Mycophenolate mofetil hampers antibody responses to a broad range of vaccinations in kidney transplant recipients: Results from a randomized controlled study.

OBJECTIVES: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.

How do group workers respond to suicidal behavior? Experiences and perceptions of suicidal female adolescents residing in secure residential youth care in the Netherlands.

BACKGROUND: Adolescent suicidal behavior, including non-suicidal self-injury, is increasingly prevalent in Secure Residential Youth Care (SRYC) in the Netherlands. Group workers play a vital role in the well-being and functioning of adolescents in SRYC as they interact with adolescents on a daily basis. However, we have little understanding of how adolescents perceive group workers' responses to suicidal behavior and we lack knowledge about the impact of these responses on adolescents and the group climate. AIM: The aim of this study is to explore (a) how adolescents value group workers responses towards suicidal behavior and (b) the impact of these responses on adolescents, as well as (c) on the group climate. The results can be used to develop care-policy to improve care for suicidal adolescents in SYRC. METHOD: Eleven suicidal female adolescents residing in SRYC were interviewed. All adolescents had previously displayed suicidal behavior, including non-suicidal self-injury. Interviews were analyzed using grounded theory. CONCLUSION: This study presents the perceptions of suicidal female adolescents residing in SRYC about group workers' responses on suicidal behavior. Adolescents prefer group workers who react responsive to suicidal behavior. Responsive care, trust and connectedness help adolescents disclose their suicidal thoughts. Participants criticize group workers who are non-responsive as being distant, and their relationship with these group workers lacked trust, communication, a sense of connection, or personal depth. All adolescents underline the devastating impact of involuntary seclusion, and stress the importance of being able to disclose without fear of coercive consequences. Findings indicate that non-responsive reactions contribute to an increase in suicidal distress as well as a closed group climate.

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series.

Background: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts. Methods: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed. Results: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact. Conclusion: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: an EAN, ESRS and ILAE-Europe consensus review.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

The burden of parenting children with frontal lobe epilepsy.

OBJECTIVE: Caring for a child with a chronic illness adds stress to the typical parenting stress in healthy developing children. This stress can place a heavy burden on parents and may increase when a child displays problem behavior. In general, parenting and child's behavior problems are associated. Furthermore, externalizing (more outgoing) behavior is reported frequently in children with frontal lobe epilepsy (FLE). Therefore, in this study, we first investigated the burden of parents of children with FLE, and second, we investigated the relation between the experienced burden and reported behavioral problems. The validity of parents' reports on proxy measures as well as duration of epilepsy is taken into account. METHODS: Thirty-one parents of children with FLE completed validated questionnaires about behavioral problems and burden of parenting. To examine if parents tend to be inconsistent or unusually negative, we used the two validity scales of the Behavioral Rating Inventory of Executive Function (BRIEF) (Negativity and Inconsistency). RESULTS: Only parents of children with FLE who have had epilepsy for 5 years or longer report more problems on the Nijmeegse Vragenlijst voor de Opvoedingssituatie (NVOS) subscales 'Able to manage', 'Child is a burden', and 'Good Interaction' compared with the healthy controls. The subscale 'Child is a burden' significantly predicts scores in about 20% to 49% on the main scales of the Child Behavior Checklist (CBCL), the Global Executive Composite (GEC), and Behavioral Regulation Index (BRI) of the BRIEF. Only 6% of parents scored in the clinical range of the negativity scale of the BRIEF. For the inconsistency scale, this was 45%. CONCLUSION: Parents of children with FLE do not report excessive parental burden. Longer duration of epilepsy might be a risk factor in experiencing burden. The findings suggest a link between parental burden and behavioral problems in children with FLE. Externalizing behavioral problems are the most marked behavioral problems, which relate to the parental burden. Parents tend to be inconsistent in their ratings.

Digital cognitive behavioral therapy for insomnia - The first Georgian version. Can we use it in practice?

Insomnia is a common sleep disorder which has a 5-6% prevalence rate and shows high social impact. At least 10% of patients with insomnia will see a medical specialist. Hence, 20,000-40,000 people in Georgia require medical help for insomnia. Treatment of insomnia is very effective. Pharmacotherapy is common, but it is recognized that cognitive behavioral therapy (CBT) is a better choice, since it is safe for patients and shows sustainable improvement. CBT of insomnia is not currently available in Georgia. The aim of our study was to evaluate a Georgian version of an innovative, internet-delivered digital CBT (dCBT) for insomnia in terms of therapeutic efficacy, adherence, and ease of handling. The Georgian digital cognitive behavioral therapy for insomnia was developed as an analogue of Dutch dCBT "i-Sleep." All online materials were made applicable for the Georgian population through translation, validation by translation back to the original language, and adaptation to the Georgian reality, in order to avoid linguistic, cultural, and social pitfalls. Fifty-two adult patients with insomnia were recruited for the study: 34 women and 18 men, aged 18-64 years (mean: 33.5 years). Inclusion criteria included: age over 18, access to internet, and sufficient skills to use electronic devices. The patients who were treated pharmacologically continued their usual medication and received dCBT in addition to this treatment. DCBT was guided by a therapist. Clinical efficacy was evaluated on the basis of Insomnia Severity Index (ISI), measured before the dCBT and one month after its completion. 25 out of 52 patients (48%) completed a full dCBT course. Mean ISI in this group dropped from 22.88 to 8.24 (P < 0.01), showing significant therapeutic effect one month after CBT completion. 27 patients (52%) stopped treatment for various reasons at different stages of dCBT. Sixteen patients dropped out from the first module (31%). 7 patients older than 50 years encountered problems with handling electronic devices and the platform itself. 9 patients stopped therapy, showing bad adherence for different reasons, mostly related to finding the sessions time-consuming and being disappointed by the absence of immediate therapeutic effect. Eleven more patients (21%) stopped at sleep restriction, finding it difficult to accomplish sleep restriction-related tasks. In general, patients found dCBT quite comprehensive and easy to handle. This data suggests that the Georgian version of dCBT for insomnia is a promising therapeutic tool, comparable with international analogues in terms of efficacy and adherence. Further studies, involving a greater number of patients and long-term follow-up are required for the final assessment of therapeutic efficacy and sustainability of results.

Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation.

Ageing is associated with changes in the peripheral T cell immune system, which can be influenced significantly by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T cell populations correlate with T cell composition of the lymph node (LN) is unclear, but is crucial for a comprehensive understanding of the T cell system. T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analysed for frequency of recent thymic emigrants using CD31 expression and T cell receptor excision circle content, relative telomere length and expression of differentiation markers. Compared with PB, LN contained relatively more CD4+ than CD8+ T cells (P < 0·001). The percentage of naive and central memory CD4+ and CD8+ T cells and thymic output parameters showed a strong linear correlation between PB and LN. Highly differentiated CD28null T cells, being CD27- , CD57+ or programmed death 1 (PD-1+ ), were found almost exclusively in the circulation but not in LN. An age-related decline in naive CD4+ and CD8+ T cell frequency was observed (P = 0·035 and P = 0·002, respectively) within LN, concomitant with an increase in central memory CD8+ T cells (P = 0·033). Latent CMV infection increased dramatically the frequency of circulating terminally differentiated T cells, but did not alter T cell composition and ageing parameters of LN significantly. Overall T cell composition and measures of thymic function in PB and LN are correlated strongly. However, highly differentiated CD28null T cells, which may comprise a large part of circulating T cells in CMV-seropositive individuals, are found almost exclusively within the circulation.

Headache in epilepsy patients: the (un)awareness of this phenomenon among Dutch neurologists.

PURPOSE: Headache is a frequently heard complaint that can strongly influence quality of life. This is probably even more so in people with a chronic illness. Knowing that headache, and especially migraine, is more frequent among epilepsy patients, the knowledge concerning this problem has been studied among Dutch neurologists. METHODS: Seven hundred and seventy two neurologists, working in 89 hospitals and two tertiary epilepsy clinics were asked to participate. Using a questionnaire, neurologists were surveyed on different subjects, e.g. whether they thought current headaches are more frequent in people with epilepsy than in the general population, their interest for epilepsy and how many patients with epilepsy visited their polyclinic per month. RESULTS: In total, 334 questionnaires were returned (response rate of 43%) of which 18 were excluded. One third of neurologists responded affirmatively that current headaches are more prevalent among people with epilepsy and eight percent knows that this is, more specified, migraine. The number of years of experience does not influence knowledge on headaches in epilepsy patients. The interest in epilepsy and the number of epilepsy patients per month on the polyclinic does. CONCLUSIONS: These results show that the occurrence of headache in people with epilepsy is underestimated by Dutch neurologists. This leaves an often bothersome and potentially treatable condition underexposed.

Periictal and interictal headache including migraine in Dutch patients with epilepsy: a cross-sectional study.

As early as in 1898, it was noted that there was a need to find "a plausible explanation of the long recognized affinities of migraine and epilepsy". However, results of recent studies are clearly conflicting on this matter. In this cross-sectional study, we aimed to define the prevalence and characteristics of both seizure-related and interictal headaches in patients with epilepsy (5-75years) seeking help in the tertiary epilepsy clinic SEIN in Zwolle. Using a questionnaire, subjects were surveyed on the existence of headaches including characteristics, duration, severity, and accompanying symptoms. Furthermore, details on epilepsy were retrieved from medical records (e.g., syndrome, seizure frequency, and use of drugs). Diagnoses of migraine, tension-type headache, or unclassifiable headache were made based on criteria of the International Classification of Headache Disorders. Between March and December 2013, 29 children and 226 adults were evaluated, 73% of whom indicated having current headaches, which is significantly more often when compared with the general population (p<0.001). Forty-nine percent indicated having solely interictal headache, while 29% had solely seizure-related headaches and 22% had both. Migraine occurs significantly more often in people with epilepsy in comparison with the general population (p<0.001), and the occurrence of tension-type headaches conforms to results in the general population. These results show that current headaches are a significantly more frequent problem amongst people with epilepsy than in people without epilepsy. When comparing migraine prevalence, this is significantly higher in the population of patients with epilepsy.

On-the-road driving performance and driving-related skills in older untreated insomnia patients and chronic users of hypnotics.

RATIONALE: Many older adults report sleep problems and use of hypnotics. Several studies have shown that hypnotics can have acute adverse effects on driving the next morning. It is unclear however whether driving of chronic hypnotic users is impaired. Therapeutic effects on insomnia and development of tolerance may reduce the residual effects on driving. OBJECTIVES: The present study aimed to compare actual driving performance and driving-related skills of chronic hypnotic users to good sleepers. To determine whether insomnia itself affects driving performance, driving and driving-related skills were compared between insomnia patients who do not or infrequently use hypnotics and good sleepers. METHODS: Twenty-two frequent users of hypnotics (using hypnotics ≥ 4 nights per week for more than 3 months), 20 infrequent users (using hypnotics ≤ 3 nights per week), and 21 healthy, age-matched controls participated in this study. On the night before testing, all subjects were hospitalized for an 8-h sleep recorded by polysomnography. Frequent hypnotic users used their regular medication at bedtime (2330 hours), while infrequent users and controls received no medication. Cognitive performance (word learning, digit span, tracking, divided attention, vigilance, and inhibitory control) was assessed 8.5 h and driving performance between 10 and 11 h after bedtime and dosing. RESULTS: Polysomnographic recordings did not significantly differ between the groups, but the insomnia patients, treated or untreated, still reported subjective sleep complaints. Results show no differences in driving performance and driving-related skills between both groups of insomnia patients and controls. CONCLUSIONS: Driving performance in chronic users of hypnotics and untreated insomnia patients is not impaired. For chronic users, this may be due to prescription of relatively safe drugs and low doses. For untreated insomniacs, this corroborates previous findings showing an absence of neuropsychological deficits in this group of patients.

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study.

RATIONALE: Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. OBJECTIVES: The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). METHODS: The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. RESULTS: Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. CONCLUSIONS: The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

The protein kinase C inhibitor sotrastaurin allows regulatory T cell function.

The novel immunosuppressant sotrastaurin is a selective inhibitor of protein kinase C isoforms that are critical in signalling pathways downstream of the T cell receptor. Sotrastaurin inhibits nuclear factor (NF)-κB, which directly promotes the transcription of forkhead box protein 3 (FoxP3), the key regulator for the development and function of regulatory T cells (Tregs). Our center participated in a randomized trial comparing sotrastaurin (n = 14) and the calcineurin inhibitor Neoral (n = 7) in renal transplant recipients. We conducted ex vivo mixed lymphocyte reaction (MLR) and flow cytometry studies on these patient samples, as well as in vitro studies on samples of blood bank volunteers (n = 38). Treg numbers remained stable after transplantation and correlated with higher trough levels of sotrastaurin (r = 0·68, P = 0·03). A dose-dependent effect of sotrastaurin on alloresponsiveness was observed: the half maximal inhibitory concentration (IC50 ) to inhibit alloactivated T cell proliferation was 45 ng/ml (90 nM). In contrast, Treg function was not affected by sotrastaurin: in the presence of in vitro-added sotrastaurin (50 ng/ml) Tregs suppressed the proliferation of alloactivated T effector cells at a 1:5 ratio by 35 versus 47% in the absence of the drug (P = 0·33). Signal transducer and activator of transcription 5 (STAT)-5 phosphorylation in Tregs remained intact after incubation with sotrastaurin. This potent Treg function was also found in cells of patients treated with sotrastaurin: Tregs inhibited the anti-donor response in MLR by 67% at month 6, which was comparable to pretransplantation (82%). Sotrastaurin is a potent inhibitor of alloreactivity in vitro, while it did not affect Treg function in patients after kidney transplantation.

Subjective sleep disturbances in children with partial epilepsy and their effects on quality of life.

PURPOSE: The purposes of this study were to explore the prevalence of sleep disturbances in a large cohort of school-aged children with partial epilepsy, to compare the findings with those in children without epilepsy of the same age and gender, and to evaluate the relationship between sleep disturbances and health-related quality of life (HRQoL). METHODS: One hundred thirty children with partial epilepsy aged 4 to 10years, who were treated in the outpatient setting of a Dutch epilepsy clinic, and 161 age- and sex-matched controls participated in this study. In addition to providing information about their child's demography and health, parents of both groups of children completed three questionnaires to measure their child's sleep [Sleep Disturbance Scale for Children (SDSC), Medical Outcomes Study-Sleep Scale (MOSS-S), and Groningen Sleep Quality Scale (GSQS)] and one questionnaire to measure quality of life (Kidscreen-27). Parents of children with epilepsy also completed the Hague Scales to measure the severity of epilepsy. The prevalence of sleep disturbances and scores on HRQoL in children with and without epilepsy were compared. Additionally, the HRQoL scores were compared between children with and without sleep disturbances in children both with and without epilepsy. RESULTS: The answers for all three questionnaires suggested worse sleep in children with epilepsy than in children of the same age and gender without epilepsy. Pathological scores (T-value>70) for total SDSC were seen twelve times more frequently in children with epilepsy (36.92% vs. 3.01%, p<0.001). Children with epilepsy also scored significantly lower for all dimensions of HRQoL. Between subgroups of children with and without disturbed sleep, insignificant differences in quality of life were found, with the lowest scores in children with sleep disturbances in both groups. CONCLUSION: This study confirms the high prevalence of disturbed sleep, as well as its effect on quality of life, in a large group of children with partial epilepsy. The abnormalities are both more prevalent and more severe than in children without epilepsy.

Sleep monitoring by actigraphy in short-stay ICU patients.

Sleep deprivation is common in intensive care unit (ICU) patients. The criterion standard for sleep monitoring, polysomnography, is impractical in ICU. Actigraphy (a wrist watch indicating amount of sleep) proved to be a good alternative in non-ICU patients, but not in prolonged mechanically ventilated patients, probably due to ICU-acquired weakness. Short-stay ICU patients do not suffer from ICU-acquired weakness. However, the accuracy of actigraphy is unknown in these patients. Therefore, we compared actigraphy to polysomnography in short-stay ICU patients. Sleep measurements were conducted in 7 postcardiothoracic surgery patients. The sensitivity (percentage of actigraphy data that agreed with sleep determined using polysomnography) and specificity (percentage of actigraphy data that agreed with awake determined using polysomnography) were calculated. The result showed that actigraphy underestimated the amount of wake time and overestimated the amount of sleep. The median specificity for actigraphy was always less than 19% and sensitivity more than 94%. Therefore, actigraphy is not reliable for sleep monitoring in short-stay ICU patients.

Predicting success of vagus nerve stimulation (VNS) from interictal EEG.

PURPOSE: Vagus nerve stimulation (VNS) has shown to be an effective treatment for drug resistant epilepsy in numerous patients, however, not in all. It is still not possible to predict which patients will profit from VNS. In this pilot study, we explore predictive interictal EEG features for seizure reduction after VNS. METHODS: 19 Patients with medically refractory epilepsy and an implanted VNS system were included. Interictal EEG registrations, recorded before implantation, were retrospectively analysed. A quantative symmetry measure, the pair wise derived brain symmetry index (pdBSI), was tested to predict VNS outcome. Reduction in seizure frequency was used to define the responders. RESULTS: 10 Patients did respond to VNS, of whom 7 patients had a seizure reduction of at least 50% in a follow-up period of 2 years. On average, we find higher pdBSI values for delta, theta, alpha and beta bands for non-responders than for responders. The average pdBSI of the theta and alpha bands could significantly discriminate between responders and non-responders. CONCLUSION: In this study, quantifying EEG symmetry using the pdBSI shows promising results in predicting the reduction of seizure frequency after VNS treatment.

Severe non-type-1 Legionella pneumophila infection without pneumonia.

We present a patient with myalgia and ongoing fever without respiratory symptoms caused by a Legionella pneumophilia infection. We conclude that in patients with fever of unknown origin legionellosis should be considered, even in the absence of pulmonary symptoms. When considering legionellosis, diagnostic tests should include the urinary antigen test.

Consensus on the use of neurophysiological tests in the intensive care unit (ICU): electroencephalogram (EEG), evoked potentials (EP), and electroneuromyography (ENMG).

STUDY AIM: To provide a consensus of European leading authorities about the optimal use of clinical neurophysiological (CN) tests (electroencephalogram [EEG]; evoked potentials [EP]; electroneuromyography [ENMG]) in the intensive care unit (ICU) and, particularly, about the way to make these tests clinically useful for the management of individual patients. METHODS: This study gathered together several European clinical neurophysiologists and neurointensivists whose leading contributions in the adult or paediatric ICU and in continuous neuromonitoring had been peer-acknowledged. It was based on both a literature review and each participant's own experience. Given the methodological impossibility to gather studies fulfilling criteria of evidence-based medicine, this article essentially relies on expert opinions that were gained after several rounds, in which each expert was invited to communicate his own contribution to all other experts. A complete consensus has been reached when submitting the manuscript. RESULTS: What the group considered as the best classification systems for EEG and EP abnormalities in the ICU is first presented. CN tests are useful for diagnosis (epilepsy, brain death, and neuromuscular disorders), prognosis (anoxic ischemic encephalopathy, head trauma, and neurologic disturbances of metabolic and toxic origin), and follow-up, in the adult, paediatric, and neonatal ICU. Regarding prognosis, a clear distinction is made between these tests whose abnormalities are indicative of an ominous prognosis and those whose relative normalcy is indicative of a good prognosis. The prognostic significance of any test may vary as a function of coma etiology. CONCLUSION: CN provides quantitative functional assessment of the nervous system. It can be used in sedated or curarized patients. Therefore, it should play a major role in the individual assessment of ICU patients.

[Interactions of epilepsy and psychiatric problems: life-threatening situations]. / Interactie van epilepsie en psychiatrische problematiek: levensbedreigend.

Epilepsy and psychiatric problems can occur simultaneously and can, quite unexpectedly, trigger interactions that may lead to life-threatening situations. This became obvious in the case of a female patient who suddenly developed a status epilepticus while admitted to hospital. The seizure was probably connected with secret self-induced vomiting which led to a low intake of antiepileptic medication. She used the vomiting to control emotionally charged post-traumatic intrusions. Both the vomiting and the number of seizures were triggered by a life event (in this case emigration). In case of epilepsy, early screening for psychopathology seems advisable because there may be interactions with epileptic variables.

[The restless legs syndrome can be treated with dopamine agonists]. / Het 'restless legs'-syndroom, te behandelen met dopamineagonisten.

In three patients, a man aged 46 years and two women aged 74 and 38 years, respectively, restless legs syndrome (RLS) was diagnosed. The second patient had a low serum ferritin concentration. The patients were successfully treated with ropirinol, iron suppletion and gabapentine, and pramipexol, respectively. With a prevalence of 7% in the general population, RLS is a frequent disease. Patients complain about unpleasant feelings in the legs and have an urge to move the legs, causing discomfort during rest. Sleep is disturbed significantly, which interferes with normal functioning of the patients during the day. RLS may be caused by anaemia, uraemia or as a side effect of drugs such as selective serotonin uptake inhibitors (SSRIs), lithium and tricyclic antidepressants. RLS can be treated successfully by dopaminergic agents, especially dopamine agonists.

Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment.

CONTEXT: Recently, several cases of sudden death in GH-treated and non-GH-treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH treatment in PWS results in a remarkable growth response and an improvement of body composition and muscle strength. Data concerning effects on respiratory parameters, are however, limited. OBJECTIVE: The objective of the study was to evaluate effects of GH on respiratory parameters in prepubertal PWS children. DESIGN: Polysomnography was performed before GH in 53 children and repeated after 6 months of GH treatment in 35 of them. PATIENTS: Fifty-three prepubertal PWS children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and body mass index of +1.0 sd score (-0.1-1.7). INTERVENTION: Intervention included treatment with GH 1 mg/m2.d. RESULTS: Apnea hypopnea index (AHI) was 5.1 per hour (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0-28.0). AHI did not correlate with age and body mass index, but central apneas decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P = 0.36). One patient died unexpectedly during a mild upper respiratory tract infection, although he had a nearly normal polysomnography. CONCLUSIONS: PWS children have a high AHI, mainly due to central apneas. Six months of GH treatment does not aggravate the sleep-related breathing disorders in young PWS children. Our study also shows that monitoring during upper respiratory tract infection in PWS children should be considered.