Multiple sclerosis (Houndmills, Basingstoke, England), Jan 6, 2016
Gender and age at onset are important epidemiological factors influencing prevalence, clinical pr... more Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, ...
Neuromyelitis optica (NMO) attacks are often severe, difficult to treat, and leave residual defic... more Neuromyelitis optica (NMO) attacks are often severe, difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. Retrospective review of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete, CR; partial, PR; no remission, NR). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEE), a patient-based statistical approach. 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1153 treatment courses comprised high-dose intravenous steroids (HD-S, n=810), plasma exchange (PE, n=192), immunoadsorption (IA, n=38), other (n=80), and unknown (n=33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, thi...
The significance of occlusal disharmony for the development of painful temporomandibular disorder... more The significance of occlusal disharmony for the development of painful temporomandibular disorder (TMD) is controversial. The ongoing biomechanical strain caused by occlusal disharmony might lead to sensitization processes in the nociceptive system. Understanding these processes might be an important step toward understanding the possible relationship between occlusal disharmony and TMD. In this study, we therefore investigated whether subjects with occlusal disharmony (n = 22) differ from healthy controls (n = 26) in their pain perception and pain modulation by stress and relaxation. Trigeminal and extratrigeminal experimental pain perception (pinprick, heat, and pressure pain) was assessed before and after stress (mental arithmetic) and relaxation (viewing of low-arousal pictures). There were no group differences in pain perception at baseline or during the stress task. Compared with controls, the occlusal disharmony group exhibited an inadequate reduction in pain perception durin...
The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies ... more The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies confirmed changes in ocular blood flow during CH attacks. Furthermore, vasoconstricting medication influences blood supply to the eye. We investigated the retina of CH patients for structural retinal alterations with optical coherence tomography (OCT), and how these changes correlate to headache characteristics, oxygen use and impaired visual function. Spectral domain OCT of 107 CH patients - 67 episodic, 35 chronic, five former chronic sufferers - were compared to OCT from 65 healthy individuals. Visual function tests with Sloan charts and a substantial ophthalmologic examination were engaged. Reduction of temporal and temporal-inferior retinal nerve fibre layer (RNFL) thickness was found in both eyes for CH patients with a predominant thinning on the headache side in the temporal-inferior area. Chronic CH patients revealed thinning of the macula compared to episodic suffers and healthy individuals. Bilateral thinning of temporal RNFL was also found in users of 100% oxygen compared to non-users and healthy controls. Visual function did not differ between patients and controls. Our OCT findings show a systemic effect causing temporal retinal thinning in both eyes of CH patients possibly due to attack-inherent or medication-induced frequent bilateral vessel diameter changes. The temporal retina with its thinly myelinated parvo-cellular axons and its more susceptible vessels for the vasoconstricting influence of oxygen inhalation seems to be predisposed for tissue damage-causing processes related to CH.
Interferon-β (IFN-β) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the ... more Interferon-β (IFN-β) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the effect of serum from 15 IFN-β-1b-treated multiple sclerosis (MS) patients on the permeability read-outs of small solutes in an in vitro BBB model consisting of human brain microvascular endothelial cells in co-culture with rat astrocytes. The addition of sera from IFN-β-treated patients resulted in a significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) reduced permeability as compared with untreated patients. Our findings show that sera from IFN-β-1b-treated MS patients have a stabilizing effect on the in vitro BBB. We suggest an unknown potentially pro-inflammatory factor in the serum of MS patients that may lead to a BBB dysfunction and can be modulated by IFN-β.
Journal of Neurology, Neurosurgery & Psychiatry, 2014
To evaluate the efficacy of an evidence-based patient information programme aiming to increase in... more To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice in MS patients. A 12-month, six-centre, double-blind randomised controlled clinical trial with 192 patients with a diagnosis of confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h interactive evidence-based educational programme was compared with a 4-h MS-specific stress management programme. The primary endpoint was informed choice after 6 months comprising risk knowledge and congruency between attitude towards immunotherapy and actual immunotherapy uptake. Secondary endpoints included autonomy preference, decision autonomy, decisional conflict and satisfaction, anxiety and depression, and number of immunotherapies. For the primary endpoint, a significant difference was shown with 50 of 85 (59%) participants in the intervention group achieving informed choice after 6 months compared with 18 of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Four weeks after the intervention, more participants in the intervention group showed good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). There were no significant differences between groups for attitude towards immunotherapy and for immunotherapy uptake. There were trends towards increased autonomy preference after the intervention and increased adherence to immunotherapies in the intervention group. The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.
Multiple sclerosis (Houndmills, Basingstoke, England), Jan 6, 2016
Gender and age at onset are important epidemiological factors influencing prevalence, clinical pr... more Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, ...
Neuromyelitis optica (NMO) attacks are often severe, difficult to treat, and leave residual defic... more Neuromyelitis optica (NMO) attacks are often severe, difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. Retrospective review of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete, CR; partial, PR; no remission, NR). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEE), a patient-based statistical approach. 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1153 treatment courses comprised high-dose intravenous steroids (HD-S, n=810), plasma exchange (PE, n=192), immunoadsorption (IA, n=38), other (n=80), and unknown (n=33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, thi...
The significance of occlusal disharmony for the development of painful temporomandibular disorder... more The significance of occlusal disharmony for the development of painful temporomandibular disorder (TMD) is controversial. The ongoing biomechanical strain caused by occlusal disharmony might lead to sensitization processes in the nociceptive system. Understanding these processes might be an important step toward understanding the possible relationship between occlusal disharmony and TMD. In this study, we therefore investigated whether subjects with occlusal disharmony (n = 22) differ from healthy controls (n = 26) in their pain perception and pain modulation by stress and relaxation. Trigeminal and extratrigeminal experimental pain perception (pinprick, heat, and pressure pain) was assessed before and after stress (mental arithmetic) and relaxation (viewing of low-arousal pictures). There were no group differences in pain perception at baseline or during the stress task. Compared with controls, the occlusal disharmony group exhibited an inadequate reduction in pain perception durin...
The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies ... more The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies confirmed changes in ocular blood flow during CH attacks. Furthermore, vasoconstricting medication influences blood supply to the eye. We investigated the retina of CH patients for structural retinal alterations with optical coherence tomography (OCT), and how these changes correlate to headache characteristics, oxygen use and impaired visual function. Spectral domain OCT of 107 CH patients - 67 episodic, 35 chronic, five former chronic sufferers - were compared to OCT from 65 healthy individuals. Visual function tests with Sloan charts and a substantial ophthalmologic examination were engaged. Reduction of temporal and temporal-inferior retinal nerve fibre layer (RNFL) thickness was found in both eyes for CH patients with a predominant thinning on the headache side in the temporal-inferior area. Chronic CH patients revealed thinning of the macula compared to episodic suffers and healthy individuals. Bilateral thinning of temporal RNFL was also found in users of 100% oxygen compared to non-users and healthy controls. Visual function did not differ between patients and controls. Our OCT findings show a systemic effect causing temporal retinal thinning in both eyes of CH patients possibly due to attack-inherent or medication-induced frequent bilateral vessel diameter changes. The temporal retina with its thinly myelinated parvo-cellular axons and its more susceptible vessels for the vasoconstricting influence of oxygen inhalation seems to be predisposed for tissue damage-causing processes related to CH.
Interferon-β (IFN-β) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the ... more Interferon-β (IFN-β) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the effect of serum from 15 IFN-β-1b-treated multiple sclerosis (MS) patients on the permeability read-outs of small solutes in an in vitro BBB model consisting of human brain microvascular endothelial cells in co-culture with rat astrocytes. The addition of sera from IFN-β-treated patients resulted in a significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) reduced permeability as compared with untreated patients. Our findings show that sera from IFN-β-1b-treated MS patients have a stabilizing effect on the in vitro BBB. We suggest an unknown potentially pro-inflammatory factor in the serum of MS patients that may lead to a BBB dysfunction and can be modulated by IFN-β.
Journal of Neurology, Neurosurgery & Psychiatry, 2014
To evaluate the efficacy of an evidence-based patient information programme aiming to increase in... more To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice in MS patients. A 12-month, six-centre, double-blind randomised controlled clinical trial with 192 patients with a diagnosis of confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h interactive evidence-based educational programme was compared with a 4-h MS-specific stress management programme. The primary endpoint was informed choice after 6 months comprising risk knowledge and congruency between attitude towards immunotherapy and actual immunotherapy uptake. Secondary endpoints included autonomy preference, decision autonomy, decisional conflict and satisfaction, anxiety and depression, and number of immunotherapies. For the primary endpoint, a significant difference was shown with 50 of 85 (59%) participants in the intervention group achieving informed choice after 6 months compared with 18 of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Four weeks after the intervention, more participants in the intervention group showed good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). There were no significant differences between groups for attitude towards immunotherapy and for immunotherapy uptake. There were trends towards increased autonomy preference after the intervention and increased adherence to immunotherapies in the intervention group. The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.
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