Testing devices for the prevention and treatment of stroke and its complications

We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals; companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the ‘real-world’ and to pick up uncommon adverse events

Non-invasive magnetic stimulation of the human cerebellum facilitates cortico-bulbar projections in the swallowing motor system

Background Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry. Methods Healthy volunteers (n = 16, eight men, mean age = 32, range 19-57 years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter-stimulus intervals (ISIs) with the cortical response amplitudes being assessed. Key Results Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5 +/- 6.9 vs 42.8 +/- 5.9 mu V, P = 0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50-200 ms (P < 0.05), an effect not seen with sham or trigeminal nerve preconditioning. Conclusions & Inferences Posterior fossa stimulation excites the cerebellum and evokes direct motor responses within the pharynx. When conditioned with TMS, the cerebellum strongly facilitates the cortical swallowing motor pathways. This finding suggests that the cerebellum exerts a modulatory effect on human swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after neural damage

Benign biliary strictures: prevalence, impact, and management strategies

Michael Xiang Ma,1,2 Vanoo Jayasekeran,1 Andre K Chong1 1Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, Perth, WA 6150, Australia; 2Midland Physician Service, St John of God Midland Public Hospital, Midland, Perth, WA 6056, Australia Abstract: Benign biliary strictures (BBSs) may form from chronic inflammatory pancreaticobiliary pathologies, postoperative bile-duct injury, or at biliary anastomoses following liver transplantation. Treatment aims to relieve symptoms of biliary obstruction, maintain long-term drainage, and preserve liver function. Endoscopic therapy, including stricture dilatation and stenting, is effective in most cases and the first-line treatment of BBS. Radiological and surgical therapies are reserved for patients whose strictures are refractory to endoscopic interventions. Response to treatment is dependent upon the technique and accessories used, as well as stricture etiology. In this review, we discuss the various BBS etiologies and their management strategies. Keywords: benign biliary stricture, endoscopic retrograde cholangiopancreatography, metal stent, plastic stent, stricture dilatation, chronic pancreatitis, liver transplantation, primary sclerosing cholangiti