[Clinical results of using Nakom in diseases of the nervous system]. / Klinicheskie rezu'ltaty primeneniia Nakoma pri zabolevaniiakh nervnoi sistemy.

Clinical investigation was performed and dopamine metabolism (renal catecholamine excretion) studied in 29 children and 5 adults with various forms of CP, 5 myasthenic children and 1 child with Strümpel disease treated with Nakom. The therapy was judged expedient in 20% of the cases of pronounced muscular rigidity and dystonia with decreased dopamine excretion. The drug proved ineffective in atonic, astatic, severe hyperkinetic arms, and in cases with severe psycho-organic signs.

[Circadian rhythm of catecholamine excretion, effect of L-DOPA and Nacom in various diseases of the nervous system]. / Sutochnyi ritm ékskretsii katekholaminov, vliianie L-DOFA i nakoma pri nekotorykh zabolevaniiakh nervnoi sistemy.

The activity of the sympathoadrenal system (SAS) was studied in 132 patients with central nervous system diseases such as parkinsonism, deforming muscular dystonia (DMD), Huntington's chorea, myopathy and asthenic neurosis. The estimation was based on determinations of urine catecholamine (CA) excretion with the help of the fluorometric method developed by E. Sh. Matlina et. al. (1965). The control group included 50 healthy subjects. The findings obtained confirmed the reported data concerning the role of CA in the pathogenesis of the studied forms of nervous pathology. The study showed a decrease in dopamine excretion (DA) in parkinsonism, its increase in Huntington's chorea and DMD, and insufficiency of SAS activity in myopathy. Furthermore, additional criteria pointing to alterations in the diurnal SAS activity in the patients were revealed. These changes manifested themselves in the disruption of the diurnal rhythm of CA excretion as well as in the deficiency of DOPA and DA synthesis and deposition following a single dose of L-DOPA and nacome.

[Pathogenesis of hyperkinesis in children]. / O patogeneze giperkinezov u detei.

Pheylalanine metabolism was studied in 56 children with various forms of hyperkinesias. It was found that in the development of slow and fast hyperkinesias a certain role belongs to dihydroxyphenylalanine (DOPA). It is probable, that in patients with Turett's syndrome the synthesis of DOPA is increased while in patients the excretion of phenylacetylglutamine was found to be disturbed: it was decreased in the patients with the fast and increased in the children with the slow hyperkinesias. Phenylalanine load led to a lowering of the DOPA level in the patients with Turett's syndrome; an intensification of the synthesis of phenylacetylglutamine and diminution of the intensity of hyperkinesias. L-glutamine load resulted in detoxication of the toxic phenylalanine metabolites which inhibited the DOPA synthesis, as well as in a short-time increase in the phenylacetylglutamine excretion and a moderation of tonic hyperkinesias that manifested by athetosis and dystonia. All this points out that in the development of various forms of hyperkinesias a certain role belongs to amino acid metabolites.

[Treatment and prognosis of the therapeutic effect of L-DOPA in dystonia musculorum deformans]. / Voprosy lecheniia i prognozirovaniia terapevticheskogo éffekta preparata L-DOFA pri deformiruiushchei myshechnoi distonii.

Clinico-biochemical examinations of 55 patients suffering from various clinical forms of deforming myodystonia were performed. L-DOPA was used in 47 cases. A correlation between the therapeutic effect and the level of phenylacetylglutamine excretion was revealed. The increase of the phenylacetylglutamine excretion was an evidence of a positive result of the treatment that was noted in 36 patients (77%). A resistance to the drug was observed in cases when the phenylacetylglutamine excretion did not exceed its normal level. The quantitative determination of phenylacetylglutamine in the daily portion of the urine can be used as a prognostic test of the therapeutic efficacy of L-DOPA in patients with deforming myodystonia.

[Catecholamine excretion in torsion dystonia]. / Ekskretsiia katekholaminov pri torsionnoi distonii.

The study concerns some results of the catecholamine metabolism in torsion dystonia. The author found certain changes of the excretion of catecholamines that were different in patients with various clinical manifestations of the disease. The most expressed changes were observed in patients with prevalent local regidity of the muscles in the clinical picture. They were seen in significant descrease of the excretion of all catecholamines and DOPA; the most expressed was a decrease of dopamine and adrenalin discharge. Along with this in prevalent torsion spastic hyperkinesis in the clinical picture there was a tendency towards an increase of dopamine excretion (in the absence of DOPA and noradrenalin changes), and a decreased adrenalin excretion. A conclusion is drawn concerning heterogeneity of torsion dystonia that deals with a clinical polymorphism of the disease. The author discusses the pathogenetical significance of the found biochemical disturbances.

[Pathogenesis and treatment of torsion dystonia]. / Voprosy patogeneza i lecheniia torsionnoi distonii.

A study of the catecholamine excretion, their precursor DOPA and final metabolites--Homovaniline and vanilylphenylglycolic acid in torsion dystonia, detected certain changes which were different in patients with various clinical forms of the disease. On the basis of clinical and biochemical data 3 forms of torsion dystonia were distinguished: 1) with a prevalence in the clinical picture of muscle rigidity, leading to the development of pathological postures; 2) hyperkinetic forms and 3) mixed forms. In patients of the first group there was a decreased excretion of all catecholamines. On the basis of obtained data the conclusion is made that there is a drop in the intensity of the process of dophamine synthesis and an increase of its catabolism. In the hyperkinetic form, on the contrary, there is a tendency to an increase of dophamine synthesis. It is assumed that there is a drop in the intensity of the process of adrenaline synthesis and an increase of its catabolism. On the basis of biochemical heterogeneity of torsion dystonia the authors recommended different approaches in treating different forms of this disease. In a prevalent muscular rigidity the functions of the dophaminergic systems should be intensified: on the one hand, by administering precursors of dophamine L-DOPA, on the other--by inhibiting antagonistic activity with the aid of different cholinolytic preparations. In a hyperkinetic form a favorable effect is attained by preparations, inhibiting the dophaminergic activity (mainly preparations of the phenothiazine and butyrophenon series).

Effect of supplemental ascorbic acid in a case of torsion dystonia.

Determinations of various catecholamines and their metabolites have been performed on 24-hr urine collecions obtained from a patient with torsion dystonia and compared to values obtained in a control population. This study was initiated following significant symptomatic worsening by the patient with supplemental ascorbic acid at a dosage of 2 g/day. Compared to base-line values, there resulted no significant alteration in urinary excretion of DOPA, dopamine, norepinephrine, epinephrine, or VMA for either the patient or a group of controls, receiving 1 g/day vitamin C. MHPG is the glycol metabolite of norepinephrine, and is produced both in central and systemic tissues, whereas VMA is not synthesized in brain. The MHPG excretion for the patient increased 150% with supplemental ascorbate, whereas the control individuals demonstrated a mean increase of 19.6%. It is possible that the symptomatic worsening by the patient and the increased excretion of MHPG in response to supplemental ascorbic acid are causally related. Ascorbic acid affects catecholamine biosynthesis at two metabolic loci; it is the necessary cofactor for dopamine-beta-hydroxylase and, by maintaining biopterin in reduced form, facilitates tyrosine hydroxylase holoenzyme activity. Thus, the vitamin may have effected increased central synthesis or turnover of norepinephrine, or both, with resultant clinical worsening.