Multiple system atrophy: causes, signs, diagnosis, treatment

Multiple system atrophy is a progressive neurodegenerative disease that symptomatically belongs to the “parkinsonism-plus” group of pathologies. It is also classified as a pathology of the autonomic system. Multiple system atrophy is characterized by irreversible damage to certain areas of the brain and part of the spinal cord, which is not associated with the action of certain provoking factors. Treatment is aimed at some relief of symptoms; at the moment there are no proven methods to cure or stop the progression of this disease.

Prevalence

Working with pesticides or other toxic substances increases the risk of developing multiple system atrophy in the future
. According to modern data, multiple system atrophy is a sporadic disease and does not have a clear hereditary predisposition. Rare familial forms of olivopontocerebellar atrophy described in the literature are considered another nosology.

The prevalence of multiple system atrophy in the world population averages 1.9–4.4 cases per 100 thousand population. But these data are approximate and most likely underestimated, which is explained by insufficient diagnosis of the disease in the general medical network. According to statistics from specialized neurological centers, about 8.2% of cases of parkinsonism are caused by multiple system atrophy. And the true prevalence of this disease is most likely at least 4.8–5.5 cases per 100 thousand population.

Prevention methods

Since the causes and pathogenesis of MSA are not fully understood, specific prevention has not been developed. Doctors recommend using respirators and other personal protective equipment when working with neurotoxic substances.

To prevent genetic predisposition, a pregnant woman is strictly prohibited from smoking, using drugs, alcohol, or taking medications with teratogenic and embryotoxic properties. Medicines are prescribed only by a doctor for strict medical reasons.

Etiology

At the moment, multiple system atrophy is considered a disease of unspecified etiology, and specific risk factors have not been identified.

According to studies (PAHanna et all, 1999), previous prolonged contact with toxic compounds was established in 11% of patients. Therefore, a predisposing factor for some people may be working in hazardous industries associated with formaldehyde, organic solvents, and pesticides.

But contact with potentially toxic compounds still cannot be considered as a clear etiological factor. Most likely, we are talking about individual increased sensitivity of the nervous system to substances coming from outside. At the same time, no genetic abnormalities characteristic of this particular disease have yet been identified. It is believed that a polymorphism in the gene for the α-synuclein protein, the pathological accumulation of which is associated with the development of multiple system atrophy, may have a certain significance.

Infectious and endocrine causes of such neurodegeneration are also excluded.

Pathogenesis

Multiple system atrophy is the progressive degeneration and subsequent death of nervous tissue with damage to certain structures of the central nervous system. This process is irreversible, its speed depends little on the treatment performed.

The main cause of cellular damage in multiple system atrophy is the pathological accumulation of α-synuclein (alpha-synuclein) in the cytoplasm and nuclei of neurons and glia. Normally, this protein is produced in small quantities and is concentrated mainly in the presynaptic endings of neurons. It is involved in the regulation of vesicular transport (transfer of substances within cells using special vesicles) and most likely affects dopamine metabolism.

With multiple system atrophy, the structure of α-synuclein changes and the process of its natural metabolic degradation is disrupted. It becomes insoluble and begins to bind to other proteins, forming thread-like structures and entire conglomerates in the cytoplasm. The resulting intracellular inclusions disrupt the process of nerve transmission and probably have a neurotoxic effect.

Initially, gliosis and synaptic dysfunction occur. Soon they are complemented by a reduction in the size and number of axons, increasing and spreading neurodegeneration. Neurons and glial cells begin to die en masse, which macroscopically looks like progressive atrophy of nervous tissue with predominant damage to certain areas.

Although multisystem atrophy is a synucleinopathy, other pathological cytoplasmic inclusions appear in the brain with this disease. Lewy bodies, amyloid tangles and other protein conglomerates are often found in small quantities. This aggravates neurodegeneration, although it does not have a key effect on the clinical picture.

In addition, a number of patients with multiple system atrophy have antibodies to cells of the locus coeruleus (a special subcortical structure of the brain). Their significance has not yet been fully clarified; scientists are exploring the possibility of using these data to improve the accuracy of intravital diagnosis of the disease.

Parkinsonism: clinical picture, diagnosis and differential diagnosis

MMA named after I.M.
Sechenov Clinical picture
Parkinsonism (P) is a syndrome associated with damage to the basal ganglia and their connections. Its main manifestations are lack of movement (akinesia) and increased muscle tone (rigidity). Therefore, P is also called akinetic-rigid syndrome.

.
In its literal sense, the term “akinesia”
means the absence of movements or their impoverishment. Akinesia is manifested by the absence of so-called associated, spontaneous movements - for example, during walking there is no physiological synkinesis in the form of swinging arms or the amplitude of this movement is sharply reduced (acheirokinesis); facial expressions are impoverished - rare blinking is noted, emotional movements are reduced (hypomimia). The concept of akinesia also includes difficulty in starting (initiating) movements. With P, there is also a slowness of voluntary motor acts and their exhaustion, which some researchers call the term “bradykinesia”. For example, when repeatedly squeezing and unclenching the hand, pronation-supination of the arms, tapping the foot on the floor, etc., it is noticeable that the amplitude and strength of the first movements is greater than the subsequent ones. In addition to akinesia, impoverishment of movements is designated by the same term - “hypokinesia” (and syndrome P - hypokinetic-rigid syndrome).

Rigidity

- This is a special type of increase in muscle tone. During passive movements in the joints (flexion-extension, pronation-supination, etc.), the researcher feels constant resistance, the same throughout the entire movement. This sensation is similar to that which occurs when bending and extending a lead pipe (in contrast to another type of increased tone - spasticity, in which the greatest resistance to passive movements is noted at the beginning of the movement. The latter is called the “jackknife phenomenon”). Rigidity in P is determined both in the muscles of the neck and torso, and in the muscles of the limbs. Often, an increase in tone predominates in the flexor muscles, which results in a bent posture of the body with the arms slightly bent at the elbow joints and brought to the body and the legs bent at the knee joints. This position is called the “flexor pose” or “supplicant pose.”

Another characteristic symptom is the "gear wheel"

" It occurs along with rigidity, but can also exist in its absence. During flexion and extension of the joints, the researcher feels uneven resistance to the movement produced, creating the impression of sliding gear teeth interlocking with each other.

At the onset of P, many patients do not notice any abnormalities. Often the patient's relatives and friends first notice decreased facial expression (often interpreting this as a sign of depression), acheirokinesis, and slowness of movement, especially when dressing, eating, and walking. Subsequently, the patients themselves note a decrease in manual dexterity, especially when performing fine movements, such as fastening buttons and tying shoelaces. Habitual activities that require manual dexterity (for example, playing a musical instrument, working on a typewriter or using a computer) are disrupted. Writing disorders occur - handwriting changes, becomes small (micrography), less legible, and at advanced stages completely incomprehensible; difficulties brushing teeth, shaving, etc. Turning in bed is significantly difficult, getting up from a chair or low chair is a problem, patients are often unable to get into and out of the bath, so they can only wash in the shower. Many patients associate these phenomena with “weakness” and make corresponding complaints. Lack of energy and fatigue are also common complaints. Subsequently, eating becomes difficult due to difficulty chewing, and choking occurs when swallowing. Due to akinesia of the pharyngeal muscles, swallowing movements become less frequent, which causes the development of drooling. The latter can be so intense that patients are forced to constantly use a scarf or towel.

Often akinesia and rigidity are combined with tremor

. A typical parkinsonian tremor is very unique and difficult to confuse with another type of tremor. Firstly, in the vast majority of cases it is noted in the arms, less often in the legs. It should be remembered that parkinsonian tremor never begins in the head, and even in very advanced stages of P, head tremor is extremely rare. Trembling of the lower jaw and tongue, on the contrary, can be observed quite often (usually in the later stages). Secondly, parkinsonian tremor is a resting tremor. This means that it is observed (or is most pronounced) in a situation when the patient’s hands lie in a relaxed state on his knees, arms of a chair, table, etc. When making movements, the trembling disappears or becomes much less intense. Thirdly, with parkinsonian tremors, the patient’s hands make circular movements, while the thumb and index fingers move towards each other. This is reminiscent of the movements made when counting money or twisting paper balls. Therefore, parkinsonian tremor is figuratively called a tremor of the “counting coins” or “rolling pills” type. It should be remembered that trembling is not an obligatory component of P. syndrome.

Parkinson's disease. Figure A shows a section of the brain of a healthy person with well-pigmented substantia nigra. Figure B shows a section of the brain of a patient suffering from Parkinson's disease. There is a noticeable lack of pigmentation of the substantia nigra.

P is also accompanied
by imbalance due to a disorder of
the so-called postural reflexes.
The latter ensure uprightness, maintaining stability during various movements (hand movements, walking, sitting down and standing up, bending, etc.), as well as during sudden destabilizing influences (for example, when pushing, stumbling, etc.). Disorder of postural reflexes manifests itself in frequent falls of patients. With milder disorders, falls are not observed, but instability occurs when a slight push to the chest or back occurs. When sitting down on a chair, patients fall onto it, often abruptly leaning back. Postural disturbances also cause the occurrence of propulsions -
one of the characteristic features of P. Propulsions are expressed in the fact that when walking the patient is “pulled forward”, he quickly walks forward in short steps, as if “catching up with his center of gravity”, and is not able to stop abruptly. Often this ends in a fall.

P is a syndrome that can occur in various diseases. The most common cause of P is idiopathic parkinsonism, or Parkinson's disease (PD).

.
P is often observed in other idiopathic degenerative diseases of the nervous system. The latter are often called parkinsonism-plus. This group includes multiple system atrophy, progressive supranuclear palsy, diffuse Lewy body disease, and corticobasal degeneration. Symptomatic P (not associated with a primary degenerative disease of the nervous system)
often occurs .
It includes medicinal, vascular, post-traumatic, post-encephalitic, toxic P, P for brain tumors and hydrocephalus. P also characterizes the clinical picture of some hereditary degenerative diseases of the central nervous system
. These include hepatolenticular degeneration (Wilson-Konovalov disease), spinocerebellar ataxia, familial calcification of the basal ganglia, Huntington's disease, etc. Thus, syndrome P is not synonymous with PD.

Diagnosis and differential diagnosis

Essential tremor

At the first stage of diagnostic work, it is necessary to make sure that the patient really has syndrome P. Most often, essential tremor

(ET) and peculiar gait changes associated with vascular pathology of the brain. Such patients are often misdiagnosed with PD.

ET is a hereditary disease (although sporadic cases are not uncommon) that is characterized by bilateral, symmetrical hand tremors. Unlike parkinsonian tremor, hand tremors in ET are absent at rest and occur during muscle activity. Usually it is most pronounced when the patient stretches his arms in front of him, and can also be present when making voluntary movements, often making everyday activities (for example, eating) difficult. Typically, with ET, there is a “no-no” or “yes-yes” head tremor and voice tremor. The latter may be the first manifestations of ET, and may also occur in isolation in the absence of limb trembling. In contrast to ET, head and voice tremors are generally not found in PD. In contrast, vertical tremor of the mandible at rest and trembling of the legs often occur in PD and rarely in ET. A characteristic sign of ET, which has diagnostic significance, is the disappearance of tremor under the influence of alcohol.

β-blockers also have a good effect on ET. In ET, the “cogwheel” phenomenon may occur, but unlike PD, true akinesia and muscle rigidity are never noted. ET most often affects older people, although it can also occur in very young people.

In the past, vascular damage to the brain was considered the most common cause of P and was even considered a cause of PD. It has now become clear that PD is a primary degenerative disease of the central nervous system and vascular damage does not play an etiological role in its development. Cerebrovascular diseases very rarely cause true P, which was the reason to introduce the concept of “atherosclerotic pseudoparkinsonism” or “vascular pseudoparkinsonism”. Designations such as “lower body parkinsonism” and “parkinsonian ataxia” are also used. Patients suffering from these disorders are typically elderly and often have a history of hypertension. The most characteristic feature of vascular pseudoparkinsonism is a pronounced gait disturbance:

patients take short steps, often spreading their legs wide apart (which is not typical for true P).
Initiation of walking and turning are often difficult, and imbalance and falls also occur. Along with this, any manifestations of P are completely absent in the upper half of the body, arms and face: the patients’ facial expressions are lively, the voice is normally modulated, hand movements are free, and acheirokinesis is absent. Tremor is also not part of the clinical picture. Vascular pseudoparkinsonism can be combined with a decrease in higher mental functions and pyramidal signs (although this is not a mandatory phenomenon). All patients with a similar clinical picture require brain imaging - magnetic resonance imaging
(MRI) or
computed tomography
(CT).

Lewy bodies in Parkinson's disease. In the cytoplasm of the neuron, an eosinophilic nucleus is identified, surrounded by an unstained zone.

The latter, as a rule, reveal multiple small foci of vascular origin (lacunae) in the area of the basal ganglia and/or changes in the white matter of the cerebral hemispheres (leukoaraiosis).
It should be borne in mind that a similar clinical picture can sometimes occur with normal pressure hydrocephalus and less often with tumor lesions of the brain. With normal pressure hydrocephalus, along with walking impairment of the type described above, dementia and dysfunction of the pelvic organs occur (this triad of symptoms is called the Hakim-Adams triad
). MRI of the head typically reveals severely dilated lateral ventricles.

Parkinson's disease

The most common cause of true P (more than 80%), as mentioned above, is PD. This is a degenerative disease in which the main pathological process develops in the nigro-striatal system. In particular, the neurons of the substantia nigra, which produce dopamine, undergo progressive degeneration. As a result, dopamine deficiency develops, which causes clinical symptoms. PD usually affects older people. All the above-described symptoms of P in PD develop fully. PD typically has an asymmetric onset.

At the onset of the disease, symptoms usually affect one side of the body, usually occurring first in the arm (usually the right), then in the leg on the same side.
Often the first manifestation of parkinsonism in the hand is micrographia and acheirokinesis. The hemiparkinsonism stage usually lasts several months, rarely several years. Symptoms then involve the contralateral limbs, as well as the muscles of the trunk and neck. Symptoms of P may appear gradually (for example, akinesia and rigidity in the hand initially appear, then trembling occurs). The opposite situation may also be true. It should be remembered that tremor is absent in 30% of patients with PD at the onset of the disease, and in some cases throughout the entire disease. In this regard, different forms of PD are distinguished
- akinetic-rigid, rigid-tremor and trembling.
At the stage of hemiparkinsonism, the patient’s arm is slightly bent at the elbow joint, does not swing while walking and is pressed against the body. At more advanced stages, when the same changes occur on the other side, and rigidity and akinesia involve the muscles of the trunk and neck, a specific parkinsonian “supplicant pose”
.
Balance problems and falls occur in advanced stages of PD, usually several years after the onset of the disease. PD does not include cerebellar or pyramidal disorders, although there is a tendency for deep reflexes to be increased on the more affected side. Sometimes an extensor position of the foot and toes may be observed, reminiscent of Babinski's symptom, the so-called striatal foot. Symptoms of PD are usually significantly reduced by levodopa
. If parkinsonian symptoms do not respond or respond poorly to sufficient doses of these drugs, the diagnosis of PD should be questioned. With long-term treatment with drugs containing levodopa, almost all patients experience side effects in the form of motor fluctuations and dyskinesias. The latter are expressed as follows: before the next dose of the drug, there is a pronounced increase in P symptoms, often to the point of complete immobility of the patient, and during the period when the concentration of the drug in the blood reaches its maximum values, akinesia and rigidity are completely absent (the “on and off” phenomenon) and are even observed excessive involuntary movements (dyskinesia). The latter are sometimes so pronounced that at first glance at the patient one gets the impression that he has chorea.

The diagnosis of PD is a clinical diagnosis.

Paraclinical research methods usually reveal nonspecific changes. Often, patients with classic PD have vascular changes in the brain. This, however, is in no way evidence of the vascular origin of the disease. It’s just that in most older people, including practically healthy ones, such changes can occur. However, in some cases, atherosclerotic pseudoparkinsonism is superimposed on PD, which may cause a gait unusual for PD and early postural disturbances.

Drug-induced parkinsonism

Drug-induced P may be caused by drugs that act on presynaptic dopamine neurons of the substantia nigra, depleting their dopamine stores (for example, reserpine) or, most often, by antipsychotics that block postsynaptic dopamine receptors, such as phenothiazine derivatives (chlorpromazine), butyrophenones (haloperidol). ), thioxanthines (flupenthixol) and benzamides (sulpiride). These drugs are often used for mental illness. P can also be caused by prochlorperazine (used for vomiting, dizziness and instability), metoclopramide (used for diseases of the gastrointestinal tract, to relieve nausea and vomiting). P may also be due to cinnarizine, which is an atypical calcium channel blocker (used for vestibular disorders). A combination of antipsychotics and antidepressants can also cause P.

In psychiatric hospitals, medicinal P is common. Hypomimia and acheirokinesis are so common among this group of patients that psychiatrists often do not even pay attention to them. Tremor is less common but may have the appearance of classic parkinsonian tremor. Moreover, drug-induced P can be asymmetrical, like PD, and is often completely indistinguishable from PD. One of the signs by which drug P should be suspected is the presence, along with akinetic-rigid syndrome, of violent movements in the form of, for example, oromandibular dyskinesia (involuntary chewing and/or sucking movements) or dystonic phenomena (spasmodic torticollis, oculogyric crises), stereotypy, akathisia (restlessness). Often, severe drug use is accompanied by severe dysarthria and dysphagia. Individual sensitivity to dopamine-blocking drugs is very diverse. Some patients tolerate long-term treatment with large doses of these substances without any problems, while others develop side effects even at small doses. More often

However,
signs of drug-induced P occur when taking large doses of antipsychotics
. Drug-induced P usually develops gradually over days or weeks. In most patients, the first signs appear 3 weeks after the start of treatment. The most common initial signs are hypomimia and insufficient swinging of the arms while walking.

The course of drug P may be different. In most cases, it gradually goes away over several weeks and sometimes days after stopping the drug that caused it. However, it is not uncommon for P to last for months, sometimes almost a year. This situation occurs when using antipsychotic drugs that can be deposited. In rare cases, drug-induced P does not go away and continues to progress despite stopping the causative agent. Such cases are more common among older people. It is believed that in such cases it is not the drug P itself that progresses, but PD begins to develop.

Multiple system atrophy

Multiple system atrophy (MSA) is a sporadic disease that occurs in adults, in which, unlike PD, not only the nigrostriatal system is subject to degeneration, but also many other formations of the central nervous system, including the cerebellum and its connections, pyramidal tracts and formations of the autonomic nervous system (hence the name of the disease). Accordingly, MSA is clinically characterized by a combination of P, cerebellar disorders, pyramidal disorders and progressive autonomic failure

(PVN). P in MSA is caused not only by damage to the cells of the substantia nigra, which causes dopamine deficiency, but also by the degeneration of those postsynaptic receptors with which dopamine must interact.

MSA most often debuts after 50 years of age and, unlike PD, significantly shortens the life expectancy of patients, causing death on average within 9 years from the onset of the first symptoms. P occurs in 90% of patients with MSA, and the dominant clinical sign is in 80%. Cerebellar and pyramidal disorders occur in 50% of patients. Almost all patients show signs of PVN. Autonomic disorders also occur in PD, so one of the key points in the differential diagnosis of MSA and PD is to determine when the signs of PVN began. In MSA, they often occur even before the onset of motor manifestations, often ahead of the latter by several years, while in PD they occur rarely and, as a rule, several years after the onset of the disease. In men, impotence is often the first symptom. A common occurrence among both men and women is urinary incontinence. Often, because of this, patients, before contacting a neurologist, are seen by a urologist and even undergo unnecessary surgical intervention. For comparison: in PD there is only an increase in urination and sometimes an imperative urge to empty the bladder as a result of hyperreflexia of the detrusor muscle. Most people with MSA also experience orthostatic hypotension (OH), which can cause lipothymic conditions and syncope. In patients with PD, OH also occurs, but less frequently and, as a rule, at advanced stages of the disease. Chilliness of the extremities is characteristic - the so-called symptom of cold hands. Approximately 13% of patients with MSA have severe respiratory stridor due to vocal cord abductor paralysis. Stridor initially occurs only during sleep and causes very loud snoring, and as it progresses, it also appears during wakefulness. Vocal cord abductor palsy is so pathognomonic of MSA that, according to some researchers, MSA should be suspected when P is combined with recent severe nocturnal snoring. Syndrome P itself in patients with MSA develops differently than in PD. In particular, MSA P usually begins with a general slowness of movement that affects the arms and legs on both the left and right sides. Although symptoms can also be asymmetrical, the stage of hemiparkinsonism, unlike PD, is usually absent. P phenomena in MSA can begin with dysarthria - the patient’s articulation becomes slower, words are less legible and pronounced less clearly (slurred speech). PD almost never begins with dysarthria. Often, patients with MSA have severe dysphonia - the voice is very muffled and intermittent, often combined with dysphagia, which causes frequent choking while eating. Resting tremor can also occur in MSA, but the classic version of parkinsonian tremor described above, the “coin counting” type, is observed in only 10% of cases. On the contrary, postural trembling and tremor during movement often occur. Irregular myoclonic twitching of the fingers, characteristic of MSA, is often mistakenly regarded as tremor. This disease is also characterized by stimulus-sensitive myoclonus. A number of patients develop so-called disproportionate antecollis

– the head is significantly tilted forward, despite the fact that in general the “bent posture” is not very pronounced. This sign, however, is not considered specific to MSA. It should be remembered that dementia is not part of the clinical picture of MSA. In general, MSA is more malignant than PD and significantly disables patients, often within the first year of the disease.

The clinical picture of MSA may be dominated by one or another symptom. Those cases in which P comes to the fore are referred to as nigrostriatal degeneration

(SND);
if the leading clinical picture is cerebellar syndrome, this condition is called olivo-ponto-cerebellar atrophy
(OPCA);
cases where the core of the clinical picture is PVN are designated by the eponymous name – Shy-Drager syndrome
(SDS).

Despite all the differences, there are often situations when MSA cannot be distinguished from PD. In such cases, one should mainly focus on the effect of levodopa drugs. In PD, these drugs have a dramatic positive effect, while in MSA this effect is less pronounced, short-lived, and often completely absent. This is due to damage to the postsynaptic receptors with which levodopa must interact.

Signs that indicate MSA in patients with P

, the following: rapid progression of symptoms; early onset balance disorders and falls; lack of improvement when treated with levodopa drugs or insufficient effect of these drugs; PVN; pyramidal and/or cerebellar signs; coldness, chilliness of the extremities; contractures; disproportionate antecollis; severe dysphonia, dysphagia or dysarthria; respiratory stridor; irregular tremors or myoclonus.

, special tests for identifying PVN, electromyography of the external ureteral sphincter or anal sphincter can help in diagnosing MSA

which reveals denervation changes in them due to damage to the sacral nucleus of Onuf, from where these muscles are innervated. MRI of the brain often reveals cerebellar atrophy, and with the high resolution of the method (with a magnetic field power of 1.5 Tesla), a hyperintense slit-shaped signal along the outer edge of the putamen is detected in a T2-weighted image. However, none of the listed changes, taken separately, are specific only to MSA, so they should be assessed only in conjunction with the clinical picture. In general, the diagnosis of MSA, like PD, is primarily a clinical diagnosis. During the patient’s lifetime, only “possible” or “probable” MSA is diagnosed on the basis of special diagnostic criteria, and reliable diagnosis is only possible during pathological examination if specific histological markers of the disease are detected - glial cytoplasmic inclusions.

Progressive supranuclear palsy

Progressive supranuclear palsy (PSP), or Steele-Richardson-Olszewski syndrome

, is another variant of degenerations that affects multiple parts of the nervous system, in which the diagnosis of PD is often mistakenly made.
PSP begins later than PD and MSA, most often after 70 years. The average life expectancy after the first symptoms appear is 6–7 years. In this disease, P is characterized by symmetry, akinesia and rigidity in the limbs are not so pronounced, sometimes practically absent, and mainly the axial muscles suffer, i.e. muscles of the trunk and neck. Often, patients with PSP have a slightly thrown back head, although the presence of this sign is not necessary; the head can also be tilted forward or be in a normal position. The first symptom of this disease in most cases is poor balance and falls.
Often, PSP debuts with dysarthria, along with which involuntary deep breaths, similar to a groan, may occur.
The clinical marker of the disease is supranuclear ophthalmoplegia
(NO), or supranuclear gaze paresis, due to damage to specific structures of the midbrain.
OI can be diagnosed when the patient is unable to voluntarily change the direction of gaze, while synkinetic and reflex eye movements are preserved. For example, with PSP, the patient cannot voluntarily move the eyeballs up and/or down, but the Bell
phenomenon - the abduction of the eyeballs upward when closing the eyes;
oculocephalic reflex
(when the gaze is fixed on one point while turning or tilting the head in any direction, the eyeballs are retracted in a friendly manner in the opposite direction).
BUT rarely develops at the onset of PSP; it usually joins other symptoms after an average of 2–4 years. At the beginning of the disease, there may be a pronounced slowing of eye movements, a kind of frozen gaze, burning of the eyes and a feeling of “sand in the eyes” due to the very rare blinking characteristic of PSP. Involuntary forced squinting of the eyes (blepharospasm) is often observed, especially when exposed to bright light or other stimuli. Because of this, some patients are forced to constantly wear sunglasses. so-called apraxia of eyelid opening
, which manifests itself in the fact that it is difficult for the patient to open closed (not necessarily closed) eyes. Due to impaired eye movement, patients may find it difficult to eat because they cannot fully see the plate in front of them. They often drop food on their chest (“dirty tie symptom”). It is difficult for them to go down the stairs; when sitting on a chair, they sit past the seat. All this, combined with a frozen gaze and rare blinking, often gives the erroneous impression that the patient is inadequate, behaves incorrectly, and is inaccessible to contact. Because of this, patients with PSP may sometimes end up seeing a psychiatrist. PSP is also characterized by pronounced pseudobulbar disorders in the form of revitalization of facial axial reflexes; patients often experience a pronounced deepening of the folds on the face (nasolabial, frontal). A pronounced slowdown in mental processes is also characteristic, which is why patients often think for a long time before answering even basic questions.

Thus, although PSP is superficially similar to PD due to the presence of axial muscle rigidity, severe hypomimia and impaired gait, upon careful examination it is revealed that in the distal parts of the limbs PSP is practically absent or very mildly expressed. Classic resting tremor almost never occurs. Levodopa drugs are usually not effective. Autonomic failure is not typical for PSP. MRI of the brain may reveal midbrain atrophy, but this is again a nonspecific finding and the diagnosis of PSP is mainly based on clinical manifestations. Just as in the case of MSA, a diagnosis of “possible” or “probable” PSP is made clinically using specially developed criteria, and a reliable diagnosis is made during pathological examination if specific markers (neurofibrillary tangles) are detected.

Diffuse Lewy body disease

Recently, a new nosological form has begun to be identified that occurs with syndrome P - diffuse Lewy body disease (DLBD). Lewy bodies are intracellular eosinophilic cytoplasmic inclusions that are found in the cells of the substantia nigra in PD and are considered a marker of this disease. In BDTL, they are found not only in the substantia nigra, but in large numbers and widely disseminated throughout the brain. The diagnosis of BDTL is a pathomorphological diagnosis.

Clinically, this disease is characterized by P, which is usually well treated with levodopa, along with dementia with severe visual hallucinations.
Fluctuation in the severity of disorders of higher mental functions
is also typical - mainly due to changes in the ability to concentrate.

Hepatolenticular degeneration (Wilson-Konovalov disease) and other diseases

There are several rarer causes of true or pseudoparkinsonism. One of them, which should always be remembered in the presence of P in people under 45 years of age (including children), is hepatolenticular degeneration, or Wilson-Konovalov disease

.
This is a hereditary disease in which there is a disturbance in the metabolism of copper in the body due to a deficiency of the enzyme ceruloplasmin. As a result, excess copper is deposited in the liver, basal ganglia and around the iris. Wilson-Konovalov disease should be suspected not only if P is present in young people, but also if they have other signs of damage to the extrapyramidal system (for example, dystonia) or mental disorders. Diagnosis is based on detection of copper deposits around the iris using a slit lamp - Kayser-Fleischer ring
.
The latter occurs in 98% of patients at the stage of neurological manifestations. The study of copper excretion in urine and the concentration of ceruloplasmin in the blood
is also of diagnostic importance . The latter, however, in the absence of the Kayser-Fleischer ring and normal copper excretion, has no diagnostic significance. If the situation remains unclear, a liver biopsy or genetic testing is performed. Wilson-Konovalov disease is quite successfully treated with D-penicillamine and zinc supplements in combination with diet.

Toxic P

may occur with manganese intoxication. P caused by the toxin MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) is often encountered, as it selectively affects the substantia nigra, causing the death of dopamine neurons. A toxin similar to this substance is produced during the homemade preparation of certain narcotic substances, so P is often observed among young people suffering from drug addiction. Along with P, pyramidal and pseudobulbar symptoms may be observed.

P occurs in boxer encephalopathy

. It is believed that in this case, the etiological role is played by regularly received multiple craniocerebral injuries. It should be remembered that boxer encephalopathy is practically the only situation where traumatic brain injury plays a role in the development of P. In general, in people who are not involved in boxing, the presence of a history of traumatic brain injury (one or more) is not given etiological significance.

P may sometimes occur with Huntington's chorea

, which usually occurs with pronounced hyperkinesis. This hereditary disease usually debuts in the fourth decade of life, but there are cases of earlier onset. Usually, the so-called juvenile form of Huntington's chorea (Westphal form) occurs with akinetic-rigid syndrome. There are also familial cases of P, including juvenile cases. Therefore, in all patients with P syndrome, collecting a hereditary history is of great importance.

Akinesia and rigidity may sometimes be observed in Alzheimer's disease, Pick's disease,

in which the core of the clinical picture is progressive dementia.
In Alzheimer's disease, memory is primarily affected, and in Pick's disease, personality disorder comes to the fore.
In these diseases, P is often manifested by moderate akinesia, rigidity is less pronounced, and parkinsonian tremor is almost never observed.

Corticobasal degeneration

(CBD) is one of the very rare causes of P. With CBD, akinesia and rigidity are strictly asymmetrical, usually present in one arm and accompanied by myoclonus in it, dystonic phenomena and apraxia.
A characteristic sign of the disease is “alien hand syndrome”
. The latter is manifested by the fact that the patient’s hand, regardless of his desires and intentions, makes various movements, sometimes even quite complex motor acts.

Postencephalitic P

nowadays it practically never occurs. Many cases have been observed since the encephalitis lethargica pandemic at the beginning of the 20th century. Since then, only a few cases have been reported in the literature.

A special endemic form of P is observed on the island of Guam

and in some other places in the eastern Pacific. In these places, there are many cases of P in combination with amyotrophies and dementia (Guam parkinsonism-dementia complex). Pathomorphologically, the brains of these patients look like the brains of patients with PSP. The histological markers are also the same.

What is affected by multiple system atrophy?

Multisystem atrophy is characterized by the involvement of certain structures of the central nervous system, which causes the formation of a typical set of symptoms.

Localization of the main foci of neurodegeneration:

the shell, and its posterior part (striatum) is predominantly affected;
caudate nucleus;
black (nigral) substance;
blue spot;
pontine nuclei (mainly vegetative);
middle cerebellar peduncles with pontocerebellar (pontocerebellar) pathways passing here;
cerebellum: the cortex of the vermis and hemispheres with Purkinje cells located here, the dentate nuclei are less affected;
lower olives;
precentral gyrus, motor and premotor cortex of the cerebral hemispheres;
lateral horns of the spinal cord (in the thoracic and sacral regions);
Onuf's nucleus, which is located in the anterior horns of the sacral segments S2–S4 and is responsible for the innervation of the striated muscles of the anal and urethral sphincters.

In general, the structures of the motor frontal-subcortical circle and autonomic formations are most susceptible to atrophy. The spinal and sympathetic ganglia, thalamus, hypothalamus, and associative cortex of the cerebral hemispheres may also be affected. But the changes here are not typical for multiple system atrophy; they are usually moderate and develop against the background of neurodegeneration and general gliosis characteristic of this disease.

Dopaminergic structures are most affected by multisystem atrophy; glutamatergic and GABAergic neurons are involved to a lesser extent in the process. As atrophy increases, a relative deficiency of acetylcholine and serotonin also develops.

Subatrophy of the brain - the first stage of senile dementia

Before clinical symptoms appear, subatrophic changes develop. There are no external symptoms. The condition is accompanied by a partial decrease in the function of a segment of the hemispheres.

Morphological types of subatrophy:

Frontal;
Frontotemporal;
Parieto-occipital.

The first type is characterized by a decrease in mental activity, loss of speech and motor functions.

Damage to the frontotemporal areas leads to a decrease in a person’s hearing ability, communication functions are lost (difficulty communicating with other people), and the functioning of the cardiovascular system is disrupted.

Subatrophy reduces the volume of gray and white matter. Disturbances in conduction and motor function and fine motor activity occur.

Symptoms

90% of people suffering from this disease develop parkinsonism.
The disease usually debuts at the age of 45–60 years. The characteristic clinical picture of multiple system atrophy includes a complex of symptoms:

Parkinsonism caused by degeneration of the entire striatonigral dopaminergic complex. It occurs in 90% of patients and often imitates the symptoms of Parkinson's disease, which can cause diagnostic errors. Tremor appears, the speed of movements slows down and their amplitude decreases during repetitions, muscle tone increases with the development of rigidity. It is possible that dystonia and dyskinesia may occur, involving the torso, limbs, and facial muscles.
Pyramidal syndrome, the development of which is associated with damage to the thin myelinated fibers of the corticospinal tract (tract). A neurological examination reveals pathological foot signs, a revival of the main tendon reflexes and an expansion of the zones of their induction are noted.
Rapidly progressing autonomic failure. Its versatility and severity is explained by damage to both the segmental and suprasegmental (central) parts of the parasympathetic and sympathetic nervous systems. Multiple system atrophy is characterized by orthostatic hypotension and urinary incontinence (total or partial). Men also develop erectile dysfunction, and women experience decreased sensitivity of the clitoris with anorgasmia. Often there is a tendency to constipation, abdominal discomfort, flatulence, and drooling.
Cerebellar disorders. Characteristic gait ataxia appears (unstable, uneven gait with widely spaced legs), ataxic dysarthria (impaired smoothness and clarity of speech, with a chanted or “explosive” nature of pronouncing words, against the background of a general slowdown and muffled sound production), constant nystagmus, and impaired coordination of limb movements.

Patients with multiple system atrophy have early onset of falls due to a combination of parkinsonism, cerebellar ataxia, and orthostatic hypotension. This may result in injury. Breathing disorders during sleep are also characteristic, which is associated with paresis of the soft palate due to damage to the bulbar group of cranial nerves and paralysis of the abductors of the vocal cords.

Dementia, limb paralysis, and generalized seizures are not common in multiple system atrophy. But some patients at advanced stages of the disease still experience cognitive decline and may develop pseudobulbar syndrome with violent laughter and crying.

Parkinson's disease

This is an atrophic disease of the brain in old and senile age, manifested by extrapyramidal and mental disorders, including dementia.

Occurs with a frequency of 0.08 to 0.2%. 11% of patients show symptoms of dementia. Men get sick more often. The disease begins between the ages of 45 and 75 years, more often at 50–65 years. The main symptoms of the disease are tremor, muscle rigidity, hypokinesia, and paralysis. Obligatory disorders also include permanent and paroxysmal autonomic disorders, as well as personality changes in the form of psychopathization. Half of the patients experience depression, including suicidal tendencies. Querulant tendencies, low-grade delirium, and, in later stages of the disease, hallucinosis, visual or tactile, and states of confusion (delirium) may occur. Visceral hallucinosis is very characteristic. In 15–25% of patients, signs of cognitive deficit are detected, and in elderly patients, in addition, defects in memory, praxis and optical-spatial activity are detected. Pictures of dementia resemble those of Alzheimer's disease. Prospective studies have shown that there is a positive correlation between the ilateral presentation of motor disorders and the risk of developing cognitive deficits.

Predisposition to the disease is transmitted in an autosomal dominant manner with 25% penetrance. The main role in the genesis of symptoms is given to dopaminergic dysfunction of the brain, especially neurons of the substantia nigra. Other brain systems, including cortical structures, may also be involved in the disease process.

The leading place in the complex treatment of the disease is occupied by therapy with L-DOPA and drugs containing it (Madopar, Sinemet, Nakom). These drugs are usually combined with the prescription of anticholinergic drugs (midantan, akineton, parkopan, cyclodol, etc.). There is evidence of positive results from the administration of bromocriptine, parlodel, selegiline, Yumex, and cognitive, which increase dopamine levels in the brain. If psychotic disorders occur, it is recommended to prescribe small doses of antipsychotics while simultaneously reducing the doses of antiparkinsonian drugs and detoxification. The prognosis of the disease is determined by the severity of neurological disorders and its progression.

Back to contents

Clinical varieties

Depending on the combination and prevalence of symptoms, several clinical types of multiple system atrophy are distinguished:

Strionic form with dominant parkinsonism. Its manifestations mask other, less pronounced symptoms. Unlike Parkinson's disease, there is usually no period of hemiparkinsonism with one-sided tremor and rigidity. Trembling can be combined with myoclonic twitching of small muscles, acquiring an arrhythmic and uneven character. Low sensitivity to dopamine-containing drugs is characteristic, and the initial effects of treatment quickly fade away.
Olivopontocerebellar form, with a predominance of cerebellar disorders.
Vegetative form, or Shy-Drager syndrome. Severe and poorly corrected orthostatic hypotension becomes the main factor of disability, leading to social and everyday disadaptation already in the early stages of the disease. It is diagnosed if, in an upright position, systolic pressure decreases by 20 or more mmHg, and diastolic pressure by 10 or more mmHg. (compared to the level in the supine position). Characteristic complaints are fatigue, non-systemic dizziness, presyncope and syncope, acrocyanosis. Orthostatic hypotension can be supplemented by nocturnal arterial hypertension and low pulse adaptability to stress.

Most often, a combination of parkinsonism with autonomic disorders occurs, and as symptoms develop, the type of disease may change. The addition of cerebellar disorders aggravates the condition, having the greatest impact on the ability to move independently safely.

Bibliography

ICD-10 (International Classification of Diseases)
Yusupov Hospital
Lutsky I. S., Evtushenko S. K., Simonyan V. A. Symposium “Parkinson’s disease (clinic, diagnosis, principles of therapy)” // Postgraduate education. — 2011. — No. 5 (43)
Glozman Zh.M., Levin O.S., Lycheva N.Yu. Impaired emotional memory and recognition of emotional states in patients with Parkinson's disease. // Human Physiology, 2003. –N6. –P.55-60.
Golubev V.L. ., Levin Ya.I., Vein A.M. Parkinson's disease and parkinsonism syndrome. M. Medpress, 1999, 415 p.

We work around the clock. Book a consultation by phone +7 (495) 104-20-16 or send a request via the form

Diagnostics

Diagnosis of multiple system atrophy is based on analysis of the clinical picture and data from neuroimaging techniques. In this case, a mandatory sign is the presence of autonomic failure, which is confirmed by special clinical tests and daily monitoring of blood pressure levels. A reliable and accessible laboratory diagnosis of this disease has not yet been developed.

MRI of the brain can reveal a number of characteristic signs:

Changes in the intensity of the signal from the putamen and globus pallidus, atrophy of the putamen, the appearance of a hyperintense (in T2 mode) slit-like stripe along the outer edge of the putamen.
Atrophy of the brainstem and cerebellar structures. Changes affect the vermis, the cerebral cortex, the middle cerebral peduncles, and the base of the pons.

A definite (completely reliable) diagnosis is possible only with a pathomorphological post-mortem examination of the nervous tissue. Signs of the disease are dense glial cytoplasmic inclusions and degenerative changes in the olivopontocerebellar and nigrostriatal region.

Types and classification of brain atrophy

According to the degree of danger, there are two types of atrophic changes in the brain:

Physiological;
Pathological.

The first type is natural. Throughout human development, the death of the umbilical arteries and ductus arteriosus (in newborns) initially accompanies it. After puberty, the tissue of the thymus gland is lost.

In old age, degenerative changes in the genital area occur. In elderly people, cortical destruction and involution of the frontal part appear. The condition is physiological.

Types of pathological atrophy:

Dysfunctional – develops with a decrease in the functional activity of the brain;
Compression – provoked by increased pressure on brain tissue (hydrocephalus, hematoma, copious accumulation of blood);
Ischemic (dyscirculatory) occurs due to narrowing of the lumen of the arteries due to atherosclerosis, blood clots, and increased neurogenic activity. Generalized cerebral hypoxia is accompanied not only by mental dementia and sclerotic intracerebral changes;
Neurotic (neurogenic) is formed due to a decrease in the flow of nerve impulses to the internal organ. The condition is formed due to gradual hemorrhages, the presence of intracerebral tumors, atrophy of the optic or trigeminal nerve. Occurs during chronic intoxication, exposure to physical factors, radiation therapy, long-term treatment with non-steroidal anti-inflammatory drugs;
Dishormonal - occurs against the background of endocrine imbalance in the ovaries, testes, thyroid gland, mammary glands.

Morphological types of brain atrophy:

Smooth – the surface of the brain is smoothed;
lumpy - uneven distribution of areas of necrosis forms a special structure;
Mixed.

Classification according to the extent of damage:

Focal - only isolated areas of atrophic damage to the cerebral cortex can be traced;
Diffuse - spreads over the entire surface of the parenchyma;
Partial – necrosis of a limited part of the brain;
Complete – atrophic changes in white and gray matter, degeneration of the trigeminal and optic nerves.

The nature of morphological changes in the brain is revealed by magnetic resonance scanning. Scanning should be done after the first clinical symptoms appear.

Treatment

A treatment regimen for multiple system atrophy may include:

Levodopa drugs to reduce the severity of parkinsonism are the main recommendation for this disease. They give some effect in the initial stages of the disease, which usually lasts for no more than 1-2 years. Their use can aggravate the manifestations of autonomic failure and does not affect the severity of concomitant myoclonus and dystonia.
Other antiparkinsonian drugs.
Alpha-adrenergic receptor agonists and their precursors for the correction of arterial hypotension.
Non-pharmacological measures for partial compensation of orthostatic hypotension. It is recommended to wear compression hosiery or tightly bandage the limbs with elastic bandages, increase water consumption, and increase the amount of salt in the diet.
Prevention of constipation: eating food with a lot of plant fiber, taking laxatives if necessary, using cleansing enemas.
M-anticholinergics (tolterodine, oxybutynin, etc.) to reduce the severity of urinary incontinence.
Catheterization and self-catheterization of the bladder for severe pelvic disorders with incomplete emptying of the bladder.

Treatment for multiple system atrophy is symptomatic, aimed at mitigating the main manifestations. Pathogenetic therapy has not yet been developed.

Signs

What are the signs of brain atrophy? At the initial stage of the disease, the symptoms are hardly noticeable and can only be detected by close people. The patient develops apathy, lack of desires, aspirations, lethargy and indifference. A lack of moral principles and increased sexual activity are often observed.

As brain cell death progresses, the following signs are observed:

The vocabulary decreases, so a person spends a long time looking for words to describe something.
Intellectual abilities decrease in a short time.
No self-criticism.
Control over actions is lost, and deterioration in body motor skills is observed.

Then, with atrophy, a deterioration in well-being appears and thought processes decrease. A person does not recognize familiar things and forgets about the rules for their use. Elimination of one's behavioral characteristics causes the appearance of the “mirror” syndrome, in which a person begins to copy other people. Then senile insanity and absolute degradation of personality are observed.

The changes in behavior that have arisen do not allow an accurate diagnosis to be made, so to establish the causes of the changes, a list of studies must be carried out. But thanks to the doctor, it will be possible to determine which part of the brain has undergone destructuring. In case of destruction in the cerebral cortex:

thought processes decrease;
the tone of speech and timbre of the voice are distorted;
the ability to remember changes;
fine motor skills of the fingers are impaired.

Symptoms of changes in the subcortical substance are determined by the functions that the affected section performs, so limited atrophy has its own characteristics. With necrosis of the tissues of the medulla oblongata, respiratory failure, digestive failure are observed, and the cardiovascular and immune systems suffer.

If damage to the cerebellum is observed, muscle tone is disrupted and coordination of movements is impaired. With the destruction of the midbrain, there is no reaction to external stimuli. When the cells of the intermediate section die, a violation of the body's thermoregulation and a metabolic failure appear.

With damage to the anterior section, all reflexes are lost. When neurons die, the function of independent maintenance of life is lost, which usually leads to death. Often, necrotic changes appear from injury or long-term poisoning by toxins.

Forecast

Treatment is exclusively symptomatic.
It is based on levodopa and other antiparkinsonian drugs. Multiple system atrophy is a currently incurable disease with a steadily progressive course. Patients' quality of life quickly deteriorates, and 5–7 years after the onset they may no longer be able to move independently and lead a semi-bed lifestyle.

As the disease progresses, complications arise. Most often noted:

recurrent urogenital infection;
bronchopneumonia against the background of increasing respiratory failure;
bulbar syndrome with swallowing disorders;
apnea (stopping breathing) during sleep;
gross disturbances in the functioning of the cardiovascular system;
acute cerebrovascular accidents due to episodes of hypotension or due to nocturnal hypertension.

The life expectancy of patients with multiple system atrophy after the development of the main symptoms is short, although cases of relative stabilization of the condition for several years have been described. Early appearance and rapid progression of autonomic failure worsens the prognosis. Mortality is usually associated with acute vascular disorders, sepsis, pneumonia, and apnea.