Genetic Testing and Hospital Length of Stay in Neonates With Epilepsy.

BACKGROUND: We evaluated changes in genetic testing for neonatal-onset epilepsy and associated short-term outcomes over an 8-year period among a cohort of patients in the neonatal intensive care unit (NICU) at a single institution before and after the introduction of sponsored genetic epilepsy testing in January 2018. METHODS: Our primary outcome was a change in length of stay (LOS) after 2018. We also ascertained severity of illness with the Neonatal Sequential Organ Failure Assessment (nSOFA), type and result of genetic testing, turnaround time to molecular diagnosis (TAT), LOS, antiseizure medications (ASMs), and use of technology at discharge. We compared outcomes using nonparametric tests and difference-in-difference analysis. RESULTS: Fifty-three infants with genetic testing were included; 20 infants were tested after 2018. A total of 4160 infants in the NICU without genetic testing were used as reference. In the genetic testing group, LOS was 25 days (interquartile range [IQR] 5, 49) pre-2018 and 19 days (IQR 6, 19) post-2018 (P < 0.001 when compared with the reference population in the difference-in-difference analysis). TAT decreased from 51 days to 17 days after 2018 (P = 0.003). ASM number decreased from 4 (IQR 2, 5) to 2 post-2018 (IQR 1, 3) (P = 0.02). Over the same time periods there was no significant change in birth weight, maximum nSOFA score, or technology dependence. CONCLUSIONS: In this cohort, changes in genetic testing for neonatal-onset epilepsy were associated with shorter LOS that was not explained by changes in severity of illness, birth weight, or the average LOS in the NICU over time. Validation of these results in a larger, multicenter sample size is warranted.

Does rTMS Targeting Contralesional S1 Enhance Upper Limb Somatosensory Function in Chronic Stroke? A Proof-of-Principle Study.

BACKGROUND: Somatosensory deficits are prevalent after stroke, but effective interventions are limited. Brain stimulation of the contralesional primary somatosensory cortex (S1) is a promising adjunct to peripherally administered rehabilitation therapies. OBJECTIVE: To assess short-term effects of repetitive transcranial magnetic stimulation (rTMS) targeting contralesional (S1) of the upper extremity. METHODS: Using a single-session randomized crossover design, stroke survivors with upper extremity somatosensory loss participated in 3 rTMS treatments targeting contralesional S1: Sham, 5 Hz, and 1 Hz. rTMS was delivered concurrently with peripheral of sensory electrical stimulation and vibration of the affected hand. Outcomes included 2-point discrimination (2PD), proprioception, vibration perception threshold, monofilament threshold (size), and somatosensory evoked potential (SEP). Measures were collected before, immediately after treatment, and 1 hour after treatment. Mixed models were fit to analyze the effects of the 3 interventions. RESULTS: Subjects were 59.8 ± 8.1 years old and 45 ± 39 months poststroke. There was improvement in 2PD after 5-Hz rTMS for the stroke-affected (F(2, 76.163) = 3.5, P = .035) and unaffected arm (F(2, 192.786) = 10.6, P < .0001). Peak-to-peak SEP amplitudes were greater after 5-Hz rTMS for N33-P45 (F(2, 133.027) = 3.518, P = .032) and N45-P60 (F(2, 67.353) = 3.212, P = .047). Latencies shortened after 5-Hz rTMS for N20 (F(2, 69.64) = 3.37, P = .04), N60 (F(2, 47.343) = 4.375, P = .018), and P100 (F(2, 37.608) = 3.537, P = .039) peaks. There were no differences between changes immediately after the intervention and an hour later. CONCLUSIONS: Short-term application of facilitatory high-frequency rTMS (5Hz) to contralesional S1 combined with peripheral somatosensory stimulation may promote somatosensory function. This intervention may serve as a useful adjunct in somatosensory rehabilitation after stroke.

Tolerance to high-internalizing δ opioid receptor agonist is critically mediated by arrestin 2.

BACKGROUND AND PURPOSE: Opioid δ receptor agonists are potent antihyperalgesics in chronic pain models, but tolerance develops after prolonged use. Previous evidence indicates that distinct forms of tolerance occur depending on the internalization properties of δ receptor agonists. As arrestins are important in receptor internalization, we investigated the role of arrestin 2 (ß-arrestin 1) in mediating the development of tolerance induced by high- and low-internalizing δ receptor agonists. EXPERIMENTAL APPROACH: We evaluated the effect of two δ receptor agonists with similar analgesic potencies, but either high-(SNC80) or low-(ARM390) internalization properties in wild-type (WT) and arrestin 2 knockout (KO) mice. We compared tolerance to the antihyperalgesic effects of these compounds in a model of inflammatory pain. We also examined tolerance to the convulsant effect of SNC80. Furthermore, effect of chronic treatment with SNC80 on δ agonist-stimulated [35 S]-GTPγS binding was determined in WT and KO mice. KEY RESULTS: Arrestin 2 KO resulted in increased drug potency, duration of action and decreased acute tolerance to the antihyperalgesic effects of SNC80. In contrast, ARM390 produced similar effects in both WT and KO animals. Following chronic treatment, we found a marked decrease in the extent of tolerance to SNC80-induced antihyperalgesia and convulsions in arrestin 2 KO mice. Accordingly, δ receptors remained functionally coupled to G proteins in arrestin 2 KO mice chronically treated with SNC80. CONCLUSIONS AND IMPLICATIONS: Overall, these results suggest that δ receptor agonists interact with arrestins in a ligand-specific manner, and tolerance to high- but not low-internalizing agonists are preferentially regulated by arrestin 2.