RESUMO
The management of Parkinson's disease (PD) tends to focus on the presenting motor syndrome; yet, in the long term, nonmotor complications of the illness and complications of treatment become increasingly troublesome. The aims of this study were to review the reasons for 761 hospital admissions for patients with a diagnosis of PD and to determine the cause of hospitalization. Only 15% were admitted for primary management of the motor syndrome. PD was the secondary diagnosis in 645 admissions. Of the latter, 39% were admitted because of falls leading to fracture, pneumonia, encephalopathy or dementia and hypotension with syncope. Cardiac and gastrointestinal diseases accounted for a further 22% of admissions. Complications of the later stages of PD and associated treatments are more likely to lead to hospital admission than management of the primary motor syndrome. Some of the emergency hospital admissions for PD may be potentially avoidable with better planning of management in the outpatient and community setting.
Assuntos
Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Admissão do Paciente/tendências , Acidentes por Quedas , Antiparkinsonianos/uso terapêutico , Hospitalização/tendências , Hospitais Universitários/normas , Hospitais Universitários/tendências , Humanos , Tempo de Internação/tendências , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Admissão do Paciente/normas , Pneumonia/epidemiologia , Pneumonia/etiologia , Austrália do Sul/epidemiologiaRESUMO
In the substantia nigra acetylcholinesterase may have a novel role unrelated to acetylcholine but linked instead to dopamine. Using a sensitive chemiluminescent system, we have investigated the effects of dopamine depletion on the vivo release of acetylcholinesterase in both the substantia nigra and the caudate putamen. Dopamine levels in the caudate putamen were significantly depleted compared to the non-lesioned side, using either of two different toxins for dopaminergic nigrostriatal cells: 6-hydroxydopamine ( 1 or 3 weeks prior to study) or N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (1 week prior to study). Spontaneous release of acetylcholinesterase from the substantia nigra was significantly reduced following all three pretreatments; however, in the caudate putamen a significant reduction in the spontaneous release of acetylcholinesterase, compared to controls, was only seen in animals studied 1 week after the administration of 6-hydroxydopamine. In all control groups, application of potassium ions (60 mM) evoked a significant release of acetylcholinesterase in the substantia nigra (p < 0.05) and this effect persisted in the surviving neurones following a partial lesion by neurotoxin pre-treatment. The results from this study are discussed in the light of a regulatory mechanism for acetylcholinesterase release from the striatum, which may come into operation depending on the extent of destruction of dopaminergic nigrostriatal neurones.
Assuntos
Acetilcolinesterase/metabolismo , Núcleo Caudado/metabolismo , Dopamina/metabolismo , Putamen/metabolismo , Substância Negra/metabolismo , Animais , Cobaias , Masculino , Oxidopamina/farmacologiaRESUMO
BACKGROUND: The treatment of Tourette's disorder with classical neuroleptics is limited by their side effects. Risperidone is a new efficacious antipsychotic with a low propensity for extrapyramidal side effects. To establish risperidone's therapeutic potential in Tourette's disorder, we studied the safety and efficacy of risperidone in comparison with pimozide in patients with Tourette's disorder diagnosed according to DSM-III-R. METHOD: In a 12-week, multicenter, double-blind, parallel-group study, 26 patients were treated with risperidone (mean daily dose = 3.8 mg), and 24 patients were treated with pimozide (mean daily dose = 2.9 mg). RESULTS: There was significant improvement of tics with respect to the Tourette's Symptom Severity Scale (TSSS) for both groups. Forty-one patients completed the study. At endpoint, 54% (14/26) of the risperidone patients and 38% (9/24) of the pimozide patients had only very mild or no symptoms on the global severity rating of the TSSS. Both treatment groups had improved significantly at endpoint in regard to Global Assessment of Functioning and Clinical Global Impressions scale outcomes. Symptoms of anxiety and depressive mood improved significantly from baseline in both groups. Obsessive-compulsive behavior improvement reached significance only in the risperidone group. Although the severity of extrapyramidal side effects was low in both groups, fewer patients in the risperidone group reported extrapyramidal side effects (N = 4) compared with the pimozide group (N = 8). Depression, fatigue, and somnolence were reported as the most prominent side effects in both treatment groups. CONCLUSION: Both drugs were efficacious and well tolerated in patients with Tourette's disorder. Risperidone may become the first-line drug in the treatment of Tourette's disorder owing to a more favorable efficacy and tolerability profile.
Assuntos
Antipsicóticos/uso terapêutico , Pimozida/uso terapêutico , Risperidona/uso terapêutico , Síndrome de Tourette/tratamento farmacológico , Adolescente , Adulto , Idade de Início , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Comorbidade , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/epidemiologia , Resultado do TratamentoRESUMO
Administration of L-DOPA plus carbidopa, or the D-2 agonist (+)-PHNO, to MPTP-treated common marmosets caused motor hyperactivity and a reversal of the parkinsonian syndrome. In contrast, administration of the putative D-1 agonist SKF 38393 was without effect on movement or motor disability. The subsequent administration of another putative selective D-1 partial agonist CY 208-243 produced a dose-related improvement in motor activity and reversal of parkinsonian motor deficits in MPTP-treated animals. The effect of CY 208-243 was inhibited by pretreatment with the D-1 antagonist SCH 23390 and, to a lesser extent, by the D-2 antagonist sulpiride. In another group of normal drug naive marmosets, the administration of CY 208-243 produced only a small increase in motor activity. Following treatment with MPTP and without other drug administration, administration of CY 208-243 produced a marked reversal of motor deficits and locomotor hyperactivity. Thus, CY 208-243, suggested to be a partial D-1 agonist exhibits antiparkinsonian activity in MPTP-treated marmosets which does not require prior or concurrent exposure to D-2 agonists.
Assuntos
Antagonistas de Dopamina , Indóis/farmacologia , Doença de Parkinson Secundária/induzido quimicamente , Fenantridinas/farmacologia , Piridinas/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Benzazepinas/farmacologia , Callitrichinae , Relação Dose-Resposta a Droga , Atividade Motora/efeitos dos fármacos , Doença de Parkinson Secundária/prevenção & controle , Receptores Dopaminérgicos/fisiologia , Receptores de Dopamina D1 , Sulpirida/farmacologiaRESUMO
We describe a simple quantitative bedside method for assessing the dopaminergic properties of new therapeutic agents, namely, by documenting their duration of action in patients with Parkinson's disease who exhibit "on-off" fluctuations. This model represents a form of human dopaminergic "bioassay".
Assuntos
Antiparkinsonianos/farmacologia , Dopaminérgicos/farmacologia , Oxazinas/farmacologia , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Avaliação de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
CQA 206-291, a new D2 dopamine receptor agonist with a biphasic dopaminergic profile, was given to six patients with idiopathic Parkinson's disease after overnight drug withdrawal. With incremental single oral doses of CQA, a dose-related, clinically significant, and prolonged antiparkinsonian effect was observed. Most subjects experienced drowsiness after the drug while a minority of subjects experienced nausea and/or vomiting or postural hypotension. Further study of this drug in humans is indicated.
Assuntos
Dopaminérgicos/uso terapêutico , Ergolinas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Dopaminérgicos/farmacologia , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Ergolinas/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Receptores Dopaminérgicos/fisiologiaAssuntos
Corpo Estriado/fisiopatologia , Dopamina/fisiologia , Neurônios/transplante , Doença de Parkinson Secundária/terapia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Callitrichinae/embriologia , Feminino , Masculino , Neurônios/fisiologia , Doença de Parkinson Secundária/induzido quimicamente , PiridinasRESUMO
A standardised method of assessment of vibration threshold (VT), with a C128-Hz tuning fork (TF), was compared to VT measured with a biothesiometer in normal patients free of neurological disease at four separate bony points. The biothesiometer is more accurate compared to a timed tuning fork. The accuracy of both declined with patient age, however, especially for patients older than 50years. The longer the nerve tested, the greater the age-related decline. The C128-Hz tuning fork, provided consistently applied, may be meaningfully employed at the thumb or hallux proximal nail fold to assess VT-TF at the bedside, but remains less able to discriminate VT at all ages.
Assuntos
Doenças do Sistema Nervoso/fisiopatologia , Exame Neurológico/métodos , Limiar Sensorial/fisiologia , Vibração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Mãos/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Exame Neurológico/instrumentação , Psicofísica/instrumentação , Fatores de Tempo , Adulto JovemRESUMO
The cause of dopamine cell death, thought to be the primary neurocytologic defect in idiopathic Parkinson's disease, remains unknown. Mitochondrial oxidative dysfunction causes premature cell death, and may be linked to accelerated apoptosis, excessive free and toxic radicals, deficient neurotrophic factors or combinations of these detrimental factors. Neurochemical imbalances result both in the substantia nigra and neostriatum, resulting in compensatory mechanisms that make this chronic neurodegenerative disease difficult to evaluate. Acute parkinsonism models have limitations when compared with chronic disease states, and caution should be present when comparing 'parkinsonism' data with human disease. Better understanding of classical neurotransmitters, neuroactive peptides and neurotrophic factors, will hopefully lead to more rational treatment approaches, cellular support strategies, and an understanding of the causes of this disease. Glial derived neurotrophic factor looks the most promising neurotrophic candidate so far tested in culture and in vivo. The result of clinical trials utilizing neurotrophic factors, both as mesencephalic implant support strategies and as definitive treatment of idiopathic Parkinson's disease, are awaited with cautious optimism.
Assuntos
Doença de Parkinson/fisiopatologia , Animais , Morte Celular/fisiologia , Corpo Estriado/fisiopatologia , Modelos Animais de Doenças , Dopamina/fisiologia , Humanos , Exame Neurológico , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , Prognóstico , Substância Negra/fisiopatologiaRESUMO
Neuro-acanthocytosis is a rare neurological disorder characterised by stereotyped chorea, especially of the mouth, areflexia and acanthocytes seen in the peripheral blood. No cases have been described in the literature from South Africa. We report here a case of neuro-acanthocytosis seen in a black woman who presented to Johannesburg Hospital.
Assuntos
Acantócitos/patologia , Coreia/etiologia , Doenças Neuromusculares/complicações , Adulto , População Negra , Coreia/patologia , Feminino , Humanos , Doenças Neuromusculares/patologia , África do SulRESUMO
Two cases of pure word deafness, both with bilateral temporal lobe lesions due to cerebrovascular disease, are presented. This rare disorder is briefly discussed.
Assuntos
Perda Auditiva Central , Percepção da Fala , Adulto , Idoso , Infarto Cerebral/complicações , Feminino , Perda Auditiva Central/etiologia , Perda Auditiva Central/patologia , Humanos , Masculino , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time. Sinemet CR4 offers a theoretically attractive method of achieving gradual sustained release of levodopa over time which may be more physiological to striatal dopamine receptors in the early stages of the disease. This study evaluated 20 patients with moderate to severe Parkinson's disease who were treated with Sinemet CR4 over a 1-year period. Eleven patients completed the full year on therapy, and nine subjects withdrew. Of the withdrawals, two subjects died from non-Parkinson's disease-related illness, three showed no therapeutic benefit, and four responded well for a minimal 6-month period, but then lost therapeutic benefit and developed more severe dystonias. A higher overall levodopa dosage was required by all patients, and side-effects of levodopa were still present in most patients. However, the nocturnal benefit of this long-acting preparation was observed by all the patients in the study. Slow onset of action of Sinemet CR4 resulted in early-morning immobility. Sinemet CR4 cannot replace standard Sinemet, but appears to be a useful form of adjunct therapy in selected patients.
Assuntos
Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/efeitos adversos , Carbidopa/efeitos adversos , Preparações de Ação Retardada , Combinação de Medicamentos , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
The results of magnetic resonance imaging (MRI) in supporting the diagnosis of multiple sclerosis in 24 South African-born white patients were studied. MRI confirmed the diagnosis in 87.5% of cases. It appears that MRI is useful in strengthening the diagnosis of multiple sclerosis in patients with clinically established disease. This study supports the validity of the clinical diagnosis of multiple sclerosis in South African patients and stresses the need for re-evaluation of the incidence and prevalence of multiple sclerosis in this country.
Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , África do SulRESUMO
The association of free radicals and particularly free iron in the pathogenesis of idiopathic Parkinson's disease and MPTP-induced parkinsonism remains controversial. Whereas the actual cause of dopamine cell death in the substantia nigra compacta (SNc) remains unknown, disturbances in lipid peroxidation and subsequent mitochondrial and cell membrane disruption has been demonstrated. In a genetically susceptible host, abnormal elimination of oxygen and trace metal free radicals may further damage dopamine cells. Using a unilaterally MPTP-treated African Green monkey, which showed obvious contralateral hemiparkinsonism, the total free iron concentration was measured. Iron, Fe2+ and Fe3+, but not other trace elements, was significantly elevated in the SNc compared with the opposite unlesioned side, which was similar to separate control animals. Iron content in the SNc, periaqueductal gray area, and crus cerebri was 228-270 ppm. Normal control SNc was 285 (+/- 59) ppm, whereas iron levels of 532 (+/- 151) ppm were found in the MPTP-lesioned SNc. These animals were drug naive and not on long-term levodopa maintenance. Proton microprobe elemental analysis was matched against adjacent immunocytochemically stained tissue slices to ensure the cells studied were in the SNc. Iron was found not only in the degenerating dopamine cells themselves but also in the surrounding matrix and glial cells. Whether free iron that is not bound to neuromelanin is responsible for dopamine cell death as suggested by these experiments remains to be proved.
Assuntos
Ferro/metabolismo , Doença de Parkinson Secundária/metabolismo , Substância Negra/metabolismo , Animais , Chlorocebus aethiops , Dopamina/metabolismo , Microanálise por Sonda Eletrônica , Ferro/análise , Intoxicação por MPTP , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doença de Parkinson Secundária/induzido quimicamente , Valores de Referência , Substância Negra/efeitos dos fármacosRESUMO
Huntington's disease is an autosomal-dominant inherited progressive neurodegenerative disease associated with an expanded trinucleotide repeat (CAG) sequence on the short arm of chromosome 4. The disease is considered rare in Africans. We report five black South African families of different ethnic origin with proven expansions typical of Huntington's disease and discuss the possible origins of the disease in Africa.
Assuntos
População Negra/genética , Testes Genéticos , Doença de Huntington/genética , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Feminino , Genes Dominantes/genética , Humanos , Doença de Huntington/diagnóstico , Masculino , Linhagem , Fenótipo , África do Sul , Repetições de Trinucleotídeos/genética , População Branca/genéticaRESUMO
Botulinum A chemodenervation of the Adductor Pollicis muscle for the treatment of the thumb-in-palm deformity in cerebral palsied hands is presented as a new therapeutic option. Early results of a clinical trial in five hemiparetic Cerebral Palsied (C.P.) children are assessed using a prospective nontrialist-biased study design based on an independent panel assessment of pre- and post-intervention photographic and videotaped records of hand function and appearance, in combination with grip dynamometry and goniometry. All cases are shown to improve in terms of both function and appearance with results approaching statistical significance (p = 0.06) when assessed by the Wilcoxon's matched-pairs signed rank test, despite the small study group. The modality is shown to be simple, safe and effective over the period reported (229 days). The benefit is sustained beyond the period of muscle paresis and ongoing long term follow-up will document the need for, and timing of, reinjection.
Assuntos
Toxinas Botulínicas , Paralisia Cerebral/complicações , Deformidades Adquiridas da Mão/terapia , Denervação Muscular/métodos , Paralisia Cerebral/fisiopatologia , Criança , Ensaios Clínicos como Assunto , Mãos/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Contenções , Fatores de Tempo , Gravação de VideoteipeRESUMO
Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient.
Assuntos
Bromocriptina/administração & dosagem , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Bromocriptina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The effect of stimulation of cerebral dopamine D-1 receptors by CY 208-243 on motor disability was tested in MPTP-treated parkinsonian marmosets and patients with Parkinson's disease. CY 208-243 (0.5-1.25 mg/kg s.c.) produced a dose-related reversal of akinesia and rigidity in the marmosets, lasting some 2 h. Single morning doses of CY 208-243 (5-40 mg) were compared with the usual morning dose of levodopa in eight patients with Parkinson's disease on long-term levodopa therapy who had developed motor fluctuations from immobility with akinesia and rigidity (off) to mobility often with dyskinesias (on). CY 208-243 alone was capable of switching such patients from off to on; five of the eight patients responded to the highest dose (40 mg), sometimes with dyskinesias. The response to CY 208-243 was comparable to that produced by levodopa in these cases. Drugs designed to stimulate both dopamine D1 and D2 receptors in the brain may improve the therapy of Parkinson's disease.
Assuntos
Analgésicos/uso terapêutico , Indóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fenantridinas/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Idoso , Animais , Callitrichinae , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/induzido quimicamente , PiridinasRESUMO
CONTEXT: Huntington's disease (HD) is a dominantly inherited condition in which the gene defect is known. As such individuals in at-risk families can be tested before symptoms occur, prenatally, or after symptoms appear to confirm the diagnosis. OBJECTIVES: To investigate the utilisation and sequelae of the predictive, prenatal and diagnostic services offered to families with suspected Huntington's disease. DESIGN: A retrospective design was used. The 1975-1997 records of the Department of Human Genetics for all families with a history of HD presenting for genetic counselling and DNA analysis were studied. SETTING: Department of Human Genetics, South African Institute for Medical Research and University of the Witwatersrand, Johannesburg. SUBJECTS: There were 30 at-risk (50% risk) subjects for predictive testing, 7 women (10 pregnancies) for prenatal testing, and 52 subjects for diagnostic testing. OUTCOME MEASURES: These were provided by the results from molecular studies and by the action taken by subjects after a predictive or prenatal result was given. RESULTS: Altogether 15 (50%) subjects for predictive testing had a positive result, but none had serious psychiatric sequelae. Two women were found to be carrying an affected fetus and both requested pregnancy termination. Of 52 diagnostic tests, 33 (63%) were positive. CONCLUSION: The service was used appropriately, and there were no traumatic incidents following positive results. There was no genotypic or sex bias in subjects presenting for testing. Black and white patients were equally likely to be positive for HD on diagnostic testing. The families appreciated the service and found it useful in the detection and prevention of HD.