Novel oral anticoagulants in secondary prevention of stroke.

In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making.

Comparison of efficacy and safety of dabigatran, rivaroxaban and apixaban in patients with atrial fibrillation using network meta-analysis.

AIM: A network meta-analysis of the three new oral anticoagulants was performed from the three trials comparing dabigatran, rivaroxaban and apixaban with warfarin in patients with atrial fibrillation. METHODS: Data were extracted of the RE-LY study of dabigatran 110 mg bid and dabigatran 150 mg bid, the ROCKET AF trial of rivaroxaban and the ARISTOTLE trial of apixaban for the composite outcome of ischemic stroke and systemic embolism, for major bleeding, intracerebral bleeding, mortality and myocardial infarction. RESULTS: Dabigatran (150 mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110 mg bid, P=0.0364) and rivaroxaban (P=0.0388). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150 mg bid, P=0.036) or rivaroxaban (P=0.0002). Intracerebral hemorrhage occurred with equal frequency for all agents except for rivaroxaban (higher risk than dabigatran 110 mg bid, P=0.0070). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all P<0.05). CONCLUSION: All-cause mortality was not different for any agent or regimen. In the absence of head-to-head comparisons, this network meta-analysis suggests that apixaban and dabigatran 110 mg bid may offer the best benefit-risk balance for stroke prevention in non-valvular atrial fibrillation. Dabigatran 150 mg bid may be preferred for patients with a high risk for embolism.

[Neurostimulation for treatment of headaches]. / Neurostimulation zur Behandlung von Kopfschmerzen.

Only a small portion of patients with primary headaches are refractory to treatment concerning relief of headache episodes and prophylactic therapy of headaches. New methods of central and peripheral neurostimulation have been developed for these patients during the last few years and experience was mostly gained in small case series. The following overview gives a description of new stimulation methods, such as deep brain stimulation, occipital nerve stimulation, vagal nerve stimulation, neurostimulation of the sphenopalatine ganglion and transcranial magnetic stimulation.

Integrated headache care.

Patients with chronic or difficult to treat headaches are generally under the care of general practictioners or neurologists in private practice. Some are referred to a headache specialist for evaluation and advice. Treatment is often provided by the referring physician. An alternative is a multidisciplinary headache centre, where care is provided by different disciplines (neurology, behavioural psychology, psychiatry, psychosomatic medicine, physical therapy, sport therapy) across sectors of the healthcare system involving out- and inpatient care and treatment. This is called integrated headache care. This review summarizes experiences in integrated headache care settings in Europe and the USA, describes these settings, and reports outcome data.

Occipital nerve stimulation for the treatment of chronic cluster headache - lessons learned from 18 months experience.

OBJECTIVE: Neuromodulation has been recognized as a valuable surgical treatment option for patients with refractory chronic cluster headache (CCH). Due to the small number of afflicted individuals, the knowledge about this specific therapy is limited. In this study, we present our experiences with bilateral occipital nerve stimulation (ONS) in patients with CCH focusing on patient selection, pre- and postoperative evaluation, surgical procedures, and outcome. PATIENTS AND METHODS: Since December 2008, 10 patients with CCH have been treated with ONS at our department. Patients were recruited and clinically followed by a neurologist and a neurosurgeon. Baseline data records on frequency, intensity, and duration of attacks as well as the use of medication were assessed with a 30-day diary. Standardized questionnaires were used pre- and postoperatively and during the follow-up on a regular basis. Surgical procedure and stimulation parameters were standardized for all patients. Lead implantation was followed by a test period of 30 days prior to implantation of the permanent generator. Mean follow-up time was 12 months (range 3-18). RESULTS: All patients responded to the stimulation treatment. Frequency, duration, and severity of the cluster attacks were reduced in 90% of the patients. One patient had a significant reduction of his concomitant tension headache. 70 % of the patients needed less medication during the attacks. All patients reported an improvement in their quality of life. The SF-36 showed a tendency toward objective improvement in the field of psychological comfort. As a major adverse event, one generator had to be exchanged due to a local infection. Another patient had to be reoperated due to a scar tissue formation around the thoracic connector. CONCLUSIONS: ONS is a valuable tool in the treatment of patients with refractory CCH. According to our data, the potential side effects and complication rates of the operation are small. With a meticulous selection of patients by an interdisciplinary team, CCH can bed improve in the majority of the patients. Yet, the optimal parameters for the stimulation regarding pulse width and frequency remain unclear. For this reason, we started a prospective single-center observational trial at our center in October 2009, including patients with ONS, to identify the best stimulation parameters.

[Bilateral occipital nerve stimulation for the treatment of chronic cluster headache: case series and initiation of a prospective study]. / Beidseitige Nervus-occipitalis-Stimulation zur Behandlung des therapierefraktären chronischen Cluster-Kopfschmerzes: eigene Fallserie und Initiierung einer prospektiven Studie.

BACKGROUND: The chronic cluster headache (CCH) is a disabling disorder for every patient. Treatment is a challenging situation for the physician. Some patients will not experience adequate resolution of their cluster attacks by medication and the prophylaxis does not reduce the attacks sufficiently. Therefore, other treatment options have to be found. METHODS: Since December 2008 seven patients with CCH have been treated by bilateral occipital nerve stimulation (ONS) at the University Hospital Essen. Implantation of the electrodes and stimulation paradigms were standardised. The maximum follow-up to date is 12 months. RESULTS: ONS was successfully employed in all patients. The intensity of the attacks decreased by 50 %. The consumption of attack medication was reduced by 77 % on average. Some patients could reduce their medication prophylaxis. A tendency towards improved quality of life was seen in all patients by means of a standardised questionnaire (SF-36). One generator had to be exchanged due to infection. Scar formations required reoperation and adhesiolysis of the thoracic connector in another patient. 6 out of 7 patients would fully recommend the operation. CONCLUSION: Bilateral ONS is a promising treatment for CCH, with a low risk profile in our experience. Further studies have to be conducted to clarify the mechanism of the stimulation and optimal parameters of ONS. For this particular reason, patients with CCH have been included in a prospective study since October 2009.

The Virtual International Stroke Trials Archive (VISTA): results and impact on future stroke trials and management of stroke patients.

BACKGROUND: The Virtual International Stroke Trials Archive was established to improve stroke care and trial design through the collation, categorization and potential access to data sets from clinical trials for the treatment of stroke. METHODS: Virtual International Stroke Trials Archive currently provides access to a combined data set of 29 anonymised acute stroke trials and one acute stroke registry with data on >27,500 patients aged between 18 and 103 (mean 71) years. RESULTS: Virtual International Stroke Trials Archive has facilitated research across a broad canvas. The prognosis was poor in patients with very high blood pressure at the time of admission or with a wide variability of systolic blood pressure during the acute phase. The late occurrence of hyperthermia following an ischaemic stroke worsens the prognosis. Stroke lateralisation is not an important predictor of cardiac adverse events or 90-day mortality. Haemorrhagic transformation is seen frequently in patients with cardio-embolic strokes and is associated with a poor prognosis when occurring after the acute phase. Virtual International Stroke Trials Archive has allowed various prognostic models for patients with ischaemic or haemorrhagic stroke to be established and validated. More direct outcomes such as lesion volume can be useful in phase II clinical trials for determining whether a phase III trial should be undertaken. New outcome measures such as 'home time' may also strengthen future trials. On a worldwide level, the prognosis of stroke patients differs considerably between various countries. CONCLUSION: Virtual International Stroke Trials Archive provides an excellent opportunity for analysis of natural history data and prognosis. It has the potential to influence clinical trial design and implementation through exploratory data analyses.

[The value of "migraine surgery". Overview of the pathophysiological concept and current evidence]. / Stellenwert der "Migränechirurgie". Ubersicht über das pathophysiologische Konzept und die aktuelle Datenlage.

Often without sufficient scientific evidence, unconventional methods for migraine treatment are being put forward. Recently a trial using "migraine surgery" has been published. Its design is based on a concept of migraine pathogenesis without any scientific background and includes several severe methodological flaws. In spite of the above, the study is frequently cited in the lay press. The surgical procedure as well as the study are critically discussed.

Differences in Chinese diagnoses for migraine and tension-type headache: an analysis of the German acupuncture trials (GERAC) for headache.

A growing number of clinical trials are testing Chinese acupuncture in the management of headache disorders. Little is known, however, about the relationship between International Headache Society diagnostic criteria and traditional Chinese medicine (TCM) diagnosis in primary headache disorders. We conducted a secondary analysis of the data of the prospective, controlled, blinded German acupuncture trials for migraine and tension-type headache. Data were collected from 1042 headache patients, of whom 633 were diagnosed with migraine and 409 with tension-type headache. We found that the diagnoses of migraine and tension-type headache were mirrored by different patterns of TCM diagnoses, with the patterns Liver Yang Rising, Liver Fire Rising, and Phlegm appearing to be best suited to differentiating between migraine and tension-type headache. Although not unexpected, given that the diagnosis of primary headache disorders in both diagnostic systems is based largely on the nature and quality of patient-reported symptoms, this finding suggests that migraine and tension-type headache are associated with different patterns of TCM diagnosis.

Antiplatelet agents in stroke prevention: acute and long-term treatment strategies.

In primary prevention, aspirin reduces the risk of stroke but not of myocardial infarction in women while in men only the risk of myocardial infarction but not stroke could be significantly reduced. Only aspirin has been shown to be safe and effective in large randomized trials in the first 48 hours after ischemic stroke. Aspirin/dipyridamole and clopidogrel both reduce the risk of a combined cardiovascular outcome in long-term secondary prevention compared to aspirin alone. More potent antiplatelet drugs or combination of aspirin and clopidogrel prevent more ischemic events, but also lead to more bleeding complications. No benefit of oral anticoagulants could be shown in patients with non-cardioembolic stroke. In patients with atrial fibrillation oral anticoagulation is more effective than aspirin in stroke prevention. The choice between oral anticoagulants and aspirin in these patients depends on age and the individual risk factor profile. Patients with symptomatic intracranial stenosis have a higher risk of intracerebral bleeding with oral anticoagulation compared to high dose aspirin. Aspirin is the recommended treatment in stroke patients with a patent foramen ovale.

Gray matter changes related to chronic posttraumatic headache.

BACKGROUND: Although up to 15% of patients with whiplash injury develop chronic headache, the basis and mechanisms of this posttraumatic headache are not well understood. METHODS: Thirty-two patients with posttraumatic headache following whiplash injury were investigated within 14 days after the accident and again after 3 months using magnetic resonance-based voxel-based morphometry. Twelve patients developed chronic headache lasting longer than 3 months and were studied a third time after 1 year. RESULTS: Patients who developed chronic headache revealed decreases in gray matter in the anterior cingulate and dorsolateral prefrontal cortex after 3 months. These changes resolved after 1 year, in parallel to the cessation of headache. The same patients who developed chronic headache showed an increase of gray matter in antinociceptive brainstem centers, thalamus, and cerebellum 1 year after the accident. CONCLUSION: We demonstrate adaptive gray matter changes of pain processing structures in patients with chronic posttraumatic headache in regard to neuronal plasticity, thus providing a biologically plausible basis for this common, disabling problem.

[Therapy of primary chronic headache: chronic migraine, chronic tension type headache and other forms of daily chronic headache]. / Therapie primärer chronischer Kopfschmerzen: Chronische Migräne, chronischer Kopfschmerz vom Spannungstyp und andere chronische tägliche Kopfschmerzen.

The criteria of the International Headache Society (IHS) define four different primary headache syndromes with daily chronic headaches: chronic migraine, episodic and chronic tension type headache, hemicrania continua, new daily persisting headache. A further important differential diagnosis is medication overuse headache (previously known as analgesia headache). The German, Austrian, and Swiss headache societies now present the first joint guidelines for therapy of these headache syndromes. The current literature was reviewed and a summary is presented. The therapy recommendations do not only include the scientific evidence but also the practical relevance.

[Current diagnosis and treatment of migraine]. / Aktuelle Diagnostik und Therapie der Migräne.

Headaches are one of the most common disorders and symptoms in daily medical practice. The prevalence of migraine is 8% in men and 12-15% in women. Dramatic progress in the areas of epidemiology, pathophysiology, and acute and preventive therapy of migraine has been made over the past 100 years, with triptans being the breakthrough for treating acute migraine attacks. Beta blockers, calcium antagonists, and neuromodulators are available for preventive migraine therapy. Nonpharmacologic treatment also plays an important role in migraine prevention. New medical care structures such as integrated headache care provide better support for patients with migraine, particularly those with chronic migraine.