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.

Evaluation of functional improvement in older patients with cognitive impairment, depression and/or delirium admitted to a geriatric convalescence hospitalization unit.

Cognitive impairment, depression and delirium are problems of high prevalence in older patients. The geriatric convalescence unit (GCU) is a hospitalization facility offering an interdisciplinary geriatric intervention program that may be more appropriate for these patients. This study intended to analyze the functional improvement (FI) in older patients with cognitive impairment, depression and/or delirium admitted to a GCU. A group of 107 patients received specific nurse care, habitually performed in GCU and they also were included in a rehabilitation program. Cognitive impairment, depression and delirium were diagnosed according to standardized protocols. The analyzed variables were: age, functional status (Barthel index) before admission (BBA), at admission (BA) and at discharge(BD), diagnostic categories, cognitive function (mini mental state examination: MMSE) and post-discharge destination. The corrected Heinemann index (CHI) was used to evaluate FI obtained during GCU-stay, where CHI = 100 x (BD-BA)/(BBA-BA), and the efficiency index(El) was used to analyze the relationship between FI and the length of stay in the GCU,where El = (BD-BA)/(days in GCU). According to CHI, patients were divided in three groups. Group I: CHI = 0 or negative (patients who lost functional capacity during hospitalization,those who died or were transferred to hospital owing to acute deterioration. Group II: CHI < 35 % (high FI). Mean age was 77.6 +/- 9.1 years, the diagnostic categories were: fractures/orthopedics 49 (45.7 %), neurological 27(25.2 %), pulmonary/cardiologic 6 (5.6 %) and other cases 25 (23.3 %). Mean MMSE and BA scores were 16.9 +/- 9.4 and 29.6 +/- 18.9, respectively. Post-discharge destinations were:63 patients (58.8 %) returned home, 28 (26.1 %) were definitively institutionalized, 11 (10.2%) died and finally 5 (4.6 %) were transferred to acute care hospital. In-Group I, there were 35 patients (32.7 %) with a mean value of the El = 0.12 +/-1.1; in Group II, 13 (12.1 %) and 0.26 +/- 0.38; in Group III, 59 (55.1 %) and 0.94 +/- 0.97, respectively. In spite of the presence of cognitive impairment, depression and/or delirium, a high proportion of patients (67.2 %)obtained a significant improvement in their functional capacity.35 % (moderate FI). Group III: CHI >/=