RESUMEN
OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.
Asunto(s)
Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Edad de Inicio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , HermanosRESUMEN
A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.
Asunto(s)
Pruebas Genéticas , Genoma , Enfermedad de Parkinson/genética , Anciano , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 9 , Dopamina beta-Hidroxilasa/genética , Distonía Muscular Deformante/genética , Ligamiento Genético/genética , Marcadores Genéticos/genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnósticoRESUMEN
N-0923 is a non-ergot, dopaminergic D(2) agonist designed to be transdermally available. It has anti-parkinsonian effects when infused intravenously. An adhesive matrix patch was developed to deliver N-0923 transdermally (N-0923 TDS). In this phase II trial, we evaluated the effectiveness of various doses of N-0923 TDS at replacing levodopa. Eighty-five Parkinson's disease (PD) patients were randomized to placebo or one of four doses of N-0923 TDS for 21 days. Change in daily levodopa dose was the primary efficacy measure. Significantly greater reductions in levodopa dose were achieved as compared to placebo for the two highest doses of N-0923 TDS. Patients treated with 33.5 mg and 67 mg N-0923 TDS decreased levodopa use by 26% and 28%, vs. 7% for placebo. N-0923 TDS was safe and well tolerated.
Asunto(s)
Agonistas de Dopamina/administración & dosificación , Levodopa/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Receptores de Dopamina D2/agonistas , Tetrahidronaftalenos/administración & dosificación , Tiofenos/administración & dosificación , Administración Cutánea , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
The medical choices are now more numerous: Dopamine agonists may have value not only for addressing the motor fluctuations of levodopa therapy but also for deferring the use of levodopa. Surgical choices are bolstered by the addition of investigational options such as neuronal transplantation, in addition to options currently approved, such as pallidotomy.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Selegilina/uso terapéutico , Actividades Cotidianas , Algoritmos , Antiparkinsonianos/efectos adversos , Humanos , Levodopa/efectos adversos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/cirugíaRESUMEN
Little is known about the underlying dimensions of impaired recognition of emotional prosody that is frequently observed in patients with Parkinson's disease (PD). Because patients with PD also suffer from working memory deficits and impaired time perception, the present study examined the contribution of (a) working memory (frontal executive functioning) and (b) processing of the acoustic parameter speech rate to the perception of emotional prosody in PD. Two acoustic parameters known to be important for emotional classifications (speech duration and pitch variability) were systematically varied in prosodic utterances. Twenty patients with PD and 16 healthy controls (matched for age, sex, and IQ) participated in the study. The findings imply that (1) working memory dysfunctions and perception of emotional prosody are not independent in PD, (2) PD and healthy control subjects perceived vocal emotions categorically along two acoustic manipulation continua, and (3) patients with PD show impairments in processing of speech rate information.
Asunto(s)
Afecto , Trastornos del Conocimiento/diagnóstico , Enfermedad de Parkinson/fisiopatología , Percepción del Habla/fisiología , Voz , Anciano , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción , Índice de Severidad de la EnfermedadRESUMEN
Objective: To assess the long-term safety and efficacy of pramipexole in advanced Parkinson's disease over a four year time period.Methods: This study is an open-label extension trial of pramipexole for Parkinson's disease open to patients completing a double-blind placebo controlled safety and efficacy trial of this drug. Three hundred and six patients entered the trial. These patients had moderate to severe PD (stage II-IV Hoehn and Yahr during off time) and were experiencing motor fluctuations. Patients were titrated over a six week period and then entered a maintenance phase which lasted up to 50 months. Patients were evaluated every 3 months using the Unified Parkinson's Disease Rating Scale (UPDRS II, III and IV) and modified Schwab and England scale (S/E).Results: Sixty-four percent (197) of the 306 patients who entered this study completed it. Patients showed steady improvement over the 6 week ascending dose interval when pramipexole was reintroduced into the trial as the open-label study medication. Over the duration of the trial patients slowly returned to their baseline levels. This was true for all measures evaluated except for the UPDRS part IV. On UPDRS part IV patients remained below their baseline score which indicated an improvement for the duration of the study. Patterns similar to the overall scores were seen when the individual components of the UPDRS scale part II for "on" and "off" periods and part III were evaluated. However tremor during "on" periods showed improvement over baseline for the duration of the trial. The most common adverse events secondary to pramipexole occurring in greater than 10% of patients included dyskinesias, asymptomatic orthostatic hypotension, dizziness, insomnia, and hallucinations.Conclusion: Pramipexole was well tolerated for up to 4 years. Pramipexole treatment appeared to show continued efficacy in the treatment of Parkinson's disease for 3 years in this open-label descriptive study. After 3 years there was a gradual return to baseline motor states perhaps suggesting progression of Parkinson's disease.
RESUMEN
In recent years, the treatment of Parkinson's disease has undergone an immense amount of research, resulting in the development of multiple new medications. This has largely been fuelled by dissatisfaction over the development of motor complications secondary to long term levodopa therapy. Different treatment approaches are applied depending on the stage of Parkinson's disease. In early and mild Parkinson's disease, selegiline offers a limited symptomatic effect. Its neuroprotective effect, although at present theoretical, has questionable clinical relevance. Increased mortality associated with selegiline has been reported, although a meta-analysis of 5 different trials did not support this finding. The newer, non-ergoline dopamine agonists, pramipexole and ropinirole, have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson's disease. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. Efficacy of the newer dopamine agonists in advanced disease seems to be comparable to that of the older agents, bromocriptine and pergolide. Adverse effects can be reduced by starting the medication at a very low dose and then slowly titrating upward. Catechol-O-methyl transferase (COMT) inhibitors are indicated for the treatment of motor fluctuations in advanced disease, particularly the 'wearing-off' phenomenon. Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time. Unfortunately, 3 deaths have been observed, which are presumably secondary to tolcapone therapy. The drug has been withdrawn in many countries, and liver enzyme testing is mandatory in the US. Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.
Asunto(s)
Antiparkinsonianos/efectos adversos , Enfermedad de Parkinson/complicaciones , Anciano , Antiparkinsonianos/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Humanos , Enfermedad de Parkinson/tratamiento farmacológicoAsunto(s)
Trastornos del Conocimiento/etiología , Enfermedad de Huntington/diagnóstico , Espasticidad Muscular/etiología , Enfermedades Neurodegenerativas/diagnóstico , Enfermedad de Parkinson Secundaria/etiología , Adulto , Diagnóstico Diferencial , Progresión de la Enfermedad , Humanos , Enfermedad de Huntington/clasificación , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/fisiopatología , Masculino , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate the nonergot dopamine agonist ropinirole as an adjunct to L-dopa in a randomized, double-blind trial in PD patients with motor fluctuations. BACKGROUND: L-dopa in the treatment of PD is associated with motor fluctuations, dyskinesia, and other adverse effects. The use of dopamine agonists in the treatment of PD delays recourse to L-dopa and thus delays the possibility of adverse effect onset. METHODS: Ropinirole (n = 95) or placebo (n = 54) was added to L-dopa, and L-dopa was then reduced in a planned manner during the 6-month trial. RESULTS: A significantly greater number of ropinirole patients were able to achieve a 20% or greater reduction in both L-dopa dose and in percent time spent "off" compared with placebo (35.0% versus 13.0%; p = 0.003). The mean daily L-dopa dose was reduced significantly with ropinirole treatment (242 mg versus 51 mg; p < 0.001) as was the percent awake time spent "off" (11.7% versus 5.1%; p = 0.039). There was no difference in the percent of patients who withdrew because of adverse effects (15.8% on ropinirole versus 16.7% on placebo). CONCLUSIONS: Ropinirole permits a reduction in L-dopa dose with enhanced clinical benefit for PD patients with motor fluctuations.
Asunto(s)
Antiparkinsonianos/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Indoles/administración & dosificación , Levodopa/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Benzofenonas/uso terapéutico , Inhibidores de Catecol O-Metiltransferasa , Inhibidores Enzimáticos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Benzofenonas/administración & dosificación , Benzofenonas/efectos adversos , Dopaminérgicos/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Nitrofenoles , Enfermedad de Parkinson/enzimología , Factores de Tiempo , Tolcapona , Resultado del TratamientoRESUMEN
Sexual dysfunction is seen in a number of neurologic diseases. In this article we review normal human sexual response, some neurologic diseases in which sexual dysfunction is seen, and Parkinson's disease (PD). With PD there is often a reduction in sexual interest and function. The studies documenting these problems are detailed. In addition, we focus on the syndrome of hyper- or aberrant sexual function seen with pharmacotherapy of PD.
Asunto(s)
Enfermedad de Parkinson/complicaciones , Disfunciones Sexuales Fisiológicas/etiología , Antiparkinsonianos/efectos adversos , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Disfunciones Sexuales Fisiológicas/inducido químicamenteRESUMEN
There is a renewed interest in sexuality in chronic disease states. Whereas there is some literature on male sexuality in Parkinson's disease (PD), no study has been devoted exclusively to women. We compared 27 women who had PD with community controls matched for age and marital status by using the Brief Index of Sexual Functioning in Women. Approximately 50% of both samples were sexually active. The women with PD were more likely to be dissatisfied with the quality of the sexual experiences. There were significant differences in the two groups with respect to anxiety or inhibition, vaginal tightness, and involuntary urination. Preoccupation with health problems interfering with sex and dissatisfaction with body appearance were also more prevalent in parkinsonian women, but not statistically different from controls. The PD patients were less satisfied with their sexual relationships and with their partners, and were more depressed as a group when compared with controls (Beck Depression Inventory of 11.8 vs 6.3). In both groups, age was associated with significant changes in satisfaction and activity. In summary, qualitative differences exist in the sexual experiences of women with PD compared with controls.
Asunto(s)
Enfermedad de Parkinson/psicología , Conducta Sexual , Distribución por Edad , Anciano , Imagen Corporal , Enfermedad Crónica , Trastorno Depresivo/psicología , Femenino , Humanos , Satisfacción Personal , Calidad de VidaRESUMEN
In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Benzofenonas/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Actividades Cotidianas , Anciano , Antiparkinsonianos/efectos adversos , Benzofenonas/efectos adversos , Diarrea/inducido químicamente , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Levodopa/efectos adversos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Nitrofenoles , Enfermedad de Parkinson/diagnóstico , Placebos , Perfil de Impacto de Enfermedad , Tolcapona , Resultado del TratamientoRESUMEN
Most patients with Parkinson's disease (PD) receiving chronic levodopa therapy eventually manifest one or more motor response complications, including "wearing-off" phenomena and "on-off" phenomena. Additionally, as the disease progresses, motor, neurologic, and neuropsychiatric complications increase and may include freezing spells, falls, dementia, depression, and psychosis. The management of patients with advanced PD presents a special clinical challenge because patients may experience an enhanced sensitivity to small changes in plasma levodopa levels and because they may suffer adverse reactions to antiparkinsonian drugs. Management of advanced PD is directed toward decreasing the dose of the offending drug while raising the dose of an alternative drug, with the goal of maintaining symptom control. In this article, the spectrum of late complications experienced by patients with advanced PD and their management are discussed.
Asunto(s)
Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Humanos , Trastornos Mentales/tratamiento farmacológicoAsunto(s)
Enfermedades de los Ganglios Basales/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Encefalitis Viral/diagnóstico por imagen , Paperas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Examen Neurológico , Enfermedades Talámicas/diagnóstico por imagenRESUMEN
Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.
Asunto(s)
Ergolinas/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Actividades Cotidianas , Adulto , Anciano , Anciano de 80 o más Años , Cabergolina , Agonistas de Dopamina/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Ergolinas/efectos adversos , Ergolinas/uso terapéutico , Femenino , Humanos , Levodopa/administración & dosificación , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Movimiento , Enfermedad de Parkinson/fisiopatología , Pacientes Desistentes del Tratamiento , Placebos , Resultado del TratamientoRESUMEN
In a preliminary study, the effects of ventroposterior medial pallidotomy were evaluated in five patients with advanced Parkinson's disease in whom medical therapy had failed. The mean age was 67.0 +/- 5.6 years, and the mean Hoehn and Yahr stage when "off" was 3.9 +/- 1.3. Three patients received unilateral pallidotomies; two of these received another pallidotomy after 8 weeks. Two other patients received staged bilateral pallidotomies. No significant differences in overall function could be seen before and after the first surgical procedure. All three patients with peak-dose dyskinesias or dystonia had marked contralateral reduction in these symptoms. Ventroposterior medial pallidotomy can ameliorate peak-dose dyskinesias in patients with advanced Parkinson's disease. Overall function improvement is not remarkable.
Asunto(s)
Globo Pálido/cirugía , Enfermedad de Parkinson/cirugía , Anciano , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Terapia Combinada , Dominancia Cerebral/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Globo Pálido/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico/efectos de los fármacos , Enfermedad de Parkinson/fisiopatología , ReoperaciónRESUMEN
Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50-100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Demencia/metabolismo , Deficiencia de Vitamina B 12/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Demencia/complicaciones , Demencia/tratamiento farmacológico , Desoxiuridina/metabolismo , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vitamina B 12/administración & dosificaciónRESUMEN
The use of the combination of fluoxetine, an anti-depressant serotonin uptake inhibitor, and selegiline, a monoamine oxidase -B inhibitor, was reviewed in a large population of patients with Parkinson's disease. All records were reviewed from a Parkinson's disease clinic to determine how many patients were treated simultaneously with selegiline and fluoxetine. Patient characteristics, duration and dose of treatment, side effects and reasons for discontinuation were noted. Twenty-three patients received both medications at the same time. No additional side effects were noted with the combination therapy that had not already been reported with each medication alone. No serious side effects were found. In this clinic population, fluoxetine and selegiline were used in combination without major side effects, but further observation is warranted.
Asunto(s)
Fluoxetina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Selegilina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Interacciones Farmacológicas , Femenino , Fluoxetina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Selegilina/efectos adversosRESUMEN
We report a patient with Lubag (X-linked dystonia-parkinsonism) who presented with severe respiratory stridor from adductor laryngeal breathing dystonia. Emergency tracheostomy was necessary, and subsequent laryngeal injection with botulinum toxin led to worsening aspiration. Botulinum toxin injection for severe lingual dystonia was successful.