Analysis of Dynamic Plantar Pressure and Influence of Clinical-Functional Measures on Their Performance in Subjects with Bimalleolar Ankle Fracture at 6 and 12 Months Post-Surgery.

Recovery after ankle fracture surgery can be slow and even present functional deficits in the long term, so it is essential to monitor the rehabilitation process objectively and detect which parameters are recovered earlier or later. The aim of this study was (1) to evaluate dynamic plantar pressure and functional status in patients with bimalleolar ankle fracture 6 and 12 months after surgery, and (2) to study their degree of correlation with previously collected clinical variables. Twenty-two subjects with bimalleolar ankle fractures and eleven healthy subjects were included in the study. Data collection was performed at 6 and 12 months after surgery and included clinical measurements (ankle dorsiflexion range of motion and bimalleolar/calf circumference), functional scales (AOFAS and OMAS), and dynamic plantar pressure analysis. The main results found in plantar pressure were a lower mean/peak plantar pressure, as well as a lower contact time at 6 and 12 months with respect to the healthy leg and control group and only the control group, respectively (effect size 0.63 ≤ d ≤ 0.97). Furthermore, in the ankle fracture group there is a moderate negative correlation (-0.435 ≤ r ≤ 0.674) between plantar pressures (average and peak) with bimalleolar and calf circumference. The AOFAS and OMAS scale scores increased at 12 months to 84.4 and 80.0 points, respectively. Despite the evident improvement one year after surgery, data collected using the pressure platform and functional scales suggest that recovery is not yet complete.

"This looks like a movie": a case report of post-surgical amnesia.

A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ischemia.. Post-operatively, he demonstrated acute loss of retrograde autobiographical memory, prosopagnosia and a loss of public semantic memory. His CT scan was normal and MRI was not possible due to intra-cardiac leads. An initial diagnosis of hypoxic-ischemic encephalopathy was considered. A neuropsychological examination undertaken 20 days after his surgery showed a severe alteration of retrograde autobiographical memory, marked alteration of semantic knowledge and prosopagnosia. He demonstrated an average performance in tasks measuring constructional praxis, visuospatial ability, and executive functions. 34 days after surgery, and after a short nap, the patient "returns" to the day before admission and consequently recovers his memory. Repeat neuropsychological assessment demonstrated performance within the normal range across all previously tested domains. This sudden recovery of memory, together with a normal MRI, led to a rethinking of the diagnosis of dissociative amnesia. This case illustrates the long-standing discussion about the organic or functional origin of some memory disorders, in which, despite advances in neuroimaging techniques, it is still difficult to know their etiology .

Measuring Recovery and Understanding Long-Term Deficits in Balance, Ankle Mobility and Hip Strength in People after an Open Reduction and Internal Fixation of Bimalleolar Fracture and Their Impact on Functionality: A 12-Month Longitudinal Study.

To analyze how balance and other physical capacities evolved after surgery in patients with a bimalleolar fracture and how these capacities and clinical variables (immobilization or unloading time) contribute to restoring patients' functionality, 22 patients and 10 healthy people (HC) were assessed for static and dynamic balance (Y-Balance test, YBT), dorsiflexion ankle mobility (ADFROM) and hip strength at 6 and 12 months after surgery. Patients' functional status was assessed through the Olerud Molander Ankle Score (OMAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Twenty-one patients with ankle fractures who completed the study showed a worse static and dynamic balance at 6 months. The YBT in the anterior direction (YBTA) revealed balance deficits in the operated limb at 12 months compared to the non-operated limb (-5.6%) and the HC (-6.7%). They also showed a decreased ADFROM compared to the non-operated limb (-7.4°) and the HC (-11°). In addition, medium-term (6 months) deficits in abductor strength hip but no hip strength deficits were found at 12 months after surgery. Relative weight analyses showed that ADFROM and hip strength explained 35-63% of the YBTA variance and AOFAS/OMAS scores. Balance, hip strength and ADFROM seem to be reliable indexes for assessing the functional status of these patients. These results could help to understand the relationship between these physical capacities and the patients' perceived functional status.

Clinical-Functional Evaluation and Test-Retest Reliability of the G-WALK Sensor in Subjects with Bimalleolar Ankle Fractures 6 Months after Surgery.

Ankle fractures can cause significant functional impairment in the short and long term. In recent years, gait analysis using inertial sensors has gained special relevance as a reliable measurement system. This study aimed to evaluate the differences in spatiotemporal gait parameters and clinical−functional measurements in patients with bimalleolar ankle fracture and healthy subjects, to study the correlation between the different variables, and to analyze the test−retest reliability of a single inertial sensor in our study population. Twenty-two subjects with bimalleolar ankle fracture six months after surgery and eleven healthy subjects were included in the study. Spatiotemporal parameters were analyzed with the G-WALK sensor. Functional scales and clinical measures were collected beforehand. In the ankle fracture group, the main differences were obtained in bilateral parameters (effect size: 0.61 ≤ d ≤ 0.80). Between-group differences were found in cadence, speed, stride length, and stride time (effect size: 1.61 ≤ d ≤ 1.82). Correlation was moderate (0.436 < r < 0.554) between spatiotemporal parameters and clinical−functional measures, explaining up to 46% of gait performance. Test−retest reliability scores were high to excellent (0.84 ≤ ICC ≤ 0.98), with the worst results in the gait phases. Our study population presents evident clinical−functional impairments 6 months after surgery. The G-WALK can be considered a reliable tool for clinical use in this population.

Quantifying balance deficit in people with ankle fracture six months after surgical intervention through the Y-Balance test.

BACKGROUND: Ankle fractures are among the most common traumatic fractures and have a great socio-economic impact. Consequences of an ankle fracture requiring surgical treatment (e.g. pain, reduced ankle range of motion (ROM), muscle weakness, etc.) lead to balance deterioration, which has a profound impact on activities of daily living. However, to the best of the authors' knowledge, no reliable clinical tests are available to monitor balance in patients after ankle surgery. OBJECTIVES: To quantify single-leg dynamic balance in patients with bimalleolar ankle fracture through the Y-Balance test (YBT). The second objective was to analyze the impact of ankle dorsiflexion ROM and hip strength on balance to optimize balance rehabilitation programs. DESIGN: Cross-sectional study. METHODS: 22 participants, who had undergone surgery after bimalleolar ankle fractures, were assessed for ankle ROM, hip strength, and dynamic balance six-months after the surgical intervention. The within-session reliability of YBT was calculated through the intraclass correlation coefficient (ICC) and the standard error of measurement (SEM). Student's t-tests were used to assess leg differences. A multiple regression analysis was performed to evaluate the role of ankle dorsiflexion ROM and hip abductor and adductor strength in predicting balance performance. RESULTS: YBT showed high-to-excellent within-session relative reliability (Healthy leg: 0.85 ≤ ICC≤0.96; Operated leg: 0.84 ≤ ICC≤0.96). SEM values were below 3.3 %. The operated leg showed significant lower YBT scores for anterior reach direction (-9.0 %; g=-0.70) and composite score (-4.5 %; g=-0.34). Multiple regression analysis showed that both, ankle dorsiflexion and hip abductor and adductor strength explained 66 % of the variance in the YBT anterior direction of the operated leg. CONCLUSIONS: The YBT is a reliable tool that allows the quantification of single-leg dynamic balance impairments from 6-months after surgery in patients with bimalleolar ankle fracture. Between-leg YBT differences in the anterior direction can be used as reference scores (3.3 %) for balance restoration. Balance rehabilitation programs should focus on improving ankle functionality and reducing hip muscle weakness with specific hip strength exercises and balance exercises with similar demands to the reaching tasks of the YBT to promote a faster recovery.

LAMP2 deficiency attenuates the neurodegeneration markers induced by HSV-1 infection.

Mounting evidence suggests a major role of infectious agents in the pathogenesis of sporadic Alzheimer's disease (AD). Among them, herpes simplex virus type 1 (HSV-1) infection has emerged as a major factor in the etiology of AD. HSV-1 is able to induce some of the main alterations of the disease such as hyperphosphorylation of tau protein and accumulation of amyloid-ß peptide. Functional genomic analysis of a cell model of HSV-1 infection and oxidative stress developed in our laboratory revealed lysosomal system to be the main pathway altered, and the lysosome-associated membrane protein 2 (LAMP2) gene one of the most strongly modulated genes. The aim of this work is to study LAMP2 as an AD candidate gene and to investigate its role in the neurodegeneration induced by HSV-1 using a LAMP2 knockdown cell model. LAMP2 deficiency led to a significant reduction of viral DNA replication and formation of infectious particles. In addition, tau hyperphosphorylation and inhibition of Aß secretion induced by the virus were attenuated by the absence of LAMP2. Finally, genetic association studies revealed LAMP2 genetic variants to be associated with AD risk. In summary, our data indicate that LAMP2 could be a suitable candidate to mediate the AD-like phenotype caused by HSV-1.

Major Surgery Affects Memory in Individuals with Cerebral Amyloid-ß Pathology.

BACKGROUND: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer's disease (AD) might predispose to cognitive deterioration after surgery. OBJECTIVE: To analyze the effect of amyloid-ß on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects. METHODS: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers. RESULTS: Cumulative incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-ß was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A+) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A + group showed a notable worsening on memory performance. CONCLUSION: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-ß deposits.

Characterization of Alzheimer's Disease Micro-RNA Profile in Exosome-Enriched CSF Samples.

Micro-RNAs (miRNAs) are small endogenous noncoding ribonucleic acids that modulate gene expression at a post-transcriptional level. miRNAs have been postulated as potential biomarkers and therapeutic targets in a wide list of human diseases including cancer, autoimmune, cardiovascular, and neurodegenerative diseases. miRNAs are secreted by the cells into exosomes. These are small cell-derived membrane vesicles that can be isolated from many body fluids including urine, saliva, blood, and cerebrospinal fluid (CSF). Exosomes contain a variety of proteins and noncoding RNAs and seem to play an important role in cell-cell communication and the regulation of immune response and other body functions. In this chapter, we will discuss the sequential procedure to characterize the miRNA profile in exosome-enriched CSF samples.

Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease.

Patients with Parkinson's disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S-associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated PD.

Hereditary pancreatitis: clinical features and inheritance characteristics of the R122C mutation in the cationic trypsinogen gene (PRSS1) in six Spanish families.

CONTEXT: Hereditary pancreatitis is an autosomal dominant disease which is caused by mutations in the PRSS1 gene. OBJECTIVE: The aim of our study was to describe the penetrance and phenotype-genotype correlations of the c.346C>T (p.R122C) mutation. DESIGN: Case series descriptive study. PATIENTS: Forty-one members of six families from whom DNA samples were analyzed. MAIN OUTCOME MEASURES: In subjects with R122C mutation symptoms, pancreatic calcifications, main pancreatic duct changes, diabetes, steatorrhea, pancreatic cancer and surgery were recorded. RESULTS: The R122C mutation was detected in 22 of the 41 family members studied, and 7 men and 2 women developed pancreatic disease, resulting in a penetrance of 40.9%. One out of the 9 patients was excluded because she died before the mutation was detected. The mean age at symptom onset was 23.5 years (range: 4-51 years). Abdominal pain was present in 6 (75.0%) of the 8 patients with the R122C mutation who developed pancreatic disease. Calcifications had developed in 5 (62.5%) at a mean age of 35.8 years (range: 14-56 years). Five (62.5%) developed changes in the pancreatic ducts at a mean age of 44.2 years (range: 19-65 years). Two patients (25.0%) developed steatorrhea during the follow-up at 26 and 35 years of disease progression. Diabetes developed in five patients (62.5%) at a mean age of 41.4 years old (range: 22-53 years). Three of the patients analyzed (37.5%) developed pancreatic cancer at 59 years of age, 63 years of age and 70 years of age. CONCLUSIONS: Penetrance of the R122C mutation is lower than that described for the R122H and N29I mutations, and there is a tendency toward a predominance of males with the R122C mutation who developed the phenotype of pancreatitis.

Case-control study of vascular endothelial growth factor (VEGF) genetic variability in Alzheimer's disease.

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and blood vessel function. Recent evidence indicates that VEGF facilitates memory and learning through stimulating angiogenesis and neurogenesis in the rat hippocampal dendate gyrus. Abnormal regulation of VEGF expression has been reported in the pathogenesis of both atherosclerosis and motoneuron degeneration in amyotrophic lateral sclerosis, with low VEGF-producing polymorphisms (-2578 allele A and -634 allele G) conferring increased susceptibility for the development of the disorders. We tested whether these polymorphisms downregulating expression of VEGF might increase the risk of developing Alzheimer's disease (AD). So, we performed a case-control study in 362 Spanish AD patients and 428 healthy controls. The current study does not demonstrate an association between VEGF (-2578) and VEGF (-634) genotypes or haplotypes and AD.