BACKGROUND:Niemann-Pick disease type C (NP-C) is a neurodegenerative disease for which only palliative treatment exists, and only miglustat is effective in stabilizing neurological manifestations of NP-C. Ketogenic dietary therapies (KDT) are successfully used in patients with seizure disorders, including those associated with various inherited metabolic diseases (IMD), to reduce seizure frequency and medication requirement as well as to confer neuroprotection. Since patients with NP-C suffer pharmacorefractory seizures associated with ongoing neurodegeneration, KDT might be beneficial. The concomitant use of miglustat and KDT in patients with NP-C has not been reported.CASE PRESENTATION:We describe our experience in a now 17-year-old female with NP-C manifest early in childhood who has been successfully and continuously treated with miglustat and KDT in a palliative care setting for 3y. Although the neurodegeneration of NP-C progressed, she benefited from a reduction in seizure activity, fewer hospital stays related to seizure exacerbation, and increased alertness.CONCLUSION:KDT could be safely deployed in our patient with NP-C, in whom its effects have been beneficial. Generally KDT is demonstratedly efficacious in patients with epilepsy and IMD. It reduces seizure activity and medication requirements and confers neuroprotection. Intracellular cholesterol trafficking and regulation of cholesterol biosynthesis are impaired in NP-C, which may prompt caution with respect to dietary lipid intake.

Background/Purpose: Perampanel (PER) is a selective noncompetitive antagonist of AMPA-glutamate receptors on postsynaptic neurons. PER is used as add-on therapy for the treatment of partial and generalized tonic-clonic seizures in patients older than 12 years of age.

Background: Landau-Kleffner syndrome is an epileptic encephalopathy which occurs predominantly in normally developed children aged between 3 and 8 years old. The main symptoms are auditory agnosia, followed by regression of active speech (paraphasia, clipping), at least a complete aphasia, an EEG with epileptic characteristics /− clinical seizures. The EEG patterns show frequent temporoparietal activity, activated in slow-wave sleep. Before or during puberty seizures and EEG-abnormalities disappear. Language impairment may persist although the EEG-abnormalities disappear. Poor prognosis includes aphasia occurring in infancy and continuation of language impairment for longer than 3 years.

Case Study: Polymerase gamma (POLG) mutation leads to a mitochondrial disease, resulting in epilepsy, movement disorders, cognitive impairment, and liver dysfunction. Usually, clinical symptoms commence in early childhood, later manifestation is also possible. Here, we present a patient with POLG mutation and rapid progression.

Aims: Recent estimates suggest that pediatric epilepsies are caused by chromosomal microdeletions and/or duplications in approximately 5 to 15% of patients. Here, we report the results of molecular karyotyping in 43 children with various patterns of epileptic seizures to find epilepsy-related micro-rearrangements.

Epilepsy is a common finding in patients with chromosomal macro‐ and micro‐rearrangements but only few aberrations show a constant pattern of seizures. DNA array‐based studies have reported causative copy number variations ( CNVs ) in 5–30% of patients with epilepsy with or without co‐morbidities. The interpretation of many of the detected CNVs remains challenging. In order to identify CNVs carrying epilepsy‐related genes we investigated 43 children with various patterns of epileptic seizures, intellectual disability (ID), and minor dysmorphism, using the Illumina® Infinium Human1M‐DuoV1 array. In three patients we found likely causative de novo CNVs , i.e. deletions in 1q41q42.12 (3.4 Mb) and 19p13.2 (834 kb), and a mosaic two‐segment duplication in 17p13.2 (218 kb) and 17p13.1 (422 kb). In six additional patients there were aberrations (a deletion in one and duplications in five patients) with uncertain clinical consequences. In total, the finding of causative chromosomal micro‐rearrangements in 3 out of 43 patients (7%) and potentially causative CNVs in 6 additional patients (14%) with epilepsy and ID but without major malformations confirms the power of DNA arrays for the detection of new disease‐related genetic regions.

American Journal of Medical Genetics Part AVolume 158A, Issue 5 p. fm i-fm v Table of ContentsFree Access Table of Contents, Volume 158A, Number 5, May 2012 First published: 19 April 2012 https://doi.org/10.1002/ajmg.a.35452AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume158A, Issue5May 2012Pages fm i-fm v RelatedInformation

Stroke-like episodes are a recognized feature of inherited metabolic disorders, including propionic acidemia [1]. In their article Broomfield et al. [2] describe a metabolic stroke-like episode in an 8-month-old patient with propionic acidemia. However, due to the lack of imaging sequences, they are unable to differentiate between a cytotoxic and vasogenic edema.

Introduction: Bromide is the oldest antiepileptic drug acting by increasing GABA induced cerebral inhibition. It is licensed for primary or secondary generalized tonic-clonic seizures and is especially useful for infantile idiopathic generalized epilepsy syndromes. Favored drug combination is with valproic acid. Usual side effects are dose related drowsiness and provoked seizures by sudden reduction. Chronic side effect is bromism with mainly dermatological problems.

Propionic acidemia caused by propionyl-CoA carboxylase deficiency frequently leads to neurologic complications. Herein we report an eleven-year-old patient with propionic acidemia having three stroke-like episodes during a period of 13 months characterized by acute reversible hemiplegia and vegetative symptoms like bradycardia or drowsiness. No biochemical signs of severe metabolic decompensation were detectable in plasma. At all three episodes, EEG was not indicative for status epilepticus, but in the acute episode it showed slowing of background activity emphasized on one side. MRI revealed reversible hyperintensities in cortical grey matter and basal ganglia. During the third episode a lumbar puncture was done in parallel with venous puncture. Concentrations of glutamine (902 micromol/L), glycine (24 micromol/L) and alanine (78 micromol/L) were elevated in CSF. In plasma glycine (1 859 micromol/L) and alanine (608 micromol/L) concentrations were also elevated, whereas the glutamine (458 micromol/L) concentration was normal. CSF/plasma ratios were elevated for glutamine (1.97) and alanine (0.13) and normal for glycine (0.01). We assume that the stroke-like episodes in our patient may be caused by an acute focal cerebral metabolic decompensation, which is detectable by unspecific changes in MRI and by measuring amino acids and lactate in CSF versus plasma.

Levetiracetam (LEV) is approved as second line treatment for partial onset seizures in adults and children older than four years of age. Recently, an intravenous formulation was developed as an alternative to standard oral medication. We report the successful treatment of two children suffering from myoclonic status epilepticus with intravenous LEV. Intravenous application of LEV was safe and not associated with significant side effects. In conclusion, intravenous application of LEV appears to be a further option in treatment of children with myoclonic status epilepticus.

SummaryWe report the CSF and plasma amino acid concentrations and their ratios in a male patient with arginase1 deficiency with an unusual early presentation at 34 days of age. He developed hyperammonaemic coma (ammonia >400 μmol/L; normal <90 μmol/L) on postnatal day 35. CSF and plasma concentrations were assayed by ion‐exchange chromatography on day 36. Arginine was increased both in plasma (971 μmol/L; controls (mean ± 2SD) 50 ± 42) and in CSF (157 μmol/L; controls 19 ± 8.6), resulting in a normal CSF/plasma ratio of 0.16 (controls 0.41 ± 0.26). Interestingly, glutamine was disproportionately high in CSF (3114 μmol/L; controls 470 ± 236) but normal in plasma (420 μmol/L; controls 627 ± 246); the ratio exceeded unity (7.4; controls 0.76 ± 0.31). The CSF/plasma ratios of most neutral amino acids were elevated but not those of the imino‐ and of the dibasic amino acids lysine and ornithine. The mechanism leading to the increase of most neutral amino acids in brain is not known.Conclusion: A normal glutamine in plasma does not exclude an increased concentration in CSF; it could be useful to ascertain by MRS that a high CSF glutamine concentration truly reflects a high concentration in brain tissue for better understanding its pathogenesis.

Introduction: Urea cycle defects lead to changes of amino acid concentrations in plasma and CSF. The aim of this study is to investigate changes in amino acid CSF/plasma-ratios in these inborn errors of metabolism.