[THE INFLUENCE OF A COMBINATION OF MODERN DRUGS NUCLEINAT AND ALFAGIN ON THE CONCENTRATION OF CIRCULATING IMMUNE COMPLEXES AND THEIR MOLECULAR COMPOSITION IN THE SERUM OF PATIENTS WITH IRRITABLE BOWEL SYNDROME ON THE BACKGROUND OF NEUROCIRCULATORY DYSTONIA IN COMPLEX MEDICAL REHABILITATION].

The effect of the combination nucleinat and alfagin in a complex of medical rehabilitation at the level of circulating immune complexes (CIC) in serum of patients and their molecular composition with irritable bowel syndrome (IBS), against neurocirculatory dystonia (NeD). It is established that the combination of nucleinat and alfagin in medical rehabilitation of patients with this comorbid disorders contributes to the normalization of the total concentration of the CEC and their molecular composition, which indicates the validity of the application of the pathogenesis combinations of drugs in complex medical rehabilitation of patients with lBS against NCD.

[THE EFFECTIVENESS OF THE MODERN IMMUNOACTIVE PREPARATION IMMUNOFAN FOR MEDICAL REHABILITATION OF PATIENTS WITH NONALCOHOLIC STEATOHEPATITISIS AGAINST NEUROCIRCULATORY DYSTONIA, AFTER INFECTIOUS MONONUCLEOSIS].

The presence of the expressed changes of cellular immunity, namely T-lymphopenia, disbalance of subpopulation structure of T-lymphocytes with primary downstroke T-helpers/inductor (CD4+), decrease immunoregulatory index CD4/CD8, and functional activity of T-cells is characteristic for the patients with nonalcoholic steatohepatitis, against neurocirculatory dystonia, after infectious mononucleosis. Including in a medical rehabilitation of such patients immunofan promoted practically full correction of the revealed infringements on the part of a cellular link of immunity.

A mutation in the IL-2 receptor gamma chain gene associated with X-linked severe combined immunodeficiency accompanying opisthotonus.

Severe combined immunodeficiency (SCID) is an inherited disease with profoundly defective T cells, B cells, and NK cells. X-linked severe combined immunodeficiency (X-SCID) is its most common form. In this report, we describe a 4-month old male with X-SCID who also showed opisthotonic posturing. Opisthotonus represents abnormal motor posturing and is defined as the posturing, in which the neck and back are arched posteriorly. The patient was referred to our hospital with liver dysfunction, respiratory distress, anal abscess, poor feeding and wasting; the patient appeared to suffer from severe and persistent infections. In fact, circulating T cells were not detectable, despite that the number of B cells was maintained in the normal ranges. Diagnosis of X-SCID was established by DNA analysis of the interleukin (IL)-2 receptor gamma chain gene; namely, we detected the novel mutation within exon 2 (221 C-->A), which leads to the substitution of tyrosine codon for stop codon (Y69stop). Computed tomography of the brain revealed mild atrophy, but no hemorrhage and no malformation. There were no pathological findings in the cerebrospinal fluid. Thus, the cause of opisthotonic posturing remains unknown. The patient died due to severe infection at the age of 7 months. It remains to be investigated to clarify the relationship between the mutation and clinical manifestations. In conclusion, we have identified the novel mutation in the IL-2 receptor gamma chain gene, which is associated with X-SCID. Furthermore, this is the first report that describes the patient with X-SCID accompanying opisthotonus.

Case of primary Sjogren's syndrome preceded by dystonia.

There are only six cases in literature that describe development of dystonia with Sjogren's syndrome (SS). We describe a case of a 43-year-old woman who presented with symptoms including movement disorder, sensory neurogenic bladder, sensory loss and neuropathic pain, migraine like headaches, musculoskeletal pain, Raynaud's phenomenon and dysautonomia. Symptoms started in 2000, with weakness that progressed to dystonia in 2003. Diagnostic work-up was inconclusive with negative inflammatory serologies, cerebrospinal fluid and MRI for many years. After patient developed sicca syndrome with dry eyes and mouth in 2009, her rheumatoid factor titre was elevated (550 IU/mL), erythrocyte sedimentation rate, anti-Sjogrens syndrome-related antigen A (anti-Ro/SSA) and anti-SSB/La: anti-Sjogrens syndrome-related antigen B (anti-La/SSB) became positive. Lip biopsy confirmed diagnosis of SS. She was diagnosed with primary SS with neurological involvement. Her symptoms responded well to intravenous methylprednisolone. Symptoms stabilised with trials of immune-suppressive therapy. This is a case that demonstrates the delay of diagnosing SS with preceding unique neurological association.

Treatment of putative immune-mediated and idiopathic cervical dystonia with intravenous methylprednisolone.

A young pregnant woman developed a persistent dystonic head tremor a few days after Rho (D) immune globulin administration; further deterioration occurred after a second administration of Rh(o) (D) immune globulin with the development of marked retrocollis. This persisted and she was treated 2 months later with a 5-day course of intravenous (1 g daily) methylprednisolone (IVMP) with resolution of her condition. We proceeded to treat similarly the next four patients with idiopathic cervical dystonia who were seen in our practice and who had current symptoms of less than 6 months duration. One also experienced persistent resolution and another had a marked, but transient, improvement after each of two separate courses of IVMP. The other two patients did not have improvement. This suggests a possible autoimmune pathogenesis for a limited subset of cervical dystonia. However, identifying which cases of recent-onset cervical dystonia will respond to IVMP therapy has yet to be determined.

Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance.

We measured serum antibodies to botulinum toxin (ABT) in 96 patients with focal dystonia who had been treated with type A botulinum toxin. The frequency of detectable ABT was 3% (three patients). Patients with ABT had received more than 50 ng of botulinum toxin, and the shortest time between two injections was significantly less than in patients without ABT. The clinical evolution of the three patients was heterogeneous: one had decreased effectiveness with repeated injections, another had persistent improvement, and the third never responded to toxin injections.

Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response.

OBJECTIVE: To compare the mouse protection bioassay (MPB) to the Western blot assay (WBA) in detecting antibodies against botulinum toxin A (BTX-A) and to correlate the assay results with clinical responses to BTX-A injections. METHODS: MPB and WBA assay results were compared in 51 patients (34 nonresponders and 17 responders) who received BTX-A injections, most commonly for cervical dystonia. A subset of patients received a "test" injection into either the right eyebrow (14) or right frontalis (12). RESULTS: Twelve patients with antibodies against BTX-A (Ab+) detected by WBA did not demonstrate antibodies (Ab-) by MPB. Conversely, five patients were Ab+ by MPB but Ab- by WBA. Specificity of the MPB was 100% on all three parameters (clinical, eyebrow, and frontalis injections), whereas WBA specificity was only 71% for clinical response but 100% for both eyebrow and frontalis responses. Sensitivities for both assays were low (33 to 53%). Of the 16 patients previously Ab+ by MPB, seven became negative on retesting after a mean interval of 33 months (range, 6 to 93 months). CONCLUSIONS: The lower specificity of the WBA compared to the MPB suggests that the WBA detects nonblocking antibodies. Eyebrow and frontalis "test" injections correlated well with MPB and WBA results and with clinical responses and may be useful in the evaluation of BTX nonresponders.

Reduced lymphoblast neopterin detects GTP cyclohydrolase dysfunction in dopa-responsive dystonia.

OBJECTIVE: To demonstrate that measurement of endogenous neopterin levels in unstimulated lymphoblasts identifies inherited GTP cyclohydrolase 1 (GCH1) dysfunction and can be a diagnostic test for dopa-responsive dystonia (DRD). BACKGROUND: DRD results from decreased dopamine biosynthesis due to dysfunctional GCH1. GCH1 is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for catecholamine synthesis. Mutations in the GCH1 coding region are identified in 60 to 70% of DRD cases; in others, the cause of GCH1 dysfunction is unknown. METHODS: Using HPLC, we measured endogenous neopterin, the main byproduct of the GCH1 reaction, in lymphoblasts under basal conditions and following GCH1 stimulation conditions. RESULTS: In a four-generation family, all identified carriers of dysfunctional GCH1 had basal neopterin levels that were below those of controls. The spouse of one carrier had a mutation in exon 6 of GCH1. Although this man's GCH1 function appeared unaffected by this, his daughter, who was a compound heterozygote with her mother's dysfunctional GCH1 and this mutation, had a phenotype that was more severe than that of typical DRD. Cytokine or phytohemagglutinin (PHA) did not induce GCH1 activity in any carrier of dysfunctional GCH1; controls who did not respond to PHA had increased neopterin levels following cytokine induction. CONCLUSIONS: Endogenous neopterin measurement in unstimulated lymphoblasts is an accurate tool to identify dysfunctional GCH1 and a potential specific diagnostic marker for dysfunctional GCH1 in DRD and other neurologic disorders. Not all mutations in GCH1 affect GCH1 enzyme activity. PHA induction alone, previously used by others, may result in incorrect identification of GCH1 dysfunction in DRD.

Movement disorders of autoimmune origin.

In recent years there has been renewed interest in the role of autoimmunity in many neurological disorders such as multiple sclerosis and neurodegenerative diseases. Research advances in this field have led to the discovery of new potential therapeutic strategies. There are, however, only a few neurological disorders in which an autoimmune origin has been adequately documented and definitely confirmed. The most important neurological diseases causing movement disorders in which an autoimmune basis has been demonstrated are summarized in this review. The possible role of immunity with the most frequent movement disorders such as parkinsonism or dystonia is also commented.

[HLA antigens in persons with a predisposition to frequent sympathetic-adrenal paroxysms]. / Antigeny HLA u lits so sklonnost'iu k chastym simpatiko-adrenalovym paroksizmam.

Comparison of the rate of HLA antigens I in 81 patients with frequently occurring sympathoadrenal paroxysms (SAP) associated with vegetovascular dystonia and 113 healthy subjects revealed the increase of the number of antigen B12 carriers among the patients as compared to the healthy subjects' group. The number of antigens A9, B35 in SAP patients was elevated whereas that of B18, B38 and B40 decreased. SAP related to age-associated hormonal rearrangements were marked by antigens Cw4 and A1, the grave SAP patterns by B12, SAP without nocturnal paroxysms and the early disease onset by the lack of antigen A19. The dominant gene that determines the onset of SAP is localizes in the HLA area. It may be associated with a hypothetical gene analogous to the locus implicated in the determination of the threshold of neuromuscular excitability of rats. It is not excluded that such a relationship is mediated via the blood content of Mg2+.

[The nondrug treatment of patients with autonomic vascular dystonia subjected to ionizing radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station]. / Nemedikamentoznoe lechenie bol'nykh vegetativno-sosudistoi distoniei, podvergavshikhsia vozdeistviiu ioniziruiushchego izlucheniia v rezul'tate avarii na Chernobyl'skoi AES.

The suggested mode of treatment combines the intravascular laser-light irradiation of blood with the visual analyzer exposure to light the brightness of which changes evenly and rhythmically with a frequency of 7-8 vibrations per minute (0.13 Hz). The combined use of the aforementioned exposures is justified due to the fact that exposure to both ionizing radiation and psychogenic factors play an important role in the pathogenesis of vegetovascular dystonia developing in the liquidators of the Chernobyl Atomic Power Plant breakdown. Change of lighting makes for the evolution of the inhibitory process in the cortex, has a sedative effect, attenuates the influence of psychotraumatizing factors. Intravascular laser-light irradiation of blood has a beneficial effect upon the organism's reactivity and immune system. Under the influence of the therapy adopted, all patients in present series (n = 67)--liquidators of the Chernobyl APP breakdown, suffering from VVD, demonstrated beneficial shifts both in the vegetovascular reactions and immune status, as evidenced by the analysis of the results of the presented mode of treatment in this patient population.

Neutralizing antibodies in dystonic patients who still respond well to botulinum toxin type A.

BACKGROUND: Complete secondary therapy failure due to antibodies against botulinum toxin A (BoNT/A-ABs) may raise extensive treatment difficulties. We tested whether neutralizing BoNT/A-ABs can be detected in dystonic patients with good clinical responses to botulinum toxin A (BoNT/A) treatment. METHODS: We used the ninhydrin sweat test (NST) and the mouse diaphragm test (MDT) in 28 subjects. Of 119 dystonic patients who responded well to BoNT/A, we randomly selected 14 and compared the results of the NST and MDT with 14 healthy controls. RESULTS: Higher BoNT/A-AB titers correlated significantly with smaller anhidrotic areas. We found seven patients with borderline antibody (AB) values (MDT 0.4 to 0.8 mU/mL) with significantly smaller anhidrotic areas (NST) compared with healthy controls and AB-negative patients. Risk factors for smaller anhidrotic areas were short injection intervals but not prolonged exposure to BoNT/A or high injection doses. CONCLUSIONS: These data demonstrate that >40% of dystonic patients who respond well to botulinum toxin A (BoNT/A) show partial nonresponsiveness on the ninhydrin sweat test and have low titers of neutralizing BoNT/A antibodies.