Advance in understanding complex region pain syndrome
A study has discovered that changes in the brain's white matter may account for many of the features associated with a chronic pain condition, and may pave the way for new treatment modalities
Recent brain examinations of people with complex region pain syndrome (CRPS) have revealed some very interesting findings that may help us to understand this mysterious condition. Scientists from Northwestern University's Feinberg School of Medicine (IL, USA), found that people affected with CRPS have had certain areas of their brains rewired, including areas related to emotion, pain perception and skin temperature.
Complex region pain syndrome is a chronic pain condition that affects approximately 200,000 people in the USA. It usually affects the hands, feet, elbows or knees, and normally begins with an injury that causes significant damage to the affected area. In the majority of people, the pain disappears once the limb is healed, but for 5% of patients the pain continues for a long time after, sometimes for the remainder of the person's life. It may also spread to other regions of the body. Other previously unexplainable features associated with this disorder include changes in skin color to blue or red, changes in skin temperature – initially an increase in temperature then a decrease overtime as the condition becomes chronic – and an increase in blood immune markers, which signifies an overdrive in the immune system.
The study involved the examination of 44 people (22 with CRPS and 22 control subjects) with an anatomical MRI and a diffusion tensor MRI, which enabled scientists to view the white matter. The team of scientists found that in people affected by CRPS, changes were seen in the brain's white matter. Researchers from the same institution have previously discovered that chronic pain caused gray matter to atrophy but this is the first study to link pain with changes in the brain's white matter. The CRPS patients’ brains also showed atrophy in the gray matter.
A Vania Apkarian, the principal investigator of the study, says: “This is the first evidence of brain abnormality in these patients. People didn't believe these patients. This is the first proof that there is a biological underpinning for the condition. Scientists have been trying to understand this baffling condition for a long time.”
The cause and effect of the changes in the white matter is not yet known; more work needs to be done to establish whether it is the chronic pain that causes the changes in the brain or if CRPS patients’ brains have pre-existing abnormalities that predispose them to this condition. However, with this discovery, scientists now have anatomical targets and can begin to search for pharmaceutical treatments to help these patients.
According to Apkarian, the white matter changes in the patients’ brains with CRPS are related to the duration and intensity of their pain and their anxiety. These findings are likely to result in the testing of white matter changes in other chronic pain conditions.
Sources: Northwestern University, IL, USA www.northwestern.edu; Geha PY, Baliki MN, Harden RN, Bauer WR, Parrish TB, Apkarian AV: The brain in chronic CRPS pain: abnormal gray–white matter interactions in emotional and autonomic regions. Neuron 60(4), 570–581 (2008).
Could anti-inflammatory therapies be used to treat schizophrenia?
Association between cerebral inflammation and the development of schizophrenia found: anti-inflammatory agents or targeting microglia may be used as potential therapies for this disease
Researchers at the Rudolf Magnus Institute for Neuroscience, The Netherlands, have found an association between cerebral inflammation and the development of schizophrenia. Using positron emission tomography (PET), the researchers investigated whether microglia activation, which is associated with an inflammatory state, occurs in patients with recent-onset schizophrenia.
Investigators examined ten patients with recent-onset schizophrenia and compared them to ten age-matched healthy control individuals. A (R)-[11C]PK11195 PET scan was performed on all subjects involved in the study. The results showed increased binding levels of [11C]PK11195, which is a radiotracer with high affinity for the peripheral benzodiazepine receptor (PBR), in patients who had been diagnosed with schizophrenia for 5 years or less. Activated microglia have higher levels of PBR, thus quantifying PBR is a good indication of assessing whether cerebral inflammation is present.
van Berckel and Kahn explain: “It was found that microglia activation is present in schizophrenia patients early after disease onset, suggesting brain cells are damaged in schizophrenia. In addition, since microglia can have either a protective or a toxic role, activated microglia may be the result, but also the cause of damage to brain cells.”
These data seem to suggest that inflammation may contribute to the early development of schizophrenia, meaning that anti-inflammatory agents may be used as a potential therapy. Targeting microglia may also be another strategy in treating this disease.
However, John H. Krystal, M.D., Editor of Biological Psychiatry stresses, “It will be important to understand whether this process takes place in a special way in association with the first onset of symptoms or whether inflammation is more generally a process that contributes to worsening of symptoms.” Further work will be needed to better understand the inflammatory mechanism underlying schizophrenia, nevertheless the work done by van Berckel and Kahn provides researchers with some clues into the mechanism of this disease.
Sources: van Berckel BN, Bossong MG, Boellaard R et al.: Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol. Psychiatry 64(9), 820–822 (2008);
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Study finds epilepsy drug may increase chance of autistic children
A study from the Liverpool and Manchester Neurodevelopment Group, UK, has identified a link between taking the epilepsy drug valproate in pregnancy and an increased chance of the child developing autism.
In an ongoing study involving 632 children, 249 were exposed to epilepsy drugs during gestation. A total of 64 children were exposed to valproate, 44 to lamotrigine, 76 to carbamazepine and 65 to other epilepsy drugs. The children were tested at 1, 3 and 6 years old and, to date, nine have been diagnosed with autism and one has shown symptoms of the disorder. None of the children in the study had any known familial history of autism.
It was found that seven of the nine children diagnosed with autism had mothers who took an epilepsy drug while pregnant. Of those, four had taken valproate and a fifth had taken a combination of valproate and lamotrigine. Thus, from the results of this study, children who were exposed to valproate during pregnancy were seven times more likely to develop autism than children whose mothers had not taken any epilepsy drug while pregnant. Furthermore, this risk was not seen with any of the other epilepsy drugs.
Study author Gus Baker concludes, “The potential risk for autism in this study was substantial for children whose mothers took valproate while pregnant, but more research needs to be done since these are early findings. However, women who take valproate while pregnant should be informed of the possible risks of autism and are encouraged to discuss them with their doctor. Those who are taking valproate should not stop their treatment without speaking to their doctor first.”
Valproate has previously been shown to increase the likelihood of birth defects more than other epilepsy drugs.
Source: Bromley RL, Mawer G, Clayton-Smith J, Baker GA; on behalf of the Liverpool and Manchester Neurodevelopment Group: Autism spectrum disorders following in uteroexposure to antiepileptic drugs. Neurology 71, 1923–1924 (2008).
New evidence shows that antiseizure drug, propofol, could be fatal
Researchers from the Mayo clinic in Rochester, MN, USA, have found that treatment with the antiseizure drug propofol may significantly increase morbidity and mortality in patients. Propofol is used as an antiepileptic in patients suffering from refractory status epilepticus (RSE) and is also used as a sedative during surgery.
“Patients with RSE treated with propofol are at high risk for propofol-related side effects because of the high propofol infusion rates and prolonged treatment duration necessary in these patients,” said Vivek Iyer, MD of the Mayo Clinic, “However, it is well described that propofol toxicity can occur even with brief exposure to the drug.”
Iyer and his research team wanted to investigate any complications/side effects associated with propofol use, such as propofol infusion syndrome (PRIS). PRIS is a usually fatal complication linked to propofol use and is commonly seen in patients that have been administered propofol at high infusion rates for long periods of time. In the analysis conducted by Iyer and his colleagues, 39 RSE patients were divided into two groups. In group A, 32 of the patients (82%) were treated with propofol for a median of 63 h and a median peak infusion rate of 67 mcg/kg/min whereas the other seven patients (18%) in group B were administered agents such as midazolam and pentobarbital. Upon analysis, it was found that 30% of patients in the propofol-treated group showed signs of PRIS (seven cases of bradycardia and three cases of sudden unexplained cardiac arrest); however, only one case of bradycardia was reported in group B. Furthermore, group A showed no obvious benefits with regards to seizure control.
The researchers concluded from these results that administration of propofol was linked to a significant increase in mortality and morbidity and thus should be used with caution when treating patients with RSE.
“There are several other medications we can turn to in the case of uncontrolled seizures,” Iyer stated. “Alternative agents should first be tried for patients with RSE and propofol should only be used after exhausting all other options.”
Sources: Iyer VN, Hoel R, Rabinstein AA: Propofol infusion syndrome in patients with refractory status epilepticus: a 10-year clinical experience. Presented at: CHEST 2008, the 74th Annual International Scientific Assembly of the American College of Chest Physicians. Philadelphia, PA, USA, 25–30 October 2008 (Abstract AP2328); Science Daily: www.sciencedaily.com/releases/2008/10/081028074315.htm