Putting our heads together

Professor Ingrid Scheffer (centre) with Dannielle Goodwin (right) and her twin sister, Prue Matthews

When Dannielle Goodwin consulted Professor Ingrid Scheffer (PhD 1998), a University of Melbourne researcher based at the new Melbourne Brain Centre, about her seizures, she did not know that she would soon become central to a landmark medical study.

Dannielle suffered her first seizure at six months of age and her childhood was plagued by uncontrolled seizures and social isolation. Her learning also slowed a little after developing normally over the first few years of her life. She refers to this period as ‘the dark times’, which took their toll on her parents and identical twin sister, Prue, as well as herself. She went on to experience a wide range of seizure types into adult life; from brief head nods to violent flexion of the limbs. The latter is often difficult to control and requires emergency treatment.

Professor Scheffer first saw Dannielle when she was nineteen and diagnosed her with Dravet syndrome, a relatively rare and severe form of epilepsy beginning in infancy. Her diagnosis was confirmed when she found the causative gene mutation behind Dannielle’s condition.

Dravet syndrome is not normally inherited from a parent. As in Dannielle’s case, it is generally caused by a mutation that occurs in the early stages of the embryo’s development. This mutation had not occurred in her identical twin and this last factor was what set Dannielle’s case apart.

‘Usually if Dravet syndrome is present [in a twin], it’s found in both identical twins,’ explains Professor Scheffer. ‘In more than 70 per cent of affected children, it is due to a mutation in the gene SCN1A that encodes a sodium channel sub-unit. This sub-unit makes a gateway into the cell through which sodium ions pass. In the case of Dannielle, the gene mutation occurred after the process of twinning, where the fertilised zygote splits into two separate embryos that become the identical twins.’

To date, through Professor Scheffer’s care, Dannielle has been able to keep the seizures at bay. In the meantime, her case will be central to Dravet syndrome research undertaken at the Melbourne Brain Centre, Austin site.

The Melbourne Brain Centre, the largest neuroscience organisation of its kind in the Southern Hemisphere, opened in March this year and is a first-time collaboration between the University of Melbourne, the Florey Neuroscience Institutes, the Mental Health Research Institute, Austin Health and Melbourne Health. The two main sites, one at the Austin Hospital in Heidelberg and the other on the University campus in Parkville, will house over 700 neuroscience researchers.

The University of Melbourne’s Professor Trevor Kilpatrick (MB BS 1982, PhD 1993) is one of the three directors of the Centre.

‘Our collective vision is to help reveal the causes behind a wide range of brain disorders that affect one in five Australians. Life threatening neurological illnesses such as stroke and epilepsy, neurodegenerative conditions including multiple sclerosis, Parkinson’s, Alzheimer’s and the broad range of mental health issues facing the community,’ he says. ‘The Melbourne Brain Centre will be at the forefront of research with multidisciplinary teams drawing on their collective skills and experience.’

The Centre will act as a magnet for brain researchers from Australia, and around the world, supporting them in their work to find cures across all neurological disease.

Diagnosis and treatment will be improved with collaborations between neuroscientists and neurologists that the new Centre will facilitate. World-class imaging equipment will offer access to patients’ brains like never before, making interventions and treatment possible to alleviate conditions like Dravet syndrome.

In terms of the impact on individual lives, Professor Scheffer explains that Dravet syndrome is one of the most debilitating epilepsies that can occur; those suffering from the condition may have a reduced life expectancy with around 15 per cent of those affected not living past the age of twenty. Children with the syndrome often develop serious physical disabilities as they get older, frequently developing a crouch gait causing them to walk with bent knees. In Australia, there are currently over 400 reported cases of Dravet syndrome.

Mild to severe intellectual disability is almost always a feature of Dravet syndrome, as are behavioural problems for many affected children. Fortunately, Dannielle has managed to defy the odds, and does not suffer from any form of intellectual impairment.

Now twenty-seven years old, Dannielle lives an independent life with her husband Daniel, who works for the Department of Human Services, and their two young children in Taralgon. Professor Scheffer attributes Dannielle’s excellent intellectual and seizure outcome to a ‘good genetic background’.

Along with carefully prescribed medications, Dannielle has managed to identify triggers to her seizures, such as a lack of sleep, stress, an elevated temperature, and getting run down. Interrupted sleep can bring on what Dannielle refers to as ‘my warning’ that precedes an attack.

‘I feel like I’m being hung upside down and tipped back and all the blood comes rushing back into my head, with a feeling of dread,’ she says. ‘I get a really dry mouth, like after you’ve had your teeth cleaned at the dentist.’

Professor Scheffer offers her medical insight. ‘When she’s having a warning, there’s a discharge from her temporal lobe, resulting in the feeling of dread and other symptoms. The seizure then progresses to cause loss of awareness followed by headache, drowsiness and tiredness after her seizures.’

The relationship between Ingrid Scheffer and Dannielle Goodwin has been beneficial for both doctor and patient. In 2007, Professor Scheffer led a team to identify 70 per cent of Dravet syndrome sufferers as having a sodium channel gene mutation, and recognising that it could become a diagnostic test in the correct clinical setting. ‘What’s unique about Dravet syndrome is that it is the main form of epilepsy for which a gene test is currently available,’ says Professor Scheffer. Her research team has also published articles about Dravet syndrome in a number of journals.

The benefits of research that the Melbourne Brain Centre will facilitate are clear for patients like Dannielle, who, because of her diagnosis, was able to receive genetic counselling and the assurance that her children won’t suffer a similar fate. ‘I would like some more awareness of Dravet syndrome,’ she says. ‘Some parents don’t even know that their children have Dravet syndrome and they are unaware that there’s a test for it.’

Professor Scheffer is a current member of the Florey team at the University of Melbourne and at the new Melbourne Brain Centre that officially launched its Heidelberg site on 21 March this year.