Leukoencephalopathy with calcifications and cysts: a purely neurological disorder distinct from coats plus.

OBJECTIVE: With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. PATIENTS AND METHODS: A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. RESULTS: The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. CONCLUSION: LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.

Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

BACKGROUND AND OBJECTIVE: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG-IgG titers in children with MOGAD in correlation with clinical presentation and disease course. METHODS: In this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG-positive. RESULTS: One hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG-negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG-negative. DISCUSSION: In this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG-negative, are shown to have a significantly reduced relapse risk.

MOG antibody associated demyelinating syndrome presenting as aseptic meningitis in a 6-year-old boy.

We describe the case of a 6-year-old boy who developed myelin oligodendrocyte glycoprotein antibody (MOG-Ab) associated demyelinating syndrome, after initially presenting with aseptic meningitis. Magnetic resonance imaging showed cerebral and spinal lesions consistent with acute disseminating encephalomyelitis. Rapid clinical improvement occurred after intravenous high dose methylprednisolone. A small number of cases with MOG-Ab associated demyelinating syndrome presenting as aseptic meningitis have previously been reported in adults, but to our knowledge, this is the first pediatric case of this new clinical phenotype.

Complementary and alternative medicine in paediatrics: a systematic overview/synthesis of Cochrane Collaboration reviews.

BACKGROUND: A high prevalence of complementary and alternative medicine (CAM) use has been documented in children with chronic illnesses. Conversely, evidence-based medicine is considered an important contributor in providing the best quality of care. METHODS: We performed a systematic overview/synthesis of all Cochrane reviews published between 1995 and 2012 in paediatrics that assessed the efficacy, and clinical implications and limitations of CAM use in children. Main outcome variables were: percentage of reviews that concluded that a certain intervention provides a benefit, percentage of reviews that concluded that a certain intervention should not be performed, and percentage of studies that concluded that the current level of evidence is inconclusive. RESULTS: A total of 135 reviews were included - most from the United Kingdom (29/135), Australia (24/135) and China (24/135). Only 5/135 (3.7%) reviews gave a recommendation in favour of a certain intervention; 26/135 (19.4%) issued a conditional positive recommendation, and 9/135 (6.6%) reviews concluded that certain interventions should not be performed. Ninety-five reviews (70.3%) were inconclusive. The proportion of inconclusive reviews increased during three, a priori-defined, time intervals (1995-2000: 15/27 [55.6%]; 2001-2006: 33/44 [75%]; and 2007-2012: 47/64 [73.4%]). The three most common criticisms of the quality of the studies included were: more research needed (82/135), low methodological quality (57/135) and small number of study participants (48/135). CONCLUSIONS: Given the disproportionate number of inconclusive reviews, there is an ongoing need for high quality research to assess the potential role of CAM in children. Unless the study of CAM is performed to the same science-based standards as conventional therapies, CAM therapies risk being perpetually marginalised by mainstream medicine.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

EEG-related functional MRI in benign childhood epilepsy with centrotemporal spikes.

The localization of epileptic foci is an important issue in children with extratemporal epilepsies. However, the value of noninvasive methods such as the EEG-assisted functional magnetic resonance imaging (fMRI) has not been sufficiently investigated in children. As a model of extratemporal epilepsies, we studied 7 patients aged 5 to 12 (median 10) years with benign childhood epilepsy and centrotemporal (rolandic) spikes. Interictal spikes were recorded during the fMRI acquisition on a MR-compatible battery-powered digital EEG system with 16 channels. The fMRI sequences were correlated off-line with the EEG spikes and analyzed with the software Statistical Parametrical Mapping SPM99. The fMRI results demonstrated the spike-related activation in the perisylvian central region in three patients; we could not demonstrate fMRI activation despite active spiking in 2 patients, and 2 patients did not produce sufficient spikes for fMRI analysis. We currently consider the spike-related fMRI as a research tool that localizes epileptic activity in selected patients. Further improvements of the technique are necessary to allow a clinical application of this method.