RESUMEN
BACKGROUND AND PURPOSE: Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. METHODS: We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants. RESULTS: DNM3 rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. CONCLUSIONS: DNM3 rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese samples. Further studies in other Asian populations will be of interest.
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Edad de Inicio , Dinamina III/genética , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Asia/epidemiología , Pueblo Asiatico , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Heterocigoto , Humanos , Estimación de Kaplan-Meier , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health-related quality of life (QoL) over a defined follow-up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2-year follow-up period. METHOD: A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non-Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire-39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm). RESULTS: The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow-up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change. CONCLUSION: Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2-year follow-up period.
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Afecto/fisiología , Apatía/fisiología , Atención/fisiología , Fatiga/fisiopatología , Memoria/fisiología , Enfermedad de Parkinson/fisiopatología , Calidad de Vida , Sueño/fisiología , Anciano , Pueblo Asiatico , Fatiga/complicaciones , Fatiga/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.
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Cadenas alfa de HLA-DR/genética , Inmunidad Innata/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Humanos , Inflamación/etnología , Inflamación/genética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnologíaRESUMEN
OBJECTIVES: To assess prevalence of headaches in patients with hemifacial spasm. To determine whether hemifacial spasm provokes headaches and identifies predictive factors. To evaluate whether botulinum toxin given for hemifacial spasm improves headaches. METHODS: Seventy patients with hemifacial spasm were evaluated for headaches. The relationship of headaches with hemifacial spasm, impact on quality of life (HIT-6), and improvement in headaches from botulinum toxin was recorded. Data on duration, severity, and impact on quality of life (HFS-7) of hemifacial spasm were collected. RESULTS: Hemifacial spasm-related headache was significantly associated with increased hemifacial spasm severity (P < 0.001) and HIT-6 (P = 0.024). Greater hemifacial spasm severity was predictive of hemifacial spasm-related headache (P = 0.006, OR 19.1, 95% CI 2.35-155.64). Botulinum toxin (BTX) for hemifacial spasm improved hemifacial spasm-related headaches (P < 0.001). CONCLUSIONS: Hemifacial spasm can complicate headaches, particularly in patients with greater hemifacial spasm severity. Individually tailored regimens of botulinum toxin may be indicated in these patients.
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Cefalea/epidemiología , Espasmo Hemifacial/epidemiología , Analgésicos/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Estudios de Cohortes , Comorbilidad , Femenino , Cefalea/tratamiento farmacológico , Cefalea/etiología , Cefalea/fisiopatología , Cefalea/psicología , Espasmo Hemifacial/complicaciones , Espasmo Hemifacial/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/uso terapéutico , Prevalencia , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
LINGO2, a member of LRR gene family, has been linked with both Essential tremor (ET) and Parkinson's disease (PD). However, there is a lack of conclusive evidence regarding the etiologic role of LINGO2 genetic variants. We investigated the association of LINGO2 variants with ET and PD in two independent Asian countries. A total of 1,262 subjects comprising 499 controls, 436 PD patients, and 327 ET patients were included. Eight LINGO2 variants, including four single-nucleotide polymorphisms (SNPs) and four coding variants, were initially analyzed in one Asian population. SNPs that showed positive association were then replicated in the second independent Asian population, and a pooled analysis was carried out. Out of the eight variants, two SNPs (rs7033345 and rs10812774) revealed significant or strong positive trend in the first Asian population, and these were analyzed in the second Asian population. In the pooled analysis, the CC genotype at rs7033345 had a higher risk of developing PD (OR = 1.67, 95% CI = 1.18, 2.35, p = 0.003) and ET (OR = 1.50, 95% CI = 1.02, 2.20, p = 0.04) under a recessive model. The C allele at rs10812774 increased the risk of ET (OR = 1.56 95% CI = 1.10, 2.22, p = 0.01) via a recessive model. The effect size and direction of trend were in the same direction in each of the two populations. Our study demonstrated for the first time that rs7033345 is associated with PD and ET and rs10812774 with ET among Asians, suggesting that LINGO2 might act as a susceptibility gene for both conditions.
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Temblor Esencial/genética , Enfermedad de Parkinson/genética , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Mutations in the GIGYF2 gene at the PARK11 locus have recently been reported in Parkinson's disease (PD). However, the pathogenicity of some of these mutations has been debated. We conducted a comprehensive genetic analysis of the entire GIGYF2 gene in a cohort of young onset and familial PD patients, followed up with screening of specific variants in a separate group of PD and healthy controls. A total of 850 study subjects [450 Parkinson's disease (PD) patients and 400 controls] from two Asian countries were included. Our analysis revealed 17 variants distributed across the entire GIGYF2 gene. Ten of these were novel variants out of which eight were non-synonymous (all heterozygous). Out of these eight, half were novel polymorphic variants (0.2-2%) whereas four were novel non-synonymous variants which were not detected in healthy controls. The seven PD patients with non-synonymous variants had a mean age and age at onset of 55.3 and 50.9 years. All had typical features of PD and only one had a positive family history. The collective frequency of these non-synonymous variants was higher in PD compared to controls (1.6 vs. 0%, P = 0.016, relative risk 1.9, 95% CI 1.2, 1.9). None of the previously reported pathogenic mutations in Italian and French patients were present in our cohort. Our data suggest that GIGYF2 is unlikely to play a major role in our Asian populations. Rare non-synonymous variants appeared to be enriched in our PD patients compared to healthy controls. However, in vivo functional studies and segregation analysis in large pedigrees will be needed to determine if these single heterozygous variants represent rare mutations, risk alleles or benign polymorphisms.
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Proteínas Portadoras/genética , Proteínas Portadoras/fisiología , Enfermedad de Parkinson/genética , Polimorfismo Genético , Adulto , Edad de Inicio , Anciano , Asia , Estudios de Casos y Controles , Estudios de Cohortes , Salud de la Familia , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Población BlancaRESUMEN
We showed that the frequency of a LRRK2 variant (c.4883G > C, R1628P) was higher in Parkinson's disease (PD) compared to controls (8.4 vs. 3.4%, P = 0.046, OR 2.5, 95% CI 1.1-5.6). In the multivariate logistic regression (with adjustments made for the effect of age, age of onset, and gender), the heterozygous R1628P genotype was associated with an increased risk of PD compared to controls (OR 3.3, 95% CI 1.4- 7.9, P = 0.007). We provided an independent confirmation that the R1628P variant increases the risk of PD among Chinese.
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Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , China , Femenino , Variación Genética , Genotipo , Heterocigoto , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
In this study, we found the sensitivity and specificity of family history data given by essential tremor (ET) patients to be 43.3% and 94.4%. Compared to relatives with less severe tremor (tremor score <24), those with more severe tremor (tremor score 24) were more likely to be identified by the ET probands (8/8 vs. 5/22, p=0.001, chi2 14.3). Our study suggests that family history information reported by ET patients was inaccurate, and poorly validated. Clinical and genetic studies in ET should take the limitation of family history data into consideration.
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Temblor Esencial/genética , Actividades Cotidianas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/etnología , Temblor Esencial/epidemiología , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Reproducibilidad de los Resultados , Singapur/epidemiología , Encuestas y CuestionariosRESUMEN
We report our experience, using mycophenolate mofetil (MyM) as an adjunctive immunosuppressive therapy in patients with severe, refractory and high dose steroid-dependent myasthenia gravis (MG). Five patients were commenced on MyM in addition to other immunosuppressive therapies. All had significant clinical improvement and no subsequent myasthenic crisis requiring intensive care unit admission. MyM was well tolerated and no serious adverse effects were observed. MyM is an effective adjunctive therapy for the treatment of severe, refractory and steroid-dependent MG in our experience.
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Inmunosupresores/administración & dosificación , Miastenia Gravis/tratamiento farmacológico , Ácido Micofenólico/análogos & derivados , Adulto , Anciano , Inhibidores de la Colinesterasa/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Prednisolona/administración & dosificación , Bromuro de Piridostigmina/administración & dosificación , Índice de Severidad de la Enfermedad , SingapurAsunto(s)
Distonía/genética , Fosfolipasas A2 Grupo VI/genética , Enfermedad de Parkinson/genética , Anciano , Encéfalo/diagnóstico por imagen , Estudios de Cohortes , Humanos , Masculino , Mutación Missense , Enfermedad de Parkinson/diagnóstico por imagen , Mutación Puntual , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos XRESUMEN
Childhood onset essential tremor (ET) is uncommon. It is not clear as to whether ethnicity-specific differences may influence the phenotypic features. To determine the frequency and clinical characteristics of childhood ET in a tertiary referral center. In a prospective evaluation of 120 consecutive ET patients in a movement disorders clinic, we found a 15.5% (19) frequency of childhood onset ET patients. The mean age of onset and mean age was 10.8 +/- 4.1 (6-16) years and 25.7 +/- 15.0 (16-73) years consisting of 73.6% (14/19) men and 26.4% (5/19) women. A positive family history of ET was present in 11 of 19 (52.6%). Presence of a head tremor was observed in 2/19 (10.5%). We highlighted a relatively high frequency (15,5%) of childhood ET in our Asian cohort. In addition, we drew attention to the male preponderance and the low frequency of head tremor in childhood ET corroborating study findings in white ET patients. These observations appear to transcend ethnic and cultural differences and lend further support that gender difference may play a role in the pathogenesis and expression of ET.
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Temblor Esencial/fisiopatología , Adolescente , Edad de Inicio , Pueblo Asiatico , Niño , Temblor Esencial/clasificación , Temblor Esencial/epidemiología , Temblor Esencial/genética , Familia , Femenino , Mano , Humanos , Masculino , Anamnesis , Prevalencia , Caracteres Sexuales , Población BlancaRESUMEN
In a face-to-face questionnaire-based survey involving a total of 111 essential tremor (ET) patients and their relatives, we demonstrated a general lack of genetic insight amongst our study subjects. There was no significant correlation between genetic knowledge of ET and age, level of education, disease duration or severity. A proactive effort is needed to encourage physicians managing ET patients to incorporate genetic information and education into their practice.
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Temblor Esencial/genética , Temblor Esencial/psicología , Familia , Conocimientos, Actitudes y Práctica en Salud , Adulto , Anciano , Pueblo Asiatico/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: It has been suggested that environmental factors may be associated with essential tremor (ET). This study was carried out to evaluate the association of caffeine intake with ET. METHOD: In a case control study, patients diagnosed with ET and healthy controls underwent a standardized questionnaire interview to evaluate the exposure to coffee and tea intake. A multivariate logistic regression analysis was carried out to evaluate the association of caffeine intake and other environmental factors with risk of ET. RESULTS: 179 subjects including 79 ET patients and 100 controls matched for age, gender and ethnicity were included in the analysis. Univariate analysis revealed that caffeine consumption in ET patients was higher than control group (median and 90th percentile range: 2300 (0, 9000) mg-years versus 1500 (0, 6090) mg-years, p=0.01). However, the multivariate logistic regression analysis demonstrated that caffeine was no longer a significant factor associated with ET (p=0.119). There was no significant correlation between amount of caffeine intake and disease duration (Spearman's r=0.194; p=0.202) or total tremor score (Spearman's r=0.045; p=0.771) in ET patients. CONCLUSION: Caffeine consumption was not associated with risk of ET in our study population. Further studies are needed to investigate the significance of gene-environmental interaction in ET.
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Cafeína/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Conducta de Ingestión de Líquido/fisiología , Temblor Esencial/etiología , Adulto , Anciano , Café/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Té/efectos adversosRESUMEN
INTRODUCTION: Recent studies suggest an association between non-motor symptoms and essential tremor (ET). Few studies have assessed psychological symptoms in ET. These studies were limited to western white populations and utilized scales that were specific to only one or two psychiatric domains. By contrast, the Symptom Checklist-90R (SCL-90R) is a validated clinical scale to screen for symptoms related to a spectrum of nine different psychological domains. OBJECTIVE: To determine whether a wide spectrum of non-motor manifestations is associated with ET in patients in an Asian cohort. METHODS: Consecutive ET patients and a group of control subjects were evaluated using the SCL-90R, which is comprised of items in nine major symptom dimensions and three global indices, including the positive symptom distress index. RESULTS: ET patients (N = 84) and controls (N = 78) were similar in age (50.0+/-18.0 vs 46.0+/-14.4 years), gender and other demographic variables. ET patients had higher scores in three of nine major symptom dimensions: anxiety, phobic anxiety (p < 0.0005) and psychoticism (p = 0.005). In multivariate analysis, the anxiety (p < 0.0005) and the positive symptom distress index scores (p < 0.0005) were greater in ET patients compared to controls after adjusting for sex, age, marital status and educational level. The severity, but not duration of ET was correlated with the severity of anxiety symptoms. CONCLUSIONS: Utilizing the SCL-90R, we highlighted that ET patients reported more non-motor symptoms than healthy controls. The more frequent occurrence of anxiety symptoms in our Asian cohort extends the observation that such non-motor manifestations should be considered in the clinical management of ET.
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Temblor Esencial/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Ansiedad/etiología , Ansiedad/psicología , Asia/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Temblor Esencial/complicaciones , Temblor Esencial/epidemiología , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Tamaño de la MuestraRESUMEN
OBJECTIVE: The posterior antebrachial cutaneous (PABC) nerve is a sensory nerve that branches out from the radial nerve at the level of the spiral groove. Thus it can be affected in a radial nerve lesion at or proximal to its origin in the spiral groove. However, there has been limited knowledge about the normal values of PABC nerve conduction studies. This study was done to determine these normal values. METHODS: Sixty-three healthy adults (23 males) with a mean age of 41.5+/-10.6 (range, 20-90) years were recruited with informed consent. A total of 126 nerves were studied. The nerve conduction studies were performed using a Dantec Counterpoint EMG machine (Dantec, Skovlunde, Denmark). RESULTS: The mean+/-standard deviation values for the onset as well as peak latency, conduction velocity, amplitude and side-to-side amplitude ratio were 2.07+/-0.16 (range, 1.80-2.60) ms, 2.35+/-0.15 (range, 2.05-2.90) ms, 58.21+/-4.29 (range, 46.15-66.67) m/s, 6.10+/-2.11 (range, 2.90-13.00) microV and 0.83+/-0.12 (range, 0.60-0.99), respectively. There was a significant correlation between the subject age and the PABC onset and peak latencies as well as the amplitudes. CONCLUSIONS: The PABC nerve is assessable for nerve conduction studies and these normal values may be useful in evaluation of patients with suspected radial nerve lesions.
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Antebrazo/inervación , Conducción Nerviosa/fisiología , Nervio Radial/fisiología , Piel/inervación , Adulto , Anciano , Anciano de 80 o más Años , Electrodiagnóstico/métodos , Electrodiagnóstico/normas , Electrofisiología/métodos , Electrofisiología/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas Aferentes/fisiología , Valores de ReferenciaRESUMEN
Radial neuropathy most commonly occurs as a result of external compression at the spiral groove region. The posterior antebrachial cutaneous nerve (PACN) conduction study was performed in 15 consecutive patients with radial palsy. Unilateral PACN abnormalities were present in 11 patients. A normal PACN study was correlated with clinical improvement at 3 months. Conversely, PACN abnormality was correlated with radial motor axon loss and a poorer prognosis. The PACN study is a simple adjunct which provides additional information relating to the diagnosis and prognosis of radial lesions.
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Conducción Nerviosa/fisiología , Nervio Radial/fisiopatología , Neuropatía Radial/fisiopatología , Adolescente , Adulto , Electromiografía , Electrofisiología/métodos , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de la radiación , Nervio Radial/efectos de la radiaciónRESUMEN
Bell's palsy is a common neurological problem causing considerable loss of self-esteem among patients. A prospective observational study was conducted to determine the short-term outcome of Bell's palsy at 1 month and 2 months after the onset and the relationship between these outcomes with facial nerve degeneration. We also determined if gender, age, diabetes, systolic and diastolic blood pressure influence the severity of facial nerve degeneration and the clinical outcome at 2 months after the onset. After clinically grading the newly diagnosed unilateral Bell's palsy patients using the House-Brackmann facial nerve grading system, nerve conduction studies of the facial nerve were done to determine the severity of facial nerve degeneration. The recovery of the facial paralysis was clinically graded again at the end of 1 month and 2 months from the onset. A total of 37 patients were recruited. There was a strong positive correlation between facial nerve degeneration and the clinical outcome of Bell's palsy at 1 month (r = 0.794; p < 0.0005) and 2 months (r = 0.732; p < 0.0005) after the onset. There was no significant correlation between either the facial nerve degeneration or the clinical outcome at 2 months with the patients' age (p = 0.288 and p = 0.799 respectively), systolic blood pressure (p = 0.425 and p = 0.933 respectively) or diastolic blood pressure (p = 0.243 and p = 0.579 respectively). Neither the severity of facial nerve degeneration nor the clinical outcome at 2 months were significantly different between male and female patients (p = 0.460 and p = 0.725 respectively) or diabetic and non-diabetic patients (p = 0.655 and p = 0.655 respectively).
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Parálisis de Bell/fisiopatología , Parálisis de Bell/terapia , Degeneración Nerviosa/fisiopatología , Degeneración Nerviosa/terapia , Conducción Nerviosa/fisiología , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Anciano , Parálisis de Bell/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/complicaciones , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
OBJECTIVES: Using a family study design, we describe the motor and nonmotor phenotype in probands with LRRK2 G2019S mutations and family members and compare these individuals to patients with idiopathic Parkinson disease (iPD) and unrelated controls. METHODS: Probands with G2019S mutations and their first-degree relatives, subjects with iPD, and unrelated control subjects were identified from 4 movement disorders centers. All underwent neurologic examinations and tests of olfaction, color vision, anxiety, and depression inventories. RESULTS: Tremor was more often a presenting feature among 25 individuals with LRRK2-associated PD than among 84 individuals with iPD. Subjects with LRRK2-PD had better olfactory identification compared with subjects with iPD, higher Beck Depression Inventory scores, and higher error scores on Farnsworth-Munsell 100-Hue test of color discrimination. Postural or action tremor was more common among 29 nonmanifesting mutation carriers compared with 53 noncarriers within the families. Nonparkinsonian family members had higher Unified Parkinson's Disease Rating Scale motor scores, more constipation, and worse color discrimination than controls, regardless of mutation status. CONCLUSIONS: Although tremor is a more common presenting feature of LRRK2-PD than iPD and some nonmotor features differed in degree, the phenotype is largely overlapping. Postural or action tremor may represent an early sign. Longitudinal evaluation of a large sample of nonmanifesting carriers will be required to describe any premotor phenotype that may allow early diagnosis.
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Predisposición Genética a la Enfermedad , Heterocigoto , Mutación , Enfermedad de Parkinson/genética , Fenotipo , Proteínas Serina-Treonina Quinasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/complicaciones , Ansiedad/genética , Defectos de la Visión Cromática/complicaciones , Defectos de la Visión Cromática/genética , Depresión/complicaciones , Depresión/genética , Familia , Femenino , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Examen Neurológico/métodos , Trastornos del Olfato/complicaciones , Trastornos del Olfato/genética , Enfermedad de Parkinson/complicaciones , Escalas de Valoración Psiquiátrica , Temblor/complicaciones , Temblor/genéticaRESUMEN
OBJECTIVE: A genome-wide association study (GWAS) in the Japanese population identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16) (OMIM 613164) and BST1. We analyzed single nucleotide polymorphism (SNPs) located at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population and also conducted a meta-analysis in Asians by pooling 2 independent replication studies from Japan. METHODS: We conducted an analysis of 13 SNPs associated with PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese subjects. RESULTS: PARK16, PARK8, and PARK1 loci but not BST1 were found to be associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1 and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects with PD and 16,669 controls revealed robust association with these 3 loci and also BST1. There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects. CONCLUSIONS: Our study reaffirms the role of GWAS-linked loci in PD in Asian subjects and the strength of association is similar between Chinese and Japanese subjects. Efforts to elucidate the associated gene within PARK16 locus are warranted.
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Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Enfermedad de Parkinson/genética , ADP-Ribosil Ciclasa/genética , Antígenos CD/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Proteínas Ligadas a GPI , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Polimorfismo de Nucleótido Simple/genética , Proteínas Serina-Treonina Quinasas/genética , alfa-Sinucleína/genéticaRESUMEN
Chemical and biological agents have been used as weapons of mass destruction for a long time and presents as a serious threat to mankind. They have been used in many great wars and terrorist attacks with devastating results. The knowledge about these weapons of mass destruction is crucial to health care providers. Early recognition of the clinical characteristics of poisoning as a result of these chemical and biological agents is important to initiate appropriate therapy and minimizing casualties. Neurophysiological investigations when integrated with clinical features are helpful in early identification of some of these agents, especially when serological confirmation is not rapidly available. In this review, we have focused on chemical and biological weapons, which affect the nervous system and the role of clinical neurophysiology in such conditions.