Kugelberg Velander disease is a spinal muscular atrophy characterized by late development and the most benign course. Characterized by atrophy of the muscles of the pelvic girdle and hips, followed by the addition of atrophy of the shoulder girdle and shoulders, a combination of muscle weakness and hypotension with fascicular twitching, the presence of pseudohypertrophy. Diagnostics is carried out with the help of an EPI of the nervous system, a study of a muscle biopsy, DNA analysis, MRI of the spine. Treatment is symptomatic and ineffective, but the slow progression of symptoms causes prolonged motor ability of patients.
G12.1 Other hereditary spinal muscular atrophy
Kugelberg Velander disease is a relatively benign type of spinal amyotrophy with slow progression and damage mainly to the muscle groups of the proximal extremities. It was described in detail in 1956 by Swiss doctors E. Kugelberg and L. Valander, after whom it was named. In practical neurology and genetics, other names are also used: juvenile amyotrophy, spinal muscular atrophy (SMA) type III.
Kugelberg Velander disease clinically manifests after the age of 2, most often in the period from 3 to 10 years. There are some cases of a later debut at the age of 14-30 years. Accurate data on the prevalence of type III SMA are not yet available. Some authors still consider this type of amyotrophy to be a late form of Werdnig Hoffmann disease.
Kugelberg-Velander disease, like other types of SMA, is determined by disorders in the genes of the 5th chromosome, namely, in the “survival of motor neurons” gene – SMN. In the case of type III SMA, gene aberrations are inherited mainly by autosomal recessive pathway. With this type of inheritance, the mutant gene is present in both the father and mother, but it is not clinically manifested. The probability of developing amyotrophy in a child does not exceed 25%.
Disorders of the genetic apparatus cause the appearance and progression of degenerative changes in the anterior horns of the spinal cord. The process affects the motor neurons localized there. The initial lesion of the lower thoracic and lumbar spinal segments is characteristic, leading to muscle weakness in the proximal parts of the legs, and then the lesion of the upper thoracic and cervical segments with weakness in the muscles of the shoulder girdle.
The disease debuts when the child already knows how to walk and run independently. The first manifestation of amyotrophy is increased fatigue during prolonged walking or while running. More than half of the patients report some instability, frequent falls. Then there are difficulties when it is necessary to climb the stairs. Over time, atrophic changes develop in the muscles of the pelvic girdle and hips. At the same time, pseudohypertrophy of the calf muscles is formed in most patients. Gradually, the patient’s gait takes the form of a “duck”.
A few years after the debut, symptoms of damage to the proximal muscle groups of the upper extremities appear. The volume of active movements in the shoulder girdle and arms decreases. There are atrophy of the muscles of the shoulders and scapular area, the formation of characteristic “wing-shaped” shoulder blades. The symmetrical nature of muscular atrophy is typical. Neurological examination reveals a decrease in the muscular strength of the affected muscles, a progressive extinction of tendon reflexes from the biceps and triceps of the shoulder, as well as knee tendon reflexes.
The Kugelberg-Velander form differs from other types of SMA in the presence of fascicular twitching in the affected muscles, and sometimes in the muscle groups of the shins and forearms. Often there is a tremor of the tongue, a small-scale tremor of the fingers.
Unlike other types of spinal muscular atrophy (type I and II), Kugelberg Velander disease is characterized by a more benign course. It is possible to form bone deformities: curvature of the spine, deformities of the chest and feet, in some cases ‒ tendon retractions and joint contractures. However, osteoarticular manifestations are moderate.
Profound disability with loss of the ability to walk and self-care occurs extremely rarely and only in the later stages of the disease. The most common complications include balance and gait disorders due to the weakness of the pelvic girdle muscles and the proximal parts of the lower extremities. Frequent falls increase the risk of pathological fractures.
Patients with Kugelberg Velander disease are supervised by pediatricians and pediatric neurologists. Anamnestic data are important: the age of the onset of the disease (after 2 years), the nature of progression, the presence of a close relative with this pathology. During the examination, attention is drawn to a decrease in the tone of the muscles of the lower extremities, weakening or loss of knee and Achilles reflexes, musculoskeletal deformities (curvature of the spine, joint contractures).
Also, 50% of patients have a typical pseudohypertrophy of the calf muscles, i.e. their increase due to the deposition of fat and the growth of connective tissue. To confirm or exclude the diagnosis, the following additional examination is prescribed:
- Laboratory tests. In routine laboratory tests, all indicators remain within the reference values, with the exception of creatine phosphokinase, which may be slightly higher than normal.
- ENMG. When performing electroneuromyography, signs of degeneration of spinal cord motor neurons are noted – spontaneous bioelectric activity, “palisade rhythm”, a decrease in the speed and amplitude of the nerve impulse.
- Muscle biopsy. Histological examination of the muscle biopsy reveals changes typical of spinal atrophy – alternation of groups of atrophic and hypertrophied muscle fibers with preserved elements of muscle tissue.
- DNA analysis. Using the polymerase chain reaction method, a mutation of the SMN gene is detected.
Differential diagnosis of Kugelberg Velander disease should be carried out with other neurodegenerative diseases that manifest in childhood. These include:
- cerebral palsy;
- Duchenne pseudohypertrophic muscular dystrophy;
- the limb-girdle form of progressive muscular dystrophy.
To undergo treatment, patients must be hospitalized in a hospital. To date, there is no etiotropic therapy with proven effectiveness. All measures are symptomatic and palliative in nature. Nevertheless, an integrated approach and strict compliance with the recommendations of specialists can significantly improve the quality of life of the patient. The following types of treatment are used:
- Physiotherapy. To improve microcirculation in muscle tissue, sessions of electrostimulation with modulated current, electrophoresis, mud applications are carried out. Physical therapy. In order to slow down muscle atrophy, regular performance of various physical exercises is necessary. Preference is given to classes aimed at strengthening the muscles of the lower extremities – squatting, running, etc.
- Orthopedics. Orthopedic devices (orthoses, corsets, etc.) are used to correct and prevent musculoskeletal deformities and joint contractures.
- Medicines. Metabolic preparations (coenzyme Q10, L-carnitine), B vitamins (B1, B6, B12) in high doses are used to improve metabolic processes in motor neurons from medicines.
Numerous studies are being conducted on the search and development of drugs that affect the key links in the pathogenesis of Kugelberg Velander disease, which will significantly slow down or completely stop the progression of neurodegenerative processes. Phase II of clinical trials of Risdiplam (RG7916), a modifier of mRNA splicing of the SMN gene, has been completed. The drug has shown high therapeutic efficacy in all types of SMA.
Prognosis and prevention
Due to its slow course and late onset, amyotrophy has a relatively favorable prognosis. For a long time, patients retain the ability to move independently, and in cases of later onset (in 20-30 years) they live to old age without losing the ability to self-serve.
The only way to prevent the development of the disease is prenatal diagnosis with subsequent termination of pregnancy. In biopsies of chorionic villi or amniotic fluid, an SMN mutation is detected. Secondary prevention consists in preventing the occurrence of adverse consequences (bone and joint deformities).