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News ReviewGetting ahead ofepilepsyYou’ve no doubt heardabout the bionic eye andthe cochlear implant —some of the most famousdevelopments in the fast-growingworld of medical bionics.But Professor Mark Cook is quietlyoptimistic that an even biggergroup of patients — the 15 millionpeople worldwide whose lives aredisabled by uncontrolled epilepsy— have reason to hope they couldbe offered new, more effectivetherapies in the not-too-distantfuture, thanks to developments inneurobionics.Currently, of the one in 100people worldwide who sufferrecurrent seizures throughout theirlives, about one-third cannot beadequately treated with availablemedications or surgical therapies,the Melbourne neurologist andworld leader in epilepsy treatmenttold the recent TeDx Wollongongevent at the university of Wollongong,NSW.“A lot of the problem with epilepsyrelates to its unpredictability.We have to soak people in medicationsto prevent seizures that mightbe occurring for only a few minutesa year,” says Professor Cook,head of neurology at St vincent’sHospital, Melbourne and chair ofmedicine at the university of Melbourne.“It prevents them driving, stopsCould developments in medical bionics lead researchersto the ‘Holy Grail’ for treating epilepsy?Megan Howethem from working, threatenstheir safety, costs their life sometimes.”But imagine if people with epilepsycould know when a seizurewas going to occur. And whatif the drugs to treat the seizurecould be delivered directly to theaffected part of the brain, exactlywhen they are needed. or, evenbetter, what if the seizure could beaverted completely?A compact, driven man withthe knack of explaining exactlywhat his complex research couldmean to patients, Professor Cooktold the conference that groundbreakingAustralian research intoimplantable devices is now makingthat kind of control over thisunpredictable condition a real possibility.one of the first implantabledevices to be trialled in humans —including 15 Australian patients— is the Seizure Advisory System,which predicts when a seizure islikely to occur.Developed by uS companyNeurovista, the system involvesneurologist ProfessorMark Cook tells thewollongong TeDx eventhow neurobionicscould help people withepilepsy.permanently implanting electrodeson the surface of the brainto monitor electrical activity 24hours a day. A pacemaker-likedevice implanted under the claviclerecords the information andtransmits the records, analysesand real-time ambulatory ieeGdata to a small pager-sized devicethat the patient carries with them.It has a series of coloured lights:blue indicates a very low risk ofseizures, white indicates a mediumrisk and red indicates a very highrisk.“If effective, it would remove alot of the disability from peoplewith seizures — it might let themget to work, play sport, conceivablyeven drive. It might be thatyou can provide therapies whentheir status changes on the recording,”Professor Cook says.While the device hasn’t provedthe answer for all the Australiantrial participants — some have hadit removed and some have gone onto have surgery — for young TasmanianJason Dent it has been lifechanging.In an interview with epilepsyAustralia 10 months after thedevice was implanted, Jason saidthat when a red light appeared onthe monitor, he took fast-actingmedication. As a result, the seizuresthat had previously dom-cont’d next pagewww.australiandoctor.com.au 10 August 2012 | Australian Doctor | 21

news ReVIewfrom previous pageinated his life — occurringsuddenly and without warning —had completely stopped.“I feel more confident in thethings that I do from day to dayand I enjoy the fact that I am nothaving seizures every fortnight,”he said. “I feel like I have morecontrol over my life, as before theseizure would come with no warningand stop me doing the thingsthat I love doing, like my cricketand timekeeping at the local footygames.”Professor Cook says Jason’simplant remains in place and,hopefully, can stay there forever.“Suddenly this changes everything.”In fact, the potential of thesedevices goes beyond simply predictingthe onset of a seizure.“Conceivably you could usedevices like these to actually controlthe release of drugs,” says ProfessorCook.To try and make this vision areality, he approached nanobionicspioneer Professor Gordon Wallace,founder and director of theuniversity of Wollongong IntelligentPolymer Research Institute,and told him he wanted to “putdrugs where they work”.Not having to give antiepilepticssystemically could avoid the damagingside effects medication hason the CNS and elsewhere in thebody.“So that’s what we do. We putThe potential of thesedevices goes beyondsimply predicting theonset of a seizure.the drugs we have in polymers andwe implant them — at the momentin animals only … over the surfaceof the brain in the part where theseizures come from.”eventually, the electrically activatedpolymers might be able toactually drive drug release, he says.“Conceivably, we could constructpolymer implants, which could notonly release the drug but detect theseizure and use the energy in theseizure itself to release the therapy.ELB0185_AD_193x540. pdf Page 1 20/ 06/ 12, 11: 22 AMepilepsy: the impactAmong epileptic people and their family members55%had been injured asa result of a seizure,with 64% of thoserequiring hospitaltreatment for theirinjuries48%considered they hadbeen unfairly treatedbecause of theirepilepsy at somestage in their lives16%had full-time jobseven though themajority were ofworking ageThis would be remarkable.”49%were living belowthe current povertylineFindings of survey of 343 participants on the Australian epilepsy Research Register, 87% of whom were people withepilepsy and 13% were family members and carers.Source: ‘Out of the Shadows’: Needs, Perceptions and Experiences of People Living with Epilepsy inAustralia. Findings from Wave 2 of the Longitudinal Survey, epilepsy Foundation of victoria, March 2012.78%faced medicinecosts between $11and $300 per monthMarriage of two worldsThe epilepsy research he is conductingwith the Intelligent PolymerResearch Institute and theBionics Institute at the universityof Melbourne marks a longoverduemarriage of two scientificworlds, says Professor Cook.“I have always been interestedin how to join the medical sciencesand the material sciences. It is difficultto understand what is possibleif you have never had exposureto what people in this area cando.”While there are still big hurdlesto overcome — the formation ofsuitable polymers for diffusing thedrugs, finding the optimal medicationsand ensuring the implantsare safe to use in humans — thereis an air of optimism among thosein the field.Human studies of the drug-61%were on multiplemedicines forepilepsy33%reported full control(ie, no seizuresover 12 months)infused implants are a couple ofyears away but Professor Cooksays it is entirely plausible that wecould see such devices available totreat uncontrolled epilepsy within5-10 years.And if the polymer implantsdo not prove the answer, he saysanother approach to suppressingseizures — electrical stimulation ofthe brain — is also under investigationin a project run by the BionicsInstitute in collaboration withSt vincent’s Hospital, Melbourne.Rather than predicting seizures,the implantable stimulator devicewill monitor the electrical activityof the brain via electrodes.If abnormal neural activity isdetected, a therapeutic waveformis then delivered to the right partof the brain to stop the seizure (seeimage above).“It might liberate us altogetherof the need to take medications totreat epilepsy,” he suggests.DIagRaM of a DeVICe (lefT): arrays of electrodes surgically implanted onthe surface of the brain will monitor the complex patterns of brain activity.These signals will be sent to a processor (similar to a bionic ear stimulator)and proceed to detect/predict the epileptic seizure. once a seizure is detected,a therapeutic electrical stimulus can be applied to the electrodes in theappropriate area of the brain to suppress the seizure.Image courtesy of Bionics Institute.The new research is finally shininga light at the end of a long tunnelfor the many people who haveunpredictable and debilitatingepileptic seizures, says epilepsyAustralia chief executive DeniseChapman.Those people face constant anxietyabout when a seizure mightoccur, meaning both the loss oftheir independence and seriousrisks to their health.“I think it’s wonderful, it’s avery exciting development,” shesays. “What promise it can holdfor people with very difficult tocontrol epilepsy to have that controland independence, to feel theycan contribute and get out andwork and participate in communitylife, “she says. “It could reallyopen doors.”In a recently published paper ontheir research into drug-infusedpolymer-based implants, ProfessorCook and fellow researchersstated: “The Holy Grail has sofar eluded researchers in the field,however, strong progress is beingmade.”So are they truly within sight ofepilepsy’s Holy Grail?”“I used that term about beingable to predict seizures and peopleridiculed me,’’ Professor Cookadmits. “We’ve got the old systemwhere you ingest drugs and theysoak the whole brain. Imagine ifyou could put the solution wherethe problem is. I think that is a bitof a therapeutic Holy Grail.” lYou can view the TEDxWollongong conference@talks online via www.tedxuwollongong.com, or watch Professor MarkCook’s presentation here: www.tedxuwollongong.com/Mark-CookPBS Information. Restricted Benefi t. For the treatmentof Major Depressive Disorder. CYMBALTA is not PBSreimbursed for the treatment of Generalised AnxietyDisorder or Diabetic Peripheral Neuropathic Pain.PLEASE REVIEW PRODUCT INFORMATION BEFORE PRESCRIBING.FULL PRODUCT INFORMATION IS AVAILABLE ON REQUESTFROM ELI LILLY.CYMBALTA (duloxetine HCl) 30 mg, 60 mg capsule. INDICATIONS: Treatment of MajorDepressive Disorder (MDD), Diabetic Peripheral Neuropathic Pain (DPNP), Generalised AnxietyDisorder (GAD). CONTRAINDICATIONS: Known hypersensitivity to duloxetine or its excipients,co-administration with MAOI or within 2 weeks after discontinuing MAOI, patients with hepaticimpairment, co-administration with potent CYP1A2 inhibitors. PRECAUTIONS: Clinicalworsening and suicide risk, hepatotoxicity (from LFT elevations to liver failure), substantialalcohol consumption, narrow angle glaucoma, history of mania, history of seizure disorder,hyponatraemia, abnormal bleeding , increased blood pressure, orthostatic hypotension/syncope,* serotonin syndrome. OTHER PRECAUTIONS: Pregnancy, including neonatal symptoms with 3rdtrimester use, lactation, children and adolescents, slowed gastric emptying. INTERACTIONS:Concurrent use with serotonergic drugs, CYP1A2 inhibitors (e.g fluvoxamine), CYP2D6substrates (e.g. thioridazine) and inhibitors, MAOI inhibitors, St Johns Wort, warfarin. ADVERSEEFFECTS: Nausea, dry mouth, GI upset, anorexia, fatigue, dizziness, somnolence, tremour,sweating increased, fl ushing, vision blurred, insomnia, sexual dysfunction, palpitations, chills,musculoskeletal pain, headache, lethargy, paraesthesia, anxiety, sleep disorder, agitation, yawning.Postmarketing events: restless legs syndrome, seizures on discontinuation, gynaecologicalbleeding. See full PI for others. DOSAGE AND ADMINISTRATION: MDD & DPNP 60 mg oncedaily; GAD 30 mg to 120 mg once daily. Start with lower dose or administer with food to improveinitial tolerability. Lower dose in end stage renal disease. Taper dose on discontinuation. Basedon PI last amended on 17 Nov 2010. PBS Dispensed Price: 30 mg $38.22; 60 mg $50.42.* Please note changes in Product Information.References: 1. Paykel ES, et al. Psychol Med 1995;25(6):1171–1180. 2. Hirschfeld RMA, et al.Depress Anxiety 2005;21:170–7. 3. CYMBALTA Approved Product Information. 4. American PsychiatricAssociation, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text revision, Washington DC:American Psychiatric Association; 2000. Eli Lilly Australia Pty Ltd, ABN 39 000 233 992, 112 WharfRoad, West Ryde, NSW 2114. 06/12 AUCYM00437 ELB0185/ADIs treating mood symptoms enough? 1More patients achieved remission ifresidual symptoms were addressed. 1TREATING MOOD AND MORE † 2,3† Targeting many of the symptoms ms of depression –DSM-IV 422 | Australian Doctor | 10 August 2012 www.australiandoctor.com.auwww.australiandoctor.com.au 10 August 2012 | Australian Doctor | 23