Links for Keyword: Movement Disorders
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Researchers at the Howard Hughes Medical Institute are unveiling a new resource that they say will speed scientists' understanding and treatment of a group of inherited disorders called ataxias that kill cells in the brain, causing loss of balance, coordination and often death. The scientists are making new data available on hundreds of interacting proteins that are involved in dozens of inherited forms of ataxia. The approach to mapping the global set of interacting proteins—called an “interactome”—could also be applied to disorders as diverse as Parkinson's disease, diabetes, and hypertension. Howard Hughes Medical Institute investigator Huda Y. Zoghbi and her colleagues reported on their studies in an article published in the May 18, 2006, issue of the journal Cell. Zoghbi and her colleagues at the Baylor College of Medicine collaborated on the studies with researchers from Harvard Medical School and the University of Notre Dame. Since proteins are the major machines that work inside cells, understanding how they interact may give researchers an opportunity to learn how they can go awry and cause disease. Furthermore, understanding these interactions offers scientists targets for drugs that can help restore normal function to such malfunctioning machinery. © 2006 Howard Hughes Medical Institute.
We all teeter and tip while first learning to walk but, for adults like retired electrical engineer Fred Kawabata — whose sense of balance was damaged when a childhood disease flared up as an adult — a simple stroll becomes something to learn all over again. "When it first struck me I was flat on my back," explains 65-year-old Kawabata from Beaverton, Oregon. "I had vertigo, I was dizzy, I could hardly get out of bed." Almost ten years ago the chicken pox he had suffered as a kid came back in the form of shingles. The virus that lay dormant for all those years in his nerves attacked the vestibular nerves of Kawabata's the inner ear, leaving him rather unsteady on his feet because of a balance disorder. "In about a month, I could get up and walk around although it was still very uncomfortable. It took a couple months before I could be reasonably comfortable walking around," he recalls. "[Now], when I'm walking on a flat surface, I generally don't have to think about it very much. But if I'm on an uneven surface like when I'm hiking and the trail is rough, then I really have to think about it. © ScienCentral, 2000-2006.
Related chapters from BP7e: Chapter 9: Hearing, Vestibular Perception, Taste, and Smell; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 6: Hearing, Balance, Taste, and Smell; Chapter 5: The Sensorimotor System
Link ID: 8729 - Posted: 06.24.2010
By Aaron J. Sender John Donoghue is building a brain decoder that could transform the lives of people paralyzed by injury or disease. Those who have lost the ability to move their limbs often have perfectly intact brains, so Donoghue hopes to implant a chip that can monitor their brain activity and convert their intentions into computer commands. In its current version, the chip’s 100 hair-thin electrodes listen to neurons firing in an area that controls arm movement and translate the activity into electronic signals. A program then decodes the brain signals into commands that direct a cursor on a computer screen. Donoghue hopes the chip can eventually control appliances or even robotic limbs. “We’re effectively rewiring the nervous system—not biologically but with real wires,” says Donoghue. So far, more than 20 monkeys have been equipped with the implanted chip, and four of them have successfully willed a cursor to follow a moving target. Now Cyberkinetics, the company Donoghue cofounded to develop the device they call BrainGate, is preparing to test it in five paralyzed humans. “People with these kinds of injuries are perfectly capable of leading full and productive lives,” says Donoghue. “They just can’t get their signals out.” Give me the big picture first. How did the idea originate and what problem were you looking to solve? D: I’ve had a long-standing basic science research program that has really been directed at how the brain computes information. In a simpler sense, how do you turn thoughts into action? The way you get at the fundamental activity is by recording with electrodes in the brain. And since it’s a procedure that requires you to introduce that electrode, you have to use a monkey or an experimental animal. A monkey has a motor cortex like ours, and its behaviors are a lot like ours, so we use it as a model. © 2004 The Walt Disney Company.
by Paul Austin The patient was lying placidly on the stretcher with her eyes closed when I introduced myself. “I’m Paul Austin, one of the ER doctors. Can you open your eyes and talk with me?” She raised her eyebrows a few millimeters, not even enough to wrinkle her forehead. Her right eye remained shut, and her left eye opened just enough to expose a narrow sliver of white. She turned her face toward me, her eyes still closed. I looked at her paperwork. She was a 63-year-old woman who said she couldn’t keep her eyes open, had difficulty swallowing, and had fallen four times the day before. She also had complaints of general weakness for about two years. That bothered me. The possible causes of overall weakness could fill a textbook. Yet in cases that have gone on for two years without a diagnosis, doctors often find no physical cause. Her chart noted that she had recently been hospitalized for schizo-affective disorder, which causes symptoms of both schizophrenia and a mood disorder, and had recently been discharged. That concerned me as well. When a psychiatric diagnosis is present, it can distract doctors from looking for an organic cause of symptoms. “Can you open your eyes for me?” I asked again. Her eyebrows moved a millimeter up. “Open them all the way.” Using her index fingers she raised both her upper eyelids. She stared at me, holding her eyelids up with her fingers, her elbows sticking out at her sides.
By BEN DAITZ, M.D. ALBUQUERQUE, In 1598, Joyce Gonzalez’s great- great- great- great -great -great -great -great -great -great -grandfather followed the famous conquistador Juan de Oñate from Spain to Mexico, then north on the Camino Real, the Royal Road to Santa Fe. In the 1800s, one of Mary Ann Chavez’s distant relatives, possibly a French fur trapper and trader from Quebec, also made his way into northern New Mexico. Mrs. Chavez and Mrs. Gonzalez, though not related, share a Hispanic heritage and a fascination with genealogy. They also share the burden of having forebears with genetic diseases that, like the remote mountain villages in this region, have remained largely hidden from medical diagnosis and treatment. Now, thanks to the efforts of patient advocates and the work of a clinic here at the University of New Mexico Medical School, these illnesses are finally being confronted and studied. “We call it the family curse,” said Mrs. Chavez, 73, “and you don’t know you’ve got it until you’re 40 or 50 when your eyelids start to droop, and you begin to have trouble swallowing and get muscle weakness.” The illness is called oculopharyngeal muscular dystrophy, or OPMD, and the largest group of Americans affected are Hispanics living in northern New Mexico. They are descendants of the wandering French-Canadian or, perhaps, early Spanish colonists. Mrs. Chavez’s son, her brother and innumerable aunts, uncles and cousins have all inherited the disease. Copyright 2007 The New York Times Company
ITHACA, N.Y. -- Using a state-of-the-art technique to map neurons in the spinal cord of a larval zebrafish, Cornell University scientists have found a surprising pattern of activity that regulates the speed of the fish’s movement. The research may have long-term implications for treating injured human spinal cords and Parkinson’s disease, where movements slow down and become erratic. The study, "A Topographic Map of Recruitment in Spinal Cord," published in the March 1 issue of the journal Nature, maps how neurons in the bottom of the fish’s spinal cord become active during slow movements, while cells further up the spinal cord activate as movements speed up. By removing specific neurons in the lower spinal cord with laser beams, the researchers rendered the fish incapable of slow movements. By removing nerves further up the backbone, the fish had difficulty moving fast. "No one had any idea that organization like this existed in a spinal cord," said Joseph Fetcho, a Cornell professor of neurobiology and behavior and an author of the study. "Now that we know the pattern, we can begin to ask how that changes in disease states." David McLean, Cornell postdoctoral researcher in Fetcho’s laboratory, was the first person to discover the pattern of neural activation and how it was associated with speed of movement. He is the lead author on the study.
Drug therapy can extend survival and improve movement in a mouse model of spinal muscular atrophy (SMA), new research shows. The study, carried out at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), suggests that similar drugs might one day be useful for treating human SMA. "This study shows that treatment can be effective when started after the disease appears," says Kenneth H. Fischbeck, M.D., of the NINDS, who helped lead the new study. The finding is important because most children with SMA are diagnosed after symptoms of the disease become obvious, he adds. The report appears in the February 22, 2007, advance online publication of The Journal of Clinical Investigation. SMA is the most common severe hereditary neurological disease of childhood, affecting one in every 8,000-10,000 children. Babies with the most common form of the disease, called SMA type I, develop symptoms before birth or in the first few months of life and have severe muscle weakness that makes it difficult for them to breathe, eat, and move. They usually die by age two. Other forms of SMA are not as severe, but still cause significant disability. While some symptoms of SMA can be alleviated, there is currently no treatment that can change the course of the disease. SMA is caused by mutations in a gene called SMN1. Investigators studying the genetics of SMA have found that there is another gene, called SMN2, on the same chromosome. While the normal form of SMN1 produces a full-length functional protein, most of the protein produced by SMN2 is truncated and unable to function. The relatively small amount of normal SMN protein produced by the SMN2 gene can reduce the severity of the disease. Therefore, investigators are searching for drugs that can increase the amount of normal protein produced by this gene.
ST. PAUL, MN -- An anticonvulsant drug typically used to control seizures and neuropathic pain may reduce symptoms among those who suffer from restless legs syndrome (RLS), a movement disorder that affects up to 10 percent of the population. A study published in the November 26 issue of Neurology, journal of the American Academy of Neurology, concludes, “Gabapentin may be a potent agent for treatment of even severe RLS, without the disadvantages of long-term complications of previously favored treatments,” according to study author Diego Garcia-Borreguero, MD, of the Fundacion Jimenez Díaz in Madrid, Spain. RLS is characterized by: an urge to move the legs, generally accompanied by unpleasant sensations; an increase of symptoms during rest and a partial, temporary relief of symptoms through activity; and worsening of symptoms in the evening or at night. Symptoms tend to progress with age. RLS is usually treated with dopaminergic drugs, such as those used with Parkinson’s disease patients. However, the side effects and likelihood of long-term complications have driven the search for RLS treatment options.
Researchers have discovered how the abnormal repetition of a genetic sequence can have disastrous consequences that lead to the death of neurons that govern balance and motor coordination. The studies bolster the emerging theory that neurodegenerative disorders can be caused by having extra copies of a normal protein, not just a mutated one. People who are afflicted with the rare neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1) suffer damage to cerebellar Purkinje cells caused by a toxic buildup of the protein Ataxin-1. Researchers knew that SCA1, Huntington's disease and other related disorders arise because of a “genetic stutter,” in which a mutation causes a particular gene sequence to repeat itself. These abnormal genetic repeats cause the resulting proteins to contain unusually long repetitive stretches of the amino acid glutamine. The new findings, which are published in the August 26, 2005, issue of the journal Cell, provide a molecular explanation for Ataxin-1's assault on cerebellar Purkinje cells. The findings should help to understand a range of diseases, including Huntington's disease, which are caused by an abnormal number of repetitive gene sequences. The discovery may also offer a new conceptual approach to understanding the pathology of Parkinson's disease and Alzheimer's disease, according to Huda Y. Zoghbi, a Howard Hughes Medical Institute investigator at the Baylor College of Medicine. © 2005 Howard Hughes Medical Institute.
Rossella Lorenzi, Discovery News -- The remains of a man who could be the world's oldest known paralysis victim have been unearthed by Australian bio-archaeologists in northern Vietnam. Found at the Neolithic cemetery site of Man Bac, some 100 kilometers (62 miles) south of Hanoi, the remains are between 3,500 and 4,000 years old and belong to an adult male who died around age 25. Called Man Bac Burial 9, or simply M9, the young man suffered from paraplegia or possibly quadriplegia due to a rare disorder called Klippel-Feil Syndrome, a condition involving congenital fusion of the spine. The disorder, which can make sufferers look as if they have a short neck, is also often associated with various complications. In the case of M9, posture-related complications forced his head to tilt to his right side, a condition known as torticollis. M9 also likely had problems chewing. spine surgery "Amazingly, this man survived in a subsistence Neolithic economy with total lower body paralysis, and at best minimal upper body mobility for at least a decade prior to death," Lorna Tilley, the Australian National University Ph.D. candidate who excavated the remains with lead researcher Marc Oxenham, told Discovery News. © 2009 Discovery Communications, LLC. Inc.
Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 6: Evolution of the Brain and Behavior
Related chapters from MM:Chapter 5: The Sensorimotor System
Link ID: 13211 - Posted: 06.24.2010
By Michael Price People with muscular dystrophy tire after even light exercise. Now a study suggests that the exhaustion is caused by an enzyme that is missing from the muscle cell membrane, and the results point to a possible treatment for the condition: Viagra. Every year, about 500 boys in the United States are born with Duchenne muscular dystrophy, the disease's most common form. All forms of muscular dystrophy, which cause skeletal muscles to gradually weaken, result from mutations that overload the body with the enzyme creatine kinase, which breaks down muscle tissue. Researchers have long known that even in milder types of the disease, such as Becker's muscular dystrophy, and in the early stages of Duchenne muscular dystrophy, patients tend to fatigue after relatively minor activities. The briefest walk can leave them far more worn out than would be expected from just having weak muscles. These effects show up in mouse models of the disease, too. About 3 years ago, Kevin Campbell, a biophysicist at the University of Iowa in Iowa City, showed a video of the tired muscular dystrophy mice in his lab at a conference. A chance comment inspired a possible solution. "One of the physicians in the audience said, 'That looks just like my Becker's [muscular dystrophy] patients,' " Campbell recalls. One of the hallmarks of Becker's muscular dystrophy is the loss of an enzyme, neuronal nitric oxide synthase (nNOS), from muscle cell membranes. Campbell wondered whether the deficiency of nNOS might be the source of fatigue. © 2008 American Association for the Advancement of Science.
Kerri Smith A monkey's paralysed wrist can be moved and controlled by electrical signals artificially routed from its brain, according to scientists who say that their experiment is a step towards helping paralysed people to regain the use of their limbs. Previously, scientists have been able to train monkeys to move robotic arms using signals routed from electrodes in their brains1. This involved decoding the activity of tens of neurons at a time to replicate actions such as grasping, and required considerable computing power. Now, Chet Moritz and his colleagues at the University of Washington in Seattle have used similar signals to deliver direct electrical stimulation from just one neuron to a paralysed muscle. They first implanted a number of electrodes in the motor cortex of two macaque monkeys. Each electrode picked up signals from a single neuron, and those signals routed through an external circuit to a computer. The neuronal signals controlled a cursor on a screen, and the monkeys were trained to move the cursor using only their brain activity. The scientists then temporarily paralysed the monkeys' wrist muscles using a local anaesthetic. They re-routed the signals from the electrodes to deliver electrical stimulation to the wrist muscles, and found that the monkeys could control their previously paralysed limbs using the same brain activity. The monkeys learnt to do this in less than an hour, the team report in Nature2. © 2008 Nature Publishing Group
By Sandra G. Boodman Bruce Munro wonders how things might have turned out if he hadn't lost it and dialed 911. The retired obstetrician had watched with mounting alarm as his wife, Bettie, seemed to get sicker by the day. For decades her health had been stable, regulated by medicines she took to control her cholesterol, blood pressure, Type 2 diabetes, a thyroid condition and a mood disorder. But in March 2006, Bettie Munro had developed a tremor that became very bad very fast. Doctors assumed she was suffering from a rapidly progressive case of Parkinson's disease, but the neurologist treating her was baffled about why the increasingly potent drugs he prescribed didn't seem to help. On Dec. 22, 2006, while Munro was getting his wife dressed for the day, he snapped. She had fallen three times and could no longer feed herself. "I thought, 'This is it, I can't handle this at home,' " Munro recalled. He picked up the phone and called for help. An ambulance whisked Bettie Munro from their house in a Loudoun County retirement community to Inova Loudoun Hospital. © 2008 The Washington Post Company
Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 11596 - Posted: 06.24.2010
By David Brown Fittingly, the first person to detect a faint signal in all the noise was the interpreter. The 33-year-old woman who worked for eight years working with Spanish-speaking patients at a medical clinic in southern Minnesota noticed something familiar as she translated the story of a young meatpacker last September. Earlier last summer, she had heard a version of it from two other workers at the same slaughterhouse, and had told it to their doctors, who were different from her current patient's. When the consultation was over, she pointed this out. The interpreter's insight set in motion a story, still unfolding, that may be making envious the ghost of Berton Roueche, the legendary chronicler of medical mysteries at the New Yorker magazine. A new disease has surfaced in 12 people among the 1,300 employees at the factory run by Quality Pork Processors about 100 miles south of Minneapolis. The ailment is characterized by sensations of burning, numbness and weakness in the arms and legs. For most, this is unpleasant but not disabling. For a few, however, the ailment has made walking difficult and work impossible. The symptoms have slowly lessened in severity, but in none of the sufferers has it disappeared completely. © 2008 The Washington Post Company
Related chapters from BP7e: Chapter 11: Motor Control and Plasticity; Chapter 8: General Principles of Sensory Processing, Touch, and Pain
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 5: The Sensorimotor System
Link ID: 11273 - Posted: 06.24.2010
Studies in mice have shown that lithium, a drug widely used to treat mood disorders in humans, can provide relief from the crushing symptoms of a fatal brain disease, according to researchers at the Howard Hughes Medical Institute (HHMI) at the Baylor College of Medicine. A team led by HHMI investigator Huda Y. Zoghbi did a series of experiments in mice that showed lithium, a psychiatric drug used to stabilize mood shifts, can ease the symptoms of spinocerebellar ataxia type 1, an inherited neurodegenerative disorder. Their research article was published on May 28, 2007, in the journal Public Library of Science (PLoS) Medicine. "The results are very exciting," said Zoghbi. "It's really hard to improve multiple symptoms (in a condition). Lithium seems to improve several in this case, not just one." The new findings are important because they suggest it may be possible to use the drug to alleviate deteriorations in motor coordination, learning and memory manifested by the spinocerebellar ataxia. At present, treatments for the condition are limited and patients, who are usually diagnosed in their thirties or forties, experience a gradual decline in motor and memory function and die within a few years of onset of the disease. © 2007 Howard Hughes Medical Institute.
When a faulty protein wreaks havoc in cells and causes disease, researchers are usually quick to point the finger at a wayward gene. Now scientists are learning that some neurodegenerative diseases can develop even though a gene is perfectly normal. The diseases can be caused when the genetic instructions contained in the gene are not executed properly, leading to a lethal buildup of malformed proteins in brain cells. The new studies by Howard Hughes Medical Institute (HHMI) investigator Susan L. Ackerman and colleagues at The Jackson Laboratory point to a novel mechanism behind the buildup of the toxic sludge that accumulates in neurons. Researchers have long known that neurodegenerative disorders can be caused by the gradual yet persistent accumulation of misfolded proteins in neurons that eventually triggers cell death. But this new mechanism points to errors in executing the genetic instructions, which are distinct from known causes of neurodegenerative diseases, such as Alzheimer's and Huntington's diseases. HHMI investigator Susan L. Ackerman and her colleagues reported their findings in an advance online publication of the journal Nature on August 13, 2006. Ackerman's group collaborated on the studies with co-author Paul Schimmel at The Scripps Research Institute. The researchers made their discovery by studying mice with a mutation called sticky (sti). Although named for the sticky appearance of their fur, the mice harbor much more serious problems beneath their unkempt coats: poor muscle control, or ataxia, due to death of Purkinje cells in a region of the brain called the cerebellum. © 2006 Howard Hughes Medical Institute.
Howard Hughes Medical Institute (HHMI) researchers have discovered a critical function for a protein involved in spinal muscular atrophy (SMA), the number one genetic killer of children under the age of two. The disease is caused when a key protein loses its ability to promote the survival and vigor of motor neurons. According to the Families of Spinal Muscular Atrophy organization, spinal muscular atrophy affects 1 in 6,000 newborns, causing progressive muscle weakness, wasting, or atrophy as motor neurons degenerate. August is National Spinal Muscular Atrophy Awareness Month. In an article published in the July 21, 2006, issue of the journal Molecular Cell, researchers led by Gideon Dreyfuss, a Howard Hughes Medical Institute investigator at the University of Pennsylvania School of Medicine, report that they now know the identity of a protein that is crucial for recognizing specific RNA molecules needed to process genetic information inside the cell. This process breaks down in people who have SMA. In 1994, researchers discovered that the gene, survival of motor neurons (Smn), is deleted or mutated in people with SMA. This observation strongly suggested that reduced levels of or mutations in the SMN protein cause spinal muscle atrophy. Dreyfuss and his colleagues subsequently showed that the SMN protein is needed by all cells to produce messenger RNA (mRNA). Production of mRNA is a critical step in gene expression, and ultimately, in the production of functional proteins. Specifically, the SMN protein plays a crucial role in the genesis of mRNA from a precursor called pre-mRNA. The conversion of pre-mRNA to mRNA takes place in the cell nucleus during a process called splicing. © 2006 Howard Hughes Medical Institute.
By Rossella Lorenzi, Discovery News Abraham Lincoln may have carried a genetic mutation responsible for the neurological disorder ataxia, according to U.S. researchers who screened descendants of the 16th president. Laura Ranum, a genetics professor at the University of Minnesota, and colleagues discovered that a type of ataxia, called Spinocerebellar ataxia type 5 (SCA5), is linked to a mutation in an amino-acid protein which plays an important role in maintaining the health of nerve cells. The gene breakthrough was made thanks to DNA from the Lincoln family: the researchers identified the mutation in an 11-generation family descended from the president's paternal grandparents, Capt. Abraham Lincoln and Bathsheba Herring. Overall, Ranum examined and collected DNA samples from 299 Lincoln family members and found that about a third have ataxia. "We are excited about this discovery because it provides a genetic test that will lead to improved patient diagnoses and gives us new insight into the causes of ataxia and other neurodegenerative diseases, an important step towards developing an effective treatment," Ranum said in a statement. © 2006 Discovery Communications Inc.
By RANDOLPH E. SCHMID WASHINGTON -- A new method of slowing the most common inherited nerve disease may point the way for novel treatments for nerve disorders. Researchers working with rats retarded the progression of CMT, which gradually reduces the ability to use the arms and legs and affects about one in 2,500 Americans. The team found success using a chemical that blocks a protein associated with more than half of all cases of CMT. People with the most common form of CMT have a genetic defect that causes overproduction of that protein. Copyright © 2003, The Associated Press
Possible link between this orphan disease and neurodegenerative disorders considered | By Brendan A. Maher A movement disorder can start as a twinge. A child's leg turns in while walking. Writing becomes difficult, painful. For many, these types of diseases--broadly termed dystonias--progress no further than persistent muscle cramps. Yet in many children affected by rare, heritable, early-onset dystonia, a generalized movement disorder called torsion dystonia develops as well. The disorder can affect the entire body: Opposing muscles work against each other, twisting the posture, causing repetitive movements, or contorting arms and legs into unnatural positions. Oftentimes, the earlier in life symptoms appear, the worse they get. To uncover the roots of this dominant trait, which has only 30% to 40% penetrance, researchers spent more than 15 years studying afflicted, diverse families and a population of Ashkenazi Jews to zero in on a responsible mutation: a three-basepair deletion in DYT1 that appears exactly the same across ethnic groups.1 Recent efforts to elucidate the function for torsinA--the protein this gene encodes--reveal that torsins may act as molecular chaperones, altering protein folding and clearing aggregates from living cells. In worms, torsins alleviate engineered poly-glutamine clumps,2 and in cell culture, torsinA suppresses a-synuclein aggregation.3 These results and others reveal ties to troublesome neurodegenerative disorders such as Parkinson, Huntington, and Alzheimer disease. Protein aggregates are hallmarks of these diseases, but their role remains controversial. Likewise, torsinA's role in clearing the aggregates is murky, and such clumps are not even found in patients with dystonia. Yet, some draw parallels between torsion dystonia and Parkinson disease: Uncontrollable movements are common to both, and some treatments, including deep-brain stimulation, seem to ameliorate symptoms, even though dystonia is not a neurodegenerative disease. ©2003, The Scientist Inc.