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Myasthenia gravis is an autoimmune disease characterized by muscle weakness and pathological fatigue due to autoaggressive phenomena with the formation of antibodies directed against various structures of the neuromuscular synapse. In most patients, the disease begins with the involvement of extraocular muscles, presenting with symptoms such as intermittent ptosis of the upper eyelid and/or binocular diplopia. In 15% of cases, clinical manifestations are limited to impairment of the levator palpebrae superioris and extraocular muscles, characteristic of the ocular form of myasthenia gravis. Specialists often encounter challenges in diagnosing this form, as serological and electrophysiological studies may be uninformative, necessitating diagnosis based on patient history and clinical picture. This literature review outlines the key aspects of the pathogenesis, clinical manifestations, methods of diagnosis and treatment of ocular myasthenia gravis.

The authors present a case of 75-year-old male patient with typical clinical and electroneuromyographic signs of Amyotrophic Lateral Sclerosis (ALS), manifested in 4 years after a diagnosis of generalized Myasthenia Gravis (MG) had been made. The aim of the article is to assess the possibility of pathogenetic integrated comorbidity of MG and ALS, which may have resulted from a common aberrant immune process and to emphasize the importance of detailed clinical analysis and adequate diagnostic methods essential for correct diagnosis and treatment. Only several cases of coexistence of MG and ALS have been described in medical literature. Exploring the pathogenetic association between MG and ALS may lead to dysregulation of thea immune system. Deficiency of T-regulatory cells, increased activity of atrophy-related atrogenes, anomalies of neuronal nitric oxide synthase can be found in both diseases. Immunoglobulin isolated from ALS patients can affect neuromuscular junction and activate AChRs, which plays an important role in the innervation and re-innervation of muscle fibers. Immunoglobulin also changes the function of Ca2+ channels. Blood level of circulatory Heat Shock Protein 70 (HSP70) antibodies in MG patients is elevated. HSP70 maintains normal conformation of cell proteins. Conversely, HSP70 antibodies cause HSP70's dysfunction and therefore, abnormal protein synthesis, which can be the main reason of neurodegenerative diseases, such as ALS. Experimental evidence indicates, that muscle and neuromuscular junctions may be initial targets of ALS. According to the "dying-back" hypothesis, neuromuscular junction damage and failure in MG patients may precede lower and upper motor neuron loss, and thus increase risk of developing ALS. Pathogenetic mechanisms of MG and ALS are the subjects of further studies. Refining the etiology of these two diseases will answer the question whether it is a transformation or a coexistence of MG and ALS in our case. The presented case demonstrates, that in spite of meeting all diagnostic criteria it is, sometimes, impossible to make the correct diagnosis. Only a detailed clinical analysis and adequate diagnostic methods contribute to correct diagnosis and adequate therapy.

Aim: To investigate the pattern of decrement in the muscles of patients with myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS)., Material and Methods: Twenty-seven patients with MG and 39 patients with LEMS were studied using low frequency repetitive nerve stimulation (3/ sec)., Results and Conclusion: The decrease of safety factor of neuromuscular transmission was equal in both groups. At the same time, a significant difference in the decrease of pattern of the amplitude compound of muscle action potential (CMAP) was found. In LEMS, by contrast with MG, another sequence of amplitude variability of CMAP from the second stimulus to the first and from the fifth stimulus to the fourth was noted. In LEMS patients, progressive decrement, manifesting by increasing ratios of late A9/A1 to early A4/A1 was found, whereas the MG patients showed retrogressive decrement expressed by the reduction in decrement ratio (from late to early). These differences reflect the mechanisms and status of acetylcholine mobilization and release from the axon terminal.

In the present work the results of the clinic-epidemiological analysis of 223 patients with the onset of the myasthenia at 60 y. o. and later, admitted and treated in the clinic of neurology for the passed 25years are represented. A dynamic growth of incidence of the late-onset myasthenia through the passed 10 years was administered. We administered a prevalence of the generalized form of the myasthenia gravis (61,5 %). The whole clinical table of the myasthenia was developed during an year in 76,7 % of the cases. A wide range of the concomitant somatic pathology in this group of the patients (especially, with a cardio-vascular pathology - 93,3 %) was found to worsen the course of the myasthenia itself. We found that the set of the therapeutic measures in myasthenia in the elderly is determined by the course of the myasthenia and the multiple organ failure due to the concomitant diseases. The scheme of complex corrective therapy of myasthenia gravis in elderly was developed.

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder caused by autoaggression directed to different antigenic goals of peripherial neuromotor apparatus. Approximately 80% of patients have detectable serum antibodies against acetylcholine receptors (ACHR). About 10-15% of the MG patients do not have ACHR - antibodies. This form is called seronegative (SN) MG. IN 35% of SN patients antibodies against muscle - specific fyrozine kinase (MUSK) is clearly observed. According to modern data, SN MG patients are resistant against traditional pathogenetic therapy of MG. In order to develop the strategy of timely and adequate treatment of SN MUSK positive MG, we decided to build up differential diagnostic criteriums for this form of MG. For this purpose we analyzed clinical - electroneuromyographic (ENMG), immunologic and pharmacological data of 9 SN MUSK positive MG patients. The specific clinical patterns for SN positive MG was not revealed. The analogical clinic - ENMG and pharmacological signs were observed in seropositive MG. Accordingly, antibodies do not determine the peculiarity of this desease. Therefore, the revelation of the antibodies has not only diagnostic value; it also defines the expediency of pathogenetic therapy of MG.

The MRC scale is traditionally used for assessment of the severity of movement disorders. The patients' effort is graded on a scale of 0-5. The use of this scale is limited by subjective biases and inadequate assessment of some functions. The quantitative scale for assessment of the severity of clinical symptoms of myasthenia (QMGS) allows to evaluate pathological muscle fatigability, the main syndrome of this disease, which is important for evaluating the severity of symptoms before and after the pathogenetic treatment or when probes with the introduction of acetylcholinesterase preparations are used.

Anti-acetylcholine receptor antibodies are detected in 80 to 90% of patients with generalized myasthenia gravis - seropositive myasthenia gravis (SPMG). Approximately 10% to 20% of patients with autoimmune MG do not have antibodies to acetylcholine receptor (AChR) - seronegative MG (SNMG). An immunological study of the blood serum of patients with SNMG revealed patients with or without antibodies to muscle specific tyrosine kinase (MuSK+ and MuSK-, respectively). A clinical study of 13 MuSK+ patients with myasthenia showed that this group was characterized by predominant affect of mimic and bulbar muscles with the rare involvement of eye movement and body muscles. In Musk+ patients with myasthenia, the clinical efficacy of antitoxin esterase drugs was minimal or absent. No unequivocal conclusion on the clinical pattern of this form of myasthenia has been made.

On the basis of clinical-EMG analyses, the researches have revealed the criteria characteristic of myasthenia associated with thyroid pathologies. The myasthenia process associated with thyroid pathology is mainly characterized as of generalized average intensity. Alongside with mup-s with reduced duration and amplitude characteristic of myasthenia, EMG exposes potentials with comparatively long duration and high amplitude (mainly when the process is associated with thyreotoxycosis). It should also be noted that spontaneous activity is intensively expressed. Considering all the above mentioned, we can conclude that these changes show disfunctioning of mup-s rather than the character of synapses caused by the process associated with the myasthenia. The results of the research will facilitate the timely revelation of the process associated with myasthenia and will lead to the unfailing adequate pathogenetic treatment.

Thirty-seven patients with myasthenia gravis (MG) underwent AChR-Ab analysis, clinical study and neurophysiological examination - repetitive nerve stimulation (RNS). About 16,2% of MG patients who were anti-AChR-negative constituted a so-called seronegative MG group (SNMG). Compared to the AChR-Ab positive patients (SPMG), the SNMG was characterized by the higher female/male ratio (6:1), higher frequency of infantile onset of MG (33,3%), absence of association with thymoma and highest frequency of myasthenic crisis (83,3%). The clinical pattern of SNMG differed from SPMG and was characterized by predominant affect of mimic bulbar and respiratory muscles that determined severity of the course and high frequency of myasthenic crises. The identical clinical pattern was found in 19,3% of SPMG patients. However the character of neuromuscular transmission in orbicularis oculi muscle was different in SNMG and this SPMG-group. The pathological decrement was observed in 83,3% muscles of the SPMG-group (from -20% to -74%) and only in one case in the SNMG-group (-48%). Besides, the absence of clinical and neurophysiological responses to anticholinesterase was noted in the SNMG-group. Cholinergic neuromuscular hyperactivity in SNMG patients manifested itself in clinical fasciculations and myokymic contractions of muscles which prevailed in facial muscles in 66,7% of SNMG patients. Neurophysiologic examination displayed extra repetitive discharges after the compound motor action potential (R-CMAP) at low-frequency stimulation after acetylcholine esterase inhibitors in 100% cases.

The article covers clinical and ophthalmologic characteristics of oculomotor disturbances in myastenic patients with endocrine ophtalmopathy, and differential diagnostic signs and peculiarities of endocrine ophtalmopathy in patients with a combination of the two diseases.

Using a set of techniques, segmentary and nonsegmentary autonomic nervous system compartments were studied at rest and under stress. Parasympathicotonia, on the background of general deficit of ascending nonspecific brain activity, was found to characterize myasthenia in general. A decrease of nonspecific brain activity level is combined with elevated anxiety. However, one may distinguish a generalized type of the disease by the presence of dissociation of the autonomic nervous system compartments due to sympathicotonia.

HLA-phenotype was determined in 59 juvenile patients of Russian nationality and in their 50 relatives by means of lymphocytotoxic test. There was a positive association with HLA-A1, B8 and DR3 and the negative one--with HLA-A2, A9, B5, B7, and DR7. The frequencies of HLA-A1, B8, DR3 were higher in boys than in girls with myasthenia. There were no significant changes of HLA frequencies in ocular form of the disease in comparison with the healthy group. The frequencies of HLA-B8 and DR3 were significantly higher in relatives of the patients with juvenile myasthenia than in control population.

Overall twenty-five patients (all women) who ranged from 16 to 56 years old were examined. They were divided into two groups: group I was formed of subjects with hyperplasia of the thymus gland, group II--thymoma. Blood serum levels of prolactin, progesterone, estriol, estradiol, testosterone hydrocortisone. All patients showed a significant increase in average blood plasma levels of estrogens, testosterone and prolactin. Average levels of progesterone and hydrocortisone in patients with thymus hypertrophy were lower than in controls, while in thymoma patients these were much higher. The data submitted are indicative of substantial differences in the endocrine status of myasthenia patients depending on tumor or nontumor lesion of the thymus gland, which fact may suggest different pathogenetic mechanisms of development of the condition.

Electrophysiological changes of the brain were investigated in 31 patients with various forms of myasthenia. Various focuses of primary excitement of the great brain cortex were revealed in the different disease forms. Focuses were mainly localized in the left temporal region. These patients had also different clinical signs. The data obtained permit to substantiate the application expediency of sedatives in the complex of treatment of myasthenia patients.

Thymectomy was carried out in 52 children with the generalized form of myasthenia at the Moscow Regional Research Clinical Institute in 1986-1991. The long-term results were studied in 50 patients in follow-up periods of 6 months to 5 years. The follow-up was studied in all patients, the muscular strength in various groups of muscles was measured according to a 5-point scale, and the function of external respiration, neuromuscular conductivity, and cellular and humoral immunity were studied. After thymectomy the symptoms of myasthenia disappeared completely or diminished significantly, the decrement was 11% on the average instead of 37% as was before the operation, the external respiration values improved, the level of circulating immune complexes and immunoglobulins became normal. The long-term results were appraised according to G. Keanes' scale. Group A was made up of 22 patients, group B of 13, group C of 5, group D of 8, and group E of 2 patients. Thus, the study shows that thymectomy is the most effective method for the treatment of myasthenia in children today.

Using needle transcutaneous electromyography of internal laryngeal muscles and kalymin tests, 40 patients with myasthenia of different forms were examined. It was found that patients with generalized and local pharyngeal-facial forms of the disease developed latent generalization of myasthenic injury. Characteristic changes can be used to determine the degree of disorders in the internal nervous-muscular apparatus of the larynx.

Seventeen patients with generalized myasthenia were treated by the enterosorbent vaulen for 20 days. Of these, 12 patients manifested an appreciable improvement of the well-being shown up by the enhancement of the power of oculomotor, mimic, bulbar, respiratory and body musculature. As a result of the treatment, the dose of anticholinesterase drugs was reduced 2-fold in 12 patients. The intake of these drugs could be fully discontinued in 3 patients. The clinically detectable improvement correlated with an increase of the amplitude of M-response and a reduction of the amplitude decrement during stimulation at a frequency of 3 imp/s. No changes in the electrolyte composition of the blood and protein fractions or other side effects of the drug were discovered. The data obtained served the basis for recommending enterosorption as one of the methods in a complex of treatment measures for patients suffering from myasthenia.

The authors describe the results of clinical and electromyography examinations of 20 patients with grave generalized myasthenia, carried out within the short-term (up to 2 weeks) and long-term period (up to 1 year) after splenectomy. In these patients, the preceding therapy (thymectomy, gamma-therapy of the thymic area, the treatment with prednisolone, azathioprine, plasmapheresis, etc) had not produced any beneficial effect. The efficacy of splenectomy was assessed according to the Keens classification (A-E). In the short-term period after splenectomy the C effect was recorded in 13 out of the 20 patients. Out of 9 patients examined in the long-term period, the B effect was revealed in 3 patients, the C effect persisted in 3 patients, and 3 patients manifested the return to the initial status, namely to the E effect. Therefore in the group of patients with grave generalized myasthenia, the efficacy of splenectomy amounted to 65%. In view of this fact the inclusion of the given treatment method into the multimodality treatment of myasthenic patients is regarded advisable.

Single injection of Ig preparations from the myasthenia-patient-blood on C57Bl mice, revealed two phases in the development of the myasthenic syndrome. The first phase started one-two hours after the injection only of the IgM preparation in a dose 2-10 mg. This phase was in progress for two days. The second phase developed during the injection of either the Igm or IgG preparations in a dose 6-10 mg (IgG) of 2-10 mg (IgM). This phase was characterized by the appearance of long myasthenic disorders in two-three week time after the experiment. Some of these mice perished. It was assumed that the absence of strict correlation between the concentration of anti-AChR-IgG antibodies and the gravity of myasthenia is connected with the IgM participation in the pathogenesis of the myasthenia and/or with the appearance of secondary autoantibodies towards the targets which differ from AChR's myoneural synapsis.

The analysis of conduction at neuromuscular junctions was performed in 25 patients with botulism and 31 patients with Lambert-Iton syndrome. These groups showed apparent differences in mechanisms of recruitment and posttetanic facilitation of the neurotransmitter release. Prolonged stimulation with the rate of 6 imp/s in ischemic muscles pointed to essential differences in the mechanisms facilitating the transmitter release. These differences of neuromuscular conduction disorders in botulism and Lambert-Iton syndrome are supposedly connected with affliction of different mechanisms of conduction facilitation in the neuromuscular synapses.

The authors have examined the status of sympathetic innervation of the skin structures (by measuring the amplitude and latent period of the appearance of the evoked skin sympathetic potential, ESSP) and the autonomic regulation of the cardiovascular system (by examining the R-R intervals of the ECG at rest and in various functional tests) in 9 patients with the Lambert-Eaton myasthenic syndrome, 10 normal subjects, and in 20 myasthenic patients (a control group). All patients examined before the treatment and 7 patients who were examined following the administration of corticosteroid therapy presented disorders of the latent period and/or the amplitude of ESSP, up to its total absence, as well as signs of cardiac arrhythmias indicative of a marked dysfunction of the cholinergic structures of the peripheral nerves. No correlation has been elicited between the depth of identified vegetative disturbances and the presence of clinical and electromyographic indicators of polyneuropathy. Medicamentous tests serve to confirm the synaptic nature of cholinergic disorders.

Based on the investigation of 33 distal and 163 proximal muscles in myasthenic patients in which posttetanic and postactivation facilitation was studied and adequate proserin doses injected, the authors have shown the "block" phenomenon to be most pronounced in proximal muscles. The authors offered to use the reversibility coefficient as reflecting the possible restoration of neuromuscular conduction. Evaluation of the "block" and a reversibility coefficient plays major role in assessment of contribution of presynaptic structures to operation of mechanisms dicturbing the neuromuscular conductance in myasthenia.

It has been shown that the overwhelming majority of myasthenia patients manifest changes in the cardiovascular system characterized by cardiac pains of different nature, duration and intensity, by electrocardiographic changes and lowering of the central hemodynamics and myocardial contractility. A direct relationship was established between heart involvement into the pathological process and myasthenia gravity as well as the underlying disease standing. The changes in cardiovascular function were not affected by the acute use of neostigmine.

Two patients with a rare combination of generalized myasthenia (M) and multiple sclerosis (MS) have been studied. The development of both diseases in the same patient, despite the rarity of such reports in the world literature, does not appear accidental and may be due to the common nature of pathogenetic mechanisms. The authors believe that the fundamental homogeneity of the diseases lies in impairment of immunological homeostasis characteristic of both autoimmune diseases. Myasthenic manifestations in MS may widely vary from mild subclinical forms of impairment of neuromuscular conductivity to severe generalized forms of M. The authors discuss possible mechanisms of blockage of the neuromuscular conductivity in cases of association of the above nosological entities.

Motor unit (MU) potentials of m. triceps br. of healthy subjects and patients with myasthenia gravis were recorded during slight isometric contractions. MU potentials were visually identified, semi-automatically coded and automatically led in the digital computer. In myasthenia the mean frequency of the MU discharges and SD of the interspike intervals were higher than in healthy states, the difference being not great, but significant. The interspike interval hystograms of single MUs were unchanged (normal). So the disturbances in pattern of motoneurone activity in myasthenia were mild. Proserin raised the muscle contraction strength and normalized the interspike interval variability but did not lower the frequency of MU discharges. The increase of the frequency may be accounted for the reduction of Renshaw inhibition.

A study was made of the evoked mechanical response of the adductor under supramaximal stimulation of the ulnar nerve in 24 normal test subjects, 10 patients with the involvement of motoneurons and their axons, 30 patients with chronic derangement of the neuromuscular transmission (myasthenia) and 8 patients with hypothyrosis. A reverse dependence was found of the Pt/Po ratio on the magnitude of post-tetanic potentiation in all the examined. The capacity of the muscle to potentiate the tension in response to the double stimulus and during the post-tetanic periods inversely related to the initial amplitude of the evoked mechanical response of the muscle and the time of the muscle contraction. It is assumed that the universal mechanism of the regulation of muscle contractile function in health and disease underlies the regularities described.

Changes of the activity potentials of motor units and muscular fibres registered with the aid of needle electrodes are compared with the results of morphological examinations of biopsy specimens of 1,096 muscles taken from 137 patients with myasthenia, combinations of myasthenia with thymoma and polymyositis, as well as from patients with terminal polyneuropathy with the myasthenic syndrome. It has been shown that characteristic of myasthenia are differentiated changes of the motor unit activity potentials: in half of the muscles examined the parameters of those potentials were found to be normal, no polyphasic or protracted potentials were observed. In the patient with combinations of myasthenia with thymoma, polymyositis, and in terminal polyneuropathy with the myasthenic syndrome pronounced changes of all the activity potentials of the motor units were observed in the form of both a sharp shortening and a prolongation of their duration; a great number of polyphasic potentials was registered and spontaneous activity of various degree was observed. Morphological examinations of 55 biopsy specimens of the muscles of the same patients revealed a correlation between the degree of the dystrophic and atrophic changes of the muscular fibres and depth of the affection as determined on the basis of electromyographic findings.