Posts Tagged Blindness

[NEWS] Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

 

Elizabeth Delacruz can’t crawl or toddle around like most youngsters nearing their second birthday.

A rare metabolic disorder that decimated her mobility has also led to cortical blindness – her brain is unable to process images received from an otherwise healthy set of brown eyes. And multiple times a day Elizabeth suffers seizures that continually reduce her brain function. She can only offer an occasional smile or make soft bubbly sounds to communicate her mood.

“But a few months ago I heard her say, ‘Mama,’ and I started to cry,” said Carmen Mejia, a subtle quaver in her voice as she recalled the joy of hearing her daughter. “That’s the first time she said something.”

Ms. Mejia realizes it may also be the last, unless doctors can find a way to detect and prevent the epileptic seizures stemming from a terminal disease called pyruvate dehydrogenase deficiency (PDHD) – which occurs when mitochondria don’t provide enough energy for the cells.

A UT Southwestern study gives parents like Ms. Mejia renewed hope for their children: By monitoring the brain activity of a specific cell type responsible for seizures, scientists can predict convulsions at least four minutes in advance in both humans and mice. The research further shows that an edible acid called acetate may effectively prevent seizures if they are detected with enough notice.

Although the prediction strategy cannot yet be used clinically – a mobile technology for measuring brain activity would have to be developed – it signifies a potential breakthrough in a field that had only been able to forecast seizures a few seconds ahead.

“Many of the families I meet with are not just bothered by the seizures. The problem is the unpredictability, the not knowing when and where a seizure might occur,” said Dr. Juan Pascual, a pediatric neurologist with UT Southwestern’s O’Donnell Brain Institute who led the study published in Science Translational Medicine. “We’ve found a new approach that may one day solve this issue and hopefully help other scientists track down the root of seizures for many kinds of epilepsy.”

Debunked theory

The critical difference between the study and previous efforts was debunking the long-held belief among researchers that most cells in epilepsy patients have malfunctioning mitochondria. In fact, Dr. Pascual’s team spent a decade developing a PDHD mouse model that enabled them to first discover the key metabolic defect in the brain and then determine only a single neuron type was responsible for seizures as the result of the metabolic defect. They honed in on these neurons’ electrical activity with an electroencephalogram (EEG) to detect which brainwave readings signaled an upcoming seizure.

“It’s much more difficult to predict seizures if you don’t know the cell type and what its activity looks like on the EEG,” Dr. Pascual said. “Until this finding, we thought it was a global deficiency in the cells and so we didn’t even know to look for a specific type.”

Predicting seizures

The study shows how a PDHD mouse model helped scientists trace the seizures to inhibitory neurons near the cortex that normally keep the brain’s electrical activity in check.

Scientists then tested a method of calculating when seizures would occur in mice and humans by reviewing EEG files and looking for decreased activity in energy-deficient neurons. Their calculations enabled them to forecast 98 percent of the convulsions at least four minutes in advance.

Dr. Pascual is hopeful his lab can refine EEG analyses to extend the warning window by several more minutes. Even then, live, clinical predictions won’t be feasible unless scientists develop technology to automatically interpret the brain activity and calculate when a seizure is imminent.

Still, he said, the discovery that a single cell type can be used to forecast seizures is a paradigm-shifting finding that may apply to all mitochondrial diseases and related epilepsies.

Potential therapy

Dr. Pascual’s ongoing efforts to extend the prediction time may be a crucial step in utilizing the other intriguing finding from the study: the use of acetate to prevent seizures.

The study showed that delivering acetate into the blood stream of PDHD mice gave their neurons enough energy to normalize their activity and decrease seizures for as long as the acetate was in the brain. However, Dr. Pascual said the acetate would probably need more time – perhaps 10 minutes or more – to take effect in humans if taken by mouth.

Acetate, which naturally occurs in some foods, has been used in patients for decades – including newborns needing intravenous nutrition or patients whose metabolism has shut down. But it had not yet been established as an effective treatment for mitochondrial diseases that underlie epilepsy.

Among the reasons, Dr. Pascual said, is that labs have struggled to create an animal model of such diseases to study its effects; his own lab spent about a decade doing so. Another is the widespread acceptance of the ketogenic diet to reduce the frequency of seizures.

But amid a growing concern about potentially unhealthy side effects of ketogenic diets, Dr. Pascual has been researching alternatives that may refuel the brain more safely and improve cognition.

Frequent seizures

Elizabeth, among a handful of patients whose EEG data were used in the new study, has been prescribed a ketogenic diet and some vitamins to control the seizures. Her family has seen little improvement. Elizabeth often has more than a dozen seizures a day and her muscles and cognition continue to decline. She can’t hold her head up and her mother wonders how many more seizures her brain can take.

Elizabeth was only a few months old when she was diagnosed with PDHD, which occurs when cells lack certain enzymes to efficiently convert food into energy. Patients who show such early signs often don’t survive beyond a few years.

Ms. Mejia does what she can to comfort her daughter, with the hope that Dr. Pascual’s work can someday change the prognosis for PDHD. Ms. Mejia sings, talks, and offers stuffed animals and other toys to her daughter. Although her little girl can’t see, the objects offer a degree of mental stimulation, she said.

“It’s so hard to see her go through this,” Ms. Mejia said. “Every time she has a seizure, her brain is getting worse. I still hope one day she can get a treatment that could stop all this and make her life better.”

‘Big questions’

Dr. Pascual is already conducting further research into acetate treatments, with the goal of launching a clinical trial for patients like Elizabeth in the coming years.

His lab is also researching other epilepsy conditions – such as glucose transporter type I (Glut1) deficiency – to determine if inhibitory neurons in other parts of the brain are responsible for seizures. If so, the findings could provide strong evidence for where scientists should look in the brain to detect and prevent misfiring neurons.

“It’s an exciting time, but there is much that needs to happen to make this research helpful to patients,” Dr. Pascual said. “How do we find an automated way of detecting neuron activity when patients are away from the lab? What are the best ways to intervene when we know a seizure is coming? These are big questions the field still needs to answer.”

via Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

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[WEB SITE] High-power prismatic devices may further expand visual fields for patients with hemianopia – ScienceDaily

Series of novel optical designs may address some limitations of existing prism technology, which can expand visual fields by up to 30 degrees

Summary: Three new eyeglasses have now been designedusing high-power prisms to optimally expand the visual fields of patients with hemianopia, a condition in which the visual fields of both eyes are cut by half. The new designs address some limitations of existing prism correction available to this population.

By embedding the current prism in a spectacle lens that has prismatic power in the opposite direction, the image shifting effect is increased by the summation of the power of both prism types. This design allows for up to 36 degrees of expansion to the visual field on the patient’s blind side. This design permits 5 degrees of scanning range to the blind side with full effect.
Credit: Massachusetts Eye and Ear

Researchers from the Schepens Eye Research Institute of Massachusetts Eye and Ear and Harvard Medical School have designed three new eyeglasses using high-power prisms to optimally expand the visual fields of patients with hemianopia, a condition in which the visual fields of both eyes are cut by half. The new designs, described in Optometry and Vision Science, address some limitations of existing prism correction available to this population.

Impairing either the left or right halves of the visual fields in both eyes, hemianopia affects more than one million Americans and is most commonly caused by stroke, brain tumors and head trauma. Hemianopia reduces the natural visual field of about 180 degrees to a mere 90 degrees. People with hemianopia have difficulty detecting hazards on their blind sides, leading to collisions, falls and other accidents. Patients with hemianopia cannot legally drive in Massachusetts, where a visual field of 120 degrees is required.

One method of treatment for hemianopia is to expand the visual field with prisms mounted on or embedded in eyeglasses. A research team led by Eli Peli, M.Sc., O.D., FAAO, Professor of Ophthalmology at Harvard Medical School and the Moakley Scholar in Aging Eye Research at the Schepens Eye Research Institute of Mass. Eye and Ear, has been developing prism devices to expand the visual field for these patients for more than 15 years. Their most recent commercially available device introduced in 2013, the peripheral prism glasses, has been shown to expand the visual fields of patients with hemianopia by as much as 30 degrees, optically shifting objects from the blind side of the visual field to the seeing side.

With the goal of expanding the visual field on the blind side even farther, the researchers explored new optical techniques to create higher power image shifting devices designed to bend the light farther than the 30-degree limit of conventional prisms. In conventional prisms, increasing the angle eventually results in the light bending back into the prism, trapped by what is called “total internal reflection.”

“It’s not just that we need a device with a higher angle of light shifting to let them see farther,” said Dr. Peli (pictured right). “We also want the new devices to provide the additional range of vision when the patient scans their eyes in both directions. The current prism devices support such flexibility only when scanning into the seeing side.”

The authors introduced three new high-power prism concept devices in the Optometry and Vision Science paper:

Yoked Prisms in the Carrier Lens

By embedding the current prism in a spectacle lens that has prismatic power in the opposite direction, the image shifting effect is increased by the summation of the power of both prism types. This design allows for up to 36 degrees of expansion to the visual field on the patient’s blind side. This design permits 5 degrees of scanning range to the blind side with full effect.

Bi-Part Double Fresnel Prism

To increase the power of the peripheral prism, the bi-part double Fresnel prism combines two prism segments angled to each other. This design allows for up to 43 degrees of expansion to the visual field on the patient’s blind side and an increase to 14 degrees scanning range into the blind side.

Mirror-Based Periscopic Prism

The third approach — not yet fully manufactured — uses a pair of angled mirrors to deflect the image from the blind side to the seeing side — not unlike prism correction. Due to the mirror-based design, this device is distortion-free and does not suffer from the color splitting effect of prisms, which reduces image clarity. It may allow for up to 40 degrees of expansion to the visual field on the patient’s blind side with much wider scanning range permitted.

The researchers intend to fully design and implement the mirror-based periscopic prism and also begin testing all three designs in patients with hemianopia.

“The new optical devices can improve the functionality of the current prism devices used for visual field expansion and may find use in various other field expansion applications such as a mobility aid for patients with tunnel vision,” Dr. Peli said.

Story Source:

Materials provided by Massachusetts Eye and Ear Infirmary. Note: Content may be edited for style and length.

Journal Reference:

Eli Peli, Alex R. Bowers, Karen Keeney, Jae-Hyun Jung. High-Power Prismatic Devices for Oblique Peripheral Prisms. Optometry and Vision Science, 2016; 93 (5): 521 DOI: 10.1097/OPX.0000000000000820

via High-power prismatic devices may further expand visual fields for patients with hemianopia: Series of novel optical designs may address some limitations of existing prism technology, which can expand visual fields by up to 30 degrees — ScienceDaily

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[ARTICLE] Electrical Stimulation of the Brain and the development of Cortical Visual Prostheses: An Historical Perspective – Full Text HTML/PDF

Highlights

  • We revisit the discovery of visual cortex and of the brain’s electrical excitability.
  • We detail early experiences with electrical stimulation of visual cortex.
  • Subsequent attempts to develop a cortical visual prosthesis are explored.
  • We detail the development of technologies critical to current prosthesis designs.

Abstract

Rapid advances are occurring in neural engineering, bionics and the brain-computer interface. These milestones have been underpinned by staggering advances in micro-electronics, computing, and wireless technology in the last three decades. Several cortically-based visual prosthetic devices are currently being developed, but pioneering advances with early implants were achieved by Brindley followed by Dobelle in the 1960s and 1970s. We have reviewed these discoveries within the historical context of the medical uses of electricity including attempts to cure blindness, the discovery of the visual cortex, and opportunities for cortex stimulation experiments during neurosurgery. Further advances were made possible with improvements in electrode design, greater understanding of cortical electrophysiology and miniaturization of electronic components. Human trials of a new generation of prototype cortical visual prostheses for the blind are imminent.

Introduction

Advances in medicine, surgery and electronics have set the stage for a fusion of the physical and biological sciences; one in which prosthetic devices may restore lost functional capacity to the disabled. The emerging field of neuro-prosthetics embodies the totality of this integration, whereby sensory (Carlson et al., 2012, Guenther et al., 2012 and Weiland and Humayun, 2014), motor (Hochberg et al., 2012) and even cognitive (Hampson et al., 2012 and Hampson et al., 2013) deficits may be addressed. A significant share of the worldwide research effort in this regard is directed towards the development of visual prosthetics for the blind. Potential stimulation targets currently being investigated for visual prostheses include the retina (Chow et al., 2004, Dorn et al., 2013, Gerding et al., 2007 and Stingl et al., 2013), optic nerve (Brelen et al., 2010, Sakaguchi et al., 2009 and Wu et al., 2010), lateral geniculate body (Panetsos et al., 2011 and Pezaris and Eskandar, 2009) and the cerebral cortex (Brindley and Lewin, 1968b, Dobelle, 2000 and Schmidt et al., 1996). Human testing of implanted cortical electrode arrays for the evocation of visual percepts predates similar attempts at the retinal level by almost 30 years (Brindley and Lewin, 1968b, Humayun et al., 1996 and Humayun et al., 1999). Moreover, visual cortical prostheses offering limited functionality were chronically implanted in a number of patients throughout the 1970’s (Brindley, 1982, Dobelle et al., 1976 and Dobelle et al., 1979). Two retinal devices recently obtained regulatory approval in Europe (Argus II and Alpha IMS), with the Argus II also having obtained regulatory approval in the US (Weiland and Humayun, 2014). Cortical devices remain experimental only. Imminent human trials of a new generation of improved cortical devices render it timely to review the history of their development, including early electrical stimulation of human cerebral cortex and the first pioneering attempts to restore visual sensation to a profoundly blind person over 50 years ago.

Full Text HTML —> Electrical Stimulation of the Brain and the development of Cortical Visual Prostheses: An Historical Perspective

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