Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures.

BACKGROUND: The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). OBJECTIVE: We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. METHODS: Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). RESULTS: Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. CONCLUSIONS: The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

Pain Assessment of Children with Autism Spectrum Disorders.

OBJECTIVE: Pain assessment of individuals with autism spectrum disorder (ASD) is largely unexplored. The core deficits of ASD may interfere with this population's ability to effectively use traditional pain assessment tools. Accurate pain assessment is essential to providing quality care. The objective was to illuminate barriers to pain assessment in children with an ASD, describe novel methods to communicate about their pain experience, and identify vocabularies that hold meaning with respect to pain to better understand pain from their context. METHODS: Qualitative descriptive study using semistructured interviews including interactive electronic technology to enhance communication. Subjects included children aged 6 to 17 years with ASD experiencing acute pain after a surgical procedure at a large urban tertiary children's hospital. RESULTS: Based on the analysis of 40 interviews, participants consisted of 34 (85%) male, 29 (72.5%) non-Hispanic white with mean age 11.75 ± 3.36 years (range: 6-17). All subjects were able to describe and locate their pain but required a variety of approaches. Assessment preferences included minimal time spent focusing on pain and simplistic language and actions using terms familiar to each subject. Notably, subjects were able to reliably demonstrate understanding of graded response and seriation. Parent involvement was essential, both in helping interpret the child's needs and providing trusted support. CONCLUSIONS: Some children with ASD require an alternate interactive approach to pain assessment. Individualized consideration and estimation of pain assessment methods for use in this population may provide more meaningful interactions, ultimately guiding better pain management interventions.

Unaltered peripheral excitatory actions of nociceptin contrast with enhanced spinal inhibitory effects after carrageenan inflammation: an electrophysiological study in the rat.

Nociceptin (orphanin FQ) is the endogenous agonist of the opioid receptor-like (ORL-1) receptor. The actions of this peptide have been studied extensively at a number of sites with diverse actions being reported. Here, in a rat model of peripheral inflammation, we examine the effects of nociceptin on the responses of dorsal horn neurones when applied directly to the spinal cord and, in separate studies, into the peripheral receptive fields in the hindpaw of the halothane anaesthetized rat. As changes in the receptor density and expression of the message for nociceptin have been reported after inflammation we have compared these actions to previously reported effects in normal animals. The dose-dependent inhibitory actions of nociceptin on C-fibre evoked responses and input (measures of presumed pre-synaptic excitability) are increased 3-4 h after inflammation whereas its inhibitory effects on post-synaptic mechanisms (wind-up) remain unchanged. These inhibitory effects were partly reversible by high doses of naloxone. This increased potency of nociceptin after inflammation is consistent with an increased receptor density in the superficial spinal cord. In contrast, the peripheral administration of nociceptin produced dose-dependent excitations of dorsal horn neurones and a degree of sensitization to mechanical stimuli. This peripheral action was unchanged after inflammation. These diverse site-dependent actions of nociceptin further emphasize the complexities of this novel opioid system.