By Mara Cvejic, M.D.
Imagine that you start to develop a tremor in one hand, and after some time notice it in the other hand. You start to drop your pencil when you are writing and it takes you an unusually long time to open up a can of soda or take your shoes off. You start having a few falls and while nobody initially notices, you find that you may trip over your own feet and cannot seem to figure out why you couldn't grab onto something in time to catch your balance. Slowly over the short span of a few months, you become very stiff and by the end of the day you can barely walk and require help getting out of your clothes and even with eating. You're exhausted, your body is stiff and rigid, and you feel like a prisoner trapped within your own body. This may sound familiar to patients who suffer from Parkinson's disease. But now imagine that you are 8 years old.
The first time I met a girl I will call Jane, she was incredibly cute and animated. She came to the office around 8:30 a.m. wearing a pink t-shirt with bows in her braided hair and had a huge lopsided grin on her face. It was an emergency appointment that had been made in response to a panicky call received from a pediatrician's office stating that she had an 8-year-old little girl with a normal medical history who was rigid and could not walk.
I was a pediatric neurology fellow at the time, and when I came into the room that morning, she was sitting on the examination table and swinging her legs violently back and forth and in the midst of our conversation became impatient and jumped off the table to join her sister on the floor playing with a coloring book. As she colored with a crayon, I thought, "What emergency?" This young lady looked pretty good to me, and she was even coloring within the lines. After a thorough examination and discussion with her parents, everything was found to be normal. Her mother looked a little embarrassed to have such a normal looking daughter in the room. She was nonplussed and explained that she was called to pick her daughter up from school in a wheelchair yesterday because she couldn't walk. She had to carry Jane to the car because she was so exhausted, and put her to bed as soon as they got home. "To be honest, I thought she might be faking it, but she looked so uncomfortable. This morning, she seems like my normal little girl," her mother said. But something that her mom mentioned reverberated in my mind: Jane got better with sleep.
The next time I met Jane was two weeks later, at 4 p.m. during an afternoon office visit, and I couldn't believe that I was looking at the same girl. One side of her face was drawn up into a snarl, her hands were awkwardly flexed at the elbow, and her fingers were clenched in a half fist. It was as if half her body was like a puppet with strings being suspended in the air. On trying to walk down the hallway, it looked like she had aged 70 years and had a bad frozen hip. She almost fell while turning twice. I looked at her brain and spine imaging and poured over the lab work we had ordered, all of which was normal. Her mom looked at me baffled, and sighed. "Well, maybe she just needs more sleep. She will be all better by tomorrow morning, I suppose."
As a sleep physician today, Jane's face still haunts me -- but in a good way. The miracles of sleep are too numerous for the scope of this article, but there is plenty of undisputed evidence to show that healthy sleep improves our mood, our heart, our ability to eat healthy, to exercise, and perform at our best during the day at work or school. It is even linked to lower cancer rates. But can it take away what appears to be Parkinson's disease and make a little girl walk? Oddly, that answer is yes. Jane had Segawa's disease.
Segawa's disease is very rare, named for the man who first described this genetic disorder in a group of young children with an average age of 6 years old in the 1970s. Deficiency in an enzyme called tyrosine hydroxylase, an important rate-limiting enzyme in the manufacturing of dopamine (an important neurotransmitter involved in motor pathways), causes gait disturbance and rigid posturing with daily progression similar to what I saw in Jane. Genetically, these patients inherit a mutation in a gene called GCH1.
Tyrosine hydroxylase (TH) depletion over the day's course is believed to be responsible for the dramatic change from morning to nighttime, with repletion during sleep. Because a newborn child's brain shows lower TH activities in this area as compared to older children, it is theorized that as a child ages, the role for TH is greater for dopamine transmission and hence movement. This explains why these children grow and develop normally until early childhood. In a teenager, the TH levels exceed the area of the terminal that they are produced from, around the time that the disease seems to stabilize and no longer progress. To understand this better, think of a car engine that relies solely on solar power at a low speed, but then as it speeds up requires gas, finally reaching a maximal speed at which point thrusters powered by electricity take over. If you are out of gas, and traveling at a middling speed like Jane, you are going to run out if your supplies are limited. And every night Jane crawls into bed with a small empty tank and fills it up with gas by morning.
The science behind this explanation is slightly more complicated, but not grim. The reality is, these patients have a good outcome. As the day goes on they deteriorate and look like patients with Parkinson's disease, but when they sleep they typically recover from their symptoms. They are distinguished from Parkinson's disease (PD) by the age of symptom onset and by the daily progression of their motor difficulties. The disease is selective for a dopamine deficiency that occurs in nigrostriatal neurons, quite different from the deficiency that occurs in the nearby pars compacta of the substantia nigra, seen in PD. They improve with the same medications that we use for Parkinson's patients, and pediatric neurologists will treat with these medications with excellent results.
Dr. Segawa had the same question that I, and many other physicians have had, which is: What are the restorative properties of sleep that improve these young children? To answer this question, he had several children complete a nocturnal sleep study and found some interesting differences from other children their age without the disease. Small twitching movements occur in normal sleep, particularly during rapid eye movement (REM) or dream sleep, which he theorized were linked to dopamine availability. The twitching was severely decreased among patients with Segawa's disease -- about 20 percent of that of normal children in the first REM cycle. It varied by age, but by the last REM cycle near morning it exceeded normal levels of twitching by more than 20 percent, suggesting morning recovery. In normal children without the disease, there was also a significant increase from first to last sleep cycle of twitching activity. This suggests that the more we sleep, the more dopamine we make, and the better our bodies will move. Taking a power nap at lunch just took on a whole new meaning for patients with this disease. And it raises a lot of questions about the miracle of sleep and just how far its benefits extend.
I have the utmost respect for that mother, who seemed to remain relatively calm for what must have seemed like a bad episode of The Twilight Zone occurring in her own home, starring her own child. Looking back, I wonder if some part of her was reassured that her daughter seemed to regenerate and spring to life in the night while sleeping peacefully in her bed just down the hall. Her mother was oddly right from the beginning -- she would be brand new in the morning. If only the solution was always that simple, we would all sleep better at night.
Mara Cvejic, M.D., is a pediatric neurologist and sleep medicine fellow at the Stanford Center for Sleep Sciences and Medicine. This Center is the birthplace of sleep medicine and includes research, clinical, and educational programs that have advanced the field and improved patient care for decades. To learn more, visit us at: http://sleep.stanford.edu/.