Hypotension syndrome in children and adults

A decrease in skeletal muscle tone (residual tension and muscle resistance to passive stretching) with a deterioration in its contractile function is defined as muscle hypotonia. This condition is a symptom of a number of congenital and acquired pathologies that are referred to as neuromuscular disorders. 

Epidemiology

General statistics for a symptom such as muscle hypotonia are not kept. But the global incidence of the most common hereditary neuromuscular disorder - Charcot-Marie-Tooth disease - is 1-3 cases per 10 thousand population. [1]

According to studies, in Japan, one case of this pathology occurs per 9 thousand of the population, in Iceland - by 8.3 thousand, in Italy - by 5.7 thousand, in Spain - by 3.3 thousand  [2], [3]

The prevalence of congenital myasthenic syndrome is one case per 200 thousand children in the first year of life, and myofibrillar myopathy is one case per 50 thousand newborns. [4]

Causes muscle hypotension

As one of the types  of muscle tone disorders , hypotension of striated muscle fibers can have various causes associated with disorders occurring at any level of the nervous system (brain and spinal cord, peripheral nerves, local neuromuscular joints), caused by disorders of muscle or connective tissues, as well as depending on metabolic pathologies or the synthesis of individual enzymes. 

But most often the etiology of this condition is a  violation of neuromuscular transmission , and muscle hypotension occurs:

• with  motor neuron disease , first of all, amyotrophic lateral sclerosis and syndrome of lower motor neurons (α-motor neurons) of the spinal cord, innervating extrafusal muscle fibers;
• due to hereditary  spinal amyotrophies , in which degenerative changes in the α-motor neurons of the anterior horns of the spinal cord lead to dysfunction of the skeletal muscles. They are also defined as  hereditary neuropathies  (motor and motor-sensory), and most often - as one example - they call Charcot-Marie-Tooth disease (amyotrophy);
• in patients with  muscular dystrophy ;
• if there is a history of  myasthenia gravis ;
• with  myelopathies  - loss of the myelin sheath of nerve fibers of autoimmune and inflammatory etiology, including multiple sclerosis and  Guillain-Barré syndrome ;
• in cases of neurological lesions in cancer patients with the development of  paraneoplastic syndrome  (Lambert-Eaton syndrome);
• due to infectious inflammation of the outer lining of the brain (meningitis) or the entire brain (encephalitis).

Pathogenesis

The mechanism of development of muscle hypotension is associated with impaired conduction of impulses along the efferent somatic nerves, which occurs either at the level of the brain and spinal cord, or at the level of a nerve that provides innervation of a specific muscle and regulates its contraction and relaxation

For example, the pathogenesis of Charcot-Marie-Tooth disease is caused by gene mutations that affect the structure and function of peripheral nerves that control movement and sensitivity. A defective gene for one of the myelin proteins leads to loss of the myelin sheath of peripheral nerves and their subsequent degeneration. As a result, the conduction of nerve signals deteriorates and muscle tone decreases.

In the development of myasthenia gravis and congenital myasthenic syndrome, an important role is played by: dysfunctions of cholinergic neuromuscular synapses caused by genetic mutations - neuromuscular connections between the motor neuron and the nerve receptor of muscle tissue (neuromuscular spindle); violation of the production of the neurotransmitter acetylcholine; blocking postsynaptic muscle cholinergic receptors with antibodies.

The biochemical basis of neuronal death with impaired transmission of nerve impulses in cases of amyotrophic lateral sclerosis is recognized as an increase in the level of such a neurotransmitter as glutamic acid, which, when accumulated on the presynaptic membranes and in the intercellular space, becomes toxic to the nerve cells of the motor cortex of the brain and leads to their apoptosis.

The development of hereditary myofibrillar myopathy, affecting protein (myosin and actin) filaments of myofibrils of red (tonic) muscle fibers of striated muscles, is associated with their genetically determined structural changes, as well as with a violation of the oxidative processes of energy production - the synthesis of ATP in the mitochondria of cells, which explains the low enzyme activity of L-lactate and succinate dehydrogenase.

A decrease in the activity of acetylcholine in the synapses of neurons and myoneural connections may be associated with the induced activity of the enzyme of the cholinergic system of the brain acetylcholinesterase, which accelerates the hydrolysis of this neurotransmitter in the synaptic cleft. Most often, this is the mechanism of the appearance of muscle hypotension in patients with   type II tyrosinemia . [5]

Symptoms muscle hypotension

Since a decrease in muscle tone is manifested in combination with other signs of etiologically related conditions, the totality of clinical symptoms is defined by specialists as a syndrome of muscle hypotension or  muscle-tonic syndrome .

Its main symptoms in violation of the neuromuscular conduction of the lower motor neurons include: increased muscle fatigue and weakness, exercise intolerance, fasciculations (periodic involuntary twitching of individual skeletal muscles), decreased or complete absence of reflex muscle contractility (hyporeflexia), decreased stretch reflexes.

Both congenital and acquired pathology can manifest itself as mild muscle hypotonia with a moderate decrease in the ability of muscles to contract -  muscle weakness  (most often in the proximal muscles of the limbs) and difficult adaptation to physical activity.

In some cases, weakness is most pronounced in the muscles that provide movement of the eyes and eyelids, due to which progressive external ophthalmoplegia and ptosis develop. Mitochondrial myopathies can also cause weakness and wasting of the muscles in the face and neck, which can lead to difficulty swallowing and slurred speech. [6]

Adults with skeletal muscle hypotonia can be awkward and often fall when walking, find it difficult to change body position, and have increased flexibility in the elbows, knees, and hip joints.

In severe forms of spinal muscular atrophy, diffuse muscular hypotension is observed with loss of body weight, pathological changes in the skeleton (kyphosis, scoliosis) and progressive weakening of the muscles that provide breathing, which leads to hypoventilation of the lungs and respiratory failure.

Muscle hypotension in children is manifested by muscle flaccidity, a marked decrease or absence of deep tendon reflexes, rigidity and limitation of movement (in particular, flexion and extension of the limbs), joint instability, muscle shortening and tendon retraction, and in some cases, convulsions. [7]

As a result of pronounced hypotonia of the postural muscles, gait disturbances and pathological changes in posture occur, reaching the inability to keep the body in an upright position and move independently. As the child grows, problems with fine motor skills, speech and general development arise.

Infants have muscle weakness; salivation; inability to turn and hold the head (there is no control of the neck muscles), turn on its side, and a little later - roll over on its stomach and crawl; difficulties with feeding (it is difficult for a child to suck and swallow) and frequent regurgitation (due to gastroesophageal reflux), and with generalized myopathy - breathing problems.

Read more in the publication -  Symptoms of muscle-tonic syndrome

Muscular hypotension in children

In children, a decrease in muscle tone can be caused by abnormalities of the neuromuscular junction, primary muscle diseases, endocrine pathologies, and other factors.

This condition, for the most part, has a congenital nature and is associated with defects in the structure of the DNA of the chromosomal apparatus of cells.

Muscular hypotension of newborns - congenital hypotonia (ICD-10 code P94.2) - is especially common in preterm infants (born before the 37th week of pregnancy), which is due to muscle underdevelopment at the time of birth.

However, decreased muscle tone in a full-term newborn may indicate CNS problems, muscle disorders, or genetic disorders, including:

• congenital myopathies - muscular dystrophies of Duchenne, Becker, Ulrich, Bethlem, Erb-Roth, Werdnig-Hoffmann's disease, Dubovitz's disease, etc.;
• cerebral paralysis;
• Down, William, Patau, Prader-Willi, Angelman, Marfan, Ehlers-Danlos syndromes, etc.

Muscle disorders present in newborns or manifested in infancy can be centronuclear or myofibrillar (rod). Centranuclear myopathy is caused by an abnormal arrangement of nuclei in the cells of muscle tissue, and core myopathy is caused by disorders of the myofibrils of striated muscles. Most children with X-linked congenital myopathy do not live for more than a year. In cases of autosomal dominant inheritance of a defective gene, the first signs of pathology in the form of a decrease in skeletal muscle tone appear in adolescence or even later.

Congenital myasthenic syndrome, caused by genetic mutations that damage the sympathetic ganglia and cholinergic synapses of the somatic nerves, also appears immediately after birth. But some types of spinal muscular atrophy (for example, Kugelberg-Welander amyotrophy) manifest at a later age. [8]

Mitochondrial myopathies associated with mutations in the DNA of the nuclei or mitochondria of muscle cells are the result of a lack of energy supply - with a decrease in the synthesis of ATP (adenosine triphosphate) in mitochondria - and manifest themselves in the form of Barthes, Alper, Pearson, etc. Syndromes.

Generalized muscle hypotonia can be a consequence of cerebellar hypoplasia, which leads to a number of severe syndromic pathologies - Joubert and Walker-Warburg syndromes - with complete developmental delay, micro or hydrocephalus, and enlarged cerebral ventricles (ventriculomegaly).

Associated with a congenital disorder of the metabolism of carbohydrates and glycogen - glycogenosis or glycogenesis disease in young children, in addition to kidney damage and heart failure, is accompanied by a progressive metabolic myopathy called McArdle's disease.

Complications and consequences

Due to violations of neurogenic control of movements in muscle hypotonia, complications such as hypokinesia develop - with a decrease in motor activity and the strength of contraction of muscle fibers, with a progressive limitation of the range of movements.

In this case, hypokinesia can lead to such consequences as loss of muscle mass -  muscle atrophy , paresis, or a complete loss of the ability to move the limbs, that is,  peripheral paralysis  (depending on the cause - mono-, para or tetraplegia). [9]

Diagnostics muscle hypotension

A decrease in muscle tone can be a sign of severe systemic conditions, therefore, diagnostics involves the study of the history of intrauterine development of the child, childbirth, features of the neonatal period, anamnesis of the parents. A complete physical examination is also necessary - to assess potential disorders from the internal organs, psychosomatic diseases and identify syndromic conditions.

To determine what caused the decrease in muscle tone - problems with nerves or muscle abnormalities, tests are required, including a general and biochemical blood test, for the level of creatine phosphokinase, aspartate aminotransferase, L-lactate in the blood serum; for anti-GM1 antibodies; for the content of serum electrolytes, calcium, magnesium, phosphate. A muscle biopsy may be required. [10]

Instrumental diagnostics includes:

• electroneuromyography ,
• functional  study of muscle strength ,
• Muscle ultrasound ,
• Ultrasound of nerves ,
• electroencephalography,
• magnetic resonance imaging (MRI) of the brain  (to detect violations of its structures).

Differential diagnosis

Differential diagnosis of muscle hypotension and other neuromuscular disorders plays a special role.

Treatment muscle hypotension

Muscle hypotension in premature babies goes away as they grow, but pediatricians recommend massage to strengthen the baby's muscles.

Otherwise, treatment is focused on improving and maintaining muscle function. For this, physiotherapy (including  electromyostimulation ),  [11] exercise therapy and massage for muscle hypotension are used. 

Depending on the cause of this condition and its severity, some pharmacological agents can be used to improve the conduction of nerve impulses to the muscles and increase their contractile function. These drugs can be a group of cholinomimetics (stimulating acetylcholine receptors) or a group of cholinesterase inhibitors: Neostigmine methyl sulfate (Proserin, Kalimin), Physostigmine, Galantamine, Ipidacrine, Centrolin, Ubretid, etc.

More information in the material -  Treatment of muscle-tonic syndrome

Prevention

Muscle hypotonia can be caused by various health problems, many of which are inherited, therefore, experts consider genetic counseling before planning pregnancy to be a measure of prevention of serious congenital syndromes and neurological pathologies.

Forecast

The long-term outlook for muscle hypotension depends on its cause and the extent of muscle damage, as well as the age of the patient. It should be understood that this condition in cases of congenital pathologies is lifelong and leads to disability. And as for complete recovery, the prognosis is poor.