A series of cases with Huntington-like phenotype and intermediate repeats in HTT.

BACKGROUND: Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They are present in the general population but there is an increasing number of cases with Huntington-like phenotype reported. METHODS: We reviewed the medical records of cases in our centre where the neurologist suspected Huntington's disease (HD) as one of the feasible diagnoses and genetic testing showed the number of CAG repeats was in the "intermediate range". We gathered the type of symptoms in all cases and the main neuroimaging findings when available. RESULTS: We found 14 cases, 8 males and 6 females, with average age at onset at 64 years old. Most cases exhibited some type of extrapyramidal symptoms. Cognitive and/or behavioral symptoms were also present in most cases (being depression, anxiety and cognitive impairment the most frequent ones). In one case we found deposits of iron in the basal ganglia in the MRI, and in another case we found diffuse cortical hypometabolism with predominantly frontal bilateral involvement and bilateral focal deficit of both caudate and thalamus in the FDG-PET. CONCLUSION: The clinical and neuroimaging findings of some cases with IA in this series are compatible with the clinical picture of HD but also with several other alternative diagnoses. Therefore we can not establish association between IA and HD. Larger series with more comprehensive diagnostic workout and neuropathological studies are needed to confirm or rule out whether IAs in the HTT gene may cause HD.

Efficacy of different doses of sugammadex after continuous infusion of rocuronium.

AIM: To evaluate the effects of two different doses of sugammadex after maintenance anesthesia with sevofluorane and remifentanil and deep rocuronium-induced neuromuscular blockade (NMB). METHODS: Patients between 20 and 65 years of age, with American Society of Anesthesiologists physical status classification I-II, undergoing gynecological surgery were included in a prospective, comparative and randomized study. NMB was induced with an injection of 0.6 mg/kg of rocuronium followed by continuous infusion of 0.3-0.6 mg/kg per hour to maintain a deep block. Anesthesia was maintained with sevofluorane and remifentanil. Finally, when surgery was finished, a bolus of 2 mg/kg (group A) or 4 mg/kg (group B) of sugammadex was applied when the NMB first response in the train-of-four was reached. The primary clinical endpoint was time to recovery to a train-of-four ratio of 0.9. Other variables recorded were the time until recovery of train-of-four ratio of 0.7, 0.8, hemodynamic variables (arterial blood pressure and heart rate at baseline, starting sugammadex, and minutes 2, 5 and 10) and adverse events were presented after one hour in the post-anesthesia care unit. RESULTS: Thirty-two patients were included in the study: 16 patients in group A and 16 patients in group B. Only 14 patients each group were recorded because arterial pressure values were lost in two patients from each group in minute 10. The two groups were comparable. Median recovery time from starting of sugammadex administration to a train-of-four ratio of 0.9 in group A and B was 129 and 110 s, respectively. The estimated difference in recovery time between groups was 24 s (95%CI: 0 to 45 s, Hodges-Lehmann estimator), entirely within the predefined equivalence interval. Times to recovery to train-of-four ratios of 0.8 (group A: 101 s; group B: 82.5 s) and 0.7 (group A: 90 s; group B: 65 s) from start of sugammadex administration were not equivalent between groups. There was not a significant variation in the arterial pressure and heart rate values between the two groups and none of the patients showed any clinical evidence of residual or recurrent NMB. CONCLUSION: A dose of 2 mg/kg of sugammadex after continuous rocuronium infusion is enough to reverse the NMB when first response in the Train-Of-Four is reached.

Are γ-secretase and its associated Alzheimer's disease γ problems?

Presenilins (PS1 and PS2) and the amyloid-ß precursor protein (AßPP) are the only known proteins as causing monogenic Alzheimer's disease. AßPP is not the unique substrate of the γ-secretase complex. Presenilins are also implicated in the processing of Notch, an important developmental protein, which is thought to compete directly with AßPP for cleavage by γ-secretase. In the context of cleavages in alpha, beta and gamma and with the recent three-dimensional models of γ-secretase complex, a kinetic study of the sequential proteolysis of AßPP prompts us to think the possible existence of two entrance sites for substrate with only one exit site, a configuration depicting a lowercase gamma letter. The quantitative distribution of the cleavage products by the γ-secretase, mainly Aß(40), Aß(42) and Aß(43), could be explained in the context of this hypothesis. Based on published results in the literature and the analyses of AßPP C99 fragment, highly abundant in Down's syndrome patients, we propose that ß- and γ-secretases can function as a supra-enzyme complex where AßPP substrate might be attached to the γ-secretase complex before ß cleavage takes place. Different studies point that a small peptide sequence, showing homology in presenilins and AßPP, plays a pivotal role and that minor alterations in the sequence of AßPP protein limit the formation of C99 and also of Aß(40) and Aß(42). The model proposed could be of importance in future studies aimed at understanding the specific events involved in course of Alzheimer disease pathophysiology and also at studying of formation/deterioration of memory.

Síndrome Confusional Agudo: un reto para la Enfermería hospitalaria / Acute Confusional Syndrome: a challenge for hospital nursing

Objetivos: determinar la incidencia del Síndrome Confusional Agudo (SCA) y las características asociadas en pacientes ingresados en la Fundación Hospital de Jove (Principado de Asturias).Material y método: estudio descriptivo longitudinal y prospectivo durante ocho meses consecutivos (1/2/09-30/9/09) en los pacientes ingresados en la Fundación Hospital de Jove.Para determinar la ocurrencia de SCA se utilizaron los criterios del Confussion Assessment Method. Variables de estudio:edad, sexo, días de ingreso, servicio de ingreso, morbilidad previa, presencia de infección, momento de debut desde el ingreso,tipo clínico, necesidad de contención mecánica, consumo de tóxicos y fármacos. Se realizaron análisis bivariantes y de regresión logística.Resultados: 69 de 3.877 pacientes (1,8%) desarrollaron SCA.Edad media: 81,13 años, predominando los varones (59,4%),con ingreso en servicios quirúrgicos 63,8%, de debut temprano(53,6; 100% hiperactivos) e inicio nocturno: 87,0%. En elSCA de los enfermos médicos, frente a los quirúrgicos, predominó la patología neurológica previa (OR = 5,83), el inicio temprano (OR = 6,35), la toma de corticoides (OR = 9,88) yla de antiparkinsonianos (OR = 1,19). En el modelo de regresión(variable dependiente: debut temprano o tardío) permanecieron únicamente el servicio de ingreso (OR = 3,61 para Medicina Interna frente Quirúrgicos) y la presencia de patología neurológica previa (OR = 3,11).Conclusiones: si bien la incidencia global del SCA en la Fundación Hospital de Jove fue del 1,8%, osciló entre el 0,6 y el7,4% según la unidad de ingreso, menor que en las series publicadas. Predominó el hiperactivo de inicio nocturno y la baja incidencia de hipoactivos, lo que sugiere la difícil identificación de este último. Es fundamental potenciar la formación de Enfermería en este problema (AU)

Objectives: to determine the incidence of the Acute Confusional Syndrome (ACS) and the characteristics associated with patients admitted to the Hospital de Jove Foundation(Principado de Asturias).Material and method: longitudinal prospective descriptive study performed over the course of eight consecutive months(1/2/09-30/9/09) in patients admitted to the Hospital de Jove Foundation. In order to determine the occurrence of ACS,Confusion Assessment Method criteria were used. Study variables:age, sex, hospitalization days, admission service,prior morbidity, presence of infection, time of on set since admission,clinical type, need for mechanical containment, substance and drug use. Bivariate and logistic regression analyses were performed.Results: 69 of 3.877 patients (1,8%) developed ACS. Meanage: 81,13 years, predominantly males (59,4%), with admission to surgical services 63,8%, early onset (53,6; 100% hyperactive) and nocturnal onset: 87,0%. In medical patients’ACS, versus that of surgical patients, prior neurological patholo -gy (OR = 5,83), early onset (OR = 6,35), use of corticoids (OR= 9,88) and use of anti-Parkinson’s drugs (OR = 1,19) were the most frequent features. Only the admission service (OR = 3,61 for Internal Medicine versus Surgical) and the presence of prior neurological pathology (OR = 3,11) remained in the regression model (dependent variable: early or delayed onset).Conclusions: although the over all incidence of ACS in the Hospital de Jove Foundation was 1,8%, it ranged from 0,6 and 7,4% depending on the admission Unit, a rate that is lower than that found in published series. The hyperactive patient with nocturnal on set and a low incidence of hypoactivepatients were predominant, suggesting that it is difficult to identify the latter. It is essential to promote Nursing training for this problem (AU)

Effects of glatiramer acetate on spasticity in previously interferon-beta-treated and treatment-naive patients with relapsing-remitting multiple sclerosis: a prospective, nonrandomized, open-label, uncontrolled, observational pilot study.

BACKGROUND: Treatment with interferon-beta (IFN-beta) has been related to worsening of muscle spasticity in patients with multiple sclerosis (MS). However, there are no specific data on the effects of glatiramer acetate (GA) on spasticity. OBJECTIVE: The aim of the present study was to assess the effects of GA on spasticity in patients with relapsing-remitting MS who had been previously treated with IFN-beta or were treatment naive. METHODS: Two cohorts of MS patients with spasticity who were about to begin treatment with GA at the approved dosage (20 mg/d) were enrolled in the study: patients who were being switched from IFN-beta due to adverse events or lack of efficacy (cohort 1) and patients who were treatment naive (cohort 2). The follow-up periods for cohorts 1 and 2 were 18 and 12 months, respectively. Patients' physical condition was assessed at baseline and at the end of follow-up using the Modified Ashworth Scale (MAS), Penn Spasm Frequency Scale (PSFS), Global Pain Score (GPS), Adductor Tone Rating Scale, Expanded Disability Status Scale (EDSS), and neurophysiologic tests (latency and amplitude of the Hoffmann reflex [H reflex] in the soleus, and ratio of maximum H reflex to maximum motor response [H/M ratio] in the lower limb). The frequency and severity of adverse events were recorded throughout follow-up, and investigators rated the causal relationship to GA (unrelated, unlikely, possibly, or probably). RESULTS: Twenty-eight patients were included in the study, 13 in cohort 1 and 15 in cohort 2. All patients were white. Cohort 1 was 76.9% female, with a mean (SD) age of 39.85 (9.25) years; cohort 2 was 66.7% female, with a mean age of 40.73 (11.52) years. Cohort 1 had significant reductions from baseline to the end of follow-up in mean scores on the MAS for the right hemibody (from 1.85 [0.61] to 1.18 [0.60]; P = 0.002) and left hemibody (from 1.86 [0.55] to 1.27 [0.65]; P = 0.045), PSFS (from 2.00 [0.91] to 0.36 [0.81]; P = 0.002), and GPS (from 47.69 [13.94] to 24.09 [17.15] mm; P = 0.002). The changes from baseline were not significant on the mean Adductor Tone Rating Scale, EDSS, H-reflex latency or amplitude on either side, or lower-limb H/M ratio on either side. Cohort 2 had significant reductions from baseline in H-reflex latency on the left side (from 30.31 [2.44] to 28.75 [2.01]; P = 0.005) and H/M ratio on the right side (from 0.45 [0.15] to 0.35 [0.19]; P = 0.025). There were no significant changes in mean scores on the MAS for either hemibody, PSFS, GPS, Adductor Tone Rating Scale, EDSS, H-reflex latency on the right side, H-reflex amplitude on either side, or lower-limb H/M ratio on the left side. Sixteen patients experienced a total of 28 adverse events. Seven mild adverse events were considered related to GA: local reaction at the injection site (3 patients); headache/migraine, anxiety, and skin reaction (1 patient each); and an unspecified adverse drug reaction (1 patient). Two serious adverse events (pyelonephritis and pyrexia) occurred during the study, neither of them considered related to GA. CONCLUSIONS: In this pilot study in patients with relapsing-remitting MS, GA treatment did not increase spasticity. Furthermore, the results suggest that GA may reduce spasticity in patients previously treated with IFN-beta. These findings support the conduct of large randomized controlled trials of the effects of GA on spasticity.

Association study and meta-analysis of Alzheimer's disease risk and presenilin-1 intronic polymorphism.

Numerous studies have tested for associations between an intronic polymorphism (rs165932) of presenilin-1 (PS-1) gene and the risk of Alzheimer's disease (AD), but results have been conflicting. To throw light on this issue, we investigate the possible involvement of PS-1 genotype in a case-control study based on a relatively stable population in Spain and a meta-analysis of published studies. An examination was conducted of 85 patients with probable or possible AD, along with controls from the same community, by using an chi(2) test for homogeneity and a binary logistic regression model. For comparison purposes, a meta-analysis of data from all available published studies was assessed. In our patients, homozygosity of the allele 2 in the PS-1 gene increased for late-onset AD (OR 2.38, 95% CI 1.07-5.29, P<0.05). The presence of at least one allele of apoE was also associated with AD (OR 4.01, 95% CI 1.93-8.34, p<0.05). The regression model showed that, overall, the presence of the apoE epsilon 4 allele and the PS-1 2/2 genotype were independent factors for the development of AD in our sample. In our genotype-based meta-analysis, the PS-1 2/2 genotype was probably related with AD for the European sub-group (fixed effects model, OR 1.19, 95% CI 1.02-1.37, p<0.05), but there are many confusing factors between different studies. Presenilin-1 2/2 genotype is a risk factor for late onset Alzheimer disease in the Spanish population, and probably, for Europeans.

Real time PCR assay with fluorescent hybridization probes for genotyping intronic polymorphism in presenilin-1 gene.

BACKGROUND: Identification of all susceptibility loci for Alzheimer's disease has been a major goal in resolving the pathogenesis of this disease. METHODS: A PCR assay with fluorescently labeled oligonucleotide hybrinization probes with subsequent fluorescent probe melting point analysis was developed. RESULTS: Allelic discrimination of intronic polymorphism of presenilin-1 gene and the restriction fragment length polymorphism method yielded identical results, proving its usefulness for genotyping PS1 gene. CONCLUSIONS: This method provides excellent robustness, speed, and accuracy, and is well suited for determination of the polymorphism in both small and large numbers of samples. This assay could help to overcome the controversy regarding the association between the PS1 s165932 intronic polymorphism and Alzheimer's disease.