Does valproate therapy in epileptic patients contribute to changing atherosclerosis risk factors? The role of lipids and free fatty acids.

BACKGROUND: We aimed to demonstrate the relationship between the valproate (VPA) treatment versus lipid and serum free fatty acids (FFAs) profiles to be the potential atherosclerosis risk factor in epileptic patients. METHODS: Fasting blood samples were taken from 21 adult VPA-treated patients and 21 controls. The profiles of lipids, FFAs, clinical parameters and body mass index (BMI) were evaluated. RESULTS: No significant differences between the study group and controls were found for any of the studied parameters. However, significant differences in the total cholesterol (CHOL), low-density-lipoprotein cholesterol (LDL), triglycerides, the CHOL/HDL (high-density-lipoprotein cholesterol) ratio, and Atherogenic Index of Plasma were observed for overweight patients when compared to those of normal weight. Patients with uncontrolled epilepsy tended to have significantly lower palmitic acid level than seizure-free patients. Oleic acid was found to be positively correlated with VPA concentration for patients with uncontrolled epilepsy, and with the dose corrected VPA concentration for all the patients. The acid was however negatively correlated with stearic acid for both the controls and the patients with uncontrolled epilepsy. PLS method revealed CHOL, LDL, triglycerides and myristic acid to be positively interrelated for the whole group under the study, whereas these parameters were found to be negatively correlated with VPA concentration, and positively with BMI. Furthermore, high sensitivity C-reactive protein was found to be negatively correlated with palmitic acid levels. CONCLUSION: Overweight VPA-treated patients are exposed to higher risk of atherosclerosis. Alterations in FFAs are likely to depend on seizures control, and on VPA levels.

Antioxidant agents and physiological responses in adult epileptic patients treated with lamotrigine.

BACKGROUND: The aim of our research was to evaluate some biochemical changes in blood during lamotrigine (LTG) monotherapy of adult patients with epilepsy, and to check possible associations between typical selenium status parameters and the frequency of seizures. METHODS: The study was performed by examining aspartate aminotransferase (AspAT), alanine aminotransferase (AlaAT), creatinine, ferric reducing ability of plasma (FRAP), serum uric acid (UA), uric-acid-independent FRAP (UAiFRAP), plasma glutathione peroxidase (GPX3), selenoprotein P (SelP), plasma superoxide dismutase (pSOD), 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum and urine, serum selenium (sSe) and zinc (sZn), in 22 adult patients with epilepsy and 22 healthy controls. Additionally, the levels of LTG were determined in patients. RESULTS: pSOD activity was higher in the study group (5.32±1.24 U/ml) compared with the controls (4.05±0.92 U/ml, p=0.008). No other statistical difference between patients and controls was found. CONCLUSION: Lack of difference in parameters other than SOD, particularly no difference in 8-OHdG concentrations between the patients treated with LTG compared to the control subjects suggests that these patients are at no particular risk of oxidative DNA damage. In patients who are well or moderately well clinically controlled, selenium status parameters (sSe, GPX3, SelP) are not directly connected with the frequency of seizures.

Healthcare and guidelines: a population-based survey of recorded medical problems and health surveillance for people with Down syndrome.

BACKGROUND: Medical problems are described in a population of persons with Down syndrome. Health surveillance is compared to the recommendations of national guidelines. METHOD: Case records from the specialised and primary healthcare and disability services were analysed. RESULTS: A wide spectrum of age-specific medical and surgical problems was described. Congenital heart defects and middle ear infections were mostly experienced by younger people, while thyroid disease, epilepsy, and Alzheimer's disease were frequent among older people. Psychiatric disorders and behavioural problems were frequent in all age groups. CONCLUSIONS: Health surveillance remained insufficient, despite the guidelines available. A joint effort by healthcare and disability service providers is required to ensure that the medical needs of people with Down syndrome are adequately met across their entire lifespan. An active provision of healthcare and monitoring for this vulnerable group is needed.

Valproic acid modulates superoxide dismutase, uric acid-independent FRAP and zinc in blood of adult epileptic patients.

We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7-14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.

[Update on current care guidelines: appropriate treatment of medical problems associated with Down's syndrome]. / Downin oireyhtymään liittyvien lääketieteellisten ongelmien hyvä hoito.

The lifetime prognosis of people with Down's syndrome has improved. Development of the services that health care and society can offer to such people is ongoing. These guidelines are targeted at defining what is required to further increase the lifespan and quality-of-life of people with Down's syndrome.

Short cognitive behavioral therapy and cognitive training for adults with ADHD - a randomized controlled pilot study.

In clinical practice, a growing need exists for effective non-pharmacological treatments of adult attention-deficit/hyperactivity disorder (ADHD). Here, we present the results of a pilot study of 10 adults with ADHD participating in short-term individual cognitive- behavioral therapy (CBT), 9 adults participating in cognitive training (CT), and 10 controls. Self-report questionnaires, independent evaluations, and computerized neurocognitive testing were collected before and after the treatments to evaluate change. There were distinctive pre-hypotheses regarding the treatments, and therefore the statistical comparisons were conducted in pairs: CBT vs control, CT vs control, and CBT vs CT. In a combined ADHD symptom score based on self-reports, 6 participants in CBT, 2 in CT and 2 controls improved. Using independent evaluations, improvement was found in 7 of the CBT participants, 2 of CT participants and 3 controls. There was no treatment-related improvement in cognitive performance. Thus, in the CBT group, some encouraging improvement was seen, although not as clearly as in previous research with longer interventions. In the CT group, there was improvement in the trained tasks but no generalization of the improvement to the tasks of the neurocognitive testing, the self- report questionnaires, or the independent evaluations. These preliminary results warrant further studies with more participants and with more elaborate cognitive testing.

Cognitive-behaviorally-oriented group rehabilitation of adults with ADHD: results of a 6-month follow-up.

OBJECTIVE: Recently, novel psychological treatments for adult ADHD have been reported with promising results. However, studies about long-term treatment effects are scanty. The authors study effects of cognitive-behaviorally-oriented group rehabilitation during a 6-month follow-up. METHOD: Participating in the rehabilitation were 29 adults, of whom 25 were reached 3 and 6 months later. ADHD and other psychiatric symptoms were assessed with self-ratings (Brown ADD Scale for Adults, Symptom Check List-90 [SCL-90], 16 ADHD-related items of SCL-90, Beck Depression Inventory). Participants from the pretreatment period served as their own controls. RESULTS: Participants having improvement in ADHD symptoms during treatment (n = 11) maintained most of the benefit during follow-up. They also had a decrease in other psychiatric symptoms, but this did not fully persist through the follow-up. Of all participants, 72% found their overall situation improved as compared to the pretreatment situation. CONCLUSION: Results suggest that cognitive-behaviorally-oriented group rehabilitation of ADHD adults might have long-term benefits.

Childhood growth and development associated with need for full-time special education at school age.

OBJECTIVE: To explore how growth measurements and attainment of developmental milestones in early childhood reflect the need for full-time special education (SE). METHODS: After stratification in this population-based study, 900 pupils in full-time SE groups (age-range 7-16 years, mean 12 years 8 months) at three levels and 301 pupils in mainstream education (age-range 7-16, mean 12 years 9 months) provided data on height and weight from birth to age 7 years and head circumference to age 1 year. Developmental screening was evaluated from age 1 month to 48 months. Statistical methods included a general linear model (growth measurements), binary logistic regression analysis (odds ratios for growth), and multinomial logistic regression analysis (odds ratios for developmental milestones). RESULTS: At 1 year, a 1 standard deviation score (SDS) decrease in height raised the probability of SE placement by 40%, and a 1 SDS decrease in head size by 28%. In developmental screening, during the first months of life the gross motor milestones, especially head support, differentiated the children at levels 0-3. Thereafter, the fine motor milestones and those related to speech and social skills became more important. CONCLUSION: Children whose growth is mildly impaired, though in the normal range, and who fail to attain certain developmental milestones have an increased probability for SE and thus a need for special attention when toddlers age. Similar to the growth curves, these children seem to have consistent developmental curves (patterns).

Adults with ADHD benefit from cognitive-behaviorally oriented group rehabilitation: a study of 29 participants.

OBJECTIVE: In clinical practice, a growing need exists for effective nonpharmacological treatments of adult ADHD. The authors present results from a cognitive-behaviorally oriented psychological group rehabilitation for adult ADHD. METHOD: A total of 29 adults with ADHD participated. Rehabilitation consisted of 10 or 11 weekly sessions. Participants were assessed with self-ratings (checklist for ADHD based on the Diagnostic and Statistical Manual of Mental Disorders , Beck Depression Inventory II, Symptom Check List-90 [SCL-90], Brown ADD Scale for Adults [BADDS]), and the ratings of their significant others (BADDS) 3 months prior to treatment, at the beginning of treatment, and at the end of treatment. Also, the Wender Utah Rating Scale questionnaire was completed prior to rehabilitation. RESULTS: Rehabilitation resulted in reduced self-reported symptoms in 16 ADHD-related items of SCL-90, BADDS total score, and BADDS subdomains of activation and affect. CONCLUSION: Results suggest that cognitive-behavioral group rehabilitation can be suitable in treating adult ADHD.

Endogenous melatonin predicts efficacy of exogenous melatonin in consolidation of fragmented wrist-activity rhythm of adult patients with developmental brain disorders: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: : We studied whether the endogenous melatonin patterns in adult patients with developmental brain disorders have any role in response to exogenous melatonin given as a sleep-promoting medicine. METHODS: : Participants included 15 adults (18-60 years, five females) with developmental brain disorders of varying etiologies, motor handicaps, and long-term history of sleep problems. According to the 24-h patterns of serum melatonin, patients were divided into two subgroups: lower and higher secretors. The pretreatment sleep disorder was characterized by a structured interview, 24-h ambulatory polysomnography and 7-day wrist actigraphy. Patients received 1, 3, or 6mg fast-release melatonin tablets, each for 4 weeks in increasing order, at a constant time of 30min before the desired sleep onset. Similarly, placebos with different codes were given during 3x4 weeks. The 7-day actigraphy was repeated at the end of each drug period. Outcome measures were six different parameters of non-parametric circadian rhythm analysis. Drug effects and 40 confounding/modulating factors were evaluated by applying two-level regression analyses with co-variables. RESULTS: : Exogenous melatonin decreased the fragmentation of the rest-activity rhythm, increased the day/night ratio of activity and advanced the onset of rest period. The effects on fragmentation and day/night ratio were more pronounced in the lower than higher secretors of melatonin. Other contributing factors in the drug effects were blindness and some features of the original sleep disorder (disrupted cyclicity of the sleep architecture in polysomnography or reported daytime somnolence). CONCLUSIONS: : Exogenous melatonin consolidated the fragmented rest-activity in about half of the patients. Low endogenous serum melatonin levels at night predicted improvement by the drug. Higher doses were not more effective than the lowest dose.

Sensory impairments and health concerns related to the degree of intellectual disability in people with Down syndrome.

The relationship between poor health and cognitive impairment is not fully understood yet. People with Down syndrome are prone to a number of health problems, including congenital heart defect, visual impairment, hearing loss, autoimmune diseases, epilepsy, early-onset Alzheimer's disease and intellectual disability. Our aim was to assess the impact of impaired health on cognitive performance in people with Down syndrome. A series of people with Down syndrome (n=129) were studied for their intellectual disability, sensory impairments and health concerns. The medical and psychological records of all persons with Down syndrome in the Intellectual Disability Service Register of Kainuu from 1970 to 2004 were analysed. The detected health issues were related to the individuals' cognitive levels. Visual impairment, poor dental health and acute neurological disease were associated with the severity of intellectual disability and ageing.

Mental health, behaviour and intellectual abilities of people with Down syndrome.

The mental health, adaptive behaviour and intellectual abilities of people with Down syndrome (n=129) were evaluated in a population-based survey of social and health care records. Females had better cognitive abilities and speech production compared with males. Males had more behavioural problems than females. Behaviour suggestive of attention deficit hyperactivity disorder was often seen in childhood. Depression was diagnosed mainly in adults with mild to moderate intellectual disability. Autistic behaviour was most common in individuals with profound intellectual disability. Elderly people often showed decline of adaptive behaviour associated with Alzheimer's disease. Case descriptions are presented to illustrate the multitude of mental health and behavioural issues seen from childhood to old age in this population.

Sleep disturbances in aspartylglucosaminuria (AGU): a questionnaire study.

Sleep disturbances are common in many progressive metabolic encephalopathies. The possible presence of disturbed sleep-wake behaviour in the lysosomal storage disorder aspartylglucosaminuria, has not been previously studied, however. The sleep-wake behaviour of 81 patients with aspartylglucosaminuria (AGU, age 3-55 years, median 22 years; 42 female and 39 male) and 49 controls (age 2-57 years, median 18 years; 25 female and 24 male) was assessed through a postal survey. A slightly modified version of the validated Basic Nordic Sleep Questionnaire was used. Fifty-eight per cent of the AGU patients were reported to suffer daily from a sleep-related problem (controls 31%, p < 0.01). In AGU adults (age >17 years) and children (age < or =17 years), the corresponding figures were 52% and 61%, respectively (control children 22%, p < 0.05 and control adults 38%, p = 0.06). In AGU children, settling difficulties were reported to occur significantly more commonly than in control children. Children with AGU were also reported to snore more often than were the controls. Adults with this disorder were found to suffer from severely fragmented night-time sleep, which was experienced as highly distressing by the parents and other caregivers. A long night sleep period was reported to be common in the ageing AGU patients (AGU 9.5 +/- 1.7 vs controls 7.2 +/- 1.0 h, mean +/- SD, p < 0.001). Parents and caregivers also often complained about disturbing movements during sleep in AGU patients. In conclusion, both children and adults with aspartylglucosaminuria were reported to display several types of sleep disturbances significantly more commonly than healthy controls.

Cancer incidence of persons with Down syndrome in Finland: a population-based study.

Individuals with Down syndrome (DS) have a predisposition to leukaemia and testicular cancer, but data on the incidence of cancers are yet sparse. A cohort of 3,581 persons with DS was identified from a National Registry of Finnish persons with intellectual disability collected between 1978 and 1986 and followed-up for cancer incidence until 2002. Standardised incidence ratios (SIRs) were defined as ratios of observed number of cancer cases to those expected from the national cancer incidence rates, by age and sex. The overall cancer risk was equal to that of the general population, but a significantly high risk of leukaemia (SIR 10.5, CI 95% 6.6-15.8) and testicular cancer (SIR4.8, CI 95% 1.8-10.4) was found.

Wrist actigraphy in estimation of sleep and wake in intellectually disabled subjects with motor handicaps.

BACKGROUND AND PURPOSE: We studied the applicability of wrist actigraphy to sleep-wake estimation in patients with motor handicaps. PATIENTS AND METHODS: Concomitant polysomnographic and actigraphic recordings (16-24 h) were compared in three groups: normally moving subjects with normal sleep (n=10), sleep-disordered subjects without motor handicaps (n=13) and sleep-disordered patients with different motor disabilities (n=16). The motor abilities of the subjects were determined by clinical evaluation using a grading scale from 0 to 10. Their actual daily activity was calculated from the recordings as average activity scores. RESULTS: In the healthy subjects, the mean difference between actigraphic and polysomnographic total sleep estimation was negligible (-1 min), while in both sleep-disordered groups, sleep was highly overestimated by actigraphy. There was a significant correlation between the motor ability score and the discrepancy between actigraphy and polysomnography, but individual data points were highly scattered. A more consistent correlation was found between the average activity score/min in actigrams and the discrepancy of actigraphic with polysomnographic total sleep estimation (Spearman's r=-0.58, P=0.0001, n=39). When the recordings with very low average activity score were rejected from the analyses (two patients without and six with motor handicaps), the overestimation of sleep by actigraphy was reduced but it still remained in both sleep-disordered groups. The mean differences of total sleep between actigraphy and polysomnography were 72 and 121 min and the rank order correlation coefficients 0.80 and 0.71 in patients without and with motor handicaps, respectively. The median discrepancy in total sleep estimation was 6% in both sleep-disordered groups. CONCLUSIONS: In subjects with rudimentary motor abilities, a standard actigraphy can produce a signal, which is related to the amount of sleep scored in polysomnograms. The sleep parameters obtained by the two methods are not equal, however. The inspection of actigrams is more reliable than the clinical scaling of motor abilities in predicting the applicability of wrist actigraphy.

Automatic blink detection: a method for differentiation of wake and sleep of intellectually disabled and healthy subjects in long-term ambulatory monitoring.

OBJECTIVES: To develop a method for automatic detection of blinks in electrooculograms and to evaluate reliability of blink rate as an indicator of wake and sleep in subjects with developmental brain disorders. DESIGN: Categorization of wake and sleep by blink rate was compared with visual sleep scoring of the polysomnograms. SETTING: Ambulatory polysomnographic recordings at home or in the sleep laboratory. PARTICIPANTS: Nine healthy volunteers for calibration, 10 for validation; 7 intellectually disabled patients for calibration, 10 for validation of the method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Blinks were detected from electrooculograms using a weighted finite impulse response median hybrid filtering and the criterion of minimum duration at amplitude threshold. More than 80% of the visually identified electrooculographic blinks were detected in most subjects. When 30-second epochs of electrooculograms with 1 or more blinks were defined as wake and those without blinks as sleep, the average agreement with polysomnographic scoring was 95% in healthy subjects and 84% in patients. The mismatch was mostly due to the 30-second epochs without blinks during waking. A contextual redefinition of wake and sleep by expanding the inspected electrooculographic span from 1 to 20 epochs (10 minutes) increased the agreement to 93% in patients. The agreement is comparable to that of actigraphy with polysomnography. The linear correlation coefficient of the proportions of sleep epochs between visual scoring and the contextual blink rate method was 0.869. The main sleep periods detected by the blink-rate method were an average of 7 minutes longer than those determined by visual scoring. This was caused by differences in the detection of sleep onsets: blinking ceased before the first stage 1 sleep period was scored. The absolute period lengths obtained by the 2 methods did not differ significantly from each other in unpaired t-tests, and the linear correlation between the values was 0.999. CONCLUSIONS: The blinks extracted from the electrooculographic signal can be used to reliably determine the main sleep and wake periods in both healthy subjects and patients with developmental brain disorders.

Sleep fragmentation in mentally retarded people decreases with increasing daylength in spring.

We studied the sleep-wake behavior of mentally retarded people from late winter to early summer at 60 degrees N. During this time the daylength increased 8 h 51 min. The data were collected by observing the sleep-wake status of 293 subjects at 20-min intervals for five randomized 24h periods (= recording days). The intervals during which the individual recording days of the same order (1st, 2nd, etc.) were carried out, were called recording periods. Consequently, there were five recording periods, each containing 293 individual recording days. Even though there was overlap among the recording periods, the median daylength from one period to another increased approximately by 100 min. In the initial statistical analysis, the number of wake-sleep transitions was found to differ significantly among the five recording periods (Friedman test, p < 0.001). The mean ranks in the Friedman test suggested that the number of wake-sleep transitions was highest during the 1st and lowest during the 5th recording period. In further statistical analyses using a program for mixed effects regression analysis (MIXOR 2.0) it was found that the increase in daylength during the study period was associated with a simultaneous decrease of approximately 0.5 wake-sleep transitions in the whole study population (p < 0.001). The decrease in the number of wake-sleep transitions was significant only in the subgroups of subjects with a daylength change of more than 350 min between the 1st and 5th recording days (Wilcoxon tests, p < 0.005). This suggests that after a marked prolongation of the natural photoperiod, the reduction in sleep episodes was more probable than after smaller changes in daylength. It is concluded that the sleep of mentally retarded people living in a rehabilitation center at a northern latitude is more fragmented in winter than in early summer and that the change is related probably to the simultaneous increase in the length of the natural photoperiod. The sleep quality of persons living in institutional settings might be improved by increasing the intensity and/or duration of daily artificial light exposure during the darker seasons.