Muscular hypotonia syndrome in children and adults

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

Epidemiology

There are no general statistics for such a symptom as muscular hypotonia. But the worldwide incidence of the most common hereditary neuromuscular disorder – Charcot-Marie-Tooth disease – is 1-3 cases per 10 thousand people. [ 1 ]

According to research, in Japan one case of this pathology occurs per 9 thousand of the population, in Iceland – per 8.3 thousand, in Italy – per 5.7 thousand, in Spain – per 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 hypotonia

Being one of the types of muscle tone disorders, hypotonia of striated muscle fibers can have different causes associated with disorders occurring at any level of the nervous system (brain and spinal cord, peripheral nerves, local neuromuscular junctions), caused by disorders of muscle or connective tissue, and also dependent on pathologies of metabolism or synthesis of individual enzymes.

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

• in motor neuron disease, primarily amyotrophic lateral sclerosis and lower motor neuron (α-motor neuron) syndrome 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 name Charcot-Marie-Tooth disease (amyotrophy);
• in patients with muscular dystrophy;
• if there is a history of myasthenia;
• in 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 damage in cancer patients with the development of paraneoplastic syndrome (Lambert-Eaton syndrome);
• due to infectious inflammation of the outer membrane of the brain (meningitis) or the entire brain (encephalitis).

Pathogenesis

The mechanism of development of muscle hypotonia is associated with a disruption in the 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 the 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 the peripheral nerves that control movement and sensitivity. A defective gene for one of the myelin proteins leads to the loss of the myelin sheath of the peripheral nerves and their subsequent degeneration. As a result, the conductivity of nerve signals deteriorates and muscle tone decreases.

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

The biochemical basis for the death of neurons with impaired transmission of nerve impulses in cases of amyotrophic lateral sclerosis is recognized to be an increase in the level of such a neurotransmitter as glutamic acid, which, when accumulated on 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 oxidative processes of energy production - the synthesis of ATP in the mitochondria of cells, which is explained by the low enzymatic activity of L-lactate and succinate dehydrogenase.

A decrease in the activity of acetylcholine in neuronal synapses 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 for the appearance of muscle hypotonia in patients with type II tyrosinemia. [5 ]

Symptoms muscle hypotonia

Since decreased muscle tone appears in combination with other signs of etiologically related conditions, the set of clinical symptoms is defined by specialists as muscle hypotonia syndrome or muscle-tonic syndrome.

Its main symptoms in case of impaired neuromuscular conduction of lower motor neurons include: increased muscle fatigue and weakness, intolerance to physical exertion, 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 as mild muscle hypotonia with a moderate decrease in the ability of muscles to contract – muscle weakness (most often of the proximal muscles of the limbs) and difficulty adapting to physical activity.

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

Adults with hypotonia of skeletal muscles may be clumsy and often fall when walking, have difficulty changing body position, and have increased flexibility in the elbows, knees, and hip joints.

In severe forms of spinal muscular atrophy, diffuse muscular hypotonia 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 hypotonia in children is manifested by muscle flaccidity, a noticeable decrease or absence of deep tendon reflexes, rigidity and limitations of movement (in particular, flexion and extension of the limbs), joint instability, shortening of muscles and retraction of tendons, 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 point of inability to hold the body in an upright position and move independently. As the child grows, problems with fine motor skills, speech and general development arise.

Infants experience muscle weakness; drooling; inability to turn and hold their head (no control of the neck muscles), turn on their side, and a little later – roll over onto their stomach and crawl; feeding difficulties (the baby has difficulty sucking and swallowing) and frequent regurgitation (due to gastroesophageal reflux), and in generalized myopathy – breathing problems.

Read more in the publication – Symptoms of muscular-tonic syndrome

Muscle hypotonia in children

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

This condition is mostly congenital and is associated with defects in the structure of the DNA of the chromosomal apparatus of cells.

Muscular hypotonia of newborns – congenital hypotonia (code P94.2 according to ICD-10) – is especially often observed in premature infants (born before the 37th week of pregnancy), which is explained by the underdevelopment of muscles at the time of birth.

However, decreased muscle tone in a full-term newborn may indicate problems with the central nervous system, muscle disorders, or genetic disorders, including:

• congenital myopathies – Duchenne, Becker, Ulrich, Bethlem, Erb-Roth muscular dystrophies, Werdnig-Hoffmann disease, Dubowitz disease, etc.;
• cerebral palsy;
• 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 (core). Centronuclear myopathy is caused by abnormal arrangement of nuclei in muscle cells, and core myopathy is caused by disorders of myofibrils of striated muscles. Most children with X-linked congenital myopathy do not survive more than a year. In cases of autosomal dominant inheritance of the defective gene, the first signs of pathology in the form of decreased tone of skeletal muscles appear in adolescence or even later.

Congenital myasthenic syndrome, caused by genetic mutations with damage to the sympathetic ganglia and cholinergic synapses of somatic nerves, also manifests itself immediately after birth. However, 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 deficiency in energy supply – with a decrease in the synthesis of ATP (adenosine triphosphate) in the mitochondria – and manifest themselves in the form of Barth, Alper, Pearson syndromes, etc.

Generalized muscle hypotonia may 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 enlargement of the cerebral ventricles (ventriculomegaly).

Associated with an inborn error of carbohydrate and glycogen metabolism, glycogenosis or glycogen storage disease in young children, in addition to kidney damage and heart failure, is accompanied by a progressive metabolic myopathy called McArdle disease.

Complications and consequences

Due to disturbances in neurogenic control of movements in muscular hypotonia, complications such as hypokinesia develop – with a decrease in motor activity and the force of contraction of muscle fibers, with a progressive limitation of the range of motion.

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

Diagnostics muscle hypotonia

Decreased muscle tone may be a sign of severe systemic conditions, so diagnostics involves studying the history of the child's intrauterine development, childbirth, neonatal period characteristics, and parents' medical history. A full physical examination is also necessary to assess potential disorders of internal organs, psychosomatic diseases, and to identify syndromic conditions.

To determine whether decreased muscle tone is caused by nerve problems or muscle abnormalities, tests are required, including a complete blood count and biochemical blood test, for serum creatine phosphokinase, aspartate aminotransferase, and L-lactate levels; for anti-GM1 antibodies; and for serum electrolytes, calcium, magnesium, and 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 (which allows identifying abnormalities in its structures).

Differential diagnosis

A special role is played by differential diagnostics of muscle hypotonia with other neuromuscular disorders.

Treatment muscle hypotonia

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

In other cases, treatment is focused on improving and maintaining muscle function. This involves physiotherapy (including electrical muscle stimulation ), [ 11 ] exercise therapy, and massage for muscle hypotonia.

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

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

Prevention

Muscle hypotonia can be caused by various health problems, many of which are inherited, so experts consider medical genetic counseling before planning a pregnancy as a preventive measure for serious congenital syndromes and neurological pathologies.

Forecast

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