Promising new finding for therapies to treat persistent seizures in epileptic patients

In a promising finding for epileptic patients suffering from persistent seizures known as status epilepticus, researchers reported today that new medication could help halt these devastating seizures. To do so, it would have to work directly to antagonize NMDA receptors, the predominant molecular device for controlling synaptic activity and memory function in the brain.

"Despite the development of new medications to prevent seizures, status epilepticus remains a life-threatening condition that can cause extensive brain damage in the patients that survive these persistent seizures," said David E. Naylor, MD, PhD, a lead researcher at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) and corresponding author of the new study. "Our research holds promise for the development of new therapies to treat this devastating condition because we have found a potential new target for medical intervention that should bolster the current standard therapies to treat the acute seizures. It may also prevent the long-term adverse effects of persistent seizure activity on the brain."

The research, reported online in the Neurology of Disease journal, used animal models to assess cellular activity in the brain during persistent seizures. It found that the seizure activity seemed to force the NMDA receptors from the interior to the surface of nerve cells causing their activity to increase by approximately 38%.

"The increased presence of the NMDA receptors on the cell surface during these seizures may explain the successful use of NMDA antagonists – medication that inhibits the activity of the NMDA receptors in the brain – in the latter stages of a seizure, long after other medications have stopped working," said Dr. Naylor. "We concluded that medications that suppress the activity of the NMDA receptors, in conjunction with other medications, may be successful in stopping persistent seizures. Further research is, of course, needed."

Innovative system for the rehabilitation of people with brain damage

The Biomechanics Institute of Valencia (IBV) is currently taking part in the European project WALKX with the aim of developing an innovative rehabilitation system to improve the quality of life of people who have suffered brain damage. This system will allow home rehabilitation and improve patient’s autonomy.

WALKX is a two-year research project for the benefit of small and medium sized enterprises (SMEs), co-funded by the European Commission through the Seventh Framework Programme.

The user friendly walking training device the partners are designing will support the patient in raising from sitting to standing position and enable the patient to perform walking training and improve his/her manoeuvrability. “An upper body stabilizing and controllable supporting vest will be developed. Early in the rehabilitation process it will be used under supervision of a therapist, but with greatly reduced need for physical support from the therapists. This is intended to reduce the need for help from others and increase freedom of movement and personal autonomy of the patient”, said Ignacio Bermejo, Market Innovation Director at IBV.

One of the novelties of this device consists of a vest with attachment points on the patient’s waist in order to regulate the mobility of the trunk. Also, the device will be modular and low cost. The role of IBV in this initiative has been to define the design specifications and preclinical testing to validate the prototype. Preclinical tests are done in collaboration with the Department of Physical Medicine and Rehabilitation at the Hospital Universitari i Politècnic La Fe of Valencia.

The project is coordinated by the Norwegian company Made for Movement Group. Besides Biomechanics Institute, other members of the consortium are Innovatsiooni Eesti Instituut (Estonia), INNORA ROBOTICS (Greece), Newtrim and MCT (UK), ENIX (France), Motus (Italy) and MOBILE ROBOTICS SWEDEN (Sweden).

Stroke (cerebrovascular accident) is the most common cause of adult disability in Europe. Roughly 75% of victims survive, but about half of these lose the ability to live independently in their own home. As strokes often result in long term disability rather than death, the rehabilitation and hospitalisation represent a major economic burden for the EU of about €34 Bn annually. Currently, the annual incidence is approximately 2 per 1,000 inhabitants in the EU, and the number is predicted to double over the next 50 years due to the aging of the population.

Rainfall, brain infection linked in sub-Saharan Africa

The amount of rainfall affects the number of infant infections leading to hydrocephalus in Uganda, according to a team of researchers who are the first to demonstrate that these brain infections are linked to climate.

Hydrocephalus — literally “water on the brain” — is characterized by the buildup of the fluid that is normally within and surrounding the brain, leading to brain swelling. The swelling will cause brain damage or death if not treated. Even if treated, there is only a one-third chance of a child maintaining a normal life after post-infectious hydrocephalus develops, and that chance is dependent on whether the child has received the best treatment possible.

"The most common need for a child to require neurosurgery around the world is hydrocephalus," said Steven J. Schiff, the Brush Chair Professor of Engineering, director of the Penn State Center for Neural Engineering and a team member.

In sub-Saharan Africa, upward of 100,000 cases of post-infectious hydrocephalus a year are estimated to occur. The majority of these cases occur after a newborn has suffered from neonatal sepsis, a blood infection that occurs within the first four weeks of life, the researchers reported in a recent issue of the Journal of Neurosurgery: Pediatrics.

Benjamin C. Warf, associate professor of neurosurgery, Harvard Medical School, Boston Children’s Hospital, noticed that about three or four months after an infant in East Africa had an infection like neonatal sepsis, the child would often return to the clinic with a rapidly growing head — hydrocephalus. Schiff joined Warf to help figure out what caused this disease so frequently.

Schiff and colleagues tracked 696 hydrocephalus cases in Ugandan infants between the years 2000 and 2005. The researchers obtained localized rainfall data for the same time frame through NOAA (National Oceanic and Atmospheric Administration) weather satellites using the African Rainfall Estimation Algorithm developed at the U.S. NOAA Climate Prediction Center.

Uganda has two peak rainfall seasons, in spring and fall. By comparing the data from NOAA and the hydrocephalus cases, the researchers found that instances of the disorder rose significantly at four different times throughout the year — before and after the peak of each rainy season, when the amount of rainfall was at intermediate levels. In Uganda an intermediate rainfall is about 6 inches of rain per month.

Schiff and colleagues previously noted that different bacteria appear associated with post-infectious hydrocephalus at different seasons of the year. While the researchers have not yet characterized the full spectrum of bacteria causing hydrocephalus in so many infants, they note that environmental conditions affect conditions supporting bacterial growth, and that the amount of rain can quench bacterial infections. The moisture level clearly affects the number of cases of hydrocephalus in this region of East Africa.

"Hydrocephalus is the first major neurosurgical condition linked to climate," said Schiff, who is also professor of neurosurgery, engineering science and mechanics, and physics, and a faculty member of the Huck Institutes of the Life Sciences. "This means that a substantial component of these cases are almost certainly driven from the environmental conditions, and that means they are potentially preventable if we understand the routes and mechanisms of infection better."

Mild brain cooling after head injury prevents epileptic seizures in lab study

Mild cooling of the brain after a head injury prevents the later development of epileptic seizures, according to an animal study reported this month in the Annals of Neurology.

Epilepsy can result from genetics or brain damage. Traumatic head injury is the leading cause of acquired epilepsy in young adults. It is often difficult to manage with antiepileptic drugs. The mechanisms  behind the onset of epileptic seizures after brain injury are not known . There is currently no treatment to cure it, prevent it, or even limit its severity.

The multi-institutional research team used a rodent model of acquired epilepsy in which animals develop chronic spontaneous recurrent seizures -the hallmark of epilepsy- after a contusive head injury similar to that causing epilepsy in humans. The rats were randomized to either mock-cooling or cooling of the contused brain by no more than 2 Celsius degrees. This degree of cooling, the authors explained, is known to be safe and to decrease mortality of patients with head injury.  The rats  were then monitored for four months after injury and epilepsy was evaluated by intracranial EEG. The contused brain was cooled continuously with special headsets engineered to passively dissipate heat. No Peltier cells or other power sources for refrigeration were needed.

The investigators report that cooling by just 2 degrees celsius for 5 weeks beginning 3 days after injury virtually abolished the later development of epileptic seizure activity. This effect persisted through the end of the study. The treatment induced no additional pathology or inflammation, and restored neuronal activity depressed by the injury.

“These findings demonstrate for the first time that prevention of epileptic seizures after traumatic brain brain injury is possible, and that epilepsy prophylaxis in patients could be achieved more easily than previously thought, said  the lead author of the study,  Raimondo D’Ambrosio, UW associate professor of neurological surgery.  He added that a clinical trial is required to verify the findings in head injury patients.

Silent stroke can cause Parkinson’s disease

Scientists at The University of Manchester have for the first time identified why a patient who appears outwardly healthy may develop Parkinson’s disease.

Whilst conditions such as a severe stroke have been linked to the disease, for many sufferers the tremors and other symptoms of Parkinson’s disease can appear to come out of the blue. Researchers at the university’s Faculty of Life Sciences have now discovered that a small stroke, also known as a silent stroke, can cause Parkinson’s disease. Their findings have been published in the journal “Brain Behaviour and Immunity”.

Unlike a severe stroke, a silent stroke can show no outward symptoms of having taken place. It happens when a blood vessel in the brain is blocked for only a very short amount of time and often a patient won’t know they have suffered from one. However, it now appears one of the lasting effects of a silent stroke can be the death of dopaminergic neurons in the substantia nigra in the brain, which is an important region for movement coordination.

Dr. Emmanuel Pinteaux led the research: “At the moment we don’t know why dopaminergic neurons start to die in the brain and therefore why people get Parkinson’s disease. There have been suggestions that oxidative stress and aging are responsible. What we wanted to do in our study was to look at what happens in the brain away from the immediate area where a silent stroke has occurred and whether that could lead to damage that might result in Parkinson’s disease.”

The team induced a mild stroke similar to a silent stroke in the striatum area of the brain in mice. They found there was inflammation and brain damage in the striatum following the stroke, which they had expected. What the researchers didn’t expect was the impact on another area of the brain, the substantia nigra. When they analysed the substantia nigra they recorded a rapid loss of Substance P (a key chemical involved in its functions) as well as inflammation.

The team then analysed changes in the brain six days after the mild stroke and found neurodegeneration in the substantia nigra. Dopaminergic neurones had been killed.

Talking about the findings Dr Pinteaux said: “It is well known that inflammation following a stroke can be very damaging to the brain. But what we didn’t fully appreciate was the impact on areas of the brain away from the location of the stroke. Our work identifying that a silent stroke can lead to Parkinson’s disease shows it is more important than ever to ensure stroke patients have swift access to anti-inflammatory medication. These drugs could potentially either delay or stop the on-set of Parkinson’s disease.”

Dr Pinteaux continued: “What our findings also point to is the importance of maintaining a healthy lifestyle. There are already guidelines about exercise and healthy eating to help reduce the risk of having a stroke and our research suggests that a healthy lifestyle can be applied to Parkinson’s disease as well.”

Following the publication of these findings, Dr Pinteaux hopes to set up a clinical investigation on people who have had a silent stroke to assess dopaminergic neuron degeneration. In the meantime he will be working closely will colleagues at The University of Manchester to better understand the mechanisms of inflammation in the substantia nigra. 

Study Details Brain Damage Triggered by Mini-Strokes

A new study appearing today in the Journal of Neuroscience details for the first time how “mini-strokes” cause prolonged periods of brain damage and result in cognitive impairment. These strokes, which are often imperceptible, are common in older adults and are believed to contribute to dementia. 

“Our research indicates that neurons are being lost as a result of delayed processes following a mini-strokes that may differ fundamentally from those of acute ischemic events,” said Maiken Nedergaard, M.D., D.M.Sc., the lead author of the study and professor of Neurosurgery at the University of Rochester Medical Center (URMC). “This observation suggests that the therapeutic window to protect cells after these tiny strokes may extend to days and weeks after the initial injury.”

The prevalence of mini-strokes, or microinfarcts, has only been recently appreciated because common imaging techniques, such as MRI, are typically not sensitive enough to detect these microscopic injuries.

Similar to severe ischemic strokes, mini-strokes are caused when blood flow is blocked to a small area of the brain, usually by particle that travelled there from another part of the body. But unlike acute ischemic strokes – which bring about immediate symptoms such as numbness, blurry vision, and slurred speech – mini-strokes usually pass without notice. However, it is increasingly appreciated that these smaller strokes have a lasting impact on neurological function.

Microinfarcts are far more common than previously understood; it is believed that about 50 percent of individuals over the age of 60 have experienced at least one mini-stroke. Studies have also correlated the presence of mini-strokes with the symptoms of dementia. An estimated 55 percent of individuals with mild dementia and upwards of 70 percent of individuals with more severe symptoms show evidence of past mini-strokes. This association has led researchers to believe that these mini-strokes may be key contributors to age-related cognitive decline and dementia.

Nedergaard and her colleagues were the first to develop an animal model in which the complex progression and, ultimately, the cognitive impact of mini-strokes could be observed. Her team found that, in most instances, these strokes result in a prolonged period of damage to the brain.

Brain-damaged man ‘aware’ of scientists’ questions

A crash victim thought to have been in a vegetative state for more than a decade has used the power of thought to tell scientists he is not in pain.

Canadian Scott Routley, from London, Ontario, communicated with researchers via a brain scan, proving that he is conscious and aware. It is the first time such a severely brain-damaged patient has been able to provide clinically relevant information to doctors.

British neuroscientist Professor Adrian Owen, who leads the research team at the Brain and Mind Institute of Western Ontario, said: “Scott has been able to show he has a conscious, thinking mind. We have scanned him several times and his pattern of brain activity shows he is clearly choosing to answer our questions. We believe he knows who and where he is.”

Prof Owen was speaking on a BBC Panorama programme to be broadcast on Tuesday night.

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OHSU researchers discover how enzyme may prevent nervous system repair in multiple sclerosis

Discovery could be ‘life-changer’ for millions with MS, stroke and other conditions that cause brain damage

Researchers at Oregon Health & Science University have discovered that blocking a certain enzyme in the brain can help repair the brain damage associated with multiple sclerosis and a range of other neurological disorders.

The discovery could have major implications for multiple sclerosis, complications from premature birth and other disorders and diseases caused by demyelination – a process where the insulation-like sheath surrounding nerve cells in the brain becomes damaged or destroyed. Demyelination disrupts the ability of nerve cells to communicate with each other, and produces a range of motor, sensory and cognitive problems in MS and other disorders.

The study was published this week in the online edition of the Annals of Neurology. The study was conducted by a team of researchers led by Larry Sherman, Ph.D., who is a professor of cell and development biology at OHSU and a senior scientist in the Division of Neuroscience at the Oregon National Primate Research Center.

"What this means is that we have identified a whole new target for drugs that might promote repair of the damaged brain in any disorder in which demyelination occurs," Sherman said. "Any kind of therapy that can promote remyelination could be an absolute life-changer for the millions of people suffering from MS and other related disorders."

High blood pressure damages the brain in early middle age

Uncontrolled high blood pressure damages the brain’s structure and function as early as young middle-age, and even the brains of middle-aged people who clinically would not be considered to have hypertension have evidence of silent structural brain damage, a study led by researchers at UC Davis has found.

The investigation found accelerated brain aging among hypertensive and prehypertensive individuals in their 40s, including damage to the structural integrity of the brain’s white matter and the volume of its gray matter, suggesting that vascular brain injury “develops insidiously over the lifetime with discernible effects.”

The study is the first to demonstrate that there is structural damage to the brains of adults in young middle age as a result of high blood pressure, the authors said. Structural damage to the brain’s white matter caused by high blood pressure previously has been associated with cognitive decline in older individuals.

Published online today in the medical journal The Lancet Neurology, the study will appear in print in the December 2012 issue. It emphasizes the need for lifelong attention to vascular risk factors for brain aging, said study senior author Charles DeCarli, professor of neurology and director of the UC Davis Alzheimer’s Disease Center.