DNA Mapping of Alzheimer’s Patients Gives Deep Dive View

Over the past 18 months, 81-year-old Bill Bunnell has visited the doctor a half-dozen times to take memory tests, provide blood samples, and undergo a spinal tap and imaging scans. It’s all part of the most extensive study ever conducted on Alzheimer’s.

Now researchers are about to take an even closer look at Bunnell, a retired engineer from Madison, Connecticut.

Working with $2 million in new grants to be announced this week, the researchers for the Alzheimer’s Disease Neuroimaging Initiative will, for the first time, start mapping the DNA of 800 participants in a study attempting to find the root causes of memory loss. The goal is to see if physical changes from Alzheimer’s can be matched to genetic disparities, which can then be compared with findings from healthy people like Bunnell.

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Childhood CT Scans Linked to Later Leukemia, Brain Cancer

Children undergoing computed tomography (CT) scans with cumulative radiation doses of about 50 mGy had about triple the risk for leukemia, and those who received doses of about 60 mGy had nearly triple the risk for brain cancer, according to the results of a retrospective cohort study published online June 7 in the Lancet.

“We’ve been doing this particular study for about 8 years, and it’s been about 20 years of research at Newcastle on radiation effects,” lead author Mark Pearce, PhD, from Newcastle University and Royal Victoria Infirmary, United Kingdom, said in a news conference. “We found that radiation exposure from CT scans in childhood could triple the risk of leukemia and brain cancer.”

The study authors note that CT scans are very useful diagnostically, but that children are more radiosensitive than adults and may therefore have additional potential risks for cancer from ionizing radiation. The study goal was to determine the excess risk for leukemia and brain tumors after CT scanning in a cohort of children and young adults.

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Safe Magnetic Resonance Image Scanning of the Pacemaker Patient

Current Technologies and Future Directions

Werner Jung; Vlada Zvereva; Bajram Hajredini; Sebastian Jäckle

Magnetic resonance imaging (MRI) is the imaging modality of choice in many clinical situations, and its use is likely to grow due to expanding indications and an ageing population. Many patients with implantable devices are denied MRI except in cases of urgent need, and when scans must be performed they are complicated by the need for burdensome and costly personnel and monitoring requirements that have the net effect of restricting access to scans. Several small studies, enrolling a total of 344 patients, suggest that some patients with conventional systems may undergo MR examinations without clinically overt adverse events. However, a number of potential interactions exist between implantable cardiac devices and the static and gradient magnetic fields and modulated radio frequency (RF) fields generated during MR scans; nearly all studies have reported pacing capture threshold changes, troponin elevations, ectopy, unpredictable reed switch behaviour, and other ‘subclinical’ issues with pacemakers and implantable cardioverter-defibrillators (ICDs) in patients who have undergone MRI. Attention has turned to devices that are specifically designed to be safe in the MRI environment. A clinical study of one such device documented its ability to be exposed to MRI in a 1.5 T scanner without adverse impact on patient outcomes or pacemaker system function. Such new technologies may enable scanning of pacemaker and ICD patients with reduced concerns regarding the short- and long-term effects of MRI. As importantly, these devices may increase the number of centres that are able to safely perform MRI and, thus, expand access to scans for patients with these devices.

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MRI may predict chemotherapy effectiveness early in breast cancer patients

Magnetic resonance imaging (MRI) scans may provide an early measure of how women will respond to chemotherapy for breast cancer, according to a new study published in the journal Radiology.

Women with breast cancer who undergo pre-surgery chemotherapy, known as neoadjuvant chemotherapy, are more likely to be able to save their breasts than those who receive chemotherapy after surgery.

Researchers from the University of California in San Francisco, who conducted the study, say contrast-enhanced MRIs can work as an early predictor of the body’s response to neoadjuvant chemotherapy by measuring the blood vessel formation in tumors, a process known as angiogenesis.  Angiogenesis is considered an earlier and more accurate marker of tumor response.

The researchers hope MRI scans in the future will work as a more reliable alternative to clinical examinations, which are the current standard for treatment.

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Alzheimer Disease Imaging MRI

Many studies have shown that cerebral atrophy is significantly greater in patients with Alzheimer disease (Alzheimer’s disease) than in persons without it. However, the variability of atrophy in the normal aging process makes it difficult to use MRI as a definitive diagnostic technique. (See the images below.)

Coronal, T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side. Axial, T2-weighted magnetic resonance imaging (MRI) scan of the brain reveals atrophic changes in the temporal lobes. Axial, T2-weighted magnetic resonance imaging (MRI) scan shows dilated sylvian fissure resulting from adjacent cortical atrophy, especially on the right side. Axial, T1-weighted magnetic resonance imaging (MRI) scan shows a dilated sylvian fissure caused by adjacent cortical atrophy. Axial, T1-weighted magnetic resonance imaging (MRI) scan shows bilateral cortical atrophy with accentuated cortical sulci; there is decreased involvement in the posterior aspect. Axial, T1-weighted magnetic resonance imaging (MRI) scan shows bilateral cortical atrophy with accentuated cortical sulci; there is decreased involvement in the posterior aspect.

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Alzheimer Disease Imaging

Current diagnosis of Alzheimer disease (Alzheimer’s disease) is made by clinical, neuropsychological, and neuroimaging assessments. Routine structural neuroimaging evaluation is based on nonspecific features such as atrophy, which is a late feature in the progression of the disease. Therefore, developing new approaches for early and specific recognition of Alzheimer disease at the prodromal stages is of crucial importance.

Alzheimer disease was first described in 1907 by Alois Alzheimer. From its original status as a rare disease, Alzheimer disease has become one of the most common diseases in the aging population, ranking as the fourth most common cause of death. Alzheimer disease is a progressive neurodegenerative disorder characterized by the gradual onset of dementia. The pathologic hallmarks of the disease are beta-amyloid (Aß) plaques, neurofibrillary tangles (NFTs), and reactive gliosis. (See the images and slideshows below.)

Coronal, T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side. Axial, T2-weighted magnetic resonance imaging (MRI) scan of the brain reveals atrophic changes in the temporal lobes.

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Magnetic resonance imaging and aneurysm clips A review

The problem of implanted metals causing tissue damage by movement in patients exposed to MRI fields has produced a confusing welter of erroneous, pseudoscientific publications about magnetics, metals, medical equipment, and tissue compatibility. Quite simply, among the devices made for implantation, only those fabricated of stainless steel have the ferromagnetic properties capable of causing such accidents. The author, who introduced the basic design of the modern aneurysm clip in the late 1960s and then a cobalt nickel alloy as an improvement over steel, while chairing the neurosurgical committee assigned to the task of establishing neurosurgical standards at American Society for Testing and Materials, exposes this flawed information and offers clear guidelines for avoiding trouble.

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Neuroanatomy and Cortical Landmarks

Focusing on the clinical applications of fMRI, this chapter will present methods to identify characteristic anatomical landmarks, and describe the course and shape of some gyri
and sulci and how they can be recognized on MR imaging.

Some redundancy is desired in order to course over cortical landmarks. If fMRI is not performed during clinical routine imaging, usually a 3D data set is acquired to overlay the results. Nowadays, fMRI is performed using echo planar imaging (EPI) with anisotropic distortion, whereas 3D T1-weighted data sets, such as MPRage (magnetization prepared rapid acquisition gradient echo) or SPGR (spoiled gradient recalled acquisition in steady state) sequences, are usually isotropic.

Normalization of the fMRI data may reduce this systemic error to some extend that is more pronounced at the very frontal aspect of the frontal lobe and the very posterior aspect of the occipital lobe. However, for individual data, normalization and overlaying fMRI results on anatomy remains crucial. No two brains, not even the two hemispheres within one subject, are identical at a macroscopic level, and anatomical templates represent only a compromise (Devlin and Poldrack 2007).

Usage of templates like the Talairach space (based on the anatomy of one brain) or the MNI template (based on 305 brains) can cause registration error as well as additional variation, and reduce accuracy; indeed, it does not warrant the shammed anatomical precision in the individual case.

Mechanisms of Radicular Low Back Pain

Radicular pain often is the result of nerve root inflammation +/- mechanical irritation. Clinical practice and research demonstrate that mechanical compression alone to the nerves causes only motor deficits and altered sensation but does not necessarily cause pain. Inflammation within the epidural space and nerve roots, as can be provoked by a herniated disk, is a significant factor in causing radicular pain.

Historical evidence of nerve root inflammation has been demonstrated during surgery in patients with radicular low back pain (LBP) from lumbar disk herniation. Animal research in dogs and rats also has revealed severe inflammation locally within the epidural space and nerve root after injection of autologous nuclear material into the epidural space. A high level of phospholipase A2 (PLA2), an enzyme that helps to regulate the initial inflammatory cascade, has been demonstrated in herniated disk material from surgical samples in humans. Leukotriene B4, thromboxane B2, and inflammatory products also have been discovered within herniated human disks after surgery. Animal models have demonstrated that injection of PLA2 into the epidural space induces local demyelination of nerve roots, with resultant ectopic discharges (which is considered to be the primary pathophysiologic mechanism for sciatica [radicular pain]).

The radicular LBP caused by spinal stenosis is probably related to the inhibition of normal nerve root vascular flow with resultant nerve root nutrition, nerve root edema, and nerve root dysfunction. Chronic nerve root compression can induce axon ischemia, impede venous return, promote plasma protein extravasation, and cause local inflammation. If dorsal root ganglia are chronically compressed and irritated, this theoretically can lead to their sensitization and resultant radicular pain. Similar mechanisms of radicular pain are postulated to occur in the thoracic and cervical spine as well.

In summary, clinical practice and animal research suggest that radicular pain is the result of inflammation of the nerve root in the epidural space provoked by leakage of disk material, compression of the nerve root vasculature, and/or irritation of dorsal root ganglia from spinal stenosis.

Epidural Steroid Injections

Author: Boqing Chen, MD, PhD Clinical Assistant Professor, Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Epidural steroid injections (ESIs) have been endorsed by the North American Spine Society and the Agency for Healthcare Research and Quality (formerly, the Agency for Health Care Policy and Research) of the Department of Health and Human Services as an integral part of nonsurgical management of radicular pain from lumbar spine disorders.

Radicular pain is frequently described as a sharp, lancinating, radiating pain, often shooting from the low back down into the lower limb(s) in a radicular distribution. Radicular pain is the result of a nerve root lesion and/or inflammation. Clinical manifestations of nerve root inflammation include some or all of the following: radicular pain, dermatomal hypesthesia, weakness of muscle groups innervated by the involved nerve root(s), diminished deep tendon reflexes, and positive straight or reverse leg–raising tests. In contrast to oral steroids, ESIs offer the advantage of a more localized medication delivery to the area of affected nerve roots, thereby decreasing the likelihood of potential systemic side effects. Studies have indicated that ESIs are most effective in the presence of acute nerve root inflammation.

The first documented epidural medication injection, which was performed using the caudal approach (see Approaches for Epidural Injections), was performed in 1901, when cocaine was injected to treat lumbago and sciatica (presumably pain referred from lumbar nerve roots).[1] According to reports, epidurals from the 1920s-1940s involved using high volumes of normal saline and local anesthetics. Injection of corticosteroids into the epidural space for the management of lumbar radicular pain was first recorded in 1952.

ESIs can provide diagnostic and therapeutic benefits. Diagnostically, ESIs may help to identify the epidural space as the potential pain generator, through pain relief after local anesthetic injection to the site of presumed anatomic pathology. In addition, if the patient receives several weeks or more of pain relief, then it may be reasonable to assume that an element of inflammation was involved in his or her pathophysiology. Since prolonged pain relief is presumed to result from a reduction in an inflammatory process, it is also reasonable to assume that during the period of this analgesia, the afflicted nerve roots were relatively protected from the deleterious effects of inflammation. Chronic inflammation can result in edema, wallerian degeneration, and fibrotic changes to the neural tissues.

In these authors’ opinion, ESIs are best performed in combination with a well-designed spinal rehabilitation program. In most cases, epidural injections should be considered as a treatment option after other treatment attempts (eg, physical therapy, including therapeutic exercise, manual therapy, and medications) have failed to improve the patient’s symptoms. However, ESIs may be indicated earlier in the treatment algorithm in some selected patients. Examples might include patients with medical contraindications to certain oral analgesics and patients whose pain severity substantially limits their ability to appropriately engage in therapeutic exercise.

A variety of approaches can be used to inject corticosteroids into the epidural space (see Approaches for Epidural Injections). For purposes of this article, the authors generally refer to all epidural steroid injections as ESIs, only specifying the specific type of approach if needed for a point of distinction or clarification.