Jörg Klepper

Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review

Abstract. Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome (MIM 138140) defines a prototype of a novel group of disorders resulting from impaired glucose transport across blood-tissue barriers. It is caused by a defect in glucose transport into brain, mediated by the facilitative glucose transporter GLUT1. Since 1991, more than 70 patients have been identified. The hallmark of the disease is a low glucose concentration in the CSF (hypoglycorrhachia) in the presence of normoglycaemia (CSF/blood glucose ratio <0.4). Clinical features are variable and include seizures, developmental delay, acquired microcephaly, hypotonia, and a complex motor disorder with elements of ataxia, dystonia, and spasticity. The GLUT1 defect can be confirmed in erythrocytes by glucose uptake studies and GLUT1 immunoreactivity, and by molecular analysis of the GLUT1 gene. Several heterozygous mutations resulting in GLUT1 haploinsufficiency have been identified. An effective treatment is available by means of a ketogenic diet as ketone bodies serve as an alternative fuel for the developing brain. Conclusion: this treatable condition should be suspected in children with unexplained neurological disorders associated with epilepsy and developmental delay and confirmed by a lumbar puncture.

Oligoclonal bands predict multiple sclerosis in children with optic neuritis

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow‐up of 4.0 years. Multiple Cox proportional‐hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39–10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32–5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02–1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84‐fold higher HR for developing MS compared to double negativity (95% CI = 12.26−58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON. Ann Neurol 2015;77:1076–1082

The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy.

The effects of a long-term ketogenic diet in children with Glut1 deficiency syndrome on metabolism are unknown. Our results indicate a characteristic effect of a long-term ketogenic diet on glucose and lipid homeostasis in Glut1 deficiency syndrome. Although serum lipids and apolipoproteins reflect a proatherogenic lipoprotein profile, adipocytokine constellation is not indicative of enhanced cardiovascular risk.

Expect the unexpected: favourable outcome in Munchausen by proxy syndrome.

Abstract Munchausen by proxy syndrome (MBPS) is a form of child abuse wherein the mother fabricates or produces illness in her child. The condition is hard to diagnose and few successful interventions have been described. Long-term outcome is associated with high family disruption, reabuse, mortality and morbidity. We report on a six-month-old girl that experienced eight hospital admissions within five months. Symptoms of repeated vomiting, bloody diarrhoea and acute life-threatening events (ALTE) were never substantiated. Finally, blood in diapers and napkins presented by the mother was shown to be of maternal origin. When confronted, the mother agreed to psychiatric admission. Following five months of treatment, her mental state stabilised and she entered supported living. She remained separated from the child, who was given to the father and developed normally on close paediatric follow-up. We report a definite diagnosis and successful intervention in MBPS. The case highlights characteristic features of this entity and illustrates that a favourable outcome depends on early intervention with separation of the child and perpetrator, as well as concomitant long-term psychiatric treatment.

Treatment of Infantile Spasms: Report of the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society for Neuropediatrics.

Objectives This report aims to define treatment goals, to summarize the evidence level (EL) of different treatment options for infantile spasms (IS), both in terms of efficacy and adverse effect, and to give recommendations for the management of IS. Methods The Cochrane and Medline (1966-July 2014) databases were searched. Literature known to the guideline working group and identified through citations was also considered. The results of previously published guidelines were taken into account in our analysis. Rating the level of evidence followed the Scottish Intercollegiate Guidelines Network. Recommendations If IS are suspected, electroencephalogram (EEG) should be performed within a few days and, if confirmed, treatment should be initiated immediately. Response to first-line treatments should be evaluated clinically and electroencephalographically after 14 days.Adrenocorticotropic hormone, corticosteroids, and vigabatrin are the first-line drugs for the treatment of IS. In children with tuberous sclerosis complex, vigabatrin is the treatment of first choice. Ketogenic diet, sulthiame, topiramate, valproate, zonisamide, and benzodiazepines can be used when first-line drugs have proved ineffective. Children refractory to drug therapy should be evaluated for epilepsy surgery, especially if focal brain lesions are present.Regular follow-up controls, including EEG (preferably sleep EEG) and standardized developmental assessment are recommended.

OP64 – 2760: Oligoclonal bands predict multiple sclerosis in children with isolated optic neuritis

Background Isolated optic neuritis (ON) in childhood may remain a single episode or mark the clinical beginning of multiple sclerosis (MS). Higher age and pathological cranial MRI (cMRI) at presentation were previously demonstrated as independent risk factors of conversion to MS. Objective To further evaluate potential MS risk factors, including cerebrospinal fluid findings (CSF), in children with ON as a first demyelinating event. Methods Children with isolated uni- or bilateral ON as a first demyelinating event below age 18 were included in this retrospective multicenter cohort study. The minimal follow-up (FU) for those not converting to MS according to McDonald 2010 was 2 years. Age, sex, laterality of ON, cMRI (no vs ≥1 MS-compatible lesion outside the optic nerves) and intrathecal oligoclonal IgG bands (OCB) were assessed as risk factors using simple and multiple Cox proportional-hazards regressions. Results Of 357 included children 284 had uni- and 73 bilateral isolated ON. Median FU of patients not developing MS was 4.2 years (range 2.0–22.0). Univariate analyses revealed age (HR 1.15, 95% CI 1.10–1.22, p Conclusion Cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON as a first demyelinating event.