Neuromuscular diseases. Amyotrophic lateral sclerosis

Myasthenia

Myasthenia is a disease, caused by lesion of neuromuscular synapse and is manifested by pathologic muscle fatigue and muscular weakness. Prevalence: 4 cases per 100 thousand populations.

Etiology and pathogenesis. Myasthenia is an autoimmune disease with the formation of antibodies to the postsynaptic membrane of neuromuscular synapse, which leads to the disturbance of conductivity in the Ger. In 60% of patients with myasthenia is revealed hyperplasia of thymus, in 10% of patients - its tumor (thymoma).Myastenic conduction syndromes are observed in bronchogenic cancer (Lambert- Eaton syndrome), with the use of penicillamine, aminoglucosides (neomycin, gentamicin, Kanamycin and other), streptomycin, polypeptide antibiotics.

Clinical picture. Characteristic manifestations of disease are weakness of muscles and their pathologic fatigue. In many cases the disease begins from the oculomotor disturbances, caused by the lesion of ocular muscles and manifested by doubling and by lowering eyelid (ocular form of myasthenia). In the morning, disturbances can be absent, and considerably increase to evening and with load (prolonged reading ). Less frequently, disease begins from the disturbances of ingestion (dysphagia), speech (dysarthria) and voice (dysphonia) or weakness in the extremities (peripheral paresis). In some (15%) of patients, manifestation of myasthenia is only [ ostayuts] local, while the rest, it gradually progress, up to the generalize form of disease. With [raspro] of [straneiii] of weakness to the muscles of extremities, as a rule more greatly suffer the muscles of proximal part of final fingers, they are frequently scalene muscle of neck. One of to more severe symptoms of myasthenias is weakness of respiratory muscles, accompanied by suffocation.

In myasthenia, rapid worsening state can be observed - myastenic crisis generalize by muscular weakness, expressed by dysphagia, dysphonia, dysarthria and respiratory disturbances. Similar to clinical manifestations of cholinergic crisis state as it appears with the overdose of being adapted [dl] of the treatment of anticholinesterase preparations and usually [sonro] [vozhdaetsya] by hypersalivation, by [oznobopodobnym] tremor, increased perspiration, diarrhea, pallor, narrow pupils, bradycardia.

Diagnosis of myasthenia is based on the clinical data and is confirmed by tests with the motor loads, which make it possible to provoke pathologic muscular fatigue. Great diagnostic value has the prozerine test - introduction of S/Cly 1-3 ml 0,05% of proserin solution (in the combination with 0,5 ml 0,1%- GO of the solution of atropine), after which after 20-40 min usually decrease muscular weakness and fatigue during 2-3 h. With electroneuromyography is noted reduction in the amplitude of muscular potentials with the stimulation of nerve with a frequency of 3-10 in second in 75% of patients. Electromyography with a study of the potentials of separate muscular fibers also possesses high informativeness. Serological studies make it possible to reveal antibodies to the synaptic choline receptors in 70% of patients with the ocular form of myasthenia and in 80- 90% of patients with the generalized form. The complete inspection, which includes serological studies, to electroneuromyography and electromyography, ensures 100% diagnostics. In all patients with myastheniais, X-ray and CT of chest showed the development thymomae or hyperplasias of thymus gland.

Treatment. As the pathogenetic treatment anticholinesterase means are employed. Proserin uses periodically, in essence for a short-term increase in the muscular force before the physical load or the food, on 2-3 ml of SQ or 1 ml of IV 0,05%- GO of solution or on 15 mg inward. Calimine is used for the prolonged method at 50-60 mg of 3-6 times in the day. In the small part of the patients, predominantly with the local form of myasthenia, the application of anticholinesterase means makes it possible to the long period to improve state and to stabilize the course of disease.

Exacerbation of disease cause significant disturbances and being be beyond en to treatment with anticholinesterases, is conducted course treatment with prednisolone through 60-100 mg/day in the flow 1-2 weeks. Before the achievement of positive effect, and then gradually is reduced the dose to that supporting (5-15 mg daily or 10-30 mg in the day). With the absence of positive result or the side effects from prednisolone, and also for the purpose of reduction in its dose it is possible to use the cytostatics: azathioprine on 50-150 mg/day or cyclosporine to 5 mg/kg in a 24 hour period for a period of several years. An improvement in the state of the patients with myasthenia can be also achieved by several sessions of plasmaphoresis or by introduction of immunoglobulin of IV from the calculation 0,4 g/kg/day for the course of 5 days.

In the presence the thymomae, and also by all patient with the generalized form of myasthenia at the age of up to 70 years, the removal of thymus gland (thymectomy), is shown, which carry out in the specialized centers. On the average improvement in [gostoyaniya] and steadfast remission (usually of up to 5 years) are observed in 70% after operation.

For stopping the myasthenic crisis, uses IV proserin, during the respiratory disturbances mechanical ventilation of lungs; in the flow 2-3 weeks. prednisolone on 60-100 mg with the gradual decrease of dose is used. Temporary cancellation AN is necessary with the cholinergic crisis cholinesterase means under a constant observation, during the respiratory disturbances - mechanical ventilation of lungs with the subsequent selection of the adequate dose of means.

Progressive muscular dystrophy

Progressive muscular dystrophias is a group of hereditary diseases, which are manifested by increasing muscle weakness and atrophy. Muscular dystrophies are caused by the primary hereditary caused lesion of muscles (myopathy), in this case, motor neurons, their axons and neuromuscular ends remain preserved. They present the most frequent reason for myopathy, which is also inflammatory, innate and metabolic against the background thyrotoxicosis, hypothyroidism, hyperparathyroidism, hypercorticoidism or acromegaly. Different types of the progressive muscular dystrophies are differed from each other in terms of genetic defect, type of inheritance, period of onset of disease localization and rapidity of development of muscular of atrophy, paresis and other associated symptoms.

Duchesne's myodystrophy is encountered more frequent than other forms - 63 cases in 1 million populations.

Pathogenesis. In Duchesne's myodystrophy, pathological gene (dystrophias) is localized in the short arm X-chromosome, and disease is transferred by recessive, coupled with the X-chromosome type; therefore boys are ill.

Clinical picture. The majority types of progressive muscular dystrophies are manifested at the children's or youthful age. Typically, there are gradual increase of symmetrical weakness and atrophy of muscles of proximal part of extremities, pelvic and shoulder girdle. With the significant degree of the lesion of muscles of pelvic belt in patients is observed “duck” gait: they walk falling over side to side. When rise from horizontal position, patient because of the muscular weakness with difficulty is turned over to the stomach, then, being abutted by hands against floor, it becomes on all fours and after this, being abutted by hands against shin, then into thighs, gradually it is straightened. The lesion of muscles of shoulder girdle is manifested by their weakness and atrophy, characteristically “wing-shaped blades”, especially during raising of hand upward, deformation of chest. There are no sensory disturbances, reflexes are usually reduced moderately.

Duchesne's Myodystrophy in early child age it is already manifested by delay of physical development: affected children begin more lately to walk, usually they run and jump badly. Muscular weakness predominates in the proximal parts of feet and the pelvic belt, changes in the gait usually are revealed at the age of 2-5 years. Gastrocnemius muscles, sometimes quadriceps muscles of thigh and deltoid, as a rule, increased in size and are condensed due to the growth of connective tissue (pseudo-hypertrophy); however, their force is reduced. Other muscles of thighs, pelvic and shoulder girdle atrophy at the early stages of disease. Gradually process ascends to shoulder girdle, muscles of back, and then to proximal parts of the hands, Heart muscle according to the type of cardiomyopathy frequently suffers. In many patients, intellect is reduced. At 10 years old, the children walk with difficulty, while at 15 years old they, as a rule, it is completely immobilized. Patients die by 2-3rd decade of life as a result of the heart insufficiency or pulmonary complications.

Diagnosis is based on clinical data and is confirmed by an increase (10-100 times) of activity of creatinine in blood serum and by the changes in electromyography, characteristic for myopathy (reduction of duration and amplitude of potentials of motor units, absence of signs of lesion of peripheral nerves or motor neurons of anterior horns of spinal cord). In rare cases, the biopsy of muscles is carried out, which separates the diffuse loss of muscular fibers and their substitution by fatty and fibrous cells. Great significance has laboratory- genetic test.In the mothers of sick children (carriers of pathologic type) usually is slightly reduced muscular force, they are increased gastrocnemius muscles is increased the activity of creatine phosphokinase in the blood serum .

Treatment. There is no effective treatment. Management is directed to prevent the development of contractures, maintaining muscular force and prolong the period of independent movement. It is recommended to do regular occupations with the therapeutic gymnastics (but without the significant load), massage, also, with the need orthopedic measures, tMedico- genetic consultation has great significance to prevent the generation of affected children, prenatal determination of floor and diagnostics of the disease of fetus in the affected families make it possible to examine a question about the curtailment of pregnancy.

Polymyositis

Polymyositis is the most frequent form of acquired myopathy as a whole. The frequency of disease is about 1 cases on 100 thousand population.

Pathogenesis. Autoimmune nature is assumed in Polymyositis with the T- cellular aggression, directed toward muscular fibers. In 30-50% of cases polymyositis is developed with background system diseases (system lupus erythematosis, nodular periarteritis, rheumatoid arthritis, and scleroderma). In 10-30% of cases polymyositis is combined with the malignant tumor (usually the cancer of lung or colon in men, cancer of mammary gland and ovaries in women) and estimates as paraneoplastic syndrome.

Clinical picture. Polymyositis more frequently appears at middle and elderly age. Characteristically, in, the course of weeks, gradual increase of weakness in the proximal parts of extremities, the muscles of shoulder and pelvic girdle, weakness of feet are manifested by difficulty to go up the stairs, getting up from deep armchair, in elbows or haunches, with the lesion of muscles of arms and proximal parts of hands to patient it is complicated to raise the hands higher than head: to comb in! [losy] or to place any object on the upper shelf.And; for the weaknesses of rear muscles of neck patient he is to difficult retain head, is possible the connection of dysphagia and dysphonia. Tendinous reflexes in the paretic finite-i [tyakh] it is only slightly weakened, atrophy usually not expressed. Pain in the muscles and their sickliness during the

palpation sometimes are noted. Frequently it is combined with the lesion of the skin - dermagomyositis.

Diagnosis. Diagnosis is based on clinical data and is confirmed by the results of electromyography. Characteristically, an increase in the activity of creatine phosphokinase, aminotransferases and aldolase in the blood serum, and also an increase in [SOE]. The histological the study of bioptata] of muscles reveals the inflammatory nature of changes. With the inspection of patient with polymyositis is necessary do oncologic investigation.

Treatment. Prolongedly (usually not less than 4-8 weeks.) Use of prednisolone is by calculation at 1 mg/kg (usually 60-80 mg/day) by the achievement of the clinical effect, evaluated on the decrease of the degree of paresis and reduction in the activity of creatine phosphokinase. Subsequently they gradually decrease the dose on 5 mg each week to 20 mg/day, which they preserve in the flow 6-12 months; the dose Of [tsPov] increases with the aggravation of disease. In the absence effect from the oral method of prednisolone it is possible it to combine with cytostatics - azathioprine (150-300 mg/day) or methotrexate (25-30 mg/[ned]. IV), and to also use an pulse- therapy methylprednisolone 1000 mg/day IV during 3-5 days (by subsequent passage to the oral method of prednisolone and cytostatic.

In the majority of the cases through 1-2 months treatment are observed the growth of muscular force, the decrease of the degree of paresis. Approximately in 20% of cases the complete regress of neurologic disturbances is noted, in the majority of the remaining cases - a substantial improvement in the state. Forecast with the idiopathic forms as a whole relatively favorable - for 10 years die only 10% of patients, forecast is worse with the presence of malignant new formation the stumps of severe system illness.

Spinal muscular atrophy/Amyotrophy (SMA)

Spinal muscular atrophies are hereditary diseases with progressive weakness paresis and atrophy of muscles due to lesion of neurons of anterior horns of spinal cord. Muscles fasciculation ocuur, but sensory disorders does not. The different types of spinal muscular atrophy are characterized by mainly the age of patient, at which they begin, with the speed of progression and by the type of inheritance. Diagnosis is confirmed by EMG, biopsy of muscles and by data of laboratory genetic investigation. There is no effective treatment, therapeutic gymnastics has great significance.

Spinal muscular atrophy I type (Wernig-Goffman disease) - autosomal- recessive disease with a frequency of 4-10 cases on 100 thousand new born. It begins into the first half a year lives, rapidly it progresses, 95% of patients die at the age up to 1 year.

Spinal muscular atrophy II type – more rare autosomal- recessive disease appears in 3 and 15 month old baby. Progression is less rapid, and majority of patients die up to 4-5 years.

Spinal muscular atrophy III type (Kugelberg- Welander disease) - autosomal-recessive or autosomal-dominance disease appears at the age from 15 months of up to 10 years. Disease slowly progresses; patients prolongedly preserve the ability of self-service and even sometimes fitness for work. Death begins usually at the mature age from the joined infectious, usually due to pulmonary diseases.

Spinal muscular atrophy IV type (Spinal amyotrophy of adult) - the rare forms of the diseases, which have the autosomal- recessive, autosomal-dominant or X-coupled recessive type of inheritance. Disease is more frequent at 30-40 year old, slowly progress; they do not substantially influence lifespan.

Brief information about some neuromuscular illnesses

Brief Info Myasthenia Polymyositis Duchesne MyodystrophyPathogenesis

Autoimmune disease, formation of antibodies to neuromuscular post-synaptic membrane

Autoimmune disease with the formation antibodies to muscle fibers

Autosomal-recessive disease X-linked chromosome

Clinical pictures

Muscles weakness and their pathologic weakness usually first inocular muscles (doubling, ptosis of eyelid), and then in majority (85% of patients) occur to others muscle, causing paresis of extremities, dysphagia, dysarthria, dysphonia and disturbances of respiration. Are possible acute worsening - myasthenic crisis

Disease frequently appears in middle and elderly age. It is characterized by exponential increase of weakness in the proximal part of extremities, humeral and pelvic girdle muscles. In 30-50% cases, poliomyositis appears with background of systemic diseases (systemic lupus erythmatosus and other), in 10-30% cases, combine with malignant tumor

Disease occurs in boys at early childhood: children badly run and jump, muscular weakness predominates in proximal part of feet and pelvic girdle. Gradually paresis of extension of shoulder girdle, spinal muscle, and then to the proximal part of hands. Frequently it reveals cardiomyopathy. children up to 15 year old, as a rule, are completely immobilized and die in 2-3rd decade of life

Electromyography (EMG)

Decrease amplitude and duration of the motor units

Decrease amplitude and duration of motor units, their polyphasia, denervation activity

Decrease amplitude and the duration of the motorunits

Electroneuromyography (ENMG)

Reduce amplitude of the repeated muscular answers with rhythmic stimulation of 3-10 imp/s

No Changes No Changes

CPK in blood serum

Usually within standard limits

Moderate increase Significant increase

Others investigation

Positive prozerine test, in blood serum, antibody to post-synaptic membrane, CT of mediastinum for development of thymoma

Oncologic search, with biopsy of muscles - inflammatory changes

In muscles biopsy - diffuse loss of muscle fibers, laboratory- genetic examination

Treatment Anti-cholinesterase (Calimin, Prozerin), corticosteroids (prednisolone), cytostatics, plasmaphoresis, immunoglobulin, remove thymoma

Corticosteroids (prednisolone), cytostatics. Good effect with treatment idiopathic forms of the disease

Therapeutic gymnastics, to symptomatic treatment

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (motor neuron disease) - rapidly progressive disease of nervous system, caused by selective degeneration the motor neurons of spinal cord, cortex and brain stem. Frequency of the disease of 1-5 cases on 100 thousand people. Approximately 5 % the cases of disease they are inherited according to the autosomal - dominant type, in some of them the insufficiency of the ferment of superoxide dismutase is revealed. Disease more frequently appears into 50-70 years.

Clinical picture. Disease is developed gradually, manifested by the weakness of muscles of extremities, muscular twitchings (fasciculation) and by the local atrophy of muscles or by the disturbance of ingestion (dysphagia) and speech (dysarthria). The first symptoms are frequently weakness p [pokhudanie] muscles of fingers with combination of spasm and fasciculation of muscles of hand or weakness in one leg in the form of the overhanging foot. At the early stages frequently are noted predominantly peripheral (sluggish) pareses or less frequent central (spastic) pareses of extremities. However, the combination of peripheral and central paresis is observed during the progression of disease in the majority of patients: the rough atrophy of muscles of upper and lower extremities and fasciculation in them with the high tendinous reflexes and pathologic symptoms (Babinski, Rossolimo and others). The combination of the bulbar and pseudo-bulbar syndromes is also characteristic: dysarthria, dysphonia, dysphagia, atrophy and the fibrillation of language with the reanimation of mandibular and throaty reflexes, the symptoms of oral automatism. Reductions in the intellect, disturbances of sensitivity and function of pelvic organs is not observed even at the last stages of disease.

Majority (90%) of patients die on average after 3 year after onset of disease, as a rule, from the respiratory disturbances and joining, frequently aspiration, pneumonia. The slower progression of disease is observed in rest.

Diagnosis it is based on clinical data and is confirmed by electromyography, with which are revealed the denervation activity (potentials of fibrillations, positive sharp waves, [fasciculation, a notable increase in amplitude and duration of motor units. CT or MRI of head and spinal cord are conducted to exclude other diseases of nervous system.

Treatment. There is no effective treatment. The introduction of riluzole (rilutek) on 100 mg in a 24 hour period somewhat detains the progression of disease and prolongs the life of patients by several months. In the quality of symptomatic therapy with the spasticity it is possible to use myorelaxants (10-30 mg of baclofen, 6-18 mg of sirdalud a day), with the unhealthy muscular spasms of legs (cramps) - 300 mg of difepine or 10-20 mg of Relanium a day, with the depression and the forced weeping - 25-50 mg of Amitriptylene on the night, in disturbance of ingestion - 90-180 mg of calimine a day.

Brief information about the amyotrophic lateral sclerosis

Brief info Amyotrophic lateral sclerosisPathogenesis Loss of the motor neurons of spinal cord, the stem of brain and cerebral cortex Clinical picture

Combination of peripheral (with fasciculations, expressed atrophy) and central paresis extremities, combination of bulbar and pseudo-bulbar of syndromes, rapidly progressive period

Diagnosis It is based on clinical picture, electromyography, the absence of others of disease of spinal cord and brain based on CT and MRI

Treatment Symptomatic