Adaptive functioning and neurodevelopment in patients with Dravet syndrome: 12-month interim analysis of the BUTTERFLY observational study.

OBJECTIVE: The BUTTERFLY observational study aims to elucidate the natural trajectory of Dravet syndrome (DS) and associated comorbidities in order to establish a baseline for clinical therapies. We present the 12-month interim analysis of the study. MATERIALS AND METHODS: Patients with a genetically confirmed diagnosis of DS were enrolled in the study. Adaptive functioning and neurodevelopmental status were measured using the Vineland Adaptive Behavior Scale, Third Edition (Vineland-III), Bayley Scales of Infant Development, Third Edition (BSID-III), and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Executive function, ambulatory function and locomotor activities, and overall clinical status were measured using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) scale, Gillette Functional Assessment Questionnaire (Gillette FAQ), and Clinician or Caregiver Global Impression of Change scales (CGI-C or CaGI-C) respectively. RESULTS: Overall, 36 patients were enrolled across three age groups, with 35 patients completing at least part or all of one post-baseline visit through Month 12. Significant improvements in receptive communication, as assessed by Vineland-III and BSID-III raw scores, and in verbal comprehension subtests, as assessed by WPPSI-IV raw scores, were observed in BUTTERFLY patients for the all-patient group. Many patients performed on the impaired end of the BRIEF-P Global Executive Composite scale at baseline suggesting difficulties in executive function, and no significant change was observed in BRIEF-P scores for the all-patient group. Most patients performed in the dynamic range of the Gillette FAQ at baseline, and no significant change was observed in Gillette FAQ scores for the all-patient group. Lastly, there was significant improvement observed in the CaGI-C scores for the all-patient group. SIGNIFICANCE: This BUTTERFLY interim analysis shows small improvements in communication skills along with stability in other developmental abilities across patients with DS enrolled in the study from baseline to Month 12.

Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease.

INTRODUCTION: This clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy. METHODS: 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini-Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double-blind, sham-controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting. Baseline Alzheimer's disease assessment scale-cognitive (ADAS-Cog) and Clinical Global Impression of Change were assessed. 129 participants were randomized to active treatment plus standard of care (SOC) or sham treatments plus SOC. RESULTS: Subjects with baseline ADAS-Cog ≤ 30 (~85% of study population) showed a statistically significant benefit favoring active over sham. Responder analysis showed 31.7% participants in the active group with ≤ -4 point improvement on ADAS-Cog versus 15.4% in the sham group. DISCUSSION: neuroAD™ Therapy System provides a low-risk therapeutic benefit for patients with milder AD (baseline ADAS-Cog ≤30) beyond pharmacologic SOC.

Validation of the Clinical Global Impression-Corrections Scale (CGI-C) by Equipercentile Linking to the BPRS-E.

Background: The Clinical Global Impression-Corrections (CGI-C) is an adaptation of the severity scale of the Clinical Global Impression for use in correctional facilities. Although it has been shown to have good inter-rater reliability, there have been no validation studies of this instrument. Method: We analyzed data from 726 initial assessments of persons detained in two correctional facilities and compared clinician's ratings for the CGI-C and modified Brief Psychiatric Rating Scale-Expanded (BPRS-E). We used equipercentile linkage and Spearman correlations to investigate concordance in the total sample, by diagnostic groups, and by gender. Results: We found that the CGI-C scores and BPRS-E scores among persons in remand settings were significantly correlated (ρ = 0.51, p < 0.001) and that correlations were the same for men and women. We found that points of equivalence can be reliably found between the two scales using equipercentile linkage, and that those with psychotic disorders had lower BPRS-E scores than those with mood/anxiety/situational stress for equivalent CGI-C scores. Conclusion: Overall, CGI-C ratings correspond well to BPRS-E ratings for both men and women remand prisoners across diagnoses, and the CGI-C appears to be a valid tool for the assessment of severity of symptoms in this setting.