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Biomedical subjects

Wolfgang H Oertel

Publications and source records attributed to Wolfgang H Oertel.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study).

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.

Adolescent↗
PubMed2006

Cyclical excitability of the motor cortex in patients with catamenial epilepsy: a transcranial magnetic stimulation study.

PURPOSE: The pathophysiology of catamenial epilepsy is still unclear. Therefore, we investigated the cortical excitability of women with catamenial epilepsy during different phases of the menstrual cycle. METHODS: Using transcranial magnetic stimulation, six patients suffering from catamenial epilepsy were investigated during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle (day 1 being the first day of menstrual bleeding), resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. The non-parametric Friedman-test for multiple comparisons and Wilcoxon signed rank test were used for statistical analysis. RESULTS: Five patients suffered from focal epilepsy (three right hemispheric, one bitemporal, one unknown origin) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. In the right hemispheres there was a significant change of CSP duration in the course of the menstrual cycle (chi(2)=8.3, P=0.041), due to a shorter CSP during the luteal phase (Z=-2.0, P=0.043) and menstruation (Z=-2.2, P=0.028) as compared to the follicular phase. There was no significant variation of CSP in the left hemispheres. RMT, ICI and ICF showed no significant changes in the course of the menstrual cycle. CONCLUSIONS: The CSP changes suggest a decreased inhibition involving GABA-ergic neurotransmission during the luteal phase and menstruation. These TMS alterations correlated with the clinical course of the epilepsies and were found in the hemispheres containing the majority of the epileptogenic zones.

Adult↗
PubMed2006

Language dominance in mesial temporal lobe epilepsy: a functional transcranial Doppler sonography study of brain plasticity.

Functional transcranial Doppler sonography was used to study hemispheric language dominance (HLD) in 24 right-handed patients with left temporal lobe epilepsy (TLE) and a structural lesion in the left temporal lobe and in 69 healthy controls. Twenty-five percent of the patients and 4% of controls showed atypical (right or bilateral) HLD. Degree of HLD was not correlated with age, Full Scale IQ, Verbal IQ, spike frequency, seizure frequency, age at seizure onset, or duration of TLE. Atypical HLD appears to be lesion-induced, independent of epilepsy characteristics.

Adolescent↗
PubMed2006

Modulation of electrically induced pain by paired pulse transcranial magnetic stimulation of the medial frontal cortex.

OBJECTIVE: Aim of this study was to investigate whether paired pulse transcranial magnetic stimulation (ppTMS) applied over the medial frontal cortex (MFC) affects acute Adelta fiber-mediated electrically induced pain. In addition, we investigated whether this effect depends on the time course of the stimulation, on the noxious stimulus intensity or on the ppTMS intensity. METHODS: For painful stimulation, the electrical stimulus for the nociceptive flexion reflex (NFR) was used. PpTMS (ISI: 50 ms) was applied over the medial frontal cortex at different intervals ranging from 0 to 1,000 ms following the previous elicited NFR in 10 healthy volunteers. Three sequences at 3 different NFR stimulus intensities (at NFR threshold, 1.3 x and 1.6 x NFR threshold) with a ppTMS stimulus intensity at 1.2 x resting motor threshold (RMT) and one sequence with elevated ppTMS at 1.6 x RMT stimulus intensity were performed. Pain intensity and pain unpleasantness were assessed by visual analogue scales. RESULTS: Pain ratings differed in dependence of the interstimulus interval between NFR and ppTMS. Post-hoc t-tests revealed an increased verbal pain report within interstimulus intervals from 25 to 75 ms at NFR threshold as well as for 25 ms at 1.3 x NFR threshold when ppTMS was applied at 1.2 x RMT and from 0 to 75 ms at 1.6 x NFR threshold when ppTMS was applied at 1.6 x RMT. CONCLUSIONS: The present data suggest that ppTMS over MFC-applied in a certain time window-can enhance pain perception of acute Adelta fiber-mediated electrically induced pain. We hypothesize that the increase of pain is due to interference between ppTMS and the incoming nociceptive input. Further pain processing might be modulated by direct effects on MFC or indirect effects on anterior cingulate cortex (ACC) or spinal nociception. SIGNIFICANCE: Brain areas involved in cognitive and emotional adaptation to pain can be used, in place of primary motor areas, as cortical targets in TMS trials of experimental or ongoing pain.

Adult↗
PubMed2006

Modulation of human motor cortex excitability by single doses of amantadine.

Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.

Adult↗
PubMed2006

Regional vulnerability of mesencephalic dopaminergic neurons prone to degenerate in Parkinson's disease: a post-mortem study in human control subjects.

Parkinson's disease (PD) is characterized by loss of dopaminergic (DA) neurons in the human midbrain, which varies greatly among mesencephalic subregions. The genetic expression profiles of mesencephalic DA neurons particularly prone to degenerate during PD (nigrosome 1 within the substantia nigra pars compacta-SNpc) and those particularly resistant in the disease course (central grey substance-CGS) were compared in five control subjects by immuno-laser capture microdissection followed by RNA arbitrarily primed PCR. 8 ESTs of interest were selected for analysis by real time quantitative reverse transcription PCR. DA neurons in the CGS preferentially expressed implicated in cell survival (7 out of 8 genes selected), whereas SNpc DA neurons preferentially expressed one gene making them potentially susceptible to undergo cell death in PD. We propose that factors making CGS DA neurons more resistant may be helpful in protecting SNpc DA neurons against a pathological insult.

Aged↗
PubMed2006

Sudden onset of sleep and dopaminergic therapy in patients with restless legs syndrome.

BACKGROUND AND PURPOSE: Sudden onset of sleep (SOS) was recently reported in patients with Parkinson's disease (PD) under dopaminergic treatment. Here, we investigated as to what extent SOS is found in patients with restless legs syndrome (RLS), who are frequently treated with dopaminergic drugs, and controls. PATIENTS AND METHODS: A questionnaire survey on SOS was administered to 156 RLS patients and 126 controls. RESULTS: While no significant difference between RLS patients and controls was detected in Epworth sleepiness scale (ESS) scores (P=0.76), the prevalence of SOS was higher in RLS patients (32.7%) than in controls (19.8%) (P=0.02). Significant predictors of SOS in RLS were ESS score (odds ratio (OR) 16.4), male sex (OR 4.6), duration of night-time sleep (OR 3.0), and age (OR 2.9), while no association was observed for duration or severity of the disease. Patients on dopaminergic therapy usually featured a lower risk of SOS than untreated patients. Falling asleep while driving was reported by 14.6% of all RLS patients with a driver's license and associated with increased risk of accident (OR 7.1). CONCLUSIONS: RLS patients who are untreated, male, and elderly should be assessed for the presence of SOS. In contrast to PD, dopaminergic drugs may reduce the risk of SOS in RLS. The possible benefit of the drugs should be investigated particularly in male patients.

Accidents, Traffic↗
PubMed2006

Release of interleukin-6 via the regulated secretory pathway in PC12 cells.

A growing body of evidence suggests that diverse growth factors such as neurotrophins (NTs), insulin-like growth factor-1 (IGF-1), and glial cell line-derived neurotrophic factor (GDNF) can be released via the regulated secretory pathway in neuronal cells, possibly representing a mechanism for preferentially supplying these growth factors to active synapses. Here we investigated whether interleukin-6 (IL-6), a member of the family of neuropoietic cytokines, can be released via stimulus-coupled secretion as well. IL-6 was expressed in PC12 cells, a neuronal model cell line that is frequently used for the study of vesicle release and trafficking. Regulated secretion of this cytokine was induced by 0.5 mM ATP and treatment with epidermal growth factor (EGF) and nerve growth factor (NGF). Release induced by 0.5 mM ATP but not by NGF or EGF depended on the presence of extracellular Ca(++). Furthermore, IL-6 colocalized with the dense core vesicle (DCV)-marker secretogranin-II (Sg-II) in transfected PC12 cells. Our data suggest that the neuropoietic cytokine IL-6 can be sorted to the regulated secretory pathway in neuronal cells and indicate a potential role for this cytokine in synaptic plasticity.

Adenosine Triphosphate↗
PubMed2006

Dopaminergic substantia nigra neurons project topographically organized to the subventricular zone and stimulate precursor cell proliferation in aged primates.

The subventricular zone of the adult primate brain contains neural stem cells that can produce new neurons. Endogenous neurogenesis might therefore be used to replace lost neurons in neurodegenerative diseases. This would require, however, a precise understanding of the molecular regulation of stem cell proliferation and differentiation in vivo. Several regulatory factors, including dopamine, have been identified in rodents, but none in primates. We have, therefore, studied the origin and function of the dopaminergic innervation of the subventricular zone in nonhuman primates. Tracing experiments in three macaques revealed a topographically organized projection from the substantia nigra pars compacta (SNpc), but not the adjacent retrorubral field, to the subventricular zone: the anteromedial SNpc projects to the anteroventral subventricular zone, the posterolateral SNpc to the posterodorsal subventricular zone. Double immunolabeling for tyrosine hydroxylase and BrdU (5-bromo-2'deoxyuridine) incorporated into the DNA of proliferating cells showed that dopaminergic fibers approach proliferating cells in the subventricular zone. We investigated the effect of this nigro-subventricular projection on cell proliferation in six aged macaques, because the rate of neurogenesis differs between young adult and aged primates and because neurodegenerative diseases mainly affect aged humans. Three macaques were treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to decrease dopaminergic innervation of the subventricular zone. A significant decrease in the number of PCNA+ (proliferating cell nuclear antigen-positive) proliferating cells (-44%) and PSA-NCAM(+) (polysialylated neural cell adhesion molecule-positive) neuroblasts (-59%) was found in the denervated regions of the subventricular zone, suggesting that an intact dopaminergic nigro-subventricular innervation is crucial for sustained neurogenesis in aged primates.

Aging↗
PubMed2006

Long-term assessment of striatal dopamine transporters in Parkinsonian patients with intrastriatal embryonic mesencephalic grafts.

PURPOSE: Single-photon emission computed tomography (SPECT) of striatal dopamine transporters (DAT) has been used to demonstrate presynaptic dopaminergic dysfunction and to monitor the progression of Parkinson's disease. In parkinsonian patients who were implanted with embryonic mesencephalic tissue in the striatum, positron emission tomography (PET) has shown an increase in striatal [(18)F]dopa uptake as an indicator of graft survival and striatal reinnervation. The aim of this study was to investigate two patients who had undergone bilateral intrastriatal transplantation of human embryonic mesencephalic tissue using SPECT and the (123)I-labelled DAT ligand N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (IPT). METHODS: Two patients were subjected to [(123)I]IPT SPECT according to a standardised protocol prospectively and repeatedly up to 8 years after transplantation. RESULTS: From baseline to year 3 after transplantation, mean striatal DAT availability increased by a mean of 61% (93% and 29% in patients 1 and 2, respectively). It then remained relatively stable up to 8 years in patient 2, but increased further by another 77% of baseline values in patient 1. Clinically, both patients experienced a moderate improvement in motor performance but developed moderate (patient 2) to severe (patient 1) off-medication dyskinesias. CONCLUSION: Our data indicate that DAT imaging using IPT and SPECT can be used to demonstrate graft survival following dopaminergic tissue implantation. Because SPECT with DAT ligands is widely available in the routine clinical setting, this methodology may be a useful alternative to [(18)F]dopa PET for repeated scanning of grafted parkinsonian patients. The relevance of the long-term increase in DAT binding for the development of off-medication dyskinesias remains to be elucidated further.

Corpus Striatum↗
PubMed2006

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.

Adult↗
PubMed2006

Validation of the "L-DOPA test" for diagnosis of restless legs syndrome.

We developed and validated a standardized test procedure to evaluate the accuracy of the supportive diagnostic criterion "response to dopaminergic treatment" in restless legs syndrome (RLS). Forty-eight patients who fulfilled at least three of the four essential criteria for RLS, thus including uncertain clinical cases for a nonexpert, were recruited. Patients received a preliminary diagnosis of RLS or non-RLS. All patients underwent a polysomnography (PSG) and were then asked to perform the diagnostic L-DOPA test at home, which consisted in the application of one single dose of 100/25 mg L-DOPA/benserazide and a subsequent observational period of 2 hours. Before, and in 15-minute intervals after, drug intake, the patients rated the severity of the "symptoms in the legs" and the "urge to move the legs" using a 100-mm visual analogue scale. Considering a 50% improvement as a positive test result, we found a sensitivity of 88% ("symptoms in the legs") and 80% ("urge to move the legs") with a specificity of 100% for both test items. A rate of 90% or 83% of all patients could be correctly diagnosed by the L-DOPA test. Both scales were able to predict the response to dopaminergic agents in the subsequent course of the treatment by 100%. The periodic leg movements arousal index as assessed by polysomnography was less appropriate for the prediction of the correct diagnosis. We recommend the L-DOPA test for diagnostic decision making in all patients with an unclear RLS diagnosis according to the essential diagnostic criteria of the International RLS Study Group.

Administration, Oral↗
PubMed2006

Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome.

Although dopamine agonists are becoming first-line therapy for restless legs syndrome (RLS), few reports describe treatment periods exceeding 12 weeks. Here, 150 RLS patients who had responded to pramipexole during a 6-month run-in period (mean dose, 0.50 mg) were randomly assigned to receive placebo or continue receiving pramipexole at an individually optimized dose of 0.125 to 0.75 mg/day for a further 3 months. Patients switched to placebo reached the primary endpoint (a predefined worsening on both the Clinical Global Impressions-Global Improvement scale and the International RLS Study Group Rating Scale) significantly more often than patients who continued to receive pramipexole (85.5% vs. 20.5%; P < 0.0001). They also reached the primary endpoint faster, in 5 versus 42 days to a Kaplan-Meier survival estimate of 0.85 and 7 versus > 84 days to an estimate of 0.5. Over the total 9 months, clinician and patient ratings of symptoms, sleep, and quality of life identified no decline in pramipexole's benefit or tolerability. The great majority of adverse events (AEs) were mild or moderate, and of expected types. Augmentation was considered an AE, but in this population of responders it did not occur.

Adult↗
PubMed2006

Status epilepticus after stroke is associated with increased long-term case fatality.

PURPOSE: The aim of this study was to determine the long-term case fatality of patients with a first episode of status epilepticus (SE group) of cerebrovascular etiology, as compared with that in acute stroke patients without SE (AS group). METHODS: Patients with SE who had been prospectively admitted to an epidemiologic study were retrospectively compared with a cohort of patients from the local stroke registry. The main outcome end point was overall survival. Survival curves were generated according to the Kaplan-Meier method and compared by using the log-rank test. An extended Cox model was used to examine the impact of patient group on the risk of death. Covariates considered potential confounders included age at diagnosis, sex, type of stroke, affected hemisphere, and localization of lesions. RESULTS: Of 166 patients who entered the study, 93 patients were in the SE group, and 73 patients were in the AS group; 53 SE patients and 35 AS patients died during the study. Patient group (SE vs. AS) showed no significant impact on survival (p=0.0832) in univariate analysis. In contrast, the results from a multivariable analysis suggest that after 6 months, patients with SE were at about twice the risk of death as were patients with AS [hazard ratio of 2.12 with 95% confidence interval, 1.04-4.32, p=0.0392]. CONCLUSIONS: The occurrence of SE in patients with cerebrovascular disease indicates a high risk of death within 3 years. In contrast, the case fatality risk attributable to recurrent status or seizures is lower.

Aged↗
PubMed2006

Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in Germany.

PURPOSE: There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center. METHODS: A "prevalence-based," cross-sectional convenience sample of adults with active epilepsy attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure-free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three-month period using questionnaires and a patient diary. Cost driving factors were identified. RESULTS: One hundred one patients were included (40.7+/-15.2 years; disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with generalized tonic-clonic seizures). The total costs of epilepsy per patient were in average euro 2610+/-4200 over the three-month period. Direct cost contributed 39% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls, and situationally inappropriate complex behavior during or after the seizure. CONCLUSIONS: Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of poorly controlled epilepsy in this German study were above average of the European costs of epilepsy.

Adolescent↗
PubMed2005

Predictive value of electrocorticography in epilepsy patients with unilateral hippocampal sclerosis undergoing selective amygdalohippocampectomy.

The purpose of this study was to evaluate the predictive value of intraoperative electro-corticography (ECoG) in patients with unilateral hippocampal sclerosis (HS) undergoing transsylvian selective amygdalohippocampectomy (sAHE). ECoG was recorded before and after resection in 22 patients with medication-resistant mesial temporal lobe epilepsy. The sAHE was performed, regardless of ECoG findings. ECoG findings recorded from the mesiobasal temporal lobe (MTL) and lateral temporal lobe (LTL) before and after the sAHE were correlated with seizure outcome 12 months later. Ten patients had right-sided and 12 left-sided HS. Average age was 37.1 years. Pre-resection spikes were restricted to the MTL in 11 patients and to the LTL in one. In three patients spikes were recorded from MTL and LTL and in seven no spikes were recorded before the resection. Fifteen patients (68%) remained completely seizure-free and 19 (86%) were in Engel's class I post-operatively. Patients with pre-resection spikes restricted to the MTL (n = 11) remained seizure-free more frequently (9/11, 82%) compared with other patients (6/11, 55%; P = 0.36). Pre-resection ECoG may be helpful in the prediction of seizure outcome in patients undergoing sAHE for mesial temporal lobe epilepsy. A larger study including more than 100 patients is needed to determine the predictive value of ECoG in patients with mesial temporal lobe epilepsy.

Adolescent↗