SINGAPORE — Five years ago, Hazwady Nazran, now 38, was hospitalised with mysterious and terrifying symptoms such as violent episodes, paranoid delusions, confusion, memory loss and seizures.

If his wife, Dr Miria Hastuti Soedarsono, 34, had not insisted that he be given a spinal tap, the music teacher and songwriter could have ended up in a mental hospital.

“Hazwady had three months of weird behaviour. He would say he could not see properly, and he would go without sleeping for three days at a stretch. He loves our son and would never scold the boy, yet he was shouting at Almizan,” recalled Dr Soedarsono.

Hazwady said: “This disease was a silent thief. It sneaked in quietly, causing anxiety, confusion and memory loss, compounded by wild emotional outbursts, hallucinations and the inability to comprehend the thoughts in my mind.”

The disease struck him in late 2018 when the family was leading “a happy, calm and pleasant life”.

“I had just launched a successful start-up while juggling a career in the shipping industry. At that time, I felt I had reached the pinnacle of life. It was a heart-wrenching decision when I had to step away from my professional endeavours because I was growing weaker and slower,” Hazwady added.

His outbursts, seizures and periods of catatonia — during which he was immobile and mute, and often appeared to be staring into space — resulted in him being strapped down in a bed in the psychiatric ward of a public hospital.

Not long after, he had a seizure that resulted in hallucinations and loss of control of his bladder.

Dr Soedarsono said: “It was frustrating. The doctors kept saying it was a mental issue because of his psychosis. Being a doctor myself, I was not convinced… and I insisted that he was to be given a lumbar puncture and an MRI (magnetic resonance imaging).”

In 2019, Hazwady was eventually diagnosed with anti-NMDA receptor encephalitis, an autoimmune disease where the body creates antibodies against the NMDA receptors in his brain, disrupting normal brain signals and causing the brain to swell.

Dr Soedarsono’s colleagues at Sengkang General Hospital treated Hazwady with steroids and some intravenous immunoglobulin, and he did better.

However, he had a relapse a few months later. This time, the same treatment did not work as well.

Dr Yeo Tianrong, a neuroimmunologist from the National Neuroscience Institute at Tan Tock Seng Hospital who became Hazwady’s main physician, said that in anti-NMDA receptor encephalitis, antibodies produced by the immune system target the NMDA protein, breaking down communication among nerve cells.

Overactivity in one nerve cell — due to the stress hormone cortisol and fight-or-flight hormone adrenaline — could cause the communication breakdown, resulting in seizures, Dr Yeo added.

“(Such) patients first have what seems to be a viral fever and, within the next few weeks, progress to neuropsychiatry manifestations, such as depression, mania, anxiety, sometimes even psychosis like hallucinations and delusions,” he said.

“There are also negative symptoms such as the lack of spontaneity or drive, attention deficit, and impoverished speech and language.”

Dr Yeo said if the condition is not properly diagnosed by this stage, the patients would go on to have seizures, disruption of the autonomic nervous system, and a movement disorder called dyskinesia, where there is repetitive, rhythmic movement of the face and mouth.

“It is usually these psychiatric and behavioural symptoms that prompt patients to seek medical treatment… and they are frequently misdiagnosed as psychiatric symptoms,” he added.

Anti-NMDA receptor encephalitis is rare, affecting one to two individuals out of a million a year. According to Dr Yeo, it typically occurs in young women, often in their 20s and 30s.

He added that about half of these women have ovarian teratoma, a type of tumour that imitates any sort of cells in the body.

“Some cells of the immune system recognise cancer cells as abnormal and kill them. Now, should the cells (in the teratoma) mimic brain tissues, in the case of (a patient with) anti-NMDA receptor encephalitis, the immune system will try to suppress them,” he said.

“In doing so, the same immune response can cause problems in the brain because of the likeness of the proteins that are there.”

But when this happens in men, Dr Yeo said, doctors do not know why “there is such loss of tolerance to self-proteins, to self-antigens” since there is no ovarian teratoma in them.

He said it was in 2007 that the first major peer-reviewed paper was published on anti-NMDA receptor encephalitis.

“I can remember a male patient about 20 years ago. It was before (the condition) was discovered. At that time, he had on-and-off recurrent seizures, and he was labelled as having epilepsy and followed up as such. He was not given any sort of immuno-treatment that would suppress the anti-NMDA receptor encephalitis,” Dr Yeo added.

“I remembered seeing him in 2014 when he came into my ward. He was behaving very bizarrely and going into a catatonic state. He was holding his hand out and staring for half an hour without moving. I had a degree of suspicion that this could be NMDA, so I did a lumbar puncture for him.

“We found that he actually had the antibody and gave him immuno-treatment. He had since returned to work running a charity organisation.”

Dr Yeo said: “What was interesting was I believed that in the late 1600s in Salem, Massachusetts, women who were accused of being witches and later burned at the stake were probably suffering from anti-NMDA receptor encephalitis.

“They were found to behave bizarrely, exhibiting strange physical behaviour such as fits, bodily contortions, unexplained pain, going into trances and being struck mute.”

As for Hazwady, he was sent to Dr Yeo for “a third opinion”, after having seen two other doctors without any improvement.

“He had very little recollection of the first part of his journey because the NMDA antibodies attacked the part of the brain called the limbic system, which is located near the central part of the brain. This is where our… short-term memories are encoded,” Dr Yeo said.

“This area also helps to regulate our emotions, our fears, so it was not surprising that he had all the neuropsychiatry manifestations and episodic memory loss. He also could not form new memories at that point.”

Dr Yeo prescribed some new oral immunosuppressants, noting that Hazwady was not compliant and even stopped taking the medication at one point.

“He had a mild relapse — headaches and photophobia, where he was very scared of bright lights. Basically something was irritating his brain and I got him admitted and repeated the MRI, and it showed evidence of an attack. I treated him with steroids and he got better,” Dr Yeo said.

Today, with proper treatment, Hazwady is able to write and teach music to children at an international school. His son is now seven years old, while his daughter is two.

“I started writing songs (and I’m) signed with a talent management company as its songwriter. I am proud that I am no longer defined by my condition,” he said.

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This article was first published in The Straits Times. Permission required for reproduction.