Stiff-person syndrome is a rare neurological disease of unknown origin, manifested by constant tonic muscle tension (rigidity) and individual painful spasms that limit the patient’s mobility. Disease is diagnosed according to the typical clinical picture and electrophysiological studies, with the exception of other pathology that can cause rigidity. Treatment is symptomatic. Benzodiazepines and baclofen are traditionally used. Alternative methods are plasmapheresis, glucocorticosteroid therapy, intramuscular administration of botulinum toxin, treatment with immunoglobulin.
General information
Stiff-person syndrome (SPS) is a rare neurological pathology, clinically manifested by muscle rigidity and spasms. Muscle rigidity is called their constant tonic tension. The consequence of rigidity is stiffness and restriction of voluntary and involuntary motor acts. In the stiff-person syndrome, rigidity prevails in the axial (running along the spine) muscles and the proximal muscles of the extremities. At the same time, the tone of the extensor muscles is higher than the flexors, which gives the patient a characteristic appearance with an unusually straight and even arched back, pronounced lumbar deflection, shoulders turned back and a slightly tilted head. For the first time, stiff-person syndrome syndrome was described in detail in 1956 by American neurologists Mersch and Voltman, after whom it is called Mersch-Voltman syndrome. Statistics on the prevalence of the syndrome are not currently collected, due to its great rarity.
Causes
Much remains unclear about the etiopathogenesis of the syndrome. Clinical studies conducted by specialists in the field of neurology have shown that the basic pathogenetic substrate of pathology is increased excitability of motor neurons localized in the anterior horns of the spinal cord. Presumably, this is due to the dysfunction of the GABAergic system, which has an inhibitory effect on the motor neurons of the central nervous system. This hypothesis is confirmed by the low content of GABA in the cerebrospinal fluid of patients with CHF and the antispasmodic efficacy of GABAergic and antiadrenergic pharmaceuticals observed in them.
In 1966, the autoimmune theory of the etiology of the syndrome was presented. In 1988, antibodies to glutamate decarboxylase, an enzyme that catalyzes the synthesis of GABA from glutamic acid and concentrates in the endings of GABAergic neurons, were found in the cerebrospinal fluid and in the blood of patients with stiff-person syndrome syndrome. However, further studies have shown that such antibodies are present in the cerebrospinal fluid only in 68% of patients with SPS, and in the blood — only in 60%. It should be noted the identity of the clinical picture in patients with and without antibodies.
The question of the pathogenetic role of the detected antibodies to gutamate decarboxylase remains unclear: whether they are the direct cause of motor neurone dysfunction or only its consequence. Along with these antibodies, stiff-person syndrome is often accompanied by the presence of other antibodies: to thyroid cells, stomach epithelium, insulin-producing pancreatic cells, antimitochondrial and antinuclear antibodies.
Symptoms
The disease can make its debut at any age, but most often the manifestation occurs in the third and fourth decades of life. Typically gradual development. As a rule, the first symptoms are transient tension (rigidity) and pain in the muscles of the back, neck and abdomen. Then the rigidity becomes permanent, against its background there are periodic intense muscle spasms. For several months, the muscles of the proximal parts of the arms and legs are involved in the process. In 25% of patients, spasms of facial muscles are observed, leading to hypomimia or involuntary movements (for example, stretching of the lips with a spasm of the circular muscle of the mouth); damage to the distal muscles (more often the muscles of the shins).
The predominance of rigidity in the extensor muscles leads to overextension of the back, the formation of pronounced lumbar lordosis, a constant elevated position of the shoulders and some tilting of the head. Due to the tonic state of the abdominal muscles, a “plank-shaped belly” is formed. The gait of a “clockwork doll” with slow, hardly carried out small steps is characteristic. In severe cases, the mobility of patients suffers sharply: they cannot independently sit on a chair or get up from it, get dressed, bend over, turn their heads. At the same time, the limbs seem to be tightly fused with the trunk and move together with it as a single block. If stiff-person syndrome syndrome is accompanied by a lesion of the respiratory muscles, then even with minor physical exertion, respiratory failure occurs in patients.
Against the background of permanent rigidity, individual muscle spasms are observed. They can be spontaneous, promotional or reflex in nature. Promotional spasms are provoked by movement, reflex — by variable external influences (touch, cold, straining, emotional reaction, etc.). Most often spastic contractions occur in the muscles of the back and legs. The duration of spasms varies from several seconds to tens of minutes. In some cases, the force of muscle contraction during spasm is so great that it leads to dislocation or fracture. With spasm of the respiratory muscles and laryngeal muscles, respiratory rhythm disorders occur. The generalized nature of the spasm causes the patient to fall. Often spasms occur with acute pain, which at the end of the spasm acquires a dull cerebellar character. In 75%, spasms are combined with emotional (anxiety, dysphoria) and vegetative (tachycardia, hyperhidrosis, mydriasis, elevation of blood pressure) symptoms.
The intensity of rigidity and muscle spasms varies throughout the day. Typically, their disappearance in a state of sleep. In some cases, there is a spastic status (frequent intense spasms), threatening the development of severe arrhythmia, heart failure, severe respiratory disorders, DIC syndrome, shock.
Diagnostics
The difficulties in diagnosing HRV are associated with its rare occurrence and the need to exclude all other possible causes of rigidity. During the examination, the neurologist draws attention to the absence of any neurological symptoms, except for muscle rigidity and increased tendon reflexes. Stiff-person syndrome syndrome should be differentiated from syringomyelia, spinal stroke, spinal cord tumor, myelitis, torsion dystonia, myotonia, Parkinson’s disease.
The main paraclinical diagnostic method is the EPI of the neuromuscular system. Electroneurography does not reveal disturbances in the conduction of impulses along nerve trunks. Electromyography detects constant activity of muscle motor units, which persists when the patient tries to relax a muscle or strains antagonist muscles. At the same time, the shape of the action potentials has not been changed. Exposure to external stimuli (electrical stimulation, noise, touch) leads to increased EMG activity, provokes simultaneous contraction of antagonist muscles. Characterized by the disappearance of muscle rigidity with the introduction of diazepam or muscle relaxants, peripheral nerve blockade.
Muscle biopsy can reveal atrophic and fibrous changes in muscle fibers, which may be a consequence of ischemia developing as a result of prolonged intense contractions. In order to identify concomitant pathology, laboratory tests, examination of cerebrospinal fluid, MRI of the brain, CT or MRI of the spine are carried out. Patients with stiff-person syndrome syndrome are often diagnosed with other diseases: vitiligo, retinopathy, pernicious anemia, hypothyroidism, etc. According to various data, 30-50% of patients have type I diabetes mellitus.
Treatment and prognosis
The therapy is aimed at relieving spasms and rigidity. A good effect is achieved with the use of benzodiazepines (diazepam, clonazepam). Treatment starts with a minimum dose taken 1-2 times a day. Then there is an increase in the dosage with the division of the daily dose into 3-4 doses. When the effect is achieved in the form of the absence of spasms and a decrease in rigidity, the dose of the drug is no longer increased. Typical for patients is good tolerance of large dosages of benzodiazepines. However, in a number of patients, it is not possible to achieve an effective therapeutic dose due to the strong sedative effect of the drugs. In such cases, baclofen, a GABA receptor agonist, is prescribed. It can be prescribed in combination with benzodiazepines, which allows to achieve a therapeutic effect at lower dosages of drugs. In severe cases, an intrathecal infusion of baclofen is performed using an implanted pump.
In cases of ineffectiveness or intolerance to the above treatment, valproates, thiagabine, vigabatrin become the drugs of choice. It is possible to inject botulinum toxin into the parotid muscles. The correction of concomitant pathology (hypothyroidism, diabetes mellitus, etc.) contributes to the reduction of rigidity. Immunotherapeutic methods of treatment have been developed based on the autoimmune etiopathogenetic hypothesis of HPV. However, their effectiveness varies in different patients. A combination of plasmapheresis and glucocorticosteroids, intravenous administration of immunoglobulin have proven themselves well. The ineffectiveness of all these therapeutic methods is an indication for the appointment of cytostatic therapy.
Stiff-person syndrome syndrome has a serious prognosis. Slow progression is characteristic. In a number of patients, it is possible to stabilize the condition and maintain the possibility of self—care through symptomatic therapy, in others, rigidity progresses and, despite the treatment being carried out, after several years makes them bed sick. Immobility leads to the occurrence of congestive pneumonia, which in most cases is the cause of death. In some patients, severe vegetative disorders or diabetic coma become the cause of death.