Isoflurane effects on the N1 and other long-latency auditory evoked potentials in Wistar rats.

Long-latency auditory evoked potentials (LLAEPs) may help further advances in understanding consciousness under general anesthesia and promote more objective means of assessing sedation depth than conventional clinical signs. Among the LLAEP components, the auditory N1 shows promise as a measure of sedation depth and a marker of consciousness, but findings are so far inconclusive. Research with animals can help elucidate the effects of various anesthetics on the N1 and other LLAEPs, but investigations of LLAEPs under anesthesia in animals is lacking. To address this deficit, we examined the P1, N1, P2, and N2, along with their corresponding peak-to-peak complexes, in 10 Wistar rats anesthetized with 1.5-2 % isoflurane in pure oxygen and again after recovery. While under anesthesia, subdermal needle electrodes were inserted and secured for electroencephalographic (EEG) recordings. LLAEPs were assessed during a 20-min, passive, two-tone (500 ms inter-tone interval) paradigm with randomized short (1 s) and long (5 s) inter-pair intervals (IPIs). Overall, while the LLAEP peaks under isoflurane were less defined, they were not eliminated. The peak-to-peak amplitudes, particularly the P1-N1, were significantly smaller under isoflurane than during post-recovery. Our preliminary findings indicate that isoflurane produces global suppression across LLAEP components, presumably reflecting impaired integration of top-down and bottom-up attention and sensory systems under profound sedation with isoflurane.

Increasing Warmth in Adolescents with Anorexia Nervosa: A Randomized Controlled Crossover Trial Examining the Efficacy of Mustard and Ginger Footbaths.

OBJECTIVE: To analyze the thermogenic effects of footbaths with medicinal powders in adolescents with anorexia nervosa (AN) in comparison to healthy controls (HCs). Intervention and Outcomes. Forty-one female participants (21 AN, 20 HCs; 14.22 ± 1.54 years) received three footbaths-warm water and mustard (MU, Sinapis nigra), warm water and ginger (GI, Zingiber officinale), or warm water only (WA), in random order within a crossover design. Data were collected before (t1), immediately after foot immersion (maximum 20 minutes) (t2), and after 10 minutes subsequently (t3). Actual skin temperature (high resolution thermography) and perceived warmth (HeWEF questionnaire) were assessed at each time point for various body parts. The primary outcome measure was self-perceived warmth at the feet at t3. Secondary outcome measures were objective skin temperature and subjective warmth at the face, hands, and feet. RESULTS: Perceived warmth at the feet at t3 was significantly higher after GI compared to WA (mean difference -1.02) and MU (-1.07), with no differences between those with AN and HC (-0.29). For the secondary outcome measures, a craniocaudal temperature gradient for the skin temperature (thermography) was noted at t1 for patients with AN and HC (AN with colder feet). The craniocaudal gradient for subjective warmth was only seen for patients with AN. CONCLUSION: Footbaths with ginger increased warmth perception at the feet longer than with mustard or warm water only for adolescents with AN as well as for HC. The impact of ginger footbaths on recovery of thermoregulatory disturbances in patients with AN repeated over extended periods merits further investigation.

Effects of Footbaths with Mustard, Ginger, or Warm Water Only on Objective and Subjective Warmth Distribution in Healthy Subjects: A Randomized Controlled Trial.

OBJECTIVE: To analyze the short-term thermogenic effects of footbaths with warm water alone (WA) versus when combined with medicinal powders. DESIGN: Randomized controlled trial with cross-over. INTERVENTIONS AND OUTCOMES: Seventeen healthy volunteers (mean age 22.1 years, SD = 2.4; 11 female) received three footbaths with WA or WA combined with mustard (MU) or ginger (GI) in a randomized order. Self-perceived warmth (Herdecke warmth perception questionnaire) and actual skin temperatures (thermography) were assessed before (t0), immediately after footbaths (t1), and 10 minutes later (t2). The primary outcome was perceived warmth in the feet. Secondary outcomes were warmth perception in the face, hands and overall, as well as actual skin temperature in the feet, face, and hands. RESULTS: Perceived warmth at the feet (primary outcome) increased significantly (all p's < .001) for MU and GI at t1 as well as for GI at t2 when compared to t0 with high effect sizes. At t2, GI differed significantly from WA (p < .001) and MU (p = .048). With regards to the secondary measures of outcome, no significant effects were seen for perceived warmth at the face or hands. Overall warmth was significantly higher at t1 compared to t0 (p = .01). Thermography assessments of skin temperature at the feet at t1 increased after all conditions (p < .001). No effects were seen in the face. At the hands, temperature decreased at t1 (p = .02) and t2 compared to t0 (p < .001). CONCLUSION: The present study provides preliminary evidence that mustard and ginger increase warmth perception at the feet more than warm water alone, with only the effects for GI enduring at the brief follow-up.

Day-hospital withdrawal for chronic migraine with medication overuse: results at 3 years follow-up.

Patients with chronic headache and medication overuse are particularly difficult to treat, with no one approach being universally accepted. Some type of withdrawal program, however, is typically implemented before beginning a pharmacological prophylaxis treatment. Different withdrawal modalities have been performed for managing these patients: at first step, in-patient withdrawal has been confirmed effective in preceding clinical experiences. In recent years, new modalities for withdrawal have been developed as day-hospital setting. Purpose of this study was to determine the clinical course of a sample of chronic migraine patients with medication overuse 3 years after day-hospital withdrawal. A group of 202 patients were treated. Patients were suffering from chronic migraine with medication overuse according with IHS criteria. All patients were submitted to a day-hospital withdrawal and then they were followed with meetings every 3 months until the first year and then every 6 months until the last follow-up 3 years after withdrawal. Eighty patients achieved the last follow-up meeting 3 years after withdrawal. Patients clinically improved, significantly, both for days of headache per month and consumption of medications per month. From these results, the day-hospital setting for withdrawal, followed by periodic clinical meetings, seems to be effective for this category of patients to improve significantly at long-term headache frequency and analgesics intake.

Behavioral treatment of headaches: extending the reach.

Behavioral treatments (predominantly biofeedback, relaxation, and cognitive-behavioral) have been utilized in headache management for many decades. Although effective, they have not been as widely implemented as desired, chiefly due to their time-intensive nature, special therapist qualifications, and patient costs. This paper focuses on ways to make these treatments more affordable and more readily accessible to patients. Various alternative delivery models have been explored. This paper reviews progress to date on three such approaches for treating recurrent headaches in adults--prudent limited office contact, Internet delivery, and mass media approaches. Clinical outcomes, advantages, and disadvantages of these approaches are reviewed in brief.

Disability in chronic migraine with medication overuse: treatment effects through 5 years.

Chronic migraine accompanied by medication overuse is particularly difficult to treat. The number of treatment investigations is limited, few have included follow-up beyond 6 months and almost none has examined whether treatment leads to concurrent improvements in disability and functional impairment. This open-label study addresses these limitations. We have been prospectively following an initial cohort of 84 chronic migraine patients with medication overuse, who at the time of this evaluation had been reduced to 58, for an extended period to assess longer-term maintenance of effects, using measurement procedures identical to those in the original investigation. Thus, the specific aim was to determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated and followed prospectively for 5 years. All patients completed a brief inpatient treatment programme, in which they were withdrawn from their offending medications and subsequently placed on more appropriate preventive antimigraine medications. Both end-point, wherein missing data points were estimated, and continuer analyses, wherein data analysis was limited to the 58 individuals with complete datasets, revealed significant improvement on all measures studied-headache days per month, analgesic consumption and Migraine Disability Assessment (MIDAS) total score. The percentage reduction from baseline to 5 years for the MIDAS total score was 76.0%, while the percentage of individuals revealing improvements of clinically significant magnitude (≥ 50%) on the MIDAS was 91.9%. MIDAS total scores were lower at 5 years than at some of the intervening follow-up intervals. Comparisons of those who completed the 5-year follow-up (n = 58) with those who did not revealed no differences at baseline. This finding, coupled with the nearly identical results for the end-point and continuers analyses, suggests that attrition did not have a bearing on outcome. None of the patients completing the 5-year follow-up had relapsed since the prior 3-year follow-up assessment. High levels of maintenance were revealed at 5 years, with disability scores showing some continued improvement over time. The implications of these findings and the limitations of the study are discussed.

Functional-MRI evaluation of pain processing in chronic migraine with medication overuse.

Withdrawal is the first step for treating patients with chronic migraine and medication overuse. Recent studies confirmed common elements in personality between these patients and subjects addicted; some neuroimaging researches showed that abnormalities revealed are related to a specific cerebral pattern and that they can return to the normal state after withdrawal. Aim of the study was to submit a group of patients suffering from chronic migraine and medication overuse (the diagnosis was made according to Silberstein-Lipton criteria) to a withdrawal, to evaluate by f-MRI the presence of specific cerebral patterns before treatment and their possible changes after withdrawal. f-MRI seems to be a useful technique to obtain information on particular neuronal changes of the pain network involved in this type of patients. The activated areas are congruent with some data of the literature and the data emerged are discussed according to preceding reports.

Non-pharmacological approaches to treating chronic migraine with medication overuse.

Medication overuse headache (MOH) is now recognized as a biobehavioral disorder, a condition wherein emotion and pain are intermingled. This review discusses the steps to consider when treating this condition. The first step involves educating patients about MOH and the pathways to chronicity. The second step concerns working with patients to identify risk factors and behaviors that are present and contributing to the condition. The final step involves behavioral intervention. Examples for accomplishing each step are provided.

Central mechanisms of controlled-release metoprolol in migraine: a double-blind, placebo-controlled study.

beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV.

Magnesium as a preventive treatment for paediatric episodic tension-type headache: results at 1-year follow-up.

The objective was to confirm the long-term utility of magnesium salts treatment on a group of young patients suffering from episodic tension-type headache (ETTH). The study was carried out at the Outpatient Headache Center at the National Neurological Institute "C. Besta," Milan, Italy, with 45 children/adolescents with ETTH reporting consecutively for treatment. Magnesium pidolate (2.25 g) was given twice per day for three months. Medication was not administered during the year of follow-up. No other treatment was provided at any time. Patients showed significant symptom reduction. Headache days decreased by 69.9%, whereas analgesics consumption was reduced by 65.4%. Overall disability levels improved by the greatest percent - 75.7%. MIDAS subscores improved as well (question A=58.0%; question B=22.5%). Although uncontrolled, these findings are encouraging and suggest that further, better controlled research investigations are warranted.

Can behavioural therapy influence neuromodulation?

This paper reviews non-invasive behavioural approaches - broadly construed as cognitive, affective, behavioural and psychophysiological interventions - and examines whether they can impact central, peripheral or autonomic nervous system components responsive to pain in general and headache in particular. It focuses on two developing bodies of literature - neurophysiology of migraine and fMRI studies of pain networks. The available literature suggests behavioural interventions can affect neuromodulation, although further research is clearly warranted.

Pharmacological treatment compared to behavioural treatment for juvenile tension-type headache: results at two-year follow-up.

Recurrent headaches are common in children and adolescents. Most current investigations have employed limited modalities (either medication or behavioural) and few have included comparisons of different treatments. In this study relaxation training, administered in a limited contact format, and amitriptyline were compared for juvenile episodic tension-type headache. The clinical improvement was significant for both groups at 1- and 2-year follow-up; in particular for behavioural treatment, the patients came regularly for the sessions, practised routinely, and appeared to be compliant and accepting of treatment, although we did not assess this formally. In this group of patients the percentage of drop-outs was lower than in the pharmacological tratment. Although clinical results were similar in both groups, relaxation therapy seems to be more accepted than medication. The limited contact modality seems to be as useful as other behavioural approaches that require a greater investment of time (by patients and therapists), without unpleasant side effects. Because the sample sizes are small, these conclusions are tentative.

What does the evidence show? Efficacy of behavioural treatments for recurrent headaches in adults.

Behavioural treatments (predominantly biofeedback, relaxation and cognitive-behavioural) have been utilised in headache management for nearly 4 decades. This paper examines their clinical efficacy, drawing upon 2 primary sources of evidence: meta-analytic and evidenced-based reviews. Behavioural treatments have demonstrated efficacy and have been endorsed by various reviewing groups, such as the US Headache Consortium. Outcomes from behavioural treatments appear to endure over longer-term follow-up intervals as well. Meta-analyses comparing behavioural and pharmacological treatments have revealed similar levels of outcome. The article closes with a brief discussion of methods investigators are exploring to make behavioural treatments more available and affordable to headache patients.

An expanded view of psychological aspects in head pain: the biopsychosocial model.

Traditionally, headache has been viewed from a limited perspective, both medically and psychologically. The authors propose that a more expanded view of headache that considers each perspective as important, as embodied in the biopsychosocial model, will greatly enhance understanding and be more useful in treatment planning. This model views pain as emanating from a complex interaction of biological, psychological and social variables. This paper describes the key behavioural, affective and cognitive influences and provides pertinent supporting examples from the literature.

Magnesium as a treatment for paediatric tension-type headache: a clinical replication series.

The objective was to determine the initial utility of magnesium salt as a treatment for paediatric episodic and chronic tension-type headache (TTH). The study took the form of a clinical replication series in the Outpatient Headache Center at the National Neurological Institute "C. Besta", Milan, Italy. The patients were five children/adolescents with episodic and four with chronic TTH reporting consecutively for treatment. Magnesium pidolate (2.25 g) was given twice per day for two months, with one year of follow-up. No other treatment was provided. Patients with episodic TTH revealed 76.0% symptom reduction, with 80% of the sample achieving reductions greater than 50%. The patients with chronic TTH revealed 87.5% symptom reduction, with 100% of the sample achieving reductions greater than 50%. Analgesic consumption decreased significantly for chronic TTH. Only one child took medication in the episodic TTH group. No significant changes occurred with respect to depression and anxiety, but these measures were not clinically elevated at the start of treatment. Although uncontrolled, the initial findings are encouraging and suggest that further, better controlled research is warranted.

Pharmacological behavioural treatment for children and adolescents with tension-type headache: preliminary data.

Recurrent headaches are a significant health problem for young patients. Most current investigations have employed limited modalities (either medication or behavioural) and few have included treatment comparisons. The purpose of this study was to compare relaxation training (provided in a limited contact format) and amitriptyline in the treatment of young tension-type headache (TTH) sufferers. Follow-up is planned for 3, 6 and 12 months, at which time patients complete headache logs and an Italian version of the Migraine Disability Assessment (MIDAS) Questionnaire that has been adapted for this age group. Two groups of TTH sufferers of similar age and characteristics were studied. Clinical results, MIDAS total score, and individual values for items A and B were collected at the first follow-up (3 months). The clinical improvement is significant for both groups. Although the clinical results are similar in both groups, relaxation therapy seems to be more accepted than pharmacological therapy. These data, however, are preliminary and the sample sizes are small, so these conclusions are tentative. We will continue our data collection for 12 months.

Chronic migraine with medication overuse: treatment outcome and disability at 3 years follow-up.

Patients with chronic migraine and medication overuse are particularly difficult to treat. No clear consensus exists about treatment strategies to be used and little data exists about the functional impact of headache in these patients. The purpose of the study was to determine (1) the clinical course of a sample of chronic migraine patients with medication overuse 36 months following treatment intervention and (2) whether functional impairment, assessed by the Migraine Disability Assessment (MIDAS) questionnaire, improved upon treatment. Of 106 patients meeting the criteria for chronic migraine with medication overuse (according to Silberstein and Lipton), 71 went on to complete a structured inpatient treatment, consisting of medication withdrawal and then prophylactic treatment. As a group, the patients were significantly improved at 36-month follow-up, with respect to 2 headache parameters (days of headache per month and number of used medications per month assessed by the diary card) and 2 measures of functional impact extracted from the MIDAS questionnaire (MIDAS total score and frequency of headache). Chronic migraine accompanied with medication overuse led to considerable disability prior to treatment. However, notable improvement both in headache parameters and in disability measures occurred concurrently with treatment. This suggests that successful treatment has more wide-ranging positive benefits beyond mere symptom reduction. To our knowledge, this is the first investigation where the MIDAS questionnaire has been used as an outcome measure in patients with chronic headache to assess disability during such a long follow-up period.

Use of the Migraine Disability Assessment Questionnaire in children and adolescents with headache: an Italian pilot study.

OBJECTIVES: To determine the suitability of the Migraine Disability Assessment (MIDAS) Questionnaire for assessing disability in children and adolescents with headache and to obtain preliminary information about disability in different primary headaches. BACKGROUND: During the last decade, researchers have begun to employ standardized methodologies to investigate the global impact of primary headaches. Disease-specific instruments have been developed to measure headache-related disability. The MIDAS Questionnaire, which is the most extensively studied of these instruments, was designed to assess the overall impact of headaches over the 3 months before compilation. The MIDAS Questionnaire is an optimal tool to assess headache-related disability in adults. METHODS: Ninety-five patients aged 7 to 17 years with tension-type headache, migraine, or both completed the validated Italian form of the MIDAS questionnaire on 2 occasions. Test-retest reliability was assessed by the Spearman rank correlation test. The Cronbach alpha assessed internal consistency. The patients answered questions about the adequacy of the questionnaire. RESULTS: The Cronbach alpha was.8. Correlation coefficients were generally high for the overall MIDAS score and for the items investigating disability in school and in family/leisure activities; they were lower for the items about housework. Most patients thought that the MIDAS Questionnaire was useful (98.9%) and that it captured the impact of their headaches (58.9%); 41% thought that questions about disability in housework were useless, 44.2% suggested adding questions regarding inability to do homework. All primary headaches had a considerable impact on daily activities, but patients with migraine tended to have lower headache frequencies and lower total disability time; those with tension-type headache suffered more days in which activities, although performed, were substantially impaired. CONCLUSIONS: The MIDAS Questionnaire is useful for assessing disability in children and adolescents with different primary headaches. Minimal changes in the phrasing and content of the items would be sufficient to render the MIDAS specific for the younger population with headache.

Behavioral treatment approaches to chronic headache.

Over 3 decades of research have shown the utility of a number of behavioral treatments, chiefly relaxation, biofeedback, and cognitive behavior therapy, for uncomplicated forms of migraine and tension-type headache. However, the literature base is much less extensive for chronic, complicated, and refractory forms of headache. This paper reviews extant work on the usefulness of behavioral treatment for headache accompanied by medication overuse; chronic, daily, high intensity headache; refractory headaches; cluster headache; chronic tension-type headache; posttraumatic headache; and headache accompanied by psychiatric comorbidity. It concludes with a discussion of the role of environmental and familial factors in influencing chronic headaches. Suggestions for future research are pointed out along the way.

Treatment of chronic daily headache with medication overuse.

Clinicians long have suspected that symptomatic medications taken by those with headache can cause rebound or drug-induced headaches if overused. This problem has been considered in the classification of headache disorders made by the International Headache Society. Patients who overuse medication must be withdrawn before their headache can be treated effectively. Sustained improvement following treatment for drug-induced headache can be difficult to achieve and at the moment there is no consensus on what approach may be more effective, in particular regarding outpatient or inpatient treatment withdrawal strategy. Clinical aspects and different therapeutic strategies for chronic daily headache patients with medication overuse are considered.