The effects of magnesium prophylaxis in migraine without aura

There are inconsistent findings about the efficacy of magnesium in the prophylaxis of migraine attacks and there is no study of magnesium prophylaxis focused on migraine subtypes without aura. In this double blind, randomized, placebo controlled study; we tried to evaluate the prophylactic effects of oral magnesium in migraine patients without aura. The prophylactic effects of 600 mg/day oral magnesium citrate supplementation were assessed by means of clinical evaluation, visual evoked potential and statistical parametric mapping of brain single photon emission computerized tomography before and after a 3 month treatment period. The results of 30 patients with migraine without aura (20-55 years old with 2-5 migraine attacks per month) on magnesium treatment were compared with those of 10 patients with similar properties on placebo treatment. Migraine attack frequency, severity and P1 amplitude in visual evoked potential examination decreased after magnesium treatment with respect to pretreatment values (p < 0.001). In a comparison of the effects of magnesium treatment with those of placebo, post/pretreatment ratios of migraine attack frequency, severity and P1 amplitude in Mg treatment group were found to be significantly lower than those in placebo treatment group (attack frequency p = 0.005, attack severity p < 0.001, P1 amplitude p < 0.05). Cortical blood flow in inferolateral frontal (p < 0.001), inferolateral temporal (p = 0.001) and insular regions (p < 0.01) increased significantly after magnesium treatment with respect to the pretreatment; while such significant changes of cortical blood flow were not observed with placebo treatment. These results have made us think that magnesium is a beneficial agent in prophylaxis of migraine without aura and might work with both vascular and neurogenic mechanisms.     

Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

BACKGROUND: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by C1-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause considerable delay in treatment and inconvenience for patients. OBJECTIVE: The aim of this study was to investigate the feasibility, efficacy, and safety of on-demand and prophylactic self-administration of C1-inhibitor concentrate in patients with frequent attacks of angioedema. METHODS: Patients with hereditary or acquired C1-inhibitor deficiency who had very frequent angioedema attacks were trained to self-administer C1-inhibitor concentrate. The study consisted of 31 patients using on-demand treatment and 12 patients using prophylaxis with C1-inhibitor concentrate. Mean follow-up was 3.5 years. RESULTS: All patients were capable of self-administering the concentrate, with technical failure rates of self-injection being less than 2%. Times between the onset of the attack and the initiation of relief or complete resolution of symptoms in the on-demand group were significantly shortened (2.2 hours and 7.9 hours, respectively) compared with the situation before the start of self-administration. In the prophylaxis group self-administration of C1-inhibitor concentrate decreased the angioedema attack rate from 4.0 to 0.3 attacks per month. CONCLUSION: Intravenous self-administration of C1-inhibitor concentrate is a feasible and safe option and results in more rapid and more effective treatment or prevention of severe angioedema attacks in patients with C1-inhibitor deficiency. CLINICAL IMPLICATIONS: Self-administration of C1-inhibitor concentrate could be a valuable and convenient treatment modality to prevent or treat angioedema attacks in patients with C1-inhibitor deficiency.     

Migraine and non-steroidal anti-inflammatory agents]

Controlled studies of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of migraine attacks or for the prophylactic long-term treatment of migraine are reviewed herein. A large number of NSAIDs have been tested against a placebo or reference drug, including aspirin, indomethacin, mefenamic acid, tolfenamic acid, flufenamic acid, ibuprofen, flurbiprofen, fenoprofen, naproxen and sodium naproxen, diclofenac and lornoxicam. For the treatment of acute attacks, published studies found that the NSAIDs were significantly more effective than the placebo and at least as effective as the reference drugs. Adverse effects were absent or mild in this indication. Studies of NSAIDs as prophylactic treatment of migraine attacks are less numerous but also point to the value of this approach. However, long-term use of NSAIDs is associated with side-effects, mainly involving the gastrointestinal tract.     

La communication intercellulaire par l’intermédiaire des jonctions gap : un nouveau mécanisme dans la physiopathologie de la migraine avec aura. Applications thérapeutiques

Migraine is a common, recurrent and disabling primary headache disorder, which affects up to 20% of the population. About a third of patients with migraine have attacks with aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms. Cortical spreading depression, a wave of electrical activity that moves across the cerebral cortex through neuronal-glial cell gap junctions, would be involved in the triggering of migraine aura. Moreover, cortical spreading depression activates perivascular trigeminal afferents in the neocortex, that through central and peripheral reflex, cause inflammatory reaction in the meninges to generate the headache. Tonabersat, a novel benzopyran compound, was selected for clinical trial on the basis of its inhibitory activity on cortical spreading depression and neurogenic inflammation in animal models of migraine. Moreover, tonabersat inhibited trigeminal ganglion neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. In clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks and in the acute treatment of migraine. In conclusion, neuronal-glial cell gap junctional intercellular communication seems to be involved in the pathophysiology of migraine with aura and is emerging as a new promising therapeutic target for prophylactic treatment of patients with chronic attacks.     

Management of acute asthma attacks in general practice.

A prospective study was carried out in a semirural group practice between June 1988 and December 1989 to investigate acute asthmatic attacks treated with nebulized salbutamol. Questionnaires were completed by the attending doctor and by the patient (or his or her parent). Sixty nine episodes, occurring in 52 patients, were recorded during the 18 month study period. The majority of the attacks were managed exclusively in the community, with hospital admission occurring on only three occasions, one patient being admitted twice. A large proportion of the patients had a severe attack of asthma as judged by their previous history. Oral steroids were prescribed in 62.3% of attacks, oral theophyllines in 31.9% and antibiotics in 37.7%; the salbutamol nebulizer was used on more than one occasion during 41.2% of attacks. Significant morbidity was experienced by the patients during the studied attack, with 85% suffering sleep disturbance and two thirds being unable to attend work or school. Only 52.5% of patients were on prophylactic treatment and 37.5% of the patients had discontinued some aspect of their asthma therapy in the three months prior to the attack. Patients' and doctors' views about the cause of the attacks differed widely: patients most commonly cited infection (26/41) and allergy (8/41) with only two patients citing poor compliance or inadequate treatment. Although doctors also attributed the cause of many attacks to infection (33/64), they cited poor compliance or inadequate treatment in 28 of 64 responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tranexamic acid: Preoperative prophylactic therapy for patients with hereditary angioneurotic edema

Short-term therapy of 96-hr duration with tranexamic acid was prophylactically effective as defined by the absence of attacks of angioedema in 14 patients with hereditary angioedema undergoing 10 dental and 4 general surgical procedures. Eight of the 14 patients had previously undergone dental extractions without prophylactic therapy with antifibrinolytic agents and each had experienced one or more attacks of angioedema. Seven of these 8 patients had a cumulative experience of 13 episodes of laryngeal edema after dental extractions and the eighth had a bout of cutaneous angioedema. Although the number of dental extractions conducted without prophylactic antifibrinolytic therapy cannot be accurately defined in retrospect, the prominence of laryngeal edema in this circumstance is striking when compared with the absence of attacks in the presence of prophylaxis with tranexamic acid. Methyltestosterone and impeded androgens are now known to be effective prophylaxis for spontaneous and, presumably, postoperative attacks when employed chronically because their administration is associated with correction of the biochemical defect of hereditary angioneurotic edema, but their chronic administration to children and women of childbearing age requires further definition because of their potential pituitary suppressive action. Tranexamic acid prophylaxis makes it possible to offer to untreated patients with hereditary angioneurotic edema dental work and other operative procedures that in the past were withheld or conducted with considerable risk.     

Calcium channel blockers and prevention of migraine]

Calcium antagonists have been proposed for the prophylactic treatment of migraine because of their putative vasodilating antispasmodic effect and of their action against the cellular consequences of brain hypoxia. Published reports of controlled double-blind studies of calcium antagonists for the prophylactic treatment of migraine are reviewed herein. The effectiveness of verapamil, diltiazem, and nifedipine in this indication cannot be considered as firmly demonstrated, when problems with trial design and the amount of available data are taken into account. Nimodipine failed to demonstrate significant effectiveness in migraine with or without an aura. In contrast, the ability of a diphenylpiperazine, flunarizine, to decrease the incidence of migraine attacks in patients with common or classical migraine has been firmly demonstrated, although there is less evidence of this agent's effectiveness on the duration and severity of attacks. The percentage of patients who respond to flunarizine seems comparable to the percentages of propranolol or pizotifen responders. However, flunarizine is associated with unpleasant (weight gain) or severe (extrapyramidal or depressive symptoms) adverse effects which limit its place to that of a second-line drug. Lastly, the analysis of these studies failed to disclose a correlation between calcium movements across the cell membrane and effectiveness for the prevention of migraine attacks. Flunarizine's effect in migraine probably involves monoamine mechanisms which bear no relation to calcium.     

Cinryze™ (C1-inhibitor) for the treatment of hereditary angioedema

Cinryze? is a pasteurized, nanofiltered plasma derived concentrate of C1-inhibitor (pdC1-INH) licensed for the prophylactic treatment of hereditary angioedema. In a double-blind placebo-controlled crossover trial to evaluate Cinryze as prophylaxis, the frequency of attacks was halved (6.26 per 12 weeks on Cinryze versus 12.73 per 12 weeks on placebo). Furthermore, attacks were generally milder and of shorter duration. For treatment of acute attacks in patients receiving Cinryze, 1000 units, within 4 h of the start of an attack, the estimated time to the onset of unequivocal relief was reduced to 2 h, compared with more than 4 h in those treated with placebo. Cinryze and other similar products are going to change the future management of hereditary angioedema and have potential in other areas of medicine.     

Cinryze (C1-inhibitor) for the treatment of hereditary angioedema

Cinryze is a pasteurized, nanofiltered plasma derived concentrate of C1-inhibitor (pdC1-INH) licensed for the prophylactic treatment of hereditary angioedema. In a double-blind placebo-controlled crossover trial to evaluate Cinryze as prophylaxis, the frequency of attacks was halved (6.26 per 12 weeks on Cinryze versus 12.73 per 12 weeks on placebo). Furthermore, attacks were generally milder and of shorter duration. For treatment of acute attacks in patients receiving Cinryze, 1000 units, within 4 h of the start of an attack, the estimated time to the onset of unequivocal relief was reduced to 2 h, compared with more than 4 h in those treated with placebo. Cinryze and other similar products are going to change the future management of hereditary angioedema and have potential in other areas of medicine.     

A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group.

BACKGROUND. Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown. METHODS. We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis. RESULTS. After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02). CONCLUSIONS. For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.     

The preliminary effectiveness of migraine lay trainers in a home-based behavioural management training

OBJECTIVES: This pilot study examined the effectiveness and trainer skills of the first migraine lay trainers (MLTs). METHODS: In a stepwise training program eight MLTs participated in a behavioural management training (BMT) aimed at the prevention of migraine attacks by proactive relaxation and trigger management. After successful reduction of their migraine attacks, three MLTs provided BMT under supervision at home to one fellow patient and subsequently to a small group. RESULTS: Migraine frequency was significantly reduced in five out of eight patients trained by MLTs (mean 48%) and medication use decreased substantially in four patients (mean 47%). Qualities of MLTs concerned their motivational assistance, knowledge of premonitory symptoms and exchange of disease specific problems. Pitfalls were that migraine symptoms hampered an active guidance of the sessions and providing tailored feedback was difficult. CONCLUSION: The first MLTs were successful in training fellow patients in behavioural prevention of migraine attacks. PRACTICE IMPLICATIONS: Continuous supervision of MLTs health and trainer skills is recommended but is likely to have implications for cost-effectiveness.     

Recombinant human C1 esterase inhibitor for the treatment of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE)

The lack of C1 inhibitor function that results in excessive production of bradykinin causing the angioedema seen in hereditary angioedema (HAE) is well established. Several drugs have been developed to treat and prevent attacks in patients suffering from HAE due to C1 inhibitor deficiency (C1-INH-HAE). Plasma-derived C1INH has been used to replace the deficiency of C1 inhibitor (C1INH) and has been approved for both treatment of attacks and for prophylactic therapy to prevent attacks. Plasma kallikrein inhibitor (ecallantide) and bradykinin receptor antagonist (icatibant) are both effective for treatment of acute attacks, but their short half-life limits the use for prophylaxis. Androgens, in particular danazol, are effective for long-term prophylaxis, but adverse event profile can limit its use. Recombinant C1 inhibitor derived from transgenic rabbits has recently been approved for use in treatment of C1-INH-HAE attacks and is effective and appears safe with minimal adverse event profile.     

Pathophysiological basis of migraine prophylaxis

Several cellular and molecular mechanisms have been implicated in migraine pathophysiology including abnormal neuronal excitability and vascular events. Drugs from different pharmacological classes are used for migraine prophylaxis. These agents may normalize neuronal excitability by modulating distinct ionic channels and various neurotransmitter systems. They can also block cortical spreading depression, prevent peripheral and/or central pain sensitization, and normalize brainstem function. Most of the drugs recently used in migraine prophylaxis have been identified by serendipidy and they have been originally approved for other indications. Subsequently, their use has been extended to migraine prevention, according to their putative mechanisms of action. More recently, trials on adequate samples of migraine patients have been conducted for several drugs. In the present review, we will present and discuss the pathophysiological bases for the use of antidepressants, β-adrenergic blockers, calcium channel blockers and antiepileptic drugs in migraine prevention. Currently, the major classes of conventional migraine preventive drugs include the antidepressant amitriptyline, the β-adrenergic blocker propranolol, and the antiepileptic drugs topiramate and valproic acid. Promising results have recently been obtained for angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers. Some limited clinical findings have also been reported for atypical antipsychotic agents, nutritional supplements and also botulinum toxin. Targets of migraine preventive treatment are to reduce frequency and intensity of attacks and to decrease disability related to chronic headache.     

Prophylactic treatment of migraine by GPs: a qualitative study

Background

Despite the considerable impact of migraine, the use of preventive medication in primary care is limited. Only about 5% of migraine patients who qualify for prophylaxis actually receive it, and adherence is far from optimal.

Aim

To explore the opinions of GPs regarding preventive medication for migraine.

Design and setting

A qualitative focus group study in Dutch general practice.

Method

Four focus groups (six GPs each) were formed. GPs were purposively sampled to acquire a range of participants, reflecting the more general GP population.

Results

GPs perceived patients'' concerns about the impact of migraine and the potential benefits of prophylaxis. However, some were hesitant to start prescribing prophylaxis due to doubts about effectiveness, potential side effects, and the risk of developing drug dependency. GPs'' decisions were often based on considerations other than those presented in national guidelines, for example, the patient''s need to control their own problem. Many GPs placed responsibility for initiating prophylaxis with the patient.

Conclusion

Various considerations hamper GPs from managing migraine with preventive medication, and various patient-related concerns cause GPs to deviate from national headache guidelines.     

Asthma death among adults in Japan 1995-1997. Analysis of 295 cases reported questionnaires sent to hospitals with more than 100 beds. Asthma Death Investigation Committee]

To clarify recent trends in adult asthma mortality, the Asthma Death Investigation Committee of Japan studied the clinical characteristics of 295 patients who died of asthma between 1995 and 1997. Males were slightly more than females among the death cases. Approximately half of the patients ranged in age from 60 to 79 years. Tendency to increase of death among young male adults continued. One third of the patient deaths involved the asphyxic type, while status asthmaticus was the cause death in 21.9%. Half of the asthmatics died in hospitals or emergency rooms, and places where the fatal attacks occurred were mainly patients' houses. The main cause fatal asthma attacks was respiratory infection, followed by fatigue, stress, and discontinuation of medication. Most of the patients were classified moderate or severe type of asthma 1 month before death. Histories of life-threatening attacks and hospitalization due to severe attacks, irregular visits to the hospital, low compliance, and insufficiency of corticosteroid treatment were suggested as the main risk factors in adult asthma deaths.     

Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients.

BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine the benefits and risks of long-term treatment with danazol. METHODS: Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before and during danazol treatment, and adverse effects to the treatment were noted. Data were collected by using standardized questionnaires. RESULTS: In all, 111 of 118 patients responded to danazol. During treatment, 54 of the 118 patients (45.8%) became symptom free or had 1 attack or less per year. In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring of patients is mandatory. However, many patients accept the adverse effects of prophylactic treatment to avoid the distressing and sometimes life-threatening attacks of this condition.     

Migraine and the influence of hormones

According to clinical observations, "pure" menstrual migraine refers to migraine attacks that occur exclusively 2 days from menstruation onset. AIM: The aim of this study was to determine the prevalence of menstrual migraine in a group of patients (N=289) attending a headache clinic; modification of migraine characteristics during pregnancy was also determined. RESULTS: Study results showed "pure" menstrual migraine to be present in 52 (18.0%) patients; 73 (25.3%) patients reported their migraine attacks to be always related to menstruation, yet also suffering attacks at other times; 95 (32.9%) patients stated that their migraine attacks were sometimes related to menstruation; and 121 (41.9%) patients observed no such relationship. In a subgroup of patients that had given birth to a child (n=145), migraine occurred for the first time in pregnancy in 14 (9.66%), improved or disappeared in 96 (66.2%), and worsened in 14 (9.66%) patients, whereas 21 (14.48%) patients reported no change in the character or frequency of migraine. CONCLUSION: Menstrual migraine is present in a high percentage of migraine patients. During pregnancy, migraine improves in the majority of patients while in a minority of patients migraine occurs for the first time or even worsens. The results of this study should serve as a basis to improve health care for patients with menstrual migraine.