“Sadie is acting strange, kind of out of it.” Over the phone, her husband’s voice sounded strained as he spoke about their 6-year-old daughter. The girl’s mother, Sara, was walking home from an errand in their Queens, N.Y., neighborhood. “Strange in what way,” she asked. “I don’t know,” he replied. “You have to come home and see this.” Sara hurried the last few blocks, and when she entered the apartment, she could see her daughter sitting on the sofa. “Sadie,” she called. Her daughter turned her head to face her mother but didn’t seem to see her. It was as if she looked straight through her. Sara immediately called 911. As they waited for the ambulance, the mother couldn’t take her eyes off Sadie. She was awake, but not really there.
Suddenly the girl’s lip twitched. Just one side, the left side, pulled up then relaxed in a failed half smile. Over and over. Her head began to jerk to the left, repeatedly. Sara had never seen anything like it. When the emergency medical technicians arrived, they took one look at the little girl and told the parents she was having a seizure. The mother rode in the ambulance with her child to the closest hospital, Elmhurst Hospital Center. The girl’s father stayed behind to arrange care for their 4-year-old daughter, before joining his wife.
As soon as mother and child arrived in the E.R., Sadie was given Ativan, a fast-acting sedative that is the drug of choice in treating ongoing seizures. While she was asleep, she was taken for a CT scan. When there was a question of a possible clot in the brain, she was taken for a second CT with contrast to better define the blood vessels. This second scan was completely normal. So why had she had this odd-looking seizure? The doctors in the E.R. weren’t sure. While there the child spiked a temperature to 101, and a blood test showed an elevated white-blood-cell count. Could it be some kind of infection? Or did she have a brain tumor or some structural brain abnormality? Those can’t always be seen in a CT scan and are common causes of seizures in a child. She would need to be admitted to the hospital in order to figure this out, the child’s mother was told. You can see the notes from Elmhurst below.
Sara had a cousin who was an adult neurologist at Columbia Medical Center, so the decision was made to move the child there. The cousin wouldn’t be directly involved in the child’s care, but it was reassuring to have family around. The E.R. doctors dosed the child with Keppra, a widely used antiseizure medication, and sent her to the Upper Manhattan hospital.
After Sadie woke from the medications she’d been given, she seemed her usual happy, active self. She moved and spoke a little slower than normal, but her mother attributed that to the powerful antiseizure medications she was given. She had an M.R.I., which was normal. The girl’s parents found that reassuring. You can see that report below. Maybe she’d just had a single seizure triggered by the fever she had? They had read that fever could be a common cause of seizures in a child.
Dr. Tristan Sands, a pediatric epilepsy specialist, was not reassured by the M.R.I. The day after her arrival, before the M.R.I. was done, the child had continued EEG monitoring accompanied by video, and that test — to Sands, the more important of the two — was markedly abnormal. It showed that the activity on the right side of the child’s brain, in the frontal lobe, was abnormally slow. In addition, the tracing showed several episodes of the spiking rhythmic waves that indicated a seizure. The parents had not seen any evidence of a seizure since they had been there, and reviewing video of the child done at the time, neither could Sands, and yet he was certain the seizures were real.
After the seizures were noted, Sadie was given more Ativan, and her dose of Keppra was increased. The seizures stopped — but only for 12 hours. That night the EEG showed that she had more seizures as she slept. The following day was just as abnormal. The electrical activity on the right side of her brain (which controls movement on the left side of the body) was slow compared with the normal-looking left side of the brain. The waves were interrupted with eight brief episodes of the electrical storm indicating a seizure over the seven hours between early morning and lunchtime. Again, looking at the child, there was no evidence that she was having a seizure. The doses of her antiseizure medications were increased again, but overnight she had 16 more seizures between 8 p.m. and 8 a.m. All the erratic signals came from the same part of her brain — the front of the right half of her brain. When larger doses of Keppra didn’t stop the seizures, the doctors added a third medication, Trileptal. With the addition of this new medication, the seizures finally became less frequent.
Sands was struck by the abnormality of the child’s brain as seen by EEG and the lively normalcy of the child herself. It wasn’t unusual to have what’s known as subclinical seizures — those that register on an EEG but don’t show up in the patient’s behavior — especially with the kinds of seizures she was having, those that come from a single region in the brain and don’t spread. What was unusual, however, was to see this kind of wildly aberrant EEG in someone who was also experiencing intermittent and focal seizures that were so low-powered that they didn’t change the child’s behavior. Sands was worried that these seizures, though local and subclinical, wouldn’t stay that way. He hoped to find the right cocktail of medications that would help reduce or, ideally, prevent additional seizures. And to find out why she was having them at all.
The most common cause of any kind of seizure is some abnormality in the brain itself. This can be a tumor or a stroke or something called cortical dysplasia, an abnormality in how the brain was made. M.R.I.s have made all these disorders much easier to detect. But Sadie’s M.R.I. was completely normal.
The little girl didn’t look as if she had an infection. She hadn’t had a fever since she arrived at the hospital, and a lumbar puncture — more commonly known as a spinal tap — done the day she arrived showed no signs of infection, either. The spinal fluid was also checked for signs of an autoimmune disorder. Sometimes antibodies will mistakenly start to attack a normal part of the body as if it were an infecting invader. None of the most common of these antibodies were found. A sample of her spinal fluid was sent to the Mayo Clinic to look for other, more unusual types of autoimmune disorders. Those results took a couple of weeks to come back, but when they did revealed no autoimmune causes of the seizures.
Sadie was in the hospital for nearly two weeks before the team figured out a cocktail of medications to reduce the number of seizures the girl had — from the dozens per day she started with, down to one a day. Sands had hoped to stop them completely but, at this point, wasn’t sure that was possible with medication alone. Sadie and her parents were thrilled by the news that she was doing well enough to go home. The little girl had seemed fine after that terrifying initial seizure. Her mom just hoped that they had figured out the problem so that Sadie could get back to school. She was a very social little girl and being stuck in the hospital or kept away from her friends was difficult for her.
Two weeks after being discharged from the hospital, Sara saw Sadie have another seizure. It was brief but still scary. She and her mom were walking to the bus when suddenly Sadie stopped. She walked toward her mom but in her eyes was the same blank, unseeing stare she’d had that one time before. She called her daughter’s name, and again there was no response. The whole episode lasted maybe a minute, but it scared her. The mother quickly called Sands. He suggested giving an extra dose of the long-acting medication they were using instead of Ativan called Onfi. There were no more episodes of staring, but later that day, Sadie’s mom thought she saw the girl’s lip twitch upward twice. Other than those two brief episodes, Sadie seemed fine.
She had another EEG at the end of the month. The results were upsetting. Although neither the patient nor her parents had noticed any seizure activity, other than the two brief episodes a couple of weeks earlier, this EEG seemed to indicate that her brain was having seizures almost all the time.
Sands knew this was bad news. His team had been working for over a month to get Sadie’s seizures under control, and they would keep trying, but they would also need to consider a different option: surgery. For patients whose seizures can’t be controlled by medicines, resecting the region of the brain causing these electrical storms can be lifesaving. For Sadie’s parents, brain surgery was a terrifying prospect. But so was the idea of a lifetime of uncontrollable seizures. Sands wasn’t ready to take the child to the operating room yet, but he wanted to introduce the idea. Doctor and parents agreed to keep trying different combinations of medications and consider the surgical option only after they failed.
The following week, the little girl went back to the hospital for another test, this one called a PET scan. This test shows where fuel is being used in the body. In Sadie’s case, they would be focusing on her brain, looking for differences in the way the right and left sides of her brain were working. The harder each area of the brain worked, and the more fuel that was being used, the brighter the scan would be in those spots. It was almost not a surprise to Sadie’s parents to hear that this scan was also quite abnormal.
On the way home from the scan, the left side of Sadie’s mouth began to jump in a strange and unnatural way. Sadie was awake and tried to speak but couldn’t. Her mouth seemed to have a mind of its own. Sara pulled out her phone and filmed the strange jumping of her daughter’s lips. When her mouth stopped moving, Sadie said that it felt like her tongue was bouncing inside her mouth, and there was nothing she could do about it. Over the next 24 hours, Sadie had dozens of episodes like this. Sara made a video of as many of them as she could and sent it to Sands. You can see that video below.
When Sands saw the video his heart sank. He recognized this type of seizure. She was having what is known as epilepsia partialis continua, or E.P.C. These are focal seizures that affect only one part of the body. The patient is awake and aware of the seizure but has no control over it. And the movements can last for hours, days or even weeks. And after the seizure is finally over, that part of the body may be quite weak for a while — a postseizure effect called Todd’s paralysis. These localized seizures are rare and usually caused by some type of inflammation in the brain. In a child like Sadie, who had a variety of different types of seizures — that were all hard to control, that came from only one side of the brain — and who developed E.P.C., an even rarer diagnosis had to be considered: Rasmussen’s encephalitis.
This disorder, first described in 1958, is characterized by hard-to-control seizures caused by inflammation limited to a single side of the brain. Unlike most other causes of seizures, Rasmussen’s is a progressive disease and results, over the course of just a few years, in the destruction of the affected side of the brain. It is rare and, like so many of the diseases of the brain, still poorly understood. Current thinking is that it is driven by an abnormality in the immune system, and so treatment is directed at medications that suppress that system. These medications may be helpful in slowing brain destruction, but the seizures often remain uncontrolled and frequently worsen. Moreover, nearly all of those given a diagnosis of this disease end up eventually with the complete loss of the affected side of the brain, whether they take these immune-suppressing medications or not.
The only treatment found to be successful in eliminating the seizures has been drastic: isolating the affected lobe by cutting the connections between the diseased part of the brain and the rest of the body. After surgery, the seizures will stop but the patient will lose the function in all the parts of the body that were controlled by that side of the brain — all movement of the body on the side controlled by the affected part of the brain: the sight in that eye, the hearing in that ear. Some function can be regained over time, with intensive physical therapy. But it is hard. It’s as if you had a massive stroke, taking out the entire brain on the one side.
After seeing the video, Sands called Sara and asked her to bring Sadie back to the hospital. He explained to the girl’s parents that he was worried that Sadie may have this terrible disease. He proposed a biopsy. It couldn’t prove that she had Rasmussen’s, but it could help them make sure she didn’t have a hidden infection. They agreed, and on Valentine’s Day this year, the child underwent surgery to remove a bit of her brain.
The biopsy results were suggestive of Rasmussen’s encephalitis. You can see the pathology report below. But to make the diagnosis of Rasmussen’s, there must be loss of brain tissue from the disease that is visible on imaging. And there must be a progressive loss of function. Sadie had subtle signs of weakness, but her brain looked unchanged. Sands was worried that it was only a matter of time. Still, the surgery is so devastating that the diagnosis must be absolutely certain. Based on the biopsy results and the fact that the EEGs showed worsening disease, the decision was made to start immune-suppressing therapy as a first step. Sadie was started on steroids and also given something known as intravenous immunoglobulins (IVIG), a collection of antibodies from hundreds of blood donors. It’s not clear why this treatment works in immune system-triggered diseases, but it is frequently effective. She was also started on a third immune-suppressing treatment — a drug called Rituximab. For most children with Rasmussen’s encephalitis, diagnosis can take years. For Sadie, because it was so early in the course of the disease, Sands hoped that aggressive suppression of her immune system might slow further brain destruction.
With all these interventions, the mouth seizures went from dozens a day to a handful every week or so. Sara sometimes noticed jerks in Sadie’s left hand, but they were few and far between. The biggest change beyond the diminished number of seizures was her weight gain. Over the course of her two months of seizures, she gained over 20 pounds. Other than that, she often seemed her old self.
After three whole weeks of virtually no seizures, they started again. First the mouth seizures — they were the worst. They distorted her face and kept her from speaking. Sadie hated them. Those seizures were replaced by spasms in her left leg. At first, they were small little jerks at the ankle, but over time they became stronger, moving up the leg from the ankle, to the knee and hip. By the end of the summer, the leg jerks were strong enough to knock her over and she walked with a visible limp.
A repeated M.R.I. midsummer seemed to show evidence of brain-tissue loss. It was subtle, but it was enough for Sands. He told Sadie’s parents he thought it was time to consider surgery. And it wasn’t just Sands. He had presented her case to the epilepsy center at Columbia. They agreed. They felt it was clear that the child had Rasmussen’s. Surgery could spare her the erratic course of the disease and give her the chance to start working on getting better. Moreover, unchecked the disease would affect not just her body, but her mind. Without treatment, children with Rasmussen’s develop cognitive losses.
More testing would be needed before surgery. First they would have to see where the child’s language center was located. Sadie was left-handed, and while most people have their language center on the left side of the brain, left-handed patients can have the center on the right side. It would be rare, but it’s something they would need to know. If either surgery or the disease itself took out her language center, she could be left unable to speak.
Before they subjected their daughter to this surgery, Sara and her husband wanted to get a second opinion. Their pediatrician recommended a pediatric neurologist at N.Y.U., and they also saw a neurologist and pediatric neurosurgeon at Mount Sinai on the Upper East Side of Manhattan.
At this point, Sadie has seen all the additional consultants. Sara and her husband are waiting for their official recommendations. The team at Mount Sinai also thinks Rassmussem’s is the likely diagnosis. The neurosurgeon, however, notes that the recent M.R.I. doesn’t show the kind of asymmetrical loss of brain tissue that is typical of the disease. The team is considering an intervention to control the child’s symptoms that is less invasive than cutting away the entire right side of the brain. If this treatment doesn’t work, the family could still try the surgery. Sara and her husband are unsure of what to do.
So let me ask you, readers. Is this something you recognize? Is this the story of someone you know? Do you have a child who was diagnosed with Rasmussen’s? What advice do you have for Sara and her husband? If you have any thoughts about Sadie’s diagnosis or about the diagnosis of Rasmussen’s encephalitis, please share it with us, and we will share it with Sara and her husband. Sara told me that if they do have to choose this devastating surgery for their child, they want to be as certain as they can be that it is the very best option for Sadie. Help us help them.
What’s Your Advice for Sadie’s Parents?
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