RESUMO
OBJECTIVE: to determine the efficacy of unilateral posteroventral pallidotomy (PVP) in the treatment of drug-induced dyskinesia (DID) in Parkinson's disease (PD). MATERIAL AND METHODS: We analyzed surgical treatment of 14 patients with PD complicated by DID who underwent unilateral PVP at the Research Center of Neurology in the period between 2012 and 2015. The clinical type of DID was mainly represented by peak-dose choreoathetoid dyskinesia, more pronounced in the distal limbs, and predominantly unilateral. The severity of drug-induced dyskinesia was assessed on the UPDRS scale (part IV-A) before surgery and at 1 week and 6 months after surgery. RESULTS: One week after pallidotomy, all of the 14 patients had a regression of contralateral dyskinesia by 68.3±9.7%; 50% of patients had a regression of ipsilateral dyskinesias by 43%, on average. In 50% of cases, the dose of levodopa was reduced by 15%, on average. On examination at 6 months after surgery, regression of contralateral dyskinesia was 55.7±8.8%, and the severity of ipsilateral DID returned to the preoperative level. The use of pallidotomy significantly improved the indicators of daily activity and quality of life of patients. There were no significant postoperative complications. Three patients had mild speech disorders in the form of dysarthria, which regressed 2-3 weeks after surgery.
Assuntos
Discinesia Induzida por Medicamentos/cirurgia , Palidotomia/métodos , Doença de Parkinson/cirurgia , Idoso , Discinesia Induzida por Medicamentos/patologia , Discinesia Induzida por Medicamentos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologiaRESUMO
The cerebrospinal fluid of patients with Parkinson's disease was shown to contain extracellular DNA. Extracellular DNA concentration in the cerebrospinal fluid was 3.3-fold lower than in blood plasma from these patients. HPLC-mass spectrometry analysis showed that the pool of extracellular DNA from the liquor is characterized by a lower content of deoxythymidine, but greater amounts of deoxycytidine and deoxyguanosine than the pool of extracellular DNA from the plasma. The level of deoxyguanosine was 2 times lower than that of deoxycytidine (as differentiated from plasma extracellular DNA with similar content of these substances). Our findings indicate that extracellular DNA from the cerebrospinal fluid contains considerable amounts of modified deoxyguanosine. These data attest to significant differences in the quantitative and qualitative characteristics of extracellular DNA from the blood and cerebrospinal fluid of patients. Specific features of extracellular DNA from the cerebrospinal fluid of patients suggest its involvement in the pathogenesis of Parkinson's disease.
Assuntos
DNA/sangue , DNA/líquido cefalorraquidiano , DNA/química , Doença de Parkinson/genética , Cromatografia Líquida de Alta Pressão , Desoxirribonucleosídeos/análise , Humanos , Espectrometria de Massas , Estatísticas não Paramétricas , Espectrometria de Massas em TandemRESUMO
Levodopa remains a 'gold standard' for the treatment of patients with Parkinson's disease (PD), but its chronic use is accompanied by fluctuations of symptoms and dyskinesias related to unfavorable pharmacokinetics of levodopa and progressing loss of the nigrostriatal neurons. Prescribing inhibitors of catechol-O-methyl-transferase (enzyme of dopamine metabolism), entacapone or tolcapone, is a perspective approach to the correction of the above-mentioned complications. We followed up 402 patients with PD who received long-term therapy with a combined preparation Stalevo (levodopa/carbidopa/entacapone) for 2-5 years (2.9 ± 0.9 years). The high (92.8%) compliancy and good tolerance of the drug in patients with PD was shown. Stalevo leads to the stabilization of the response to levodopa, improvement of patients' functional capacities, increase in their everyday activity, and improvement of quality of life. Stalevo may be regarded as a preparation of choice in the treatment of motor complications in elderly patients, correction of night symptoms of PD and in a number of other clinical situations arising in hospital and outpatient practice.
Assuntos
Carbidopa/administração & dosagem , Catecóis/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbidopa/efeitos adversos , Catecóis/efeitos adversos , Agonistas de Dopamina/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Resultado do TratamentoRESUMO
Therapeutic efficacy of the plant neuroprotector Phytomix-40 in Parkinson's disease was demonstrated. This preparation consists of the components from extracts of 40 plants, including some adaptogens (ginseng, eleutherococcus, Rhodiola rosea, etc.). The preparation normalized immune, antioxidant, and hormonal parameters in patients. The neuroprotective plant adaptogen can be used in complex therapy for Parkinson's disease for improving its efficacy.
Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/prevenção & controle , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-IdadeRESUMO
The results of mirapex (pramipexol) treatment of 402 patients with Parkinson's disease and juvenile parkinsonism during the period from 6 months to 7 years are summarized. Mirapex was used in monotherapy as well as in combination with levadopa and other antiparkinsonic drugs. The drug was well tolerated and effective in rest tremor, hypokinesia, muscle rigidity and depression, the more pronounced effect being seen at the early stage of the disease. The use of mirapex allows an effective control of motor fluctuations developing during long-term continuous levodopa therapy. The results obtained characterize mirapex as a drug of choice in the treatment of juvenile parkinsonism. In case of a break in mirapex treatment, the recommencement of treatment usually is not accompanied by reduced sensitivity to drug effect.
Assuntos
Antiparkinsonianos/uso terapêutico , Benzotiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Benzotiazóis/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pramipexol , Receptores de Dopamina D1/antagonistas & inibidores , Fatores de Tempo , Resultado do TratamentoRESUMO
Content of neurotransmitter amino acids before and after treatment with He-Ne-laser was measured in blood of two groups of the Parkinson's disease patients distinguished by low (first group) and high (second group) activity of monoamine oxidase B and Cu/Zn-superoxide dismutase. An increase in taurine level at the early stage of the disease (first group of patients) suggests that taurine may be a marker of compensatory abilities of the organism. The violation of the glutamate/taurine balance at the later stages of the disease and its normalization following the laserotherapy accompanied improvement of neurological symptoms.
Assuntos
Neurotransmissores/sangue , Doença de Parkinson/sangue , Feminino , Humanos , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Monoaminoxidase/sangue , Doença de Parkinson/terapia , Superóxido Dismutase/sangueRESUMO
The influence of laser therapy on the course of Parkinson's disease (PD) was studied in 70 patients. This influence appeared adaptogenic both in the group with elevated and low MAO B and Cu/Zn SOD activity. Laser therapy resulted in reduction of neurological deficit, normalization of the activity of MAO B, Cu/Zn-SOD and immune indices. There was a correlation between humoral immunity and activity of the antioxidant enzymes (SOD, catalase). This justifies pathogenetically the use of laser therapy in PD.
Assuntos
Terapia com Luz de Baixa Intensidade , Doença de Parkinson/imunologia , Doença de Parkinson/radioterapia , Idoso , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/química , Catalase/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Peso Molecular , Monoaminoxidase/sangue , Doença de Parkinson/sangue , Doença de Parkinson/fisiopatologia , Valor Preditivo dos Testes , Valores de Referência , Superóxido Dismutase/sangueRESUMO
Serum levels of interferon-gamma (IF gamma), tumor necrosis factor alpha (TNF alpha) and autoantibodies (a-AT) to these cytokines were investigated in patients with Parkinson's disease (PD). The increased levels of TNF alpha (50%) and IF gamma (35%) were found in PD patients. There was close correlation between the serum level of TNF alpha and the manifestation of neurological symptoms (r = 0.434; p < 0.05), and between levels of IF gamma and the duration of this disease (r = 0.4511, p < 0.05) and patients age as well (r = 0.4358; p < 0.05). There was increased level of a-AT to TNF alpha in PD patients versus healthy controls (130.3 +/- 11.92 and 105.3 +/- 4.62, respectively, p < 0.05). The combined increase of levels of a-AT to TNF alpha and IF gamma (r = 0.91, p < 0.01) close reverse correlation between duration of PD and levels of a-AT to TNF alpha and IF gamma (r = 0.4644 and r = 0.606, respectively, p < 0.01) were also recognised. The data obtained suggest the involvement of TNF alpha and IF gamma into the pathological process during PD, which requires further investigation in this direction.
Assuntos
Autoantígenos/sangue , Interferon gama/sangue , Doença de Parkinson/sangue , Fator de Necrose Tumoral alfa/metabolismo , Estudos de Casos e Controles , Humanos , Técnicas Imunoenzimáticas , Interferon gama/imunologia , Doença de Parkinson/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The effect of He-Ne laser radiation on activity of MAO B, Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinson's disease was studied in vivo and in vitro. The effects of intravenous in vivo irradiation (intravenous laser therapy) were more pronounced than those observed in similar in vitro experiments. It is concluded that generalized effect of laser therapy involves interaction between blood cells.
Assuntos
Sangue/efeitos da radiação , Lasers , Doença de Parkinson/sangue , Doença de Parkinson/radioterapia , Plaquetas/citologia , Plaquetas/metabolismo , Catalase/metabolismo , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/efeitos da radiação , Monoaminoxidase/metabolismo , Doença de Parkinson/fisiopatologia , Superóxido Dismutase/metabolismoRESUMO
Two novel protein antigens-Hbmp-1 and Hbmp-2 have been isolated from human brain tissue. Test-systems for determining auto-antibodies (a-Ab) to above mentioned proteins, as well as to basic myelin protein, S-100 beta and glial fibrillary acid protein have been developed. Sixty-three HLD patients have been examined. Increased a-Ab levels to the novel proteins has been shown in HLD patients; no difference between HLD patients and control groups being found for a-Ab levels to other proteins. Correlation has been observed between a type and course of the disease, on the one hand, and a-Ab levels to Hbmp-1 and to Hbmp-2, on the other hand.
Assuntos
Autoanticorpos/imunologia , Proteína Glial Fibrilar Ácida/imunologia , Degeneração Hepatolenticular/imunologia , Proteína Básica da Mielina/imunologia , Proteínas S100/imunologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatolenticular degeneration (HLD) is a severe autosomal-recessive disorder of the copper metabolism. It is characterized by excessive accumulation of copper in the brain and in viscera and is conditioned by the damage in the gene of copper ATP-ase (ATP7B). The paper presents the results of screening of ATP7B gene mutation in 42 patients with HLD from Russian population. The regions of ATP7B gene that are the most frequently exposed to the mutation have been studied (the exzones 14, 15, 16, 18). It is demonstrated that A-->C mutation in the 14-th exzone that led to the change of histidine1069 amino acid for glutamine, was found in more than 60% of patients--Slavs from the European Russia. This mutation was observed in both homo- and heterozygous states. The deletion of (CCC-->CC) nucleotide in the 15-th exzone of the gene was observed in 2 cases. The detailed analysis of the clinical-genetic correlations was performed in patients with the determined damages of ATP7B gene. In Russia the experience of the direct DNA-diagnosis of HLD is described for the first time. It is significant for early evaluation of the patients in preclinical state and for prescription of the preventive copper-eliminating therapy.
Assuntos
Adenosina Trifosfatases/genética , Degeneração Hepatolenticular/genética , Mutação Puntual/genética , Área Programática de Saúde , Análise Mutacional de DNA , Éxons/genética , Deleção de Genes , Degeneração Hepatolenticular/epidemiologia , Humanos , Reação em Cadeia da Polimerase , Federação Russa/epidemiologiaAssuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Distúrbios Distônicos/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Adolescente , Adulto , Idoso , Toxinas Botulínicas Tipo A/farmacologia , Distúrbios Distônicos/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Fármacos Neuromusculares/farmacologia , Índice de Gravidade de DoençaRESUMO
18 patients with hepatolenticular degeneration (Wilson's disease, WD) aged 15-38 years were subjected to an overall clinical and neurophysiologic examinations. As a result, the data obtained enable to evaluate functional reserves of CNS of the WD patients in correlation with the illness duration and severity of neurologic symptoms. Correlation between an increase of interpeak I-V and the degree of neurological deficit and, also, level of ceruloplasmin was established (r = -0.45; p < 0.05). Correlation between an increase of latency P300 and the degree of manifestation of neurologic symptoms was identified as well (r = 0.63; p < 0.05). Positive dynamics of evoked potentials was followed in 4 WD patients during copper-eliminative drugs treatment.
Assuntos
Potenciais Evocados P300/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Degeneração Hepatolenticular/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
Limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM) are autosomal recessive disorders caused by mutations in the dysferlin gene on chromosome 2p13. The authors studied a large Russian family with both LGMD2B and MM. All affected individuals, as well as one preclinical boy with dystrophic changes on muscle biopsy, were found to be homozygous for a novel dysferlin mutation, TG573/574AT (Val67Asp). This finding supports the view that additional factors (e.g., modifier genes) contribute to the phenotypic expression of causative mutations in dysferlinopathies.
Assuntos
Proteínas de Membrana , Proteínas Musculares/genética , Músculos/patologia , Distrofias Musculares/genética , Adulto , Criança , Disferlina , Feminino , Humanos , Masculino , Distrofias Musculares/patologia , Mutação/genética , Linhagem , FenótipoAssuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Degeneração Hepatolenticular/genética , Cromossomos Humanos Par 13/genética , ATPases Transportadoras de Cobre , Humanos , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Federação RussaRESUMO
Autosomal recessive progressive muscular dystrophies may be clinically subclassified into limb-girdle muscular dystrophy (LGMD) and distal myopathy (DM), each clinical form being genetically heterogeneous. Genes for LGMD type 2B and Miyoshi myopathy (a form of DM) have been mapped to essentially the same region on chromosome 2p. We described recently a large inbred family with autosomal recessive muscular dystrophy in which the LGMD and the DM phenotypes were manifested in separate affected members, and we assigned the gene for this condition to the same locus as in LGMD2B and Miyoshi myopathy. Here we report extended haplotypes in this family generated from 15 markers located at the region of interest on chromosome 2p13. Key recombinants allowed us to reduce further the candidate region for this polymorphic condition and defined the loci D2S327 and D2S2111 as the most likely boundaries of the mutant gene.
Assuntos
Cromossomos Humanos Par 2/genética , Ligação Genética , Distrofias Musculares/genética , Mapeamento Cromossômico , Feminino , Genes Recessivos , Marcadores Genéticos , Haplótipos , Humanos , Escore Lod , Masculino , Distrofias Musculares/classificação , Mutação , Linhagem , FenótipoRESUMO
The serum samples from 29 patients with Parkinson's disease were analysed for the levels of the autoantibodies (a-AB) and antiidiotype antibodies (AIAB) to the proteins of nervous system S-100, GFAP, NKP and MP-65. High levels of a-AB or AIAB to at least 3 proteins were seen in patients with severe course of the disease. No significant changes of these levels were observed in patients with light course of the disease. The plasmapheresis was carried out to some patients with severe course of the disease. After this procedure the decrease of neurological deficit from number 21 +/- 2 to 8 +/- 1 on Webster's scale and decrease of a-AB and AIAB levels to normal values (in some cases it became lower than normal values) were observed. It can be concluded that the levels of the a-AB to the nervous tissue proteins correlate with clinical condition of the patient.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Autoanticorpos/sangue , Proteínas do Tecido Nervoso/imunologia , Doença de Parkinson/imunologia , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína Glial Fibrilar Ácida/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Proteínas S100/imunologiaRESUMO
A unique inbred Avar family from an isolate of the Dagestan highland was studied. Unusual phenotypic expression of autosomal recessive progressive muscular dystrophy was revealed in 12 members of this family from three generations. Limb-girdle (proximal) muscular dystrophy (LGMD) was detected in nine patients, while the other three patients displayed typical distal myopathy (DM). Genetic linkage analysis with several candidate loci determining various forms of muscular dystrophy allowed a gene for this polymorphic syndrome to be assigned to chromosome 2p13. In spite of the difference in clinical manifestation, all patients appeared to be homozygous for a unique haplotype. This implies the founder effect and proves the same genetic basis of LGMD and DM in the family. Recombination analysis showed that the centromeric and telomeric ends of the gene region are marked with D2S2111 and D2S327, respectively (genetic distance < 1 cM). This region is overlapped by two larger regions in which the genes for LGMD type 2B (LGMD2B) and Miyoshi myopathy were recently mapped. Complex analysis of clinical and genetic data indicated that LGMD2B, Miyoshi myopathy, and the revealed polymorphic syndrome may represent allelic variants of 2p13-linked autosomal recessive muscular dystrophy.
Assuntos
Cromossomos Humanos Par 2 , Genes Recessivos , Distrofias Musculares/genética , Altitude , Mapeamento Cromossômico , Daguestão , Progressão da Doença , Feminino , Haplótipos , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , Recombinação GenéticaRESUMO
We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene.
Assuntos
Distrofias Musculares/genética , Adolescente , Criança , Mapeamento Cromossômico , Cromossomos Humanos Par 2 , Distrofina/genética , Feminino , Ligação Genética , Haplótipos , Humanos , Masculino , Distrofias Musculares/patologia , Linhagem , FenótipoRESUMO
All the cases of hereditary motor and sensory neuropathy (HMSN) in an eastern part of Kirov region (Russian north-east) were ascertained (N = 42 including 11 persons with pre/subclinical forms; m: f = 1). HMSN prevalence is 15.95 +/- 2.47.10(-5) being higher in rural than in urban populations. The distribution of HMSN families (total 16) in 9 districts of the region is uneven. HMSN is the most common of all hereditary muscular disorders in the region. Autosomal dominant inheritance was established in 12 families, AD gene frequency is 10.90 +/- 2.90.10(-5) gene penetrance being 90%. Sporadic cases were few (N = 4; 9.76%). No proven autosomal recessive or X-linked inheritance was found out.