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.

FLIP&FLAP-a training programme for children and adolescents with epilepsy, and their parents.

OBJECTIVE: The objective of this article is to present the development, contents and efficacy of the FLIP&FLAP programme for children and adolescents with epilepsy, and their parents. INTERVENTION: The programme is mainly directed at age-appropriately developed children and adolescents between 6 and 16 who take antiepileptic drugs. It is conducted as a 2.5-day group training programme; children and parents are grouped separately. The main focuses are: EVALUATION STUDY: We performed a multi-centre non-randomised two-group pre-/post-trial using a waiting-list control group design. 10 German epilepsy centres participated. The intervention group, IG (21 children 8-11 years, 44 adolescents 12-16 years, 72 parents) completed standardised questionnaires immediately before the FLIP&FLAP course and 6 months later; the waiting control group, WCG (31 children, 39 adolescents, 72 parents) 6 months before and immediately before the course. Compared to the WCG, the children and parents of the IG showed significantly improved knowledge of epilepsy, with medium to large effect sizes (univariate analysis of variance with repeated measurements, d=0.6-1.4). Parents of the IG reported improved self-management skills (d=0.7) and communication skills (d=0.8) of their child and fewer epilepsy-related worries (d=0.5). Children and adolescents of the IG reported improved HRQOL in the Social Exclusion dimension (d=0.3). CONCLUSION: FLIP&FLAP is an effective child- and family-centred programme. It is currently being established in Northern Germany to test its usefulness in routine care.

[Congenital syphilis after reactivation of "healed" maternal primary infection]. / Lues connata nach Reaktivierung einer "ausgeheilten" mütterlichen Primärinfektion.

UNLABELLED: The congenital syphilis is an infectious fetopathy which is able to affect the whole organism. In most cases symptoms are not obvious before week fourth to twelve of life. The infection of the mother is the precondition for the child's disease. The placental transfer takes place after the fifth to sixth month of gestation. We report about an eight week old baby with congenital syphilis. The positive maternal laboratory findings in the 4th month of pregnancy have been interpreted as a completely cured earlier infection causing a sero scar. The diagnosis became evident by serological tests detecting reactivation of maternal infection in late pregnancy and the clinical signs of acute infection of the child. CONCLUSION: There is a high risk of reactivation of maternal syphilis in the third trimenon even if the mother does not show any symptoms. In this case further serological tests in the prenatal care and careful examination of the newborn must be initiated.

[A comparative study about the therapeutic effect of theophylline and doxapram in apnoeic disorders]. / Vergleichende Untersuchung zur Wirkung von Theophyllin und Doxapram bei Apnoen.

The objective of this study was to prove the superiority of doxapram compared to theophylline therapy in apneas of prematurity in very low birth weight infants. Therefore all VLBW infants (gestational age < 35 weeks) were randomized if they had in a 2 hours-interval more than 2 apneas, 4 bradycardias or 4 oxygen desaturations. They received either theophylline (loading dose 5 mg/kg b. w., 3 mg/kg b. w. bid) or doxapram by continuous infusion of 0.5 mg/kg/h. Apneas, bradycardias and desaturations were recorded from the trend analysis of our monitoring system over the first 3-days and a 7 days period and compared statistically (Mann-Whitney U-test). Plasma levels of both drugs and a polysomnographic recording were obtained during steady state conditions in parallel to a behavioral observation according to Prechtl. The recorded events were again compared using the Mann-Whitney U-test. Twenty patients were treated with theophylline, 14 with doxapram. In 9 patients of each group we could perform a polysomnography and behavioral observation. The incidence of apneas, bradycardias and desaturations in a 7 days-interval was not significantly different between both groups. Analyzing the first 3 days of treatment, however, we could detect a significantly lower rate of apneas in the doxapram group (2.5 apneas compared to 7 in the theophylline group, p < 0.037). In the polysomnographic recording and in our behavioral observations we could not record any significant differences between both groups. Therefore we can conclude that theophylline and doxapram are comparable in the treatment of apneas of prematurity, however, doxapram is superior to theophylline in reducing the rate of apneas in the first 3 days of treatment.

[Factitious skin lesions as an expression of a family crisis]. / Artifizielle Ekchymosen als Ausdruck einer familiären Krise.

The factitious disorder is a deliberately induced, hidden self-mutilation based on a psychic conflict. We present a previously healthy nine-year old girl with initially obscure symmetric skin lesions. Family history, psychological exploration, special tests like pictural expression and scenial exhibition revealed the child's fear of a divorce of her parents and her own identity problem. These examinations aroused the suspicion that the girl could only express her conflict of ambivalence by self-injury behavior in the meaning of artificial disease. Guided by this impression, an intensive conversation with both parents was undertaken, focussing the familiar crisis. Afterwards, the skin lesions disappeared the girl admitted the self-mutilation. A family therapy was initiated.

Pre-PTCA detection of chronic but reversible postischemic myocardial dysfunction by nicardipine.

The aim of the study was to find out whether in patients (n = 24) with one-vessel coronary artery disease, reversibility of related left ventricular (LV) wall motion abnormalities after successful percutaneous transluminal coronary angioplasty (PTCA) can be predicted by the immediate effect of calcium antagonist nicardipine. Dynamic quantitative left cineventriculography performed four times successively (as the control, 30 minutes after oral nicardipine, 10 minutes after PTCA, and 6 months after PTCA) and hemiaxis method (mean relative hemiaxis shortening or Xdeltar%) were used for wall motion analysis of 48 poststenotic LV myocardial segments divided into three groups: hypokinetic noninfarcted (PNHS, n = 25), infarcted (PIS, n = 12), and normokinetic noninfarcted (PNNS, n = 11) and of 24 normal LV myocardial segments (NS). In PNHS and PIS close correlation (r = 0.75, P < 0.0001 and r = 0.71, P < 0.005) was demonstrated between postnicardipine improvement (21 +/- 4% to 37 +/- 9%, P < 0.0001, and 16 +/- 7% to 20 +/- 8%, P < 0.0005) and 6 months after PTCA improvement (21 +/- 4% to 33 +/- 7%, P < 0.0001, and 16 +/- 7% to 19 +/- 9%, P < 0.0005) of wall motion. It was loose in PNNS and absent in all three groups immediately after PTCA. The sensitivity of the nicardipine test for 6 months after PTCA reversible LV segmental hypokinesia was high in PNHS (95%) and lower in PIS and PNNS (67% and 60%, respectively). The specificity was 100% in PIS, lower in PNNS (67%), and absent in PNHS (owing to lack of true nonresponders). Immediately after PTCA, contraction significantly improved only in PNHS; the nicardipine test was 100% sensitive but nonspecific. Significant improvement of contraction of all groups of poststenotic LV wall segments is expected 6 months after successful PTCA of related artery stenosis, being well predictable by the pre-PTCA effect of nicardipine, at least in PNHS and in PIS. Immediately after PTCA, only in PNHS can significant improvement of contraction be expected.

Prevention of pacing-induced silent myocardial ischaemia by nifedipine in coronary heart disease.

In 11 patients with angiographically documented significant coronary heart disease silent (asymptomatic) segmental myocardial ischaemia was induced by rapid atrial pacing using the sub-threshold rate (10 impulses min-1 less than angina-threshold rate). The effect of pacing-induced silent myocardial ischaemia on the left ventricular contraction was studied from three consecutive quantitative cineventriculographies--performed in control conditions (I) and during sub-threshold pacing before (II) and after (III) 20 mg nifedipine sublingually. On this basis, left ventricular mean relative hemiaxis shortening (X delta r%) for anterior, inferior and apical segments as well as ventricular volumes and ejection fraction using an area-length method were determined for every patient. Sub-threshold atrial pacing significantly (P less than 0.0005) reduced X delta r% of non-infarcted post-stenotic myocardial segments (36 +/- 10%----23 +/- 10%; N = 14) having no significant effect on the contraction of normal and infarcted segments. As a consequence, left ventricular ejection fraction (72 +/- 10%----64 +/- 14%; P less than 0.005) and end-systolic volume (33 +/- 16 ml----43 +/- 20 ml; P less than 0.005) deteriorated too. After 20 mg nifedipine sublingually in post-stenotic non-infarcted segments characterized by pacing-induced silent ischaemia, normalization of X delta r% (23 +/- 10%----42 +/- 11%; P less than 0.0005) was observed together with significant improvement of ejection fraction (64 +/- 14%----75 +/- 10%; P less than 0.005) and with reduction of the aortic end-diastolic pressure (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of sublingual nifedipine on segmental and global left ventricular function in coronary artery disease; an angiographic study.

In 12 patients with significant coronary artery disease (CAD) segmental and global left ventricular (LV) function was studied by quantitative cineventriculography before and 5 min after sublingual administration of 20 mg nifedipine (N). Significant increase of mean relative hemiaxes shortening of inferior (24 +/- 10%----38 +/- 13%) and apical (31 +/- 10%----42 +/- 14%) wall segments, as well as improvement of ejection fraction (61 +/- 14%----75 +/- 14%), mean circumferential fiber shortening velocity (1.05 +/- 0.46 ccf/s----1.41 +/- 0.47 ccf/s) and end-systolic volume (57 +/- 26 ml----37 +/- 27 ml) of the LV were found after administration of N. The highest increase of segmental contraction (28 +/- 11%----44 +/- 16%; p less than 0.001) was noted in 20 noninfarcted wall segments, perfused by significantly stenosed coronary arteries. No significant improvement could be detected in 6 infarcted segments. A second group consisting of 12 patients with CAD showed a significant reduction of the aortic end-diastolic pressure (89 +/- 9 mm Hg----79 +/- 7 mm Hg; p less than 0.001) but no significant change of isovolumic contractility indices and heart rate was observed after N administration. The study suggests that acute improvement of LV function, found 5 min after sublingual administration of N, is mainly due to improved contraction of ischemic myocardial wall segments. Among different possible reasons for this improvement LV afterload reduction after N administration seems to be the most important one.

Intrahisian block in cardiomyopathy.

Two patients with cardiomyopathy and intrahisian atrioventricular [A-V] block are described. The first patient with underlying non-obstructive hypertrophic cardiomyopathy had split His bundle potentials only during atrial pacing and presented associated conduction abnormalities: enhanced A-V nodal conduction and sick sinus syndrome. The second patient had progressive muscular dystrophy and a complete intrahisian A-V block. Attention is called to the possible interrelationship between different conduction abnormalities and to their clinical implications.

[Fibromyxoma of the left ventricle as a cause of heart aneurysm and recurrent thromboembolism]. / Fibromiksom levega prekata kot vzrok srcne anevrizme in ponavljajocih se tromboembolij.

Primary heart tumours are a rarity but no more an academic curiosity. When recognised they may be successfully surgically treated. A Cardiac tumour is to be suspected in thromboembolism of young people especially in the absence of cardiac symptoms. A short review of possible symptoms and diagnostic methods available in the present is given. A successfully operated case of fibromyxoma of the left ventricle with consecutive cardiac aneurysm and peripheral thromboembolism is presented. Selective coronary angiography and cine-cardioangiography were the deciding investigations. The nature of the tumour is shown by means of classical histology as with the aid of electron microscopy.

[Systolic time intervals of the left ventricle in neuromuscular diseases]. / Die systolischen Zeitintervalle der linken Herzkammer bei neuromuskulären Krankheiten

In 64 patients having neuromuscular disease and in 11 healthy persons, preejection period (PEP), ejection time index (LVETI) and PEP/LVET ratio of the left ventricle were studied by indirect method. PEP was significantly longer, ejection time index was significantly shorter and PEP/LVET ratio was significantly higher in patients with progressive muscular dystrophy than healthy persons. In 75% of patients having this disease LVETI was shortened and only in 30% of them Ecg abnormalities could be detected. These findings are postulated to be due to diffusely decreased contractility of the left ventricular heart muscle in progressive muscular dystrophy.

Myocardial contractility in primary nonobstructive myocardiopathy.

Left ventricular myocardial function was studied in 13 patients with primary nonobstructive myocardiopathy and compared to the values determined in two control groups. Peak rate of rise of ventricular pressure (max dp/dt) and rate of the proportional rise of ventricular pressure at max dp/dt [(max dp/dt)p-1] were significantly decreased and interval t-max dp/dt was significantly prolonged in primary myocardiopathy, indicating that decreased contractility is characteristic of this disease. Left ventricular pre-ejection period (PEP) was significantly prolonged and PEP/LVET (left ventricular ejection time) ratio was significantly higher in patients with primary myocardiopathy. Increased end diastolic volume (EDV) and end diastolic pressure (EDP) were not characteristic of this diease. Best correlations were found between (max dp/dt)p-1 and t-max dp/dt (r = 0.71). Good correlations between PEP/LVET and internal indices of myocardial contractility qualify this ratio as a simple and useful index of myocardial contractility in various heart diseases.