Category Archives: Medical Research

Epilepsy Drug Therapies To Be Improved by New Targeted Approach

Via: Neuroscience News

Source: University of Liverpool

New research from the University of Liverpool, in collaboration with the Mario Negri Institute in Milan, published today in the Journal of Clinical Investigation, has identified a protein that could help patients with epilepsy respond more positively to drug therapies.

Epilepsy continues to be a serious health problem and is the most common serious neurological disease. Despite 30 years of drug development, approximately 30% of people with epilepsy do not become free of fits (also called seizures) with currently available drugs.

New, more effective drugs are therefore required for these individuals. We do not fully understand why some people develop seizures, why some go onto develop epilepsy (continuing seizures), and most importantly, why some patients cannot be controlled with current drugs.

Inflammation

There is now increasing body of evidence suggesting that local inflammation in the brain may be important in preventing control of seizures. Inflammation refers to the process by which the body reacts to insults such as having a fit. In most cases, the inflammation settles down, but in a small number of patients, the inflammation continues.

The aim of the research, undertaken by Dr Lauren Walker while she was a Medical Research Council (MRC) Clinical Training Fellow, was to address the important question of how can inflammation be detected by using blood samples, and whether this may provide us with new ways of treating patients in the future to reduce the inflammation and therefore improve seizure control.

The research focused on a protein called high mobility group box-1 (HMGB1), which exists in different forms in tissues and bloodstream (called isoforms), as it can provide a marker to gauge the level of inflammation present.

Predicting Drug Response

The results showed that there was a persistent increase in these isoforms in patients with newly-diagnosed epilepsy who had continuing seizure activity, despite anti-epileptic drug therapy, but not in those where the fits were controlled.

An accompanying drug study also found that HMGB1 isoforms may predict how an epilepsy patient’s seizures will respond to anti-inflammatory drugs.

Dr Lauren Walker, said: “Our data suggest that HMGB1 isoforms represent potential new drug targets, which could also identify which patients will respond to anti-inflammatory therapies. This will require evaluation in larger-scale prospective trials.”

Innovative Scheme

Professor Sir Munir Pirmohamed, Director of the MRC Centre for Drug Safety Science and Programme lead for the MRC Clinical Pharmacology scheme, said: “The MRC Clinical Pharmacology scheme is a highly successful scheme to train “high flyers” who are likely to become future leaders in academia and industry.

“Dr Walker’s research is testament to this and shows how this innovative scheme, which was jointly funded by the MRC and Industry, can tackle areas of unmet clinical need, and identify new ways of treating patients with epilepsy using a personalised medicine approach”.

Children with Cerebral Palsy May Require More Pain Management, Study Says

Via: Cerebral Palsy News Today

By: Patricia Inacio

Children with cerebral palsy (CP) often have pain that is overlooked by therapists and caregivers, a new study found. This pain frequently has articular (joints) and orthopedic origins, and can be linked to scoliosis and therapies for spasticity, among other causes.

The report, “Prevalence of pain in 240 non-ambulatory children with severe cerebral palsy,” was published in the journal Annals of Physical and Rehabilitation Medicine.

Assessing the level of pain in children with CP is important because it occurs frequently and can be aggravated by care. Previous studies have reported the varying frequency of pain in children with CP, but comparing the results of these studies is difficult, the authors stated.

Researchers set out to “estimate the prevalence of pain among a homogeneous population of young and non-ambulatory children with CP and to identify the factors associated with a high risk of pain.”

The team analyzed data from an ongoing clinical trial (NCT01840930) with non-ambulatory children with CP, ages 3 to 10. Researchers determined if pain was present by directly posing two questions to the child and the child’s family, as long as the patient could communicate and understand the questions.

“We also asked whether the child was given analgesics occasionally, which represented a way to better detect the criterion ‘presence of pain,’” researchers wrote.

The level of pain was assessed via a visual analog scale for children able to communicate and with the Douleur Enfant San Salvadour (DESS) scale, a specific measurement for non-communicating children.

In total, 240 children were included in the analysis (107 girls and 133 boys).

Overall, 65 children experienced pain for an estimated pain prevalence of 27.1%. The pain in all of these children was orthopedic in origin. Twenty-six children (45.6%) also experienced pain of another origin.

Regarding pain care, 47.4% of the children were occasionally given analgesics.

“The most frequent pain sites were the hips (43.4%) and the feet (26.9%). The circumstances of pain were joint mobilization in 35/60 children (58.3%). The sitting position was mentioned as painful for 6/58 children (10.3%),” the researchers wrote.

Moreover, the team found that pain increased with scoliosis (43.1% versus 24.1%, with and without pain, respectively) and spasticity treatment (32.3% versus 17.2%, respectively). Scoliosis is a term that describes an abnormal, side-to-side curvature of the spine. Spasticity is a condition in which certain muscles are continuously contracted.

The study suggests that children with CP are often burdened with pain, particularly articular and orthopedic pain. This is often overlooked by caregivers.

“We point to the importance of systematically evaluating pain in these children, especially by therapists and caregivers, as a recommendation or at least as questioning. The treatment of pain should begin as soon as possible, to prevent not only the excentration of hips but also deformation of feet and scoliosis,” the team concluded.

Spare the Surgery: Drugs may Combat Hydrocephalus, Yale Study Finds

Via: MDLinx.com

Information courtesy Yale School of Medicine News

Clinically available drugs may help combat a potentially lethal form of hydrocephalus now treated mainly by brain surgery, a new Yale–led study has found.

Post–hemorrhagic hydrocephalus (PHH), characterized by a buildup of cerebrospinal fluid (CSF) following hemorrhage of blood vessels in the brain, affects one in a thousand children and is currently treated almost exclusively by the surgical insertion of shunts in the brain.

“Shunts, like any hardware implant, are particularly susceptible to malfunction and infection, and therefore often require patients over the course of their lives to go back to the operating room numerous times,” said Dr. Kristopher T. Kahle, assistant professor of neurosurgery, pediatrics, and cellular & molecular physiology and senior author of the study published July 10 the journal Nature Medicine. “This is really a devastating problem for kids and their families so there is a great need for a pharmacological solution for a condition historically treated only by invasive neurosurgery.”

The most common explanation for this form of hydrocephalus is a failure of the brain to reabsorb cerebrospinal fluid due to clotting of blood or scarring of tissue. However, this model was based on little experimental evidence and new research shows that blood buildup triggers inflammation of the choroid plexus, a group of cells that produce CSF, and can cause an increase in CSF secretion. This can result in an increase in both CSF volume and intracranial pressure.

In work with an animal model of PHH, the Yale team – led by Kahle, also the director of Developmental Anomaly Neurosurgery at Yale–New Haven Hospital, and student Jason Karimy – showed that an approved diuretic and another drug originally designed to treat sepsis can mitigate this immune system response and reduce the secretion of CSF in the brain.

Researchers plan to pursue further pre–clinical studies and then launch a small clinical trial to see if a drug regimen and help reduce need for surgical interventions in patients with PHH due to brain bleeding after aneurysm rupture.

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