Preclinical assessment of onabotulinumtoxinA for the treatment of mild traumatic brain injury-related acute and persistent post-traumatic headache.

OBJECTIVE: Investigation of onabotulinumtoxinA in a murine model of acute and persistent post-traumatic headache. METHODS: Mild traumatic brain injury was induced with a weight drop method. Periorbital and hindpaw cutaneous allodynia were measured for 14 days. Mice were then exposed to bright light stress and allodynia was reassessed. OnabotulinumtoxinA (0.5 U) was injected subcutaneously over the cranial sutures at different post-injury time points. RESULTS: After milt traumatic brain injury, mice exhibited periorbital and hindpaw allodynia that lasted for approximately 14 days. Allodynia could be reinstated on days 14-67 by exposure to stress only in previously injured mice. OnabotulinumtoxinA administration at 2 h after mild traumatic brain injury fully blocked both transient acute and stress-induced allodynia up to day 67. When administered 72 h post-mild traumatic brain injury, onabotulinumtoxinA reversed acute allodynia, but only partially prevented stress-induced allodynia. OnabotulinumtoxinA administration at day 12, when initial allodynia was largely resolved, produced incomplete and transient prevention of stress-induced allodynia. The degree of acute allodynia correlated positively with subsequent stress-induced allodynia. CONCLUSION: Mild traumatic brain injury induced transient headache-like pain followed by long lasting sensitization and persistent vulnerability to a normally innocuous stress stimulus, respectively modeling acute and persistent post-traumatic headache.. Administration of onabotulinumtoxinA following the resolution of acute post-traumatic headache diminished persistent post-traumatic headache but the effects were transient, suggesting that underlying persistent mild traumatic brain injury-induced maladaptations were not reversed. In contrast, early onabotulinumtoxinA administration fully blocked both acute post-traumatic headache as well as the transition to persistent post-traumatic headache suggesting prevention of neural adaptations that promote vulnerability to headache-like pain. Additionally, the degree of acute post-traumatic headache was predictive of risk of persistent post-traumatic headache.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention for tension-type headache in recent five years].

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.

Neurological soft signs in primary headache patients.

Neurological soft signs (NSS) are semeiotic anomalies not assessed by the standard neurological examination, primarily developed in psychiatric settings and recently proposed as potential markers of minor brain circuit alterations, especially the cerebellar-thalamic-prefrontal network. Primary headache patients present with normal neurological examination and frequent psychiatric comorbidity. Aim of this exploratory study consisted in assessing NSS in 20 episodic frequent migraine (MH) and in 10 tension-type headache (ETTH) outpatients compared to 30 matched healthy controls. NSS were assessed by the Heidelberg scale; clinical characteristics and brain MRI were additionally obtained in all patients. NSS were increased by ∼70 and ∼90% in ETTH and MH, respectively, with respect to controls (p<0.001) and the difference remained significant even after controlling for age and education. Headache type and characteristics did not influence NSS presentation, while headache patients with white matter hyperintensities (WMH) at brain MRI had higher NSS scores compared both to normal controls and patients without WMH. NSS identify a subset of primary headache patients sharing the same comorbidities or minimal brain anomalies, suggesting that tailored prophylactic options might apply.

Chronic headache: stop the pain before it starts.

Familiarity with the risks associated with medication overuse and the importance of headache prophylaxis is key to easing your patient's pain.

Headache: insight, understanding, treatment and patient management.

Tension-type headache and migraine are the most frequent primary headaches. Diagnosis is based on the patient's history and a normal neurological examination. Most patients with these two headache entities treat headache episodes with over-the-counter analgesics or non-steroidal anti-inflammatory drugs (NSAIDs). There is good scientific evidence from randomised, placebo-controlled trials indicating that aspirin, ibuprofen, ketoprofen, diclofenac and naproxen are effective in tension-type and migraine headache. Paracetamol seems to be less effective. In patients with migraine who do not respond to analgesics or NSAIDs, triptans should be prescribed. Frequent primary headaches should not be treated with frequent intake of analgesics or triptans. In these cases, preventive therapy needs to be implemented.

[Is the management of migraine and tension headache in Croatia satisfactory?]. / Je li lijecenje migrene i tenzijske glavobolje u Hrvatskoj zadovoljavajuce?

According to the epidemiological study conducted in Croatia, 15% of the population suffer from migraine, 20.6% from tension-type headache and 2.4% from chronic headache. Although migraine is a frequent primary headache and poses a major problem to both the affected individuals and the society, it is considered that migraine is underdiagnosed. The study revealed half of patients with headache and even 36.3% of respondents with migraine to have never visited a doctor. Migraine and tension-type headache are not satisfactorily treated; in the study, one-quarter of the respondents were fully satisfied with the treatment of their headaches, approximately half were partially satisfied, one-fifth were mostly unsatisfied, and 10% were completely unsatisfied. It should be noted that specific therapy for migraine attacks, i.e. triptans, are available on the market and can be administered for moderate and severe headache attacks. Triptans are prescribed rarely, not only in Croatia but also in the world, although studies have shown that the use of triptans increases productivity at work and improves the quality of life in migraineurs. Prophylaxis may significantly improve the quality of life; the Croatian epidemiological study showed only 14% of respondents with migraine to have ever used prophylactic therapy. Considering that migraine is an 'expensive disorder', appropriate treatment of patients with migraine will decrease the costs that include visits to general practitioners, emergency departments and cost of hospitalization. Even indirect costs will decrease as well, including the costs caused by absenteeism from work and costs caused by reduced efficiency at work. It is necessary to educate the population about migraine and therapeutic options. Lack of time, unrecognized patients and insufficient knowledge about current treatment of migraine and other primary headaches are probably the reasons why patients do not receive appropriate therapy. Continuous campaigns, which should include lectures and workshops for physicians and inclusion of media for better spread of information about primary headaches among the population should be encouraged.

Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in individuals with tension-type headache and postoperative dental pain.

BACKGROUND: Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache. OBJECTIVE: We sought to compare the efficacy and safety profiles of aspirin, acetaminophen with codeine, and placebo in the treatment of post-operative dental pain and tension-type headache. METHODS: These were 2 randomized, double-blind, placebo-controlled, single-dose clinical trials that assigned participants (2:2:1) to receive either aspirin (1000 mg), acetaminophen (300 mg) with codeine (30 mg), or placebo. The primary efficacy end point was the sum of pain intensity differences from baseline (SPID) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study. Other common analgesic measures, in addition to safety, were also evaluated. RESULTS: The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points. Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0-4) (P = 0.028). In the tension-type headache study, aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0-4) and SPID(0-6) (P < 0.001) and for total pain relief (P < 0.001). There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID (P ≥ 0.070), complete relief (P ≥ 0.179), or time to meaningful relief (P ≥ 0.245). Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies. CONCLUSIONS: These 2 randomized, double-blind, placebo-controlled studies demonstrate that treatment with aspirin (1000 mg) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen (300 mg) with codeine (30 mg) therapy after impacted third molar extraction and in tension- type headache.

[Headaches of tension and psychogenic headaches: assessment of the treatment with venlafaxine].

The modern classifications of headaches include primary headaches, e.g., migraines and headaches of tension (HAT), and secondary psychogenic headaches of tension (PHT). Forty-one patients with chronic variants of HAT and PHT were studied. In the first step, 12 patients with HAT and 11 patients with PHT were compared by clinical and psychometric scores on the following scales (the VAS, the McGill Pain Questionnaire, the MMPI). In the second step, 11 patients with HAT and 7 with PHT were treated with venlafaxine XR (velaxin) in dose 75 mg/d during 2 months. It has been shown that PHT differs from HAT by pain intensity and relationship with functional-neurologic symptoms as well as by personality deviations measured with MMPI and correlations between the pain intensity and MMPI peaks. The 2 month treatment with velaxin has improved significantly the state of patients. The significant decrease of pain severity, amount of analgesics and pain-associated symptoms as well as the normalization of functions of antinociceptive systems (the increase in nociceptive flexor reflex threshold) were noted in both groups. It has been concluded that venlafaxine is an effective drug in the treatment of both HAT and PHT.

Antidepressant use and off-label prescribing in children and adolescents in Dutch general practice (2001-2005).

PURPOSE: To study the use of antidepressants in children and adolescents in Dutch general practice in 2001 and 2005 and to determine off-label prescribing. METHODS: Data were obtained from the Netherlands Information Network of General Practice (LINH) that comprised 97 practices in 2001 and 73 practices in 2005. General practitioners (GPs) recorded prescriptions with their indication in the medical records of the patients during one calendar year. We selected boys and girls aged 0-17 years (n = 83 442 in 2001; n = 62 969 in 2005) and identified those who got prescribed antidepressants (N06A). Prevalence of use, indications and percentage of off-label prescriptions were compared between 2001 and 2005. RESULTS: The prevalence of selective serotonin reuptake inhibitor (SSRI) use decreased from 1.2 to 1.1 per 1000 children and adolescents between 2001 and 2005. The use of tricyclic antidepressants (TCAs) and other antidepressants also decreased (0.8 to 0.7 and 0.3 to 0.2, respectively). TCAs were often prescribed for nocturnal enuresis, but in patients aged 12-17 years hyperactivity was the leading indication in both years. GPs continued to prescribe SSRIs for depression (about half of the prescriptions) after the safety warnings, while venlafaxine prescribed for depression decreased in favour of anxiety. Off-label prescribing of SSRIs increased from 16.7% to 34.4% and that of venlafaxine from 22.2% to 58.3%. All SSRI and venlafaxine prescriptions were unlicensed for age. CONCLUSIONS: The decreased use of SSRIs and venlafaxine suggests an impact of the safety warnings. A point of concern is the enlarged off-label prescribing and insight in the underlying reasons and its appropriateness is needed.

Peppermint oil.

Peppermint leaf and peppermint oil have a long history of use for digestive disorders. Recent evidence suggests that enteric-coated peppermint oil may be effective in relieving some of the symptoms of irritable bowel syndrome. A combination product including peppermint oil and caraway oil seems to be moderately effective in the treatment of non-ulcer dyspepsia. Topical application of peppermint oil may be effective in the treatment of tension headache. Because of its relaxing effects on smooth muscle, peppermint oil given via enema has been modestly effective for relief of colonic spasm in patients undergoing barium enemas. Peppermint oil is well tolerated at the commonly recommended dosage, but it may cause significant adverse effects at higher dosages.

[Headache]. / Hovedpine.

Headache is the most frequent pain disorder, and 31% of the adult Danish population has sought medical assistance due to headache. In addition, the socio-economic costs of headache are substantial, and a national treatment strategy is therefore important. With respect to treatment of migraine, considerable scientific progress has been made, whereas the scientific interest in and treatment of the highly prevalent tension-type headache are insufficient. The most frequent primary headache disorders, their differential diagnosis and the current treatment strategy are briefly reviewed.

A randomized controlled trial of an internet-based treatment for chronic headache.

Chronic headache is a significant public health problem in Western nations. Although controlled trials demonstrate the efficacy and cost-effectiveness of face-to-face behavioral therapy, most headache sufferers have limited access to these treatments. Delivery of behavioral interventions using Internet technology has the potential to reach a larger number of headache sufferers and reduce the burden of disease. This randomized controlled study evaluated an Internet-delivered behavioral regimen composed of progressive relaxation, limited biofeedback with autogenic training, and stress management versus a symptom monitoring waitlist control. Treatment led to a significantly greater decrease in headache activity than symptom monitoring alone. Thirty-nine percent of treated individuals showed clinically significant improvement on self-report measures of headache symptoms at post-treatment. At two-month follow-up, 47% of participants maintained improvement. Treatment had a significant impact on general headache symptoms and headache-related disability. There was a 35% within-group reduction of medication usage among the treated subjects. The Internet program was more time-efficient than traditional clinical treatment. Treatment and follow-up dropout rates, 38.1% and 64.8%, respectively, were typical of behavioral self-help studies. This approach to self-management of headache is promising; however, several methodological and ethical challenges need to be addressed.

[Botulinum toxin in tension-type headache]. / Botulinumtoxin beim Kopfschmerz vom Spannungstyp.

Botulinum toxin has meanwhile been approved for a number of indications. It is also gaining acceptance in other indications with a major focus on pain. The most common type of headache is tension-type headache (TTH) the pathogenesis of which has not yet been unfolded. As it looks there are vascular, myofascial and supraspinal factors intertwined. It is felt that headache is triggered by myofascial stimuli. The application of botulinum toxin is an intelligent alternative since the favorable effect of pharmacologic and other therapies is limited. Application of BTX should be considered when the pericranial muscles are involved. One of the effects produced lies in the reduction of muscular stress, muscular ischemia and muscle tone. We still don't know whether additional mechanisms such as retrograde uptake and direct antiinflammatory potential are involved. Current data permit the conclusion that headaches are decreased in their frequency and distinctiveness. Significant untoward effects are not to be expected. Neither the ideal dose nor the optimum selection of injection sites have been established as yet, an individual injection scheme is apparently most promising. Injection of the trigger points seems to make sense.

Variations among emergency departments in the treatment of benign headache.

STUDY OBJECTIVE: The practice patterns of US emergency departments in the treatment of patients with isolated benign headache have been recently described. How treatment varies among EDs has not been reported. To assess institutional variability in the pharmacotherapy of patients with benign headache, we describe and analyze the practice patterns of 3 US EDs. METHODS: This health records survey included a cohort sample of consecutive adult patients aged 16 to 65 years treated with parenteral medication for isolated benign headache at 3 nonaffiliated US EDs: a large, group-model health maintenance organization, a tertiary-care academic center, and a rural community hospital. Patients who underwent a diagnostic search for intracranial pathology, who had any nonheadache secondary diagnosis, or who had coexistent trauma, fever (temperature of > or =38.0 degrees C [100.4 degrees F]), or known pregnancy were excluded from study analysis. Demographic, clinical, and pharmacotherapeutic variables were collected for each ED visit. Descriptive analyses were performed; comparisons were made with t tests. RESULTS: Of the 490 eligible patients treated during the 4-month study period, the mean age was 36.4 years, and 374 (76%) were women. During their 629 visits, 364 (58%) received a migraine diagnosis, and 258 (41%) received a nonspecific headache diagnosis. Polypharmacy was common: 515 (82%) received 2 or more medications, and 154 (25%) received 3 or more medications. Pharmacotherapy varied greatly among the EDs. Use of opioid agonists showed the widest variation (16% to 72%), although use of dihydroergotamine (5% to 16%), prochlorperazine (32% to 59%), and adjunct diphenhydramine with prochlorperazine (42% versus 88%) also varied. CONCLUSION: Great institutional variability exists among US EDs in the parenteral treatment of patients with isolated benign headache.

Butalbital-containing agents: should they be banned? No.

Butalbital compounds are of proven efficacy in the treatment of tension headache. Decades of experience have established their value in the treatment of other mild-to-moderate headaches. Untold numbers of people rely on these medications as their drug of choice or use them when vasoconstrictors, opioids, or nonsteroidal anti-inflammatory agents are contraindicated. The medications are cost-effective with only occasional and minor immediate adverse effects. Their overuse may cause the evolution of episodic primary headaches to chronic daily headaches; however, removal of these agents from the market would reduce the chronic daily headache in the general population by a small fraction of 1%.

Should butalbital-containing analgesics be banned? Yes.

In the United States analgesic-overuse headache is often caused by butalbital-containing analgesics. These agents can cause physical and psychological dependency, and dangerous withdrawal syndromes. Butalbital-containing analgesics have already been banned in several European countries. They are proven effective in tension-type headache, but not in migraine; there are many alternative treatments for migraine and tension-type headache. In the 20 years since analgesic overuse headache was widely recognized, butalbital overuse has remained distressingly common. It is time to ban these agents.

[The importance of headaches in neurology clinics. Study groups of neurologists of Aragon]. / Importancia de las cefaleas en las consultas de neurología. Grupo de estudio de Neurólogos Aragoneses.

OBJECTIVE: To analyze the patients sent to Neurology Clinics for headache and to investigate the differences in epidemiology, clinical findings and therapeutics as compared with those consulting for other neurological disorders. PATIENTS AND METHODS: Eighteen neurologists from all the Outpatient Departments of the Community of Aragon Health Service were analysed using a specially designed questionnaire for all the patients who attended the Neurology Clinics for the first time during a period of three months. RESULTS: Of 3,489 patients assessed, 25.5% complained of headache. Of these, 70% were women of an average age of 41.2 +/- 18.8 years. In 42% the consultation was for migraine followed by chronic tension headache in 30.1%. Family doctors sent 86.7% of the patients and requested complementary tests for 31.1%. Cerebral TAC (12.4%) and EEG (7.6%) were the investigations most often requested. Treatment was given to 68.6% of the patients with headache. Calcium-antagonists and anti-depressants were the drugs most used. CONCLUSIONS: Headache is the commonest cause for consulting a neurologist. It affects young adults, with marked predominance of the female sex. There are significative differences in clinical attention (fewer complementary tests are requested and less follow-up is necessary, although more treatment is given) than for other neurology patients.