Madam Lau Kan How had her first stroke when she was 58 years old. The former superintendent of schools was addressing a crowd at a mathematics conference in 2000 when she realised she “was not speaking” what she wanted to say.

She stopped her speech and was sent to the hospital immediately. The single mother of three retired from civil service soon after, although she continued to travel to other countries to run courses as an education consultant.

Madam Lau was diagnosed with moyamoya disease in her early 60s.

It is a rare, progressive cerebrovascular disorder caused by blocked arteries at the base of the brain. The cause of the disease is not known.

Moyamoya means “puff of smoke” in Japanese and is used to describe the tangled appearance of tiny blood vessels that have become larger to compensate for the blockage.

Patients tend to get strokes because these vessels cannot compensate enough to supply blood to the brain.

Three strokes and three “mini strokes” – transient ischaemic attacks – later, Madam Lau remains strong and in full control of her mind. She will turn 83 in August.

MEDICAL MYSTERY

“I was told that younger patients with moyamoya disease and with better brain scans than me have already passed on,” she says wryly.

 ST PHOTO: NEO XIAOBIN

Thankful for the support of medical professionals, friends and family who helped her and encouraged her since her first stroke, she was moved to do something for those suffering from the same life-threatening condition.

Madam Lau signed up in May 2024 to donate her brain after her death to BBS.

The facility was officially opened on Nov 27, 2019.

To date, 420 people have pledged to donate their brains. The young brain bank has also retrieved 11 brains and seven spinal cords thus far.

The brain is divided in two hemispheres; one hemisphere is snap-frozen, while the other is fixed in formalin – a process of preserving biological tissue using a solution of formaldehyde in water.
BBS staff preparing a brain for dissection. A high-resolution camera is mounted above the workstation to photograph dissected brain regions for precise documentation.

The research aims to help prevent, diagnose, treat and cure conditions that affect the brain, such as Parkinson’s and Alzheimer’s disease.

Photographing dissected brain regions is crucial for anatomical documentation. It also helps researchers trace the origin of each tissue sample, ensuring accurate correlation with histological findings.

BBS is a partnership between the National Neuroscience Institute, Lee Kong Chian School of Medicine, National Healthcare Group, NUS Yong Loo Lin School of Medicine, Agency for Science, Technology and Research and Duke-NUS Medical School.

In his speech at BBS’ fifth anniversary in November 2024, Singapore’s director-general of health, Professor Kenneth Mak, said neurological diseases are a key research priority here, given the rising prevalence of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, as the population continues to age.

In Singapore, it is estimated that more than 100,000 people will have dementia by 2030, he added.

(Clockwise from bottom left): The cerebrum, dura, and half of the cerebellum and brain stem, which is partially obscured. Dura is the outermost layer of connective tissues that surrounds and protects the brain and spinal cord.

While life expectancy in Singapore is one of the highest in the world, the nation’s population is rapidly ageing.

As neurodegenerative diseases are more common in older individuals, it is anticipated that the incidence and prevalence of such conditions will increase with an ageing population.

“However, our understanding of these diseases is limited because we are unable to retrieve brain tissue and study it at a high level of detail in living patients,” says Dr Yeo Tianrong, BBS deputy director and senior consultant at the National Neuroscience Institute’s Department of Neurology.

“Additionally, we still do not know how the Asian genetic background influences the nature of neurodegenerative diseases because there could be important, undiscovered mechanistic differences that are present which prevent us from developing therapies targeted at Asian patients,” he explains.

SHEDDING LIGHT

The work at BBS is important because post-mortem brain donation is the only way to gain a deeper understanding into neurodegenerative diseases with an Asian focus.

BBS staff preparing for the dissection process at the downdraft table. The table provides continuous downward airflow that pulls and remove fumes – particularly from formalin – as well as fine airborne particles, helping to protect staff and maintain a safe laboratory environment. ST PHOTO: NEO XIAOBIN

Technological advances in recent years have empowered researchers to examine the brain in extensive detail.

Phosphate-buffered saline is used to moisten gauze during tissue dissection. Keeping the brain tissue moist maintains structural integrity while handling and photographing samples.

A deeper understanding of biological pathways will help researchers formulate therapies that can stop further injury to brain cells, and in some instances, repair damaged cellular components.

A brain hemisphere being sliced on a customised cutting board to produce uniform 0.5cm-thick slabs for examination and sampling. Special care is taken to slice the brain cleanly and evenly, and ensure consistency across samples.

“For a country like Singapore, once we reach 2,000 to 3,000 registered donors, we can anticipate a steady and substantial number of brain donations annually,” says Dr Yeo.

Research associate Russel Vidal slicing a brain hemisphere. Ms Vidal takes special care to ensure that the brain is sliced cleanly and evenly, often at a standard thickness, to preserve anatomical landmarks and maintain consistency across samples.

With more brain and spinal cord samples, larger studies can be planned. Furthermore, local and international tissue requests will be possible to enable more researchers to study these neurological diseases.

Ms Vidal carefully transferring a dissected brain slice onto a clean board, which will be brought to the photography station.
Dissected brain slices are carefully arranged on a clean board to be transported to the photography station.

BBS currently conducts public outreach programmes by setting up booths at events to engage the public, providing information about the brain donation process and sharing research goals.

Its staff also conduct talks as part of public outreach efforts, for example, in public libraries.

BBS manager Priscilla Martin (left) and Ms Vidal carrying slices of brain samples for imaging.

Apart from collaborating with healthcare institutions, BBS also teams up with nursing homes, residents’ committees, hospices, and non-profit organisations like Parkinson Society, Singapore National Stroke Association, Dementia Singapore and Multiple Sclerosis Society Singapore.

Dissected brain slices are neatly arranged on a board for overhead imaging.
Ms Martin capturing an overhead image of all the dissected brain slices using a mobile phone. While a professional camera is used for high-resolution close-ups, the phone allows for a wide-angle shot to document the full set of slices in a single frame – essential for maintaining a complete anatomical reference.

But challenges still remain, as limited public understanding of brain donation and its importance for research contributes to a smaller donor pool.

Tissue samples being carefully selected from different regions of the brain as each region serves a different function and is affected differently by a disease.

People are sometimes hesitant about brain donation due to cultural or religious considerations regarding burial or cremation without the brain.

Histology slides are sent to Imperial College London for detailed pathological analysis by a neuropathologist. The neuropathology report typically takes around two to three months to be completed.

Some individuals have misconceptions about the retrieval process and have expressed concerns that brain donation will alter their appearance, especially if they are intending to have an open casket.

The support room is equipped with a monitoring system to track temperature and humidity levels.

Others decide against donating to avoid imposing additional responsibilities on their grieving families, such as coordinating the brain retrieval process.

This tray contains dissected tissue samples from a single donor, with each compartment labelled according to its corresponding location on the brain slice. An acetate sheet is used to map each slice and region, allowing researchers to visually match the photographed brain with the sample layout. This system ensures precise tracking and selection of specific brain regions for research.

Dr Yeo says: “Brain Bank Singapore would like to assure donors and their families that the shape of the head is preserved during the donation process. In very rare cases, a small area at the back of the head may need to be shaved for the incision. However, this does not affect the facial appearance, and an open casket funeral remains entirely possible.”

Ms Martin transfering brain tissue into a freezer set at minus 80 deg C. This temperature is critical for preserving the molecular integrity of the samples.

He adds: “Also, all the family members need to do is to call the brain bank once the donor passes; the brain bank will coordinate and assist in all processes including transporting the body for brain donation, brain retrieval, and returning the body to the family for funeral proceedings.”

A comprehensive report is generated, detailing clinical history, macroscopic and microscopic findings, and a final neuropathological diagnosis. This report can be shared with the donor’s family, who may wish to have a clinician’s perspective to interpret the findings and understand their implications.

Having been an educator all her life, the sprightly Madam Lau is full of life lessons and stories.

FINAL TALE

Upon her death, she hopes the last story that her brain tells will be a meaningful one.

 ST PHOTO: NEO XIAOBIN

“Studying my brain may help doctors understand how I am able to continue functioning so well, and contribute to advancing research concerning moyamoya disease, finding the cause of and cure for the disease, so that those who suffer from it will be able to receive better treatment that is cheaper and more effective,” she says.

For more information on brain donation, contact Brain Bank Singapore on 6592-6952 or WhatsApp 9730-9503.