Renal resistive index as a predictor of postoperative complications in liver resection surgery. Observational study.

Mortality after liver surgery reduced during the last three decades to less than 2%, but post-operative morbidity occurs in 20-50% of cases. Patients are often considered eligible for post-operative intensive-care unit (ICU) admission. Predicting which patients that are at higher risk could lead to a more precise perioperative management. We investigated whether renal resistive index (RRI), alone or along with other items, can predict post-operative complication after hepatic resection. All consecutive patients undergoing hepatectomy for primary or metastatic neoplasm at our Institution between February 2015 and March 2017 were enrolled. They received RRI measurement before entering in operative room and after awakening from general anesthesia. 183 Patients were enrolled. High surgical invasiveness, surgery time > 360 min, pre-operative RRI and postoperative serum lactate clearance < - 6%, showed to be associated with postoperative complications. Pre-operative RRI, complex liver resection, long-lasting surgery and poor lactate clearance (cLac) close to awakening from general anesthesia, all together may permit to classify the risk of post-operative adverse outcome after hepatic resection surgery.

Human ribosomes from cells with reduced dyskerin levels are intrinsically altered in translation.

Dyskerin is a pseudouridine (ψ) synthase involved in fundamental cellular processes including uridine modification in rRNA and small nuclear RNA and telomere stabilization. Dyskerin functions are altered in X-linked dyskeratosis congenita (X-DC) and cancer. Dyskerin's role in rRNA pseudouridylation has been suggested to underlie the alterations in mRNA translation described in cells lacking dyskerin function, although relevant direct evidences are currently lacking. Our purpose was to establish definitely whether defective dyskerin function might determine an intrinsic ribosomal defect leading to an altered synthetic activity. Therefore, ribosomes from dyskerin-depleted human cells were purified and 1) added to a controlled reticulocyte cell-free system devoid of ribosomes to study mRNA translation; 2) analyzed for protein contamination and composition by mass spectrometry, 3) analyzed for global pseudouridylation levels. Ribosomes purified from dyskerin-depleted cells showed altered translational fidelity and internal ribosome entry site (IRES)-mediated translation. These ribosomes displayed reduced uridine modification, whereas they were not different in terms of protein contamination or ribosomal protein composition with respect to ribosomes from matched control cells with full dyskerin activity. In conclusion, lack of dyskerin function in human cells induces a defect in rRNA uridine modification, which is sufficient to alter ribosome activity.

Pharmacological Modulation of Ischemic-Reperfusion Injury during Pringle Maneuver in Hepatic Surgery. A Prospective Randomized Pilot Study.

BACKGROUND: The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N-acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection. METHODS: Forty-eight patients were enrolled in a pilot double-blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality. RESULTS: All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min. CONCLUSIONS: The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.

MMPs and angiogenesis affect the metastatic potential of a human vulvar leiomyosarcoma cell line.

Gynaecological leiomyosarcoma (gLMS) represent a heterogeneous group of soft tissue sarcoma, characterized by rare incidence, high aggressiveness and propensity to infiltrate secondary organs, poor prognosis and lethality, because of the lack of biological mechanisms that underlying their progression and effective pharmaceutical treatments. This study was focused on some of the aspects of progression and dissemination of a subtype of gLMS namely vulvar LMS (vLMS). We therefore used a vulvar LMS-derived cell line namely SK-LMS-1, coupled with in vitro and in vivo assays. We observed that SK-LMS-1 cells have a strong invasive capacity in vitro, through the activity of matrix metalloproteinases 2 and 9, while in vivo these cells induce a strong angiogenic response and disseminate to the chick embryo liver. Therefore, we postulate that metalloproteinases are involved in the spreading behaviour of SK-LMS-1. Further investigations are necessary to better understand the molecular and cellular machinery involved in the progression of this malignancy.

Dyskerin expression in human fetal, adult and neoplastic intrahepatic bile ducts: correlations with cholangiocarcinoma aggressiveness.

AIMS: To investigate the immunohistochemical expression of dyskerin, a biomarker involved in ribosome production and telomere maintenance, in human fetal, adult and neoplastic bile ducts, and possible correlations with cholangiocarcinoma aggressiveness. METHODS AND RESULTS: Sixty consecutive intrahepatic cholangiocarcinomas were collected and used for tissue microarray construction (total: 176 cores); clinical data and follow-up were also collected. Five fetal and 10 normal adult livers were included as controls. Automated immunohistochemistry for dyskerin, p53, and Ki67, and nucleolar silver staining, were performed. In normal livers, dyskerin expression was negative in smaller bile ducts (mean 44.8 µm) and positive in bile ducts of larger diameter (mean 116.1 µm; P < 0.001). Expression was positive in 56.7% of cholangiocarcinomas, and correlated with p53 mutation (P = 0.008) and a higher proliferative (Ki67) index (P = 0.003), which were included as markers of tumour aggressiveness. Finally, dyskerin-positive cholangiocarcinomas showed a negative trend in disease-free survival (P = 0.078) on univariate analysis. CONCLUSIONS: The non-neoplastic biliary tree seems to progressively lose dyskerin expression from the major branches to the peripheral portal bile ducts. Similarly, intrahepatic cholangiocarcinomas showed two patterns of dyskerin expression, and the dyskerin-positive phenotype seemed to characterize more aggressive cholangiocarcinomas.

Dyskerin depletion increases VEGF mRNA internal ribosome entry site-mediated translation.

Dyskerin is a nucleolar protein encoded by the DKC1 gene that (i) stabilizes the RNA component of the telomerase complex, and (ii) drives the site-specific pseudouridilation of rRNA. It is known that the partial lack of dyskerin function causes a defect in the translation of a subgroup of mRNAs containing internal ribosome entry site (IRES) elements such as those encoding for the tumor suppressors p27 and p53. In this study, we aimed to analyze what is the effect of the lack of dyskerin on the IRES-mediated translation of mRNAs encoding for vascular endothelial growth factor (VEGF). We transiently reduced dyskerin expression and measured the levels of the IRES-mediated translation of the mRNA encoding for VEGF in vitro in transformed and primary cells. We demonstrated a significant increase in the VEGF IRES-mediated translation after dyskerin knock-down. This translational modulation induces an increase in VEGF production in the absence of a significant upregulation in VEGF mRNA levels. The analysis of a list of viral and cellular IRESs indicated that dyskerin depletion can differentially affect IRES-mediated translation. These results indicate for the first time that dyskerin inhibition can upregulate the IRES translation initiation of specific mRNAs.

A wearable system for gait training in subjects with Parkinson's disease.

In this paper, a system for gait training and rehabilitation for Parkinson's disease (PD) patients in a daily life setting is presented. It is based on a wearable architecture aimed at the provision of real-time auditory feedback. Recent studies have, in fact, shown that PD patients can receive benefit from a motor therapy based on auditory cueing and feedback, as happens in traditional rehabilitation contexts with verbal instructions given by clinical operators. To this extent, a system based on a wireless body sensor network and a smartphone has been developed. The system enables real-time extraction of gait spatio-temporal features and their comparison with a patient's reference walking parameters captured in the lab under clinical operator supervision. Feedback is returned to the user in form of vocal messages, encouraging the user to keep her/his walking behavior or to correct it. This paper describes the overall concept, the proposed usage scenario and the parameters estimated for the gait analysis. It also presents, in detail, the hardware-software architecture of the system and the evaluation of system reliability by testing it on a few subjects.

5'-Untranslated region of heat shock protein 70 mRNA drives translation under hypertonic conditions.

In mammalian cells, adaptation to hypertonic conditions leads to the activation of an array of early (cell shrinkage, regulatory volume increase) and late (accumulation of compatible osmolytes) responses and increased level of HSPs (heat shock proteins). Protein synthesis is strongly inhibited few minutes after the hypertonic challenge as demonstrated in whole cells and as reproduced under controlled conditions in cell-free systems. Different mechanisms known to mediate the accumulation of HSP70, such as mRNA transcription and stabilization, require fully active protein synthesis. We show that the 5'-untranslated region of HSP70 messenger drives a hypertonicity-resistant translation (up to 0.425 osmol/kg of water), whereas cap-dependent protein synthesis is almost totally blocked under the same conditions. The results, obtained in cell-free systems and in whole cells, might help to explain why HSP70 is accumulated in cells when total protein synthesis is impaired. We also observed that translation initiated by viral IRES (from Cricket paralysis virus) is highly efficient in cells exposed to hyperosmolarity, suggesting that the resistance to hypertonic conditions is a more general feature of cap-independent translation. The described mechanism may also play a role in the control of translation of other messengers encoding for proteins involved in the adaptation to hypertonicity.

Change in conformation with reduction of alpha-helix content causes loss of neutrophil binding activity in fully cytotoxic Shiga toxin 1.

Shiga toxins (Stx) play an important role in the pathogenesis of hemolytic uremic syndrome, a life-threatening renal sequela of human intestinal infection caused by specific Escherichia coli strains. Stx target a restricted subset of human endothelial cells that possess the globotriaosylceramide receptor, like that in renal glomeruli. The toxins, composed of five B chains and a single enzymatic A chain, by removing adenines from ribosomes and DNA, trigger apoptosis and the production of pro-inflammatory cytokines in target cells. Because bacteria are confined to the gut, the toxins move to the kidney through the circulation. Polymorphonuclear leukocytes (PMN) have been indicated as the carriers that "piggyback" shuttle toxins to the kidney. However, there is no consensus on this topic, because not all laboratories have been able to reproduce the Stx/PMN interaction. Here, we demonstrate that conformational changes of Shiga toxin 1, with reduction of α-helix content and exposition to solvent of hydrophobic tryptophan residues, cause a loss of PMN binding activity. The partially unfolded toxin was found to express both enzymatic and globotriaosylceramide binding activities being fully active in intoxicating human endothelial cells; this suggests the presence of a distinct PMN-binding domain. By reviewing functional and structural data, we suggest that A chain moieties close to Trp-203 are recognized by PMN. Our findings could help explain the conflicting results regarding Stx/PMN interactions, especially as the groups reporting positive results obtained Stx by single-step affinity chromatography, which could have preserved the correct folding of Stx with respect to more complicated multi-step purification methods.

Recommended number of strides for automatic assessment of gait symmetry and regularity in above-knee amputees by means of accelerometry and autocorrelation analysis.

BACKGROUND: Symmetry and regularity of gait are essential outcomes of gait retraining programs, especially in lower-limb amputees. This study aims presenting an algorithm to automatically compute symmetry and regularity indices, and assessing the minimum number of strides for appropriate evaluation of gait symmetry and regularity through autocorrelation of acceleration signals. METHODS: Ten transfemoral amputees (AMP) and ten control subjects (CTRL) were studied. Subjects wore an accelerometer and were asked to walk for 70 m at their natural speed (twice). Reference values of step and stride regularity indices (Ad1 and Ad2) were obtained by autocorrelation analysis of the vertical and antero-posterior acceleration signals, excluding initial and final strides. The Ad1 and Ad2 coefficients were then computed at different stages by analyzing increasing portions of the signals (considering both the signals cleaned by initial and final strides, and the whole signals). At each stage, the difference between Ad1 and Ad2 values and the corresponding reference values were compared with the minimum detectable difference, MDD, of the index. If that difference was less than MDD, it was assumed that the portion of signal used in the analysis was of sufficient length to allow reliable estimation of the autocorrelation coefficient. RESULTS: All Ad1 and Ad2 indices were lower in AMP than in CTRL (P < 0.0001). Excluding initial and final strides from the analysis, the minimum number of strides needed for reliable computation of step symmetry and stride regularity was about 2.2 and 3.5, respectively. Analyzing the whole signals, the minimum number of strides increased to about 15 and 20, respectively. CONCLUSIONS: Without the need to identify and eliminate the phases of gait initiation and termination, twenty strides can provide a reasonable amount of information to reliably estimate gait regularity in transfemoral amputees.

Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leucocytes through a common receptor.

The main cause of acute renal failure in children is HUS (haemolytic uraemic syndrome), a consequence of intestinal infections with Escherichia coli strains producing Stx (Shiga toxins). Stx released in the gut by the non-invasive bacteria reach the bloodstream and are targeted to cerebral and renal endothelium triggering HUS. PMN (polymorphonuclear leucocytes) seem to be involved in Stx delivery through an unidentified membrane receptor (Kd=10⁻8 M; 2×105 binding sites) which does not allow internalization. Some experts in the field have defined the Stx-PMN interaction as non-specific and of little biological significance. In the present study, we show that the A chain of ricin, the well-known plant RIP (ribosome-inactivating protein), interacts with PMN (Kd=10⁻9 M; 2×105 binding sites) competing for the same receptor that recognizes Stx, whereas diphtheria toxin and several agonists of TLRs (Toll-like receptors) or the mannose receptor were ineffective. No toxic effects of ricin A chain on PMN were observed, as assessed by measuring protein synthesis and the rate of spontaneous apoptosis of leucocytes. Moreover, two single-chain RIPs (gelonin and saporin S6) had the same competing effect. Thus RIPs and Stx1 share structural similarities, the same enzymatic activity and a common receptor on PMN. These observations reveal that the Stx-PMN interaction is specific, confirming that PMN recognize molecular patterns common to different foreign molecules.

Perioperative Management of Complex Hepatectomy for Colorectal Liver Metastases: The Alliance between the Surgeon and the Anesthetist.

Hepatic resection has been widely accepted as the first choice for the treatment of colorectal metastases. Liver surgery has been recognized as a major abdominal procedure; it exposes patients to a high risk of perioperative adverse events. Decision sharing and the multimodal approach to the patients' management are the two key items for a safe outcome, even in such a high-risk surgery. This review aims at addressing the main perioperative issues (preoperative evaluation; general anesthesia and intraoperative fluid management and hemodynamic monitoring; intraoperative metabolism; administration policy for blood-derivative products; postoperative pain control; postoperative complications), in particular, from the anesthetist's point of view; however, only an alliance with the surgery team may be successful in case of adverse events to accomplish a good final outcome.

Gait symmetry and regularity in transfemoral amputees assessed by trunk accelerations.

BACKGROUND: The aim of this study was to evaluate a method based on a single accelerometer for the assessment of gait symmetry and regularity in subjects wearing lower limb prostheses. METHODS: Ten transfemoral amputees and ten healthy control subjects were studied. For the purpose of this study, subjects wore a triaxial accelerometer on their thorax, and foot insoles. Subjects were asked to walk straight ahead for 70 m at their natural speed, and at a lower and faster speed. Indices of step and stride regularity (Ad1 and Ad2, respectively) were obtained by the autocorrelation coefficients computed from the three acceleration components. Step and stride durations were calculated from the plantar pressure data and were used to compute two reference indices (SI1 and SI2) for step and stride regularity. RESULTS: Regression analysis showed that both Ad1 well correlates with SI1 (R2 up to 0.74), and Ad2 well correlates with SI2 (R2 up to 0.52). A ROC analysis showed that Ad1 and Ad2 has generally a good sensitivity and specificity in classifying amputee's walking trial, as having a normal or a pathologic step or stride regularity as defined by means of the reference indices SI1 and SI2. In particular, the antero-posterior component of Ad1 and the vertical component of Ad2 had a sensitivity of 90.6% and 87.2%, and a specificity of 92.3% and 81.8%, respectively. CONCLUSIONS: The use of a simple accelerometer, whose components can be analyzed by the autocorrelation function method, is adequate for the assessment of gait symmetry and regularity in transfemoral amputees.

A computational modelling approach to investigate different targets in deep brain stimulation for Parkinson's disease.

We investigated by a computational model of the basal ganglia the different network effects of deep brain stimulation (DBS) for Parkinson's disease (PD) in different target sites in the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and the globus pallidus pars externa (GPe). A cellular-based model of the basal ganglia system (BGS), based on the model proposed by Rubin and Terman (J Comput Neurosci 16:211-235, 2004), was developed. The original Rubin and Terman model was able to reproduce both the physiological and pathological activities of STN, GPi, GPe and thalamo-cortical (TC) relay cells. In the present study, we introduced a representation of the direct pathway of the BGS, allowing a more complete framework to simulate DBS and to interpret its network effects in the BGS. Our results suggest that DBS in the STN could functionally restore the TC relay activity, while DBS in the GPe and in the GPi could functionally over-activate and inhibit it, respectively. Our results are consistent with the experimental and the clinical evidences on the network effects of DBS.

Ambulatory measurement of shoulder and elbow kinematics through inertial and magnetic sensors.

Inertial and magnetic measurement systems (IMMSs) are a new generation of motion analysis systems which may diffuse the measurement of upper-limb kinematics to ambulatory settings. Based on the MT9B IMMS (Xsens Technologies, NL), we therefore developed a protocol that measures the scapulothoracic, humerothoracic and elbow 3D kinematics. To preliminarily evaluate the protocol, a 23-year-old subject performed six tasks involving shoulder and elbow single-joint-angle movements. Criteria for protocol validity were limited cross-talk with the other joint-angles during each task; scapulohumeral-rhythm close to literature results; and constant carrying-angle. To assess the accuracy of the MT9B when measuring the upper-limb kinematics through the protocol, we compared the MT9B estimations during the six tasks, plus other four, with the estimations of an optoelectronic system (the gold standard), in terms of RMS error, correlation coefficient (r), and the amplitude ratio (m). Results indicate that the criteria for protocol validity were met for all tasks. For the joint angles mainly involved in each movement, the MT9B estimations presented RMS errors <3.6 degrees , r > 0.99 and 0.9 < m < 1.09. It appears therefore that (1) the protocol in combination with the MT9B is valid for, and (2) the MT9B in combination with the protocol is accurate when, measuring shoulder and elbow kinematics, during the tasks tested, in ambulatory settings.

Effects of Parkinson's disease and levodopa on functional limits of stability.

BACKGROUND: The voluntary, maximum inclined posture reflects the self-perceived limits of stability. Parkinson's disease is associated with small, bradykinetic postural weight shifts while standing but it is unclear whether this is due to reduced limits of stability and/or to the selection of abnormal strategies for leaning. The aim of this study was to investigate the effects of Parkinson's disease and levodopa medication on voluntary limits of stability and strategies used to reach these limits. METHODS: Fourteen subjects with Parkinson's disease (OFF and ON levodopa) and 10 age-matched controls participated in the study. Functional limits of stability were quantified as the maximum center of pressure excursion during voluntary forward and backward leaning. Postural strategies to achieve functional limits of stability were assessed by (i) body segments alignment, (ii) the difference between center of pressure and center of mass in preparation for a lean, (iii) the timing and the velocity of the preparation phase. FINDINGS: Functional limits of stability were significantly smaller in subjects with Parkinson's disease compared to control subjects. Subjects with Parkinson's disease maintained their stooped posture while leaning, initiated leaning with a smaller difference between center of pressure and center of mass and had a slower leaning velocity compared to control subjects. Levodopa enlarged the limits of stability in subjects with Parkinson's disease because of an increase in maximum forward, but not backward leans, but did not significantly improve postural alignment, preparation for a leaning movement, or velocity of leaning. INTERPRETATION: Parkinson's disease reduces functional limits of stability as well as the magnitude and velocity of postural preparation during voluntary, forward and backward leaning while standing. Levodopa improves the limits of stability but not the postural strategies used to achieve the leaning.

Identification of Characteristic Motor Patterns Preceding Freezing of Gait in Parkinson's Disease Using Wearable Sensors.

Freezing of gait (FOG) is a disabling symptom that is common among patients with advanced Parkinson's disease (PD). External cues such as rhythmic auditory stimulation can help PD patients experiencing freezing to resume walking. Wearable systems for automatic freezing detection have been recently developed. However, these systems detect a FOG episode after it has happened. Instead, in this study, a new approach for the prediction of FOG (before it actually happens) is presented. Prediction of FOG might enable preventive cueing, reducing the likelihood that FOG will occur. Moreover, understanding the causes and circumstances of FOG is still an open research problem. Hence, a quantitative characterization of movement patterns just before FOG (the pre-FOG phase) is of great importance. In this study, wearable inertial sensors were used to identify and quantify the characteristics of gait during the pre-FOG phase and compare them with the characteristics of gait that do not precede FOG. The hypothesis of this study is based on the threshold-based model of FOG, which suggests that before FOG occurs, there is a degradation of the gait pattern. Eleven PD subjects were analyzed. Six features extracted from movement signals recorded by inertial sensors showed significant differences between gait and pre-FOG. A classification algorithm was developed in order to test if it is feasible to predict FOG (i.e., detect it before it happens). The aim of the classification procedure was to identify the pre-FOG phase. Results confirm that there is a degradation of gait occurring before freezing. Results also provide preliminary evidence on the feasibility of creating an automatic algorithm to predict FOG. Although some limitations are present, this study shows promising findings for characterizing and identifying pre-FOG patterns, another step toward a better understanding, prediction, and prevention of this disabling symptom.

Serum lactate in liver resection with intermittent Pringle maneuver: the "square-root- shape.

BACKGROUND: Serum lactate (sLac) concentration during liver resection with intermittent hepatic hilum clamping (i.e. Pringle maneuver, PM) was retrospectively investigated. METHODS: A total of 133 patients who underwent liver resection were enrolled. We analyzed the sLac peri-operatively. Correlations were searched between the PM and lactatemia and its variations (i.e. lactate clearance, cLac) and other factors which it might be related to. Lactatemia in triplicate intraoperatively was recorded, just after the awakening, and 1 and 2 h later. The cLac between two consecutive measurements [(sLac1 - sLac2 )/sLac1 ] was computed. RESULTS: A reliable dependence of sLac was found from the cumulative PM. More than 76 min of cumulative Pringle Time (cPT) exposed patients to a worse cLac at the end of the resection phase (P < 0.0001). We found cPT >76 min, global operation time >365 min and bleeding >225 ml to be predictors of hyperlactatemia (sLac >4 mmol/L). Normal liver resulted as a risk factor for hyperlactatemia and steatosis was not (P = 0.030 vs. P = 0.325). Finally, cLac showed a "square-root- shape, just like the mathematical operation sign. CONCLUSIONS: Lactatemia during liver resection depends on the duration of PM, bleeding and the duration of the operation. Normal liver may expose the patient to the risk of hyperlactatemia.

Identification of distinct characteristics of postural sway in Parkinson's disease: a feature selection procedure based on principal component analysis.

We selected descriptive measures of the centre of pressure (CoP) displacement in quiet standing, by means of a procedure based on principal component analysis, in two groups particularly different in terms of postural behaviours, such as subjects with Parkinson's disease (PD) in the levodopa off and on states. We computed 14 measures of the CoP: 5 measures of CoP trajectory over the support surface, 3 measures that estimated the area covered by the CoP, 1 measure that estimated the principal CoP sway direction, 1 measure that quantified the CoP total power, 1 measure that estimated the variability of CoP frequency content and 3 measures of characteristic CoP frequencies [L. Rocchi, L. Chiari, A. Cappello, Feature selection of stabilometric parameters based on principal component analysis, Med. Biol. Eng. Comput. 42 (2004) 71-79; L. Rocchi, L. Chiari, F.B. Horak, Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease, J. Neurol. Neurosurg. Psychiatry, 73 (2002) 267-274]. The feature selection, independently applied to the measures obtained in the two groups, resulted in different principal component (PC) subspaces of the 14-dimension original data set (4 PCs in the off and 3 PCs in the on state to account for over 90% of the original variance), but in the same 5 CoP measures (selected features) needed to describe the different postural behaviours: root mean square distance; mean velocity; principal sway direction; centroidal frequency of the power spectrum; frequency dispersion. The five selected features were found to provide insight into the postural control mechanisms and to describe changes in postural strategies in the two groups of PD subjects, off and on levodopa. Thus, the five selected features may be recommended for use in clinical practice and in research, in the direction toward the definition of a standard protocol in quantitative posturography.

Step initiation in Parkinson's disease: influence of initial stance conditions.

In this study, we investigated how the size of preparatory postural adjustments prior to step initiation, and step length and velocity depend on initial stance width in patients with Parkinson's disease (PD) both in the ON and OFF levodopa states and in healthy elderly subjects. Twenty-one subjects with idiopathic PD and 24 age-matched healthy control subjects took two steps starting with feet on a two-plate force-platform, from either narrow or wide stance width. We measured how the magnitude of anticipatory postural adjustments (APA) and step characteristics scaled with stance width. Results showed that preparation for step initiation from wide stance was associated with a larger lateral and backward center of pressure (CoP) displacement than from narrow stance. Velocity and length of the first step were also sensitive to initial stance conditions, probably in relation with the differences in the corresponding APA. On the contrary, the duration of APA was not significantly affected by initial stance width, but it was longer in PD compared to healthy subjects, and speeded up by levodopa. Although subjects with PD did scale up the size of their APA with stance width, they had much more difficulty initiating a step from a wide stance than from a narrow stance, as shown by the greater differences from control subjects in the magnitude of the APA. Our results support the hypothesis that PD subjects maintain a narrow stance as a compensation for their inability to sufficiently increase the size of their lateral APA to allow fast step initiation in wide stance.