Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Health-Related Quality of Life Outcomes from Botulinum Toxin Treatment in Spasticity.

OBJECTIVE: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment. METHODS: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed. RESULTS: BoNT improved the EQ visual analog scale (EQ VAS). In addition, state of health and pain maxima improved. The EQ VAS improvement correlated with pre-injection characteristics of the EQ VAS and life satisfaction in the "movement disorders" domain. CONCLUSION: EQ VAS is sensitive for monitoring HR-QoL outcomes in an unselected real life observational cohort. This study may inform future studies intended to validate prediction variables that could inform on HR-QoL effects of BoNT treatment in spasticity.

Health-related quality of life outcomes from botulinumtoxin treatment in blepharospasm.

OBJECTIVE: Blepharospasm associates with impairment in generic health-related quality of life (HR-QoL). Albeit botulinum toxin is widely used to alleviate the motor symptoms of blepharospasm, its effect on generic health-related quality of life (HR-QoL) is heterogeneous. PATIENTS AND METHODS: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5 L) from botulinum toxin (BoNT) injection in a prospective cohort of patients with blepharospasm (n = 55). Additionally, we characterized motor and non-motor signs of blepharospasm including motor symptom improvement, life satisfaction, depressive symptoms, pain and sleep quality. Patients were assessed at the end of a regular three-month period from last injection (Timepoint1) and four weeks after the re-injection of BoNT (Timepoint2). RESULTS: There was no improvement of generic HR-QoL on group-level. Individual findings were heterogeneous, dividing patients in three groups of responders (RESP), unchanged outcomes (UNCHN), and worsening (WORSE). We identified, that these subgroups differed at Timepoint 1 with respect to EQ-5D-5 L, EQ-VAS, life satisfaction (health and movement disorders domains), Beck's Depression inventory, and sleep quality (One-way ANOVAs, P <  0.05, adjusted for multiple comparisons). In post-hoc Tuckey tests, RESP or WORSE showed distinct differences from UNCHN that might help to separate the subgroups in future. As such, RESP showed higher impairment in EQ-5D-5L, EQ-VAS, and Beck's Depression Inventory compared to UNCHN (unlike WORSE), whereas WORSE showed higher impairment in life satisfaction 'movement disorders' domain (unlike RESP). CONCLUSION: Our study suggests, that several dependent non-motor, life satisfaction and generic HR-QoL measures associate to individual patient outcomes. The variables identified in this study may be validated in future studies to predict HR-QoL outcomes in patients with blepharospasm.

Increased serotonin transporter availability in the brainstem of migraineurs.

For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central serotonergic system is located in the raphe nuclei and the adjacent reticular formation in the brainstem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand (123)I-ADAM [2-((2-((dimethylamino) methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine serotonergic system being involved in the pathophysiology of migraine. Nineteen migraine patients and 10 healthy, age- and sex-matched controls were enrolled. The neuroimaging study was performed interictally during the pain-free interval. Single Photon Emission Computed Tomography (SPECT)-images were coregistered with MRI-scans. Region of interest (ROI)-analysis revealed a highly significant increase of (123)I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, (123)IADAM uptake in the thalamus did not differ significantly between migraineurs and controls. Our study demonstrates for the first time a significant increase of brainstem SERT-availability in migraineurs, suggesting a dysregulation of the brainstem serotonergic system. It remains to be elucidated whether the altered SERT-availability is causally related to migraine pathophysiology or whether it reflects secondary pathophysiological mechanisms.

Health-related quality of life outcomes from botulinum toxin treatment in hemifacial spasm.

BACKGROUND: Although botulinum neurotoxin (BoNT) injections may alleviate involuntary muscle contractions in hemifacial spasm substantially, it is less clear whether the motor effect would translate into improvements of health-related quality of life (HR-QoL). METHODS: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5L) from BoNT in a prospective cohort of patients with hemifacial spasm (n = 73). Additionally, we characterized appendicular motor and nonmotor signs on motor symptom improvement, depressive symptoms, pain and sleep quality. Patients were assessed at the end of a regular 3-month period from last injection (timepoint1) and 4 weeks after the reinjection of BoNT (timepoint2). RESULTS: Patients showed improved HR-QoL on the EQ-VAS (visual analogue scale) at timepoint2 compared with timepoint1. Moreover, we identified, that impairments in HR-QoL at timepoint1 correlated with life satisfaction and depressive symptoms, respectively. However, these associated variables did not predict the therapeutic effect. Instead, EQ-VAS at timepoint1 accounted for 34.5% of the variance of EQ-VAS improvement expressed as the difference between timepoint2 and timepoint1. CONCLUSION: Our study supports HR-QoL improvements in hemifacial spasm and the value of generic HR-QoL measures to estimate therapeutic outcome. However, the findings should be considered descriptive, and future high quality trials are needed for confirmatory purposes in order to refine treatment referral in hemifacial spasm with respect to QoL.

Botulinumtoxin Improves both Generic and Disease-Specific Quality of Life in Cervical Dystonia.

Botulinumtoxin injection (BoNT) into affected muscles is effective to improve motor symptoms of cervical dystonia (CD) by reducing muscle contraction and involuntary dystonic movement and posturing. However, the understanding of the effect on health-related quality of life (HR-QoL) and patient referral under HR-QoL aspects is incomplete. In this open-label clinical prospective observational study, we characterized the outcomes in CD (n = 159) from botulinumtoxin on both generic HR-QoL (EuroQol; EQ-5D-5L) and disease-specific HR-QoL [craniocervical dystonia questionnaire (CDQ-24)]. Additionally, we characterized motor and non-motor signs of dystonia including motor symptom improvement, depressive symptoms, pain, and sleep quality. We assessed patients at the end of a regular 3-month period from last injection (Timepoint1) and 4 weeks after the re-injection of BoNT (Timepoint2). We aimed to define outcomes on both generic and disease-specific HR-QoL and to evaluate predictors of therapeutic outcome in terms of stepwise multiple regression models. Patients with CD showed a robust improvement of both generic and disease-specific HR-QoL. Furthermore, motor and non-motor signs improved. Multiple regression analyses revealed that EQ-5D-5L and "satisfaction with health" (Fragen zur Lebenszufriedenheit-G) at Timepoint1 predicted treatment response on generic HR-QoL outcome (R2 = 0.284; P = 0.019). Similarly, CDQ-24 and Beck's Depression inventory at Timepoint1 predicted the treatment response on disease-specific HR-QoL (R2 = 0.253; P = 0.026). Our study underscores both generic and disease-specific HR-QoL improvements in CD, and provides useful predictors on HR-QoL outcomes.

Catechol-o-methyltransferase and blood pressure in humans.

BACKGROUND: Whether catechol-O-methyltransferase (COMT), the enzyme that metabolizes extraneuronal norepinephrine, contributes to blood pressure regulation in humans is unknown. METHODS AND RESULTS: We studied incremental doses of the COMT inhibitor entacapone, the sympathetic stimulant yohimbine, and placebo in 7 patients with multiple system atrophy (Shy Drager syndrome). We selected these unique subjects because norepinephrine exerts an exaggerated increase in blood pressure in these patients. Autonomic regulation was characterized with intravenous phenylephrine, nitroprusside, and trimethaphan. Patients were extremely hypersensitive to phenylephrine and nitroprusside. Trimethaphan elicited a profound depressor response. Phenylephrine sensitivity increased only slightly during ganglionic blockade. Entacapone increased systolic blood pressure dose-dependently; however, the pressor response to yohimbine was approximately 3.5 times greater than the maximal response to entacapone. CONCLUSIONS: COMT inhibition elicits a moderate, dose-dependent pressor response in the setting of severely impaired baroreflex buffering. Patients with multiple system atrophy allow for the characterization of subtle manipulations of norepinephrine turnover and blood pressure regulation in small numbers of subjects.

Baroreflex buffering and susceptibility to vasoactive drugs.

BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

High doses of pergolide improve clinical global impression in advanced Parkinson's disease:- a preliminary open label study.

We evaluated the efficacy and safety of high-dose pergolide treatment in patients with moderate to severe Parkinson's disease (PD) in an open-label multicenter clinical trial. The primary objective was to assess the amount of reduction in levodopa, the improvement in Unified Parkinson's Disease Rating Scale (UPDRS) and adverse reactions. We treated 32 patients with PD presenting with motor fluctuations. Pergolide treatment started with a dose escalation period of 12 weeks followed by a 12-week continuation period. Pergolide doses were increased up to a maximum of 12 mg/day in combination with a simultaneous decrease of levodopa doses in 100mg steps. Levodopa was reduced from 500 mg/day (median) to 250 mg/day. Mean UPDRS part III improved significantly (p=0.01). Clinical global impression improved significantly after 24 weeks (p<0.01). Most frequent adverse events were hallucinations, asthenia, anxiety, abdominal pain, and peripheral edema. Twenty-two patients finished the complete study according to protocol. A possible relationship to the study medication was assumed for two serious adverse events reporting psychosis. We conclude that high doses of pergolide are efficacious in advanced stages of PD if given in appropriate regimens.

Solving the Issue of Restenosis After Stenting of Intracranial Stenoses: Experience with Two Thin-Strut Drug-Eluting Stents (DES)-Taxus Element™ and Resolute Integrity™.

PURPOSE: Thin-strut, flexible DES are suitable for intracranial stenting and may improve long-term vessel patency. The purpose of this study was to report our experience with two new-generation DES for the treatment of intracranial atherosclerotic disease. PATIENTS AND METHODS: We retrospectively reviewed all patients treated with Taxus Element™ or Resolute Integrity™ stent for an intracranial atherosclerotic stenosis between March 2011 and August 2013. Technical success was defined as the ability to deploy the device at the desired location and reduce the degree of stenosis below 50 %. All procedure-related strokes were recorded. Control angiography was scheduled after 6 weeks, 3, 6, and 12 months and yearly thereafter. A luminal narrowing ≥50 % was regarded as a restenosis. Stroke recurrence in the territory of the treated artery was reported. RESULTS: In the defined period we treated 101 patients harboring 117 intracranial stenoses. The procedure was successful in 100 (85.5 %) lesions. Procedure-related strokes occurred in 10 (9.9 %) patients with a permanent morbidity in 3 (3.0 %). Follow-up angiography was available for 83 of 100 (83.0 %) successfully treated lesions with an average of 355 days (IQR 153-482 days). Three (3.6 %) asymptomatic restenoses were detected. All occurred after treatment with Resolute Integrity™, none after Taxus Element™ (p = 0.059). New strokes in the territory of the treated artery were encountered in 2 (2.6 %) occasions. CONCLUSION: Thin-strut DES improve long-term patency and reduce the risk of subsequent stroke. Differences between devices may exist. Feasibility is comparable to bare-metal balloon-mounted stents and procedure-related strokes occurred within the expected range.

Subthalamic stimulation differentially modulates declarative and nondeclarative memory.

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems.

Treatment of acute cluster headache with 20 mg sumatriptan nasal spray--an open pilot study.

We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was "pain free" 30 minutes after treatment. Secondary end-points included "headache response" (defined as headache improvement from "very severe", "severe" or moderate" pain to "mild" or "no" pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 "moderate" to "very severe" cluster headache attacks. 30 minutes after nasal spray application, 50% of attacks were completely aborted and 58% of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered "excellent" in two, "good" in four, "reasonable" in two and "poor" in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy.

Deep brain stimulation in dystonia.

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.

A fluorescence-based method to assess plasma protein extravasation in rat dura mater using confocal laser scanning microscopy.

We describe a nonradioactive, fluorescence-based method to assess plasma protein extravasation (PPE) in rat dura mater using confocal laser scanning microscopy (CLSM). Unilateral PPE can be induced by electrical stimulation of the ipsilateral trigeminal ganglion (TG) and is widely used as an experimental migraine model. The gold standard to determine PPE in the meninges is based on the detection of radiolabeled albumin ([125]I-BSA). The aim of this study was to develop a nonradioactive, histological method to quantify PPE in the meninges. The fluorescent dye Evans Blue (50 mg/kg) was injected intravenously to the rat 7 min prior to TG stimulation. PPE in dura mater was detected by a CLSM. The amount of extravasated Evans Blue in the dura mater was measured at six to eight regions of interest (ROIs) in the vicinity of large meningeal vessels. The ratio of the average fluorescence intensity within dura mater of the "stimulus side", compared to the contralateral "control side", was calculated for each animal. By using this method, The PPE ratio was 1.67+/-0.12 (n=5). Intravenous injection of three different dosages of the 5HT(1B/1D)-receptor agonist sumatriptan (25, 50, and 100 microg/kg) 15 min prior to stimulation attenuated PPE by 42+/-12%, 49+/-9%, and 86+/-15%, respectively (p<0.01). The approximated ED(50) value was 48 microg/kg. Our results are in accordance with previous reports in the literature using the radioactive approach. We conclude that CLSM is a safe, sensitive, and reliable method to assess PPE in rat meninges in an experimental migaine model.

The modified Bose method for the endovascular treatment of intracranial atherosclerotic arterial stenoses using the Enterprise stent.

BACKGROUND: Balloon dilatation and deployment of a self-expanding stent is a safe treatment for intracranial atherosclerotic stenoses. The significant recurrence rate might be related to the high radial force of the Wingspan stent. OBJECTIVE: To evaluate the procedural safety and stenosis recurrence rate by the use of a stent with reduced radial force (Enterprise). METHODS: Two hundred nine atherosclerotic stenoses (189 patients) were treated (median age, 68 years; 132 male) in a single center. Lesion locations included internal carotid artery (n = 27), middle cerebral artery (n = 62), vertebral artery (n = 64), basilar artery (n = 55), and posterior cerebral artery (n = 1). Pre- and postmedication included acetylsalicylic acid and Clopidogrel for at least 12 months. Preprocedural and follow-up examinations included magnetic resonance imaging (MRI), neurological assessment, and digital subtraction angiography (6, 12, 26, and 52 weeks). Data registry included age, sex, normal vessel diameter, degree of stenosis, residual stenosis after stent, minimal in-stent diameter, and occurrence of ischemic symptoms during follow-up. RESULTS: Median pre- and postprocedural stenosis rate was 65.4 ± 1% vs 25.1 ± 1%. Technical success rate was 100%. Major procedural complications occurred in 16 patients (8.1%). Combined neurological morbidity and mortality rate at 30 days was 2 patients (0.9%). In 174 stenoses (83%) angiographic follow-up was obtained (mean, 10.2 months). A restenosis (>50%) was observed in 43 (24.7%) cases after 4.2 months (mean) with 4 (9.3%) symptomatic lesions. Incidence of recurrent ischemia related to the stented artery was 2.2% during 10.2 months of mean follow-up. CONCLUSION: Undersized balloon angioplasty and deployment of an Enterprise stent is safe and effective for intracranial stenoses. Follow-up results were equal to or better than those reported for bare-metal balloon-expandable or self-expanding stents and yielded excellent protection from recurrent ischemia.

Do neurologists in Germany adhere to the national Parkinson's disease guideline?

Implementation of guidelines can improve clinical practice. The aim in this study was to investigate whether neurologists in Germany adhered to the national Parkinson's disease guideline. Data were obtained from a cross-sectional survey of 60 neurologists. Analyses were performed on 320 patients with idiopathic Parkinson's disease with either low grades of functional impairment (Hoehn and Yahr stage I) or higher grades of functional impairment (stage II-V) but without motor complications. The sample was divided into four groups depending on age and grade of functional impairment. For each group, a biometric parameter on the use of dopamine agonists and L-dopa was defined based on the guideline. In patients aged <70 years, the recommendation to use dopamine agonists without L-dopa (parameter 1) was observed in 53% of patients with lower grades of functional impairment, whilst recommended use of dopamine agonists in more functionally impaired patients (parameter 2) was followed to a greater extent (84%). In patients aged ≥70 years, recommendations to use L-dopa without dopamine agonists were adhered to in only 50% of less functionally impaired (parameter 3) and 52% of more functionally impaired (parameter 4) patients. In conclusion, our results indicated there was moderate but not full adherence to the guideline.

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.

BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719.

Effects of parecoxib on plasma protein extravasation and c-fos expression in the rat.

OBJECTIVE: We aimed to investigate the effects of the cyclooxygenases-2 (COX-2) inhibitor parecoxib on meningeal plasma protein extravasation (PPE) and on c-fos expression in the nucleus trigeminalis caudalis in an animal model of trigeminovascular activation. Background.-Recent reports about the efficacy of COX-2 inhibitors in migraine treatment suggest the involvement of COX-2 in migraine pathophysiology. So far, studies on the role of COX-2 in animal models of migraine are lacking. METHODS: Unilateral electrical stimulation of the trigeminal ganglion was performed in anesthetized male Sprague Dawley rats. We assessed PPE in the ipsilateral dura mater and expression of c-fos within the ipsilateral trigeminal nucleus caudalis (TNC) under control conditions and after pretreatment with parecoxib. RESULTS: Parecoxib significantly attenuated PPE in the rat dura mater. The PPE ratio under control conditions (1.73 +/- 0.19 (mean +/- SD)) was reduced by 58.9 +/- 30% after pretreatment with 10 mg/kg parecoxib and by 78.1 +/- 23% after pretreatment with 50 mg/kg. c-fos experiments: Compared with vehicle, all doses of parecoxib (1 mg/kg, 10 mg/kg, 50 mg/kg) significantly reduced the number of c-fos positive cells in the ipsilateral TNC (P < .05). The number of c-fos positive cells in the ipsilateral TNC was 50 +/- 2.7 (mean +/- SEM) under control conditions and 9.1 +/- 0.6 after pretreatment with 50 mg/kg parecoxib. CONCLUSION: Our study results suggest that COX-2 is involved in neurogenic inflammation of the rat dura mater. Moreover, the study points to a role of COX-2 inhibitors in trigeminal nociception at the second-order level.

Effect of hyperoxia on neurogenic plasma protein extravasation in the rat dura mater.

OBJECTIVE: We aimed to study the effect of normobaric hyperoxia on neurogenic inflammation of the rat dura mater. BACKGROUND: Inhalation of 100% oxygen is a first-line therapy for the treatment of acute cluster headache (CH). However, the mechanisms underlying the antinociceptive effect of oxygen are poorly understood. Sumatriptan, which is also effective in aborting CH attacks, is known to inhibit neurogenic inflammation of the dura mater. We hypothesized that hyperoxia reduces dural plasma protein extravasation in the model of electrically stimulating the rat trigeminal ganglion. METHODS: Unilateral stimulation of the trigeminal ganglion was performed in anesthetized male Sprague-Dawley rats. We assessed plasma protein extravasation (PPE) in the ipsilateral dura mater under normoxic (group 1) and hyperoxic conditions (group 2: pO(2) 200 mmHg; group 3: pO(2) 300 mmHg; group 4: pO(2) 400 mmHg). The study results were compared to the effect of sumatriptan (300 microg/kg) on dural PPE. RESULTS: Under normoxic conditions, the calculated extravasation ratio was 1.72 +/- 0.2. Hyperoxic treatment (groups 2, 3, 4) significantly attenuated dural PPE. At oxygen levels of 400 mmHg, the PPE ratio was 1.14 +/- 0.2 (P < .01). After IV application of sumatriptan (300 microg/kg), PPE was nearly abolished (PPE ratio: 1.06 +/-0.17). CONCLUSION: Our findings demonstrate that hyperoxia is able to inhibit dural PPE. Hyperoxia may play an anti-inflammatory role in neurogenic inflammation, but further studies are needed to clarify whether this effect is either caused by prejunctional mechanisms or by modulation of the vascular permeability at postcapillary venules.

Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study.

Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.