2018 Summer Brainwaves Newsletter

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brainWAVES The Newsletter of the Brain Foundation

Summer 2018-2019

We need to talk about . . .


Your brain is for life….not just a sporting career There has been a lot in the media recently about the effect of concussion, not just in sporting heroes, but in everyday players and also as a result of brain injury from accidents and medical conditions. Concussion can be obvious, with a knock out now removing a player immediately from the game. But it can also be very subtle, where the symptoms can develop in the days, weeks and even months following the injury. Dizziness, headaches, memory loss and confusion are not uncommon. There is also a concern for players who suffer multiple and repetitive subtle head knocks throughout a game with growing evidence that long term cognitive and motor impairment might be suffered as a result.

“When in doubt, sit it out”. It is not a question of not playing sport. Whilst there are growing numbers of players of all ages suffering concussions, the opposite effect is another medical epidemic: obesity. What we need is a strong, unified approach to treating concussion with the doctor having the final word on when a player can return. But we also need to understand the physical effects suffered by the brain. It is with this in mind, that Brain Foundation has proposed a ‘Concussion Initiative’.

Goodbye and thank you Gerald It is with a mixture of sadness and excitement for the future, that we bid farewell to Gerald, our erstwhile ‘commander and leader’ for the last 15 years. When the Brain Foundation was formed in 1970, there were no organisations doing dedicated research into brain disorders. Practitioners began their own organisation to investigate disorders and potential treatments.

A study which will look into the changes in the brain and a protein which can be developed in some individuals. What is the effect of this protein? Are these players more susceptible to early onset dementia or CTE (Chronic Traumatic Encephalopathy)? There are many questions yet to be answered. To help us along with funding this great new initiative, Brain Foundation ran an initial campaign of 4 videos with the Sydney Swans. We had a video on the big screen prior to the game and we engaged the Swans Academy for junior players to help raise awareness of this issue among young players and our research proposal.

In the early 2000’s, Gerald came along at a time when research organisations were being formed in hospitals and labs around the country. Competition for donations to fund research became much more competitive and the Brain Foundation had to change with the times to remain relevant and vital to Australia’s young researchers. Gerald managed to achieve this and very much more. Today, the Brain Foundation remains essential to the early careers of researchers, with our annual grants being very strongly sought after. Our financial position is strong, and our path to the future assured. For this, we have Gerald to thank.

We are looking forward to progressing this area of research and to be able to contribute to the greater community. For more Brain Foundation information on 02 9437 5967 this initiative info@brainfoundation.org.au Matthew Kiernan, Gerald, incoming CEO Trevor Thompson, David Burke AO Chairman Scientific Committee

So, Gerald, from the directors and staff, we are sad to see you go and wish you all the very best for your future endeavours.

Matthew Kiernan, President, Brain Foundation

Contact the Brain Foundation PO Box 579, Crows Nest NSW 1585 Telephone: 02 9437 5967 or 1300 886 660 Email: info@brainfoundation.org.au Visit our websites brainfoundation.org.au and headacheaustralia.org.au

Fabulous Fundraisers Sporting heroes are simply the best . . . Clare Balken

David Smith

– City 2 Surf

– Melbourne Half Marathon

Thankyou Clare, and your wonderful (growing) team who ran the City 2 Surf for the second time this year. Claire and her family do the run in Memory of her father Geoff. Your support of our cause is gratefully received.

What a hero! David has been diagnosed with Dystonia. Anyone who knows about Dystonia would know that making a commitment to do a half marathon is a big deal indeed. But that is just what Dave and his two ‘support daughters’ did. And on October 14, they walked the hallowed turf of the MCG to the finishing line.

Clare and her growing team at the finish of the race

David and his ‘support daughters’

Max Rolls

Worldwide Tandem Bike Ride

– Tri-State Swim

In our last issue of Brainwaves, we introduced you to Louis and Lloyd – 2 emergency doctor mates who are Tandem Bike riding around the world and picking up a Guinness World Record at the end of their journey.

We brought you Max and his Swim against Huntingtons disease last newsletter. Max, and his family, have excelled at rallying everyone behind their efforts to fund research into this terrible disease which has touched their lives.

Walking the hallowed turf to the finish line

Starting in Adelaide in August this year, they are still pedalling – hard! Currently roughly somewhere in Russia, they are having the adventure of a lifetime raising funds for Brain Foundation and Spinal Research UK. Don’t you wish it was you??

Ovoo mongolia

Max and Pat Rolls with Caroline and Gerald

Caulfield Grammar – Shaw House Fun Run Thanks to all the teachers and students of Caulfield Grammar who participated in their Annual Fun Run recently. It is always a great day and we appreciate your continuing support towards Brain Tumour Research.

Day 75 - boys



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FOLLOW THEM ON THEIR WEB PAGE www.worldtandem.com or Facebook or show your support for them via My Cause – Tandem World Cycle 2018

Thank you to all our sporting heroes for all the sweat and tears that went into training for these events and for your wonderful fundraising efforts for our Research programme.

Fabulous Fundraisers Claudia VanGerven What happens when a beautiful girl decides to shave her head in the name of fundraising? She’s still a very beautiful girl who has now donated a lot of money for research.


STEPS – Brain Injury Group The STEPS Program Brain Injury Group had a wonderful day recently for Brain Injury Awareness Week at Mareeba, Qld. The STEPS Program is a Qld-wide info and skills program for people with Acquired Brain Injury (ABI), Aneurysm, Concussion, Post Concussion Syndrome (PCS), Stroke, Traumatic Brain Injury (TBI), Tumours and their carers, families and friends. Brain Foundation is happy to offer support to this valuable group.

Team Spirit @ Cooly Rocks On Festival What’s that you say?? Team Spirit are a group of good friends who meet each year at the festival in Coolangatta which celebrates all things 50’s, 60’s, 70’s. While all having a great time, they also organise a massive raffle to donate to charity. This year, Brain Foundation was the beneficiary of funds to go to Aneurysm research. Thanks to Gary Rose and all on the team. It looks like you have a lot of fun along the way.


Thank you so much Claudia and all who supported her Shave Away Brain Decay fundraiser earlier this year. Hope you are enjoying the many new hairstyles you will have along the way. Louise Anderson-Clemence, Leeanne Stathooles, Jeanene Bolton and Pam Vawdrey.

My Story

The mighty wheelbarrow of goodies

Team Spirt

Zombies take it to the streets

– Nathan Nguyen In the category of people who inspire us with their amazing efforts to raise funds is Nathan Nguyen. Having suffered a traumatic stroke in a workplace accident, Nathan has undergone multiple surgeries and months of rehabilitation. On the road to recovery, Nathan decided to join in a 2.5km run at the RAAF Base Edinburgh by walking the distance. While a crowd of over 300 runners tested themselves against the clock, Nathan was spurred on by his colleagues at the end as he completed the course. Bravo Nathan and all who supported him.

Well 2018 has shown no mercy for the public in Townsville, Sydney, Canberra and Surfers Paradise with hoards of Zombies descending for their annual ghoulish parade. Whilst the public may be hiding inside, the Zombies love nothing more than to walk the streets and send the ‘normal’ humans running. Sydney was held on Saturday 27th in the city centre and had over 4,000 zombies roaming the streets and this year also saw the first Fest-Evil weekend event on the Gold Coast held over 26th to 28th October. The weekend was well supported with events on Friday and Saturday evening and the big walk on Sunday with well over 1,000 zombies turning up. Thank you to all the organisers of all the events and zombie walkers for their great support of our cause.

MORE CAN BE SEEN AT NATHAN'S SITE: afterstroke.org. Left: Nathan Below: The support crew urging Nathan to the finish line


Brain Foundation issues a very big ‘Thank you’ to our fundraisers. You contribute significant funding towards our annual Research Gift Awards

Summer 2018-2019


Headache Australia Professors James Lance and Peter Goadsby Inaugural Annual Migraine Symposium Brain Foundation Director, Professor Tissa Wijeratne, has produced a documentary of case studies about the experiences of those suffering migraines and ways in which they deal with their plight. This documentary was launched at the Western Centre for Health Research and Education, Sunshine Hospital during the Inaugural Professors James Lance and Peter Goadsby Migraine Symposium, another initiative by Professor Wijeratne in October this year As our register members would be aware, Migraine has been identified as the leading cause of disability in Australia and the very impressive programme at the presentation reflected the importance being given to help those suffering. The features of the programme were: • The launch of “Move Against Migraine” by Professor Wijeratne; • The launch of an interactive, mobile GP ‘Mastering Migraine Management Programme’ in conjunction with the University of Melbourne; • The inaugural James Lance oration was made by Peter Goadsby, who developed the breakthrough “CGRP” peptide blocker treatment. Incredibly, his research started in 1985 and, with funding difficult to obtain

Headache and Migraine Week 10 to 14 September, 2018 A series of live seminars were organised for capital cities this year to promote migraine information along with current best practice and new treatments. The events planned to promote understanding about migraine in the community were very well attended. Invitations went to those on the National Register and some further participants were picked up from perusing our Facebook page. Seminars were held in Brisbane led by Dr Nicole Limberg, Sydney had the benefit of Dr Bronwyn Jenkins while in Melbourne Dr Michael Eller ran the Q & A session. 4

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for what was then a very radical view, the medication was only approved by the FDA in May this year and the TGA in July this year. • The documentary, “Out of Sight, Out of Mind, the Hidden Cost of Migraine”;

The steps in this symposium represent the biggest advances that will lead to vastly improved care and treatment from more accurate diagnoses and translational research for migraine.

Prof. Wijeratne’s documentary will be of great value to Headache Australia. It will assist migraineurs by showing they are understood, not alone and enable them to see how others manage their affliction. We will also be promoting the documentary widely in the community to help build understanding that migraine is a complex neurological disorder that affects vision, balance and causes nausea.

The symposium was attended by Secretary General Gerald Edmunds, CEO Designate, Trevor Thompson our PR consultant, Blanche de Wynter who will formulate a public PR awareness campaign and former director, Val Gibson in her role as National Chair of Inner Wheel. Val will take a short version of the movie to be distributed though the network to members, and the connection with Rotary will facilitate distribution throughout their branches. Employer groups and associations such as the Human Resource Institute will also be on the list to break down the stigmas that is attached to migraine.

The other group to be targeted will be employer groups with the subtext that between episodes, people who are prone to migraine are as capable as any other employer and given a little leeway with leave will respond with great loyalty and application. In fact, many do manage their migraines with minimum need for sick leave. Those who suffer frequently and for extended periods are not able to join the workforce. That number could be as high as 500,000. That still leaves a pool of over 4,000,000 who can be efficient and effective employees.

Incoming Brain Foundation CEO, Trevor Thompson, Gerald, Blanche de Winter, Val Gibson, Edwina Collier, Uni Melbourne and Tissa.

• The Guest of Honour, Professor David Dodick, Director and Chair, Mayo Clinic. Professor Dodick’s presentation was via video.

Secretary General, Gerald, introduced the Migraine Documentary in Adelaide with Dr Andrew Moey and then in Perth with Dr Julian Rodriguez who was on hand for the Q & A session. The Sydney presentation was streamed to Facebook. We sincerely thank the above practitioners who selflessly give of their time so that we can bring this up to the minute information to sufferers. To complement the live seminars – and because we understand that migraine sufferers cannot always attend, repeats of the following presentations were also streamed during the week. • Professor Paul Martin, Behavioural Treatment with an emphasis on Trigger M Management; • A/Professor Dale Nyholt, The Genetics of Migraine – What have we learnt? • Dr David Williams, Migraine Management, Best Practice; • Professor Tissa Wijeratne, Living Well with Migraines;

• Dr Nicloe Limberg, Non-Migraine Headaches: Diagnoses and Treatment; and • Drs Bronwyn Jenkins and Susan Tomlinson, The Latest on Migraines: Medications, Hormones and Treatments. The total of those attending and those joining via our media was over 12,000 and our National Register and Headache Support Group gained new members. We were very pleased with this result and hope that everyone gained some new insight into their condition and treatment options Unfortunately, it is difficult to gain wider media attention for seminars about migraines and headaches without a breakthrough treatment. The Foundation did benefit from a lift in publicity with the launching earlier in the year of a new treatment “CGRP”. This radically new treatment was developed by internationally recognised Australian neurologist Professor Peter Goadsby. Headache Australia has been forefront of getting this valuable new drug registered on the PBS. Join the Headache Register for further updates on this progress.

Headache Australia Migraine in Australia – Deloitte Access Economics Report There are many, many different brain diseases and disorders. Nearly all of them have no treatment and so lead to an inevitable conclusion. However, there are some which sufferers can ‘live’ with. Migraine is one such condition. It will very rarely lead to death, but in severe cases, it can effectively take away your ‘life’. We understand this very well at Headache Australia and part of our mission is to inform the wider public of the impact of this terrible neurological condition.

Migraine remains the least funded neurological disorder relative to its economic impact. Everybody is looking for something better. The doctors want to be more effective.

‘Migraine in Australia’ by Deloitte Access Economics provides a groundbreaking insight. Described as a hidden epidemic, there are nearly 5 million sufferers in Australia – 71% of these are women. And, of course, migraine does not just affect them: families, friends and employers are all impacted.

The health care system would like to reduce costs.

Migraine is a complex neurological disorder that affects men, women and children with varying intensity, frequency and duration. The World Health Organisation has said that a severe migraine attack is among the most disabling of illnesses, comparable to dementia, quadriplegia and active psychosis. Getting access to effective treatments to prevent or treat acute attacks is difficult. Migraine is a hidden disease with sufferers frequently treated with scepticism and accusations of hypochondria. It peaks in middle life when individuals need to work and look after family and it can drive a wedge between the sufferer and significant relationships.

Employers would like greater productivity. And, patients would like better results. Headache Australia is committed to increasing the awareness and support for headache patients from consultation, in the office and in the public domain.

The cost of migraine is not just bourne by the individual. The cost to the health system and the lost productivity in Australia is over $35 billion. But this could be reduced with effective treatment and management.


General practitioners need greater education to diagnose, treat and manage migraines. Patients need access to proven self-managed strategies and their needs to be greater awareness, support and information.

Join our free Headache Register today. headacheaustralia.org.au

What's happening with CGRP (Erenumab)?

2019 Migraine World summit This is your opportunity to learn more from over 30 world leading migraine experts and specialists. On from March 20 to 28, 2019, it is free and online. Registration is required prior to the event at migraineworldsummit.com


We know that many of our register members and migraine sufferers are anxiously waiting for news on this new treatment. A submission was made earlier this year to have this drug listed on the PBS. Unfortunately, it was not approved. We anticipate that a further application will be made in the near future and we remain committed to pursuing this approval to enable affordable access to this drug for Australian patients.

In the meantime, you should discuss this option with your doctor. Register Members, keep an eye out for more information via email and in our next newsletter.


Keep up to date with regular emails. Registration is free on our web site, headacheaustralia.org.au

Our Register Members receive regular email updates of current information as we receive it. We send information about new research trials that you can choose to be involved with. All donations made by Register Members go only to Headache research. Your email address is required. Register at headacheaustralia.org.au

Disclaimer: Headache Australia is not a medical office and cannot offer medical advice. We stress the importance of discussing any issues you have with your medical practitioner.

Summer 2018-2019


2018 Research Gift Awards Every year at this time, it is our greatest pleasure to present the next round of Research Grants to our talented pool of Australian researchers. Receiving more that 140 applications, it is indeed an honour for the recipients to have our funding to investigate leading edge projects to solve some of the mysteries of the brain. In 2018, we have funded 19 projects. You can read all about them on the following pages. The Directors thank our Scientific Committee, who each year put in a lot of work assessing all the applications before a final decision is made.

We also extend a very big thank you to all our donors, fundraisers, and corporate sponsors without whom we could not continue this valuable work.


Alzheimer type protein deposition in people with Type 2 diabetes mellitus Chief Investigator: A/Prof Amy Brodtmann The Florey Institute of Neuroscience and Mental Health, Victoria

and a strong association between diabetes and Alzheimer’s disease - the most common form of dementia.

Co-Investigators: Professor Louise Burrell, DR Sheila Patel, Dr Matthew Pase, Dr Carolina Restrepo Dementia and diabetes are two of the most common and disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment (worsening memory, thinking and perception) common in people with diabetes,

Individuals with diabetes are known to have greater rates of brain volume loss with aging, but it is not known which patients will develop dementia over time, and which factors will predict cognitive impairment in these patients. Therefore, biological markers are needed to better manage the complications of diabetes. Left ventricular hypertrophy is an enlargement and thickening of the left lower chamber of the heart, which is common in patients with diabetes and a strong

independent predictor of heart failure, stroke and death. There is also evidence that diabetes and heart disease may accelerate the production of two proteins named beta-amyloid and tau, and the increased deposition of these in the brain is associated with Alzheimer's disease. To date, no studies have investigated the association between left ventricular hypertrophy, brain aging, cognitive impairment, amyloid and tau aggregation in people with diabetes.

in their brains, compared to people with diabetes but without left ventricular hypertrophy. We will also establish whether amyloid and tau levels are associated with brain volume and thinking skills in these two groups.

In this study we will establish whether people with diabetes and left ventricular hypertrophy have a higher amyloid and/or tau burden

Cell-free DNA profiling in cases and disease – mimics to develop a biomarker test for Amyotrophic Lateral Sclerosis Chief Investigator: Dr Fleur Garton University of Queensland Co-Investigators: Professor Naomi Wray, A/Prof Noah Zaitlen Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressing neurodegenerative disease with a lifetime risk of ~1 in 400 and no known cure. Initially, the presenting symptoms may involve a single area such as a limb or facial muscle weakness, however this often quickly spreads across multiple body regions. The two



populations of motor neurons that are affected in ALS are the ‘upper’ populations in the motor cortex of the brain and the ‘lower’ populations in the brain stem and spinal cord. Diagnosis and tracking involves a clinical examination with a questionnaire-based scale (ALSFRS-R) and a nerve conduction test. This process measures a person's physical function, assesses the extent of degeneration and eliminates other less-severe mimics that initially, are indistinguishable from ALS. Onset and presentation vary between individuals, however

ALS is also known as Lou Gehrig’s disease

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50% of cases die within three years and 90% within five years. This premature death accentuates the inefficiencies with the current 12 month diagnostic process and highlights the critical need for objective, economical biomarker that could be ordered at symptom presentation and help assess new therapeutics. Our group is exclusively devoted to understanding complex traits and disease with unique and robust methodologies. While the last five years have seen rapid discovery in identifying genetic causes of ALS, parallel

investigations into ALS treatments desperately need an effective, objective biomarker of disease state. We have been involved in intensively understanding the genetic complexity of ALS and have helped establish an Australian ALS National Collection network (SALSA-SCG). This has been spurred on by the recognition that large harmoniously collected samples are critical to understand complex diseases such as ALS. Our primary objective is to translate this research into a clinical tool for diagnosis and tracking in ALS.

ALS progression: multimodal approach to assessing cortical dysfunction me and other members of my group has shown that a brain functional change called hyperexcitability is an early and reliable diagnostic marker of ALS.

Chief Investigator: Dr Parvathi Menon, University of Sydney, NSW Amyotrophic Lateral sclerosis (ALS) is a progressive, eventually fatal disease of the human motor system. The commonest variant of the disease is rapidly progressive with average survival of 3-5 years after diagnosis. Research undertaken by

My next study was aimed at assessing regional differences in brain hyperexcitability which may underlie spread of physical symptoms in affected patients. There was evidence of hyperexcitability being greater over muscle worse affected in ALS, of hyperexcitability being greater over the controlling brain hemisphere in patients with onset of muscle weakness on one side of the body.

A striking finding in the above studies was the early occurrence of hyperexcitability throughout the brain in ALS despite predominance over selective muscles and brain hemispheres. Further, body regions supposedly less dexterous in their movement and considered to have less dense brain connections seem to develop the phenomenon of inexcitability quite early in ALS. These findings led us to consider other modalities of assessing changes in brain function in ALS. One of the approaches we have used is of MRI studies of the brain with analysis of a unique aspect of brain function which is the

connectivity between regions and the formation of so called functional and resting networks. Our early MRI studies have shown increase in inter-regional connectivity in patients with ALS which correlates with brain hyperexcitability. A new technique we are using to understand brain connectivity is the technique of TMS EEG. With this multimodal approach I, along with colleagues, hope to closely observe and study ALS patients using clinical and standard testing techniques complemented by the multimodality research tools to provide a clearer understanding of the brain changes driving ALS.



"Cage Fighting” for Parkinson’s Disease: how can we prevent the spread of abnormal proteins?

Targeting Lin28 for the control of childhood medulloblastoma

Chief Investigator: Dr Lyndsey Collins-Praino, University of Adelaide, SA Co-Investigators: Dr Andrew Care, Professor Mark Hutchinson Parkinson’s disease (PD) is a significant global problem, affecting 10 million people worldwide. In Australia alone, 1 in every 350 Australians suffer from PD, with 32 new cases diagnosed each day. PD is associated with significant burden to the Australian economy, with total financial costs per year adding up to almost $1.1 billion, a number that has almost doubled since 2005. Given that the prevalence of PD is estimated to double by 2030, the search for an effective treatment for the disease is critical. Currently, the limited treatments available for PD treat only the symptoms and do not actually modify the brain mechanisms that contribute to the disease. A major contributor to the spread of Parkinson’s disease throughout the brain is the transmission of an abnormally folded protein called alpha synuclein from brain cell to brain cell. Alpha synuclein normally helps to maintain normal communication between brain cells. In PD, for reasons that are not yet understood, the alpha synuclein begins to misfold and aggregate. While some of this alpha synuclein forms clumps called Lewy bodies within brain cells, alpha synuclein may also be released from brain cells into the extracellular space. There, it can be taken up by neighbouring brain cells, triggering the misfolding and aggregation of alpha synuclein within those cells. Thus, PD pathology can spread throughout the brain and lead to the emergence of both motor and nonmotor symptoms of PD. The aim of this project is to pioneer a novel technology to target this alpha synuclein within the extracellular space and clear it from the brain. This may help to stop the brain transmission of alpha synuclein, halting the spread of the disease, and leading to a disease-modifying treatment strategy for PD.

Chief Investigator: Dr Iman Azimi University of Tasmania Medulloblastoma (MB) is the most common fatal childhood brain cancer. Despite significant advances in the treatment of lowrisk MB patients, children with high-risk MB have low survival rates and there are currently very few treatment options available including surgery, radiotherapy and chemotherapy. Due to the harsh nature of these treatments, children who survive the cancer often show severely impaired physical, cognitive, social and emotional function for the rest of their lives. There is therefore a clear need for new treatment options for high-risk MB. We have identified a protein that its level is significantly higher in samples from high-risk MB patients. This high expression is associated with increased cancer aggressiveness and lower patient survival rates. This protein is known in some other systems to be a key regulator of metabolic pathways and stem cell features, two critical processes that are also important players in cancer growth, metastasis and resistance to therapies. In this project, the role of this protein in MB progression and metastatic characteristics will be explored. Furthermore, the potential of its targeting for the control of MB will be assessed. This project may introduce a novel potential therapeutic target for the control of high risk MB in children.


Medulloblastoma (MB) is the most common fatal childhood brain cancer and there are currently very few treatment options for high-risk MB patients

Summer 2018-2019


2018 Research Gift Awards ▼ EPILEPSY

Defining the clinical features of antibody associated epilepsy

Chief Investigator: Dr Lisa Gillinder Mater Centre for Neurosciences, Queensland Co-Investigators: Professor Patrick Chauvel, Dr Sash Dionisio, A/Prof Paul Thomas, Dr David Gillis, Dr Bill Mantzioris

Epilepsy affects more than 250,000 Australians, with many of these being refractory to conventional therapies. This is a very costly condition to treat and it causes significant psychosocial burden. Our current research into a unique epilepsy subgroup which are refractory to conventional therapies is addressing this important health issue. This study will define the clinical phenotype associated with neuronal autoantibodies in chronic refractory epilepsy. This involves a multimodality approach to diagnosis that will test the hypothesis that these antibodies are associated with a definable clinical phenotype, which can be used to generate diagnostic criteria similar to what exists for autoimmune encephalitis. Patients will undergo thorough

clinical evaluation guided by the stereo-electroencephalography methodology aimed at localisation of the epileptogenic zone. This involves evaluation of seizure semiology, epilepsy risk factors, medical background, neuropsychiatric and neuropsychological assessments. Prolonged electroencephalographic (EEG) recordings will be used to define the electroclinical features of these epilepsies and advanced neuroimaging techniques will be used to evaluate for inflammatory abnormalities in these cases. Our pilot study found that these antibodies are associated with perisylvian network epilepsies, as defined by seizure semiology and unique EEG changes. We also found an association with certain epilepsy risk factors, and a very high prevalence of mental health

disorders in this population. Most importantly, we demonstrated a clear response to immunotherapy, with many of these refractory patients becoming seizure free. If our hypothesis is correct and we can confirm our preliminary findings in a large cohort, this will change the clinical approach to chronic epilepsy. Once these patients are clinically recognisable as a distinct subgroup they can be more easily identified and will therefore receive more appropriate treatment. This will also lead directly to randomised trials to determine which immunotherapies are most effective. This would have health-cost savings and will result in an effective cure for this subgroup of epilepsy, which currently have limited treatment options available.

The development and management of post-traumatic epilepsy

Chief Investigator: Dr Joshua Laing Monash University, Victoria Co-Investigators: Professor Terrence O’Brien, Professor Patrick Kwan, Dr Piero Perucca



Post traumatic epilepsy (PTE) is a significant health burden on patients who suffer traumatic brain injury (TBI), which is observable and may be preventable. PTE is often treatment resistant, and associated with significant morbidity and mortality. Investigation of epileptogenesis, the development of epilepsy, presents an opportunity for intervention prior to the development of PTE. This study will take advantage of a major NIH funded international, multicentre, study of epileptogenesis post TBI (EpiBioS4Rx) to investigate biomarkers associated with acute symptomatic seizures and PTE. Using international and local databases from trauma services and epilepsy monitoring units,

this study aims to identify clinical, diagnostic and management factors associated with PTE. Preclinical biochemical, imaging and electrophysiological data suggests candidate biomarkers of epileptogensis for further evaluation in humans. Patients with moderate-severe TBI require intensive care therapy in hospital and represent an ideal patient group that may be investigated. Acute seizures may be detected by continuous EEG monitoring in the ICU which are largely non-convulsive and subclinical, currently performed in centres overseas, and have been associated with deleterious metabolic changes. Neuromonitoring via continuous EEG has yet to be utilised in

Australia and has potential to detect seizures and aid at the bedside. Continuous EEG monitoring will be performed in all patients recruited to evaluate for seizures and associated EEG biomarkers, and correlate these findings with other clinical and investigational biomarkers of PTE. Treating seizures detected by continuous EEG will be reviewed for its effects on overall outcomes, and effect on epileptogenesis as a disease modifying therapy. Overall, this study aims to observe epileptogenesis in humans and assess biomarkers contributing to the development of PTE, with a view to informing novel disease modifying and curative therapies that may be transferable across other forms of epilepsy.

Epilepsy is a neurological disorder in which brief, recurrent changes in the electrical activity of the brain lead to seizures or ‘fits’, lasting from a few seconds to several minutes. There are many causes of epilepsy, including an injury to the brain, certain infections such as encephalitis and meningitis, and brain tumours. In the majority of cases, however, the specific cause is unknown.

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How the brain controls the heart and blood vessels in epilepsy Chief Investigator: Professor Vaughan Macefield Baker Heart & Diabetes Institute, Victoria Co-Investigators: Professor Terrence O’Brien, Professor Luke Henderson

In addition to the motor consequences of epilepsy, seizures result in cardiovascular and respiratory consequences that, in some individuals may lead to death. Indeed, Sudden Unexplained Death in Epilepsy (SUDEP) is one of the most poorly understood consequences of epilepsy. By definition, the mechanisms leading to DUSEP are unknown. This Brain Foundation grant builds on the work we have been doing in humans to

understand how functional and structural changes in the brain lead to increased cardiovascular risk in various disease states, extending the work to epilepsy. We are the only group in the world using direct microelectrode recordings of sympathetic nerve activity (MSNA) in combination with functional magnetic resonance imaging (fMRI) of the brain to identify areas of the brain responsible for the generation of MSNA. Using this state-of-the-

art brain imaging protocol, this research promises to identify changes in the brain associated with epilepsy that increase the probability of SUDEP in certain individuals. By documenting changes in areas of the brain involved in cardiovascular control we hope to be able to identify individuals at risk of SUDEP, ultimately preventing sudden death in epilepsy from occurring.


The role of Immune cells (microglia and a cell membrane protein in human brain tumours – a bed to bench side research study Chief Investigator: Dr Mastura Monif Royal Melbourne Hospital, Victoria Co-Investigators: Professor Kate Drummond, Professor Terry O’Brien, Professor David Williams, Professor Katrina Kan Human brain tumours (gliomas) generally afflict young individuals in their 30s-40s with significant

implications for the individual, their family, as well as a large burden of disease for the community. Currently there are no cures for high grade gliomas and the conventional therapy on average only improves survival by a few months. Our research focuses on the contribution of the immune system in human brain tumour growth and proliferation. We have previously shown that microglia (brain immune cells)

are an integral part of human brain tumours and our aims are to understand if these microglia promote or inhibit tumour growth? In addition, we have been able to show that human brain tumour associated microglia express a specific membrane protein (P2X7 receptor). P2X7R is a channel protein that sits on the membrane of microglia. By inhibiting P2X7R in the laboratory we have been successful in reducing tumour cell

numbers. This is a very exciting finding and with support from the Brain Foundation we will be investigating this further with the ultimate aim of hopefully finding effective therapies to combat human brain tumours.


Thrombotic nanodisks to block abnormal blood vessels in the brain Chief Investigator: Dr Zhenjun Zhao, Macquarie University, NSW Co-Investigators: Professor Marcus Stoodley, Dr Bingyang Shi, Dr Lucinda McRobb, Dr Libing Fu Brain arteriovenous malformations (AVMs) are abnormalities of blood vessels, in which direct connections form between arteries and veins. This leads to a high risk of rupture causing stroke which carries a 50% risk of death or disability in the children and young adults typically affected by AVMs. Current treatments such as surgical removal and radiosurgery aim to prevent rupture, however each has limitations. No effective treatment

is available for large and deep AVMs (one third of patients). There is an urgent need for an effective new treatment.

specific molecular changes on the surface of AVM vessels, making vascular targeting a possibility for these lesions.

‘Vascular targeting’ may be an attractive approach for AVM treatment. This is the deliberate induction of blood clotting (thrombosis) in abnormal blood vessels. This technique utilises molecular differences between abnormal and normal vessels to specifically deliver drugs only to diseased vessels. Specific binding to unique molecules by antibodies linked to a clotting reagent induces thrombosis selectively in these vessels. Although unique molecules have not been identified on AVM vessels, priming with radiation has the potential to induce

In this study, we will develop nanotechnology to increase the efficiency and specificity of thrombotic agent delivery to irradiated AVM vessels. Disk shape nanoparticles (nanodisks) will be prepared that are linked with Annexin V (which targets and binds a radiation-stimulated molecule called phosphatidylserine), and thrombin (a thrombotic agent. We will test the efficacy of various formulations of these phosphatidylserine-targeting prothrombotic nanodisks in a flow chamber designed to artificially mimic the environment within

an artery. This uses whole blood flowing over a layer of blood vessel cells to assess clotting on their surface in response to nanodisks in the presence or absence of radiation. Successful introduction of nanotechnology may improve the efficacy of our vascular targeting occlusion of AVM vessels.

Summer 2018-2019


2018 Research Gift Awards â–ź NEUROMUSCULAR DISEASES

Early diagnosis of amyloid- and paraprotein- associated neuropathies

Chief Investigator: Dr Antonia Carroll Brain and Mind Centre, University of Sydney, NSW Co-Investigators: Dr Neil Simon

Amyloid and paraproteinassociated neuropathies (APAN) are a neglected group of debilitating peripheral nerve disorders, resulting in weakness, sensory disturbance, pain and functional impairment for patients, including difficulty walking and performing activities of daily living. APAN are frequently misdiagnosed, leading to delays in correct diagnosis, accumulated disability and side effects from inappropriate treatments. APAN are a growing problem in an ageing population; while 1% of the population have a paraprotein during their lifetime, this increases to 7% by age 80. Furthermore, 10% of patients with peripheral neuropathy of unclear cause are found to have a paraprotein during their work up. Despite

the prevalence and breadth of the APAN, there is currently no consensus on the best diagnostic pathways or treatment in most of these cases. Early diagnosis of APAN is increasingly important, as new therapies have been developed, which only improve patient outcomes if individuals are treated early in the disease course. Early diagnostic techniques and definition of the optimum time to initiate treatment is therefore particularly important in this group. This project aims to identify the distinguishing clinical and investigative features of the various APAN in order to improve diagnostic algorithms. In addition, we will evaluate the utility of electrophysiological and imaging

techniques, identifying biomarkers to aid early diagnosis of APAN. Furthermore, we will evaluate the use of biochemical testing to identify markers of early damage to the peripheral nerve and disease progression. By identifying early diagnostic markers and biomarkers to monitor disease progression, this research has the potential to significantly improve patient outcomes and quality of life in the APAN. Research providing further clarity to the underlying pathological mechanisms of APAN and early diagnostic tools are essential to the development and success of novel, targeted treatments, and hence positive long term outcomes for patients.

Creating a biobank for children with nerve disorders

Chief Investigator: Dr Michelle Farrar University of New South Wales Co-Investigator: Professor Matthew Kiernan


Peripheral nerve diseases result in progressive muscle weakness and wasting, and many with childhood onset may lead to significant disability and reduced survival. Spinal muscular atrophy (SMA) is a noteworthy exemplar, characterised by progressive muscle weakness and is the leading inherited cause of infant mortality. The therapeutic landscape for SMA is being transformed, with the first disease modifying treatment that may extend quality and quantity of life reaching children with SMA from June 2018, following PBS listing in Australia. Notwithstanding this milestone, there are many uncertainties regarding treatment response, effects and long term outcomes across a broad clinical population. There are critical gaps in identifying reliable, relevant,

sensitive and standardised biomarkers across the SMA spectrum. Essential to supporting ongoing SMA/neuropathy research and future therapeutic development is the availability of human bio specimens. As such, it is essential to establish specific research infrastructures to ensure collection and management of high-quality samples and data. The present study is designed to address these issues by establishing an Australian biobank for paediatric peripheral nerve disorders, with an initial focus on spinal muscular atrophy (SMA). This will provide a rich resource for future studies, to expand scientific knowledge regarding pathophysiology and treatment responses, extending our clinical and neurophysiological

prospective ‘new natural history’ studies. The present project is built upon years of strong collaborative work and represents a key step essential to further interdisciplinary innovative research. Funding will be utilised to support a research co-ordinator within the neuromuscular research team to establish the collaborative biobanking programme to support long-term biomarker studies. The goal is to implement the infrastructure, capability and standard operative procedures to initiate a long-term programme of paediatric peripheral neuropathy biological sample collection and storage. This will provide a rich resource for numerous studies to guide future therapeutic development.

Dystonia is a disorder characterized by involuntary muscle contractions that cause slow repetitive movements or abnormal postures. The movements may be painful, and some individuals with dystonia may have a tremor or other neurologic features. There are several different forms of dystonia that may affect only one muscle, groups of muscles, or muscles throughout the body. Some forms of dystonia are genetic but the cause for the majority of cases is not known.


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Measuring changes in brain tissue volume over time using Magnetic Resonance Imaging in a group of Multiple Sclerosis patients from a single Australia MS clinic

Screen for OSA in MS-related fatigue Chief Investigator: Dr Rodrigo Tomazini Martins Eastern Health, Box Hill Hospital, Victoria Co-Investigators: Professor Helen Dewey, Dr Patrick Carney, Dr Katherine Buzzard, Professor Helmet Butzkueven, Dr Alan Young, Dr Denise O’Driscoll, Professor Danny Eckert

Chief Investigator: Dr Heidi Beadnall Brain and mind Centre, University of Sydney, NSW Co-Investigator: Mr Chenyu Wang

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease affecting the brain and spinal cord. There are over 25,000 Australians living with MS and it is one of the most common causes of neurological (brain and spinal cord) disability in young adults. In MS clinical practice the appearance of white matter lesions on magnetic resonance imaging (MRI) scans is used to help assess whether inflammatory disease is occurring. However, to date accurate measures of the neurodegenerative component of the disease are lacking and unavailable for use in the clinical setting. The measurement of brain volumes and brain volume change over time using specialised MRI software techniques have been proposed to address this need. Multiple MRI techniques, that measure brain volumes and volume change, have been previously researched in MS clinical trial populations. Studies indicate that whole brain volume loss in untreated MS patients occurs at a rate of 0.5–1.35% per year, compared to 0.1–0.3% per year in age-matched healthy individuals. Research has also shown that brain volume loss, as measured by specialised MRI software techniques, is associated with and predictive of disability and cognitive decline at the group level. This project aims to further explore and validate the use of MRI brain volume measurement techniques in a real-world Australian MS patient group. Investigating of the use of these techniques in individual patients will be a particular focus. Both gold standard and novel fully automated MRI software techniques will be studied. Through their association with clinical patient outcomes, MRI brain volume and volume change measures have the potential to help guide MS management decisions and assist with monitoring treatment response; these important aspects will also be explored as part of the project.


Fatigue is a chronic and debilitating feature of multiple sclerosis (MS) which is not fully understood. It is multifactorial and often reduces quality of life of those individuals. Obstructive sleep apnoea (OSA) is likely to be one of its contributing factors. Its prevalence in MS patients is approximately 20% in newly diagnosed patients and can increase to nearly 90% during disease course. A common screening questionnaire (STOP-BANG) to assess risk of OSA only identifies 56% of those patients. Due to the nature of the central nervous system inflammatory lesions present in MS, majority of the people with OSA are non-obese, which suggests that nonanatomical causes, such as impaired upper airway sensation and poor muscle responsiveness during sleep, are the contributing factors to OSA in MS people. This causes transient disruptions in nocturnal breathing and reductions in overnight oxygen saturation, which characterises OSA. These events apart from leading to daytime sleepiness and feeling of waking up unrefreshed are associated with increased or cardiovascular disease and motor vehicle accidents. Upper airway sensation testing with monofilaments during wakefulness has been routinely used in research protocols. It was shown to have a high sensitivity (80%) to detect nocturnal upper airway occlusion (OSA). Thus, the aim of this project is to recruit 30 fatigued MS patients, fill in 2 groups (low vs high risk) of OSA according to the STOP-BANG questionnaire. Additional upper airway sensation will be tested in all enrolled participants and they will undergo formal gold standard sleep test, polysomnography (PSG), to compare the results. With this protocol we expect to better detect fatigued MS individuals with high propensity to OSA and to facilitate the referral to PSG, rather than referring every single patient. Consequently, a better management of the fatigue in those individuals is likely to be achieved as a reduction to the economic burden to public health in the light of the changes of the billing practices for sleep studies implemented by Medicare in 2017-18.


Multiple Sclerosis (MS) is the most common acquired chronic neurological disease affecting young adults. 3 out of 4 Australians diagnosed are women.

Dystonia is the third most common movement disorder worldwide. The cause, while neurological in origin, is unknown. ADSG Website: australiandystoniasupportgroup.wordpress.com/ ADSG Community Page: facebook.com/AustralianDystoniaSupportGroup ADSG Closed Support Group on Facebook: facebook.com/groups AustralianDystoniaSupportGroup/

Summer 2018-2019


2018 Research Gift Awards ▼ NEURO – TRAUMA

Promoting peripheral nerve regeneration by inhibiting a gene, miRNA-23a Chief Investigator: Dr Rabia Islam, Deakin University, Victoria Co-Investigators: Dr Professor Aaron Russell, Dr Victoria Foletta, Dr Paul Della Gatta, Dr Frederico Gerlinger-Romero When trauma or disease damages the connection between the motor nerves and skeletal muscle, muscle wasting occurs. This leads to impaired mobility, lack of independence and may even lead to death. Some of the peripheral nerves are able to repair and recover functional connections with skeletal muscle. However, the amount of nerve regeneration is often not sufficient. This leads to permanent muscle weakness, long-term disability and other health issues. Therefore, a major goal for treatment of nerve damage is to repair the nerve processes effectively and to facilitate maximal re-connection with muscle to allow full functional recovery. In patients with motor neurone disease (MND) and mouse models of MND, we have observed that the progressive loss of motor neurons and muscle wasting, is associated with an increase in a small gene called miRNA-23a/miR-23a. We therefore postulated that miRNA-23a may contribute to motor neurone disease progression. Suppression of miRNA-23a may delay disease on-set and severity. Our preliminary studies revealed that miRNA-23a suppression in a mouse model of MND reduces muscle wasting and alleviates the loss of body weight. Furthermore, the mice display improved mobility and strength indicating improved muscle health and motor nerve connection with skeletal muscle. This was confirmed by further molecular analyses. Based on these results, we currently hypothesize that suppression of miRNA23a will help form new motor nerve connections with skeletal muscle, thereby reducing muscle wasting and weakness. To test this hypothesis, we will investigate the effect of miRNA-23a inhibition on nerve repair using an acute nerve crush injury model. Following nerve crush injury, skeletal muscle strength and movement will be measured in mice with either normal or suppressed levels of miRNA-23a. The newly formed connections between muscle and nerve will also be imaged in muscle cross-sections. These experiments will determine whether miRNA-23a is important for nerve regeneration. It will delineate the specific role it plays in the molecular pathways during regeneration. This information is a prerequisite for the development of potential new therapies for peripheral nerve injury and neuropathies.



Fluid flow in spinal cord cysts Chief Investigator: Dr Sarah Hemley Macquarie University, NSW Co-Investigators: Professor Marcus Stoodley, Professor Lynne Bilston, Dr Magdalena Lim, Dr Shinuo Liu Traumatic spinal cord injury is a devastating condition affecting approximately 600 people each year in Australia and 13,000 in the USA. Of these, up to one third will develop syringomyelia. This condition is characterised by the formation of a fluid-filled cyst, which may lead to pain, paralysis, muscle weakness and wasting, loss of reflexes, and loss of sensitivity to pain and temperature. Additional neurological deficits due to syringomyelia are particularly devastating in spinal cord injury patients, who can be transformed from disabled but independent people into patients requiring assistance with basic daily tasks. If syringomyelia affects the brain stem or respiratory function (breathing) it is lifethreatening. Treatment for post-traumatic syringomyelia usually involves surgery to reduce the pressure the cyst places on the spinal cord, by draining the fluid from the cavity, and removing any obstructions to the normal cerebrospinal fluid flow. Most clinical studies report long-term surgical failure rates of approximately 50%. Syringomyelia occurring as a result of spinal cord injury has proven particularly difficult to treat, because the injured spinal cord is at substantial risk of further mechanical damage with any surgery. Determining the factors responsible for cyst formation and resolution is essential to define surgical goals and for improving treatment. We have shown that cardiac pulsations are important drivers of cerebrospinal fluid flow. Breathing, coughing, and straining also affect cerebrospinal fluid flow surrounding the brain and spinal cord. The possibility that pressure changes that occur in the chest during the respiratory cycle might contribute to spinal cord cyst formation has not been studied. The proposed research will determine the effect of respiration on fluid flow into the spinal cord of control animals and in an animal model of post-traumatic syringomyelia. In addition, we will determine if there are distinct pathways for fluid movement into the cyst using electron microscopy to study the ultrastructure at sub-nanometer resolution. A greater understanding of the specific anatomical pathways may provide precise targets for future treatment strategies.

Huntington’s Disease is an inherited disease of the brain that affects the nervous system. It is characterised by jerky, involuntary movements, but sometimes causes rigidity without abnormal movements, changes in using the limbs, loss of control of bodily functions, and dementia, including a progressive deterioration of memory, speed of thought, judgement, lack of awareness of problems and planning.

The Newsletter of the Brain Foundation


Assessing brain based recovery in children with concussion following brain stimulation

Chief Investigator: Dr Kartik Iyer University of Queensland Co-Investigators: A/Prof Karen Barlow, Dr Luca Cocchi

Childhood concussion is on the rise. Over 1 in 10 children who present to an emergency care setting with a mild traumatic brain injury (mTBI) will develop persistent concussion symptoms 4 weeks after their injury. The impact of this injury is concerning as it occurs in a critical brain development window. It can lead to significant problems in cognitive, emotional, and social functions that may become chronic. Currently, treating for persistent concussion symptoms in children is problematic. Clinical management of the condition is approached case-by-case, with heterogeneous results. An emerging therapy to manage symptoms of concussion is noninvasive brain stimulation (NiBS).

The targeted use of NiBS is thought to promote the functional reorganisation of local and diffuse patterns of communications between brain regions (i.e. stimulation promotes better whole-brain connectivity). Such brain stimulation methods have gained an established role for the treatment of adult conditions such as major depression and stroke. As such, NiBS presents a safe and non-invasive therapy to potentially alleviate symptoms of concussion in children. A major impediment for the use of NiBS in paediatric populations is the knowledge gap in the understanding of the effects NiBS on the brain of children recovering from concussion. Cutting-edge techniques that allow an in-

vivo measure of whole-brain connectivity are best placed to determine how NiBS contributes to the restore of brain functions in children with mTBI. Our trial will monitor brain activity (EEG, functional MRI) in 50 children with persistent concussion symptoms whilst receiving NiBS therapy. Using brain activity recordings, we will examine the change in wholebrain brain connectivity to examine how NiBS promotes better clinical outcomes for children with persistent concussion symptoms. This new knowledge will significantly advance our understanding of a child’s brain following a concussion and how they may benefit from a targeted intervention such as NiBS therapy.

Blocking ROCK2 to improve recovery from brain injury dementia. Unfortunately beneficial treatments are lacking due largely to our limited understanding of how TBI promotes these events.

Chief Investigator: Dr Jana Vukovic University of Queensland Co-Investigators: A/Prof Kelli MacDonald, A/Prof Marc Ruitenbergi


Traumatic brain injury (TBI) is a leading cause of disability in Australia and worldwide. The effects of TBI are profound and often long term. Adverse outcomes are wide ranging and can include confusion, memory loss, depression, cognitive decline, epilepsy and eventual development of

TBI can be divided into two mechanistically distinct stages: the primary and secondary insult. The primary injury is the immediate and irreversible damage caused by mechanical forces during the accident. The damage caused by the primary insult is irreversible, however, the secondary injury is a driven largely by the ensuing inflammation that causes further cell death in the brain and adversely affects brain function. Importantly, early interventions to limit the inflammatory response following a significant brain impact represents a novel strategy to minimize secondary injury and

improve outcomes. We have found that the protein ROCK2 is rapidly increased in the brain following TBI. ROCK2 has an established role in driving pathogenic immune responses in multiple inflammatory diseases. In clinical studies, inhibitors of ROCK2 have been shown to limit inflammation to attenuate disease and reverse pathology in patients with psoriasis and pulmonary fibrosis. In the proposed study we will use our well established preclinical models to elucidate the mechanisms by which ROCK2 promotes injury following TBI, and test whether ROCK2 inhibition with a highly selective orally available small molecule inhibitor of ROCK2 (KD025) improves cognitive and behavioural outcomes.

Are you part of a support group for another neurological condition that you would like to share with other sufferers. Please let us know so that we can publish the details. No one should have to go it alone. Being with others with the same condition offers a great deal of comfort and support!

Summer 2018-2019



▼ NEURO – Trauma CONTinued

Cognitive decline following spinal cord injury: Does neuroinflammation play a role?

The James Lance Award

Chief Investigator: Dr Anna Leonard The University of Adelaide, SA Co-Investigator: Dr Lyndsey Collins-Praino Approximately 200-300 individuals sustain a traumatic spinal cord injury (SCI) each year within Australia, however globally this number is far greater with 250,000 to 500,000 SCIs occurring worldwide. Fortunately, due to improvements in clinical care, survival rates following SCI are very high. While this is undoubtedly a positive outcome, it has also led to concern surrounding the chronic care of SCI individuals. Certainly, these are individuals who typically sustain their injury in young adulthood and, subsequently, life with a SCI for a long period of time. One such area of concern is that individuals who have sustained a SCI are showing signs of cognitive dysfunction as they age when compared to the general population. Our research will investigate the effect of SCI on chronic cognitive function in a pre-clinical model. This study will comprehensively characterise how the brain reacts, through inflammatory processes, following a traumatic SCI. In particular, we will investigate whether there is a graded response by the brain dependent on how severe the SCI is. Additionally, this study will investigate a potential treatment (Fyn kinase inhibition), which can reverse the inflammatory effects and therefore reduce any observed cognitive decline. Previous research in an Alzheimer’s model has demonstrated that administration of a novel Fyn kinase inhibitor led to improvements in both spatial recognition memory and depressive-like behavior. Given that both of these are of significant concern in an SCI population, it has led us to hypothesise about the potential utility of Fyn kinase inhibition for the treatment of cognitive impairment and depression in SCI. The results of our study will therefore help to elucidate the link between cognitive decline and neuroinflammation following SCI as well as develop a potential therapeutic treatment to improve and maintain such cognition, thus improving quality of life.

Nerve excitability studies in familial hemiplegic migraine Chief Investigator: Dr A/Prof Karl Ng Royal North Shore Hospital, NSW Co-Investigators: Professor Lyn Griffiths, Ms Hsin-Yee Chen Nerve excitability in sporadic migraine and monogenic familial hemiplegic migraine. Migraine is very common, affecting almost 1 in 3 women and about 1 in 8 men and costs Australians about $36bn dollars a year. For many of the more severely affected, it is a constant struggle to function day by day. Many believe this disorder to be due to excessive sensitivity of the trigeminocervical system which conveys sensation from the head and neck. A genetic load may confer a vulnerability that contributes to a process of central sensitization. There are three known monogenic (single gene disorder that on its own is responsible for the characteristics) causes of familial hemiplegic migraine, a form of migraine that can sometimes looks like a stroke. This population may have a disorder of ionic channels in the nerve membrane, and the technique of nerve excitability will be utilised to study the peripheral nerves of patients with this disorder, and compare them with patients with migraine without a defined genetic cause (the majority, as well with normal individuals. We may in this way be able to discover what is happening at the nerve membrane level that makes nerves possibly 'fire' more often, and see if this can be predictive of medication response or modified by drugs. Funded by the North West Committee of the Brain Foundation

The 2nd ‘David Marsden Memorial Movement Disorders Symposium’ The second of these memorial symposia was organised by our very active Director Professor Tissa Wijeratne as part of the University of Melbourne – Western Health Collaboration. In addition to presentations by eight leading specialists with a sub-speciality in movement disorders, there were special video inputs from Professor Kailash Bhatia, Consultant to the National Hospital of Neurology, Queen Square, London, Professor Mark Hallett, Chief, Human Motor Control Section, Bethesda and Professor Anthony E Lang, Chair of Movement Disorders, Toronto Western Hospital. The seminar was well attended with a strong cohort of Registrars. Professor Marsden is regarded as the ‘father’ of the movement disorders field. He was very prolific and by his early death at 60, had authored or co-authored 800 full papers, 200 book chapters and books and more than 60 invited reviews. 14

The Newsletter of the Brain Foundation

Pictured are the enthusiastic regristrars from Sunshine Hospital along with Gerald and Jinani Rajakeerthi – Tissa’s assistant and Prof Tissa Wijeratne.

Healthy brain Elizabeth Penfold Simpson Prize


A long day in Adelaide was had by Gerald in September. Beginning with the fundraising walk by Nathan Nguyen at 6.30am, Gerald presented the Penfold Simpson Award for the best research project in South Australia that evening.


84% of people reading this will not find the the mistake in this A,B,C,D,E,F,G,H,I, J , K , L , M , N , O , P, Q , R,S,T,U,V,W,X,Y,Z.


How can you throw a ball as hard as you can and have it come back to you, even if it doesn’t bounce off anything? There is nothing attached to it, and no one else catches or throws it back to you.



Dr Hordacre's research found that this non-invasive technology has the potential to greatly assist stroke rehabilitation. The presentation was planned during National headache Week as we had an event for Migraine that week and another to raise funds at RAAF Edinburgh. The latter, planned by Nathan Nguyen, a former RAAF Officer who suffered an injury that led to a stroke partly paralysing his left side – read about his extraordinary efforts in our Fabulous Fundraisers section (p3).

What occurs once in every minute, twice in every moment, yet never in a thousand years?


What’s full of holes but still holds water?


What flies without wings?


Where will you find roads without vehicles, forests without trees, and cities without houses?


What are two things you cannot eat for supper?


What word looks the same upside down and backward?


What five letter word becomes shorter when you add two letters to it?


A boy was rushed to the hospital emergency room. The ER doctor saw the boy and said, “I cannot operate on this boy. He is my son.” But the doctor was not the boy’s father. How could that be?


What can you keep but cannot share and once you share it, you can’t keep it anymore?


You leave home and go to your right. You reach a corner and turn left. You reach another corner and turn left again. You reach another corner and turn left again and go home. When you get there, there is a person with a mask there waiting for you. What’s happening?

Coincidently, the winning project by Dr Brenton Hordacre was about successful external direct current stimulation of the motor cortex in Stroke, which had direct relevance to Nathans condition. The long-standing Elizabeth Simpson Prize is awarded once every two years and applications were called earlier this year. The Prize is awarded to the peer-reviewed and published neuroscientific research paper considered to be the best in South Australia during the previous two years. The amount of the prize is determined by the average of the Trust’s income over the two-year period. Dr Brenton Hordacre of The Samsom Institute of Health Research at the University of South Australia was selected for his work about:

Neuroplacsticity and network connectivity A transcranial direct current stimulation study.






The story that this research could help with his rehabilitation and Nathan’s desire to raise funds for further research was so moving that Channel 10 featured it nationwide. Their coverage can be seen on our Facebook page. Stroke is a global leading cause of disability. Despite recent advancements in stroke care, many stroke survivors are still forced to live with persistent impairment that impacts their quality of life. As a result, there is an urgent requirement to improve stroke rehabilitation and this has motivated several avenues of research. One technique that has received a lot of interest in recent years is non-invasive brain stimulation as it may help facilitate recovery through a process known as neuroplasticity. Despite early promising results, responses to brain stimulation are variable from one person to the next, limiting potential for clinical utility. Since stroke is a highly heterogeneous condition with differences in size and location of the lesion, we sought to determine whether a measure of brain activity was able to identify stroke survivors who were likely to benefit from this treatment. We found that brain connectivity obtained using electroencephalography (EEG) was able to predict the response to brain stimulation. People with stroke who had stronger connectivity between ipsilesional motor cortex, ipsilesional parietal cortex and contralesional frontotemporal cortex prior to stimulation demonstrated the expected increase in brain activity following stimulation. The results of this study confirm brain stimulation is not a one-size-fits-all treatment. However, it may be that brain connectivity obtained very quickly and safely with EEG can be used as a biomarker to identify people with stroke who are likely to benefit from this treatment. We are currently in the process of continuing to explore the potential for brain connectivity to be used as a ‘screening tool’ in the hope that brain stimulation can prove to be a helpful adjuvant therapy for those people living with the effects of stroke.

Gerald presenting the prize to Dr Brenton Hordacre

Nathan and his family along with Brenton, his wife and Gerald after the presentation

Solutions on back page

Summer 2018-2019


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Why not Fundraise to support Research

Clare and girls with medals from this year’s City to Surf

We are often asked ‘what can we do to fundraise?’ Well, the answer is many and varied. If you are creative, you can up with your own event. Or, if you would prefer, you can join a Community Event, such as a fun run or walk. Whichever you decide suits you, these sites can make it easy for you to raise money and take the hassle out of collecting it.

Our very sincere thanks go to the families and friends who have donated in Memory of their loved ones. We appreciate your support at this very difficult time.

See – mycause.com.au : everydayhero.com.au : gofundraise.com.au, then select Brain Foundation as your charity. It is as simple as selecting the one which suits you best.

Rosemary McDONALD

– Frankie’s Legacy, Tess Stokes – Williams Family In Memoriam, Run for Isaac, Taylor Boyd who donated his birthday to his son. Everyday Hero – Nathan Nguyen – Steps for Stroke, Fiona Galbally

Antiono PAGLIANITI Stephen John MANN Yvonne HAXTON

Our thanks to the following fundraisers: My Cause – Lloyd and Louis on the Tandem World Cycle, Sydney and Gold Coast Zombies, Cyclicle 4 Brain Foundation, Caulfield Grammar Fun Run, Denise Clarke – the brains to swim the English Channel, Antonia Petrakis


in the Pete Mac Fun Run, Clare Balken and team – City2Surf, David Smith – Melbourne Half Marathon, Team Tom in the City2Bay Go Fundraise – Caitlyn Robson

Want some BIG FUN?


BEQUEST We thank the Estate of Flora Maria De KAMPER for their generous contribution.

Then you should try BIG TRIVIA If you want to host a fun family and friends event, then consider Big Trivia by Brain Foundation. We have packaged this event to make it easy for you to have participants register and enjoy.


Please ring our office for all the information and support you need.

Regular Giving Would making small, regular donations suit you better than one bigger donation per year? Perhaps you should think about making a regular monthly or quarterly donation. Contact our office or download a form and we will do the rest for you.

To all our wonderful donors, a very big thank you for your support in 2018 and our wishes for a Happy Christmas and holiday break.

Workplace Giving is an easy alternative and your company may even match your donation. Speak to your paymaster for further information.

Estate Planning and Bequests: Our benefactor, Australian Executor Trustees offers reduced rates for Brain Foundation supporters. For more information, please call our office on 1300 886 660.

good2give.ngo is a new site which makes workplace giving a breeze. Have a look and see if it is for you. Healthy Brain Solutions Answer 1 – “The” is repeated. Answer 2 – Throw the ball up in the air.


Answer 3 – The letter “M”. Answer 4 – A sponge. Answer 5 – Time. Answer 6 – A map. Answer 7 – Breakfast & Lunch. Answer 8 – SWIMS.

Thank you for supporting brain research through the Brain Foundation To make a donation please visit our website brainfoundation.org.au/donate or use the donation form on the letter enclosed.

Answer 9 – The word short. Answer 10 – The doctor was his mum. Answer 11 – A secret. Answer 12 – You are playing baseball.