RESUMEN
OBJECTIVE: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). METHODS: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. RESULTS: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). CONCLUSION: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
Asunto(s)
Disfunción Cognitiva/genética , Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Glucosilceramidasa/genética , Pruebas Neuropsicológicas , Enfermedad de Parkinson/genética , Adulto , Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/genética , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Demencia/genética , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/genética , Femenino , Pruebas Genéticas , Genotipo , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/genética , Escala del Estado Mental , Persona de Mediana Edad , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/genética , Enfermedad de Parkinson/diagnóstico , Fenotipo , Proteínas Serina-Treonina Quinasas/genética , Ubiquitina-Proteína Ligasas/genética , beta-Glucosidasa/genéticaRESUMEN
BACKGROUND: Mutations in parkin are a known genetic risk factor for early onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives. METHODS: We collected psychiatric information using the Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped individuals including 88 probands with early onset PD (41 with parkin mutations, 47 without) and 240 first and second-degree relatives without PD. RESULTS: Genotype was not associated with depression risk among probands. Among unaffected relatives of EOPD cases, only compound heterozygotes (n = 4), and not heterozygotes, had significantly increased risk of depressed mood (OR = 14.1; 95% CI 1.2-163.4), moderate to severe depression (OR = 17.8; 95% CI 1.0-332.0), depression (score ≥ 15) on the Beck Depression Inventory II (BDI-II) (OR = 51.9; 95% CI 4.1-657.4), and BDI-II total depression score (ß = 8.4; 95% CI 2.4-11.3) compared to those without parkin mutations. CONCLUSIONS: Relatives of EOPD cases with compound heterozygous mutations and without diagnosed PD may have a higher risk of depression compared to relatives without parkin mutations. These findings support evidence of a genetic contribution to depression and may extend the phenotypic spectrum of parkin mutations to include non-motor manifestations that precede the development of PD.
Asunto(s)
Depresión/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/psicología , Ubiquitina-Proteína Ligasas/genética , Adulto , Edad de Inicio , Análisis Mutacional de ADN , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Pruebas Neuropsicológicas , Fenotipo , Factores de RiesgoRESUMEN
BACKGROUND: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown. OBJECTIVE: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives. METHODS: We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 44 probands in the Consortium on Risk for Early-Onset Parkinson Disease study with PD onset ≤50 years (10 Parkin mutation heterozygotes, 9 compound heterozygotes, 25 noncarriers) and 80 of their family members (18 heterozygotes, 2 compound heterozygotes, 60 noncarriers). In the probands, linear regression was used to assess the association between UPSIT score (outcome) and Parkin genotype (predictor), adjusting for covariates. Among family members without PD, we compared UPSIT performance in heterozygotes vs noncarriers using generalized estimating equations, adjusting for family membership, age, gender, and smoking. RESULTS: Among probands with PD, compound heterozygotes had higher UPSIT scores (31.9) than heterozygotes (20.1) or noncarriers (19.9) (p < 0.001). These differences persisted after adjustment for age, gender, disease duration, and smoking. Among relatives without PD, UPSIT performance was similar in heterozygotes (32.5) vs noncarriers (32.4), and better than in heterozygotes with PD (p = 0.001). CONCLUSION: Olfaction is significantly reduced among Parkin mutation heterozygotes with PD but not among their heterozygous relatives without PD. Compound heterozygotes with PD have olfaction within the normal range. Further research is required to assess whether these findings reflect different neuropathology in Parkin mutation heterozygotes and compound heterozygotes.
Asunto(s)
Enfermedad de Parkinson/genética , Olfato , Ubiquitina-Proteína Ligasas/genética , Adulto , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Enfermedad de Parkinson/fisiopatologíaRESUMEN
OBJECTIVES: Depression and antidepressant use, especially selective serotonin reuptake inhibitors (SSRIs), are common in Parkinson disease (PD). The objective of this clinical trial was to assess the efficacy of atomoxetine, a selective norepinephrine reuptake inhibitor (SNRI), for the treatment of clinically significant depressive symptoms and common comorbid neuropsychiatric symptoms in PD. METHODS: A total of 55 subjects with PD and an Inventory of Depressive Symptomatology-Clinician (IDS-C) score > or = 22 were randomized to 8 weeks of atomoxetine or placebo treatment (target dosage = 80 mg/day). Depression response (> 50% decrease in IDS-C score or Clinical Global Impression-Improvement [CGI-I] score of 1 or 2) was assessed using intention-to-treat modeling procedures. Secondary outcomes included global cognition, daytime sleepiness, anxiety, apathy, and motor function. RESULTS: There were no between-groups differences in a priori-defined response rates. Using a more liberal response criterion of > 40% decrease in IDS score from baseline, there was a trend (p = 0.08) favoring atomoxetine. Patients receiving atomoxetine experienced significantly greater improvement in global cognition (p = 0.003) and daytime sleepiness (p = 0.001), and atomoxetine was well-tolerated. CONCLUSIONS: Atomoxetine treatment was not efficacious for the treatment of clinically significant depressive symptoms in PD, but was associated with improvement in global cognitive performance and daytime sleepiness. Larger studies of SNRIs in PD for disorders of mood, cognition, and wakefulness are appropriate. CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence that atomoxetine (target dosage = 80 mg/day) is not efficacious in improving clinically significant depression in PD.
Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Depresión/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Propilaminas/uso terapéutico , Inhibidores de Captación Adrenérgica/efectos adversos , Anciano , Clorhidrato de Atomoxetina , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/epidemiología , Comorbilidad , Depresión/epidemiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Propilaminas/efectos adversos , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.
Asunto(s)
Agnosia/diagnóstico por imagen , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/análisis , Compuestos de Organotecnecio , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tropanos , Agnosia/etiología , Agnosia/fisiopatología , Unión Competitiva/fisiología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiopatología , Progresión de la Enfermedad , Dopamina/deficiencia , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Examen Neurológico , Vías Olfatorias/diagnóstico por imagen , Vías Olfatorias/metabolismo , Vías Olfatorias/fisiopatología , Compuestos de Organotecnecio/metabolismo , Compuestos de Organotecnecio/farmacocinética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Radiofármacos , Olfato/fisiología , Transmisión Sináptica/fisiología , Tropanos/metabolismo , Tropanos/farmacocinéticaRESUMEN
We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p < 0.0001) of PD patients compared to controls. Using the posterior putamen as the main region of interest resulted in the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.
Asunto(s)
Compuestos de Organotecnecio , Enfermedad de Parkinson/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único/normas , Tropanos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories. METHODS: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients. RESULTS: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy. CONCLUSION: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.
Asunto(s)
Demencia/fisiopatología , Enfermedades Neurodegenerativas/fisiopatología , Anciano , Encéfalo/patología , Encéfalo/fisiopatología , Demencia/diagnóstico , Demencia/patología , Femenino , Humanos , Juicio , Imagen por Resonancia Magnética , Masculino , Matemática , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/patología , Pruebas Neuropsicológicas/estadística & datos numéricos , Reconocimiento Visual de ModelosRESUMEN
Recently, the authors demonstrated linkage in idiopathic PD to a region on chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The authors examined NAT1 and NAT2 for association with PD using family-based association methods and single nucleotide polymorphisms (SNPs). The authors did not find evidence for association with increased risk for PD between any individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580 individuals).
Asunto(s)
Arilamina N-Acetiltransferasa/genética , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Polimorfismo Genético , Anciano , Alelos , Cromosomas Humanos Par 8/genética , Femenino , Frecuencia de los Genes , Ligamiento Genético , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Isoenzimas/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Medición de RiesgoRESUMEN
CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.
Asunto(s)
Enfermedad de Parkinson/genética , Ubiquitina-Proteína Ligasas , Adulto , Edad de Inicio , Anciano , Antiparkinsonianos/uso terapéutico , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 6 , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Resistencia a Medicamentos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Levodopa/uso terapéutico , Ligasas/genética , Escala de Lod , Repeticiones de Microsatélite , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Factores de RiesgoRESUMEN
CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.
Asunto(s)
Enfermedad de Parkinson/genética , Proteínas tau/genética , Edad de Inicio , Anciano , Cromosomas Humanos Par 17 , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
The etiology of parkinsonism is varied. Symptomatic parkinsonism is seen in the setting of genetic disorders, infectious processes, structural lesions, and as a result of concomitant medications. A thorough history and good examination will differentiate PD from the diverse group of conditions that can mimic it.
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Trastornos Parkinsonianos/clasificación , Trastornos Parkinsonianos/etiología , Diagnóstico Diferencial , Humanos , Trastornos Parkinsonianos/diagnósticoRESUMEN
Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.
Asunto(s)
Esófago/fisiopatología , Manometría , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Espasmo Esofágico Difuso/etiología , Unión Esofagogástrica/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , PeristaltismoRESUMEN
Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a feature of achalasia. This article documents similar findings in six patients with Parkinson's disease. Parkinson's disease and achalasia share many common features neurologically. Both have Lewy bodies in the esophageal myenteric plexuses and the substantia nigra, in addition to evidence of degeneration of the dorsal motor nucleus of the vagus. The esophageal features radiologically and manometrically are also similar. Repetitive proximal esophageal contractions may represent another link between these diseases. They have also been reported in scleroderma. We speculate that the common link between all three disease processes may be poor distensibility of the esophagus.
Asunto(s)
Acalasia del Esófago/metabolismo , Acalasia del Esófago/fisiopatología , Cuerpos de Lewy/metabolismo , Contracción Muscular/fisiología , Músculo Liso/fisiopatología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Acalasia del Esófago/diagnóstico , Femenino , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , PeriodicidadRESUMEN
BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.
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Acetamidas/efectos adversos , Acetamidas/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Cooperación del Paciente , Receptores de GlutamatoAsunto(s)
Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Linaje , Factores de Riesgo , Sinucleínas , alfa-SinucleínaRESUMEN
Although the clinical manifestations of PD remain similar to those described by Parkinson in the nineteenth century, knowledge of associated findings has increased dramatically. The ability to characterize the myriad of findings associated with PD enables clinicians to care better for patients with PD. Knowledge of the associated symptoms as well as the cardinal manifestations allows clinicians to target treatment to specific symptoms and thereby improve the quality of life of those affected with PD.
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Enfermedad de Parkinson/diagnóstico , Actividades Cotidianas , Humanos , Enfermedad de Parkinson/complicacionesRESUMEN
Movement disorders cause difficulty with ambulation. Hypokinetic disorders produce a slow gait with short strides and impairment of balance. The hyperkinetic disorders are also marked by an impairment of balance, caused by rapid or uncontrollable movements of the limbs or trunk, that interferes with the normal rhythm of walking. The gaits of different movement disorders help the clinician to classify them. Appropriate diagnosis and treatment of the disorder may significantly improve ambulation and quality of life.
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Marcha , Trastornos del Movimiento , Humanos , Hipercinesia/fisiopatología , Hipercinesia/terapia , Trastornos del Movimiento/complicaciones , Trastornos del Movimiento/fisiopatología , Trastornos del Movimiento/terapia , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapiaRESUMEN
The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential.
Asunto(s)
Mapeo Encefálico/métodos , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Imagen por Resonancia Magnética , Monitoreo Intraoperatorio/métodos , Enfermedad de Parkinson/terapia , Cuidados Preoperatorios/métodos , Técnicas Estereotáxicas , Núcleos Talámicos Ventrales/patología , Mapeo Encefálico/instrumentación , Estudios de Evaluación como Asunto , Humanos , Microelectrodos , Monitoreo Intraoperatorio/instrumentación , Esclerosis Múltiple/complicaciones , Temblor/etiología , Temblor/terapia , Interfaz Usuario-ComputadorRESUMEN
Dysphagia is common in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Although it is believed to be more common in PSP, there are no controlled data and no comparison of swallowing function between these two disorders. Our aim was to assess dysphagia and swallow function in patients with PSP and PD. Seven patients with PSP were matched to seven patients with PD on the basis of disease duration. Self-rated dysphagia, movement disorder disability, modified barium swallow results, and abnormalities noted on manometry of the lower esophageal sphincter, esophageal body, upper esophageal sphincter, and pharynx were compared between the two groups. Neither severity nor duration of dysphagia differed between the two groups. Patients with PSP had a significantly greater degree of disability [median (range) Hoehn & Yahr score, 4 (3-5) vs. 2 (1-2); P < 0.002]. Manometric abnormalities were similar for the two groups. Oral-phase abnormalities on modified barium swallow were significantly more frequent in PSP (four patients with PSP vs. no patients with PD; p < 0.005). Pharyngeal abnormalities did not differ. Modified barium-swallow scores correlated well with self-reported dysphagia severity for patients with PSP (r = 0.93; p < 0.05) but not for those with PD (r = 0.42; p = NS). The frequency of abnormalities noted during the oral phase was significantly increased in PSP. It is hypothesized that the sensory information conveyed due to this may account for the better correlation between symptoms and swallowing abnormalities and the belief that swallowing problems are more common in PSP.