Longitudinal Data in Patients with Niemann-Pick Type C Disease Under Combined High Intrathecal and Low Intravenous Dose of 2-hydroxylpropyl-ß-cyclodextrin.

Niemann-Pick Type C disease (NPC) is a rare, incurable, autosomal-recessive, lysosomal storage disorder with protean and progressive neurovisceral manifestations characterized by accumulation of intracellular unesterified cholesterol. The investigational use of 2-hydroxypropyl-beta-cyclodextrin (HP-ß-CD) in the treatment of NPC has shown promising results in improving life expectancy and reducing neurological damage in this patient population. This case report describes two children with the neurological form of NPC: a 5-year-old male patient in advanced stage of the disease and an 11-year-old female patient in moderately advanced stage. Despite treatment with the enzyme inhibitor, miglustat, both patients continued to exhibit severe neurodegeneration. High intrathecal (900mg) and low intravenous (350-500mg/kg) doses of HP-ß-CD (Trappsol®Cyclo™) were administrated twice monthly to the patients in addition to miglustat therapy. The patients were monitored clinically as well as by imaging, laboratory, and biomarker (e.g., total tau protein [T-tau]; phosphorylated tau [P-tau]; neurofilament light [NFL], oxysterols) studies over a period of 16 to 22 months. The combination therapy of miglustat and HP-ß-CD resulted in disease stabilization in both patients. The combination therapy demonstrated a good safety profile, and no adverse effects on hearing were observed. Additionally, CSF biomarkers appeared useful in monitoring neuronal damage. Large, randomized studies are needed to confirm these findings.

Effect of levetiracetam monotherapy on lipid profiles and thyroid hormones in children with epilepsy: A prospective study.

Long-term treatment with some older antiepileptic drugs may lead to dyslipidemia or thyroid disturbances. The effect of levetiracetam (LEV), a newer broad spectrum antiepileptic agent, on cardiovascular risk factors is not yet sufficiently investigated. The purpose of this study was to investigate prospectively the effect of LEV monotherapy on serum lipid profile and thyroid hormones levels in children with epilepsy. The study population consisted of 39 children (21 females, 18 males, mean age 6.8 ± 4,1 years, range 2-15 years) that were treated for new-onset epilepsy with LEV monotherapy. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), lipoprotein (a) [Lp(a)], thyroxine (T4), free thyroxine (FT4) and thyrotropin (TSH), were evaluated before and at 6 and 12 (n = 28) months of LEV monotherapy. TGs were significantly decreased at 6 and 12 months of LEV treatment (p = 0.026 and p = 0.001, respectively). TGs/HDL-C ratio was significantly decreased at 6 and 12 months of LEV treatment (p = 0.024 and p = 0.003, respectively), while LDL-C/HDL-C ratio was significantly decreased at 12 months of LEV treatment (p = 0.025). There were no significant alterations in the other parameters during the study. In conclusion, long-term LEV monotherapy does not cause adverse alterations on thyroid hormones and serum lipids in children with epilepsy. More studies are needed to clarify whether LEV monotherapy have a favourable effect on serum lipids and whether LEV may be considered as a safer alternative drug for the prevention of antiepileptic drug-induced cardiovascular complications in adult life.

Short-Term and Long-Term Effects of Levetiracetam Monotherapy on Homocysteine Metabolism in Children with Epilepsy: A Prospective Study.

BACKGROUND AND PURPOSE: Long-term treatment with some older antiepileptic drugs may lead to hyperhomocysteinemia. Levetiracetam (LEV) is a newer broad-spectrum antiepileptic agent whose effects on homocysteine concentrations remain unclear. The purpose of this study was to prospectively determine the short-term and long-term effects of LEV monotherapy on homocysteine metabolism in children with epilepsy. METHODS: The study population consisted of 32 children [18 females, 14 males; age 5.94±4.10 years (mean±SD), age range 1-15 years] who received LEV monotherapy for new-onset epilepsy. Serum folate, serum vitamin B12, and plasma total homocysteine (p-tHcy) were measured before and at 2 months (n=32), 6 months (n=25), and 12 months (n=18) of LEV monotherapy. RESULTS: p-tHcy was significantly decreased at 2 months of treatment (p=0.031). Furthermore, analysis of covariance showed statistically significant decreases in p-tHcy at 2 months (p=0.013) and 6 months (p=0.015) of LEV treatment after controlling for age, sex, body mass index, and LEV dose. There were no significant alterations in the other parameters during the study. The drug doses were 18.1±7.1, 20.1±9.2, and 21.2±11.8 mg/kg at 2, 6, and 12 months of LEV treatment, respectively. CONCLUSIONS: In contrast with older antiepileptic drugs, long-term LEV monotherapy in children with epilepsy does not cause adverse alterations on homocysteine metabolism. Larger prospective studies are needed to definitively clarify whether LEV may be considered a safer alternative drug for preventing antiepileptic-drug-induced cardiovascular complications in adult life.

Long-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: A prospective study.

Studies evaluating the effect of Levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Short-term effects on haematological parameters in children with epilepsy, at 2 and 6 months of LEV treatment, have been previously reported in the literature. Purpose of the current study was to further investigate the long-term changes on haematological parameters in children with epilepsy during LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 20 children (11 females, mean age 6,5 ±â€¯4,4 years, range 2-15 years) with epilepsy, before and after 12 months of LEV monotherapy. Lymphocyte count was significantly decreased at 12 months (p = 0.003) of LEV treatment. Three children (15%) at 12 months of treatment had lymphocyte count below 10th percentile for age. Neutrophils counts were significantly increased and platelets counts were significantly decreased at 12 months of treatment (p = 0.046 and p = 0.006, respectively). In addition, haematocrit and mean corpuscular volume were significantly increased at 12 months of treatment (p = 0.036 and p = 0.031, respectively). There were no significant alterations in the other parameters evaluated during the study. No association was found between all parameters and LEV dosage (mg/kg) at 12 months of treatment. Large, prospective studies are needed to investigate the clinical significance of the above haematological changes and whether these parameters should be monitored periodically in children taking LEV.

Sleep architecture and epileptic characteristics of drug naïve patients in childhood absence epilepsy spectrum. A prospective study.

PURPOSE: Childhood absence epilepsy (CAE) is an epileptic syndrome presenting between 2nd-10th years. The spells are elicited with hyperventilation (HV) while sleep seems to exacerbate the electrical activity. Our aim is to describe sleep architecture and its relationship with epileptic discharges (EDs) in patients with CAE, before treatment and one year later. METHODS: Twenty-eight, drug-naive children were recruited (21 girls), mean age 90.1 ±â€¯32.6 months. Routine-EEG and overnight EEG-polygraphy were conducted upon diagnosis and one year later. Patients were separated in two groups of similar mean age, according to their clinical response at the second recording: group A: children with absolute control of absences and group B: children with partial control. Sleep parameters, EDs and arousals were measured. The effect of medication on sleep parameters was examined, according to 2 groups: valproic-treated and non valproic-treated. RESULTS: Group A showed significant improvement in total sleep time, REM-sleep latency, REM-sleep, arousals-number/hour and arousals-duration/hour between the two recordings. Comparing the two groups for each recording separately, group A initially demonstrated greater epileptic activity and worse sleep parameters, whereas in the second recording exhibited total elimination of the EDs and significantly less arousals. Group B demonstrated persisting EDs and slight deterioration in some sleep parameters during the second recording, despite the lower epileptic load initially. No significant difference was identified between valproic and non-valproic treated patients, regarding the effect on sleep parameters. CONCLUSION: Absolute control of absences and normalization of the electroencephalogram are accompanied by more continuous, stable and efficacious sleep in children with CAE.

OC35 - Child Friendly Healthcare Initiative, implementation project in a paediatric department in Greece.

UNLABELLED: Theme: Accreditation and quality improvement. INTRODUCTION: Child Friendly Healthcare Initiative (CFHI) aims to improve quality of experience and health care given to children and families by improving realisation of children's rights and reducing unnecessary fear, anxiety and suffering during and because of health care. AIM: To present results of preliminary CFH assessment. METHODS: Implementation was initiated in a paediatric department of a University Hospital in Athens, Greece, consisting of a 37-bed ward, Outpatient Clinic and Emergency Department. For the preliminary assessment of the CFHI tool No1, which is for parents-caregiverschildren and health workers, this was translated into Greek. 112 parents-caregivers and six children were interviewed by an independent interviewer. In total, 24 health workers - 5 paediatricians, 11 residents and 8 nurses - responded to the CFHI tool No 1. RESULTS: Issues highlighted were mostly about CFH Standard 3 and Standard 7. Suggestions for improvement in all Standards were suggested. CONCLUSIONS: Preliminary assessment revealed the quality of care needs improvement. The next step is the training health workers, planning and making improvements.

A case of startle epilepsy associated with IL1RAPL1 gene deletion.

BACKGROUND: Startle epilepsy is a type of reflex epilepsy in which the seizures are mainly precipitated by unexpected sensory stimuli. PATIENT: We present an 18-month-old boy with global developmental delay and multiple episodes of loss of tone after auditory cues. RESULTS: The neurophysiologic study (video-electroencephalographic monitoring) revealed the epileptic nature of the stimulus-induced drop attacks, and the comparative genomic hybridization analysis revealed a microdeletion encompassing the interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene. The drop attacks were refractory to initial antiepileptic treatment, but they had a satisfactory response to a synthetic adrenocorticotropic hormone analogue. CONCLUSIONS: The IL1RAPL1 gene is located on Xp21.2-p21.3 and codes a synaptic adhesion protein involved in neuronal differentiation and synapse localization, stabilization, and maturation. The coexistence of startle epilepsy and IL1RAPL1 gene deletion in this child may not be coincidental and suggests a possible involvement of IL1RAPL1 in the dysregulation of excitatory synapses and the pathogenesis of startle epilepsy.

Short-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: a prospective study.

Studies evaluating the effect of levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Clinical trials have also reported an unexplained increased incidence of pharyngitis and rhinitis in LEV-treated patients. The objective of this study was to evaluate prospectively the changes in haematological parameters in children treated with LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 22 children (13 females, mean age 6.70±4.23 years) with epilepsy, before and after 2 and 6 months of LEV monotherapy. Lymphocyte count was significantly decreased at 6 months (p=0.019) of treatment and this effect was not dose dependent. One child (4.5%) at 2 months and four children (18%) at 6 months of treatment had lymphocyte count below 10th percentile for age. There were no significant alterations in the other parameters evaluated during the study. LEV monotherapy may significantly decrease lymphocyte count at six months of treatment in children with epilepsy. Further prospective studies are needed to investigate the effect of LEV on haematological parameters and the possible association with the higher incidence of infections reported in children receiving LEV.