Effects of Constraint-Induced Movement Therapy on upper limb activity according to a bi-dimensional kinematic analysis in progressive multiple sclerosis patients: a randomized single-blind pilot study.

Multiple sclerosis (MS) is a chronic disease of the central nervous system, characterized by demyelinization and axonal loss resulting, in 66% of cases, in upper limb motor impairment. The effects of constraint-induced movement therapy (CIMT) have recently been investigated in MS patients. The aim of this randomized single-blind pilot study was to assess the effects of CIMT on upper limb activity, specifically smoothness of movement, in patients affected by progressive MS. Patients affected by MS, and reporting reduced use primarily of one upper limb, were enrolled and randomly allocated to two different groups: a CIMT group, where treatment was performed with the less affected limb immobilized by a splint, and a control group, submitted to intensive bi-manual treatment. All evaluations were performed at baseline (T0) and after two weeks of treatment (T1) by an operator unaware of the patients' allocation. The primary outcome was the difference in movement smoothness, measured by means of a bidimensional kinematic evaluation. Secondary outcomes were: endpoint error and arm trajectory mean speed. Furthermore, patients performed the Hand Grip Strength Test (HGS) and 9-Hole Peg Test (9HPT), for both arms, at both time points. Ten patients with MS (4 males, 6 females; mean age 51.0±7.7 years) were randomly allocated to the CIMT group (n=5) and control group (n=5). There were no significant differences between groups in any of the data assessed at baseline. In the CIMT group subjects, the treatment effect, in terms of movement smoothness, was significant at the more affected limb (p=0.0376). The CIMT group displayed statistically significant improvements, versus the baseline values, in muscle strength (HGS:22.4±8.3 vs 26.0±6.0; p<0.05) and dexterity (9HPT: 31.8±6.1 vs 27.4±4.9; p<0.05) of the more affected limb. A positive, although not significant, trend in terms of muscle strength and upper limb dexterity was observed, for both limbs, in the control group after the two-week treatment. Bi-dimensional kinematic evaluation demonstrated that the CIMT group showed a significant reduction of endpoint error and higher mean speed for the more affected arm; these data are in line with the significant improvements recorded on the HGS and 9HPT. Moreover, in the CIMT group, a non-significant worsening of muscle strength was recorded for the less affected upper limb.

Quantitative evaluation of functional limitation of upper limb movements in subjects affected by ataxia.

BACKGROUND AND PURPOSE: The design of useful and effective treatment strategies for movement disorders largely depends on the ability to objectively quantify changes in performances, providing reliable outcome measures. Evaluation of ataxia remains mainly assigned to different clinical scales, providing a semi-quantitative assessment. The aim of this study was to quantitatively characterize functional changes in upper limb movements in ataxic patients, using an optoelectronic system for objective measurements. METHODS: Fourteen patients with cerebellar ataxia and 27 healthy subjects were analyzed using an optoelectronic system with passive markers during pointing task and hand-to-mouth movement. Quantitative parameters capable of characterizing ataxic movements were defined using recorded kinematics. RESULTS: In both the considered functional movements, ataxic patients showed increased adjustment during the last phase of movement. The movement was less smooth than that in controls, with a fragmented trajectory presenting more direction changes than controls. CONCLUSIONS: The proposed protocol allows the quantitative characterization of the motion pattern of ataxic subjects in a non-invasive way. We believe that this analysis could represent a good tool for ataxia evaluation in a clinical context such as neurorehabilitation.

Depression is the main determinant of quality of life in multiple sclerosis: a classification-regression (CART) study.

PURPOSE: Quality of life in multiple sclerosis has been often measured through the SF-36 questionnaire. In this study, validation of the SF-36 summary scores, its 'physical' component, and its 'mental' component was attempted by exploring the joint predictive power of disability (EDSS score), of anxiety and depression (HADS-A and -D scores, respectively), and of disease duration, progression type, age, gender and marital status. METHOD: The sample consisted of 75 patients suffering from multiple sclerosis admitted to an inpatient rehabilitation unit. The interplay between potential predictors was assessed through a particular regression model (classification and regression tree, CART). Two main advantages of this technique are its robustness with respect to distributional assumptions (rarely met by scores coming in from questionnaires) and its sensitivity to high-order interactions, between independent variables, difficult to detect through conventional multiple regression. RESULTS: Predictive variables for physical component of the SF-36 were EDSS and HADS-D (36.8% variance explanation). The only predictive variable for mental component of SF-36 was HADS-D (39.1% variance explanation). CONCLUSION: Results confirm previous findings showing that in patients with multiple sclerosis quality of life is heavily determined by person's mood, whatever his/her neurological or functional severity. The usefulness and validity of the SF-36 as an index representative of quality of life is debatable, as long as depression explains much of its variance. Further refinement of quality of life definition and measurement is worth further psychometric and statistical research.

How does stroke restrict participation in long-term post-stroke survivors?

OBJECTIVE: To explore the factors determining 'restricted participation' in a selected population of long-term post-stroke survivors. MATERIALS AND METHODS: Seventy-three consecutive post-stroke inpatients were scored for mood and restriction in participation by means of self-administered questionnaires, respectively the Hospital Anxiety and Depression Scale (HADS/A; HADS/D) and London Handicap Scale (LHS). Neurological impairment and functional disability were evaluated with the Unified Neurological Stroke Scale (UNSS) and Functional Independence Measure (FIM). RESULTS: Physical independence and occupation were the most severely affected domains on the LHS. UNSS, FIM, HADS/A, HADS/D scores were significant determinants of restriction in participation at univariate analysis performed with each LHS domain. FIM score and emotional status finally emerged as the independent determinants of restricted participation for the LHS domains most related to body function (mobility, physical independence, occupation). Depression was the determinant factor for orientation and social integration. CONCLUSION: Functional disability and mood disorders may independently contribute to the restricted participation of post-stroke patients. Most of the LHS domains remain stable over time.

Body composition in advanced-stage Parkinson's disease.

Little is known about body composition in Parkinson's disease (PD). We studied 35 patients (20 male, 15 female subjects; mean age 69.7+/-5.8 years) with advanced PD by anthropometry, dual-energy X-ray absorptiometry (DEXA), and serum 25-OH vitamin D measurement. Over 70% of patients had a disease duration of more than 4 years; all were on L-dopa treatment. Low levels of serum 25-OH vitamin D were present in 41% of the patients. The mean body mass index (BMI) was 25.3+/-4.3 kg/m(2) (range 17.1-37.3). Mid-arm muscle circumference was below the 10th percentile in 23%. For whole-body mean (+/-SD) bone mineral density, the T score was below -1 SD in 35% of patients, and the Z score was below -1 SD in 24%. Percent fat mass measured with DEXA was 30.6+/-11.4% (range 10.1-45.5) in the overall sample; it was 21.1+/-8.8% (range 10.1-30.4) in male subjects and 38.1+/-9.2% (range 25.8-45.5) in female subjects. We conclude that advanced-stage PD may show excess adiposity coexisting with depletion of lean body mass (sarcopenic obesity), in addition to decreased whole-body bone mineral density associated with low serum 25-OH vitamin D. A low level of physical activity and inadequate exposure to sunlight are likely to be among the putative causes.

Are the neurophysiological techniques useful for the diagnosis of diaphragmatic impairment in multiple sclerosis (MS)?

OBJECTIVE: To characterize cortico-diaphragmatic pathway involvement in multiple sclerosis (MS) by means of transcranial magnetic stimulation (TMS), and verify its clinical impact. METHODS: TMS from diaphragm (Dia), and abductor digiti minimi (AbdV degrees ) was performed in 26 MS patients. Phrenic nerve (PN) conduction study was also performed. Expanded disability status scale (EDSS) and fatigue descriptive scale (FDS) were measured. Forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), peak expiratory flow (PEF) were tested: the predicted percentage value (% pred) was considered. RESULTS: Cortical motor evoked potential (Cx-MEP) latency and central motor conduction time (CMCT) were prolonged, respectively, in 31 and 23% of patients from Dia, in 76 and 79% from AbdV degrees. PN-compound motor action potential (CMAP) was normal. EDSS correlated to Cx-MEP from AbdV degrees (P<0.01), and PN-CMAP amplitude (P<0.05), FEV1 % pred (P<0.01), PEF % pred (P<0.01). PN-CMAP amplitude correlated to FVC % pred P=0.05, FEV1 % pred P<0.01, PEF % pred P<0.01. Fatigue was related to AbdV degrees Cx-MEP and CMCT (P<0.05 and P<0.01). CONCLUSIONS: Cortico-diaphragmatic pathway is impaired only in a minority of MS patients. Lack of correlation between TMS findings from Dia and respiratory tests argues against its routinary use to detect subclinical respiratory alterations. Fatigue seems to be related to the motor impairment rather than to respiratory distress.

Controlled-release transdermal apomorphine treatment for motor fluctuations in Parkinson's disease.

This study evaluated the efficacy in Parkinson's disease (PD) of a new pharmacologic preparation of apomorphine included in microemulsions and administered by transdermal route, which provides a constant release of the drug for several hours (Apo-TD). Twenty-one PD patients with motor fluctuations were treated with L-dopa alone, with L-dopa plus oral dopamine-agonists, or with L-dopa plus Apo-TD. Apo-TD improved UPDRS-III and tapping test scores in "off" conditions, and reduced duration of "off" periods; no improvement in "on" conditions occurred. We conclude that Apo-TD shows its efficacy particularly by reducing "off" period duration and disability rather than improving motor performances in "on" conditions and therefore it seems a promising treatment for uncontrolled "off" phases in PD patients.

Oxygen uptake and cardiac performance in obese and normal subjects during exercise.

Work capacity and cardiopulmonary performance were studied in a group of 11 young obese subjects (BMI 39.9 kg/m2) and a group of 10 young normal subjects (BMI 22 kg/m2). First of all they underwent an incremental cycle ergometer test up to exhaustion. Subsequently, every subject of the two groups performed a constant work rate test at different work loads to estimate cardiac output (Q) below anaerobic threshold (AT) by a 20-second CO2 rebreathing method. Obese subjects had a significantly lower AT (79 vs. 109 W). The ratio between oxygen uptake and heart rate (VO2/HR) (O2 pulse) was higher in the obese group; nevertheless, this variable became significantly lower if we took into consideration the ratio between O2 pulse and kilogram fat-free body mass or kilogram body weight. Both these observations suggest that their reduced work tolerance is linked with a reduced oxygen supply to the muscles in activity. Q increased in similar ways in obese and normal subjects at the preset work rates. The ratio Q/body surface (cardiac index; CI) that we considered in order to try to minimize the differences in body sizes between the two groups, increased less in response to increasing work rates in our obese subjects than in normal subjects. As a whole, these data appear to be in line with a relatively less efficient cardiac performance during progressive work rates in obese subjects.

Metabolic aspects and sympathetic effects in the obese subject undergoing exercise testing.

An impaired plasma Epinephrine (E) and Norepinephrine (NE) response has been described in obese patients during physical exercise. Serum potassium level is influenced either by physical exercise or by the adrenergic system. We studied 12 young obese patients and 12 young controls, all without any cardio-respiratory disorders, who underwent a cycloergometric test with steps of 20 watts every four minutes until exhaustion. During the test we recorded serum potassium levels, E and NE, insulin, glucose and RQ to confirm or not the observation of the reduced adrenergic response in obese patients. During exercise, although both groups reached a not significantly different mean peak value of maximal activity, E and NE increased, more in the controls than in the obese subjects (at peak of exercise 221 +/- 44.1 vs 71 +/- 21.5 pg/ml respectively for E; 2035 +/- 164.8 vs 1141 +/- 313.7 pg/ml respectively for NE). RQ was constantly lower in the obese patients than in the normals both during and after the stress. In both groups potassium increased significantly, but the obese patients had a significantly lower increment at peak of activity when compared to the controls (delta K+: 0.52 +/- 0.11 vs 1.007 +/- 0.17 meq/l respectively, p < 0.05). Insulin and glucose had a behaviour in line with literature in both groups. The behaviour of potassium could be an index of a higher effect of beta-adrenergic system in obese patients than in normals despite the different increases of catecholamines in the two groups. This hypothesis may agree with the preferential metabolic use of fatty acids in our obese patients as indicated by RQ values.

Catecholamine-stimulated potassium transport in erythrocytes from normal and obese subjects.

The beta adrenergic-modulated Na+/K+ ATPase pump rate of red blood cells was measured in vitro in 18 non diabetic obese patients. After challenge of erythrocytes with beta adrenergic selective agonist Salbutamol, the decrement of the K+ concentration in the suspending medium was assumed to be related to the Na+/K+ ATPase pump rate or to the number of beta 2 receptors. The mean K+ uptake was markedly increased in the erythrocytes of obese patients (1.58 mEq/l SD 0.18) if compared with 38 normal subjects (1.30 mEq/l SD 0.11) and with a population of 30 atopic patients that we have previously reported to have a reduced red cells beta 2 receptor activity (1.09 mEq/L SD 0.11). These results are not consistent with the hypothesis that a reduction in the Na+/K+ ATPase pump rate (at least in red blood cells) may be responsible for decreased metabolic rates leading to obesity. Since the autonomic nervous system is involved in the regulation of the cardiovascular system, it is conceivable that an increased Na+ ATPase pump rate (or supersensitivity) may be responsible of the increased incidence of hypertension, congestive heart failure and unexplained sudden death associated with obesity in some patients.

Relationship between body mass and tolerance to physical stress in obese patients.

Eleven obese patients, 5 males; age: 17-42; body mass index (BMI): 40; % of ideal weight: 187%, and 10 normal subjects (5 males; age: 19-39; BMI: 22; % of ideal weight: 103%), both groups without heart and respiratory disorders, underwent a cycloergometric test with subsequent 20-watt increases every 4 min until exhaustion. During the test, ventilation/minute, expiratory gas concentration and heart rate were measured, and the anaerobic threshold (AT) was determined in each subject. The obese patients showed a significantly lower AT than normal subjects (p less than 0.01); showing values which decreased with the increase in the grade of obesity expressed in BMI or in percent of their ideal weight. Moreover, in the obese patients, the O2 consumption (VO2) had significantly increased compared to that of normal subjects at no resistance and at all work levels. The negative correlation between the AT value and the BMI in obese patients can attribute their increase in VO2 during stress to (1) the inertial overloading caused by obesity especially considering the adipose tissue of their legs, or (2) to their level of 'fitness' being lower than that of normal subjects.