Jacob Kaplanski

Age-Related Changes of Postural Control: Effect of Cognitive Tasks

Background: Postural control and falls in the elderly constitute a major health problem. The interest in balance deficits is growing, as concern about the rising costs of health care increases. This issue is particularly relevant to the elderly population in which falls occur most frequently. Postural control in the elderly was studied using a cognitive approach. Objective: The purpose of this study was to study the characteristics of central processing of postural control while performing cognitive tasks. Methods: A dual-task procedure was developed to estimate the level of automaticity of a quiet upright standing task. The effect of a concurrent attention-demanding task (modified Stroop test) on the efficiency of balance control in the elderly was determined using force platform and electromyography measurements. Results: It was found that there is an increase in postural sway in old subjects compared with young subjects when performing single tasks and dual-task tests. The results of the study demonstrate that postural adjustments require cognitive processing; young and old subjects showed similar interference effects on postural steadiness (postural sway) caused by the concurrent attention-demanding task. The results are corroborated by the hypothesis that a dual task gives information on the restoration of automaticity of postural control in old age by a central reorganization process. When performing a dual task tested on a narrow base of support, the old subjects decreased their body sway, while the younger did not. According to electromyography measurements, the older subjects increased their muscle activity in the tibialis anterior and soleus muscles, using slow-twitch motor units compared with the younger subjects. Conclusions: Both alterations (cognitive and base of support) have a substantially greater effect on the elderly than on the young. The older subjects decreased their body sway by activating a cocontraction strategy of postural control around the ankle joint, probably because of the danger to their postural stability.

Effects of Regular Walking on Postural Stability in the Elderly

Background: Both age and lack of physical activity may be responsible for poor health and poor balance control. Conversely, physical activity may modulate postural control in elderly people. Objective: An observational study was performed in older adults to explore whether walking on a regular basis might prove to be beneficial not only to the cardiovascular system but also to maintaining a good balance. Methods: Twenty-two healthy older subjects walking on a regular basis (DW group) and 121 healthy control older subjects who did not walk regularly (NW group) were studied. The subjects included in the study were free from major gait and postural disorders. An instrumented force platform was used to measure the time-varying displacements of the center of pressure under eight static conditions and postural limit tests. An isometric test was performed to evaluate lower limb muscle strength, and a static two-point discrimination test evaluated the innervation density of the slowly adapting receptors of the sole of the first toe. Results: The DW group had a significantly better (p < 0.05) postural stability under static conditions than the NW group. There were no significant differences in postural limit tests and in two-point discrimination between the groups. The DW group had significantly higher values of ankle plantar flexor and knee extensor strengths, while there were no significant differences in ankle dorsiflexors and knee flexors. None of the DW group reported experiencing a fall during the previous 6 months compared with 16% in the NW group who reported at least two falls during the last half year. Conclusions: Walking on a regular basis in old age may have the potential to modulate stability. It was found that healthy older subjects, who walked on a regular basis since their retirement, have better postural control, especially in their static balance, than those who do not. The laboratory results were accompanied by the important finding that although older subjects who walk on a regular basis walked much more than nonwalkers, they did not suffer from falls.

Comparison of efficacy of Adeli suit and neurodevelopmental treatments in children with cerebral palsy

This study compared the efficacy of Adeli suit treatment (AST) with neurodevelopmental treatment (NDT) in children with cerebral palsy (CP). Twenty‐four children with CP, Levels II to IV according to the Gross Motor Function Classification System (GMFCS), were matched by age and functional status and randomly assigned to the AST or NDT treatment groups. In the AST group (n=12; eight males, four females; mean age 8.3y [SD 2.0]), six children had spastic/ataxic diplegia, one triplegia and five spastic/mixed quadriplegia. In the NDT group (n=12; nine males, three females; mean age 8.1y [SD 2.2]), five children had spastic diplegia and seven had spastic/mixed quadriplegia. Both groups were treated for 4 weeks (2 hours daily, 5 days per week, 20 sessions). To compare treatments, the Gross Motor Function Measure (GMFM‐66) and the mechanical efficiency index (EIHB) during stair‐climbing were measured at baseline, immediately after 1 month of treatment, and 10 months after baseline. The small but significant time effects for GMFM‐66 and EIHB that were noted after 1 month of both intensive physiotherapy courses were greater than expected from natural maturation of children with CP at this age. Improvements in motor skills and their retention 9 months after treatment were not significantly different between the two treatment modes. Post hoc analysis indicated a greater increase in EIHB after 1 month (p=0.16) and 10 months (p=0.004) in AST than that in NDT, predominantly in the children with higher motor function (GMFCS Levels II and III). The results suggest that AST might improve mechanical efficiency without a corresponding gain in gross motor skills, especially in children with higher levels of motor function.

Association between ankle muscle strength and limit of stability in older adults

SIR—Loss of balance and falls in the elderly constitute a major problem associated with human suffering as well as high costs for society [1]. Falls might occur during various daily activities, such as tripping or tangling the feet, reaching movements or bending [2]. Many of these activities are constrained by limits of stability (LOS). LOS can be described as the maximum distance a person can intentionally displace his/her centre of gravity, and lean his/her body in a given direction without losing balance, stepping or grasping. Accordingly, ones LOS capacity is likely to be an important prerequisite for the successful planning and execution of movements such as using a step stool to reach into a high cabinet as well as bending over from standing position to pick up an object from the floor. Ageing is associated with decreased LOS [3–5], muscle strength [6] and foot sensation [7]. Investigators have reported significant correlations between postural stability, quadriceps, ankle dorsiflexion and hand-grip strength [8–11], tibialis anterior latency [8] and functional clinical balance testing [12] among older adults. However, the relationships between lower-limb muscle strength and falls are unclear. Several studies show minimal or no differences in strength between fallers and non-fallers [13, 14] while others show no strength–falls relationships [15]. Cutaneous mechanoreceptors at the soles of the feet contribute to postural stability when standing [16]. Those with reduced feet sensation have a higher risk of falling [17] and greater instability [18]. Reduced foot sensation may contribute to reduced LOS, since older adults might not properly detect when the centre of gravity approaches the LOS. To our knowledge, no one has studied how postural control during LOS relates to ankle strength and foot sensation among older adults. The aims of this study are to investigate how two specific tests of postural control, LOS and postural stability, relate to ankle muscle strength and foot sensation in older adults. Identification of sensorimotor factors associated with both types of balance control can help us to understand better the balance problems facing older adults. Given that LOS likely requires highly active muscular control and that postural stability requires careful sensory monitoring of stance, we hypothesised that ankle muscle strength (and not foot sensation) will be significantly correlated with LOS and that foot sensation (and not ankle muscle strength) will be significantly correlated with postural stability. Data from this study may lead to a better understanding of the mechanisms underlying falls that occur during reaching and bending movements.

Chapter 9 Brain eicosanoids and LPS fever: species and age differences

The results of the present study, summarized in Table 2, demonstrate that different species and strains of rodents (rats and mice) and birds (chickens) exhibit rather specific fever response. Systemic administration of LPS caused monophasic elevation in Tb of chickens, biphasic changes in Tb of rats (initial drop followed by an increase in Tb), whereas mice failed to develop hyperthermia and responded by a decreased Tb. The LPS-induced alterations in hypothalamic prostanoid synthesis were also rather species-specific and differ markedly even between the two strains of mice. We failed to find a common direct correlation between LPS-induced changes in Tb and hypothalamic prostanoid production in rodents (rats and mice). This observation is supported by our recent study on age-related changes in fever response in rats, where we found that hypothalami of LPS-treated old and young adult rats produced similar amounts of PGE2 and PGI2, in spite of more pronounced and prolonged hypothermia, and a delayed elevation in Tb of old rats, as compared with young (Fraifeld et al., 1995b). Moreover, the hypothalamus of febrile chickens did not display any detectable activation of PGE2 production, suggesting that PGE2 is not a common central mediator of fever in homeotherms (Fraifeld et al., 1995a). Apparently, the actual body temperature not always reflects the functional state of central thermostat, and increased PGE2 production in hypothalamus would not directly, at least in rodents, lead to body temperature elevation. Furthermore, peripheral effects, including PG-mediated ones, of pyrogens can interfere and even overcome their centrally-mediated effects (Morimoto et al., 1991; Burysek et al., 1993). Previously, we have shown that no additional elevation in hypothalamic PGE2 production occurs in response to doses of LPS over 10 micrograms in rats and 25 micrograms in mice, while the increased doses led to further changes in Tb response (Kaplanski et al., 1993). Morimoto et al. (1991) have considered that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and, hence, these opposing actions, both being induced by LPS, may act together to determine the final thermoregulatory response. Other possibilities could be related to counterbalance of endogenous antipyretics (Kluger, 1991; Kozak et al., 1995), that may occur not only at the level of thermoregulatory center but also outside the CNS (Klir et al., 1995), and to the existence of PG-independent mechanisms of LPS fever. The latter have been shown for IL-8 (Rothwell et al., 1990; Zampronio et al., 1994) and MIP-1 (Davatelis et al., 1989; Minano et al., 1990; Hayashi et al., 1995; Lopez-Valpuesta and Myers, 1995), which are, apparently, mediated via CRF (Strijbos et al., 1992; Zampronio et al., 1994), and INF-alpha, mediated via the opioid receptor mechanisms (Hori et al., 1991, 1992). However, it has been shown recently that in different species the same pyrogenic cytokines (IL-8) may induced fever via different, PG-independent (in rats; Zampronio et al., 1994) or PG-dependent (in rabbits; Zampronio et al., 1995) mechanisms. It should be noted that fever response is not always accompanied by an elevation in Tb. The final effect of pyrogens on body temperature depends upon the balance between heat production and heat loss, which in turn is highly dependent upon body size and ambient temperature, especially in small animals. Perhaps, the hypothermic response observed in our mice and rats at 22 degrees C may be in part attributed to ambient temperature, which was below a thermoneutral zone. The reduced febrile response is considered, at least in part, to contribute to an increased mortality and prolonged recovery from infections (Kluger, 1986). From this point, it is difficult to suggest whether the hypothermia observed in our mice and rats could be of somewhat adaptive significance. It has been shown that at the ambient temperature of 30 degrees C, Swiss Webster mice can re

Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice

The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-α (TNF-α), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 μg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-α level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-α. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-α bioactivity.The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-alpha (TNF-alpha), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 microgramg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-alpha level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-alpha. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-alpha bioactivity.

Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures

Several lines of evidence link inflammation with neurodegenerative diseases, which are aggravated by the age-related decline in estrogen levels in postmenopausal women. Lipopolysaccharide (LPS) is used widely to stimulate glial cells to produce pro-inflammatory mediators such as NO, PGE2, and TNF-α, and was found to be toxic in high doses. We examined the effects of a physiological dose of 17β-estradiol (E2) against LPS-induced inflammation and toxicity (cell death) in rat primary glial and neuronal cultures. Cultures were treated with 0.1 nM E2 for 24 h and then exposed to LPS 0.5—200 µg/ml for another 24 h. Levels of NO, PGE2, and TNF-α in the culture medium were determined by the Griess reaction assay, radio-immunoassay, and enzyme-linked immunoassay, respectively. Cell death was quantified by measuring the leakage of lactate dehydrogenase (LDH) into the medium from dead or dying cells using the non-radioactive cytotoxicity assay. E2 significantly reduced the LPS-induced increase in NO and TNF-α (but not PGE2) production in glial cells. PGE 2 and TNF-α were undetectable in neuronal cultures, while only basal levels of NO were detected, even after stimulation with LPS. Moreover, pretreatment with E2 significantly reduced LPS-induced cell death, as measured by the release of LDH, in both glial and neuronal cultures. These results suggest that the neuroprotective effects attributed to E2 are derived, at least in part, from its anti-inflammatory and cytoprotective effects in both glial and neuronal cells.

Effectiveness of motor learning coaching in children with cerebral palsy: a randomized controlled trial

Objective: To evaluate effectiveness of motor learning coaching on retention and transfer of gross motor function in children with cerebral palsy. Design: Block randomized trial, matched for age and gross motor function. Setting: Coordinated, multinational study (Israel, Jordan and Palestinian Authority) in schools and rehabilitation centers. Subjects: 78 children with spastic cerebral palsy, gross motor functional levels II and III, aged 66 to 146 months. Interventions: 1 hr/day, 3 days/week for 3 months treatment with motor learning coaching or neurodevelopmental treatment: two groups. Main measures: Gross motor function Measure (GMFM-66), stair-climbing mechanical efficiency (ME) and parent questionnaire rating their child’s mobility. Immediate treatment effects were assessed after 3 months and retention determined from follow-up measurements 6 months after treatment. Results: GMFM-66, ME and parent questionnaires were obtained from 65, 31 and 64 subjects, respectively. Although both groups increased GMFM-66 score over 3 months, measurements 6 months later indicated retention was significantly superior by 2.7 in the motor learning coaching children of level-II. Similar retention trend was evident for ME, increasing 6 months after motor learning coaching by 1.1% and declining 0.3% after neurodevelopmental treatment. Mobility performance in the outdoors and community environment increased 13% from 3 to 9 months after motor learning coaching and decreased 12% after neurodevelopmental treatment. Minor group differences occurred in children of level-III. Conclusions: In higher functioning children with cerebral palsy, the motor learning coaching treatment resulted in significantly greater retention of gross motor function and transfer of mobility performance to unstructured environments than neurodevelopmental treatment.

Is hypothalamic prostaglandin E2 involved in avian fever

In chickens, the effect of Escherichia coli lipopolysaccharide (LPS) on body temperature and ex vivo hypothalamic prostaglandin E2 (PGE2) production was examined to test the possible involvement of PGE2 in mechanisms of avian fever. PGE2 is reported to be the major central mediator of fever in mammals; it has not been examined in birds. An intraperitoneal injection of LPS caused an elevation of body temperature but not an elevation of hypothalamic PGE2 production. It seems that: (a) hypothalamic PGE2 is not involved in the development of the febrile response in birds; (b) central mechanisms of avian fever differ from those in mammals.

Time-dependent effect of LPS on PGE2 and TNF-α production by rat glial brain culture: influence of COX and cytokine inhibitors

This study was undertaken to investigate the effect of lipopolysaccharide (LPS) stimulation on the time course of prostaglandin E2 (PGE) and tumor necrosis factor alpha (TNF-α) production by rat glial brain culture. A concentration of 210 µg/ml LPS from Escherichia coli was used as stimulation treatment. The effect of pentoxifylline (PXF), nimesulide (NIM), indomethacin (INDO) and dexamethasone (DEX) on the regulation of PGE2 and TNF-α production was tested. Stimulation of rat glial cells with LPS resulted in different time-dependent production patterns of PGE2 and TNFα. The time course of TNF-α elevation was short, reaching its peak at 6 h post LPS and decreasing to undetectable levels after 24 h. On the other hand, the time course of PGE2 elevation was longer, starting at 6 h post LPS treatment and increasing 100-fold compared with basal levels, 24 h post LPS exposure. The COX inhibitors (NIM and INDO) and DEX were found to inhibit the LPS-induced elevation in PGE2 production, while PXF lacked such an inhibitory effect. Furthermore, NIM, DEX and PXF were found to reduce the LPS-induced elevation in TNF-α levels, while INDO caused a greater elevation in TNF-α levels. These results may cast further light on the LPS-induced production of PGE2 and TNF-α by rat glial cell cultures and the relation between the two systems.