RESUMEN
BACKGROUND: Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS). METHODS: We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem. RESULTS: Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with l-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies. CONCLUSION: Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated.
Asunto(s)
Depresión/complicaciones , Temblor Esencial/complicaciones , Salud de la Familia , Trastornos Parkinsonianos/complicaciones , Síndrome de las Piernas Inquietas/complicaciones , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Proteínas de Unión al ADN/metabolismo , Depresión/diagnóstico por imagen , Depresión/genética , Complejo Dinactina , Temblor Esencial/diagnóstico por imagen , Temblor Esencial/genética , Factor 4G Eucariótico de Iniciación/genética , Femenino , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Estudios Longitudinales , Masculino , Escala del Estado Mental , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/genética , Tomografía de Emisión de Positrones/métodos , Proteínas Serina-Treonina Quinasas/genética , Síndrome de las Piernas Inquietas/diagnóstico por imagen , Síndrome de las Piernas Inquietas/genética , alfa-Sinucleína/genéticaRESUMEN
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.
Asunto(s)
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
OBJECTIVE: Mutations in both alleles of parkin have been shown to result in Parkinson disease (PD). However, it is unclear whether haploinsufficiency (presence of a mutation in only 1 of the 2 parkin alleles) increases the risk for PD. METHODS: We performed comprehensive dosage and sequence analysis of all 12 exons of parkin in a sample of 520 independent patients with familial PD and 263 controls. We evaluated whether presence of a single parkin mutation, either a sequence (point mutation or small insertion/deletion) or dosage (whole exon deletion or duplication) mutation, was found at increased frequency in cases as compared with controls. We then compared the clinical characteristics of cases with 0, 1, or 2 parkin mutations. RESULTS: We identified 55 independent patients with PD with at least 1 parkin mutation and 9 controls with a single sequence mutation. Cases and controls had a similar frequency of single sequence mutations (3.1% vs 3.4%, p = 0.83); however, the cases had a significantly higher rate of dosage mutations (2.6% vs 0%, p = 0.009). Cases with a single dosage mutation were more likely to have an earlier age at onset (50% with onset at < or =45 years) compared with those with no parkin mutations (10%, p = 0.00002); this was not true for cases with only a single sequence mutation (25% with onset at < or =45 years, p = 0.06). CONCLUSIONS: Parkin haploinsufficiency, specifically for a dosage mutation rather than a point mutation or small insertion/deletion, is a risk factor for familial PD and may be associated with earlier age at onset.
Asunto(s)
Dosificación de Gen/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Secuencia de Bases/genética , Análisis Mutacional de ADN , Femenino , Eliminación de Gen , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Mutación Puntual/genética , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously observed linkage finding. METHODS: We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test whether variants in GIGYF2 are causative or increase susceptibility for PD. RESULTS: We detected three novel variants as well as one of the previously reported seven variants in a total of five multiple PD families; however, there was no consistent evidence that these variants segregated with PD in these families. We also did not find a significant increase in risk for PD among those inheriting variants in GIGYF2 (p = 0.28). CONCLUSIONS: We believe that variation in a gene other than GIGYF2 accounts for the previously reported linkage finding on chromosome 2q36-37.
Asunto(s)
Proteínas Portadoras/genética , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Mutación/genética , Enfermedad de Parkinson/genética , Anciano , Secuencia de Bases/genética , Mapeo Cromosómico/métodos , Cromosomas Humanos Par 2/genética , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Lectura Abierta/genética , Linaje , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. METHODS: We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. RESULTS: Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. CONCLUSIONS: This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.
Asunto(s)
Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Glucosilceramidasa/genética , Mutación/genética , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Variación Genética/genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/enzimologíaRESUMEN
Since the original 1995 report of a parkinsonian kindred, four individuals have been affected (mean age at onset, 65 years). All four had cardinal signs of Parkinson disease (PD) and good response to levodopa. Four autopsies showed neuronal loss and gliosis in the substantia nigra. Lewy bodies (LB) limited to brainstem nuclei were detected in one case, diffuse LB in the second, neurofibrillary tangles (NFT) without LB in the third, and neither NFT nor LB in the fourth. Genetic studies suggested linkage to the PARK8 locus on chromosome 12.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Trastornos Parkinsonianos/genética , Tauopatías/genética , Anciano , Encéfalo/patología , Cromosomas Humanos Par 12/genética , Familia , Femenino , Estudios de Seguimiento , Ligamiento Genético , Variación Genética , Humanos , Inmunohistoquímica , Cuerpos de Lewy/patología , Masculino , Mutación , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/patología , Linaje , Fenotipo , Sustancia Negra/patología , Sinucleínas , Ubiquitina-Proteína Ligasas/genética , Proteínas tau/genéticaRESUMEN
BACKGROUND: Autonomic dysfunction occurs in Parkinson's disease (PD), but few studies have addressed it in a comprehensive manner. METHODS: Autonomic symptoms were evaluated by a questionnaire in sixty-eight subjects (44 patients and 24 controls). RESULTS: PD patients experienced higher frequency and severity of autonomic dysfunction. When all autonomic symptoms were pooled into an aggregate score, differences between patients and controls were highly statistically significant (p<0.0001). 'Increased salivation', 'frequency of dysphagia', decreased 'BM (bowel movement) frequency', i.e. constipation, and 'orthostatic dizziness' were more frequent in PD patients (p<0.05). A prediction model to determine the predictors of autonomic dysfunction was unsuccessful. CONCLUSION: Differences in the prevalence of autonomic symptoms in PD and non-parkinsonian controls are apparent from this study.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedad de Parkinson/complicaciones , Anciano , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Prevalencia , Valores de Referencia , Análisis de Regresión , Índice de Severidad de la EnfermedadRESUMEN
We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, Family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical Lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and Lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. Lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease.
Asunto(s)
Encéfalo/patología , Trastornos Parkinsonianos/patología , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 2/genética , Femenino , Ligamiento Genético , Predisposición Genética a la Enfermedad/genética , Alemania/etnología , Humanos , Estudios Longitudinales , Masculino , Trastornos Parkinsonianos/genética , Linaje , Estados UnidosRESUMEN
Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), characterized by an autosomal dominant inheritance pattern, has recently been recognized as a distinct entity that can display a confusingly broad clinical phenotype. The pallido-ponto-nigral degeneration (PPND) variant is the prototypical example of the parkinsonism-predominant pattern of FTDP-17. A longitudinal videotape demonstration of the clinical progression of this entity in a single individual, along with brief videotape segments from three additional affected individuals, is presented in order to facilitate recognition of this disorder.
Asunto(s)
Cromosomas Humanos Par 17 , Demencia/genética , Ligamiento Genético/genética , Trastornos Parkinsonianos/genética , Adulto , Demencia/diagnóstico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Trastornos Parkinsonianos/diagnóstico , Grabación de Cinta de VideoRESUMEN
Missense mutations at the alpha-synuclein gene have been associated with familial parkinsonism. We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa-responsive parkinsonism maps to chromosomal region 4q21-23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the alpha-synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the alpha-synuclein gene at a time point before symptom onset. In conclusion, reduced alpha-synuclein gene expression may be important in the pathogenesis of parkinsonism.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Alelos , Femenino , Ligamiento Genético/genética , Humanos , Escala de Lod , Masculino , Linaje , Fenotipo , Mutación Puntual/genética , Reacción en Cadena de la Polimerasa , Sinucleínas , alfa-SinucleínaRESUMEN
The authors administered electroconvulsive therapy (ECT) to four patients with intractable Parkinson's disease who were free from depression or dementia. After an initial "acute" phase, subjects received bitemporal maintenance ECT every 3 to 4 weeks for up to 12 months. Serial measures of mood, cognition, and motor function were performed. One subject developed cognitive impairment after seven maintenance treatments, and another developed delusions during the acute phase of the study. The two subjects completing the 12-month maintenance phase noted significant reductions in "off" time without impairment of cognitive functioning.
Asunto(s)
Terapia Electroconvulsiva , Enfermedad de Parkinson/terapia , Anciano , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/terapia , Resistencia a Medicamentos , Terapia Electroconvulsiva/efectos adversos , Femenino , Humanos , Cuidados a Largo Plazo/métodos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Factores de Tiempo , Resultado del TratamientoRESUMEN
Dementia with Lewy bodies (DLB) may be one of the most common causes of dementia. It should be of particular interest to psychiatrists because hallucinations are common presenting symptoms and because patients with DLB may be particularly sensitive to neuroleptics with respect to developing extrapyramidal symptoms. The authors describe 2 patients with DLB who were intolerant of clozapine, showing not extrapyramidal side effects, but an increase in confusion and behavioral symptoms.
Asunto(s)
Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Confusión/inducido químicamente , Demencia/tratamiento farmacológico , Cuerpos de Lewy , Psicosis Inducidas por Sustancias , Anciano , Demencia/patología , Humanos , MasculinoAsunto(s)
Ciclosporina/efectos adversos , Inmunosupresores/efectos adversos , Cirrosis Hepática Biliar/cirugía , Trasplante de Hígado/inmunología , Mielinólisis Pontino Central/inducido químicamente , Temblor/inducido químicamente , Adulto , Ciclosporina/administración & dosificación , Diagnóstico Diferencial , Femenino , Humanos , Inmunosupresores/administración & dosificación , Mielinólisis Pontino Central/diagnóstico , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/diagnóstico , Temblor/diagnósticoRESUMEN
Brain-derived neurotrophic factor (BDNF) promotes the differentiation and growth of developing dopamine (DA) neurons and supports the survival of mature DA cells in culture. However, the neurotrophic role of endogenous BDNF in the adult DA system in vivo has not been well established. To investigate the hypothesis that blockade of endogenous BDNF expression results in DA dysregulation, we used an 18-mer antisense oligodeoxynucleotide (ODN) targeted to the first ATG codon of the BDNF transcript. The biological activity of the antisense ODN was initially tested in vitro. In cultured dopaminergic MES 23.5 cells, antisense BDNF (20 microM) effectively reduced BDNF protein expression and cell survival. Furthermore, in primary embryonic mesencephalic cultures, antisense BDNF reduced the number of tyrosine hydroxylase positive neurons and inhibited [3H]DA uptake in a time- and dose-dependent manner. The specificity of the antisense molecule was confirmed by comparing its effects with those of a control ODN having the same base composition but in scrambled sequence. In rats, two days following an intranigral or intrastriatal injection of antisense BDNF (0.5 microg), we observed a two-fold and five-fold increase in nigral DA levels, respectively, but no change in striatal DA content. Seven days after an intrastriatal antisense BDNF injection, DA levels were elevated in the striatum apparently due to decreased DA turnover. These observations suggest that inhibition of endogenous BDNF expression tends to augment rather than inhibit nigrostriatal DA transmission. Thus, the biological effects of endogenous BDNF on the nigrostriatal DA system in the adult organism merits further investigation.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Cuerpo Estriado/fisiología , Dopamina/metabolismo , Dopamina/fisiología , Mesencéfalo/fisiología , Neuronas/fisiología , Oligonucleótidos Antisentido/farmacología , Sustancia Negra/fisiología , Animales , Transporte Biológico , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Células Cultivadas , Cuerpo Estriado/efectos de los fármacos , Embrión de Mamíferos , Células Híbridas , Cinética , Masculino , Mesencéfalo/efectos de los fármacos , Neuroblastoma , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sustancia Negra/efectos de los fármacos , Tirosina 3-Monooxigenasa/análisisRESUMEN
Gastrointestinal dysfunction is a frequent and occasionally dominating symptom of Parkinson's disease (PD). Features of gastrointestinal dysfunction include disordered control of saliva, dysphagia, gastroparesis, constipation in the sense of decreased bowel movement frequency, and defecatory dysfunction necessitating increased straining and resulting in incomplete evacuation. Excess saliva accumulates in the mouth because of decreased swallowing frequency. Dysphagia develops in approximately 50% of patients and may be a reflection of both central nervous system and enteric nervous system derangement. Gastroparesis may produce a variety of symptoms, including nausea, and also may be responsible for some of the motor fluctuations seen with levodopa therapy. Bowel dysfunction in PD may be the result of both delayed colon transit and impaired anorectal muscle coordination.
Asunto(s)
Enfermedades Gastrointestinales/etiología , Enfermedad de Parkinson/complicaciones , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/terapia , Gastroparesia/etiología , Gastroparesia/terapia , Humanos , Enfermedades Intestinales/etiología , Enfermedades Intestinales/terapia , SalivaciónRESUMEN
The finding that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) elicits parkinsonism in human beings suggests that endogenous or xenobiotic neurotoxic compounds may be involved in the etiology of Parkinson's disease (PD). We have shown that cerebrospinal fluid (CSF) of newly diagnosed and drug untreated patients with PD contains a low molecular weight substance(s) which inhibits the growth and function of dopaminergic neurons in culture. In addition, selegiline in a dosage below the level that inhibits monoamine oxidase B (MAO-B), protects dopaminergic neurons in culture against toxic factor(s) present in the CSF of patients with PD, and the said effect is mediated via elaboration of brain-derived neurotrophic factor (BDNF). In view of the fact that 6-hydroxydopamine (6-OHDA) or MPTP causes parkinsonism by generating free radicals, and inducers of metallothionein (MT) isoforms avert the said neurotoxicity, we intended to learn whether MT isoforms were capable of scavenging free radicals. By employing electron spin resonance spectroscopy (ESR), we examined for the first time the free radical scavenging effects of MT-I and MT-II isoforms on four types of free radicals. Solutions of 0.15 mM of MT-I and 0.3 mM of MT-II scavenged the 1,1-diphenyl-2-picrylhydrazyl radicals completely. Furthermore, they were able to scavenge hydroxyl radicals generated in a Fenton reaction. Moreover, MT-I scavenged almost 90% of the superoxide generated by the hypoxanthine and xanthine oxidase system, while MT-II could only scavenge 40%. By using 2,2,6,6-tetramethyl-4-piperidone as a "spin-trap" for the reactive oxygen species (containing singlet oxygen, superoxide and hydroxyl radicals) generated by photosensitized oxidation of riboflavin, and measuring the relative signal intensities of the resulting stable nitroxide adduct, 2,2,6,6-tetramethyl-4-piperidone-1-oxyl, we observed that MT-II could scavenge 92%, while MT-I could completely scavenge all the reactive species generated. The results of this investigation are interpreted to suggest that selegiline by preventing the generation of free radicals, MT isoforms by scavenging free radicals, and neurotrophins by rescuing dopaminergic neurons are capable of attenuating oxidative stress and of providing neuro-protection in PD.
RESUMEN
We evaluated the reliability of patient history and the effect of psyllium on symptoms and colorectal function in 12 patients with Parkinson's disease (PD) and constipation. In all but two, constipation anteceded the development of parkinsonian symptoms. A comparison with prospectively obtained stool diaries confirmed the patients' reported constipation in 7 of the 12 patients. Those patients with confirmed constipation had lower stool weights and reported more straining at stool. Measures of colonic and anorectal function were similar in those who were truly constipated and those who were not. Among those PD subjects with confirmed constipation, psyllium increased stool frequency and weight but did not alter colonic transit or anorectal function. We conclude that prospectively obtained stool diaries should be employed to confirm constipation in PD and that psyllium produces both subjective and objective improvements in constipation related to PD.
Asunto(s)
Catárticos/uso terapéutico , Estreñimiento/complicaciones , Estreñimiento/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Psyllium/uso terapéutico , Anciano , Canal Anal/anatomía & histología , Canal Anal/fisiología , Defecación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
Impaired olfactory function is commonly observed in idiopathic Parkinson's disease (IPD). However, it is unknown whether it is also found in familial parkinsonism. To address this issue we administered a smell test to 12 affected, three monosymptomatic, and 12 at-risk individuals from six large parkinsonian kindreds. Three kindreds exhibited an IPD phenotype and three exhibited a parkinsonism-plus syndrome (PPS) phenotype. All but one of the affected individuals had impaired olfactory function. In contrast, only five of the 12 at-risk individuals had impaired olfactory function. The degree of olfactory impairment in the at-risk individuals was less severe than in the affected individuals. The difference in the degree of olfactory impairment in individuals exhibiting the IPD and the PPS phenotypes was not statistically significant. These findings suggest that olfactory dysfunction is a phenotypic characteristic of familial parkinsonism and that it is independent of the kindred phenotype. The appearance of olfactory dysfunction soon after disease onset raises the possibility that it is part of the neurodegenerative disease process.