Syndrome of "the rigid person"

Description:

Syndrome of "the rigid person" (Mersha-Voltman's syndrome) — the sporadic disease of not clear etiology which is characterized by the progressing rigidity and painful muscular spasms in axial muscles and proximal departments of extremities and connected with a hyperactivity of motive units.

The term "syndrome of the rigid person" (stiffman syndrome) is entered in 1956 by the American neurologists of F.P.Moersch and H.W.Waltman who submitted the description of 14 patients with earlier unknown disease which was characterized by "the progressing fluctuating muscular rigidity and spasms in axial muscles".

Syndrome symptoms of "the rigid person":

The syndrome of the rigid person is most often shown on 3 — the 5th decades of life, but cases from the beginning of a disease at senile and children's age are described. It was reported also about an inborn form of a syndrome. Men and women suffer approximately to the same extent.

Symptoms develop gradually. First patients are disturbed by only incidental pains and a muscle tension of a back, stomach or neck. But gradually muscular tension (rigidity) increases, becomes a constant, muscular spasms join. Having begun with truncal muscles, process in several months involves (more or less symmetrically) a muscle of proximal departments of all four extremities.

Dominance of a tone in razgibatel is characteristic of a syndrome of the rigid person. The constant tension of juxtaspinal muscles leads to formation of the fixed lumbar lordosis which can remain at a trunk inclination forward or in a prone position. The upper back is usually straightened, the head is sometimes a little rejected kzad. Shoulders are often tightened up. But at some patients in cervicothoracic department the kyphosis is noted. Muscles of a stomach are strained and have doskoobrazny density.

Against the background of constant rigidity there are muscular spasms, the proceeding several seconds or minutes, more rare longer. They can be spontaneous, reflektory or promotional. Reflex spasms are provoked by sudden noise, a touch, a passive muscle strain, a natuzhivaniye (for example, at bladder emptying), sudden emotional reaction, a fright, cold. At repeated action of the same irritant expressiveness of spasms usually decreases. Promotional spasms are caused by autokinesia.
(for example, feeling of numbness or crawling of goosebumps).

Most often spasms are involved by extensor muscles of a back and the lower extremities. But they can also develop in a diaphragm and other respiratory muscles, breaking a respiratory rhythm. Difficulty of breath is capable to be caused and the spasm of muscles of a throat, and a spasm of a cricopharingeal muscle happens the reason of obstruction of a gullet and a passing dysphagy. Intensity and a regularity of spasms are variable. Sometimes they are so strong that lead to a fracture or dislocation. As a result of an unexpected generalized spasm of the patient can suddenly fall.

Quite often spasms cause the megalgia forcing the patient to scream, and leave behind long dull mozzhashchy ache in muscles. Spasms often are followed by alarm, a dysphoria and sharp vegetative shifts (profuse sweating, tachycardia, increase in arterial pressure).

Distal departments of extremities and cranial muscles, as a rule, remain intact. But approximately at a quarter of patients are noted involvement of cranial muscles (for example, tension of mimic muscles causing a gipomimiya or a violent pulling of lips) or spasms in shin muscles.

As a result of constant muscular tension mobility in lumbar department and hip joints is sharply limited. Any change of a pose, first of all a rising from a bed or a chair is complicated. In hard cases patients are not able to put on, bend independently forward to put on socks or to tie laces on footwear, to sit down on a chair. The trunk and an extremity move the uniform block. When involving cervical department of the patient cannot turn the head to look on the parties. At damage of muscles of a thorax the respiratory insufficiency which is shown an asthma at the slightest exercise stress is possible.

At a late stage of a disease owing to a constant muscle tension there can be a pathological installation of extremities.

The patient moves slowly with small steps, with big effort overcoming rigidity of a trunk and the lower extremities. Any careless movement can provoke a spasm and falling. Walking of patients is compared sometimes to gait of a clockwork toy. At an early stage when expressiveness of rigidity and spasms is not so big, many patients have a fear to lose balance, especially strong when crossing open space without support.

This fear (astazobazofobiya) can sometimes invalidizirovat the patient more than actually motive frustration also quite often is the cause for wrong diagnosis of a psychogenic disease as at this stage of a disease at neurologic survey of any essential objective symptoms can not come to light. Wrong diagnosis is promoted also by the affective lability characteristic of many patients.

Expressiveness of rigidity and spasms can fluctuate significantly within a day and from day by day. Rigidity and spasms usually pass in a dream, but in hard cases the expressed deformation of a backbone sometimes remains even in a dream.

At survey the unusual pose of patients (the expressed lumbar hyperlordosis, the shoulders tightened up, etc.), a sharp hypertrophy of juxtaspinal muscles, slowness of autokinesias, restriction of their volume usually pays attention. In typical cases of decrease in an animal force, disturbances of sensitivity and coordination, pathological-foot signs does not come to light. Perhaps only revival of tendon jerks. Miokimiya, fastsikulyation and a lockjaw are not inherent to SRCh. At a late stage the atrophy of muscles from inaction sometimes develops. The intelligence does not suffer.

At some patients, along with spasms, more bystry myoclonic twitchings in axial and proximal muscles, sometimes generalized most of which often have reflex character (myoclonic option of SRCh) are observed. Usually they appear in several years after the beginning of a disease and, unlike rigidity and a spasm, can be resistant to diazepam. Sometimes myoclonic twitchings arise only during sleep (a night myoclonia). At 10% of patients epileptic seizures are noted, however remains not clear whether they are connected pathogenetic with SRCh.

Also the combination of a syndrome of the rigid person with the progressing cerebellar ataxy is described — both syndromes can be connected with antibodies to DGK.

Vegetative symptoms (a mydriasis, arterial hypertension, profuse sweating, etc.) come to light in 75% of cases, but to a thicket have tranzitorny character, arising only during spasms. However at a part of patients more permanent vegetative frustration are observed (for example, arterial hypertension). The tachypnea and fever are sometimes observed. Against the background of frequent intensive spasms (status spamodicus) there can be sharp strengthening of vegetative frustration with development of vegetative crisis, disturbance of conductivity of heart, heart and respiratory failure, shock, a coma, the IDCS.

Sometimes in similar cases the heart attack of a miokrad as owing to intesivny reductions of muscles in blood there is an increase in level of muscular enzymes is mistakenly diagnosed.

Syndrome reasons of "the rigid person":

The etiology and pathogeny of the syndrome of the rigid person (SRP) in many respects remain not clear. Disappearance of rigidity and spasms in a dream, at blockade of peripheral nerves, the general anesthesia, purpose of diazepam indicate communication of a syndrome with TsNS dysfunction. It is obvious that at the heart of muscular rigidity and spasms increase in excitability of alpha motor-neurons of front horns lies, however its reasons are still not established. Data of electrophysiologic researches allow to connect pathological activity of motive units with dysfunction of the descending nadsegmentarny stvolovospinalny systems controlling a functional condition of internuncial neurons of a spinal cord which in turn brake activity of alpha motor-neurons of front horns.

Confirm it diffusion strengthening of the polisinaptichesky musculocutaneous reflexes which are becoming isolated through segmented network of internuncial neurons and being under control of nadsegmentarny systems.
Assume that at a syndrome of the rigid person the Gamkergichesky descending system rather selectively suffers that leads to disturbance of balance between the noradrenergichesky (exciting) and Gamkergichesky (brake) descending systems. In favor of this assumption testify the GAMK low level in cerebrospinal liquid, strengthening of spasms under the influence of katekholaminergichesky means (for example, levodopas or a klomipramina), and also reduction of spasms under the influence of Gamkergichesky means (for example, diazepam or Baclofenum) and anti-adrenergic means (a clonidine and a tizanidin).

It is impossible to exclude and the possibility of primary strengthening of noradrenergichesky influences — on it specifies the increased level of metabolites of noradrenaline in urine.

The data which are saved up so far allow to assume that autoimmune process is the reason of dysfunction of neurons of TsNS. For the first time this assumption was made by R.Young (1966) observing SRCh at the patient with two other autoimmune diseases — pernicious anemia and a thyroiditis. The autoimmune hypothesis received an additional reinforcement after M.Solimena and P. De Camilli (1988) was found in patients with SRCh in blood and cerebrospinal liquid of an autoantibody to Gamkergichesky neurons. Autoimmune genesis is demonstrated also by increase in the IgG level and oligoklonalny antibodies in cerebrospinal liquid, communication of a disease with a certain haplotype of HLA (B44, DR-3/4, DQB 1*0201), and also efficiency of immunomodulators.

The subsequent researches showed that these antibodies are directed against enzyme of the decarboxylase of glutaminic acid (DGA) which catalyzes transformation of glutaminic acid into GAMK and concentrates on a cytoplasmatic surface of synoptic bubbles in the terminations of Gamkergichesky neurons (especially in a spinal cord). However antibodies to DGK come to light in blood only at 60% of patients, and in cerebrospinal liquid — at 68% of patients with SRCh. It testifies to etiopatogenetichesky heterogeneity of SRCh. Essential clinical distinctions between the patients having and not having an antibody to DGK do not come to light. However in the presence of antibodies the accompanying autoimmune diseases, and also antibodies to other antigens are found more often.

DGK is found also outside TsNS, first of all in pancreas beta cells that explains a frequent combination of SRCh to an insulin-dependent diabetes mellitus. Antibodies to DGK come to light at 22% of patients with an insulin-dependent diabetes mellitus. The antiserum capacity to DGK at a diabetes mellitus is 100 — 500 times lower, than at SRCh. In neurons and cells of a pancreas, apparently, the DGK different isoenzymes (with a molecular weight of 65 and 67 cd) which have homologous sites come to light, but are products of different genes. Therefore SRCh and a diabetes mellitus can arise independently from each other. At SRCh antibodies to epitopes of an izoenzi-m weighing 65 cd which are absent at a diabetes mellitus come to light, however two other regions of the same isoform interact with the antibodies revealed at patients with a diabetes mellitus.

K.Ishizawa et al. (1999) assumed that at patients with a syndrome of the rigid person antibodies to Gamkergichesky neurons of the descending trunk and spinal ways which brake segmented spinal polisinaptichesky circles are developed. Antibody In vitro to DGK are capable to brake activity of enzyme and process of development of GAMK.

However the pathogenetic role of antibodies to DGK is not finalized. They can be the cause of pathology of nervous cells or arise for the second time — owing to primary destruction of cells therefore remains to unknown whether cause antibodies dysfunction of cells or are only a disease marker. Not clearly also, how there is a presentation of DGK which is intracellular antigen, immune system.

At patients with a syndrome of the rigid person also other types of antibodies connected with the accompanying autoimmune diseases as organospetsifichesky (to cells mucous a stomach, a thyroid gland, etc.), and organonespetsifichesky (antinuclear, anti-mitochondrial, antibodies to unstriated muscles) that indicates system defect of immune system come to light.

In not numerous pathomorphologic researches any specific macro - or microscopic changes it was not found. Reduction of quantity of internuncial neurons in front horns of a spinal cord, sometimes — an atrophy and a gliosis of a spinal cord with dystrophic changes in area of back columns, decrease in number of neurons in medial departments of the front horns innervating axial muscles is only in some cases noted. Are revealed decrease in a chislennostya of Gamkergichesky neurons in cerebellar bark, reduction of the sizes of cells of Renshaw in a spinal cord.

Treatment of the Syndrome of "the rigid person":

Basis of symptomatic therapy of a syndrome of the rigid person is use of Gamkergichesky means, first of all benzodiazepines (diazepam, clonazepam) and Baclofenum which block the increased activity of spinal motor-neurons and allow to reduce expressiveness of spontaneous and reflex muscular spasms, to a lesser extent — rigidity, postural disturbances, mobility restriction.

Drug of the choice is diazepam (Relanium, Sibazonum) which not only strengthens Gamkergichesky transfer, but also to some extent slows down noradrenergichesky transfer. Treatment with diazepam is begun with the minimum dose (2,5 mg of 1 — 2 time a day). Then the dose is gradually raised to effective, suppressing spasms and reducing rigidity of axial muscles. Range of effective doses is very big (from 10 to 200 mg/days) that reflects various individual sensitivity of patients. Drug is accepted in 3 — 4 receptions.

Characteristic of patients with a syndrome of the rigid person — good tolerance even of very high doses of diazepam (in certain cases its dose is raised to 300 — 400 mg/days). However at a part of patients the dose of diazepam does not manage to be lifted to effective because of side effect, first of all the expressed sedation. Instead of diazepam clonazepam in a dose of 2 — 10 mg/days can be appointed (1 mg of clonazepam is approximately equivalent to 4 — 5 mg of diazepam).

At inefficiency of benzodiazepines use Baclofenum which is an agonist of GAMK-receptors of type B. Baclofenum is often added to benzodiazepine, but its appointment and as monotherapy is possible. Baclofenum dose is also titrated gradually, bringing as much as possible to 100 — 120 mg/days (in 3 receptions). The most frequent side effect of Baclofenum, as well as in case of benzodiazepines, is drowsiness.

At a combination of benzodiazepine and Baclofenum the necessary effect is often reached by means of lower doses, than at monotherapy that reduces risk of side effects. In hard cases efficiency of intrathecal introduction of Baclofenum by means of an infusional pomp at which the system effect of drug is minimized is shown, and high local concentration in a spinal cord is reached. However at disturbance of functioning of a pomp heavy vegetative complications are possible.

It is necessary to avoid the sudden termination of reception of benzodiazepine or Baclofenum (even at their seeming inefficiency) as it is fraught with sharp deterioration with development of the expressed vegetative shifts.

(for example, Depakinum, 600-2000 mg/days), тиагабин (4 — 12 mg/days) or вигабатрин (1500 mg/days) which strengthen Gamkergichesky transfer too and are capable to reduce deficit of GAMK at the spinal level. Use of anti-adrenergic means (тизанидин, a clonidine) gives less permanent effect. In hard cases effectively repeated introduction to paraspinal muscles of botulotoxin A. Correction of endocrine disturbances (a diabetes mellitus, a hypothyroidism, etc.) which can reduce expressiveness of rigidity and spasms is important.

Carbamazepine, дантролен, Phenytoinum (dipheninum), phenobarbital, Mydocalmum, циклобензаприн, Mephenesinum, a levodopa, 5 hydroxytryptophane, glycine, cholinolytics, dipropyl acetate, sodium hydroxybutyrate, Gammalonum, милацемид are usually inefficient. Purpose of a klomipramin or Reserpinum can provoke a sharp aggravation of symptoms of patients. In the past reception of these drugs was suggested to be used as diagnostic provocative test, but in a type of its danger now this reception is not recommended.

At a sharp aggravation of symptoms with development of heavy vegetative frustration of the patient it has to be placed in intensive care unit where carry out correction of cardiovascular and respiratory frustration, metabolic disturbances. In the presence of signs of a hyperactivity of a sympathetic nervous system (tachycardia, arterial hypertension) use of beta-blockers is shown.

Adequate symptomatic therapy allows to achieve in some cases long stabilization of a state and maintenance of functionality of the patient at the level necessary for self-service. But in certain cases the condition of patients continues to worsen.

Data on possible autoimmune genesis of a syndrome formed the basis for development of methods of an immunotherapy of SRCh. However efficiency of immunotropny means at SRCh, despite separate brilliant results, on average is moderate. Nevertheless, in recent years resort to them even more often, especially when by means of symptomatic therapy it is not possible to stabilize a condition of the patient.

Apply corticosteroids, a plasma exchange to treatment of a syndrome of the rigid person and in/in immunoglobulin. It should be noted a considerable individual varibelnost in reaction of patients with SRCh on the specified methods: at some of them corticosteroids, at others — in/in immunoglobulin, at the third — a plasma exchange are most effective. Predictors of efficiency of this or that method are not defined yet. Corticosteroids more often appoint in average doses (for example, 40 — 80 mg of Prednisolonum inside daily), but in recent years quite often use also high doses.

Against the background of treatment by corticosteroids improvement can become noticeable in several weeks, but sometimes it develops even more slowly (within several months). At a dose decline of a corticosteroid a recurrence is possible. According to Meinck (2000), analyzing results of treatment of 34 patients with SRCh of the most effective there was a scheme providing appointment Prednisolonum methyl in a dose of 500 mg in/in with the subsequent a gradual dose decline to 5 — 10 mg inside every other day as a maintenance dose. In some cases it was succeeded to cancel a maintenance therapy completely.
The favorable result is noted and at a plasma exchange combination to corticosteroids.

Use in/in immunoglobulin is more often than other methods of an immunotherapy brings positive takes. Immunoglobulin — rather safe drug, but at a part of patients causes moderate side effects, most often a headache (usually in the persons who earlier had migraine), nausea, a fever, fever, vomiting, an arthralgia and a dorsodynia, a lowering of arterial pressure, allergic reactions. Casuistic cases of the slight medicinal meningitis which is spontaneously regressing within 3 — 5 days are described.

Before administration of drug it is necessary to investigate the content of immunoglobulins in blood serum: at patients with the low level of immunoglobulin A products of anti-IgA of antibodies with potential risk of an anaphylaxis are possible. The drugs of immunoglobulins of new generation which appeared in recent years (such as IS-vein, octadin, etc.) differ in high degree in the cleaning in particular minimizing a possibility of infection with viral diseases, extremely low content of immunoglobulin A that ensures their good tolerance and safety.

At inefficiency of the specified measures in hard cases perhaps prolonged use of tsitostatik (for example, Azathioprinum or cyclophosphamide).