Psychosocial health and quality of life in ICSI and naturally conceived adolescents: a cross-sectional comparison.

PURPOSE: Psychosocial health (PH) and quality of life (QoL) are important health outcomes. We compared PH and QoL of adolescents conceived with intrazytoplasmatic sperm injection (ICSI) and of naturally conceived controls. The impact of disclosure of ICSI-conception on QoL and PH was quantified. METHODS: The cross-sectional sample consisted of 545 ICSI-conceived adolescents and 427 unmatched singleton controls aged 14-18 years. Adolescents reported PH with the 'Strengths and Difficulties Questionnaire' (low values indicating high PH), and QoL with the KINDL questionnaire (high values indicating high QoL). Because of clustering of multiples within families, adjusted linear regressions with generalized estimating equations were used to compare ICSI- and naturally conceived adolescents. Missing values were treated by multiple imputation. Minimal importance was defined as half a standard deviation. RESULTS: Both ICSI and control adolescents had high PH (low mean 'total difficulties' score: 9 of 40) and high QoL (mean 'total KINDL' score: 75 of 100). Differences were generally in favour of the ICSI group. Significant differences occurred for 'impact of behavioural problems' (p = 0.033), the 'total KINDL' score (p = 0.021) and the dimensions 'physical wellbeing' (p = 0.031) and 'school' (p = 0.005), but all differences were far below minimal importance. About 80% of ICSI adolescents were informed about their mode of conception. PH and QoL were slightly higher in informed adolescents; behavioural difficulties ('total behavioural problems' and 'conduct problems') were significantly lower (p = 0.013 and p = 0.003), behavioural strengths ('prosocial behaviour') and 'physical QoL' significantly higher (p = 0.004 and p = 0.018), but differences remained clearly below minimal importance. CONCLUSIONS: Our results are reassuring for parents using ICSI and their children. Speaking openly about an ICSI conception in the family may be beneficial.

Childhood Stroke: Long-Term Outcomes and Health-Related Quality of Life with a Special Focus on the Development of Epilepsy.

BACKGROUND: Childhood stroke is rare and can predispose to post-stroke epilepsy. The purpose of this study was to evaluate long-term quality of life (QoL) in patients with childhood stroke, focusing on epileptic aspects. METHOD: This involves a retrospective study of 98 patients with childhood stroke (pre- and neonatal strokes excluded), who had been inpatients between 1986 and 2003 for early rehabilitation. Data were obtained via interviews using a standardized questionnaire: QoL evaluation with KINDL, functional outcome with Barthel Index, and motor handicaps-assessment with modified Rankin Score. RESULTS: Forty-nine of 98 patients (31 males, mean follow-up 16 years, range 8-25 years) were included. Six patients passed away (three of sudden unexpected death in epilepsy). At least one epileptic seizure occurred in 27/49 patients (occurrence: 2 days-13 years.; mean 3.3 years.). Epilepsy manifested in 19/49 patients. No correlation was found between the development of epilepsy and the location or etiology of the stroke. The presence of functional independence was significantly higher in seizure-free patients and in patients without epilepsy. For the external assessment (filled in for the patient by the parent/caregiver), there was no significant difference in QoL in patients with and without epilepsy; however, in the in-person KINDL questionnaire a significantly lower QoL was noted in epilepsy patients compared with patients without epilepsy. CONCLUSION: One important finding in our study is that in the long-term course 39% of patients developed epilepsy after a childhood stroke. It occurred as late as 13 years after the acute episode and affected the QoL especially in cognitively less handicapped patients.

Mapping risk factors for cumulative life course impairment in patients with chronic skin diseases - a systematic review.

Patients with chronic skin diseases suffer from physical and psychosocial impairments which can lead to a cumulative life-long burden. Therefore, the concept of cumulative life course impairment (CLCI) was introduced, referring to the non-reversible damage due to the persistent life-long burden. This systematic review (PROSPERO registry number: CRD42020179141) aimed at mapping the risk factors and the associated burden over time in patients with psoriasis, atopic dermatitis (AD) and hidradenitis suppurativa (HS). Three electronic databases were searched (date of the last search: December 2019). Studies with a longitudinal study design that assessed the association between a risk factor and the associated burden over time in patients with psoriasis, AD and HS were included. Quality assessment of the included studies was done using Critical Appraisal Skills Programme (CASP) checklists. In total, 40 publications reflecting 25 different studies were included: nine studies addressed patients with psoriasis, 13 patients with AD, two studies included patients with HS and one study enrolled patients with psoriasis and AD, respectively. Twenty-two potential risk factors with underlying evidence were found in this review. These risk factors include mainly sociodemographic (such as age or gender) and clinical (such as disease severity or comorbidities) variables. Disease severity and comorbidities were the most often studied risk factors, while only a few studies evaluated psychosocial risk factors over time. Patients with chronic skin diseases are at high risk to develop a life-long negative impact from the disease. However, there is a lack of data that evaluates the psychosocial burden and its influence on the patients' life course over time. The risk factors found in this review help to identify patients at risk, to treat them adequately and, ultimately, to prevent CLCI. These results can be the basis to develop a highly needed tool to assess the risk for CLCI in the future.

Significance of chronic pruritus for intrapersonal burden and interpersonal experiences of stigmatization and sexuality in patients with psoriasis.

BACKGROUND: 60-90% of patients with psoriasis suffer from pruritus and 65% report itching as one of the most burdensome symptoms, raising significant quality of life (QoL) impairments. However, pruritus is not only an intrapersonal symptom but also a psychosocial interactive phenomenon and little is known about the effects of itching on interpersonal experiences. OBJECTIVES: This study aimed to compare the disease burden and patient needs between patients with none/mild vs. moderate/severe pruritus, and to examine the impact of disease parameters and intrapersonal burden on perceived stigmatization and sexual relationships. METHODS: This cross-sectional study included German patients aged ≥ 18 years with psoriasis vulgaris. Disease severity was assessed with Psoriasis Area and Severity Index; patients reported on intensity of pruritus, skin-generic and pruritus-specific QoL, patient needs and benefits, anxiety and depression symptoms, dysmorphic concerns, perceived stigmatization and sexual dysfunction. RESULTS: A total of 107 patients with psoriasis participated (mean age = 46.3 ± 14.6 years; 52.3% male): 64 with none/mild pruritus (NRS ≤ 3) and 43 with moderate/severe pruritus (NRS ≥ 4). Patients with moderate/severe pruritus reported more QoL impairments, depression and anxiety symptoms and dysmorphic concerns, but less treatment benefits, than those with none/mild pruritus. The patient needs most frequently rated as 'very/quite important' were 'be healed of all skin defects' (88.8%), and 'be free of itching' (87.0%), with no differences between the groups. Younger age, disease severity, frequency of scratching behaviours, dysmorphic concerns and treatment benefits were positively associated with stigmatization experiences; disease severity, sleeping problems and skin-generic QoL impairments were positively associated with sexual dysfunction. CONCLUSIONS: Pruritus induces significant burden in patients with psoriasis. Along with disease severity, intrapersonal burden has a great impact on social and dyadic relationships. Treatment choices that are effective in reducing pruritus should be prioritized in patient-centred healthcare.

Disease burden and patient needs and benefits in anogenital psoriasis: developmental specificities for person-centred healthcare of emerging adults and adults.

BACKGROUND: Establishing romantic relationships involving cohabitation and/or sexual intercourse is an overriding task for many people during emerging adulthood, i.e. from their late teens through the twenties. The diagnosis of anogenital psoriasis may hinder social/intimate relationships, resulting in higher disease burden in this age group. OBJECTIVES: To compare the disease burden and patient needs/benefits between emerging adults (18-30 years) and adults (>30 years) with psoriasis, with and without anogenital involvement; and to identify sociodemographic/clinical variables accounting for better patient-reported outcomes. METHODS: Patients aged ≥18 years with psoriasis vulgaris were recruited within a cross-sectional nationwide survey randomly assigning 157 dermatology practices/clinics in Germany. Anogenital involvement was established based on a high-resolution grid on the topology of psoriasis. The main outcome measures were the Psoriasis Area and Severity Index (PASI), the EuroQoL visual analogue scale (EQ-VAS), the Dermatology Life Quality Index (DLQI) and the Patient Benefit Index (PBI). RESULTS: Participants were 1921 patients: 173 emerging adults and 1749 adults >30 years. Anogenital involvement was observed in 621 patients (32.3%). Patient with anogenital psoriasis reported decreased health and more QoL impairments compared with those without anogenital lesions. Emerging adults presented more QoL impairments and less treatment benefits than older patients, and they were more prone to underrate a wide range of needs, except when the anogenital area was affected. Beyond anogenital involvement and higher disease severity, less treatment benefits were associated with more QoL impairments, particularly for emerging adults. CONCLUSIONS: The developmental instability of many emerging adults may result in difficulties to establish/adhere to treatment goals and thus in decreased perception of treatment benefit and more QoL impairments. Anogenital involvement is a risk factor for increased disease burden regardless of age. Assessing anogenital involvement in all patients and helping younger patients to define/adhere to treatment goals should be prioritized in patient-centred healthcare for psoriasis.

Refractory focal epilepsy in a patient with methylmalonic aciduria: case report on positive and long-lasting effect of rufinamide.

We report on a 5-year-old boy with methylmalonic aciduria, an autosomal recessive inborn error of metabolism leading to accumulation of methylmalonic-CoA and thereby causing intoxication with leading symptoms of hyperammonaemia and metabolic acidosis. Hyperammonemia itself causes brain oedema. In our patient, this led to a vast metabolic stroke of the left hemisphere and subsequent pharmacoresistant epilepsy. Guided by his main seizures--drop attacks--the orphan drug rufinamide (RUF) was introduced as "off-label use" and led to freedom of drop attacks and tonic-clonic seizures over a period of 14 months as well as normalisation of the electroencephalogramm. Only once during an episode of fever and diarrhoea with reduced level of RUF did some provoked seizures with focal complex semiology for the time period of infection occur. In the 16 months follow-up, the patient also improved in his development, showing a more stable gait with the hemiparesis and understanding more complex sentences.

Levetiracetam as add-on therapy in different subgroups of "benign" idiopathic focal epilepsies in childhood.

Several recent studies have shown that levetiracetam (LEV) can be beneficial in the treatment of children with typical rolandic epilepsy (RE). Reports about the effectiveness of LEV in the treatment of children with the less benign variants in the spectrum of "benign" idiopathic focal epilepsies are still rare. Little is known about the effect of LEV on interictal epileptiform discharges in these syndromes. We report on LEV therapy in 32 children (mean age: 10.6 years, range: 4-14) with RE or variants like atypical benign idiopathic partial epilepsy of childhood (ABIPEC), Landau-Kleffner syndrome (LKS), and continuous spikes and waves during sleep (CSWS) and in children with benign idiopathic focal epileptiform discharges of childhood (BIFEDC). Cognitive and behavioral problems, not seizures, may be related to the pathological EEG. Patients with a reduction in seizure frequency >50% and/or reduction in BIFEDC >90% 3 months after having started LEV therapy were defined as responders. The average dose of LEV was 39 mg/kg body wt per day; LEV was given in monotherapy to 31.3% of the patients. Overall, 20 of 32 patients (62.5%) did benefit: 12 of 24 patients had a >50% reduction in seizure frequency; 2 of 24 patients (8.3%) were completely seizure free; 18 of 32 patients (56.3%) had a >90% reduction in BIFEDC (including CSWS); 6 of 32 (18.8%) had an EEG completely free of epileptiform discharges; and 17 of 32 (53.1%) showed improvement in cognition and/or language functions and/or behavior. Surprisingly, LEV tended to be more helpful in atypical rolandic epilepsies and other variants.

Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.

OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). CONCLUSIONS: Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome.

[Primary headache in children]. / Wann und wie müssen Sie eingreifen?

Primary idiopathic headache in childhood can usually be reliably diagnosed on the basis of a comprehensive anamnesis and neurological examination. Wherever necessary, an individualized work-up (including imaging procedures) may be needed to exclude secondary headache. Overall, treatment of headaches is integrative and multimodal, and includes pharmacotherapy, psychological interventional measures, modification. of the daily routine (e.g. drinking, sleeping) and trigger point-based physiotherapy. Fundamental to the treatment of migraine in children is a rapid and appropriate administration of analgesics. In the case of tension headache, the main therapeutic thrust is directed towards adaptation of behavior.

MRI-imaging and clinical findings of eleven children with tick-borne encephalitis and review of the literature.

OBJECTIVES: The incidence of tick-borne encephalitis (TBE) is increasing in many countries. Magnetic resonance imaging (MRI) in the course of TBE is not regularly performed in children. The aim of our study was evaluating MRI-findings of children and adolescents with TBE. PATIENTS AND METHODS: Retrospective evaluation of the charts and MRIs of patients who had been treated for TBE in the four participating hospitals in the last twenty years. RESULTS: 11 patients (5 male; age at TBE 3 weeks-15 9/12 years; mean 104.9 months) were included. MRI (within the first week after admission) revealed symmetric or asymmetric T2-hyperintensities in both thalami in 7/11 patients with additional bilateral lesions in putamen and/or caudate nucleus in 3 patients, and additional cortical lesions in 2 patients. Our youngest patient presented with T2-hyperintensities affecting the whole left cerebral hemisphere including white and grey matter and both cerebellar hemispheres. One patient had a minimal reversible T2-hyperintensity in the splenium of the corpus callosum (RHSCC). 3/11 patients had a normal MRI. 4/11 patients showed complete neurological recovery (2/4 with a normal MRI, RHSCC patient). 6/11 children survived with significant sequelae: hemiparesis (n = 4); cognitive deficits (n = 4); pharmacoresistant epilepsy (n = 2). One patient died of a malignant brain edema. DISCUSSION: A spectrum of MRI findings can be found in children with TBE, often showing involvement of the subcortical deep grey matter structures. In children presenting with a meningoencephalitis and bilateral thalamic involvement TBE should be included in the differential diagnosis.

Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

OBJECTIVE: Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. METHOD: Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. RESULTS: The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. SIGNIFICANCE: Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.

First long-term experience with the orphan drug rufinamide in children with myoclonic-astatic epilepsy (Doose syndrome).

INTRODUCTION: We evaluated the long-term efficacy and tolerability of the orphan drug rufinamide (RUF) in children with pharmacoresistant myoclonic-astatic epilepsy (MAE, Doose syndrome). METHODS: This was a retrospective European multicenter study on eight patients who had started an intention-to-treat trial of RUF between July 2007 and June 2010. Clinical information was collected via questionnaire. Responder rate was defined as reduction of seizure frequency ≥50% in comparison to four weeks before starting RUF. Maximum follow-up was eighteen months. RESULTS: Responder rates were 7/8 patients after 3 months, 6/8 patients after 6 months and 5/8 patients after 12 months. RUF seemed particularly effective in the prevention of myoclonic-astatic seizures (comparable with drop attacks in Lennox-Gastaut-Syndrome, for which RUF is particularly effective). Some loss of efficacy was noticed in the long-term observation. Side-effects occurred in two patients. Seizure aggravation was not observed. CONCLUSION: RUF seems to be a promising therapeutic option in children with MAE. Further studies are warranted to confirm these first observations.

Association of myocardial infarction with mononuclear cell expression of the cytomegalovirus chemokine receptor US28 in patients with NIDDM.

BACKGROUND: Infectious agents have been linked to atherosclerosis and its acute manifestations; however, little is known about their influence in the context of established risk factors. OBJECTIVE: To elucidate the role of the cytomegalovirus (CMV)-encoded chemokine receptor US28 in myocardial infarction (MI) afflicting patients with or without type II diabetes mellitus (NIDDM) on a molecular level. PATIENTS AND METHODS: In a group of patients (n=112) with a high prevalence of NIDDM and coronary artery disease, CMV serology was performed, and mRNA expression of US28 and immediate early 1 gene as markers of CMV reactivation were analyzed in peripheral mononuclear blood cells by a nested reverse transcription-polymerase chain reaction. Moreover, transendothelial chemotaxis assays using mononuclear cells transfected with or without US28 were performed in vitro. RESULTS: While the incidence of smoking was higher in nondiabetic patients with MI than in those without MI, significant differences in other risk factors, such as cholesterol, low density lipoprotein, fibrinogen, blood pressure, and Chlamydia pneumoniae immunoglobulin G or CMV immunoglobulin G titres, were not observed. In contrast, the levels of C-reactive protein reflecting inflammation or infection were raised in NIDDM patients with or without MI. Notably, mRNA expression of intermediate early 1 gene and US28 indicative of CMV reactivation was detected in a small subset (four of 21) of NIDDM patients with MI but not in those without MI (P<0.03). Transfection of US28 in mononuclear cells conferred transendothelial chemotaxis to monocyte chemokines, inferring a mechanism for deleterious effects of CMV under permissive conditions. CONCLUSIONS: Results show that MI was associated with mononuclear expression of CMV genes such as functional chemokine receptor US28 in a subset of patients with NIDDM, inferring that this association may predispose to MI. Ongoing infection or inflammation in NIDDM patients as shown by increased C-reactive protein may account for susceptibility to CMV reactivation and MI.