Prolonged sporadic hemiplegic migraine associated with a novel de novo missense ATP1A2 gene mutation

Hemiplegic migraine is a rare form of migraine characterized by periodic attacks of migraine with neurologic aura and transient hemiplegia. There are familial and sporadic cases, both on a genetic basis; we describe the case of a 6-year-old boy affected by sporadic hemiplegic migraine, showing a novel ATP1A2 gene missense mutation (p.Gly715Arg) in exon 16. Long-term treatment with flunarizine resulted in good clinical response and prevention of further attacks

Pharmacogenomics of episodic migraine: time has come for a step forward

Migraine is characterized by heterogeneous behavior in response to drugs. Many resources have been invested in attempting to unravel the genetic basis of migraine, while the role of genetics in responses to currently available drugs has received less attention. We performed a systematic literature search identifying original articles pertaining to pharmacogenomics of episodic migraine. Few primary studies on the pharmacogenomics of symptomatic and preventive medication in episodic migraine were found. The number of patients studied in the individual articles ranged from 40 up to 130. There was a strong heterogeneity among these studies. We believe that pharmacogenomics studies, if properly designed, could contribute towards optimizing the treatment and reducing the burden of migraine, in turn helping patients and optimizing resources. Our knowledge on the pharmacogenomics of migraine is growing too slowly, and concerted measures should be undertaken to speed up the process

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

Background: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). Methods: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. Discussion: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. Trial registration: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019