Citations

Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful hindlimb stepping in spinal rats. Recent clinical and preclinical evidence indicates that motor training with ES plays a crucial role in tuning spinal neural circuitry to generate meaningful motor output. Concurrently administered pharmacology can also facilitate the circuitry to provide near optimal motor performance in SCI rats. However, as of today, the evidence for pharmacological agents to enhance motor function in persons with complete SCI is insignificant. These and other recent findings discussed in this review provide insight into addressing the translational gap, guide the design of relevant preclinical experiments, and facilitate development of new approaches for motor recovery in patients with complete SCIs.

Synaptic loss is the structural basis for memory impairment in Alzheimer’s disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse. We localized Pin1 to dendritic rafts and postsynaptic density (PSD) and found the pathological loss of Pin1 within the synapses of AD brain cortical tissues. The loss of Pin1 activity may alter the ubiquitin-regulated modification of PSD proteins and decrease levels of Shank protein, resulting in aberrant synaptic structure. The loss of Pin1 activity, induced by oxidative stress, may also render neurons more susceptible to the toxicity of oligomers of Aβ and to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest that loss of Pin1 activity could lead to the loss of synaptic plasticity in the development of AD.

AbstractBackgroundThe acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity.ObjectiveThe objective was to assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non‐IV BDZ efficacy in the real world with regard to failure rates (primary outcome), interval to seizure control, and observed complications (secondary outcomes).MethodsA systematic review was performed using Medline, Embase, and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi‐randomized controlled trials directly comparing IV to non‐IV (buccal, rectal, intranasal, or intramuscular) BDZ were included.ResultsOur search strategy retrieved 2,604 citations for review. A total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non‐IV BDZ was superior to IV BDZ (odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56–0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74–1.81). Non‐IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69–5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52–0.95 minutes). Respiratory complications requiring intervention were similar between non‐IV BDZ and IV BDZ, regardless of administration route (risk difference = 0.00; 95% CI = –0.02 to 0.01).ConclusionNon‐IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher‐quality studies and further evaluation in different age groups are warranted.

Objective: To describe a novel case of congenital profound bilateral sensorineural hearing loss in a patient with bilateral nodular internal auditory canal and labyrinthine enhancement and temporal bone dysplasia. Patients: A 76-day-old female was referred to the authors’ center for evaluation of congenital deafness. Behavioral observations and objective audiometric evaluation demonstrated bilateral profound sensorineural hearing loss and a comprehensive multidisciplinary evaluation identified compound heterozygous pathogenic variants in MYO7A , a gene associated with Usher Syndrome Type 1B or DFNB2. Computed tomography and contrast-enhanced magnetic resonance imaging studies demonstrated bilateral temporal bone anomalies with unique middle and inner ear malformations, as well as unique contrast enhancement in the membranous labyrinth, internal auditory canals, and cranial nerves, which have not been previously described with MYO7A variants. Interventions: Given the potential risk for progressive bilateral labyrinthitis ossificans, bilateral simultaneous cochlear implantation was performed at 4 months of age. Main Outcome Measures: Subsequent audiologic follow up after implantation shows significantly improved access to auditory information and increased vocalizations. At last testing, speech and language skills for both receptive and expressive language abilities were found to be commensurate with her chronological age. Conclusion: We report a novel presentation and imaging findings of congenital bilateral profound sensorineural hearing loss in a patient with nodular internal auditory canal and labyrinthine enhancement and coexisting inner ear dysplasia. Despite the multiple radiologic abnormalities, the patient has demonstrated good benefit from cochlear implantation. Future study of rare variants of congenital deafness, such as this, is critical toward defining new disease processes and determining optimal treatment.