Posts tagged peripheral neuropathy
Articles and news from the latest research reports.
Dissecting the Distinctive Walk of Disease
Pitt multidisciplinary research team proposes mathematical model that examines multiple walking patterns and movements in adults older than 65
Older adults diagnosed with brain disorders such as Parkinson’s disease often feel a loss of independence because of their lack of mobility and difficulty walking. To better understand and improve these mobility issues—and detect them sooner—a University of Pittsburgh multidisciplinary research team is working toward building a more advanced motion test that addresses a wider range of walking patterns and movements.
In a recent issue of IEEE Transactions on Neural Systems and Rehabilitation Engineering, researchers from Pitt’s Swanson School of Engineering, School of Health and Rehabilitation Sciences, and School of Medicine propose a mathematical model that can examine multiple walking, or gait-related, features in healthy and clinical populations. To date, no study has brought together such a team to examine such a high number of movement features comparing healthy and clinical older adults. Previous studies have typically only measured one or two types of movement features in just one population.
“Right away, you can tell whether an older individual has difficulties walking by conducting a simple gait test,” said Ervin Sejdic, lead author of the paper and an assistant professor of engineering in the Swanson School. “But can we quantify these changes and document them earlier? That’s the biggest issue here and what we’re trying to model.”
Thirty-five adults older than 65 were recruited for the study, including 14 healthy participants, 10 individuals with Parkinson’s disease, and 11 adults who had impaired feeling in their legs owing to peripheral neuropathy (nerve damage). Walking trials were performed using a computer-controlled treadmill, and participants wore an accelerometer—a small box attached with a belt—and a set of reflective markers on their lower body that allowed for tracking of the participants’ movements through a camera-based, motion-analysis system. These two systems allowed the team to examine the torso and lower body movements of patients as they walked. Participants completed three walking trials on the treadmill—one at a usual walking pace, another while walking slowly, and another that included working on a task while walking (i.e. pushing a button in response to a sound).
The accelerometer signals were used to examine three aspects of movement: participants moving forward and backward, side to side, and up and down. The researchers then used advanced mathematical computations to extract data from these signals.
The results—integrated into the mathematical models—showed significant differences between the healthy and clinical populations. These metrics were able to discriminate between the three groups, identifying critical features in how the participants walked.
The Pitt team is now looking to conduct this type of study on a larger scale—evaluating the gait patterns of older adults residing within independent living facilities.
“Our results indicate that we can potentially develop these mathematical models as biomarkers to predict changes in walking due to diseases like Parkinson’s disease,” said Sejdic. “Now, we want to take it further. We’re especially hoping to help those individuals in independent living facilities by predicting the declines in their walking even earlier.”
“What also makes this study unique is the multidisciplinary team approach we used,” said Jennifer S. Brach (SHRS ’94G, ’00G) coprincipal investigator of the study and associate professor in Pitt’s Department of Physical Therapy. “Here we brought together a research team that included engineers, physical therapists, and experts in geriatrics to work on an important problem in older adults—changes in mobility.”
(Source: news.pitt.edu)
New clues to causes of peripheral nerve damage
Anyone whose hand or foot has “fallen asleep” has an idea of the numbness and tingling often experienced by people with peripheral nerve damage. The condition also can cause a range of other symptoms, including unrelenting pain, stinging, burning, itching and sensitivity to touch.
Although peripheral neuropathies afflict some 20 million Americans, their underlying causes are not completely understood. Much research has focused on the breakdown of cellular energy factories in nerve cells as a contributing factor.
Now, new research at Washington University School of Medicine in St. Louis points to a more central role in damage to energy factories in other cells: Schwann cells, which grow alongside neurons and enable nerve signals to travel from the spinal cord to the tips of the fingers and toes.
The finding may lead to new therapeutic strategies to more effectively treat symptoms of this highly variable disorder, the scientists report March 6 in the journal Neuron.
“We found that a toxic substance builds up in Schwann cells that have disabled energy factories, leading to the same kind of nerve damage seen in patients with neuropathies,” says senior author Jeffrey Milbrandt, MD, PhD, the James S. McDonnell Professor of Genetics and head of the Department of Genetics. “Now, we’re evaluating whether drugs can block the buildup of that toxin, which could lead to a new treatment for the condition.”
The most common cause of peripheral neuropathy is diabetes, which accounts for about half of all cases. The condition also can occur in cancer patients treated with chemotherapy, which can damage nerves.
In the body, Schwann cells wrap tightly around nerve axons, the fibers that relay nerve signals. Graduate student and first author Andreu Viader and colleagues in Milbrandt’s lab studied Schwann cells in mice with genetically disabled mitochondria, or cellular energy factories. Under normal conditions, these mitochondria produce fuel and intermediates of energy metabolism that allow nerve cells to function.
The researchers showed that the crippled mitochondria activated a stress response in the Schwann cells. Instead of synthesizing fatty acids, a key component of Schwann cells, the cells burned fatty acids for fuel.
Over time, inefficient burning of fatty acids by the crippled mitochondria leads to a build up of acylcarnitines, a toxic substance, in the Schwann cells. The researchers found levels of acylcarnitines up to 100-fold higher in these mutant Schwann cells than in healthy Schwann cells.
And the bad news doesn’t end there. Eventually, the toxin leaks out of the Schwann cells and onto the nerve axons. Studying neurons in petri dishes, the researchers showed that acylcarnitines damage nerve axons and disrupt the ability of nerves to relay signals.
“The toxin leaking out of the Schwann cells and onto the adjacent nerve axons causes damage that results in pain, numbness, tingling and other symptoms,” Milbrandt says. “We think that is a likely mechanism to explain the degeneration of axons that is known to occur in peripheral neuropathies.”
The new research suggests that drugs that inhibit the buildup of acylcarnitines may block axonal degeneration. Milbrandt and his team now are evaluating the drugs in mice with disabled Schwann cells to see if they can slow or alleviate the decay of axons.
Brain tumours and peripheral neuropathy
Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international team which has for the first time identified the role of a tumour suppressor in peripheral neuropathy in those suffering multiple tumours of the brain and nervous system.
One in 25,000 people worldwide is affected by neurofibromatosis type 2 (NF2), a condition where the loss of a tumour suppressor called Merlin results in multiple tumours in the brain and nervous system.
Sufferers may experience 20 to 30 tumours at any one time and such numbers often lead to hearing loss, disability and eventually death. Those with NF2 may also experience peripheral neuropathy, which is when the nerves carrying messages to and from the brain and spinal column to the rest of the body do not work.
Peripheral neuropathy leads to further complications for NF2 sufferers, such as pain and numbness, muscle problems, problems with body organs and other symptoms of nerve damage, such as bladder problems, uncontrollable sweating and sexual dysfunction.
Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international research team which has for the first time identified the role of a tumour suppressor called Merlin in regulating the integrity of axons. Axons are nerve fibres which transmit information around the body and it is these are that damaged in peripheral neuropathy.
The research team showed that Merlin regulates a protein called neurofilament which supplies structural support for the axon. A better understanding of this mechanism could lead to effective drug therapies to alleviate the symptoms of peripheral neuropathy in patients with NF2.
The results of the research is published this week in Nature Neuroscience.
(Source: plymouth.ac.uk)