Completely paralyzed man voluntarily moves his legs, UCLA scientists report

Mark Pollock and trainer Simon O’Donnell (credit: Mark Pollock)

A 39-year-old man who had been completely paralyzed for four years was able to voluntarily control his leg muscles and take thousands of steps in a “robotic exoskeleton” device during five days of training, and for two weeks afterward, UCLA scientists report.

This is the first time that a person with chronic, complete paralysis has regained enough voluntary control to actively work with a robotic device designed to enhance mobility.

In addition to the robotic device, the man was aided by a novel noninvasive spinal stimulation technique that does not require surgery. His leg movements also resulted in other health benefits, including improved cardiovascular function and muscle tone.

The new approach combines a battery-powered wearable bionic suit that enables people to move their legs in a step-like fashion, with a noninvasive procedure that the same researchers had previously used to enable five men who had been completely paralyzed to move their legs in a rhythmic motion.

That earlier achievement is believed to be the first time people who are completely paralyzed have been able to relearn voluntary leg movements without surgery. (The researchers do not describe the achievement as “walking” because no one who is completely paralyzed has independently walked in the absence of the robotic device and electrical stimulation of the spinal cord.)

Mountain racing blind? No problem. Paralyzed? “Iron ElectriRx” man is aceing that too

In the latest study, the researchers treated Mark Pollock, who lost his sight in 1998 and later became the first blind man to race to the South Pole. In 2010, Pollock fell from a second-story window and suffered a spinal cord injury that left him paralyzed from the waist down.

At UCLA, outfitted with the robotic exoskeleton, Pollock made substantial progress after receiving a few weeks of physical training without spinal stimulation and then just five days of spinal stimulation training in a one-week span, for about an hour a day.

“In the last few weeks of the trial, my heart rate hit 138 beats per minute,” Pollock said. “This is an aerobic training zone, a rate I haven’t even come close to since being paralyzed while walking in the robot alone, without these interventions. That was a very exciting, emotional moment for me, having spent my whole adult life before breaking my back as an athlete.”

Even in the years since he lost his sight, Pollock has competed in ultra-endurance races across deserts, mountains and the polar ice caps. He also won silver and bronze medals in rowing at the Commonwealth Games and launched a motivational speaking business.

“Stepping with the stimulation and having my heart rate increase, along with the awareness of my legs under me, was addictive. I wanted more,” he said.

The research was published by the IEEE Engineering in Medicine and Biology Society, the world’s largest society of biomedical engineers.

Expanding the clinical toolbox for the paralyzed

“It will be difficult to get people with complete paralysis to walk completely independently, but even if they don’t accomplish that, the fact they can assist themselves in walking will greatly improve their overall health and quality of life,” said V. Reggie Edgerton, senior author of the research and a UCLA distinguished professor of integrative biology and physiology, neurobiology and neurosurgery.

The procedure used a robotic device manufactured by Richmond, California-based Ekso Bionics that captures data that enables the research team to determine how much the subject is moving his own limbs, as opposed to being aided by the device.

“If the robot does all the work, the subject becomes passive and the nervous system shuts down,” Edgerton said.

The data showed that Pollock was actively flexing his left knee and raising his left leg and that during and after the electrical stimulation, he was able to voluntarily assist the robot during stepping; it wasn’t just the robotic device doing the work.

“For people who are severely injured but not completely paralyzed, there’s every reason to believe that they will have the opportunity to use these types of interventions to further improve their level of function. They’re likely to improve even more,” Edgerton said. “We need to expand the clinical toolbox available for people with spinal cord injury and other diseases.”


Edgerton Lab, University of California Los Angeles | Paralyzed subject Training in Ekso during spinal cord stimulation

The future of spinal-cord research

Edgerton and his research team have received many awards and honors for their research, including Popular Mechanics’ 2011 Breakthrough Award.

“Dr. Edgerton is a pioneer and we are encouraged by these findings to broaden our understanding of possible treatment options for paralysis,” said Peter Wilderotter, president and CEO of the Christopher and Dana Reeve Foundation, which helped fund the research. “Given the complexities of a spinal cord injury, there will be no one-size-fits-all cure but rather a combination of different interventions to achieve functional recovery.

“What we are seeing right now in the field of spinal cord research is a surge of momentum with new directions and approaches to remind the spine of its potential even years after an injury,” he said.

NeuroRecovery Technologies, a medical technology company Edgerton founded, designs and develops devices that help restore movement in patients with paralysis. The company provided the device used to stimulate the spinal cord in combination with the Ekso in this research.

Edgerton said although it likely will be years before the new approaches are widely available, he now believes it is possible to significantly improve quality of life for patients with severe spinal cord injuries, and to help them recover multiple body functions.

In addition to the Reeve foundation, the research was funded by the National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering, the F. M. Kirby Foundation, the Walkabout Foundation, the Dana and Albert R. Broccoli Foundation, Ekso Bionics, NeuroRecovery Technologies and the Mark Pollock Trust.

Almost 6 million Americans live with paralysis, including nearly 1.3 million with spinal cord injuries.


Abstract of Iron ‘ElectriRx’ Man: Overground Stepping in an Exoskeleton Combined with Noninvasive Spinal Cord Stimulation after Paralysis

We asked whether coordinated voluntary movement of the lower limbs could be regained in an individual having been completely paralyzed (>4 yr) and completely absent of vision (>15 yr) using a novel strategy – transcutaneous spinal cord stimulation at selected sites over the spinal vertebrae with just one week of training. We also asked whether this stimulation strategy could facilitate stepping assisted by an exoskeleton (EKSO, EKSO Bionics) that is designed so that the subject can voluntarily complement the work being performed by the exoskeleton. We found that spinal cord stimulation enhanced the level of effort that the subject could generate while stepping in the exoskeleton. In addition, stimulation improved the coordination patterns of the lower limb muscles resulting in a more continuous, smooth stepping motion in the exoskeleton. These stepping sessions in the presence of stimulation were accompanied by greater cardiac responses and sweating than could be attained without the stimulation. Based on the data from this case study it appears that there is considerable potential for positive synergistic effects after complete paralysis by combining the overground stepping in an exoskeleton, a novel transcutaneous spinal cord stimulation paradigm, and daily training.

First US patients treated with noninvasive focused ultrasound for Parkinson’s disease

University of Maryland medical doctors monitor focused ultrasound treatment for essential tremor, guided by magnetic resonance imaging (MRI) (credit: University of Maryland School of Medicine)

Researchers at the University of Maryland have performed the first focused ultrasound treatments on a deep structure within the brain related to Parkinson’s disease* called the globus pallidus.

These treatments are part of international pilot studies of 40 patients assessing the feasibility, safety, and preliminary efficacy of focused ultrasound treatments for Parkinson’s disease, guided by magnetic resonance imaging (MRI).

The researchers are using MRI to help them guide ultrasound waves through the intact skin and skull to reach the globus pallidus part of the brain. If successful, focused ultrasound could offer an alternative approach for certain patients with Parkinson’s disease who have failed medical therapy or become disabled from medication-induced dyskinesia (tremor). To date, seven patients in Korea and one patient in Canada have been treated in studies.

The new Parkinson’s procedure

ExAblate Neuro system (credit: Insightec)

The non-invasive ultrasound and MRI imaging procedures are done on an outpatient basis in the Center for Metabolic Imaging and Image-Guided Therapeutics (CMIT) MRI suite, using the ExAblate Neuro system developed by Insightec.

During the Parkinson’s procedure, patients lie in an MRI scanner with a head-immobilizing frame fitted with a transducer helmet. Ultrasonic energy is targeted through the skull to the globus pallidus of the brain, and images acquired during the procedure give physicians a real-time map of the area being treated.

“We’re raising the temperature in a very restricted area of the brain to destroy tissue,” explained principal investigator Howard M. Eisenberg, MD, the Raymond K. Thompson Chair of Neurosurgery. “The ultrasound waves create a heat lesion that we can monitor through MRI.”

The entire procedure lasts two to four hours, and patients are awake and able to interact with the treatment team. This allows the physicians to monitor the immediate effects of treatment and make adjustments if necessary.

Researchers from the University of Virginia Health System reported in the New England Journal of Medicine in 2013 that 15 patients with essential tremor** — a related disorder — who received focused ultrasound saw “significant improvement” in their dominant hand tremor. Patients treated in the initial phase of the study at the University of Maryland experienced similar results.

The Michael J. Fox Foundation for Parkinson’s Research and the Focused Ultrasound Foundation are funding the new Parkinson’s study.

* As many as one million Americans have Parkinson’s disease, a chronic, degenerative disorder for which there is no cure. The second most common movement disorder, Parkinson’s results from the malfunction or loss of brain cells crucial for movement and coordination. Symptoms include motor difficulties such as tremor, rigidity and postural instability. People with Parkinson’s can also experience non-motor symptoms of cognitive impairment, depression, and anxiety, and autonomic dysfunction.

** Essential tremor, which is eight times more common than Parkinson’s disease, causes debilitating shaking that can be resistant to drug therapy. It mainly affects the hands, head and voice, making aspects of daily life like eating, drinking and writing extremely difficult.


Abstract of A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor

Background

Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.

Methods

From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients’ perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability).

Results

Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001).

Conclusions

In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure’s efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.)

Life expectancy climbs worldwide but people spend more years living with illness and disability

Life expectancy at birth, both sexes, 2013 (credit: Institute for Health Metrics and Evaluation)

The good news: as for 2013, global life expectancy for people in 188 countries has risen 6.2 years since 1990 (65.3 to 71.5). The bad news: healthy life expectancy (HALE) at birth rose by only 5.4 years (56.9 to 62.3), due to fatal and nonfatal ailments (interactive visualization by country here).

In other words, people are living more years with illness and disability. Ischemic heart disease, lower respiratory infections, and stroke cause the most health loss around the world.

That’s according to a study published in the medical journal The Lancet on August 27, conducted by an international consortium of researchers working on the Global Burden of Disease study, led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington.

“The world has made great progress in health, but now the challenge is to invest in finding more effective ways of preventing or treating the major causes of illness and disability,” said Professor Theo Vos of IHME, the study’s lead author.

For dozens of countries — including Botswana, Belize, and Syria — healthy life expectancy in 2013 was not significantly higher than in 1990. In some of those countries, including South Africa, Paraguay, and Belarus, healthy life expectancy has actually dropped (by as much as 10 years) since 1990.

Causes of health loss

The fastest-growing global cause of health loss between 1990 and 2013 was HIV/AIDS, which increased by 341.5%. But this dramatic rise masks progress in recent years; since 2005, health loss due to HIV/AIDS has diminished by 23.9% because of global focus on the disease. Ischemic heart disease, stroke, low back and neck pain, road injuries, and COPD have also caused an increasing amount of health loss since 1990.The impact of other ailments, such as diarrheal diseases, neonatal preterm birth complications, and lower respiratory infections, has significantly declined.

Across countries, patterns of health loss vary widely. The countries with the highest rates of DALYs are among the poorest in the world, and include several in sub-Saharan Africa: Lesotho, Swaziland, Central African Republic, Guinea-Bissau, and Zimbabwe. Countries with the lowest rates of health loss include Italy, Spain, Norway, Switzerland, and Israel.

The number of DALYs due to communicable, maternal, neonatal, and nutritional disorders has declined steadily, from 1.19 billion in 1990 to 769.3 million in 2013, while DALYs from non-communicable diseases have increased steadily, rising from 1.08 billion to 1.43 billion over the same period.

Ethiopia: a case study in progress

Ethiopia is one of several countries that have been rising to the challenge to ensure that people live lives that are both longer and healthier. In 1990, Ethiopians could expect to live 40.8 healthy years. But by 2013, the country saw an increase in healthy life expectancy of 13.5 years — more than double the global average — to 54.3 years.

“Ethiopia has made impressive gains in health over the past two decades, with significant decreases in rates of diarrheal disease, lower respiratory infection, and neonatal disorders,” said Dr. Tariku Jibat Beyene of Addis Ababa University. “But ailments such as heart disease, COPD, and stroke are causing an increasing amount of health loss. We must remain vigilant in addressing this new reality of Ethiopian health.”

Countries with highest healthy life expectancy, both sexes, 2013

1 Japan
2 Singapore
3 Andorra
4 Iceland
5 Cyprus
6 Israel
7 France
8 Italy
9 South Korea
10 Canada

Countries with lowest healthy life expectancy, both sexes, 2013

1 Lesotho
2 Swaziland
3 Central African Republic
4 Guinea-Bissau
5 Zimbabwe
6 Mozambique
7 Afghanistan
8 Chad
9 South Sudan
10 Zambia

Leading causes of DALYs or health loss globally for both sexes, 2013

1 Ischemic heart disease
2 Lower respiratory infection
3 Stroke
4 Low back and neck pain
5 Road injuries
6 Diarrheal diseases
7 Chronic obstructive pulmonary disease
8 Neonatal preterm birth complications
9 HIV/AIDS
10 Malaria


Abstract of Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition

Background: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

Methods: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

Findings: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

Interpretation: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Funding: Bill & Melinda Gates Foundation.