RESUMO
BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Cloridrato de Fingolimode/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Resultado do TratamentoRESUMO
The prescription of methylprednisolone for multiple sclerosis acute relapse involves sterilization of urine. An observational study was conducted to clarify the benefit of antibiotic prophylaxis in case of asymptomatic bacteriuria found before methylprednisolone. Ninety-seven patients were included; 32 patients had asymptomatic bacteriuria. Seventeen patients were treated and 15 were not. The number of urinary tract infections in the month following the methylprednisolone was the same in the two groups. The results seem in favor of a therapeutic abstention. A larger study will be performed to confirm these results and determine appropriate recommendations.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/estatística & dados numéricos , Bacteriúria/tratamento farmacológico , Imunossupressores/uso terapêutico , Hemissuccinato de Metilprednisolona/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Procedimentos Desnecessários/estatística & dados numéricos , Infecções Urinárias/prevenção & controle , Adulto , Doenças Assintomáticas , Bacteriúria/complicações , Bacteriúria/microbiologia , Progressão da Doença , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Infusões Intravenosas , Masculino , Hemissuccinato de Metilprednisolona/administração & dosagem , Hemissuccinato de Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Resultado do Tratamento , Infecções Urinárias/epidemiologiaRESUMO
The medicinal treatment of spasticity includes use of oral treatments (baclofène and tizanidine), botulinum toxin, intrathecal baclofène and local application of alcohol or phenol. However, spasticity may not be uncomfortable and may even be useful. Therefore, all spastic diseases do not systematically require treatment. First-line treatments (oral treatments and botulinum toxin) can be considered depending on the local or diffuse nature of the spasticity and depending on the etiology.
Assuntos
Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Algoritmos , Aminas/administração & dosagem , Aminas/uso terapêutico , Baclofeno/administração & dosagem , Baclofeno/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Clonidina/administração & dosagem , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Ácidos Cicloexanocarboxílicos/administração & dosagem , Ácidos Cicloexanocarboxílicos/uso terapêutico , Dantroleno/administração & dosagem , Dantroleno/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Gabapentina , Humanos , Bombas de Infusão Implantáveis , Injeções Espinhais , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/reabilitação , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/reabilitação , Bloqueio Nervoso , Fármacos Neuromusculares/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Espasmo/tratamento farmacológico , Espasmo/etiologia , Espasmo/fisiopatologia , Vigabatrina/administração & dosagem , Vigabatrina/uso terapêutico , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
BACKGROUND: There have been few epidemiologic studies on neuromyelitis optica (NMO) and none used the recent 2006 diagnostic criteria. Here we describe the clinical, laboratory, MRI, and disability course of NMO in a French cohort of 125 patients. METHODS: We performed an observational, retrospective, multicenter study. Data were collected from September 2007 through August 2008, corresponding to the endpoint of the study. We identified 125 patients fulfilling the 2006 NMO criteria. Selection was made using hospital files and a specific clinical questionnaire for NMO. RESULTS: Mean age at onset was 34.5 years (range 4-66) with a mean disease duration of 10 +/- 7.8 years at the endpoint. The patients were mainly (87%) Caucasian, with a female:male ratio of 3:1. In 90% of cases, the association of optic neuritis, longitudinal extensive myelitis, and a Paty-negative initial brain MRI was sufficient to fulfill the supportive criteria. Eighty-eight percent of patients were treated with immunosuppressive therapies. Median delay from onset to Expanded Disability Status Scale (EDSS) score 4 was 7 years; score 6, 10 years; and score 7, 21 years. The first episode of myelitis was immediately followed by an EDSS score > or = 4 in 37.3% of cases, and a severe residual visual loss was observed in 22% of patients after the first episode of optic neuritis. Multivariate analysis did not reveal any predictors of a poor evolution other than a high number of MRI brain lesions at diagnosis, which were predictive of a residual visual acuity < or = 1/10. CONCLUSIONS: Our demographic data provide new data on disability in patients with neuromyelitis optica, most of whom were receiving treatment.
Assuntos
Neuromielite Óptica/epidemiologia , Adolescente , Adulto , Idoso , Encéfalo/patologia , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/patologia , Neuromielite Óptica/terapia , Prognóstico , Estudos Retrospectivos , Medula Espinal/patologia , Adulto JovemRESUMO
Multiple sclerosis is responsible for a functional handicap essentially associated with the onset and the deterioration of a motor deficit, which is nearly constant after a certain number of years of progression and has an effect upon the patient's walking capacity. In this article, we study this motor deficit in the first phase of the disease, its progression, and its role as a prognostic factor.
Assuntos
Destreza Motora/fisiologia , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Desempenho Psicomotor/fisiologia , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/fisiopatologia , PrognósticoRESUMO
Immunomodulatory treatments for relapsing-remitting multiple sclerosis (RRMS) are not efficacious or tolerated in all patients. It is important to evaluate alternative classes of treatment in patients failing first-line therapy. The objective of this prospective observational study was to evaluate the efficacy and safety of glatiramer acetate in patients, to whom beta-interferons could not be administered. The study included patients with RRMS who were intolerant to or had contraindications to beta-interferon. After initiation of glatiramer acetate treatment, follow-up visits were made every 3 months, when data on neurologist-ascertained relapses and disability [Expanded Disability Status Scale (EDSS) score] were collected. Tolerability was evaluated by spontaneous adverse event reporting. Overall, 205 patients were studied and 113 (55.1%) treated for at least 4 years. The proportion of patients presenting over three relapses per year decreased from 51.2% to 8.4% in the 2 years following treatment initiation. Over 5 years of treatment, mean annualized relapse rates and mean EDSS scores remained stable (0.4-0.6 relapses/year and 3.6 +/- 1.8-3.3 +/- 2.1 respectively). Adverse events were reported by 179 patients, leading to discontinuation of treatment in 10 patients. Patients with RRMS to whom beta-interferons cannot be prescribed can benefit from treatment with glatiramer acetate.
Assuntos
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Acetato de Glatiramer , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Esclerose Múltipla Recidivante-Remitente/patologiaRESUMO
We report the first case of a 33-year-old woman with multiple sclerosis, who developed a livedo-like dermatitis after injection of Copolymere-1. This disease is characterized by the development of acute violent pain during or immediately after injection, and a livedo-like plaque followed by necrosis corresponding to an arterial ischemia by vasospasm or thrombosis. Early treatment with vasoactive and anticoagulation agents is required. Surgery may be necessary.
Assuntos
Toxidermias/etiologia , Imunossupressores/efeitos adversos , Peptídeos/efeitos adversos , Doença Aguda , Adulto , Anticoagulantes/uso terapêutico , Braço/irrigação sanguínea , Artéria Braquial/patologia , Toxidermias/tratamento farmacológico , Feminino , Acetato de Glatiramer , Humanos , Imunossupressores/administração & dosagem , Injeções Intra-Arteriais , Isquemia/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Necrose , Dor/induzido quimicamente , Peptídeos/administração & dosagem , SíndromeRESUMO
BACKGROUND: In multiple sclerosis (MS), case control studies have shown that anticardiolipin antibodies (aCL Ab) are more frequent than in the general population and that aCL Ab positivity may be associated with specific clinical characteristics. OBJECTIVES: To determine whether patients with MS who are positive for aCL Ab have specific characteristics. METHODS: 285 consecutive patients with MS were tested for aCL Ab positivity. Patients also underwent complete autoimmune screening and were systematically evaluated for clinical characteristics and individual or family history of autoimmune disease. RESULTS: aCL Ab positivity was found in 42 patients (15%). The main isotype was aCL IgM (32 patients, 11%). Demographics and clinical characteristics including sex, age at onset, course of the disease, expanded disability status scale score, and progression index were not different between aCL Ab positive and aCL Ab negative patients. Clinical systems involved at onset or during the course of the disease were not different from what is usually observed in MS. aCL Ab positivity was not associated with an increased frequency of autoimmune disease and was not predictive of a family history of autoimmune disease. Patients positive for aCL IgM were more frequently positive for the presence of non-organ specific antibodies (53% v 39%, respectively, p = 0.02). CONCLUSIONS: These results do not support the hypothesis that patients with MS with aCL Ab constitute a subgroup of MS according to demographic clinical and familial characteristics. The greater frequency of other antibodies in aCL Ab positive patients suggests that they only reflect a more general autoimmune activation in MS.
Assuntos
Anticorpos Anticardiolipina/sangue , Esclerose Múltipla/classificação , Esclerose Múltipla/imunologia , Adulto , Idade de Início , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Biomarcadores/análise , Demografia , Progressão da Doença , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Anamnese , Pessoa de Meia-Idade , Esclerose Múltipla/patologiaRESUMO
The presence of anticardiolipin antibodies (aCL) is a recognized risk factor for ischaemic stroke and a predictor of recurrent ischaemic events in young patients, but the significance of positive aCL tests is uncertain in the elderly. We evaluated the frequency of aCL and the risk of recurrence of stroke and other vascular events in a series of 242 consecutive patients aged over 60 years, admitted for brain infarction. All underwent aCL immunoreactivity (ELISA; measured by IgG antiphospholipid, GPL, units) and transoesophageal echocardiography and were later examined or contacted by telephone (mean 2.33 +/- 1.25 years, max. 4). Fifty patients (21 %) had at least l0 GPL units aCL. There were no differences between these and the other patients in the results of transoesophageal echocardiography, including mitral or aortic valvular thickening, atrial thrombus, atrial spontaneous contrast, strands, and aortic plaques thickness. None had IgG higher than 80 GPL units or was positive for anti-beta2 glycoprotein I. Patients with at least 10 GPL units more often had a past history of cerebral infarction than patients lower aCL level. However, the incidence of recurrent stroke was 4.5 per 100 person-year in patients with more than 10 GPL units, and 2.7 per 100 person-year in those with more than 10 GPL units. Kaplan-Meier analysis for any vascular events showed no differences between the two groups. In contrast to young patients, elderly patients with 10 or more GPL units aCL and negative for anti-beta2 glycoprotein I do not seem to have a higher risk of vascular events.
Assuntos
Anticorpos Anticardiolipina/análise , Isquemia Encefálica/patologia , Acidente Vascular Cerebral/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Isquemia Encefálica/imunologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/imunologiaRESUMO
There is mounting evidence to implicate complex atherosclerotic aortic plaques as a significant independent risk factor for embolic stroke. Ulcerated plaques at autopsy, plaques thicker than 4 to 5mm at transesophageal echocardiography and those with mobile components are more likely to be associated with stroke. Mobile thrombus in the lumen may be a source of cerebral emboli. Among patients with ischemic stroke, those with plaques thicker than 4mm in the aortic arch have the highest risk of recurrent stroke, myocardial infarction, other vascular event including vascular death. However, since no randomized trials have been conducted to evaluate the role of any antithrombotic therapies in patients with aortic atheroma, no recommendation can be made regarding the best treatment strategies. Antiplatelet agents, oral anticoagulant, thrombolytic therapy, and elective surgical endarterectomy or graft replacement are all reasonable options that have been proposed and that must be evaluated in term of benefit/risks ratio in specific randomized controlled trials. Meanwhile, antiplatelet agents and aggressive risk factor management appear to be the first line treatment. No recommendation can be made to use oral anticoagulation in these patients nor for a target INR. Concerns also exist on the possibility of anticoagulation driven cholesterol embolism in these patients.
Assuntos
Doenças da Aorta/complicações , Arteriosclerose/complicações , Infarto Cerebral/etiologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Doenças da Aorta/terapia , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/patologia , Arteriosclerose/terapia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Ecocardiografia Transesofagiana , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: A population-based study is reported of MS in French Afro-Caribbeans (FAC) in Martinique. FAC are descendants of interracial mating that occurred between French Caucasians and black Africans in the 17th and the 18th centuries. METHODS: The authors surveyed the entire island of Martinique (area 1,128 km(2), population 357,000) between November 1997 and October 1999. RESULTS: Sixty-two patients (46 females, 16 males, ratio 2.9:1) were identified with definite or probable disease by the Poser criteria. Prevalence for all patients on December 31, 1998, was 17.4/10(5) (95% CI 13.1 to 21.7) and 14.3/10(5) (95% CI 10.4 to 18.2) for clinically definite cases (n = 51). Age range of patients on prevalence day was 17 to 73 years (mean +/- SD 39 +/- 11.3 years). Mean age at onset was 31.2 +/- 11 years. Overall, 9.7% had primary progressive disease and 19.4% had benign MS. A low proportion of definite and probable MS cases had oligoclonal bands in CSF (50.9%). Seventeen patients, 13 of whom were alive on prevalence day, had a relapsing form of neuromyelitis optica. CONCLUSION: The island of Martinique appears to have a low to medium prevalence of MS. MS was almost unknown in FAC in Martinique until the late 1970s. The apparent recent increase may be explained by improved recognition of patients, increased availability of MRI for diagnosis, increased disease awareness among physicians, increased survival of MS patients, or an actual increase in disease frequency.
Assuntos
Genes MHC da Classe II/genética , Esclerose Múltipla/epidemiologia , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/genética , Adolescente , Adulto , África/etnologia , Fatores Etários , Idade de Início , Idoso , Alelos , Feminino , Haplótipos , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Fatores SexuaisRESUMO
The empiric recurrence risk of multiple sclerosis (MS) of relatives of French MS patients is not known. Using a standardized interview, we collected the family histones of 357 consecutive patients followed at our MS clinic; adequate information was obtained on 4784 relatives up to the third degree. Thirty-five patients (9.8%) had a relative with MS. The risk-curve for relatives was the same as in other studies conducted with a similar methodology in Canada. England and Flanders. but the crude overall MS recurrence risk for relatives was lower in France. The genetic burden of MS may be lower in France than in areas of higher MS prevalence.
Assuntos
Esclerose Múltipla/genética , Adulto , Saúde da Família , Feminino , França/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Prevalência , RiscoRESUMO
OBJECTIVES: To determine whether there is an excess of respiratory tract infections in the 5-week, 3-month, and 12-month periods before MS symptom onset and if there is an association between MS and a history of infectious mononucleosis (IM). BACKGROUND: The etiology of MS remains unknown, but infection is frequently suggested as a putative etiologic agent. Epidemiologic studies have produced inconsistent evidence for an etiologic role of respiratory tract infections (RTI) and IM in MS. METHODS: The authors performed a case-control study using the General Practice Research Database from the United Kingdom. There were 225 subjects with definite or probable MS, and 900 controls matched for age, sex, and physician practice. Using computerized patient records, the authors compared the mean rates of RTI per patient in the 5-week, 3-month, and 12-month periods before the date of onset of the first symptoms compatible with MS (index date). They also compared histories of IM. RESULTS: In all periods, an increased frequency of RTI was associated with a significantly increased risk of MS. A history of IM was associated with greater than five times the risk of MS (OR = 5.5 [95% CI 1.5 to 19.7]). CONCLUSIONS: These results support an association between a history of IM and subsequent MS. Respiratory tract infections may precipitate disease onset.
Assuntos
Esclerose Múltipla/epidemiologia , Infecções Respiratórias/epidemiologia , Adulto , Distribuição por Idade , Idade de Início , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Mononucleose Infecciosa/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Distribuição por Sexo , Reino Unido/epidemiologiaRESUMO
Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by pro- gressive spasticity of the lower limbs. Five AD-HSP loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21-p22 has been shown to account for approximately 40% of all AD-HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD-HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%). The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and permitted the redefinition of this frequent form of AD-HSP.
Assuntos
Adenosina Trifosfatases/genética , Genes Dominantes , Mutação , Paraplegia/genética , Adenosina Trifosfatases/fisiologia , Adolescente , Adulto , Idoso , Criança , Códon sem Sentido , Genótipo , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Fenótipo , Polimorfismo Genético , Splicing de RNA , EspastinaRESUMO
Multiple sclerosis (MS) is associated with autoimmune disorders (AIDs) in individual patients, and limited data suggest a possible familial association of MS and AIDs; however, no systematic study has been conducted on the occurrence of AIDs in the families of MS patients. Using a standardized interview focused on AIDs, we obtained the family histories of 357 consecutive patients from our MS clinic. Adequate information was obtained on 1971 first-degree relatives. Fifty-five patients (15.4%) had first-degree relatives with MS (n=22, 6.2%) another AID (n = 30, 8.4%), or both (n = 3, 0.8%). In 16 families (4.5%), at least 3 first-degree relatives had MS or another AID. MS, Grave's disease, rheumatoid arthritis, vitiligo, type 1 insulin-dependent diabetes mellitus, and uveitis, were the most common AIDs in these families. Such multiplex families (families with MS plus AID) are appropriate for identifying susceptibility genes that may be common to MS and other AIDs.
Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Adulto , Doenças Autoimunes/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Fatores de RiscoRESUMO
Although the general course of multiple sclerosis is well known from natural history studies, the determination of a detailed prognosis in a given individual is almost an insurmountable task. Cerebral magnetic resonance imaging is the best predictor of conversion to definite multiple sclerosis after a first demyelinating event. The main factors indicative of long-term bad prognosis are: onset after the age of 40, initial pyramidal or cerebellar signs, high relapse rate during the first two years, and onset of the progressive phase. Altogether, up to 20% of patients have a benign course.
Assuntos
Esclerose Múltipla/diagnóstico , Idade de Início , Córtex Cerebral/patologia , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
Five patients with oropharyngeal cancer treated with 5-fluorouracil and cisplatin had ischemic stroke within 2 to 5 days after the drug infusion. This occurred during the second course of chemotherapy in three patients, and during the third course in two patients. There may be a relation between treatment and brain infarction because 1) there was no other cause identified despite extensive tests, including postmortem examination in one patient; 2) there was a short delay between treatment infusion and stroke; and 3) there was a similar pattern of ischemic stroke after the second or third course of chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Infarto Cerebral/induzido quimicamente , Cisplatino/efeitos adversos , Fluoruracila/efeitos adversos , Idoso , Cisplatino/administração & dosagem , Evolução Fatal , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/tratamento farmacológicoRESUMO
Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Endometrioide/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Doenças do Sistema Nervoso/diagnóstico , Exame Neurológico/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológicoRESUMO
Autosomal dominant familial spastic paraplegia (AD-FSP) is a degenerative disorder of the central motor system characterised by progressive spasticity of the lower limbs. AD-FSP has been divided into pure and complicated forms. Pure AD-FSP is genetically heterogeneous; three loci have been mapped to chromosomes 14q (SPG3), 2p (SPG4), and 15q (SPG6), whereas no loci responsible for complicated forms have been identified to date. Here we report linkage to the SPG4 locus in a three generation family with AD-FSP complicated by dementia and epilepsy. Assuming that both forms of AD-FSP are caused by mutations involving the same FSP gene, analysis of recombination events in this family positions the SPG4 gene within a 0 cM interval flanked by loci D2S2255 and D2S2347.