Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.

Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.

In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.

Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.

ClinicalTrials.gov NCT02332291

This research aimed to study the short-term seizure outcomes following treatment with 8 mg/kg/day prednisolone in children with infantile spasms (IS) refractory to vigabatrin. We hypothesized that high-dose prednisolone may result in similar rates of electroclinical remission when compared to published ACTH rates.

All consecutive children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without IS, who had been treated with vigabatrin as first-line anti-seizure medication (ASM) followed by high-dose oral prednisolone (8 mg/kg/day; maximum 60 mg/day) in cases who did not respond to vigabatrin, were included. Clinical and electroclinical response (ECR) at 2 weeks following initiation of treatment and adverse effects were assessed.

Sixty-five children were included. A genetic etiology was seen in 38.5% cases. Complete ECR was seen in 30.8% (20/65) of the patients 2 weeks after vigabatrin. Complete ECR was noted in 77.8% (35/45) of the patients, 2 weeks after prednisolone initiation in children who failed vigabatrin, and this was sustained at 6 weeks in 66.7% (30/45) patients. Prednisolone was generally well tolerated.

High-dose (8 mg/kg/day) oral prednisolone resulted in sustained complete ECR (at 6 weeks) in two-thirds of the children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without parentally reported IS. It was generally well tolerated and found to be safe.

Several guidelines currently recommend acute diffusion weighted imaging (DWI) for the detection of ischemia in transient ischemic attack (TIA). However, DWI hyperintensities resolve early and only 30%–50% with clinically defined TIA show acute DWI positivity. A recent meta-analysis reported an unexplained 7-fold variation in DWI positivity in TIA across studies, concluding that DWI does not provide a consistent basis for defining ischemia. Intracortical excitability, measured using transcranial magnetic stimulation (TMS), has previously been shown to be altered after TIA and associated with ABCD2 scores; however, whether altered cortical excitability is associated with clinical and DWI-based definitions of TIA remains unclear.

Individuals with TIA symptoms (N = 23; mean age = 61 ± 12) were prospectively recruited and underwent DWI and paired-pulse TMS. Multivariate linear regression was used to estimate associations between TMS-derived excitability thresholds, and clinical TIA diagnosis, and imaging-based evidence of cerebral ischemia (DWI positivity). Area under the curve (AUC) analyses was used to compare the discriminability of TMS-derived thresholds and clinical TIA diagnoses.

Thresholds for intracortical inhibition in the TIA-unaffected hemisphere were significantly associated with the clinical diagnosis of TIA. No associations between TMS-derived thresholds and DWI positivity were observed. TMS thresholds showed low-moderate discriminability and values differed by age (65+) and sex.

In this small sample, TMS-derived markers of intracortical excitability were associated with clinical TIA diagnoses but not DWI positivity. Our results provide preliminary evidence for the potential discriminative utility of TMS for the diagnosis of TIA and highlight the need for future work in larger cohorts.

Spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons causing muscle atrophy and weakness. Nusinersen, the first effective SMA therapy was approved by Health Canada in June 2017 and has been added to the provincial formulary of all but one Canadian province. Access to this effective therapy has triggered the inclusion of SMA in an increasing number of Newborn Screening (NBS) programs. However, the range of disease-modifying SMN2 gene copy numbers encountered in survival motor neuron 1 (SMN1)-null individuals means that neither screen-positive definition nor resulting treatment decisions can be determined by SMN1 genotype alone. We outline an approach to this challenge, one that specifically addresses the case of SMA newborns with four copies of SMN2.

To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result.

An SMA NBS pilot trial in Ontario using first-tier MassARRAY and second-tier multi-ligand probe amplification (MLPA) was launched in January 2020. Prior to this, Ontario pediatric neuromuscular disease and NBS experts met to review the evidence regarding the diagnosis and treatment of children with SMA as it pertained to NBS. A post-referral evaluation algorithm was developed, outlining timelines for patient retrieval and management.

Ontario’s pilot NBS program has created a standardized path to facilitate early diagnosis of SMA and initiation of treatment. The goal is to provide timely access to those SMA infants in need of therapy to optimize motor function and prolong survival.

In 1998, the California Department of Health Services invited all healthcare facilities in California (n = 2,532) to participate in a statewide, voluntary sharps injury surveillance project The objectives were to determine whether a low-cost sharps registry could be established and maintained, and to evaluate the circumstances surrounding sharps injuries in California.

Approximately 450 facilities responded and reported a total of 1,940 sharps-related injuries from January 1998 through January 2000. Injuries occurred in a variety of healthcare workers (80 different job titles). Nurses sustained the highest number of injuries (n = 658). In hospital settings (n = 1,780), approximately 20% of the injuries were associated with drawing venous blood, injections, or assisting with a procedure such as suturing. As expected, injuries were caused by tasks conventionally related to specific job classifications. The overall results approximate those reported by the Centers for Disease Control and Prevention's National Surveillance System for Health Care Workers and the University of Virginia's Exposure Prevention Information Network.

These data further support findings from previous studies documenting the complex and persistent nature of sharps-related injuries in healthcare workers. In the future, mandated reporting using standardized forms and consistent application of decision rules would facilitate a more thorough analysis of injury events.