When he was seven years old, he got a strange disease like a zombie.

Have you ever seen the "zombies" of the apocalypse in movies and TV shows? Their limbs never seem to stand upright, they walk crookedly, and their whole bodies twitch.

7-year-old Xiaohao (pseudonym) suffered from a strange "zombie"-like disease: At first, only his right hand spasmed, and then spread to his limbs. The disease progressed quickly, and the spasms became more and more frequent. Later, his body was always in a twisted state and he could not stand.

To others, this is a very painful and strange posture.

Strange Disease

On the last day of 2009, 26-year-old Lu welcomed her first child, named Xiaohao. Six years later, her younger sister also came into the world. A son and a daughter filled this family of six with joy. Lu felt that happiness had never been so close to her.

At that time, her life was like that of any ordinary family, with the daily necessities of life, picking up and dropping off the children from school, and occasionally some small quarrels. The onset of the disease changed this originally stable family, just like the old saying goes: every unhappy family has its own misfortune.

Xiaohao went to primary school in a blink of an eye. His grades were always in the top tier, and his small home was filled with awards of all sizes.

In March 2017, Lu found that Xiaohao's handwriting was a little crooked, so she enrolled him in a writing class. But not long after, the teacher of the writing class gave her feedback: Did this child have an arm injury?

Sister Lu observed carefully and found that when Xiaohao was writing, his elbows were raised high, as if he was struggling with himself. His eating posture was also strange, with his arms raised high, and they felt very stiff, like sticks.

At the end of June, when summer vacation was about to start, the school's morning exercise teacher found Sister Lu and said to her: "The child can't keep up with the morning exercises now, and his limbs are a little uncoordinated."

Sister Lu recalled that her child had been quite active before and wondered if he had ADHD.

Sister Lu took Xiaohao to the local hospital, but no problems were found. But his condition became more and more serious. He began to walk with his feet turned inward, and even couldn't stand steadily. His lower limbs showed more and more strange movements. The couple thought carefully about their son's life from childhood to adulthood, but they didn't find any other abnormalities.

With a glimmer of hope, the couple set out to seek medical treatment in Beijing. Sister Lu took her son to a large hospital in Beijing that is famous for its adult neurology department. They had many tests and all the results were normal. In order to further investigate the condition, Xiaohao also underwent genetic testing, but still could not find the specific cause.

In order to save money, Sister Lu took Xiaohao home first.

progress

The journey to seek medical treatment continued. After returning home, Sister Lu took Xiaohao to various major hospitals in Shandong, but the doctors gave similar responses: "The cause of the disease is unclear", "It cannot be cured, do more rehabilitation treatment", "Try taking medicine"... Xiaohao took more and more medicines, some of which had a slight effect, but after a few days he returned to his original state.

In the second half of 2017, Xiaohao's condition progressed very quickly. He leaned forward with his head on the ground, completely lost the ability to walk, twisted his body constantly, and his arms and legs were stretched straight like lead pipes. Even lying down became a luxury. When he was awake, Xiaohao could only feel pain, and he could only feel a little more comfortable when he was asleep. Sleeping pills became his "regular medicine".

Due to the long-term contraction of the muscles throughout the body, Xiaohao's throat muscles were also affected. He ate very slowly, and it was difficult for him to swallow the food in his mouth, and he choked easily. It was also very difficult for him to defecate, and he usually had to go to the toilet three or four times to complete it.

In order to supplement the family income, Dad went to work far away from home, and Sister Lu went to work in a nearby store. The family took turns to take care of Xiaohao 24 hours a day, with Grandpa and Grandma taking care of him during the day and Sister Lu accompanying him to sleep at night.

Xiaohao no longer plays toys with his sister, and apart from basic life needs, he no longer communicates with his family. An extroverted child gradually becomes silent due to the torture of illness, and there is no more laughter in the house.

The "strange disease" put the family in trouble.

Transition

When Yang Haibo, a pediatric neurosurgeon at Peking University First Hospital, saw Xiaohao for the first time, he vaguely guessed that he had a disease - dystonia.

This is a type of movement disorder. Dystonia refers to the involuntary and continuous contraction of the muscles of the same body, resulting in abnormal body posture, just like the "zombies" mentioned at the beginning of the article.

"They fall over easily," Yang Haibo knew what was going on as soon as he saw these children. "(Because they can't stand steadily) their heads are covered with lumps or wounds. Some of the wounds have thickened the bones due to repeated falls. Some children often fall on the back of their heads, and they have so many scars that they don't even have hair growing on the back of their heads."

When Sister Lu brought Xiaohao to Beijing again, Yang Haibo skipped the cumbersome procedures and consulted him directly.

Children with dystonia are prone to die from lung infections. On the one hand, due to difficulty swallowing, they are prone to choking on food when eating, causing pneumonia. On the other hand, in the case of dystonia, the patient's entire spine is twisted like a bow. Long-term muscle stiffness and low immunity can also easily cause lung infections.

At that time, a small cold was enough to kill Xiao Hao. In March 2018, in order to further investigate, Xiao Hao once again underwent "whole exome gene testing", which focused on the newly discovered pathogenic genes that cause childhood dystonia. A month later, Xiao Hao was diagnosed with DYT28 primary dystonia.

The causes of dystonia can generally be divided into three categories:

Hereditary: With a proven genetic origin, including autosomal dominant, autosomal recessive, or X-linked genetic diseases.

Acquired: that is, dystonia caused by acquired factors, such as dystonia caused by certain drugs.

Idiopathic: That is, the cause is unknown.

Among them, primary dystonia is related to genetic origin. Primary dystonia usually occurs in childhood and initially affects only the trunk or lower limbs, but then usually develops to the whole body. In severe cases, it can manifest as a twisted and fixed strange posture, and eventually requires the use of a wheelchair.

In the "First List of Rare Diseases" jointly released by the National Health Commission and other departments in 2018, primary hereditary dystonia is one of the 121 rare diseases. Epidemiological statistics show that the prevalence of dystonia is 370/1 million, and there are about 400,000 patients in China, of which primary dystonia accounts for about 70%.

Yang Haibo told Guokr that the affected gene in Xiaohao's body is a gene sequence called "KMT2B". This type of gene sequence was not discovered until 2017, and there are less than 30 publicly reported cases worldwide.

This also explains why Xiaohao's previous genetic testing was difficult to obtain accurate results. Once the disease is diagnosed, the next step is treatment. Medication is not very effective, and the only effective method is "deep brain stimulation" (DBS).

Difficulties

Three years ago, there was a blank in the history of treatment of primary dystonia in children in China. Working in the best pediatric neurology hospital in the country, Yang Haibo had only seen it at international conferences and related paper journals. He knew that "deep brain stimulation" might be a treatment option.

However, no doctor in China knows the specific effect. In February 2017, one year before Xiaohao was diagnosed, Yang Haibo treated a little girl who also had primary dystonia. The disease was so serious that she could hardly stand or lie flat. Her spine was completely deformed and she could only fall asleep by taking 4 and a half sleeping pills a day.

"We recommended her to a hospital that had experience in deep brain stimulation for adults..." Yang Haibo recalled, "but soon the patient came back to us because no one dared to try deep brain stimulation for children."

Having no access to medical treatment was a true reflection of the situation for children with primary dystonia at that time.

The principle of the operation is not complicated. The human brain is like a combination of various circuits and components. Our daily behavior is derived from the correct signals sent by the brain. As long as the brain's electrical signals are corrected - microelectrodes are implanted into the basal ganglia (gray matter masses buried deep in the cerebral hemispheres on both sides), and a pulse generator is used to generate electrical signals of a certain frequency to correct the original electrical signals - the patient may return to normal.

But compared to adults, surgery for children carries many risks.

The first is the risk of anesthesia. Adults can undergo surgery with local anesthesia, but children cannot. On the one hand, children will feel pain during the operation, and on the other hand, it is difficult to control the convulsions of children, which will affect the effect of the operation. However, compared with local anesthesia, general anesthesia itself has greater risks and a higher probability of side effects, especially for children with this disease.

"Precise positioning" is the most difficult step. Under local anesthesia, adults can perform a "position accuracy test" during surgery to confirm whether the position of the implanted microelectrode is accurate. Children are under general anesthesia and cannot be tested. As children grow older, their brains will also grow and develop. If the implantation position is not appropriate, the operation will still end in failure.

Yang Haibo decided to give it a try. He was also very nervous when he performed the operation for the first time. "What if it doesn't work if we put something worth 200,000 or 300,000 yuan in?" But he wanted to give the child a chance. "At worst, we can pay for it ourselves."

A miracle happened. After about a month, the girl's stiff body relaxed and she was able to fall asleep. It was from this operation that Yang Haibo has devoted his energy to the research of this disease for the past three years.

Operation

Xiaohao's operation was not as smooth as expected.

On the third day before the operation, Xiaohao suddenly developed a fever and his body was covered with red rashes. These seemingly simple symptoms prompted an emergency consultation among doctors from the Pediatric Surgery, Pediatric Neurology, and Pediatric Nephrology departments.

Due to long-term contraction and stiffness of the whole body, Xiaohao's muscle tissue was severely damaged, and he was diagnosed with "rhabdomyolysis", which can be generally understood as muscle cells rupturing due to overload. This is a disease with a mortality rate of up to 20%. Fortunately, with emergency medication, Xiaohao was pulled back from the brink of death.

On May 23, 2018, Yang Haibo and his colleagues gave Xiao Hao general anesthesia and put a "stereotactic frame" on him. It is like having a coordinate axis with a scale to accurately locate the position of the implanted microelectrode.

Then, a group of people took Xiaohao to do an MRI with oxygen cylinders, oximeters and other equipment. Worried that Xiaohao's life would be in danger under general anesthesia, the anesthesiologist was always by his side to monitor his vital signs.

With the concerted efforts of everyone, Xiaohao successfully completed the brain MRI. Afterwards, he was pushed into the operating room. Through the MRI scan results and the stereotactic frame to calculate the target coordinates, Yang Haibo accurately implanted the electrode wire into the brain nucleus, and finally buried the extension wire connecting the electrode and the pulse generator under the skin, and placed the pulse generator under the clavicle.

Three hours later, the operation was successfully completed. Seeing the doctor coming out of the operating room, Xiaohao's father couldn't bear it anymore and burst into tears. During the observation period, Xiaohao's postoperative CT scan and wound recovery were both good. Ten days later, Yang Haibo planned to turn on the implanted pulse generator.

get well

On the first day of production, Xiao Hao did not feel any discomfort, but was a little sleepy.

On the second day of filming, Xiaohao's body was visibly relaxed.

In this way, Xiaohao could slowly draw a simple circle with a pen, and could walk slowly with the help of the wall when he was discharged from the hospital. Half a month after returning home, Xiaohao could eat and drink by himself, and could also walk in the square with his mother.

The two-year nightmare finally ended. Three months after the operation, Xiaohao was already running around. He was the first patient in China to be diagnosed with and undergo surgical treatment for DYT28 primary dystonia, filling the gap in the treatment of this disease in China.

There is no doubt that Xiaohao is lucky. Most patients with primary dystonia can greatly improve their condition through deep brain stimulation surgery. If nothing goes wrong, Xiaohao only needs to charge the pulse generator for 15 to 20 minutes every half a month. After 20 years, when the battery life is exhausted, he only needs to undergo a small operation to replace the battery, and he can live and work like a normal person until he grows old.

"I never say discouraging words to patients." Yang Haibo, who has been practicing medicine for 14 years, understands the difficulties behind the disease. "The patients who come to us have already spent a lot of money, especially those from poor families. Many children have been treated as having cerebral palsy, and even some folk remedies have been tried. But because the diagnosis was inaccurate at the beginning, the treatment effect is often limited."

During the years that Yang Haibo was studying dystonia, other hospitals in China also began to revisit past cases. Peking Union Medical College Hospital reexamined more than 50 patients and found three with the same gene sequence as Xiaohao's disease - DYT28 primary dystonia.

The number of operations Yang Haibo has performed is still increasing. There were 3 cases in 2017, 6 cases in 2018, 20 cases in 2019, and as of October this year, he has completed 40 pediatric dystonia surgeries.

This also means that more and more people know that dystonia is treatable.

Medical progress has benefited more patients. In recent years, dystonia has become one of the fastest-growing areas in the field of neuroscience. "Overseas, Musk's brain-computer interface technology has been tried in the clinic to treat some children with movement disorders," said Yang Haibo. "Diseases that are now considered untreatable may be improved in the next three, five or even ten years."

Xiaohao's life has gradually returned to normal. Although it is difficult for Lu Jie to return to the ordinary life she longed for, she is still very satisfied: "I never thought that Xiaohao could go to school before. I thought it would be good as long as he could take care of himself."

December 8, 2018, six months after the operation. Xiaohao gained 40 pounds. Sister Lu took Xiaohao to Tiananmen Square to watch the flag-raising ceremony. Sister Lu finally had time to take him around Beijing.

From one gene to another, from one pathway to another, we clearly feel the huge changes that the tip of the iceberg of disease brings to life. This is especially true for rare diseases, where the complexity of the causes makes diagnosis and treatment even more difficult. But in the war against disease, we are amazed at our own resilience, creativity and resilience.

Science is a process of repetition and accumulation. Mysteries are solved one by one, and each one contributes some vague images to the larger concept. Now those diseases that we think are "hopeless" or even "incurable" may finally see the dawn of hope with the efforts of doctors and patients.

Thanks to the interviewees of this article: Sister Lu (pseudonym) and Yang Haibo, attending physician of pediatric functional neurosurgery at Peking University First Hospital.

Sharing of personal experiences does not constitute medical advice and cannot replace the doctor's individualized judgment on specific patients. If you need medical treatment, please go to a regular hospital.

Author: Ant

Editor: Li Xiaoqiu