A person born with a port-wine birthmark on his or her face and eyelid(s) has an 8 to 15 percent chance of being diagnosed with Sturge-Weber syndrome. The rare disorder causes malformations in certain regions of the body’s capillaries (small blood vessels). Port-wine birthmarks appear on areas of the face affected by these capillary malformations.
Aside from the visible symptoms of Sturge-Weber, there are also some more subtle and worrisome ones. Sturge-Weber syndrome can be detected by magnetic resonance imaging (MRI). Such images can reveal a telltale series of malformed capillaries in regions of the brain. Brain capillary malformations can have potentially devastating neurological consequences, including epileptic seizures.
Frustratingly, since doctors first described Sturge-Weber syndrome over 100 years ago, the relationship between brain capillary malformations and seizures has remained somewhat unexplained. In 2013, a Johns Hopkins University team found a GNAQ R183Q gene mutation in about 90 percent of sampled Sturge-Weber patients. However, the mutation’s effect on particular cells and its relationship to seizures still remained unknown.
But recently, some new light has been shed on the mystery. At Boston Children’s Hospital, Sturge-Weber patients donated their brain tissue to research after it was removed during a drastic surgery to treat severe epilepsy. An analysis of their tissue, funded by Boston Children’s Translational Neuroscience Center (TNC), has revealed the cellular location of the Sturge-Weber mutation. The discovery brings new hope of finding ways to improve the lives of those with the disorder. …
“My biggest fear is that if I am not there to help him, when I wake him up he will be dead from seizures.”
That mother’s fear has a sound basis. The risk for sudden death from epilepsy, or SUDEP, is as high as 1 in 100 in the sickest children with epilepsy, says Tobias Loddenkemper, MD, of the Epilepsy Center at Boston Children’s Hospital. Many of those seizures occur in sleep.
Loddenkemper has been testing a novel wristband that uses motion and sweat sensors to detect the onset of a seizure—upon which the device would sound an alert. So far, the device has performed well on tests at Boston Children’s, picking up more than 90 percent of generalized tonic-clonic (grand mal) seizures, says Loddenkemper. But more work is needed to reduce false alarms (often generated when children are playing video games) and enable to device to spot more subtle seizures that are less convulsive in nature.
“This work is triggered by some very personal experiences of parents calling my office telling me their child died in sleep from seizures,” says Loddenkemper. “I dread these calls. We want to prevent those calls.”
The device manufacturer has created a fundraising site to help further the wristband’s development.
As Epilepsy Awareness month closes out and we embark upon the holiday season, we’re pleased to see an innovation initiated here at Boston Children’s Hospital move toward commercial development. This wearable device for patients with epilepsy, called Embrace, is like a “smoke alarm” for unwitnessed seizures that may potentially prevent tragic cases of sudden, unexpected death from epilepsy (SUDEP) in the future.
The Bluetooth-enabled, sensor-loaded wristband, using technology developed and tested in collaboration with the MIT Media Lab, can detect the onset of a convulsive seizure based on the wearer’s movements and autonomic nervous system activity. …
Imagine you’re a clinician or researcher and you want to find the source of a newborn’s seizures. Imagine being able to record, in real time, the neural activity in his brain and to overlay that information directly onto an MRI scan of his brain. When an abnormal electrical discharge triggered a seizure, you’d be able to see exactly where in the brain it originated.
For years, that kind of thinking has been the domain of dreams. Little is known about infant brains, largely because sophisticated neuroimaging technology simply hasn’t been designed with infants in mind. Boston Children’s Hospital’s Ellen Grant, MD, and Yoshio Okada, PhD, are debuting a new magnetoencephalography (MEG) system designed to turn those dreams into reality. …
It’s become clear that our DNA is far from identical from cell to cell and that disease-causing mutations can happen in some of our cells and not others, arising at some point after we’re conceived. These so-called somatic mutations—affecting just a percentage of cells—are subtle and easy to overlook, even with next-generation genomic sequencing. And they could be more important in neurologic and psychiatric disorders than we thought.
“There are two kinds of somatic mutations that get missed,” says Christopher Walsh, MD, PhD, chief of Genetics and Genomics at Boston Children’s Hospital. “One is mutations that are limited to specific tissues: If we do a blood test, but the mutation is only in the brain, we won’t find it. Other mutations may be in all tissues but in only a fraction of the cells—a mosaic pattern. These could be detectable through a blood test in the clinic but aren’t common enough to be easily detectable.”
That’s where deep sequencing comes in. Reporting last month in The New England Journal of Medicine, Walsh and postdoctoral fellow Saumya Jamuar, MD, used the technique in 158 patients with brain malformations of unknown genetic cause, some from Walsh’s clinic, who had symptoms such as seizures, intellectual disability and speech and language impairments. …
This is the third post in a series about new approaches for seizures and epilepsy. Read the first and second posts.
We already know that there’s some kind of connection between epilepsy and autism: Children who have seizures as newborns not uncommonly develop autism, and studies indicate that about 40 percent of patients with autism also have epilepsy. New research at Boston Children’s Hospital finds a reason for the link, and suggests a way to break it — using an existing drug that’s already been given safely to children.
When a 2- or 3-year-old child begins losing milestones like language, walking skills and fine motor abilities, or is slow to achieve them, it’s devastating for families. The good news, at least for some children, is that it might be treatable.
Tobias Loddenkemper, MD, a neurologist in the Epilepsy Center at Boston Children’s Hospital, suspected that some children with developmental delay have seizure-like activity in the brain at night. These spikes of electrical activity, referred to medically as sleep-potentiated epileptiform activity, can be readily and inexpensively detected by electroencephalography, or EEG, and readily treated with nighttime anti-seizure drugs.
But likely, no one’s thought of it. “Very few physicians have been looking to see what’s happening at night,” Loddenkemper says.
He and research fellow Iván Sánchez Fernández, MD, with other colleagues, decided to look themselves. …
Seizures are often hard to track in children with epilepsy, making it difficult for doctors to optimize their treatment. For parents, the greatest worry is that their child will have a life-threatening seizure in the middle of the night or away from home, unable to get help. And what about when that child goes off to college?
Loddenkemper also wanted to better understand his patients’ seizure patterns so he could better time the dosing of their medications. He’s been testing a wristband sensor system, developed by Rosalind Picard, ScD, and colleagues at the MIT Media Lab (Epilepsia, March 20), and thinks it could be part of the solution. …
It’s well known that babies who have seizures soon after birth have roughly a 50-50 chance of developing long-term intellectual and memory deficits and cognitive disorders like autism. But until now, it wasn’t understood why these deficits occur, much less how to prevent them from happening.
In the December 14 Journal of Neuroscience, researchers at Children’s Hospital Boston, led by neurologist-neuroscientist Frances Jensen, detail in a rat model how early-life seizures affect brain development at the cellular and molecular level. But more to the point, they show that it might be possible to ward off these effects with drug treatment soon after the seizure – using a drug called NBQX or similar drugs that are already approved by the FDA.
Jenson was particularly interested in what seizures do to synapses, the connections between neurons that are rapidly developing in the infant brain.
Addison Lennon met all her early milestones: she sat up on time, crawled on time and walked on time. At about 4 months, however, she had a seizure, and her parents started to worry. By 9 months, her head appeared small for her age.
Her neurologist reassured the family that Addison could still be within the lowest 5 percent of the normal range. “We were thinking she was typical,” says Kari Lennon, “she would be in that 5 percent.”
At 15 months, however, Addison had another seizure that was a lot more severe. She had been tested for everything. No one could pinpoint the cause of her so-called microcephaly, or small head.
Kari spent countless hours online in search of answers. “How I could fix Addie? How could I make her better?” (Read on, or watch this video:)