SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy.

Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state. None of the patients displayed spasticity or pyramidal signs. Ataxia, which was noted in only three patients, was consistent with a sensory ataxia. Nerve conduction and nerve biopsy studies showed mixed demyelinating and axonal neuropathy. Brain MRI scans were either normal or revealed isolated upper vermis atrophy of the cerebellum. Our findings confirm the broad clinical spectrum associated with SACS mutations, including pure polyneuropathy without characteristic clinical and brain imaging manifestations of ARSACS.

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.

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.

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.

Glucose transporter deficiency syndrome (GLUT1DS) and the ketogenic diet.

Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1DS, OMIM 606777) is caused by impaired glucose transport into brain mediated by GLUT1, the glucose transporter at the blood-brain barrier. The condition is diagnosed by hypoglycorrhachia, impaired glucose uptake into erythrocytes, and heterozygous mutations in the SLC2A1 gene (OMIM 138140, gene map locus 1p35-31.3). Patients present with early-onset epilepsy, developmental delay, and a complex movement disorder. The phenotype is highly variable and several atypical variants have been described. The ketogenic diet (KD) provides ketones as an alternative fuel to the brain. Calculation, administration, supplements, and adverse effects of the KD in GLUT1DS do not differ from patients treated for intractable childhood epilepsy. In GLUT1DS, the KD should be introduced early to meet the energy demands of the developing brain and should be maintained into puberty. Seizures are effectively controlled, but the effects on neurodevelopment and on the movement disorder are less impressive. The KD remains the treatment of choice for GLUT1DS, but recent insights into anticonvulsive diet mechanisms, animal models for GLUT1DS, and the development of alternative KDs provide new opportunities to improve the treatment of this condition.

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

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.

GLUT1 deficiency with delayed myelination responding to ketogenic diet.

Monitoring effects of a ketogenic diet in GLUT1 deficiency syndrome without seizures is difficult. Neuroimaging is considered uninformative. We report the case of a boy with neurodevelopmental delay, severe ataxia, an E54X-mutation in the SLC2A1 gene (previously GLUT1), and neuroimaging abnormalities indicative of delayed myelination. Six months on a ketogenic diet resulted in an improved high subcortical white matter signal on T2-weighted images and a reduced N-acetylaspartate/creatine ratio. We conclude that delayed subcortical myelination may occur in GLUT1 deficiency syndrome as a nonspecific finding reflecting developmental delay. In patients without seizures, cranial magnetic resonance imaging and magnetic resonance spectroscopy may prove useful tools to monitor the response to a ketogenic diet.

Exhaled nitric oxide in children after accidental exposure to chlorine gas.

Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children.

The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.

PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures. METHODS: On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction. RESULTS: Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects. CONCLUSION: The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.

Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan.

We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3-O-methyl-D-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.