RESUMO
Transgene silencing provides a significant challenge in animal model production via gene engineering using viral vectors or transposons. Selecting an appropriate strategy, contingent upon the species is crucial to circumvent transgene silencing, necessitating long-term observation of in vivo gene expression. This study employed the PiggyBac transposon to create a GFP rat model to address transgene silencing in rats. Surprisingly, transgene silencing occurred while using the CAG promoter, contrary to conventional understanding, whereas the Ef1α promoter prevented silencing. GFP expression remained stable through over five generations, confirming efficacy of the Ef1α promoter for long-term protein expression in rats. Additionally, GFP expression was consistently maintained at the cellular level in various cellular sources produced from the GFP rats, thereby validating the in vitro GFP expression of GFP rats. Whole-genome sequencing identified a stable integration site in Akap1 between exons 1 and 2, mitigating sequence-independent mechanism-mediated transgene silencing. This study established an efficient method for producing transgenic rat models using PiggyBac transposon. Our GFP rats represent the first model to exhibit prolonged expression of foreign genes over five generations, with implications for future research in gene-engineered rat models.
Assuntos
Elementos de DNA Transponíveis , Proteínas de Fluorescência Verde , Ratos Transgênicos , Animais , Elementos de DNA Transponíveis/genética , Proteínas de Fluorescência Verde/genética , Ratos , Técnicas de Transferência de Genes/veterinária , Transgenes , Masculino , Inativação Gênica , Feminino , Regiões Promotoras GenéticasRESUMO
Background While the introduction of automated urine analyzers is expected to reduce the labor involved, turnaround time and potential assay variations, microscopic examination remains the "gold standard" for the analysis of urine sediments. In this study, we evaluated the analytical and diagnostic performance of five recently introduced automated urine sediment analyzers. Methods A total of 1016 samples were examined using five automated urine sediment analyzers and manual microscopy. Concordance of results from each automated analyzer and manual microscopy were evaluated. In addition, image and microscopic review rates of each system were investigated. Results The proportional bias for red blood cells (RBCs), white blood cells (WBCs) and squamous epithelial cells in the automated urine sediment analyzers were within ±20% of values obtained using the manual microscope, except in the cases of RBCs and WBCs analyzed using URiSCAN PlusScope and Iris iQ200SPRINT, respectively. The sensitivities of Roche Cobas® u 701 and Siemens UAS800 for pathologic casts (73.6% and 81.1%, respectively) and crystals (62.2% and 49.5%, respectively) were high, along with high image review rates (24.6% and 25.2%, respectively). The detection rates for crystals, casts and review rates can be changed for the Sysmex UF-5000 platform according to cut-off thresholds. Conclusions Each automated urine sediment analyzer has certain distinct features, in addition to the common advantages of reducing the burden of manual processing. Therefore, laboratory physicians are encouraged to understand these features, and to utilize each system in appropriate ways, considering clinical algorithms and laboratory workflow.
Assuntos
Bioensaio/métodos , Microscopia/métodos , Urinálise/métodos , Automação , HumanosRESUMO
BACKGROUND: The correlation between the electrode location and the clinical outcome for internal globus pallidus (GPi) deep brain stimulation (DBS) has not been fully elucidated. OBJECTIVE: The aim of this study was to determine the discrepancies between the theoretical target planned by magnetic resonance imaging (MRI) and the actual electrode location in postoperative MRI, as well as to find the correlation between the final electrode locations and the clinical outcome after GPi DBS. METHODS: Thirty-six patients who underwent GPi DBS for dystonia were included in this retrospective study. The X coordinate was defined as the lateral distance from the midline, the Y coordinate as the anterior distance from the midcommissural point, and the Z coordinate as the inferior distance from the intercommissural line. RESULTS: All coordinates showed a significant difference between theoretical and actual values for all electrode locations (p < 0.05). In particular, greater differences were exhibited for Y than for the X and Z coordinates. There was no significant difference in the accuracy of the localization of the left-side versus the right-side electrode for any coordinates. The patients whose electrodes were located within or near the posteroventral GPi showed better clinical outcomes. CONCLUSIONS: The actual electrode location was slightly more posterior to the theoretically planned target. Electrodes concentrated near the posteroventral GPi tended to yield favorable outcomes.
Assuntos
Estimulação Encefálica Profunda/métodos , Distonia/cirurgia , Eletrodos Implantados/efeitos adversos , Globo Pálido/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Criança , Estimulação Encefálica Profunda/efeitos adversos , Distonia/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Internal globus pallidus (GPi) deep brain stimulation (DBS) has been widely accepted as an effective treatment modality of medically refractory dystonia. However, there have been few studies regarding the safety issue of pregnancy and childbirth related with DBS. This report describes a female patient who was pregnant and delivered a baby after GPi DBS surgery. A 33-year-old female patient with acquired generalized dystonia underwent bilateral GPi DBS implantation. She obtained considerable improvement in both movement and disability after DBS implantation. Four years later, she was pregnant and the obstetricians consulted us about the safety of the delivery. At 38-weeks into pregnancy, a scheduled caesarian section was carried out under general anesthesia. After induction using thiopental and succinylcholine, intubation was done quickly, followed by DBS turn off. For hemostasis, only bipolar electrocautery was used. Before awakening from the anesthesia, DBS was turned on as the same parameters previously adjusted. After delivery, she could feed her baby by herself, because the dystonia of left upper extremity and hand was improved. Until now, she has been showing continual improvement and being good at housework, carrying for children, with no trouble in daily life. This observation indicates that the patients who underwent DBS could safely be pregnant and deliver a baby.
Assuntos
Estimulação Encefálica Profunda , Distúrbios Distônicos/diagnóstico , Encéfalo/diagnóstico por imagem , Cesárea , Eletrodos Implantados , Feminino , Globo Pálido , Humanos , Imageamento por Ressonância Magnética , Gravidez , Extremidade Superior/fisiopatologiaRESUMO
Even though the pathophysiology is not completely understood, cerebellar dysfunction has been invoked in essential tremor (ET). We evaluated cerebellar dysfunction in ET with the presence of perverted head-shaking (pHSN) and positional downbeat nystagmus (pDBN) which are known to reflect cerebellar dysfunction. First, we reviewed the videooculography (VOG) of 185 patients with ET from March 2007 to April 2010. Seventeen of 28 patients with pHSN and pDBN were followed up for at least a 1.8-year interval from baseline to determine the clinical course. And then, we recruited 52 consecutive patients with ET and compared their ocular motor findings with 51 normal controls using VOG. Among the 185 patients with ET, 28 (15.1 %) showed pHSN (n = 23, 12.4 %) or pDBN (n = 8, 4.3 %). Seventeen of them who were followed up did not develop Parkinsonism or other neurologic deficits during the observation period. The subsequent case-control study showed a higher prevalence of pHSN or pDBN (11/52, 21.2 %, pHSN in nine and pDBN in five) in patients with ET than in the normal controls (2/51, 3.9 %, pHSN only, P = 0.015). The tremor rating scale or involved body sites did not differ between the patients with and without pHSN/pDBN. pHSN and pDBN were more common in patients with ET than in the normal controls. This result supports that cerebellar dysfunction is associated with ET.
Assuntos
Tremor Essencial/fisiopatologia , Movimentos da Cabeça/fisiologia , Nistagmo Patológico/fisiopatologia , Tremor/fisiopatologia , Vertigem/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A pathogenic mutation (VPS35 p.D620N) within the retromer complex has been shown to segregate with late-onset Parkinson's disease (PD). Several studies have subsequently detected the mutation in patients with PD and not in controls. METHODS: Mutation screening of the coding regions of the retromer cargo recognition complex genes (VPS26A/B, VPS29, and VPS35) was carried out in patients with PD (n = 396), atypical parkinsonism (n = 229), and in 368 controls. RESULTS: Overall, we identified five rare nonsynonymous mutations in VPS26A and one in VPS35; none were observed in VPS26B or VPS29. Three VPS26A variants (p.K93E, p.M112V, and p.K297X), identified in patients with atypical parkinsonism, were not observed in controls from this study (n = 368) or from publically available data sets (n = 4,426). CONCLUSION: Our results support the hypothesis that rare variants in the retromer complex genes may be involved in the development of parkinsonism, although further studies are warranted before any solid conclusions can be drawn.
Assuntos
Predisposição Genética para Doença/genética , Variação Genética/genética , Transtornos Parkinsonianos/genética , Proteínas de Transporte Vesicular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, -0.1-1.7; P = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [clinicaltrial.gov: NCT00950664]
Assuntos
Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Torcicolo/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Torcicolo/complicações , Resultado do Tratamento , Adulto JovemRESUMO
In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.
Assuntos
Aceleração , Reflexo Vestíbulo-Ocular , Ataxias Espinocerebelares/fisiopatologia , Adulto , Idoso , Feminino , Teste do Impulso da Cabeça/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Rotação , Índice de Gravidade de Doença , Testes de Função Vestibular/métodos , Núcleos Vestibulares/fisiopatologiaRESUMO
BACKGROUND: Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA. METHODS: PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time. RESULTS: Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC. CONCLUSIONS: Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01723904 . Trial registration date: November 6, 2012.
Assuntos
Agonistas de Dopamina/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Atividades Cotidianas , Administração Cutânea , Idoso , Benzotiazóis/administração & dosagem , Feminino , Humanos , Indóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pramipexol , Transtornos do Sono-Vigília/etiologiaRESUMO
A question to be addressed in the present study is how different the eyes-closed (EC) and eyes-open (EO) resting states are across frequency bands in terms of efficiency and centrality of the brain functional network. We investigated both the global and nodal efficiency and betweenness centrality in the EC and EO resting states from 39 volunteers. Mutual information was used to obtain the functional connectivity for each of the four frequency bands (theta, alpha, beta, and gamma). We showed that the cortical hubs with high betweenness centrality were maintained in the EC and EO resting states. We further showed that these hubs were associated with more than three frequency bands, suggesting that these hubs play an important role in the brain functional network at multiple temporal scales in the resting states. Enhanced global efficiency values were found in the theta and alpha bands in the EO state compared with those in the EC state. Moreover, it turned out that in the EO state the functional network was reorganized to enhance nodal efficiency at the nodes related to both the default mode and the dorsal attention networks and sensory-related resting-state networks. This result suggests that in the EO state the brain functional network was efficiently reorganized, facilitating the adaptation of the brain network to the change in state, which could help in understanding brain disorders that have a disturbance in communication with external environments by using the adaptation ability of brain functional networks.
Assuntos
Ondas Encefálicas/fisiologia , Encéfalo/fisiologia , Olho , Magnetoencefalografia , Vias Neurais/fisiologia , Adulto , Eletroculografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
OBJECTIVE: To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD). METHOD: A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised manners. RESULTS: Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects. CONCLUSIONS: A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.
Assuntos
Corpo Estriado/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Dopamina/fisiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/psicologia , Antiparkinsonianos , Mapeamento Encefálico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , TropanosRESUMO
Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.
Assuntos
Alucinações/patologia , Doença de Parkinson/patologia , Neurônios Retinianos/patologia , Idoso , Estudos de Casos e Controles , Feminino , Alucinações/complicações , Alucinações/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Tomografia de Coerência ÓpticaRESUMO
OBJECTIVES: To determine whether α-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. RESULTS: Twenty-one sites contributed data for 6,154 cases. There was no significant association between α-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01). CONCLUSIONS: In our large consortium study, α-synuclein REP1 genotypes were not associated with survival in PD. Further studies of α-synuclein's role in disease progression and long-term outcomes are needed.
Assuntos
Repetições de Dinucleotídeos/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Sobrevida , alfa-Sinucleína/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/mortalidadeRESUMO
Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study.
Assuntos
Distúrbios Distônicos/genética , Distúrbios Distônicos/fisiopatologia , Oxirredutases do Álcool/genética , Diagnóstico Diferencial , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Distúrbios Distônicos/diagnóstico , GTP Cicloidrolase/genética , Humanos , Mutação , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/fisiopatologia , Tirosina 3-Mono-Oxigenase/genética , Proteínas Vesiculares de Transporte de Monoamina/genéticaRESUMO
Essential tremor (ET) is one of the most common movement disorders. The prevalence of ET varies substantially among studies. In Korea, there is no well-designed epidemiological study of the prevalence of ET. Thus, we investigated the prevalence of ET in a community in Korea. Standardized interviews and in-person neurological examinations were performed in a random sample of the elderly aged 65 yr or older. Next, movement specialists attempted to diagnose ET clinically. People who showed equivocal parkinsonian features underwent dopamine transporter imaging using [(123)I]-FP-CIT SPECT, to differentiate ET from parkinsonism. A total of 714 subjects participated in this population-based study. Twenty six of these subjects were diagnosed as having ET. The crude prevalence of ET was 3.64 per 100 persons. Age, gender, or education period were not different between the ET patients and the non-ET subjects. The prevalence of ET was slightly lower than those reported in previous studies. Further studies including more subjects are warranted.
Assuntos
Tremor Essencial/diagnóstico , Tremor Essencial/epidemiologia , Avaliação Geriátrica/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Distribuição por SexoRESUMO
We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7 ± 16.8 spikes/sec, n=78) and the right side MERs (35.5 ± 17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.
Assuntos
Anestésicos Intravenosos/farmacologia , Estimulação Encefálica Profunda , Fentanila/farmacologia , Doença de Parkinson/prevenção & controle , Propofol/farmacologia , Núcleo Subtalâmico/efeitos dos fármacos , Idoso , Eletrodos Implantados , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Microeletrodos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Núcleo Subtalâmico/fisiologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate anatomical changes in the substantia nigra (SN) of Parkinson disease (PD) patients with age-matched controls by using ultra-high field magnetic resonance imaging (MRI). METHODS: We performed 7T MRI in 10 PD and 10 age-matched control subjects. Magnetic resonance images of the SN were obtained from a 3-dimensional (3D) T(2)*-weighted gradient echo sequence. Region of interest-based 3D shape analysis was performed to quantitatively compare images from the 2 groups. RESULTS: The boundary between the SN and crus cerebri was not smooth in PD subjects. Undulation in the lateral surface of the SN appeared more intense in the side contralateral to that with the more severe symptoms, and more prominent at the rostral level of the SN than at the intermediate or caudal levels. In addition to the lateral surface, there was a striking difference in the dorsomedial aspects of the SN between PD and control subjects. In control subjects, a brighter signal region was observed along the dorsomedial surface of the lateral portion of SN, whereas in PD subjects, this region was observed as a dark region containing a hypointense signal in T(2)*-weighted images. The measurement of SN volumes, normalized to the intracranial volumes, showed higher values in PD subjects than in control subjects. INTERPRETATION: This study demonstrates that 3D 7T MRI can definitively visualize anatomical alterations occurring in the SN of PD subjects. Further pathological studies are required to elucidate the nature of these anatomical alterations.
Assuntos
Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/patologia , Substância Negra/patologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnósticoRESUMO
BACKGROUND: Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. METHODS: The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. RESULTS: Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. CONCLUSIONS: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.
Assuntos
Frequência do Gene , Predisposição Genética para Doença , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Estudos de Associação Genética , Genética Populacional , Genótipo , Haplótipos , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Epidemiologia Molecular , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Musculoskeletal problems are very common and are an important contributor to poor quality of life in Parkinson's disease. However, they are under-appreciated, under-evaluated, and under-treated. This paper will address the prevalence of musculoskeletal problems in Parkinson's disease, and review the clinical characteristics of selected musculoskeletal conditions, such as shoulder problems, low back pain, arthritis, deformity, osteoporosis and fracture. Finally, a variety of treatment modalities for musculoskeletal problems will be reviewed.
Assuntos
Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/epidemiologia , Doença de Parkinson/complicações , Humanos , Medição da Dor , Prevalência , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Wilson's disease (WD) is a genetic disorder which can be controlled fairly well with decupuration therapy. However, symptoms, on rare occasions, can worsen even when WD is being treated. Herein, we report a case involving unusual neurological deterioration during decupuration therapy for WD. CASE PRESENTATION: A 28-year-old man was diagnosed with WD 13 years prior to his clinical visit; however, his drug compliance has been poor over the years. He was treated with trientine because tremors and dysarthria have presented in recent years. However, dysarthria and dystonia developed in his limbs, which were worse on the right side and had been aggravated for several weeks despite good drug compliance. His symptoms were fluctuating. It was initially misdiagnosed as dystonia; although, it turned out to be a seizure due to cortical degeneration. These symptoms were completely resolved with antiepileptic drugs. Moreover, the cortical enhancement of bifrontal degeneration has disappeared on the MRI. CONCLUSION: This case showed unusual epileptic neurologic deterioration due to cortical degeneration during decupuration therapy. Seizures in WD can easily be mistaken as part of dystonia. However, the fluctuating symptoms suggest a seizure.