RESUMEN
Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based "circuitopathies," aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.
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Encéfalo/anatomía & histología , Conectoma/métodos , Estimulación Encefálica Profunda/métodos , Imagen de Difusión Tensora/métodos , HumanosRESUMEN
BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.
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Enfermedad por Cuerpos de Lewy/genética , Chaperonas Moleculares/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente) , Exones , Femenino , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
OBJECTIVE: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid ß (Aß) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aß and tau as markers of early or presymptomatic PD. METHODS: CSF Aß42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with 18F-6-fluoro-l-dopa (FD), 11C-(±)-α-dihydrotetrabenazine (DTBZ), and 11C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement. RESULTS: Reduced CSF Aß42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aß42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau. CONCLUSIONS: The disposition of Aß and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers.
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Péptidos beta-Amiloides/líquido cefalorraquídeo , Mutación , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas tau/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/genética , Biomarcadores/líquido cefalorraquídeo , Femenino , Genotipo , Heterocigoto , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/genética , Fenotipo , Proteínas tau/genéticaRESUMEN
BACKGROUND AND PURPOSE: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson's disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease. METHODS: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson's disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson's disease, 344 controls) and five separate Caucasian series' (combined sample size 1962 Parkinson's disease patients, 1900 controls). RESULTS: We observed no evidence of association for rs4877365 and rs4878104 and risk of Parkinson's disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. CONCLUSION: These specific DAPK1 intronic variants do not increase the risk of Parkinson's disease. However, further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins.
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Proteínas Reguladoras de la Apoptosis/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Proteínas Quinasas Asociadas a Muerte Celular , Femenino , Predisposición Genética a la Enfermedad/etnología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Multimerización de Proteína , Adulto JovenAsunto(s)
Temblor Esencial/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos/genética , Atrofia de Múltiples Sistemas/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas tau/genética , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , Temblor Esencial/etiología , Frecuencia de los Genes , Humanos , Atrofia de Múltiples Sistemas/etiología , Oportunidad Relativa , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD. METHODS: Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552. RESULTS: Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects. CONCLUSIONS: In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk.
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Epistasis Genética/genética , Glucógeno Sintasa Quinasa 3/genética , Enfermedad de Parkinson/genética , alfa-Sinucleína/genética , Proteínas tau/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Variación Genética/genética , Glucógeno Sintasa Quinasa 3 beta , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etnología , Polimorfismo de Nucleótido Simple/genética , Estudios Prospectivos , Medición de Riesgo/métodos , Adulto JovenRESUMEN
BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.
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Proteínas Reguladoras de la Apoptosis/genética , Proteínas de Unión al ADN/genética , Trastornos Distónicos/genética , Variación Genética/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Missense/genética , Linaje , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Calcium levels have been proposed to play an important role in the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient-control series. METHODS: We genotyped rs1805874 in four independent Caucasian patient-control series (1543 PD patients, 1771 controls). RESULTS: There was no evidence of an association between rs1805874 and disease risk in individual populations or in the combined series (odds ratio: 1.04, 95% CI: 0.82-1.31, P = 0.74). DISCUSSION: Our study shows there is no association between rs1805874 and risk for PD in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity.
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Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Proteína G de Unión al Calcio S100/genética , Adulto , Anciano , Anciano de 80 o más Años , Calbindina 1 , Calbindinas , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Noruega , Polonia , Factores de Riesgo , Análisis de Secuencia de ADN , Estados Unidos , Población Blanca/genéticaRESUMEN
BACKGROUND AND PURPOSE: Whilst an association between the tau gene (MAPT)-containing H1 haplotype and supranuclear gaze palsy (PSP) has long been recognized, the effect of H1 on risk for Parkinson's disease (PD) has remained more contentious. METHODS: Herein, we examined the association of H1 and PD in three Caucasian PD patient-control series from Ireland, Norway, and the US (combined: n = 2619), by genotyping two H1/H2 single nucleotide polymorphisms (SNPs) in MAPT (rs1052553) and in the Saitohin gene (rs62063857) and one H1-specific SNP (rs242557). RESULTS: We identified a significant association between H1/H2 and risk of PD (rs1052553 OR: 1.43, CI: 1.23-1.64; rs62063857 OR: 1.45, CI: 1.27-1.67), but no effect of the H1-specific SNP rs242557 (OR: 0.92, CI: 0.82-1.03). CONCLUSIONS: Our findings show that the H1 haplotype is a significant risk factor for PD. However, one H1-specific SNP (rs242557) previously implicated in PSP did not alter the risk of PD, indicating that distinct H1 sub-haplotypes probably drive the associations with PD and PSP.
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Enfermedad de Parkinson/genética , Proteínas tau/genética , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Irlanda , Masculino , Noruega , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Análisis de Secuencia de ADN , Parálisis Supranuclear Progresiva/genética , Estados Unidos , Población Blanca/genéticaAsunto(s)
Predisposición Genética a la Enfermedad/genética , Proteínas de Homeodominio/genética , Mutación/genética , Proteínas de Neoplasias/genética , Síndrome de las Piernas Inquietas/epidemiología , Síndrome de las Piernas Inquietas/genética , Anciano , Secuencia de Bases , Estudios de Casos y Controles , Secuencia Conservada/genética , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Patrón de Herencia/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Proteínas del Tejido Nervioso , Linaje , Prevalencia , Estructura Terciaria de Proteína/genética , Síndrome de las Piernas Inquietas/fisiopatología , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration. METHODS: In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with Parkinson disease (PD), frontotemporal lobar degeneration (FTLD), or ALS. RESULTS: This analysis revealed 36 novel variants (9 missense, 5 silent, and 22 noncoding). Segregation analysis in families and association studies in PD, FTLD, and ALS case-control series did not identify any variants segregating with disease or associated with increased disease risk. CONCLUSIONS: This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis.
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Esclerosis Amiotrófica Lateral/genética , Demencia/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Asociadas a Microtúbulos/genética , Enfermedad de Parkinson/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Complejo Dinactina , Exones/genética , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Pruebas Genéticas , Variación Genética/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación/genéticaRESUMEN
BACKGROUND AND PURPOSE: A single nucleotide polymorphism in the 3'-untranslated region of the progranulin gene (GRN; 3'UTR+78C>T; rs5848) was reported to alter the risk for frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). rs5848 is located within a micro-RNA binding site and affects the expression of GRN. METHODS: As FTLD-U patients often present with parkinsonism, we investigated the association of GRN rs5848 and risk of Parkinson's disease in two Caucasian patient-control series (n = 1413) from the US and Poland. RESULTS: No association was observed between rs5848 and susceptibility to Parkinson's disease (individual series and combined analysis). CONCLUSIONS: This finding shows that GRN rs5848 does not affect the risk of Parkinson's disease in the US and Polish populations.
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Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intercelular/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Polonia/epidemiología , Progranulinas , Factores de Riesgo , Estados Unidos/epidemiología , Población Blanca/genética , Adulto JovenAsunto(s)
Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/genética , Síndrome de las Piernas Inquietas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Frecuencia de los Genes/genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Síndrome de las Piernas Inquietas/complicacionesRESUMEN
The purpose of this study was the development of a new method to correlate functional surgery with outcome measures. Lesions following microelectrode guided globus pallidus internus (GPi) pallidotomy for Parkinson's disease are presented to demonstrate this new method in regard to clinical outcome. A clinical series of 26 patients with extensive neurological and neuropsychological data were studied. Three-month postoperative MRI lesion borders at the AC-PC plane were scaled to a standard size, and the lesions were stored in a virtual array with a cell size of one voxel. The average outcome measure for each voxel is presented graphically. Unified Parkinson's disease rating scale (UPDRS) motor scores improved more with posterolateral and centrally located GPi lesions than with anteromedial lesions. A correlation of lesion location to outcome was also visible for subscales of the UPDRS. The distributions were similar for the left and right sides, as well as for ipsi- and contralateral measurements. In general, verbal fluency decreased after lesioning the dominant hemisphere, and posterolateral lesions caused less impairment. This method enables associative analyses between brain area and outcome down to the size of a few voxels. This may be particularly helpful for planning and validating neurosurgical targets for various disorders.
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Cognición/fisiología , Lateralidad Funcional/fisiología , Globo Pálido/cirugía , Actividad Motora/fisiología , Palidotomía/métodos , Enfermedad de Parkinson/cirugía , Actividades Cotidianas , Antiparkinsonianos/uso terapéutico , Mapeo Encefálico/métodos , Femenino , Globo Pálido/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Microelectrodos , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patologíaRESUMEN
Recent case-series studies indicated that a medication used to treat Parkinson's disease (PD), in particular Pramipexole, is associated with gambling. A case-series study cannot test this hypothesis; therefore, we need to design a case-control or cohort study to test the aforementioned hypothesis. Typical of a case-control design, we sampled on the dependent variable, which we defined as incident gambling in PD. A research neurologist, who was kept uninformed of the case-control status, retrospectively measured the exposure of interest (i.e. medications used to treat PD) by using the medical database system of Mayo Clinic Jacksonville. Eleven patients with PD without history of gambling, but had newly developed gambling, were matched by age and sex to the control group of 37 PD patients without gambling at a ratio of one case to at least three controls. Disease duration, age, and sex did not differ between cases and controls. Combined therapy with Pramipexole and levodopa did not increase the risk of gambling as compared to monotherapy with Pramipexole (OR, 0.15; 95% CI, 0.01-1.26). Treatment with Pramipexole was associated with increased risk of gambling and this association approached significance (OR, 3.6; 95% CI, 0.9-14.9). Patients with PD who newly developed gambling behavior were more likely to have been taking Pramipexole than other anti-PD medication. However, the association between Pramipexole and gambling behavior is not necessarily etiologic.
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Antiparkinsonianos/efectos adversos , Benzotiazoles/efectos adversos , Juego de Azar , Anciano , Estudios de Casos y Controles , Intervalos de Confianza , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/tratamiento farmacológico , Pramipexol , Estudios Retrospectivos , Literatura de Revisión como Asunto , RiesgoRESUMEN
OBJECTIVE: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C. METHODS: We identified 33 affected and 15 unaffected LRRK2 c.4321C>T (p.R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. RESULTS: The clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p.R1441C mutation. CONCLUSIONS: The distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis.
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Sustitución de Aminoácidos/genética , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/fisiopatología , Proteínas Serina-Treonina Quinasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Arginina/genética , Cisteína/genética , Análisis Mutacional de ADN , Femenino , Glicina/genética , Haplotipos/genética , Humanos , Internacionalidad , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Serina/genéticaRESUMEN
In 9 patients with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with a P301S tau mutation, the predominant phenotype was frontotemporal dementia in 3 and parkinsonism in 6. Comparison of the tau genotype/haplotype carrying the mutation and the initial clinical sign showed association between H1/H1 and parkinsonism and between H1/H2 and personality change. Thus, the tau haplotype carrying the mutation and the tau genotype may be related to the clinical phenotype throughout the disease course.
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Cromosomas Humanos Par 17/genética , Degeneración Lobar Frontotemporal/genética , Ligamiento Genético , Mutación/genética , Trastornos Parkinsonianos/genética , Proteínas tau/genética , Adulto , Femenino , Degeneración Lobar Frontotemporal/patología , Genotipo , Haplotipos/genética , Humanos , Masculino , Trastornos Parkinsonianos/patología , Adulto JovenRESUMEN
OBJECTIVES: To examine the utility of baseline factors to predict disease progression among a clinical cohort of patients diagnosed with essential tremor. MEASURES: Tremor Rating Scale (TRS). METHODS: A clinical series of 128 consecutive patients diagnosed with essential tremor was included for study. 45 (35%) patients had at least one follow-up exam (mean = 3.6 years). Baseline predictive factors examined included age, age at onset of symptoms, disease duration, sex, handedness, total tremor rating score, asymmetric tremor ratings, location of initial tremor onset, use of drugs for movement disorders, ETOH responsiveness of tremor, association of head or neck tremor, history of depression, familial history of essential tremor, Parkinson's disease, Alzheimer's disease and other movement disorders. RESULTS: On average, the TRS total score increased by <1 point per year before the first visit to the clinic and by about 2 points per year during the observed study period. The increase of 2 points per year during the observed study period represented an approximate 12% annual change from the mean TRS total score at the first clinic visit. Significant (p<0.05) predictive factors associated with increased tremor severity at the initial clinic visit included older age, longer disease duration, use of movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25, 0.19). The major factors associated with an increase in tremor severity from the initial clinic visit to the last follow up included asymmetrical tremor ratings, unilateral initial tremor onset and longer follow-up duration (r = 0.32, 0.31, 0.30). Multivariate regression analysis accounted for about 17-30% of the variance in tremor ratings (p<0.05). CONCLUSION: Essential tremor is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course.
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Temblor Esencial/patología , Índice de Severidad de la Enfermedad , Anciano , Estudios de Cohortes , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The etiology for Parkinson's disease (PD) remains unknown. Genetic causes have been identified with several distinct mutations. Recently, 9 mutations involving a novel gene, leucine-rich repeat kinase 2 (LRRK2), have been identified as the cause of autosomal dominant PD in kindreds, with some of them previously linked to the PARK8 locus on chromosome 12. LRRK2 mutations are relatively common genetic causes of familial and sporadic PD. In addition, these mutations have been identified in diverse populations. The clinical and pathologic features of LRRK2-associated PD are indistinguishable from idiopathic PD; however, considerable clinical and pathologic variability exists even among kindreds. This short review highlights the clinical and pathologic features in LRRK2-associated parkinsonism.