage of the disease, levodopa pharmaceuticals are effective in a third of patients, but they aggravate dystonic symptoms and the course of orthostatic hypotension. In the absence of a therapeutic effect, pronounced side effects of levodopa are canceled. Agents that improve the metabolism of cerebral tissues are used: vasoactive, neurometabolic drugs. Treatment of orthostatic dysfunction is carried out by applying compression bandages on the lower extremities, increasing the salt content in the diet, lifting the head end of the bed.
Prognosis and prevention
To date, multifocal atrophy refers to incurable diseases. Symptomatic therapy makes it possible to alleviate the patient’s condition somewhat, but it cannot stop the progression of degenerative processes. The life expectancy of patients does not exceed 7 years. The fatal outcome is caused by complications of bulbar syndrome, intercurrent infections, and cardiovascular insufficiency. Preventive measures have not been developed, since there is no accurate data on the etiology of the lesion.
