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, t
Medico- 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 Myasthenia Polymyositis Duchesne

Info Myodystrophy
Pathoge Autoimmune Autoimmune disease Autosomal-recessive
nesis disease, formation with the formation disease X-linked
of antibodies to antibodies to muscle chromosome
neuromuscular post- fibers
synaptic membrane
Clinical Muscles weakness Disease frequently Disease occurs in boys
pictures and their pathologic appears in middle at early childhood:
weakness usually and elderly age. It is children badly run and
first inocular characterized by jump, muscular
muscles (doubling, exponential increase weakness
ptosis of eyelid), of weakness in the predominates in
and then in majority proximal part of proximal part of feet
(85% of patients) extremities, humeral and pelvic girdle.
occur to others and pelvic girdle Gradually paresis of
muscle, causing muscles. In 30-50% extension of shoulder
paresis of cases, poliomyositis girdle, spinal muscle,
extremities, appears with and then to the
dysphagia, background of proximal part of hands.
 dysarthria, systemic diseases Frequently it reveals
dysphonia and (systemic lupus cardiomyopathy.
disturbances of erythmatosus and children up to 15 year
respiration. Are other), in 10-30% old, as a rule, are
possible acute cases, combine with completely immobilized
worsening - malignant tumor and die in 2-3rd decade
myasthenic crisis of life

Electro Decrease amplitude Decrease amplitude Decrease amplitude

myogra and duration of the and duration of and the duration of the
phy motor units motor units, their motor
(EMG) polyphasia, units
denervation activity
Electron Reduce amplitude of No Changes No Changes
euromy the repeated
ography muscular answers
(ENMG) with rhythmic
stimulation of 3-10
imp/s
CPK in Usually within Moderate increase Significant increase
blood standard limits
serum
Others Positive prozerine Oncologic search, In muscles biopsy -
investig test, in blood serum, with biopsy of diffuse loss of muscle
ation antibody to post- muscles - fibers, laboratory-
synaptic membrane, inflammatory genetic examination
CT of mediastinum changes
for development of
thymoma
Treatme Anti-cholinesterase Corticosteroids Therapeutic
nt (Calimin, Prozerin), (prednisolone), gymnastics, to
corticosteroids cytostatics. Good symptomatic treatment
(prednisolone), effect with treatment
cytostatics, idiopathic forms of
plasmaphoresis, the disease
immunoglobulin,
remove thymoma

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 infoAmyotrophic lateral sclerosis

Pathogen Loss of the motor neurons of spinal cord, the stem of brain and
esis cerebral cortex
Clinical Combination of peripheral (with fasciculations, expressed atrophy)
picture 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
Treatmen Symptomatic
t