Posts tagged globus pallidus
Articles and news from the latest research reports.
Deep Brain Stimulation Improves Non Motor Symptoms in Parkinson’s Disease as well as Motor Symptoms
Deep brain stimulation (DBS) has become a well-recognized non-pharmacologic treatment that improves motor symptoms of patients with early and advanced Parkinson’s disease. Evidence now indicates that DBS can decrease the number and severity of non motor symptoms of patients with Parkinson’s disease (PD) as well, according to a review published in the Journal of Parkinson’s Disease.
“Non motor features are common in PD patients, occur across all disease stages, and while well described, are still under-recognized when considering their huge impact on patients’ quality of life,” says Lisa Klingelhoefer, MD, a fellow at the National Parkinson Foundation International Centre of Excellence, Department of Neurology, King’s College Hospital and King’s College, London.
For example, DBS of the subthalamic nucleus (STN) is effective for alleviating sleep problems and fatigue associated with PD, producing noticeable long-term improvements in sleep efficiency and the quality and duration of continuous sleep. DBS also decreases nighttime and early morning dystonia and improves nighttime mobility. “DBS can contribute to better sleep, less daytime somnolence, improved mobility, and less need for dopamine replacement therapy,” says Dr. Klingelhoefer.
The effects of DBS on some other non motor symptoms of PD are less clear cut and transient worsening of neuropsychological and psychiatric symptoms have been reported. For instance, behavioral disorders such as impulsivity (e.g. hypersexuality, pathological gambling, and excessive eating) can occur or worsen in PD patients after STN DBS. While pre-existing drug-induced psychotic symptoms like hallucinations often disappear after STN DBS, transient psychotic symptoms such as delirium may emerge in the immediate post-operative period. Similarly, conflicting reports have found that STN DBS improves, worsens, or does not change mood disorders such as depression, mania, or anxiety.
“Further work is required in order to fully understand the mechanisms and impact of DBS of the STN or other brain structures on the non motor symptoms of PD,” concludes Dr. Klingelhoefer. She suggests that in the future, non motor symptoms of PD may become an additional primary indication for DBS.
PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most characteristic symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non motor symptoms, such as worsening depression, anxiety, olfactory dysfunction, sweating, bladder and bowel dysfunction, and sleep disturbances, can appear prior to the onset of motor symptoms.
3-D Computer Model May Help Refine Target for Deep Brain Stimulation Therapy for Dystonia
Although deep brain stimulation can be an effective therapy for dystonia – a potentially crippling movement disorder – the treatment isn’t always effective, or benefits may not be immediate. Precise placement of DBS electrodes is one of several factors that can affect results, but few studies have attempted to identify the “sweet spot,” where electrode placement yields the best results.
Researchers led by investigators at Cedars-Sinai, using a complex set of data from records and imaging scans of patients who have undergone successful DBS implantation, have created 3-D, computerized models that map the brain region involved in dystonia. The models identify an anatomical target for further study and provide information for neurologists and neurosurgeons to consider when planning surgery and making device programming decisions.
“We know DBS works as a treatment for dystonia, but we don’t know exactly how it works or why some patients have better, quicker results than others. Patient age, disease duration and other underlying factors have a role, and we believe electrode positioning and device programming are critical, but there is no consensus on ideal device placement and optimal programming strategies,” said Michele Tagliati, MD, director of the Movement Disorders Program in the Department of Neurology at Cedars-Sinai.
“This modeling paves the way for the construction of practical therapeutic and investigational targets,” added Tagliati, senior author of an article now available on the online edition of Annals of Neurology.
Medications usually are the first line of treatment for dystonia and several other movement disorders, but if drugs fail – as frequently happens – or side effects are excessive, neurologists and neurosurgeons may supplement them with deep brain stimulation. Electrical leads are implanted deep in the brain, and a pulse generator is placed near the collarbone. The device is later programmed with a remote, hand-held controller.
To calm the disorganized muscle contractions of dystonia, doctors generally target a brain structure called the globus pallidus, but studies on precise positioning of electrode contacts and the best programming parameters – such as the intensity and frequency of electrical stimulation – are rare and conflicting. Finding the most effective settings can take months of fine-tuning.
In this retrospective study, investigators examined a database of 94 patients with the most common genetic form of dystonia, DYT1, who had been treated with DBS for at least a year. They selected 21 patients who had good responses to treatment, compiled their demographic and treatment information, and used magnetic resonance imaging scans to create 3-D anatomical models with a fine grid to show exact location of relevant brain structures.
The investigators then simulated the placement of electrodes as they were positioned in the patients’ brains and input the actual stimulation parameters into a computer program – a “volume of tissue activation” model – which calculated detailed information specific to each patient and each electrode. The model draws on principles of neurophysiology – the way nerve cells respond to DBS – the biophysics of voltage distribution from electrodes, and the anatomy of the globus pallidus and surrounding structures.
“We found that clinicians were applying relatively large amounts of energy to wide swaths of the globus pallidus, but the area in common among most individuals was much smaller. We interpret this as being the potential ‘target within the target,’ and if our results are validated in further research and clinical practice, computer modeling may offer a physiologically-based, data-driven, visualized approach to clinical decision-making,” Tagliati said.
(Source: newswise.com)
Contrast Agent Linked with Brain Abnormalities on MRI
For the first time, researchers have confirmed an association between a common magnetic resonance imaging (MRI) contrast agent and abnormalities on brain MRI, according to a new study published online in the journal Radiology. The new study raises the possibility that a toxic component of the contrast agent may remain in the body long after administration.
Brain MRI exams are often performed with a gadolinium-based contrast medium (Gd-CM). Gadolinium’s paramagnetic properties make it useful for MRI, but the toxicity of the gadolinium ion means it must be chemically bonded with non-metal ions so that it can be carried through the kidneys and out of the body before the ion is released in tissue. Gd-CM is considered safe in patients with normal kidney function.
However, in recent years, clinicians in Japan noticed that patients with a history of multiple administrations of Gd-CM showed areas of high intensity, or hyperintensity, on MRI in two brain regions: the dentate nucleus (DN) and globus pallidus (GP). The precise clinical ramifications of hyperintensity are not known, but hyperintensity in the DN has been associated with multiple sclerosis, while hyperintensity of the GP is linked with hepatic dysfunction and several diseases.
To learn more, the researchers compared unenhanced T1-weighted MR images (T1WI) of 19 patients who had undergone six or more contrast-enhanced brain scans with 16 patients who had received six or fewer unenhanced scans. The hyperintensity of both the DN and the GP correlated with the number of Gd-CM administrations.
"Hyperintensity in the DN and GP on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations," said lead author Tomonori Kanda, M.D., Ph.D., from Teikyo University School of Medicine in Tokyo and the Hyogo Cancer Center in Akashi, Japan. "Because gadolinium has a high signal intensity in the body, our data may suggest that the toxic gadolinium component remains in the body even in patients with normal renal function."
Dr. Kanda noted that because patients with multiple sclerosis tend to undergo numerous contrast-enhanced brain MRI scans, the hyperintensity of the DN seen in these patients may have more to do with the large cumulative gadolinium dose than the disease itself.
The mechanisms by which Gd-CM administration causes hyperintensity of the DN and GP remain unclear, Dr. Kanda said. Previous studies on animals and humans have shown that the ion can be retained in bone and tissue for several days or longer after administration.
"The hyperintensity of DN and GP on unenhanced T1WI may be due to gadolinium deposition in the brain independent of renal function, and the deposition may remain in the brain for a long time," Dr. Kanda suggested.
Dr. Kanda emphasized that there is currently no proof that gadolinium is responsible for hyperintensity on brain MRI. Further research based on autopsy specimens and animal experiments will be needed to clarify the relationship and determine if the patients with MRI hyperintensity in their brains have symptoms.
"Because patients who have multiple contrast material injections tend to have severe diseases, a slight symptom from the gadolinium ion may be obscured," Dr. Kanda said.
There are two types of Gd-CM , linear and macrocyclic, with distinct chemical compositions. Since the patients in the study received only the linear type, additional research is needed to see if the macrocyclic type can prevent MRI hyperintensity, according to Dr. Kanda.