Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration

Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell–mediated therapies

EEG biomarkers for the diagnosis and treatment of infantile spasms

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computational markers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computational measures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Crisis Standard of Care: Management of Infantile Spasms during COVID‐19

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/2/ana25792_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/1/ana25792.pd

A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE). METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome. RESULTS: For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements. CONCLUSIONS: These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR

Treatment efficacy for infantile epileptic spasms syndrome in children with trisomy 21

BackgroundInfantile Epileptic Spasms Syndrome (IESS) is the most common epilepsy syndrome in children with trisomy 21. First-line standard treatments for IESS include adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Among children with trisomy 21 and IESS, treatment with ACTH or oral corticosteroids may yield higher response rates compared with vigabatrin. However, supporting data are largely from single-center, retrospective cohort studies.MethodsLeveraging the multi-center, prospective National Infantile Spasms Consortium (NISC) database, we evaluated the efficacy of first-line (standard) treatments for IESS in children with trisomy 21. We assessed clinical spasms remission at two weeks, clinical spasms remission at three months, and improvement of EEG (resolution of hypsarrhythmia) three months after initiation of treatment.ResultsThirty four of 644 (5.3%) children with IESS were diagnosed with trisomy 21. In all children with trisomy 21, epileptic spasms was their presenting seizure type. Twenty of 34 (59%) children were initially treated with ACTH, nine (26%) with oral corticosteroids, and five (15%) with vigabatrin. Baseline demographics did not vary among treatment groups. The overall clinical remission rate after two weeks of treatment was 53% including 13 of 20 (65%) receiving ACTH, three of nine (33%) receiving oral corticosteroids, and two of five (40%) receiving vigabatrin (p = 0.24). The continued clinical response rate at three months was 32% including 8 of 20 (40%) receiving ACTH, two of nine (22%) receiving oral corticosteroids, and one of five (20%) receiving vigabatrin. Thirty of the 34 (88%) children presented with hypsarrhythmia (88%). EEG improvement at three months was better for children treated with ACTH (74%) or oral corticosteroids (83%) than vigabatrin (20%; p = 0.048). Adjustment for time from epileptic spasms onset to treatment did not alter results.ConclusionsIn our cohort, epileptic spasms were the first presenting seizure type in all children with trisomy 21. Among first-line standard treatment options, ACTH may have superior efficacy for clinical and electrographic outcomes for IESS in children with trisomy 21

Medical insurance claims as a source of data for research: accuracy of diagnostic coding.

Validation of diagnostic codes in a sample of Hawaii medical insurance claims in 1986 to 1987 revealed 96% accuracy in hospital claims, high enough to supply data for research purposes. In physician claims the accuracy was only 62%. Initiation of two feedback loops to physicians from the insurer in 1989 resulted in a marked improvement of diagnostic coding accuracy by 1992 to 1994