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Biomedical subjects

V Limmroth

Publications and source records attributed to V Limmroth.

At least 19 recordsLinked to original sources
PubMed2003

Rates and predictors for relapse in medication overuse headache: a 1-year prospective study.

The authors prospectively studied 98 patients with medication overuse headache. The 1-year relapse rate was 38% but was lower for patients with migraine compared with tension-type headache (22% vs 73%, p < or = 0.002) and combination of migraine and tension-type headache (22% vs 77%, p < or = 0.0001). The rate was also lower for patients overusing triptans than ergots (19% vs 20%, NS) and analgesics (19% vs 58%, p < or = 0.001). The long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Adult↗
PubMed2003

Ethical aspects of placebo in migraine research.

Randomized placebo-controlled clinical trials have been the 'golden standard' during the last decades in the development of new drug therapies. This scientifically valid approach has recently been questioned in the fifth revised version of the Declaration of Helsinki, which states that the use of placebo-controlled clinical trials is only acceptable when no proven treatment exists for the studied disease. The World Medical Association further claims that no national ethical, legal or regulatory requirements should be allowed to reduce or eliminate any of the statements in the declaration. In spite of this, the document is not generally accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations. In the evaluation process for a drug to be approved in many countries today, clinical investigators at the hospitals and researchers at the pharmaceutical companies are obliged to use study protocols that would be rejected if the new declaration were to be fully adopted. Adherence to the clinical trial guidelines of the International Headache Society could also mean violation of the new Helsinki declaration of ethics. Some ethics committees have already adopted the new declaration, which has caused concern among clinical investigators, who find this document to be vastly out of the line with common practice. At the moment, the situation is unclear and debated with increasing polarity concerning the scientific and ethical issues regarding the use of placebo in clinical trials.

Adolescent↗
PubMed2002

Features of medication overuse headache following overuse of different acute headache drugs.

OBJECTIVE: To investigate pharmacologic features such as mean critical duration until onset of medication-overuse headache (MOH) (MCDO), mean critical monthly intake frequencies (MCMIF), and mean critical monthly dosages (MCMD) as well as specific clinical features of MOH after overuse of different acute headache drugs, with a focus on newly approved triptans. METHODS: In a prospective study 98 patients with MOH according to International Headache Society (IHS) criteria underwent standardized inpatient withdrawal from their medication. Patient diaries and structured interviews were used to calculate the MCDO, MCMIF, and MCMD for each substance group. RESULTS: The MCDO was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). The MCMIF was lowest for triptans (18 single doses per month), higher for ergots (37), and highest for analgesics (114). Although patients overusing ergots and analgesics typically had a daily tension-type headache, patients with triptan-induced MOH were more likely to describe a (daily) migraine-like headache or an increase in migraine frequency. CONCLUSION: Overuse of triptans leads to MOH faster and with lower dosages compared with ergots and analgesics. Clinical features of MOH depend on the type of overused headache medication. Pharmacologic and clinical characteristics of triptan-induced MOH call for the renewal of the current IHS classification.

Acute Disease↗
PubMed2002

Balo's concentric sclerosis. Evolution of active demyelination demonstrated by serial contrast-enhanced MRI.

We report a case of Balo's concentric sclerosis with peculiar MRI findings. Unlike previously published cases all concentric rings in our case showed marked enhancement, supporting the view of synchronous active demyelination in the lesion. Follow-up MRI disclosed a change of the lesions into a confluent pattern more resembling a typical large MS plaque. There were no oligoclonal bands or intrathecal Ig-G synthesis. The hypothesis concerning the pathophysiology of the lesions' typical and peculiar morphological appearance and its relationship to multiple sclerosis are briefly discussed.

Adult↗
PubMed2002

Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects.

It has been suggested that the immune-endocrine communication plays an important role in development and progression of multiple sclerosis (MS). Interferon beta (IFN beta-1b) treatment is the therapy of choice in patients suffering from relapsing remitting or secondary chronic progressive multiple sclerosis. While typical adverse events of IFN beta-1b treatment such as flu-like symptoms or fatigue are well studied, little is known about the acute changes in the immune and neuroendocrine system. Therefore, we analyzed the short-term effects of IFN beta-1b on cortisol, epinephrine, norepinephrine, prolactin and growth hormone (GH) plasma levels before and 4, 8 and 24 h after IFN beta-1b administration in healthy subjects. Moreover, we determined heart rate, blood pressure, body temperature, leukocyte and lymphocyte subsets and plasma levels of interleukin (IL)-1 beta, IL-6, IL-10 and tumor necrosis factor (TNF)-alpha. IFN beta-1b led to an increase in body temperature and heart rate, and in parallel, elevated cortisol, prolactin and GH plasma levels at 4 and 8 h after IFN beta-1b injection. There were no significant alterations in blood pressure, norepinephrine or epinephrine plasma levels. Simultaneously, IFN beta-1b injection led to an immediate granulocytosis while concomitantly decreasing peripheral lymphocytes, especially natural killer (NK) cells. At the same time, IL-6, IL-10 and TNF-alpha plasma levels showed an overall increase. Overall, cytokine administration exerts strong stimulatory effects on the hypothalamic-pituitary-adrenal (HPA)-axis that may contribute to the side effects of IFN beta-1b therapy and affect the efficacy of IFN beta-1b treatment.

Adjuvants, Immunologic↗
PubMed2001

Clinical features of withdrawal headache following overuse of triptans and other headache drugs.

BACKGROUND: Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances. METHOD: In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days. RESULTS: The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02). CONCLUSION: The duration and severity of withdrawal clearly depend on the type of overused headache drug only.

Adult↗
PubMed2001

An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system.

Calcitonin gene related peptide (CGRP) released from the C-fibers projecting from the trigeminal ganglion to the meninges has been suggested to play a crucial role in the pathophysiology of headache, particularly migraine. In humans it has been shown that CGRP is released during migraine-attacks, and this is attenuated by the administration of typical anti-migraine drugs such as dihydroergotamine or sumatriptan. We describe a new rat model which allows the study of CGRP release from the meninges into venous blood following activation of the trigeminal vascular system. The effects of classical and new anti-migraine drugs such as acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) were evaluated in comparison with the established model of neurogenic inflammation in the meninges. Sumatriptan and donitriptan inhibited CGRP release as well as neurogenic inflammation. ASA, however, attenuated neurogenic inflammation, but not CGRP release, confirming the concept of prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the further study of prejunctional pharmacology and mechanisms of neuropeptide release in the trigeminal vascular system, which might be crucial for the further development of potent, more effective anti-migraine drugs.

Animals↗
PubMed2001

The prevention of migraine: a critical review with special emphasis on beta-adrenoceptor blockers.

Migraine is one of the most frequent neurological disorders affecting up to 15% of the general population. Many patients require not only management of individual migraine episodes but also prophylactic treatment. beta-adrenoceptor blockers, flunarizine and valproic acid have been established as first-line agents for the prophylaxis of migraine attacks. Among the beta-adrenoceptor blockers propranolol and metoprolol are best documented and hence deserve preferential use. On the other hand, it appears that other beta-adrenoceptor blockers, perhaps with the exception of those with intrinsic sympathomimetic activity, can be equally effective. Uncertainties regarding the relative merits of various treatment modalities are largely caused by lack of adherence to specific requirements for clinical trials on migraine prophylaxis. Therefore, this article reviews internationally recommended conditions for reliable studies on migraine prophylaxis and appraises individual agents in the light of these criteria.

Adrenergic beta-Antagonists↗
PubMed2001

Drug-induced headache: long-term follow-up of withdrawal therapy and persistence of drug misuse.

Patients suffering from migraine, tension-type headache (TTH), or combined headache (CH) are at risk of developing drug-induced headache (DIH) due to regular use of analgesics, ergot alkaloids, and triptans. The aim of our study was to determine (1) the clinical features of DIH, (2) the outcome of withdrawal therapy using high methodological standards, and (3) predictors which could explain the high relapse rate (more than 40%) after a previously successful withdrawal therapy. We retrospectively reviewed 103 patients with migraine or TTH who underwent withdrawal therapy between 1994 and 1998. The long-term follow-up (2-4 years after therapy) was conducted by phone and by specially trained psychologists using a structured interview which enclosed characteristics of headache and medication behavior as well as patients global assessment of success. Complete sets of data were available from 83 patients (38 migraine, 26 TTH, 19 CH). The most frequently abused drugs were caffeine-combined analgesics (24%), followed by caffeine-combined ergotamines (19%), pure ergot alkaloids (17%), and monoanalgesics (17%). 48.5% of the patients suffered an abuse relapse within 4 years and developed the complete features of DIH again. Analgesic and ergot alkaloid combinations with caffeine lead significantly more often to a relapse. A long-term successful therapy is connected with a significant reduction of the frequency of headache attacks. Under relapse conditions, the patients reached their former headache frequency level. The data show a higher relapse rate than previously assumed and that certain substance groups bear a higher relapse risk.

Adult↗
PubMed2001

Analgesics.

Analgesics such as acetaminophen (paracetamol), acetylsalicyclic acid and non-steroidal anti-inflammatory drugs are effective in the treatment of migraine attacks. Comparative studies indicate that their efficacy is similar or slightly inferior to sumattriptan, a specific antimigraine drug. Few data on the efficacy of opioid drugs in the treatment of migraine are available. They seem to be effective but carry the risk of dependency and may cause drug-induced headache.

Acetaminophen↗
PubMed2001

Advances in pharmacological treatment of migraine.

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation.

Adult↗
PubMed2001

Medication overuse headache: a focus on analgesics, ergot alkaloids and triptans.

Medication overuse headache (MOH, formerly known as drug-induced headache) is a well known disorder following the frequent use of analgesics or any other antiheadache drug including serotonin 5-HT(1B/D) agonists (triptans). Recent studies suggest clinical features of MOH depend on the substance class that has been overused. The delay between the frequent intake of any antiheadache drug and daily headache is shortest for triptans (mean 1.7 years), longer for ergot alkaloids (mean 2.7 years) and longest for analgesics (mean 4.9 years). Treatment includes withdrawal followed by structured acute therapy and initiation of specific prophylactic treatment for the underlying primary headache. The relapse rate within 6 months after successful withdrawal is about 30% and increases steadily up to 50% after 5 years.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Effects of alniditan on neurogenic oedema in the rat dura mater and on contraction of rat basilar artery.

The non-indole 5-HT receptor agonist, alniditan (R 91274), was tested and compared to sumatriptan in an in vivo model of neurogenic inflammation within the meninges of rats and in rat basilar artery in a Mulvany-Halpern chamber in vitro. Alniditan dose dependently attenuated the neurogenic inflammation and was more potent than sumatriptan. The alniditan response was blocked by the 5-HT(1B/D) receptor antagonist, GR 127935 (2'-methyl-4'-(5-methyl-[1,2, 4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide), but not by ketanserin, indicating that the effect is mediated through 5-HT(1B/D) receptors. Alniditan did not attenuate substance P-induced inflammation, suggesting that the mediating receptors are located prejunctionally. In vitro alniditan exhibited less vasoconstrictive effects on the rat basilar artery than did sumatriptan, although at a very high concentration (1 mM), alniditan caused intensive constriction, most likely through a mechanism independent from 5-HT receptor activation.

Animals↗