RESUMEN
Because the prevalence of idiopathic Parkinson's disease (PD) with or without dementia remains controversial, we initiated a population-based investigation in the Washington Heights-Inwood section of New York, NY, so that nearly complete case ascertainment could be achieved. A "registry" was developed for the study, and we advertised in periodicals and on radio and television. Subjects, or their records, were examined by experienced neurologists, and most underwent a battery of neuropsychological tests specifically designed for assessment in this community. All data were reviewed by a team of clinicians to achieve a consensus diagnosis. The crude prevalence of idiopathic PD, with and without dementia, was 99.4 per 100,000, increasing from 2.3 per 100,000 for those younger than 50 years to 1144.9 per 100,000 for those aged 80 years and older. The crude prevalence for PD with dementia alone was 41.1 per 100,000 and also increased with age from zero for those younger than 50 years to 787.1 per 100,000 for those aged 80 years and older. Prevalence ratios were comparable with those of other published population-based studies in similar settings. After standardization, men had PD with and without dementia more frequently than did women. The major difference between patients with and without dementia was a later estimated age at onset of motor manifestations. We conclude that PD is a frequent disorder in the elderly population that affects men and whites more frequently than women and nonwhites. Moreover, dementia in patients with PD is more frequent than previously recognized and is strongly related to the age at onset of motor manifestations.
Asunto(s)
Demencia/epidemiología , Enfermedad de Parkinson/epidemiología , Anciano , Demencia/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , New York/epidemiología , Enfermedad de Parkinson/complicaciones , Población , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Action tremor is often noted in patients with Parkinson disease (PD), yet the clinical correlates of this type of tremor have been the focus of few studies. It is not clear whether this action tremor is a manifestation of the underlying basal ganglia disease. OBJECTIVE: To determine whether the severity of action tremor in PD is associated with age, age at disease onset, disease duration, levodopa dose, severity of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations of PD. METHODS: Patients with PD (N = 197) were ascertained as part of a familial aggregation study. All patients underwent a neurological examination. Rest tremor was rated with the Unified Parkinson Disease Rating Scale; and action tremor, with the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale. RESULTS: Action tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met criteria for definite essential tremor. The action tremor score was not associated with age, age at onset, or disease duration. The action tremor score was associated with the rest tremor score (r = 0.37; P<.001), and more strongly with the ipsilateral than contralateral rest tremor score. The association between the action tremor score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when we excluded these 63 patients with re-emergent tremor. Neither the action nor the rest tremor score was associated with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination score. CONCLUSIONS: Action tremor was associated with rest tremor in PD, suggesting that, at least in part, action tremor is a manifestation of the underlying basal ganglia disease. Neither tremor was associated with other motor and nonmotor manifestations of PD. This in turn suggests that tremor in PD may represent an underlying pathophysiological process different from these other manifestations.
Asunto(s)
Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Temblor/etiología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/uso terapéutico , Brazo , Femenino , Humanos , Hipocinesia/fisiopatología , Levodopa/uso terapéutico , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Actividad Motora/fisiología , Movimiento/fisiología , Rigidez Muscular/fisiopatología , Enfermedad de Parkinson/psicología , Examen Físico , Postura , Descanso , Temblor/fisiopatología , Grabación en VideoRESUMEN
Forty-three of 101 outpatients with parkinsonism reported that they regularly experienced primary sensory symptoms, i.e., spontaneous abnormal sensations not caused by somatic disease. This is in contrast to similar symptoms reported by only 8 percent of a control population. The most striking and severe symptom was burning of the trunk and proximal extremities, occurring in 11 patients. Twenty-nine patients reported spontaneous pain; a variety of other paresthesialike sensations, e.g., tingling, numbness, and formication, occurred in 32 patients. These subjective sensory phenomena were not associated with sensory loss or autonomic or motor signs. In 20 percent of affected individuals (9 percent of the total), sensory symptoms preceded the onset of the movement disorder, causing difficulty in diagnosis. It is concluded that at least some sensory symptoms originate within the nervous system as a manifestation of the disease process and are not secondary effects of the motor disorder.
Asunto(s)
Enfermedad de Parkinson/fisiopatología , Sensación/fisiología , Anciano , Femenino , Humanos , Levodopa/efectos adversos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/inducido químicamente , Dolor/complicaciones , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Parestesia/inducido químicamente , Parestesia/complicaciones , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson Posencefalítica/fisiopatología , Síndrome de las Piernas Inquietas/complicacionesRESUMEN
Fifty-three patients with parkinsonism, either with intractable symptoms despite optimum-dosage levodopa therapy or with adverse effects from levodopa limiting its usefulness, were treated with bromocriptine, with gradually increasing doses until benefit or adverse effect was encountered. All were initially maintained on optimal levodopa therapy. Improvement was seen in 26 patients, of whom 19 (36 percent of the total 53 patients) had sustained improvement. Effective doses of bromocriptine ranged from 5 to 90 mg per day. Improvement occurred in all categories of clinical problems, including patients who lost some benefit from chronic levodopa therapy as well as those with adverse effects from levodopa. A high incidence (70 percent) of adverse effects of bromocriptine limited the usefulness of this drug. Since one cannot predict which patients might benefit from bromocriptine, this drug is worth a trial in patients not doing well on levodopa therapy if other means to improve their condition are not successful.
Asunto(s)
Bromocriptina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Bromocriptina/administración & dosificación , Bromocriptina/efectos adversos , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/inducido químicamenteRESUMEN
Concentric hyaline inclusions (Lewy bodies), found in the cytoplasm of pigmented and nonpigmented neurons, are considered characteristic of idiopathic Parkinson's disease. The finding of cytoplasmic inclusions identical to Lewy bodies in ganglion cells of the colonic myenteric plexus in a patient with idiopathic Parkinson's disease and acquired megacolon suggests primary involvement of the enteric nervous system by Parkinson's disease.
Asunto(s)
Cuerpos de Inclusión/patología , Megacolon/etiología , Plexo Mientérico/ultraestructura , Enfermedad de Parkinson/complicaciones , Humanos , Masculino , Megacolon/patología , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Recto/inervaciónRESUMEN
The goal of this study was to characterize the changes in cognition associated with the earliest, or preclinical, stages of dementia in Parkinson's disease (PD). We administered a comprehensive neuropsychological test battery to a group of initially nondemented PD patients participating in a longitudinal community-based epidemiologic study. We used Cox proportional hazards models to assess the relative risk of incident dementia associated with baseline scores on the neuropsychological tests. Baseline performance on two verbal fluency tasks (letter fluency and category fluency) was significantly and independently associated with incident dementia. Tests of memory, orientation, abstract reasoning, naming, and constructional skill were less sensitive predictors of subsequent dementia. The neuropsychological pattern characterizing the preclinical stages of dementia in PD differed from that described previously in preclinical Alzheimer's disease. Results suggest that poor performance on tests of verbal fluency may represent a distinct characteristic of the preclinical phase of dementia in PD.
Asunto(s)
Demencia/psicología , Enfermedad de Parkinson/psicología , Anciano , Anciano de 80 o más Años , Demencia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Factores de RiesgoRESUMEN
We evaluated the current status of 131 patients with idiopathic parkinsonism who were receiving levodopa therapy. The residual parkinsonian symptoms and signs were tabulated, as were the adverse effects from medication. Response to therapy was correlated with duration of the disease and with duration of treatment. Patients with on-off or wearing-off effects were likely to have been treated for 4 years or longer. Patients treated with levodopa for 4 to 8 years were significantly more impaired with parkinsonism than patients treated for 0 to 3 years, even when patients were matched for total duration of disease. These data suggest that the deterioration of responsiveness after several years of levodopa therapy may be due to the therapy itself. Our findings support the concept that utilization of levodopa therapy should be delayed until a patient becomes significantly impaired in occupational or social situations.
Asunto(s)
Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Adolescente , Adulto , Anciano , Corea/inducido químicamente , Encefalitis/complicaciones , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Factores de TiempoRESUMEN
OBJECTIVE: To analyze the relationship of specific motor impairment in idiopathic PD to incident dementia. BACKGROUND: The total Unified PD Rating Scale (UPDRS) motor score at baseline has been associated with an increased risk of developing dementia in PD. METHODS: A cohort of 214 nondemented community-dwelling patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of baseline motor impairment with incident dementia was analyzed using Cox proportional hazards models. Facial expression, tremor, rigidity, and bradykinesia were analyzed as part of subscore A (indicative of dopaminergic deficiency); speech and axial impairment were analyzed as part of subscore B (indicative of predominantly nondopaminergic deficiency). The correlation between the six motor domains and age was also analyzed. RESULTS: Of 173 patients followed for at least 1 year, 50 became demented according to the Diagnostic and Statistical Manual of Mental Disorders, revised 3rd edition (DSM III-R) criteria (mean follow-up, 3.6 +/- 2. 2 years). When both subscores A and B were entered into the Cox model, subscore B was associated with incident dementia (relative risk = 1.19; 95% CI, 1.09 to 1.30; p = 0.0001), in addition to gender, age, and education, whereas subscore A was not (relative risk = 1.03; 95% CI, 0.99 to 1.07; p = 0.19). Of the six motor domains, speech and bradykinesia were associated with incident dementia (p < 0.05), and axial impairment approached significance (p = 0.06). Only axial impairment was correlated with age (correlation coefficient = 0.32; p < 0.001). CONCLUSION: The findings suggest that motor impairment mediated predominantly by nondopaminergic systems is associated with incident dementia in PD. Axial impairment may be the result of a combined effect of the disease and the aging process.
Asunto(s)
Envejecimiento , Demencia/epidemiología , Discinesias/epidemiología , Enfermedad de Parkinson/epidemiología , Factores de Edad , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Ciudad de Nueva York/epidemiología , Oportunidad Relativa , Enfermedad de Parkinson/fisiopatología , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Distribución por SexoRESUMEN
OBJECTIVE: To evaluate the association of incident dementia with mortality in a cohort of patients with idiopathic PD who were nondemented at baseline evaluation, controlling for extrapyramidal sign (EPS) severity at each study visit. BACKGROUND: The development of dementia has been associated with reduced survival in PD. Because EPS severity is associated with both dementia and mortality in PD, the association of dementia with mortality may be confounded by disease severity. METHODS: A cohort of patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of incident dementia and the total Unified PD Rating Scale (UPDRS) motor score with mortality in PD was examined using Cox proportional hazards models with time-dependent covariates. All analyses were adjusted for age at baseline, sex, years of education, ethnicity, and duration of PD. RESULTS: Of 180 PD patients, 41 (22.8%) died during a mean follow-up period of 3.9 +/- 2.2 years. Among those who died during the study period, 48.8% (20 of 41) became demented during follow-up, as compared to 23.0% (32 of 139) of those who remained alive. Both incident dementia (RR: 2.2, 95% CI: 1.1 to 4.5, p = 0.04) and the total UPDRS motor score at each study visit (RR: 1.04, 95% CI: 1.02 to 1.07, p = 0.001) were associated with mortality in PD when included in the same Cox model. CONCLUSIONS: Incident dementia has an independent effect on mortality when controlling for EPS severity. The development of dementia is associated with a twofold increased mortality risk in PD.
Asunto(s)
Demencia/mortalidad , Enfermedad de Parkinson/mortalidad , Anciano , Anciano de 80 o más Años , Enfermedades de los Ganglios Basales/fisiopatología , Estudios de Cohortes , Demencia/complicaciones , Demencia/fisiopatología , Femenino , Humanos , Masculino , Examen Neurológico , Pruebas Neuropsicológicas , Casas de Salud , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Desempeño Psicomotor/fisiología , Medición de Riesgo , Factores de TiempoRESUMEN
The possibility that GABA may have its origin in putrescine was investigated in the rat pancreas, relative to the brain. These studies show that radioactive putrescine is converted to GABA at a similar rate in both the pancreas and brain, but that putrescine accounts for only a small fraction of the GABA found in these organs. Inhibitors of diamine and monoamine oxidases do not significantly change the GABA level in the pancreas. In contrast to the brain, where putrescine is catabolized to GABA via monoamine oxidase, the primary catabolic pathway of putrescine to GABA in the pancreas is via diamine oxidase. In vivo studies show that AOAA inhibits GABA-T activity to the same degree in the pancreas as in the brain, elevating GABA levels more than 2-fold in 4 h. GABA is metabolized more rapidly in the brain than the pancreas. Turnover times of GABA in the pancreas and brain are 1.9 and 1.0 h, respectively. The slower turnover of GABA in the pancreas than in the brain may relate to a neuromodulatory role for GABA, similar to that for neuropeptides. Developmental studies in the postnatal pancreas suggest a role for GABA in the maturation of insulin secretion.
RESUMEN
Thermoregulatory, cardiovascular and endocrine changes were simultaneously monitored in 11 post-menopausal women with frequent hot flashes (catecholamine and LH levels were measured in 5 and 6 subjects respectively). Plasma samples were obtained at 1- and 5-min intervals. Hot flashes were accompanied by abrupt increases in plasma epinephrine (about 150%) and concomitant decreases in norepinephrine (about 40%). Increased luteinizing hormone was associated with most hot flashes. A detailed sequence of hot flash-associated changes was established. An aura preceded the onset of the hot flash by several seconds. HR and FBF increased just before the onset of the flash and reached peak levels of 10-20 beats/min and 30-fold respectively. Coincident with vasodilation and sweating, finger temperature increased an average of 3.9 degrees C and esophageal temperature fell 0.2-0.6 degrees C. Flashes of both discrete and prolonged intervals were observed. Sensation was a reliable index of flash occurrence and intensity as measured physiologically. Our observations are consistent with the hypothesis that hot flashes are due to a change in the thermoregulatory set point. Furthermore, the changes in catecholamine levels are consistent with the cardiovascular changes accompanying hot flashes.
Asunto(s)
Regulación de la Temperatura Corporal , Climaterio , Epinefrina/sangre , Hemodinámica , Hormona Luteinizante/sangre , Norepinefrina/sangre , Femenino , Dedos/irrigación sanguínea , Frecuencia Cardíaca , Humanos , Persona de Mediana Edad , Flujo Sanguíneo Regional , Temperatura Cutánea , SudoraciónRESUMEN
Evidence of impaired cognitive function requires careful evaluation to arrive at correct diagnosis and, possibly, treatment. Steps in this evaluation that might be undertaken in primary care are enumerated and discussed. The role of brief formal tests of cognitive functions in such an evaluation is emphasized.
Asunto(s)
Anciano/psicología , Trastornos del Conocimiento/diagnóstico , Técnicas de Laboratorio Clínico , Humanos , Entrevistas como Asunto , Pruebas NeuropsicológicasAsunto(s)
Regulación de la Temperatura Corporal , Dihidroxifenilalanina/uso terapéutico , Mano/irrigación sanguínea , Enfermedad de Parkinson/fisiopatología , Factores de Edad , Anciano , Temperatura Corporal , Femenino , Humanos , Persona de Mediana Edad , Boca , Enfermedad de Parkinson/tratamiento farmacológico , Factores de Tiempo , Sistema Vasomotor/fisiopatologíaAsunto(s)
Envejecimiento , Encéfalo/metabolismo , Acetilcolinesterasa/metabolismo , Adaptación Fisiológica , Adenosilmetionina Descarboxilasa/metabolismo , Adulto , Anciano , Butirilcolinesterasa/metabolismo , Catecolaminas/metabolismo , Dopa-Decarboxilasa/metabolismo , Glutamato Descarboxilasa/metabolismo , Humanos , Melaninas/metabolismo , Persona de Mediana Edad , Neurotransmisores/metabolismo , Ornitina Descarboxilasa/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Ácido gamma-Aminobutírico/metabolismoAsunto(s)
Ergolinas/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Adulto , Anciano , Ergolinas/administración & dosificación , Ergolinas/efectos adversos , Femenino , Humanos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Masculino , Persona de Mediana Edad , Pergolida , Trastornos Respiratorios/inducido químicamenteRESUMEN
OBJECTIVE: To evaluate the frequency of glucocerebrosidase (GBA) mutations in cases and controls enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. METHODS: We sequenced all exons of the GBA gene in 278 Parkinson disease (PD) cases and 179 controls enrolled in GEPD, with a wide range of age at onset (AAO), and that included a subset of 178 Jewish cases and 85 Jewish controls. Cases and controls were recruited without knowledge of family history of PD, and cases were oversampled in the AAO < 50 years category. RESULTS: 13.7% of PD cases (38/278) carried GBA mutations, compared with 4.5% of controls (8/179) (odds ratio [OR] 3.4, 95% CI 1.5 to 7.4). The frequency of GBA mutations was 22.2% in 90 cases with AAO < or = 50 years, compared with 9.7% in 185 cases with AAO > 50 years (OR 2.7, 95% CI 1.3 to 5.3). Adjusting for age at the time of evaluation, sex, family history of PD, and Jewish ancestry, GBA carriers had a 1.7-year-earlier AAO of PD (95% CI 0.5 to 3.3, p < 0.04) than noncarriers. The average AAO of PD was 2.5 years earlier in carriers with an AAO < or = 50 years compared with noncarriers (95% CI 0.6 to 4.5, p < 0.01) and this was not seen in the AAO > 50 years group. The frequency of GBA mutations was higher in a subset of 178 cases that reported four Jewish grandparents (16.9%) than in cases who did not report Jewish ancestry (8.0%) (p < 0.01). Nine different GBA mutations were identified in PD cases, including 84insGG, E326K, T369M, N370S, D409H, R496H, L444P, RecNciI, and a novel mutation, P175P. CONCLUSIONS: This study suggests that the Glucocerebrosidase gene may be a susceptibility gene for Parkinson disease and that Glucocerebrosidase mutations may modify age at onset.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Glucosilceramidasa/genética , Mutación/genética , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Edad de Inicio , Anciano , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Heterocigoto , Humanos , Patrón de Herencia/genética , Judíos/genética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnologíaRESUMEN
OBJECTIVE: To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). METHODS: We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the < or =50 age at onset (AAO) category. RESULTS: The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (chi(2) = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO < or =50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases. CONCLUSIONS: The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes/genética , Pruebas Genéticas , Genotipo , Haplotipos/genética , Heterocigoto , Humanos , Patrón de Herencia/genética , Judíos/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Penetrancia , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Putrescine is the major source of gamma-aminobutyric acid (GABA) in the rat adrenal gland. Diamine oxidase, and not monoamine oxidase, is essential for GABA formation from putrescine in the adrenal gland. Aminoguanidine, a diamine oxidase inhibitor, decreases the GABA concentration in the adrenal gland by more than 70% after 4 h, and almost to zero in 24 h. Studies using [14C]putrescine confirm that [14C]GABA is the major metabolite of putrescine in the adrenal gland. Inhibition of GABA transaminase by amino-oxyacetic acid does not change the GABA concentration in the adrenal gland, as compared with the brain, where the GABA concentration rises. With aminoguanidine, the turnover time of GABA originating from putrescine in the adrenal gland is 5.6 h, reflecting a slower rate of GABA metabolism compared with the brain. Since GABA in the adrenal gland is almost exclusively derived from putrescine, the role of GABA may relate to the role of putrescine as a growth factor and regulator of cell metabolism.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Putrescina/farmacología , Ácido gamma-Aminobutírico/metabolismo , Glándulas Suprarrenales/efectos de los fármacos , Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Femenino , Glutamato Descarboxilasa/metabolismo , Guanidinas/farmacología , Masculino , Pargilina/farmacología , Poliaminas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Organotypic cultures of chick-embryo sympathetic ganglion chains maintained in vitro for 3-4 weeks rapidly synthesized catecholamines, as demonstrated by the conversion of L-[U-14C]tyrosine to catechol derivatives and by histofluorescence assay. The biosynthesis of catechols from radioactive L-tyrosine leveled off at 6 hr of incubation and dropped slightly at 10 hr. The addition of DL-alpha-methyl-p-tyrosine to the culture medium did not affect protein synthesis, but produced a complete block in the synthesis of catecholamines from L-tyrosine, with consequent loss of fluorescence in the bodies and proximal processes of adrenergic neurons in 2 hr, and essentially complete loss in 6 hr. Our observations suggest that a major portion of the catecholamines were synthesized in the perikarya and transported via neuronal processes to their terminals. The addition of monoamine oxidase inhibitors to the incubation medium produced a moderate to pronounced increase in fluorescence; reserpine caused a rapid and profound loss of catecholamines. When added to the culture medium, crude biopterin produced an increase in the synthesis of catechol derivatives from radioactive L-tyrosine and a marked increase in fluorescence, beginning in the neuronal perikarya. This effect was completely blocked by DL-alpha-methyl-p-tyrosine. The mechanism of biopterin's action in the synthesis of catecholamines in cultures of sympathetic ganglia is not completely elucidated from these studies, but may be related to the role it plays as cofactor for tyrosine hydrocylase.