Disease severity and prefrontal cortex activation during obstacle negotiation among patients with Parkinson's disease: Is it all as expected?

BACKGROUND: Previous reports indicate that patients with Parkinson's disease (PD) activate the prefrontal cortex (PFC) during complex activities such as obstacle negotiation to compensate for impaired motor function. However, the influence of disease severity on PFC activation has not been systematically evaluated. Here, we examined the effects of disease severity on PFC activation during obstacle negotiation. METHODS: 74 patients with PD (age 68.26 ± 7.54 yrs; 62.2% men) were divided into three groups based on Hoehn and Yahr stages. All patients walked along an obstacle course while negotiating anticipated and unanticipated obstacles (long/low available response time) at heights of 50 mm and 100 mm. PFC activation was measured using functional near-infrared spectroscopy (fNIRS) and was compared between groups and tasks using mixed model analyses. RESULTS: Participants with more advanced PD (i.e., Hoehn & Yahr 3) had higher PFC activation levels when negotiating anticipated obstacles, compared to participants with milder PD (i.e., Hoehn & Yahr 1, 2) (p < 0.001). Moreover, higher LEDD correlated with higher prefrontal activation during the higher anticipated obstacle. In contrast, during the negotiation of unanticipated obstacles, the differences in PFC activation were not associated with disease severity in a linear manner. CONCLUSIONS: The present study suggests that with increased disease severity, patients with PD rely more on the PFC when negotiating anticipated obstacles, perhaps to compensate for attention and motor deficits. These findings support the role of cognition in fall risk and the need to improve attention and cognition in fall prevention programs, especially among patients with more advanced disease.

Which obstacle attributes place additional demands on higher-level cognitive function in patients with Parkinson's disease?

BACKGROUND: Previous reports show that patients with Parkinson's disease (PD) rely on prefrontal activation to compensate for impaired motor function during complex activities such as obstacle negotiation. However, the influence of the properties of the obstacles on prefrontal activation has not been systematically evaluated. Here, we examined the effects of obstacle height and anticipation time on prefrontal activation in patients with PD and older adults. METHODS: 34 patients with PD (age: 67.4 ± 5.7 years; 14 women) and 26 older adults (age: 71.3 ± 8.9 years; 11 women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles (long/short available time response, ART) at heights of 50 mm and 100 mm. Prefrontal activation was measured using functional Near-Infrared Spectroscopy (fNIRS); obstacle negotiation performance was measured using Kinect cameras. RESULTS: PD patients showed greater increases in prefrontal activation during and after obstacle crossing compared to the older adults (p < 0.001). Obstacle height affected prefrontal activity only when crossing anticipated obstacles (ARTxheight interaction, p = 0.011), in which case higher obstacles were accompanied by higher prefrontal activity. PD patients showed higher levels of activation during unanticipated obstacles, compared to older adults (groupXART: p = 0.015). Different correlations between prefrontal activation and obstacle negotiation strategies were observed in patients and controls. CONCLUSIONS: These results point to the use of prefrontal activation as a compensatory mechanism in PD. Moreover, the higher activation observed when negotiating more challenging obstacles suggests that there is greater reliance on cognitive resources in these demanding situations that may contribute to the higher risk of falls in PD patients.

A multi-modal virtual reality treadmill intervention for enhancing mobility and cognitive function in people with multiple sclerosis: Protocol for a randomized controlled trial.

BACKGROUND: Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training. METHODS: This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. Primary outcome measures include dual-task gait speed and information processing speed, which will be measured prior to training, one-week post-training, and three months following training. DISCUSSION: This study will provide insight into the ability of a multi-modal cognitive-motor intervention to reduce dual-task cost and to enhance information processing speed in those with MS. This is one of the first studies that is powered to understand whether targeted dual-task training can improve MS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.

Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome.

BACKGROUND: Hyponatraemia is the commonest electrolyte disorder in the elderly. Data on severe hyponatraemia and the prevalence of cerebral salt wasting syndrome (CSWS) in elderly hospitalized patients are lacking. We studied the incidence, frequency of various aetiologies, outcome and the possible role of CSWS in severe hyponatraemia in elderly medical patients. METHODS: A prospective, observational, non-interventional study conducted over a 5-month period in medical wards. Eighty-six patients aged over 65 years with serum sodium levels < or =125 mEq/L were included. All patients were examined by one of the authors, who also evaluated potential contributing factors. Demographic, clinical and outcome data were extracted from the medical records. RESULTS: The mean age of the patients was 82.1 + 8.7 years. The prevalence of hyponatraemia was 6.2% (8.1% women and 4.0% men (P < 0.001)). There was no increase in incidence of hyponatraemia with age. The leading cause of hyponatraemia was the syndrome of inappropriate antidiuretic hormone secretion (SIADH), whose aetiology could be determined in only 46% of cases. Aetiology was multifactorial in 51% of patients (1.7 aetiological factors per patient). All patients with thiazide-induced hyponatraemia had other contributing factors. Hyperglycaemia and hypoalbuminaemia were predictors of neurological manifestations of hyponatraemia. Overall in-hospital mortality was 19%. Only hypoalbuminaemia was found as an independent risk factor for death. In none of the patients was the hyponatraemia due to CSWS. CONCLUSION: Severe hyponatraemia in elderly hospitalized medical patients is more frequent in women and of multifactorial aetiology in 50% of cases. It is most commonly caused by SIADH; CSWS is an unlikely cause.

Stable dicentric chromosomes induced by chemical mutagens in L5178Y mouse lymphoma cells.

Stable, tandem dicentric chromosomes were discovered in two mutant cell colonies resulting from exposure of L5178Y mouse lymphoma cells to chemical mutagens. These unusual dicentrics were present in all metaphase cells examined from these colonies, even after approximately 65 cell generations in culture. Observation of cells in metaphase and anaphase suggests that the interstitial centromere in these dicentrics is non-functional, and that the terminal centromere is solely responsible for their orderly anaphase segregation.

Chromosome analysis of trifluorothymidine-resistant L5178Y mouse lymphoma cell colonies.

Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities. Analysis of G-banded metaphase chromosomes from 34 sigma-TFTr colonies revealed that cells from 20 (59%) possessed one or more chromosomal abnormalities. The most frequent (16/20 colonies) abnormality observed in cells from sigma-TFTr colonies involved the addition of extra chromatin to the distal region of one chromosome number 11. In 13 of these 16 colonies, the origin of the chromatin translocated to chromosome number 11 could not be identified; the chromatin was not missing elsewhere in the genome. The remaining three sigma-TFTr colonies with an abnormal chromosome number 11 had apparently whole chromosomes translocated, in tandem, to the distal region of chromosome number 11. Chromosomal abnormalities observed in cells from sigma-TFTr colonies with normal number 11 chromosomes included 2N/4N and 2N/4N/8N mosaicism (two colonies), a Robertsonian translocation involving chromosome 10 and a marker chromosome (one colony), and trisomy 7 (one colony). In most (14/16) sigma-TFTr colonies with structural damage to chromosome number 11, the cells within a colony were heterogeneous in that some possessed chromosomal damage whereas others were apparently normal. Analysis of chromosomes in cells from eight lambda-TFTr colonies revealed one colony in which all cells had a Robertsonian translocation involving chromosomes 1 and 16 plus other structural abnormalities. The chromosomes of cells from the remaining lambda-TFTr colonies were apparently normal.

Sister-chromatid exchange and cell replication kinetics in fetal and maternal cells after treatment with chemical teratogens.

Effects of selected chemical teratogens on sister-chromatid exchange (SCE) frequencies and cell replication kinetics (CRK) in pregnant mice and their fetuses were investigated. Maternal and fetal cells were analyzed for SCE and classified as to whether they had gone through 1 (M1), 2 (M2), or 3 or more (M3+) cell cycles for quantifying cell replication kinetics and estimating average generation time (AGT). The teratogens tested in this system were mitomycin C (MMC), cyclophosphamide (CP), ethylnitrosourea (ENU), dimethylnitrosamine (DMN), lead acetate (LA), benzene (BEN), diethylstilbestrol (DES), diphenyldantoin (DPH), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and dimethyl sulfoxide (DMSO). MMC, CP, ENU, DMN, LA and BEN induced significant increases in SCE in both maternal and fetal cells compared with control values. DES and DPH induced increases in SCE in fetal cells only, whereas MNNG and DMSO did not induce any increase in SCE in either maternal or fetal cells. Chi-square analysis of the relative numbers of M1, M2 and M2+ cells revealed significant heterogeneity among test chemical doses in both maternal and fetal cells treated with all of the chemicals except DES. DES had an effect on fetal cells but not on maternal cells. A significant linear relationship between AGT and test chemical dose was noted for ENU and DMSO in maternal cells and DPH and MNNG in fetal cells. Although statistically significant, the effects of DPH, MNNG, and DMSO on AGT were small, with increases in AGT of only 1 h or less at the highest doses tested. ENU, however, resulted in more than a 2-h increase in the AGT of maternal cells. Average generation time was consistently lower in fetal cells as compared with maternal cells (overall mean AGT +/- S.D. from solvent controls was 8.6 +/- 0.3 h for fetal cells and 11.6 +/- 0.7 h for maternal cells). The results indicate that SCE induction and cell replication inhibition can occur independently, and that the assessment of SCE and CRK in maternal and fetal cells may be a promising approach to the identification of teratogenic agents.