Ataxia hereditary cerebellar Pierre-Marie. Friedreich's ataxia - hereditary, family

Hereditary cerebellar ataxia of Pierre-Marie is a genetic-familial disease caused by a progressive cerebellar disorder aggravated by damage to the pyramidal tracts. It is characterized by increased tendon reflex, scanned speech, imbalance of motor coordination, impaired vision and oculomotor motility. The pattern of inheritance is autosomal dominant. The mutant gene has a high population: skipping generations is rare.

Among hereditary diseases, spinocerebellar ataxias are in second place in terms of incidence after neuromuscular pathologies. According to statistics, cerebellar ataxia of Pierre-Marie affects 1 person per 200 thousand of the population.

The genetic disorder is asymptomatic in childhood and adolescence and appears in the third decade of life.

Causes and course of Pierre-Marie ataxia

Damage to the functions of the cerebellum is caused by genetic pathology according to the autosomal dominant type of inheritance. To develop ataxia, a genetic disorder inherited from one parent is sufficient.

The cerebellum is the main coordinating center for motor tasks. Its hemispheres are responsible for the coordination of movements, and the cerebellar vermis is responsible for stability and balance.

Pathological signs of the disease are expressed by cerebellar hypoplasia, reduction of the inferior olives and depletion of the pons. Against this background, as a rule, degeneration of the spinocerebral tracts, destruction of cells of the cerebellar cortex and nuclei, degenerative disorders of the medulla oblongata and in the nuclei of the pons occur.

Depending on the concentration of the cerebellar lesion, ataxia is divided into dynamic and static-locomotor. In the first case, pathological disorders are found in the hemispheres, which causes desynchronization of muscle rhythms (dysmetria, scanned speech, involuntary trembling of the torso, head, limbs, etc.). In the static-locomotor form, the worm is affected, which causes a disorder of gait, stability and balance.

Despite its congenital nature, Pierre-Marie's ataxia manifests itself starting at age 20 and older. Provoking factors are infectious diseases (salmonellosis, zoonotic infection, bacterial pneumonia, typhoid or typhus, pyelonephritis, meningitis, etc.). Exogenous causes may include traumatic brain injury, fracture of the pelvic bones or chest, deep burns and intoxication of various natures.

Hereditary cerebellar pathology is characterized by continuously progressive manifestations. Symptomatic therapy does not provide periods of remission. External pathogenic factors in the form of various diseases worsen the patient's condition. Subsequently, the serious condition passes and the typical symptom complex of cerebellar pathology returns.

Symptoms of Pierre-Marie ataxia

The main symptom of a hereditary disease will be neuromuscular motor disorders that are not limited to a single muscle group or specific movements.

Cerebellar ataxia is characterized by characteristic symptoms:

gait disturbance;
static disorder;
tremor of the limbs and body;
muscle twitching;
involuntary frequent oscillatory eye movements;
slow speech;
change in handwriting towards a significant increase in letters;
decreased muscle tone.

Ataxia begins to develop with a disturbance in gait: the patient moves swaying. Sometimes the first symptoms will be shooting in the lumbar region. Then the pathology affects the hands, their trembling is noted.

With Pierre-Marie's disease, paresis of the limbs can be observed, against the background of which tendon reflexes are increased. Often, flexion and extension pyramidal reflexes of the feet are recorded in the patient. Cerebral symptoms are quite common: drooping of the upper eyelid (ptosis), difficulty converging the eyes, optic nerve atrophy.

50% of patients have mental and mental disorders: dementia, mental retardation, depression.

Differential diagnosis of Pierre-Marie ataxia

Of no small importance in diagnosis is the scrupulous collection of information about the genetic morbidity of immediate relatives and the characteristics of the clinical picture.

Diagnostics involves laboratory and instrumental studies:

Electroencephalography (EEG). Detects diffuse delta/theta activity and attenuation of alpha rhythm;
Electromyography. Detects axonal demyelinating disorder of peripheral nerve fibers;
Magnetic resonance imaging. Records morphological changes in the structures of the spinal cord and brain;
DNA test. Determines the genetic nature of ataxia;
Laboratory tests. Allows you to recognize disorders of amino acid metabolism.

An isolated case in a family of cerebellar ataxia requires a more in-depth examination and differential diagnosis. In addition to the above diseases that have the symptom complex of ataxia, an examination is carried out to exclude a cerebellar neoplasm, abscess or hematoma of the brain, cerebellitis and hydrocephalus.

In case of ophthalmological disorders, examination by an appropriate specialist is required.

To confirm a preliminary diagnosis of familial ataxia, genetic consultation is necessary.

Diagnosis of Pierre-Marie ataxia

The symptom complex of cerebellar ataxia is identical to the clinical picture of Friedreich's hereditary ataxia. Therefore, difficulties arise when making a diagnosis.

The main difference is the type of inheritance. Dominant inheritance is characteristic of cerebellar Pierre-Marie disease. The recessive form is characteristic of Friedreich's ataxia. The age at which symptoms of the disease appeared is taken into account. Earlier manifestation is characteristic of the autosomal recessive nature of the disease.

The neurologist examines changes in tendon reflexes, which are increased in the cerebellar form of ataxia and decreased in Friedreich's disease. In addition, Pierre-Marie ataxia is not characterized by bone deformities and loss of sensation.

It is very difficult to differentiate multiple sclerosis and cerebellar ataxia. Both diseases are characterized by pyramidal defects of the feet, oculomotor disorders, and neuromuscular motor disorders. However, with multiple sclerosis, as opposed to ataxia, periods of remission are possible. In addition, deep paraparesis and more pronounced pelvic disorders are hallmarks of sclerosis.

Treatment and prognosis of Pierre-Marie ataxia

The leading doctor in this case is a neurologist. He develops a regimen of conservative therapy, which is aimed at eliminating symptoms and includes:

General strengthening medicinal complex. Drugs that suppress the enzyme cholinesterase (disaggregants), prevent damage to brain neurons (neuroprotectors), and vitamins PP, B and C are prescribed;
Therapeutic exercise and kinesiotherapy are the main rehabilitation measures. The goal of the training is to treat movement, strengthen muscles and alleviate the symptoms of incoordination. For statistical cerebellar ataxia, exercises are selected to train balance. For dynamic ataxia, a training complex is being developed that increases the coordination and accuracy of movements.
Physiotherapy. It is carried out to prevent contracture of the limbs, muscle atrophy, correct gait, improve coordination, and maintain general physical fitness;
Massage, manual and reflexology. Carried out to improve metabolic processes.

The prognosis of hereditary ataxia of Pierre-Marie is unfavorable for work activity. Symptoms progress throughout life, work ability decreases, and mental disorders worsen. The patient becomes disabled.

However, provided that symptomatic therapy is constantly followed and a gentle regimen is followed, the prognosis for life is good.

Pierre-Marie disease is a hereditary cerebellar ataxia.

Reasons

Pierre-Marie disease (or hereditary cerebellar ataxia) is inherited in a dominant manner. Manifestations of the disease are observed at the age of 20-45 years.

Characteristic features are moderate cerebellar hypoplasia, atrophy of the pons, and pronounced degeneration of the cerebellar and pyramidal tracts in the spinal cord.

Symptoms

First of all, pronounced paresis of the extremities (especially the lower ones) attracts attention. At the same time, tendon reflexes are increased, and foot pyramid signs are frequent. Quite often there are cerebral symptoms: ptosis, paresis of the abducens nerves, difficulty in convergence, optic nerve atrophy. At least 50% of patients have mental disorders - memory loss, dementia, depression. In families with cerebellar ataxia, mental retardation is quite common. In this case, deformation of the spine and feet does not occur, and the rest of the clinical picture resembles Friedreich's ataxia, i.e., there is nystagmus, tremors, incoordination of speech, and dysarthria. It should only be noted that in this disease the cerebellar component is more prominent.

The progression of the disease begins unnoticed and quite slowly. Acute infections, physical and mental stress worsen the course of the disease.

Treatment

Symptomatic drugs are used (antidepressants, anticonvulsants and sedatives). For such patients, it is important to correctly distribute the period of work and rest; repeated courses of vitamin therapy (taking vitamins B, PP, C), balneotherapy, and apitherapy are recommended.

Genetically determined, steadily progressive damage to the cerebellum associated with its degenerative changes. Develops after age 20. In the clinical picture, cerebellar ataxia is combined with hyperreflexia, ophthalmological disorders and decreased intelligence. The diagnostic algorithm includes a neurological and ophthalmological examination, MRI of the brain, ultrasound or MRA of cerebral vessels, and genetic counseling. Radical therapy has not been developed; symptomatic treatment is carried out with antidepressants, muscle relaxants, sedatives and nootropics. Exercise therapy, vitamin therapy and hydrotherapy are recommended.

General information

Differential diagnosis of Pierre-Marie ataxia

A neurological examination allows us to exclude other types of ataxia (vestibular, sensitive) and establish its cerebellar nature. In contrast to Friedreich's ataxia, which is characterized by hyporeflexia and decreased muscle tone, the neurological status of patients with Pierre-Marie's ataxia is characterized by increased tendon reflexes and muscle hypertension. Spastic tone in the legs is especially typical, causing foot clonus. Severe skeletal deformations typical for Friedreich's disease are absent.

The symptoms of hereditary cerebellar ataxia and multiple sclerosis may be very similar. A distinctive feature of the first is a gradual, steady progression without periods of remission, however, various infectious diseases and injuries can change the nature of its course, causing significant difficulties in making a diagnosis. In such cases, it is important to carefully study the anamnestic data, identifying the symptom complex typical for multiple sclerosis: more clear pyramidal symptoms (usually lower paraparesis of the spastic type with significant hyperreflexia and pathological reflexes), disappearance of abdominal reflexes, pelvic disorders (urgency), blanching of the optic discs with temporal sides.

Diagnosis of Pierre-Marie ataxia

In the presence of a typical clinic and tracing it over several generations, the diagnosis does not present any particular difficulties for the neurologist. Sporadic cases of the disease require a more in-depth examination of the patient and careful differential diagnosis with other types of cerebellar ataxia, multiple sclerosis, and neurosyphilis.

If necessary, acquired organic pathology should be excluded: cerebellar tumors (

HEREDITARY CEREBELLAR PIERRE-MARIE ATAXIA is a chronic progressive disease, the main manifestation of which is cerebellar ataxia. The disease is hereditary and is transmitted in an autosomal dominant manner. The pathological gene has high penetrance; generation gaps are rare.

The main pathoanatomical sign of the disease is cerebellar hypoplasia, in some cases - atrophy of the inferior olives and pons. Along with this, as a rule, there is a combined degeneration of the spinal systems, reminiscent of the picture of Friedreich's spinocerebellar ataxia.

Clinical picture. The main symptom of the disease is ataxia, which is of the same nature as in Friedreich's ataxia. The disease usually begins with a gait disorder, which is then joined by ataxia in the hands, speech impairment, and facial expressions. Severe static ataxia, dysmetria, and adiadochokinesis occur. Patients may experience shooting pains in the legs and lumbar region, involuntary muscle twitches. There is a significant decrease in strength in the muscles of the limbs, a spastic increase in muscle tone, mainly in the legs. Tendon reflexes are increased and pathological reflexes may be caused. Oculomotor disorders are often observed - ptosis, abducens nerve paresis, convergence insufficiency; in some cases, optic nerve atrophy, Argyll Robertson's sign, narrowing of visual fields and decreased visual acuity were observed. Sensitive disorders, as a rule, are not detected.

One of the characteristic signs of cerebellar ataxia is changes in the psyche, manifested in a decrease in intelligence, sometimes depressive states. The disease is characterized by great clinical variability, both between different families and within the same family. Rudimentary forms of the disease occur in many families; Extrapyramidal symptoms are sometimes observed. Numerous transitional forms between cerebellar ataxia and Friedreich's ataxia have also been described.

The average age of onset of the disease is 34 years, in some families there is an earlier onset in subsequent generations. The course of the disease is steadily progressive. As with Friedreich's ataxia, various infections and other exogenous hazards have an adverse effect on the manifestation and course of the disease.

The differential diagnosis between cerebellar ataxia and Friedreich's ataxia is very difficult. The main distinguishing features between these diseases are the nature of inheritance (dominant in cerebellar and recessive in Friedreich's ataxia) and the state of tendon reflexes, which are absent or decreased in Friedreich's ataxia and increased in cerebellar ataxia. In addition, with cerebellar ataxia there is a later onset of the disease, bone deformations and sensory disorders characteristic of Friedreich's ataxia are rare, and dementia and oculomotor disorders are much more common.

Considerable difficulties may arise when distinguishing cerebellar ataxia from multiple sclerosis, which is also characterized by a combination of cerebellar, pyramidal and oculomotor disorders. Multiple sclerosis is also characterized by a remitting course, greater severity of lower spastic paraparesis, pelvic disorders and blanching of the temporal halves of the optic nerve nipples.

Hereditary cerebellar ataxia- a chronic progressive disease, the main manifestation of which is cerebellar ataxia. The disease is hereditary and is transmitted in an autosomal dominant manner. The pathological gene has high penetrance, skipping generations is rare.

The main pathological sign of the disease - cerebellar hypoplasia, in some cases - atrophy of the inferior olives, cerebral bridge (pons). Along with this, as a rule, there is a combined degeneration of the spinal systems, reminiscent of the picture of Friedreich's spinocerebellar ataxia.

Clinical picture .

The main symptom of the disease is ataxia, which is of the same nature as in the disease. The disease usually begins with a gait disorder, which is then joined by ataxia in the hands, speech impairment, and facial expressions. Static ataxia, dysmetria, and adiadochokinesis are pronounced.

Shooting may be observed pain in the legs and lumbar region, involuntary muscle twitching. Strength in the muscles of the extremities is significantly reduced, and a spastic increase in muscle tone is noted mainly in the legs. Tendon reflexes are increased and pathological reflexes may be caused.

Often develop oculomotor disorders- ptosis, abducens nerve paresis, convergence insufficiency; in some cases, optic nerve atrophy, Argyll Robertson's symptom, narrowing of visual fields and decreased visual acuity were observed. Sensitive disorders, as a rule, are not detected.

One of the characteristic signs of cerebellar ataxia is mental changes, manifested in decreased intelligence, sometimes depressive states.

Computed tomography reveals atrophy of the cerebellum and brain stem. The disease is characterized by great variability in the clinical picture both in different families and within the same family. In many families, rudimentary forms of the disease, sometimes extrapyramidal symptoms, occur. Numerous transitional forms between cerebellar ataxia and Friedreich's ataxia have also been described.

The average age of onset of the disease is 34 years, in some families there is an earlier onset in subsequent generations. The course of the disease is steadily progressive. As with Friedreich's ataxia, various infections and other exogenous harmful factors adversely affect the manifestation and course of the disease.

Differential diagnosis.

In addition, with cerebellar ataxia, the onset of the disease is later, bone deformations and sensory disorders characteristic of Friedreich's ataxia are rare, and dementia and oculomotor disorders are much more common.

Considerable difficulties can arise when distinguishing from which is also characterized by a combination of cerebellar, pyramidal and oculomotor disorders. Multiple sclerosis is characterized by a remitting course, greater severity of lower spastic paraparesis, pelvic disorders and blanching of the temporal halves of the optic nerves.

Treatment is symptomatic.

Use a special system therapeutic gymnastics, aimed primarily at reducing coordination disorders. When prescribing exercises, it is necessary to take into account the possibility of cardiac pathology, in the presence of which appropriate therapy is prescribed.
Shown general strengthening agents (vitamins),
Drugs affecting tissue metabolism (piracetam, aminalon, acephen, cerebrolysin), treatment which should be repeated periodically.