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PubMed1998

Cytokine mediation of ozone-induced pulmonary adaptation.

Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.

Adaptation, Physiological↗
PubMed1968

An extrarenal mechanism of potassium adaptation.

Rats fed a diet high in potassium for several days survive an acute load of potassium that is lethal to animals on a regular diet. Previous data suggested that this survival occurred because of enhanced kaluresis. Although increased urinary excretion may occur, the major mechanism of this potassium adaptation phenomenon has been found to be extrarenal. Despite nephrectomy just before study, rats previously fed a high potassium diet maintained lower plasma potassium concentrations for at least 2 hr after an acute potassium load than did rats fed a regular diet. Prior adrenalectomy abolished adaptation. Furthermore, rats fed a low sodium diet as an alternative stimulus to aldosterone secretion demonstrated adaptation to potassium loading, as did adrenalecomized rats given large doses of deoxycorticosterone for several days. Adrenalectomy just before the test load of potassium did not abolish adaptation nor did a large dose of aldosterone at that time reproduce it. These data indicate that adaptation is dependent on a chronic increase in aldosterone secretion. The extra potassium removed from the extracellular fluid by adapted rats was not lost into the gastrointestinal tract. It is concluded that more rapid lowering of plasma potassium after acute potassium loads by adapted rats is due to enhanced uptake of potassium by one or more tissues stimulated by chronic aldosteronism.

Adaptation, Physiological↗
PubMedDate not supplied

Malnutrition impairs postresection intestinal adaptation.

BACKGROUND: Postresection intestinal adaptation is influenced by several factors, including luminal nutrients. Adaptation is impaired in the absence of luminal nutrients, even if the nutrition is maintained via total parenteral nutrition (TPN). Reduced enteral intake also inhibits adaptation if malnutrition is present, but the mechanism has not been completely defined. Our aim was to study the effect of reduced enteral nutrition on adaptation and enterocyte production and death after 50% proximal resection in rats. METHODS: Eighteen Lewis rats underwent either transection (n =6) or 50% proximal resection (n =12). The resected animals either ate ad libitum (n = 6) or were offered 75% of ad libitum intake (n =6). Nutritional status and intestinal adaptation were determined 14 days after surgery. RESULTS: Resected animals receiving 75% normal intake had decreased body weight (89% +/- 4% vs 112% +/- 2% and 112% +/- 1%, p < .05) and serum albumin (2.7 +/- 0.1 vs 3.2 +/- 0.0 g/dL and 3.0 +/- 0.1 g/dL, p < .05) compared with resection with normal intake and transection, respectively. Intestinal weight (0.32 +/- 03 vs 0.22 +/- 0.02 g/cm and 0.19 +/- 0.03 g/cm, p < .05) and diameter (10.5 +/- 0.5 vs 8.5 +/- 1.0 mm and 7.8 +/- 0.8 mm, p < .05) increased after resection alone compared with transection and malnourished resection groups. Gut weight and diameter and villus height were lower in malnourished resected animals than with transection. Crypt cell production rate was significantly lower in the reduced intake animals. Apoptosis was increased in both crypt and villus enterocytes in normally nourished but not malnourished resected animals. Villus apoptosis correlated with villus height. CONCLUSIONS: Intestinal adaptation is impaired by a 25% reduction in enteral nutrients, confirming that both the route and quantity of nutrient intake are important in this process. Both enterocyte production and loss via apoptosis are decreased by reduced enteral intake and malnutrition after resection. The correlation between villus height and apoptosis suggests that the reduced apoptosis reflects the smaller enterocyte number in malnourished animals rather than an adaptive response to maintain intestinal structure.

Adaptation, Physiological↗
PubMed1993

Adaptation to chronic illness: a program of research for testing nursing theory.

The adaptation to chronic illness framework, an elaboration of the Roy adaptation model for chronic illness, provided direction for a program of nursing research. The purposes of investigations within the program were (a) to identify predictors of adaptation to chronic illnesses and (b) to determine whether the relationships between the variables differed by diagnostic group. A total of 597 adults, representing various chronic illness groups, participated in longitudinal studies during a seven-year period. Health-related hardiness and engagement in health promotion activities consistently predicted both physiological and psychosocial adaptation in all chronic illness groups. In addition, the individual's perception of the degree of disability caused by the illness was related to psychosocial functioning. Comparison of adaptive responses between the groups revealed significant differences in physiological adaptation but no significant differences in psychosocial adaptation. Results clarify relationships posited using the theoretical framework and support the value of using nursing models to guide nursing research.

Adaptation, Psychological↗
PubMed2006

Saccadic adaptation in children.

Saccades are fast-orienting eye movements. Saccadic adaptation, a form of motor learning, is a corrective change in the amplitude of saccades in response to error. The aim of the study was to ascertain whether saccadic adaptation occurs in typically developing children. We recorded saccades with an infrared eye tracker in 39 children, aged 8 to 19 years, at baseline to 12-degree horizontal target steps and after an adaptive task. During the adaptive task, a saccadic hypometric error was induced. This task consisted of 200 12-degree target steps that stepped backward 3 degrees during the initial saccade and without the participants' awareness. The initial saccade triggered the back-step. This paradigm required a corrective reduction of the amplitude of the initial saccades in response to the induced error. Saccadic adaptation was achieved in 26 participants, whose mean saccadic amplitudes decreased by 13% (P < .05). Saccadic adaptation was not influenced by age. We conclude that children as young as 8 years old have established functions of the neural circuits responsible for the motor learning required for saccadic adaptation.

Adaptation, Physiological↗
PubMed2005

Avoid, attack or do both? Behavioral and physiological adaptations in natural enemies faced with novel hosts.

BACKGROUND: Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation), neutralization of the defensive innovation (physiological adaptation) or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i) to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii) to study the factors that govern the relative investment in each adaptation mode. RESULTS: Our results show that (i) a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When (i) holds, we find that (ii) the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. CONCLUSION: Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties.

Adaptation, Biological↗
PubMed2026

Global disparities in COVID-19 vaccine coverage associated with trajectories of SARS-CoV-2 adaptation.

BACKGROUND: Vaccination serves as an effective intervention for health promotion and disease prevention across the socioecological systems and has played an important role during the COVID-19 pandemic. However, global disparities in vaccine coverage have increased uncertainty about the trajectories of viral adaptation, and the potential interplay between SARS-CoV-2 adaptation and vaccine rollout warrants further quantification. METHODS: Using over 13&#xa0;million SARS-CoV-2 genomes across 86 countries from March 2020 to September 2022, we analyzed nonlinear associations between SARS-CoV-2 adaptation and vaccination coverage, considering public health and social measures, international travel, and infection dynamics, before and after the emergence of Omicron. Additionally, we examined the relationship between SARS-CoV-2 adaptation and COVID-19 mortality. RESULTS: During the pre-Omicron period, we found positive associations between nonsynonymous to synonymous divergence (dN/dS) ratios in the S1 subunit and medium levels of adjusted vaccine coverage (effect size: 0.96 [95% CI 0.47, 1.45]), while the association became insignificant at high levels (effect size: -1.89 [95% CI -4.20, 0.43]). However, no significant associations were found when Omicron dominated, possibly due to the immune escape ability of Omicron variants and the complex immune landscape shaped by mass hybrid immunity. Moreover, we observed evidence of dynamic interdependence and positive correlations between COVID-19 mortality and SARS-CoV-2 adaptation, with COVID-19 mortality interpreted as a proxy for uncontrolled viral spread. CONCLUSIONS: Our findings suggest a complex nonlinear relationship between vaccine-induced immunity and SARS-CoV-2 adaptation, with high vaccine coverage potentially linked to lower positive selection. We also observed directional coupling between COVID-19 mortality and SARS-CoV-2 adaptation. This may have implications for fair and fast vaccination in pandemic preparedness and response. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗
PubMed2005

The role of gravity in adaptation of the vertical angular vestibulo-ocular reflex.

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adapted in side-down and prone positions in two monkeys and tested in four planes: left-/right-side down; forward/backward; and two intermediate planes that lie approximately in the planes of the vertical semicircular canal pairs, left anterior/right posterior (LA/RP) and right anterior/left posterior (RA/LP). Gain changes, expressed as a percent of preadapted values, were plotted as a function of head orientation in the planes of tilt, and fitted with sinusoids to obtain the gravity-dependent (amplitude) and gravity-independent (bias) components of adaptation. Gravity-dependent gain changes were always maximal when tested in a plane that included the head orientation in which the aVOR gain had been adapted. Changes were minimal when the head was tilted in a plane orthogonal to the plane of adaptation, and were smaller but still significant when tested in the two intermediate planes. Gravity-independent VOR gain changes were uniform over all planes of head tilt. Thus, the gravity-dependent and gravity-independent components could be separated experimentally. The aVOR gain changes from the head tilts in different directions were utilized to reconstruct the gain changes in three dimensions. They formed a continuous surface, which peaked in and around the position of adaptation. These studies support the postulate that gain adaptation has both gravity-independent and gravity-dependent components, and further show that these gain changes have a three-dimensional structure. These results are similar to those in humans, indicating that the gravity-dependent adaptation of the aVOR is likely to be a common phenomenon across species.

Acclimatization↗
PubMed2001

Melanotrope cell plasticity: a key mechanism for the physiological adaptation to background color changes.

The intermediate lobe of the pituitary secretes the melanotropic hormone alpha-MSH, which in amphibians plays a crucial role in skin color adaptation. It has been previously demonstrated that, in the frog Rana ridibunda, the intermediate lobe is composed of two distinct subpopulations of melanotrope cells that can be separated in vitro by using Percoll density gradients. These two melanotrope cell subsets, referred to as high-density (HD) and low-density (LD) cells, differ in their ultrastructural characteristics as well as in their biosynthetic and secretory activity. However, the specific, physiological role of the heterogeneity displayed by melanotrope cells remains elusive. In the present study, we investigated the effects of background color adaptation on melanotrope cell subpopulations. We found that adaptation of frogs to dark or white environment did not modify either the overall number of cells per intermediate lobe or the apoptotic and proliferation rates of melanotrope cells. On the other hand, adaptation of the animals to a white background significantly increased the proportion of hormone-storage HD cells and caused a concomitant decrease in that of LD cells (which exhibit higher levels of alpha-MSH release and POMC messenger RNA than HD cells). Conversely, after black-background adaptation the proportion of LD cells was markedly increased, suggesting that interconversion of HD cells to LD cells occurs during physiological activation of the intermediate lobe. In addition, black-background adaptation also enhanced alpha-MSH release by both cell subpopulations and increased inositol phosphate production in LD cells. These data indicate that, in frog, the proportions of the two melanotrope cell subsets undergo marked modifications during skin color adaptation, likely reflecting the occurrence of a secretory cell cycle whose dynamics are highly correlated to the hormonal demand imposed by the environment.

Adaptation, Physiological↗
PubMed2005

Local vascular adaptations after hybrid training in spinal cord-injured subjects.

PURPOSE: Studies investigating vascular adaptations in non-exercised areas during whole body exercise training show conflicting results. Individuals with spinal cord injury (SCI) provide a unique model to examine vascular adaptations in active tissue vs adjacent inactive areas. The purpose of this study is to assess the effects of 4 wk of voluntary arm and electrically stimulated leg exercise (8-12 sessions) on vascular adaptations in active areas (thigh and arms) and inactive areas (calf). METHODS: Vascular characteristics were measured by plethysmography (blood flow and vascular resistance) and echo Doppler (diameter and flow-mediated dilation (FMD) after 13 min of ischemia). RESULTS: After training, increased thigh baseline and peak blood flow, decreased thigh baseline vascular resistance, and increased diameter of the common femoral artery were found in the stimulated thigh tissue. Forearm and calf arterial parameters and FMD, in both superficial femoral artery and brachial artery, did not change. The lack of activity in the calf and concomitant insufficient elevation of blood flow during training, and the high initial training status of the arms are suggested to explain the absence of vascular adaptations in these areas. CONCLUSION: The presence of vascular adaptations after only 4 wk of FES cycling indicates that adaptations occur in an early phase. In addition, 4 wk of whole body exercise training in SCI individuals leads to vascular adaptations in the exercised tissues (thigh) but not in nonstimulated passive tissue (calf).

Adaptation, Physiological↗
PubMed1998

The adaptive response in radiobiology: evolving insights and implications.

The first of the regularly reproducible experiments to show that very low doses of ionizing radiation, like very low doses of chemical agents, could induce mechanisms whereby cells become better fit to cope with subsequent exposures to high doses were carried out on the induction of chromosome aberrations in cultures of human lymphocytes. If cells that had been exposed to a very low dose (1 cGy) of X rays were subsequently exposed to a relatively high dose (1 Gy), approximately half as many chromosome breaks were induced. Subsequent experiments showed that this adaptive response to low doses requires a certain minimal dose before it becomes active; occurs only within a relatively small window of dose; is dose-rate dependent; and depends on the genetic constitution of the people or animals exposed, with some being unresponsive. It was further shown that the response to the low-dose preexposure was not instantaneous but took approximately 4 to 6 hr to become fully active, and could be prevented if during this period protein synthesis was inhibited, i.e., a necessary protein (enzyme) was being induced. In fact, subsequent experiments with two-dimensional gel electrophoresis showed new proteins in cells irradiated with 1 to 2 cGy. The adaptation induced by low doses of radiation was therefore attributed to the induction of a novel efficient chromosome break repair mechanism that if active at the time of challenge with high doses would lead to less residual damage. This hypothesis was strengthened by a series of experiments in which it was found that inhibitors of poly(ADP-ribose)polymerase, an enzyme implicated in DNA strand break rejoining, could prevent the adaptive response. Although the phenomenon is well established in cellular systems, it is still problematical as to whether or not it will have any utility in establishing risks of ionizing radiation to humans. Newer experiments have now been carried out on the mechanisms underlying the effect and whether or not the effect can manifest itself as a decrease in the number of induced cancers and radiation-induced mortality. Experiments with restriction enzymes now indicate that double-strand breaks in DNA can be triggering events in adaptation. In addition, preliminary experiments on the survival of whole-body irradiated mice have shown that multiple exposures to low adapting doses can have profound effects on survival, and other experiments have shown that adaptation can affect the induction of thymic lymphoma in irradiated mice. It therefore appears that the initial experiments behind the adaptive response have led to a vigorous worldwide effort to understand the basic mechanisms behind it. This effort is stimulated both by a desire to understand the basic cell biology behind the response and a desire to see if indeed this phenomenon affects the estimation of risks of low-level radiation exposure.

Adaptation, Physiological↗
PubMed1977

Analysis of chromatic-adaptation effect by a linkage model.

Hunt suggested that an adaptation-dependent linkage in the visual pathway from the retina to the brain can explain the variation of saturation produced by change of adapting luminance. If variation of saturation is caused by change of linkage, this change must also be involved in chromatic adaptation to light sources that have different chromaticities. By considering the effective adaptation levels of receptors, the model is extended and formulated for application to prediction of chromatic adaptation. It is tested by use of experimental results for chromatic adaptation obtained by Burnham et al. Suitable selection of parameters that specify the state of linkage produces good predictions of the effects of chromatic adaptation.

Adaptation, Ocular↗
PubMed1988

Effects of chromatic adaptation on phase-dependent sensitivity to heterochromatic flicker.

Temporal modulation sensitivity was measured as a function of the relative phase of two equiluminous chromatic sources (564 and 625 nm) for temporal frequencies from 6 to 20 Hz. The difference between 180 degrees and the phase of least sensitivity was computed as the measured phase shift. A 2 degree test field was superimposed upon 8 degrees chromatic adapting fields with luminances from 100 to 3000 Td and chromaticities of 500, 600, and 650 nm. For each adapting field, the 564-nm source was set to 175 Td, and the 625-nm source was matched to it with heterochromatic flicker photometry (giving an effective mean luminance of 350 Td). The 650-nm adapting fields produced large changes in photometric setting but only small changes in the measured phase shift. The 600- and 500-nm adapting fields produced smaller changes in photometric setting but larger changes in the measured phase shift. In general, increased adapting luminance resulted in an increase in the measured phase shift for 600-nm adaptation and a decrease in the measured phase shift for 500-nm adaptation.

Adaptation, Physiological↗
PubMed2006

Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins.

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a signaling cascade known as the unfolded protein response (UPR). Although activation of the UPR is well described, there is little sense of how the response, which initiates both apoptotic and adaptive pathways, can selectively allow for adaptation. Here we describe the reconstitution of an adaptive ER stress response in a cell culture system. Monitoring the activation and maintenance of representative UPR gene expression pathways that facilitate either adaptation or apoptosis, we demonstrate that mild ER stress activates all UPR sensors. However, survival is favored during mild stress as a consequence of the intrinsic instabilities of mRNAs and proteins that promote apoptosis compared to those that facilitate protein folding and adaptation. As a consequence, the expression of apoptotic proteins is short-lived as cells adapt to stress. We provide evidence that the selective persistence of ER chaperone expression is also applicable to at least one instance of genetic ER stress. This work provides new insight into how a stress response pathway can be structured to allow cells to avert death as they adapt. It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome.

Adaptation, Biological↗
PubMed2002

Bone adaptation response to sham and bending stimuli in mice.

This study presents inbred-strain-related differences in tibial bone adaptation response to low-force loading in four-point bending and sham (pad pressure) arrangements in mice. Our previous work in mice has shown that at relatively high but equal bending forces (9 N or a bending moment of 16.88 N-mm), C57BL/6J mice respond with significantly greater bone formation than C3H/HeJ mice. Because of high tibial strains, the majority of the bone response in our previous study was woven bone. In this, study, we reduced the loading forces to 5 N or a bending moment of 9.38 N-mm (to decrease the woven-bone formation response) and investigated inbred-strain-related bone adaptation differences resulting from bending and sham loading (reported here for the first time in C57BL/6J) in these mice. Twenty-four female mice within each inbred mouse strain (C3H/HeJ [C3H] and C57BL/6J [B6]) were randomly divided into the two loading groups (12 per group sham and bending, total of 48 mice). All of the external loading was done for 36 cycles at 2 Hz, 3 d/wk for 3 wk. The bone adaptation response at lower forces exhibited a pattern similar to that seen for the higher forces in the previous study, suggesting that the patterns of bone adaptation were inbred strain related and independent of bending force magnitude. The bending-related periosteal mineral apposition surface (pMS) and mineral apposition rate (MAR) were respectively 40% and 45% greater in B6 than in C3H. The cortical bone adaptation response to bending was greater when compared to sham or pad pressure for each inbred strain of mice, suggesting that the majority of the bone adaptation response was the result of bending stimulus and not local pressure from pad contact. In addition, regardless of loading arrangement (sham or bending), the bone adaptation response in C57BL/6J mice was greater than C3H/HeJ.

Adaptation, Physiological↗
PubMed2006

Cerebellar contributions to locomotor adaptations during splitbelt treadmill walking.

Locomotor adaptability ranges from the simple and fast-acting to the complex and long-lasting and is a requirement for successful mobility in an unpredictable environment. Several neural structures, including the spinal cord, brainstem, cerebellum, and motor cortex, have been implicated in the control of various types of locomotor adaptation. However, it is not known which structures control which types of adaptation and the specific mechanisms by which the appropriate adjustments are made. Here, we used a splitbelt treadmill to test cerebellar contributions to two different forms of locomotor adaptation in humans. We found that cerebellar damage does not impair the ability to make reactive feedback-driven motor adaptations, but significantly disrupts predictive feedforward motor adaptations during splitbelt treadmill locomotion. Our results speak to two important aspects of locomotor control. First, we have demonstrated that different levels of locomotor adaptability are clearly dissociable. Second, the cerebellum seems to play an essential role in predictive but not reactive locomotor adjustments. We postulate that reactive adjustments may instead be predominantly controlled by lower neural centers, such as the spinal cord or brainstem.

Adaptation, Physiological↗
PubMed1987

Effect of anaesthetics on PRL and LH secretion in rats. Importance of pre-anaesthetic adaptation and involvement of monoaminergic neurons.

General anaesthesia has been reported to interact with neuroendocrine functions leading to large variations in basal and stimulated plasma levels of several hormones, but the findings are often contradictory. In the present investigation we have attempted to clarify the importance of the experimental procedure when evaluating the influence of anaesthetics on the secretion of PRL and LH in male rats. One group of rats (non-adapted) were anaesthetized (ip) with pentobarbital (P), urethane (U), ketamine (A), or althesin (A) without being accustomed to the laboratory environment prior to anaesthesia. Another group of rats (adapted) were kept for 90 min in their individual cages before induction of anaesthesia with P or U. In non-adapted rats the plasma concentration of PRL declined rapidly during the first 30 min following administration of all anaesthetics or saline (controls) and attained a steady level after 60 min. Except for a brief rise following U injection, the LH concentration was not affected by anaesthesia in the non-adapted rats. In adapted rats, the concentration of both PRL and LH declined markedly during the pre-anaesthetic adaptation period and had stabilized at the end of that period. Following administration of U, P or saline, no further changes in the hormone concentrations were observed. Injection of the dopamine receptor antagonist pimozide prevented the decrease in plasma PRL during the adaptation period, but had no effect on LH secretion. In pimozide-treated rats, U caused a 5-fold increase in the PRL concentration. This effect of U was inhibited by the serotonin receptor antagonist methysergide. The PRL response to 30 micrograms of histamine was similar in conscious and U-anaesthetized rats, whereas P anaesthesia caused a reduction in the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2004

Longitudinal assessment of adaptive behavior in infants and young children with newly diagnosed epilepsy: influences of etiology, syndrome, and seizure control.

OBJECTIVES: The outcomes of childhood-onset epilepsy are highly varied and have several potential determinants. We examined the independent effects of syndrome type, seizure control, and etiology over time on adaptive behavior as measured by the Vineland Scales of Adaptive Behavior. METHODS: As part of a prospective community-based study of newly diagnosed epilepsy, parents of children who were younger than 3 years at the time of initial onset of epilepsy completed the Vineland Adaptive Behavior Scales screener version at entry into the study and once a year thereafter for up to 3 years. Longitudinal analyses were performed on the composite score as the primary outcome and on the 4 domain scores (communication, socialization, motor, and daily living) as confirmatory/secondary outcomes to determine the effects of syndrome (epileptic encephalopathy or other), seizure control (intractable or not), and etiology (symptomatic or not) on adaptive behavior at the time of initial diagnosis and over time. RESULTS: A total of 613 children were enrolled in the study, and 191 (31%) of these children met the age criterion for this analysis. Of these, 172 (90%) had adequate follow-up and had completed baseline and at least 1 subsequent Vineland assessment. Overall, Vineland scores (composite and individual domains) were somewhat below average at baseline (initial diagnosis). All declined significantly over time. All of the effects at baseline, however, were limited to children with epileptic encephalopathies and symptomatic etiology. Substantial declines over time occurred in these children, and there was an independent effect of intractable seizures as well. In children with none of these factors ( approximately 75% of the study group), baseline scores were consistent with average performance for the test norms and there was no evidence of any decline over time. CONCLUSIONS: Children with an underlying symptomatic etiology or a syndrome that can be characterized as 1 of the epileptic encephalopathies demonstrate impaired adaptive behavior at the time of initial diagnosis and experience additional declines in assessments of age-adjusted performance over time. Our results suggest that future seizure outcome is not strongly reflected in adaptive behavior at initial diagnosis but that it takes its toll on the child over time. Understanding how each of these factors affects development and how they interact with each other is the next step in designing effective interventions for lessening the impact of these disorders on the child. In the majority of children with onset of epilepsy during infancy or early childhood, adaptive behavior is within the normal range and does not show any evidence of declining over time. Although this is encouraging, it does not contradict other studies that have demonstrated behavioral and relatively subtle cognitive difficulties in school-aged children with epilepsy. Long-term follow-up in this cohort will permit us to examine the predictive value of the Vineland for later behavioral and cognitive difficulties in this group that, so far, seems to be doing well.

Activities of Daily Living↗