Amyotrophic lateral sclerosis (and ALS syndrome)

Tuberous sclerosis: about the disease and its treatment

Tuberous sclerosis (Bourneville disease) is a rare genetic disorder that can be inherited from a parent or occur as a result of a spontaneous genetic mutation.
One in 6,000 to 10,000 newborns has a mutation in one of the genes that causes this disease. 1 in 6–10 thousand people has a gene mutation that causes tuberous sclerosis.

The disease causes the occurrence of multiple benign tumors (hamartomas), which lead to disruption of the vital systems of the body.

The multisystem nature of tuberous sclerosis is expressed in damage to almost all organs - the brain, central nervous system, kidneys, heart, skin, retina, digestive tract, lungs, etc.

The manifestations of tuberous sclerosis that most affect quality of life are most often associated with its effects on the brain, and include epileptic seizures, developmental delays, including mental retardation, and autism. However, many patients are able to live full independent lives and be professionally in demand, working, for example, as doctors, lawyers, teachers and engineers.

Treatment methods

The main goal of therapy for multiple sclerosis is to prevent further development of the disease, prevent exacerbations and relieve symptoms.

Therapeutic measures involve the use of medications. To combat the consequences, hormonal agents, cytostatics and plasmapheresis are prescribed.

Immunomodulators, beta-interferon, Glatiramer acetate, Natalizumab and some other medications help to exclude the progression of pathology. They are aimed at reducing the risk of relapse, preventing disability and suppressing further spread of plaques.

Various pharmacological groups are used as symptomatic therapy to normalize the functioning of organs and systems, relieve pain, improve motor activity, memory and attention.

If treatment for multiple sclerosis is started in a timely manner, then severe complications can be avoided and the duration of remission can be maximized.

Symptoms

This disease is quite rare and therefore not fully studied. Its signs are varied, many organs and systems are affected, and therefore sometimes an accurate diagnosis can be made only after a comprehensive examination.

The signs of tuberous sclerosis are varied, many organs and systems are affected, and therefore sometimes an accurate diagnosis can be made only after a comprehensive examination.

Usually the first symptoms of the disease are polymorphic formations on the skin. Nodular tubercles with a diameter of 0.5 to 1 cm appear on different parts of the body (usually on the face - nose, cheeks, on the scalp in the scalp), as well as spots in the shape of “leaves”. Such depigmented areas of coffee-milky or whitish color on the skin can appear anywhere on the body. The probability of their appearance in newborns up to one year is 80%, in the second year – up to 100%. The number of areas with uneven depigmentation increases as the child grows older. In 15% of cases, both types of spots can occur - whitish and coffee-milky.

In addition to skin symptoms, signs of this type of sclerosis include: • myoclonic seizures, • tonic-clonic generalized seizures, • hemianopsia.

During myoclonic convulsions, the patient does not lose consciousness; individual muscle groups contract involuntarily and randomly. This pathological shock muscle twitching quickly passes. During generalized tonic-clonic seizures, a person suddenly loses consciousness. With massive spasm, involuntary separation of urine and trauma to the tongue may occur (the patient may bite it).

Hemianopsia is the partial loss of a person’s field of vision with limited space around.

3.Diagnosis of the disease

Diagnosing sclerosis is not always easy. The first symptoms can be very vague and often coincide with signs of other diseases. Diagnosis of multiple sclerosis

is not given if there is no certainty that the patient has had at least two manifestations of the disease (attack). The doctor examines the patient, asks questions about symptoms, and may also perform several special tests. MRI is often used to confirm the diagnosis, as it allows you to see the areas affected by the disease.

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Forms and causes of the disease. Prevention of the disease

There are two forms of tuberous sclerosis: - hereditary - spontaneous (de novo mutations)

Tuberous sclerosis is a hereditary disease. But even if the parents have a mutation in the genes, the birth of a healthy baby is quite likely. To do this, when planning a pregnancy, it is important to undergo a complete examination by a geneticist.

Bourneville disease is an autosomal dominant type. This is a type of inheritance in which a genetic disease manifests itself if a person has at least one mutated gene corresponding to it. The disease can be inherited from either parent with a 0-50% chance. Boys and girls get sick with the same frequency. The disease is not diagnosed immediately - either in infancy (up to 1 year) or in adolescence. Approximately one third of cases of tuberous sclerosis are due to heredity, the remaining two thirds are spontaneous, unpredictable genetic mutations.

Genes on chromosomes 9 and 16 are responsible for controlling the synthesis of hamartin and tuberin, proteins that suppress tumor processes. But when these genes are mutated, the barrier to the pathological growth of abnormal tissue disappears - and tumors form.

If the gene on chromosome 9 is damaged, tuberous sclerosis type I (TSC1) develops. With a mutation on chromosome 16, a diagnosis is made of TSC2 - type II of the disease.

But even if the parents have a mutation in the genes, the birth of a healthy baby is quite likely. Therefore, if there are hereditary diseases in the family, before planning a child, it is necessary to visit a geneticist for consultation and examination in order to exclude the possibility of the birth of a sick baby.

If tuberous sclerosis is suspected, it is necessary to consult a specialist (neurologist, dermatologist, geneticist, ophthalmologist, nephrologist, cardiologist, gastroenterologist, etc.) as soon as possible and undergo a comprehensive examination to reduce the risk of complications.

Fever

Avoid exposure to heat. At high ambient temperatures, the functioning of the nerves and brain can be disrupted, which will intensify existing neurological disorders. It is recommended not to be in the open sun, in a hot room, not to visit a bathhouse or sauna, or to take a hot shower. To create a comfortable environment, use air conditioning (at home, in a car, when calling a taxi, indicate this need). If you are unable to avoid the effects of elevated temperature, remember that the increase in symptoms is temporary and there is no permanent damage to your nervous system.

Diagnostics and types of examination

When you first contact a doctor, you should tell about how long ago the first signs of the disease appeared, what kind of complaints are bothering you (convulsions, nodules on the tongue, skin, its depigmentation, partial blindness with the inability to see some part of the space), as well as whether there were any such illnesses in someone's family.

Mandatory examinations:

• General blood analysis
• General urine analysis
• Radiography
• Consultations with neurologists, ophthalmologists, dermatologists and geneticists
• MRI and CT
• EEG and ECG
• Echocardiography
• Ultrasound

General clinical tests - blood and urine - are required. If there is pathology in the blood test, the level of urea and creatinine may increase, since they are products of protein metabolism and indicate kidney function. If the kidneys are affected by the disease, blood may appear in the urine (hematuria).

Radiography is also prescribed to detect tumor growths in tissues.

At an appointment with a neurologist, you need to draw the doctor's attention to disturbing attacks of seizures, headaches, vomiting, changes in behavior and intellectual disorders.

Today it is impossible to undergo a comprehensive examination without tomography - magnetic resonance imaging (MRI) and computer computed tomography (CT). Thanks to their use, specialists can: • engage closely in a layer-by-layer study of the structure of the brain; • identify tumors in it (they are more often found at the border of gray matter with white matter); • detect signs of abnormal development of brain matter and areas with reduced density of its nervous tissue; • identify accumulations of cerebrospinal fluid (cerebrospinal fluid that supplies the brain with nutrition and metabolic processes) in the cavities of the brain.

Using electroencephalography (EEG), specialists assess brain activity in different areas. This method of examination makes it possible to search for foci with increased impulses that provoke convulsive attacks in tuberous sclerosis.

To determine whether there are growths in the heart muscle (rhabdomyomas), the patient is sent for echocardiography.

Electrocardiography (ECG) is recommended for all patients because Cardiac arrhythmia, although rare, can lead to sudden death. Ultrasound (ultrasound) will help check for the presence of kidney tumors and cysts in their tissue.

The ophthalmologist will conduct a series of examinations: • using a slit lamp (biomicroscopy) to examine the fundus of the eye; • using tables to check visual acuity (visometry); • perimetry to determine the edge of the visual field to identify defects in it; • assessment of the condition of the retina, the fundus of the eye and its vessels, the disc (nipple) of the optic nerve (ophthalmoscopy) to determine the presence of pathological changes (swelling of the nipple, retinal hamartomas).

At your appointment, the dermatologist will definitely pay attention to the presence of formations on the skin in the form of reddish nodules around the nails, tubercles, growths, fibrous plaques and areas with insufficient pigmentation.

A comprehensive examination cannot be done without the help of a geneticist, who will prescribe a special test to identify mutational changes in the genes of the 9th and 16th chromosomes (TSC1, TSC2). If necessary, a consultation with a neurosurgeon or psychiatrist is prescribed.

Multiple sclerosis

Morphologically, multiple sclerosis (MS) is characterized by numerous foci of demyelination in the brain and spinal cord, which differ from normal nervous tissue in color and consistency.
Microscopically, this is a picture of periaxial demyelination of nerve fibers. Microglia of the connective tissue grow, and glial scars form, replacing the dead tissue. This forms an inactive MS plaque, which is dense to the touch and has a grayish tint. Despite many years of research, the cause of MS is still unclear. Conventionally, the study of etiological factors can be divided into two groups.

1. Study of the genetic factor. MS is a multigene disease involving loci of varying significance in different ethnic groups. The manifestation of a genetic predisposition to MS also depends on external factors.
2. Study of the external factor. MS occurs more often in large cities with a population of more than 1 million inhabitants, as well as in people who have numerous contacts with other people due to their profession. A high level of morbidity and its severe course is observed in areas with developed industry and a polluted environment.

External etiological factors also include the infectious factor of exogenous intoxication.

• MS Clinic

In the variety of clinical manifestations of MS, two groups of symptoms can be distinguished.

The first group includes the most common classical symptoms, which are a direct manifestation of damage to the brain pathways. This also includes symptom complexes that reflect the characteristics of the clinical manifestations of a multifocal demyelinating process. The second group includes rare clinical manifestations of the disease.

• Typical clinical symptoms

Symptoms of damage to the pyramidal tract. This is the most common lesion in MS, accounting for 85-97%. Depending on the location of the lesion, hemi- or paraparesis occurs, and less commonly, monoparesis. The lower extremities are most often affected, less often the upper; they get involved later. Clinically manifested are pathological pyramidal reflexes, increased periosteal and tendon reflexes, decreased or complete absence of abdominal reflexes. The last symptom is a subtle, early manifestation of interest in the pyramidal tract lesion.

Central paresis and paralysis are accompanied by changes in muscle tone - both spasticity and hypotension, dystonia. One of the problems for patients with MS seems to be an increase in tone of the spastic type. As a rule, it is observed in patients with lower paraparesis.

Symptoms of cerebellar damage. Occurs in 62-87% of cases. Patients complain of impaired gait and balance. Clinically manifested by impaired coordination and decreased muscle strength. Dynamic and strategic ataxia, dysmetria, asynergia, intentional tremor, scanned speech, and megalography are common. Characteristic is a paroxysmal increase in ataxia to the point of inability to walk.

Symptoms of damage to the cranial nerves. Observed in 36-81% of cases. Foci of demyelination often form in the intracerebral parts of the nerves, so symptoms of both central and peripheral damage to the motor cranial nerves, most often the III, V, VI, VII pairs of nerves, may be observed. The most common clinical symptom of brain stem damage is oculomotor disturbances that cause double vision.

A characteristic symptom is discoordinated movement of the eyeballs, under-direction of the eyeballs to the sides, and sometimes mild ptosis is observed. Changes in pupillary reactions are rare. One of the main manifestations of MS is nystagmus as a consequence of damage to the upper parts of the trunk.

Symptoms of sensory impairment. Occurs in 56-92% of patients. One of the most common symptoms of MS is changes in deep and superficial sensation. More often in the early stages there is a slight disorder of pain sensitivity and dysesthesia in the distal extremities. A feature of sensitivity disorders is that patients cannot clearly describe them and often complain of numbness and burning in the extremities.

Symptoms of visual impairment. Occurs in 36-52% of cases. Visual disturbances include decreased visual acuity, as well as changes in visual fields. Often retrobulbar neuritis is the first symptom of the disease. An ophthalmological examination reveals central scotomas, narrowing of visual fields, and a transient decrease in visual acuity.

Symptoms of dysfunction of the pelvic organs. Observed in 26-53% of cases. This is one of the first and most common symptoms of MS. Urinary disorders of the central type manifest themselves most early; there can be both frequency and urinary retention, as well as imperative urges. In later stages it is usually urinary incontinence. In men, there may be a decrease in potency associated with damage to the spinal cord due to demyelination.

Neuropsychological symptoms. Occurs in 65-95% of cases. They may include memory impairment, mental acuity, and all sorts of emotional disturbances. Depression with states of apathy and anxiety deserves special attention. Often with MS there is euphoria, combined with a decrease in intelligence. Women experience hysterical reactions, which is the reason for the discrepancy between the patient's complaints and objective neurological symptoms.

• Rare clinical manifestations

1. Paroxysmal states 5-17%. These may include brief sensory and motor disturbances, tonic spasms, hemifacial spasms, acute attacks of hiccups and yawning.
2. Autonomic disorders. These include sympatho-adrenal crises, attacks of hypotension, and bradycardia.
3. Symptoms of damage to the peripheral nervous system. This includes polyneuropathy syndrome, as well as the development of muscle atrophy.

• MS in childhood

The age limits for MS are currently being revised. There are reports of the development of the disease in both elderly and senile age. But the problem of the disease in childhood is more pressing.

Cases of the development of MS at the age of two have been described, and in the materials of the Research Institute of Neurology of the Academy of Medical Sciences, the earliest onset of the disease is noted at the age of 11-15 years. Diagnosis of MS in childhood is even more difficult due to the variety of syndromic variants and types of course.

• Modern methods of diagnosing MS

The polymorphism of MS greatly complicates early diagnosis. The number and range of errors remain significant. The most important diagnostic criteria:

• onset of the disease at a young age;
• polymorphism of clinical manifestations;
• flickering of “symptoms” even throughout the day;
• undulating course of the disease.

The optimal diagnostic algorithm has been determined for examining patients with suspected MS:

1. Clinical picture, identification of neurological damage.
2. MRI of the brain, spinal cord.
3. Ophthalmological examination.

Pathological changes on MRI are most often localized in the periventicular region. Rarely, foci of demyelination are visible in the brainstem and cerebellum. There is no clear connection between the number of demyelination foci and the severity of the disease.

• Differential diagnosis of MS

In the initial stages, MS should be differentiated from VSD, neurotic disorders, Meniere's syndrome, retrobulbar neuritis, tumors of the brain and spinal cord, cerebellum, disseminated encephalomyelitis, and degenerative diseases of the nervous system. Spinal forms of MS may present similarly to spinal cord tumors. But the symptoms of MS in the initial stages are characterized by less severe paresis, sensory and pelvic disorders. MS differs from Strumpel's disease in the presence of signs of damage to other parts of the nervous system.

• Flow options and forecast

The course of MS is chronic. Most clinics use the following terms to refer to periods of illness.

1. Exacerbation: the appearance of a new symptom or group of symptoms after the patient's condition has remained stable for a month.
2. Remission: a clear improvement in the patient’s condition in the form of a decrease in the severity or disappearance of a symptom or group of symptoms, which lasts at least a day.
3. Chronic progression: an increase in the severity of the disease symptom within two months without stabilization of the condition.
4. Stabilization: absence of exacerbation, progression and remission for at least one month.
5. Remitting course: a course with exacerbations and remissions without signs of progression. There are also mild and malignant forms of MS. The first includes a long course (10-15 years or more) of the disease, accompanied by minimal disturbances. With a malignant course, the patient becomes completely disabled within the first five years.

If people over 40 years of age fall ill, and the disease is remitting in nature with the first remission of at least a year and the duration of the first exacerbation of no more than three months, then we can talk about a favorable disease process. All other cases are considered unfavorable.

• MS treatment

Treatment of MS consists of measures aimed at combating demyelination of the central nervous system and symptomatic therapy. Methods aimed against demyelination include the treatment of exacerbations and chronically progressive disease. Some types of therapy can reduce the frequency and severity of relapses. Since none of the known methods causes remyelination, the main task is to slow down or stabilize the growth of the neurological defect.

Corticosteroids and ACTH drugs remain the drugs of choice for the treatment of MS. It is believed that their use is especially indicated during acute episodes and frequent relapses.

These agents are designed to limit the inflammatory process and the degree of myelin destruction.

One treatment for MS is plasmapheresis, usually in combination with hormone therapy. A positive effect is observed during treatment with betaferon. It is effective mainly in relapsing-remitting forms of MS. It is prescribed to reduce the frequency of exacerbations, as well as to reduce the rate of progression of the pathological process. This suggests that betaferon does not cure completely, but only stops the progressive development of the disease.

As for the effectiveness of biological drugs, it is difficult to judge this, since there are no objective laboratory markers to assess the activity of the demyelinating process.

Symptomatic treatment of MS includes treatment of spasticity and flexor spasms. In these cases, muscle relaxants are used.

During the period of remission, restorative, nootropic, vascular therapy is prescribed, and physical activity is encouraged.

For the purpose of prevention, patients should avoid injections, intoxication, overwork; climate change is not recommended; hyperinsolation is contraindicated. We are discussing the issue of pregnancy and childbirth, although more often in the literature there is evidence of exacerbation of the disease during this period.

Clinical case

A 32-year-old woman complained of transient weakness in her left arm and leg for a year. This symptom had almost completely disappeared two months before hospitalization, but during the last week before hospitalization the left leg became so weak that the patient often stumbled when walking. Over the past three months, there has been intermittent urinary incontinence. At the age of 18 years, there was an episode of diplopia, which spontaneously regressed.

A neurological examination revealed pallor of the temporal half of the left optic nerve, weakness in the left hand when shaking, increased reflexes on the left extremities, absence of superficial abdominal reflexes on both sides, Babinski's sign on the left. A hemiplegic gait was observed. Myelography and cerebrospinal fluid examination revealed no pathological changes. Characteristic changes were revealed on CT (Fig. 2)

Thus, the patient was diagnosed with multiple sclerosis.

Exercise stress

Physical activity will help you cope with the symptoms of the disease, but in order to ensure the safety of your training program, you must follow a number of precautions:

The most important thing to remember is don't overdo it. Excessive load can disrupt the functioning of your muscles and create a state of stress for the nervous system.

Before starting your next training program, discuss the following with your doctor:

What types of physical activity are best for you, what types of activities are best to avoid.

What is the permissible intensity of physical activity?

What is the duration of the load and are there any restrictions.

Before starting a training program, seek the advice of a medical specialist who can ask any questions you may have.