Estudio observacional sobre seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer leve a moderadamente grave / Observational study on safety, tolerability and effectiveness of galantamine in patients with mild to moderately severe Alzheimer's disease

Introducción. Ensayos clínicos controlados han demostrado la seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer (EA). Se presenta un estudio realizado en España, de carácter observacional y multicéntrico, con galantamina en el tratamiento de la EA leve a moderadamente grave en condiciones asistenciales reales. Métodos. Se llevaron a cabo cinco visitas durante un período de observación de 6 meses. El tratamiento con galantamina fue iniciado según la pauta estándar. Se recogieron todos los acontecimientos adversos (AA) comunicados por los pacientes, con especial atención a los considerados graves. También se exploraron las áreas cognitiva, actividades de la vida diaria, los síntomas conductuales y la calidad del sueño. Resultados. De los 723 pacientes reclutados se excluyeron 74, quedando una muestra total de 649 (71% mujeres y 29% varones). El 56.3% completó todas las visitas. La puntuación basal media del Mini-Examen Cognoscitivo (MEC) fue de 19,4 (DE: 4,7). El 29,3% de los pacientes comunicaron un total de 400 AA. Los AA más frecuentes fueron: náuseas (9,7%), vómitos (7,1), mareo (4,6%) y diarrea (4,5%). La puntuación del MEC se estabilizó a lo largo del estudio y hubo diferencias significativas favorables en la valoración de la conducta y la calidad del sueño. Conclusiones. La galantamina es un tratamiento bien tolerado en pacientes con EA leve a moderadamente grave y ha mostrado efectividad cognitiva, funcional y conductual en la práctica clínica habitual (AU)

INTRODUCTION: Several controlled clinical trials have demonstrated safety, tolerability, and efficacy of galantamine in patients with Alzheimer's disease (AD). We present an observational and multicenter study carried out in Spain. Its main objective was the assessment of the safety and tolerability of galantamine in the treatment of mild to moderately severe dementia of the Alzheimer type under real clinical conditions. METHODS: The study had five visits over a 6-month period. Titration of galantamine was performed on a standard basis. All the adverse events (AE) reported were recorded. Serious AE were particularly considered. Effectiveness was also assessed covering cognitive, functional, behavioral and sleep domains. RESULTS: 723 patients were enrolled but 74 were excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3% patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD: 4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini-Mental scores were stable over time and favorable and significant differences in behavioral and sleep evaluations were observed. CONCLUSIONS: Galantamine is a safe and well-tolerated treatment, and provides cognitive, functional, and behavioral benefits in patients with mild to moderately severe AD (AU)

[Observational study on safety, tolerability and effectiveness of galantamine in patients with mild to moderately severe Alzheimer's disease]. / Estudio observacional sobre seguridad, tolerabilidad y efectividad de la galantamina en pacientes con enfermedad de Alzheimer leve a moderadamente grave.

INTRODUCTION: Several controlled clinical trials have demonstrated safety, tolerability, and efficacy of galantamine in patients with Alzheimer's disease (AD). We present an observational and multicenter study carried out in Spain. Its main objective was the assessment of the safety and tolerability of galantamine in the treatment of mild to moderately severe dementia of the Alzheimer type under real clinical conditions. METHODS: The study had five visits over a 6-month period. Titration of galantamine was performed on a standard basis. All the adverse events (AE) reported were recorded. Serious AE were particularly considered. Effectiveness was also assessed covering cognitive, functional, behavioral and sleep domains. RESULTS: 723 patients were enrolled but 74 were excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3% patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD: 4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini-Mental scores were stable over time and favorable and significant differences in behavioral and sleep evaluations were observed. CONCLUSIONS: Galantamine is a safe and well-tolerated treatment, and provides cognitive, functional, and behavioral benefits in patients with mild to moderately severe AD.

Phenotypic variability in familial prion diseases due to the D178N mutation.

BACKGROUND: Between January 1993 and December 2003, 19 patients with familial prion diseases due to the D178N mutation were referred to the regional epidemiological registry for spongiform encephalopathies in the Basque Country in Spain, a small community of some 2,100,000 inhabitants. METHODS: Ten further patients belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the patients, the diagnosis was confirmed by analysing DNA obtained from paraffin blocks. In this article, we report on the clinical, genetic, and pathological features of the 23 patients carrying the D178N mutation confirmed by genetic molecular analysis. Haplotyping studies suggest a founder effect among Basque born families, explaining in part this unusually high incidence of the D178N mutation in a small community. Only two patients (8%) lack familial antecedents. RESULTS: We have observed a phenotypic variability even among homozygous 129MM patients. Our findings challenge the currently accepted belief that MM homozygosity in codon 129 is always related to a fatal familial insomnia (FFI) phenotype. Indeed, seven out of 17 patients with a 129MM genotype in this series presented with a Creutzfeldt-Jakob disease (CJD) clinicopathological picture. CONCLUSIONS: The considerable clinical and pathological overlapping observed among homozygous 129MM patients favours the view that FFI and CJD178 are the extremes of a spectrum rather than two discrete and separate entities. Other genetic or environmental factors apart from the polymorphism in codon 129 may play a role in determining the phenotypic expression of the D178N mutation in the PRNP gene.

[Values of GERMCIDE neuropsychological protocol in a sample of normal subjects]. / Valores del protocolo neuropsicológico GERMCIDE en una muestra de sujetos normales.

INTRODUCTION: The diagnosis of patients with cognitive deterioration or dementia requires a global approach in which the neuropsychological examination is a key piece. As part of the GERMCIDE study (Group for the Study and Multicenter Registry of Incident Cases of Dementia in Spain), a protocol was designed that included an assessment of the different cognitive functions that are most frequently altered in dementias (memory, orientation, speech, praxis, abstraction capacity and executive function). METHODS: In order to obtain data in normal subjects, this neuropsychological protocol was applied to a group of persons over 50 years without cognitive deterioration or dementia. RESULTS: A total of 103 subjects whose ages ranged from 50 to 95 years (mean: 73.5; SD: 9.3 years); 39 (37.9%) men and 64 (62.1%) women were studied. The mean score on the Mini-Mental State Examination (MMSE) was 27/30 (SD: 2.0). In the speech and praxis tests, 90% of the subjects obtained the maximum value, while performances were more unequal in memory, reasoning and programming. Mean score, standard deviation and distribution in percentages for each subtest are presented. CONCLUSIONS: The values obtained in this sample of normal subjects and their distribution in percentages may be very helpful to facilitate the interpretation of the findings of the neuropsychological examination with the GERMCIDE protocol in the general neurology clinic visits and also in the specialized visits in dementia.

Peripheral neuropathy detected on electrophysiological study as first manifestation of metachromatic leucodystrophy in infancy.

A case of infantile metachromatic leucodystrophy is described in which symptoms started at 1 year of age with weakness and hypotonus in the lower extremities. The electrophysiological status was typical of a polyneuropathy, showing fibrillation and a reduction of the nerve conduction velocity to 30 percent of the average for normal children of the same age. Clinical signs of a central lesion and mental regression were not evident until a year later. Nerve biopsy showed metachromatic granules in the phagocytes and in the Schwann cells, confirming the diagnosis of metachromatic leucodystrophy. In peripheral neuropathy in infancy without obvious cause, a nerve biopsy is the most appropriate method for diagnosis of the metachromatic leucodystrophy.