Recent Findings Shed Light on Causes of
Headache, Patients' Experiences
Abnormal brain activity in migraineurs is not restricted to attacks, suggesting that the longstanding characterization of migraine as an episodic disorder may not be accurate. Findings presented at the American Headache Society's (AHS) 52nd Annual Scientific Meeting in Los Angeles in June by Dr. Till Sprenger and his team from UCSF Headache Group and Technische Universität München show increased network activity or stronger functional connectivity bilaterally in the visual, auditory and sensorimotor network in migraineurs. “There is an extensive alteration of functional connectivity in multiple networks reflecting the migrainous phenotype, emphasizing that migraine is a disorder of the brain,” Dr. Sprenger said in a statement summarizing his team's findings.
- Sleep deprivation leads to changes in the levels of key proteins that facilitate events involved in the underlying pathology of migraine, new data show. Presented at the AHS meeting, the data extend previous research showing that sleep quality is linked to migraine. Paul L. Dunham, PhD and researchers from Missouri State University's Center for Biomedical and Life Sciences used an established model of sleep deprivation to measure levels of proteins that lower the activation threshold of peripheral and central nerves involved in pain transmission during migraine. When subjects were deprived of REM sleep, expression of the proteins p38, PKA, and P2X3, was increased. These proteins are known to play an important role in initiating and sustaining chronic pain.
- Experiences of emotional, physical and sexual abuse in childhood may lead to frequent headaches and chronic migraines in adulthood, an analysis of data from the Adverse Childhood Experiences (ACE) Study of 17,337 adult members of the Kaiser Health Plan in San Diego shows. Gretchen E. Tietjen, MD, of the University of Toledo College of Medicine, and colleagues determined that the number of ACEs showed a graded relationship to the likelihood of experiencing frequent headaches. The eight adverse experiences examined—emotional, physical, or sexual abuse, witnessing domestic violence, growing up with mental illness in the home, having household members who were incarcerated or were abusing drugs, and experiencing parental separation or divorce—were all found to increase the risk for frequent adult headaches; the frequency of headaches correlated with the number of adverse experiences.
- For patients with chronic migraine, the experience of stigmatization may be worse than that for patients with episodic migraine and other neurological diseases, including stroke, epilepsy and MS.
Jung E. Park, MD and colleagues from Jefferson Headache Clinic at Thomas Jefferson University Hospital in Philadelphia surveyed 123 outpatients with chronic migraine (CM) and 123 with episodic migraine (EM) ages 18 to 65 using the Stigma Scale for Chronic Illness (SSCI), the Migraine Disability Scale (MIDAS), and the SF-12, a quality of life measure. Chronic migraine patients had a marked increase in SSCI scores (54.05±20.15) compared to EM patients (41.6±14.84); mean SSCI for patients with stroke, epilepsy, multiple sclerosis, Alzheimer's, ALS and Parkinson's disease was 42.7±19.7.
FDA OKs Larger Aricept Dose
The FDA has approved a larger dose the Alzheimer's drug Aricept (donepezil) for patients who have already been taking the smaller dose. Drug makers Eisai and Pfizer said the higher dose improved scores on a patient test that measures cognition. There was no difference identified using a different test of global function. The approval came on the heels of a study of 1,467 patients with moderate to severe AD. The dose is recommended for patients who have been taking smaller doses of Donepezil for at least three months.
Europe Issues Modafinil Warnings
The European Medicines Agency recommends restriction of medicines containing modafinil and says they should only be used to treat sleepiness associated with narcolepsy. The agency says physicians should not prescribe the drug for the treatment of idiopathic hypersomnia, excessive sleepiness associated with obstructive sleep apnea, or chronic shift work sleep disorder.
A review was initiated due to concerns of psychiatric disorders, skin and subcutaneous tissue reactions, as well as significant off-label use and potential for abuse. A subcommittee determined the risk of serious skin and hypersensitivity adverse reactions appears to be higher in children than in adults, identified some cardiovascular risks, and recommended modafinil be contraindicated in patients with uncontrolled moderate to severe hypertension or with cardiac arrhythmias.
As of the last agency update±April 30± FDA says it is evaluating the issue of convulsions associated with modafinil and is looking at potential safety issues but are not recommending physicians stop prescribing the drug or that patients stop taking the medication.
More Positive Results for DBS in PD
Deep brain stimulation (DBS, with Medtronic device) improves motor function for up to two years in patients with advanced Parkinson's disease (PD), results from the largest, randomized, controlled study of DBS in PD show (New England Journal of Medicine, June 3). Results were equally strong for the two most common surgical targets used for the therapy: the subthalamic nucleus (STN) or globus pallidus interna (GPi). The study, involving 299 patients from one Veterans Affairs and six university hospitals, compared the 24-month results of patients randomly assigned to receive DBS via one of the two targets.
Both groups experienced a significant improvement in average Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Daily time spent in the “on” state increased, and daily time in the “off” state decreased similarly in both groups. Quality of life improved in all patients on six of eight subscales measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). Serious adverse events (SAEs) occurred in approximately half of GPi and STN patients, with the most common SAE among both groups being surgical site infection (in less than 10 percent of each group). One death was reported in the study related to the surgical procedure (intracranial hemorrhage) and one GPi patient committed suicide. Ninety-nine percent of the SAEs were resolved by the 24-month study follow-up.
Incobotulinum Toxin Approved
A new neurotoxin is now available on the US market. The FDA in July approved Xeomin (incobotulinum toxin A, Merz Pharmaceuticals) for the treatment of adults with cervical dystonia or blepharospasm. Xeomin, which does not require refrigeration prior to reconstitution, will be available in 50-unit and 100-unit vials allowing dosing flexibility for administration.
Steerable Guidewire Released
A newly developed steerable guidewire facilitates the placement of diagnostic or therapeutic catheters within the neurovasculature. NeuroScout 14 Steerable Guidewire from Codman and Shurtleff, Inc. features a flattened distal segment with a stainless steel core that retains its shape over time, enabling easy vessel access and re-access.
Pain Drug Approved
Butrans (buprenorphine, Purdue Pharma) Transdermal System received FDA approval for the management of moderate to severe chronic pain in patients needing a continuous, around-the-clock opoid analgesic for an extended period of time. Buprenorphine, a partial agonist at mu opioid receptors and an antagonist at kappa opioid receptors. Butrans' efficacy was evaluated in four 12-week double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe chronic low back pain or osteoarthritis using pain scores as the primary efficacy variable. Two studies in low back pain demonstrated efficacy while one study in low back pain failed to show efficacy and one study in osteoarthritis, that included an active comparator, failed to show efficacy for Butrans and the active comparator. In a placebo-controlled study of opioid naive patients who were suboptimally responsive to non-opioid therapy, 53 percent of patients who entered the open-label titration period were able to titrate to a tolerable and effective dose.