Stories about: epilepsy

Robot-enhanced neurosurgery for nimbler seizure mapping

implanting electrodes for seizure monitoring, with robotic assistance
Scellig Stone and Joseph Madsen in surgery with the robot.

Head shaved, a little boy rests on the operating table, deep under anesthesia. His parents have brought him to Boston Children’s Hospital in hopes of determining the cause of his seizures. Now, neurosurgeons Scellig Stone, MD, PhD, Joseph Madsen, MD, and their colleagues in the Epilepsy Center are performing a procedure designed to monitor seizure activity in the 3-year-old’s brain.

But as the team members crowd around the table, they’re not alone. With the push of a button, a large robotic arm rotates and lowers right next to the boy’s head, helping the physicians pinpoint the precise location to drill. “This is a real game-changer,” murmurs one of the clinicians observing the surgery. “It’s going to transform the way we practice.”

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Fast brain waves: A better biomarker for epilepsy

EEG and MEG detection of HFOs, fast brain waves associated with epilepsy
Localization of fast brain waves, called HFOs, with scalp EEG (left) and MEG (right). HFOs present a new biomarker for areas of the brain responsible for epileptic seizures.

In the U.S., about one in 100 people have some form of epilepsy. A third of those people have seizures that cannot be controlled with drugs, eventually requiring surgery to remove the area of their brain tissue that is triggering seizure activity.

“If you can identify and surgically remove the entire epileptogenic zone, you will have a patient who is seizure-free,” says Christos Papadelis, PhD, who leads the Boston Children’s Brain Dynamics Laboratory in the Division of Newborn Medicine and is an assistant professor in pediatrics at Harvard Medical School.

Even experts in this field were skeptical for years about the non-invasive detection of HFOs. But now, thanks to our study and other researchers’ work, these people are changing their minds. At present, however, these surgeries are not always successful. Current diagnostics lack the ability to determine precisely which parts of an individual’s brain are inducing his or her seizures, called the epileptogenic zone. In addition, robust biomarkers for the epileptogenic zone have been poorly established.

But now, a team at Boston Children’s Hospital is doing research to improve pre-surgical pinpointing of the brain’s epileptogenic zone. They are using a newly-established biomarker for epilepsy — fast brain waves called high-frequency oscillations (HFOs) — that can be detected non-invasively using scalp electroencephalography (EEG) and magnetoencephalography (MEG).

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Looking between seizures to map seizures’ origins

seizure mapping

When epilepsy can’t be controlled with drugs, neurosurgery is sometimes curative, if the seizures are coming from discrete brain tissue that can be safely removed.

Finding these diseased areas, however, can require invasive surgery to place grids of electrodes on the brain’s surface. That’s followed by long-term, 24-hour EEG monitoring — typically for a week — until a seizure happens. Neurosurgeons then use this data to map a surgical path. But to actually remove the diseased tissue, a second operation is needed.

That’s enough to deter many families from epilepsy surgery. But what if seizure origins could be mapped without having to actually observe a seizure?

Joseph Madsen, MD, director of Epilepsy Surgery at Boston Children’s Hospital, and Eun-Hyoung Park, PhD, a computational biophysicist in the Department of Neurosurgery, think they have a way to do that — with an algorithm originally used for economic forecasting. 

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Patients’ brain tissue unlocks the cellular hideout of Sturge-Weber’s gene mutation

A diagram of the skull and brain showing the leptomeninges, which is affected by Sturge-Weber syndrome
Sturge-Weber syndrome causes capillary malformations in the brain. They occur in the brain’s leptomeninges, which comprise the arachnoid mater and pia mater.

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.

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News Notes: Pediatric science roundup

A quick look at recent research Vector finds noteworthy.

Tracking infants’ microbiomes

cute microbes-shutterstock_317080235-croppedMicrobiome studies are blooming as rapidly as bacteria in an immunocompromised host. But few studies have been done in children, whose microbiomes are actively forming and vulnerable to outside influences. Two studies in Science Translational Medicine on June 15 tracked infants’ gut microbiomes prospectively over time. The first, led by researchers at the Broad Institute and Massachusetts General Hospital, analyzed DNA from monthly stool samples from 39 Finnish infants, starting at 2 months of age. Over the next three years, 20 of the children received at least one course of antibiotics. Those who were repeatedly dosed had fewer “good” bacteria, including microbes important in training the immune system. Overall, their microbiomes were less diverse and less stable, and their gut microbes had more antibiotic resistance genes, some of which lingered even after antibiotic treatment. Delivery mode (cesarean vs. vaginal) also affected microbial diversity. A second study at NYU Langone Medical Center tracked 43 U.S. infants for two years and similarly found disturbances in microbiome development associated with antibiotic treatment, delivery by cesarean section and formula feeding versus breastfeeding.

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News notes: Headlines in science & innovation

An occasional roundup of news items Vector finds interesting.

Blood-brain barrier on chip

vector news - blood brain barrier chip
(Wyss Institute at Harvard University)

The blood-brain barrier protects the brain against potentially damaging molecules, but its gate-keeping can also prevent helpful drugs from getting into the central nervous system. Reporting in PLoS One, a team at the Wyss Institute for Biologically Inspired Engineering describes a 3-D blood-brain barrier on a chip — a hollow blood vessel lined with living human endothelial cells and surrounded by a collagen matrix bearing human pericytes and astrocytes.

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CDKL5: Understanding rare epilepsies, patient by patient, neuron by neuron

CDKL5 epilepsy
Haley with her parents and neurologist Heather Olson (right)

Nine-year-old Haley Hilt has had intractable seizures all her life. Though she cannot speak, she communicates volumes with her eyes. Using a tablet she controls with her gaze, she can tell her parents when her head hurts and has shown that she knows her letters, numbers and shapes.

Haley is one of a growing group of children who are advancing the science around CDKL5 epilepsy, Haley’s newly recognized genetic disorder. When Boston Children’s Hospital geneticist Joan Stoler, MD, diagnosed Haley in 2009, there were perhaps 100 cases known in the world; today, there are estimated to be a few thousand. Haley’s neurologist, Heather Olson, MD, leads a CDKL5 Center of Excellence at the hospital that is bringing the condition into better view.

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TriVox Health: improving care through shared online tracking

Screen Shot 2015-11-04 at 12.27.22 AM

Since we spoke with the founders of TriVox Health in 2014, their disease management program has taken off. The program began in Boston Children’s Hospital’s Division of Developmental Medicine as a way to more efficiently collect information on children’s ADHD symptoms from parents and teachers. It is now a user-friendly, web-based platform for tracking multiple conditions, incorporating medication confirmation, side effects reporting, disease symptom surveys and quality of life measures.

Vector sat down with founders Eric Fleegler, MD, MPH and Eugenia Chan, MD, MPH to learn about TriVox Health’s rapid growth over the past year, and what their plans are for the future.

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An eye on epilepsy: The work, life and innovations of Tobias Loddenkemper, MD

Epileptologist Tobias Loddenkemper, MD, director of clinical epilepsy research at Boston Children’s Hospital, is a seizure whisperer. He keeps a close watch on his patients, trying to discern seizure patterns and head off the developmental and learning problems that seizures can cause. A pioneer in the emerging field of chronoepileptology, he has partnered with Empatica and other companies to develop reliable seizure detection devices that could help doctors better time medication dosing and help prevent death from seizures, a real risk in children with severe epilepsy.

Mouse over the icons above to learn more.

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Brain stimulation for status epilepticus?

Seizure-storm concept-Linda Bucklin-shutterstock_172455803Status epilepticus, a state of prolonged seizures, is a life-threatening medical emergency. The average mortality rate is 20 percent, and people who survive sustain lasting neurologic damage. Aborting the seizures is of the essence, but about 30 to 40 percent of patients don’t respond to lorazepam, the first-line drug usually given, and the drug itself can cause respiratory depression.

A study in rat model of status epilepticus, led by Alexander Rotenberg, MD, PhD, of Boston Children’s Hospital’s Department of Neurology, is the first to test an emerging approach known as transcranial direct-current stimulation (tDCS) as a way of halting acute seizures. tDCS applies a weak, direct current to the brain via scalp electrodes, to either increase or—more relevant for seizures—decrease excitability in selected areas. In the study, tDCS reduced the duration of acute seizures in the rats. When it was used together with lorazepam, the combination appeared to have a synergistic effect, also preventing new seizures from starting.

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