Should epileptic seizures as a first presentation be considered part of diagnostic criteria for relapsing remitting multiple sclerosis?

We report two children who presented with seizures prior to Multiple Sclerosis (MS) diagnosis. A 12-year-old female presented in status epilepticus with periventricular white matter lesions on MRI. Eleven months later, she had a severe clinical relapse fulfilling MS diagnostic criteria. A 14-year-old male, was found on neuroimaging for cholesteatoma to have multiple cortical and subcortical T2 lesions, with a focal-onset seizure 1-year later. Serial neuroimaging showed new lesions. Oligoclonal bands were positive for both patients. Epileptic seizures can be the first presentation in pediatric MS patients prior to typical demyelination symptoms, with potential for inclusion in future diagnostic criteria

De Novo Development of Mitochondria-Targeted Molecular Probes Targeting Pink1

Mitochondria play central roles in maintaining cellular metabolic homeostasis, cell survival and cell death, and generate most of the cell’s energy. Mitochondria maintain their homeostasis by dynamic (fission and fusion) and quality control mechanisms, including mitophagy, the removal of damaged mitochondria that is mediated mainly by the Pink1/Parkin pathway. Pink1 is a serine/threonine kinase which regulates mitochondrial function, hitherto many molecular mechanisms underlying Pink1 activity in mitochondrial homeostasis and cell fate remain unknown. Peptides are vital biological mediators that demonstrate remarkable potency, selectivity, and low toxicity, yet they have two major limitations, low oral bioavailability and poor stability. Herein, we rationally designed a linear peptide that targets Pink1 and, using straightforward chemistry, we developed molecular probes with drug-like properties to further characterize Pink1. Initially, we conjugated a cell-penetrating peptide and a cross-linker to map Pink1’s 3D structure and its interaction sites. Next, we conjugated a fluorescent dye for cell-imaging. Finally, we developed cyclic peptides with improved stability and binding affinity. Overall, we present a facile approach to converting a non-permeable linear peptide into a research tool possessing important properties for therapeutics. This is a general approach using straightforward chemistry that can be tailored for various applications by numerous laboratories

Ripples on rolandic spikes : A marker of epilepsy severity

Objective: Children with rolandic spikes may or may not have seizures, ranging from benign rolandic epilepsy to severe atypical rolandic epilepsy. We investigated whether ripples (80–250 Hz), superimposed on rolandic spikes in surface electroencephalography (EEG), can differentiate between different entities. Methods: In this cohort study we analyzed the EEG studies of children with rolandic spikes without other EEG or magnetic resonance imaging (MRI) abnormalities. They were divided into the following three groups: (1) rolandic spikes but no epilepsy, (2) typical rolandic epilepsy, and (3) atypical and symptomatic rolandic epilepsy. Ripples superimposed on rolandic spikes were marked in 10 minutes of EEG, and compared to the number of seizures before the EEG. Receiver operating characteristic (ROC) curves were constructed to determine the predictive value of ripples and spikes for having epilepsy (groups 2 and 3) and for differentiating benign courses (groups 1 or 2) from atypical and symptomatic epilepsy (group 3). Ripples were also marked in the time frequency spectrum of averaged rolandic spikes. Results: Ripples were found in 13 of 22 children. Children without epilepsy showed no ripples, except for a single child with only one ripple. The number of ripples showed a significant positive correlation with the number of seizures (ρ = 0.70, p = 0.001), whereas spikes had a borderline significant correlation (ρ = 0.43, p = 0.05). Presence of more than two ripples was a predictor for having seizures (area under the curve [AUC] 0.84), whereas spikes could not predict having seizures (AUC 0.53). More than five ripples predicted the difference between benign courses and atypical and symptomatic epilepsy (AUC 0.91, sensitivity 63%, specificity 100%). Ripples in the time frequency spectra appeared in all children and were not related to seizures. Significance: Absence of ripples on top of rolandic spikes predicts a relative benign clinical entity, whereas in the presence of several ripples, the child is likely to have more seizures than classical rolandic epilepsy, and pharmacologic treatment might be needed