Wolfgang Jost
Albert-Ludwigs-Universität Freiburg, Department of Neurology, Faculty Member
- Professor of Neurology, Head of the Parkinson-Hospital Ortenau, Wolfachedit
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Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of monoamine oxidase type B of the second generation. Rasagiline is indicated for the treatment of Parkinson's disease (PD) as monotherapy (without... more
Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of monoamine oxidase type B of the second generation. Rasagiline is indicated for the treatment of Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. The efficacy and tolerability of rasagiline has been demonstrated in large-scale, controlled clinical studies in patients with early PD as well as with more advanced PD. This multicentred post-marketing observational study included an investigation of the efficacy and tolerability of rasagiline in a large patient population under conditions of the daily routine in neurologic practice with a special attention on the collection of data regarding a patients' subjective evaluation of quality of life. A total of 754 patients with Parkinson's disease were enrolled, 545 of the patients (63% male patients, mean age 68 years, mean duration of PD 6 years, Hoehn & Yahr stage II to III in 69% of the patients) started rasagiline 1 mg/day as adjunct therapy for up to 4 months. The PD symptoms were rated by the physicians using the Columbia University Rating Scale (CURS) and the clinical fluctuations subscale of the Unified Parkinson's Disease Rating Scale (UPDRS, part IV B). Different aspects of quality of life were rated by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39). In addition, patients documented the number of hours spend in the OFF-state in "24-hour" home diaries prior to each of the assessment visits. During the treatment period rasagiline was most frequently co-administered with levodopa/DCI (81.7%) and/or dopamine agonists (65.8%). The mean treatment duration was 117.4 (+/-36.4) days, during which PD medication remained unchanged in 86.6% of the cases. The improvement rates in each of the CURS items ranged between 31.1% to 48.4% and the total score was reduced by 22% under the therapy of rasagiline. In the motor part (tremor, rigidity, bradykinesia) the total score was reduced from 6.2 to 4.8, within the other items from 14.7 to 11.5. The proportion of patients without OFF-periods increased from 33.3% to 49.5%. Determined from "24-hours" home diaries, time spend in the OFF-state during wake time decreased from 120 minutes to 45 minutes. In all 8 aspects of quality of life rated by the patients an reduction of the disability could be documented. The PDQ-39 total score was reduced from 36.4 by 7.3 points (20.1%). In total, 29 of the 545 patients who received rasagiline as combination therapy had switched directly from previous combination therapy with selegiline. In this subgroup CURS total score improved from 17.0 to 12.9 points during treatment. The proportion of patients without OFF-periods increased from 36% to 48% and the daily time spent in the OFF-state was reduced from 45 minutes to 30 minutes. The PDQ-39 total score improved by 6.5 points (22.2%). All in all, adverse events were reported by 8.4% of the patients. In conclusion this post-marketing observational study has shown that in patients with pre-existing combination therapy the add-on medication of rasagiline resulted in improvements of motor and non-motor functions. Furthermore, motor complications were significantly reduced and led to an improved quality of life in the self-estimation of the patients. This also applies to those patients with selegiline pre-treatment.
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Research Interests: Psychology, Cognitive Science, Neurology, Medicine, Anxiety, and 15 moreMovement disorders, Humans, Female, Male, Mental Disorders, Clinical Sciences, Visual Analogue Scale, Aged, Middle Aged, ANXIETY, Cross Sectional Studies, Neurosciences, Parkinson Disease, Motor activity, and Severity of Illness Index
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Research Interests: Psychology, Cognitive Science, Psychometrics, Depression, Medicine, and 15 moreMovement disorders, Humans, Movement, Female, Male, Beck Depression Inventory, Clinical Sciences, Aged, Middle Aged, Adult, Indexation, Receiver Operating Characteristic, Parkinson Disease, Psychiatric Status Rating Scales, and mass Screening
It is becoming increasingly apparent that the so-called idiopathic Parkinson’s disease is a conglomerate of many variants, including tremor-dominant type, akinetic-rigid type and equivalence type; indeed, in light of the increasing number... more
It is becoming increasingly apparent that the so-called idiopathic Parkinson’s disease is a conglomerate of many variants, including tremor-dominant type, akinetic-rigid type and equivalence type; indeed, in light of the increasing number of PD cases due to, or associated with, a genetic abnormality, this is even more important. These genetic abnormalities are mostly related to disturbances of the mitochondria or the proteasomal pathway. Genetic abnormalities are thus a major contributor to the etiopathogenesis of PD. In addition, this supplement presents data on inflammatory processes in the basal ganglia, problems in energy metabolism and oxidative stress. Therapy in PD is highly influenced by the concept of continuous dopamine replacement therapy and continuous dopamine receptor stimulation. It is generally accepted that this will allow good motor control and prevent the occurrence of dyskinesia. A new drug, ropinirole extended release, works under this principle, and maintains very stable plasma concentrations throughout the day. It may also offer the advantage of increased compliance, as it is a once-a-day formulation. Early treatment in PD should be initiated with a modern dopamine agonist in combination with the MAO-B inhibitor rasagiline, which has shown disease modifying action in two independent studies. The recent recognition of early symptoms of PD, such as loss of olfaction, constipation, depression and REM sleep behaviour disorder should, in the near future, allow for the earlier identification of PD, thus providing an opportunity to commence treatment earlier. For this purpose we would need medication with proven neuroprotective action. Whilst rigidity, akinesia, resting tremor and postural instability are regarded as the main symptoms of PD, it is becoming increasingly obvious that for many patients autonomic symptoms, depression and dementia are as great a problem: these non-motor symptoms decrease the quality of life even further. Thus, diagnosis and treatment of non-motor features is becoming more and more important. These introductory remarks indicate that the 9th German Expert Meeting in PD was a platform to discuss eminent and relevant features in PD, which are summarized in this supplement of the Journal of Neurology.
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Seit über 20 Jahren haben sich die COMT(Catechol-O-Methyltransferase)-Hemmer in der Therapie des Parkinson-Syndroms etabliert. Sie gelten als Mittel der Wahl bei motorischen Fluktuationen. Die verfügbaren Substanzen Entacapon, Opicapon... more
Seit über 20 Jahren haben sich die COMT(Catechol-O-Methyltransferase)-Hemmer in der Therapie des Parkinson-Syndroms etabliert. Sie gelten als Mittel der Wahl bei motorischen Fluktuationen. Die verfügbaren Substanzen Entacapon, Opicapon und Tolcapon unterscheiden sich pharmakokinetisch hinsichtlich ihrer Halbwertszeiten, mit Folgen für die Einnahmefrequenz, hinsichtlich ihrer Indikationsvoraussetzungen und ihres Nebenwirkungsspektrums, darunter Diarrhöen und eine Gelbverfärbung des Urins. Viele Patienten mit motorischen Fluktuationen werden aktuell nicht mit COMT-Hemmern behandelt und erhalten deshalb vermutlich keine individuell optimale medikamentöse Therapie. Das vorliegende Manuskript fasst die Ergebnisse eines Arbeitstreffens mehrerer Parkinson-Experten zusammen, in dem der Stellenwert der COMT-Hemmer kritisch diskutiert wurde.
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ABSTRACT Objective To validate the DEpression Screening in PARkinson’s disease (DESPAR) self-administered questionnaire, a subscale of a recently developed new screening tool for secondary depression.Background Although depression has a... more
ABSTRACT Objective To validate the DEpression Screening in PARkinson’s disease (DESPAR) self-administered questionnaire, a subscale of a recently developed new screening tool for secondary depression.Background Although depression has a high prevalence in PD, it often remains undetected. Currently, the Beck Depression Inventory (BDI-1A) is the gold standard screening tool for PD depression, but as a result of its length and complexity it is of limited suitability as a quick and easy screening device. The DESPAR is a short 15-item self-administered questionnaire especially designed for the screening of depression in PD.Methods We assessed 215 Patients with PD (mean [SD] age: 68 ± 9 years) at Hoehn and Yahr stages I–V (median: II.0) in a multicenter study using the DESPAR and the BDI-1A. Psychiatric diagnoses were made using the structured Mini International Neuropsychiatric Interview (M.I.N.I). External validity for detection of depression and combined depression/dysthymia was evaluated by receiver operating curve (ROC) analysis.ResultsTwo hundred and eleven patients (98.1%) completed the DESPAR. Internal consistency of the DESPAR was good (Cronbach’s α = 0.91). ROC analysis showed that both questionnaires adequately detected depression without differences in the validity indices (0.897 [95%CI: 0.838–0.956] for DESPAR; AUC 0.924 [95%CI: 0.887–0.960] for BDI-1A; P = 0.463). The optimal cut-off value for detection of depression and combined depression/dysthymia with equal sensitivity and specificity was 29/30 points.Conclusion The DESPAR showed good internal reliability and external validity for screening for depression and dysthymia in PD. It is thus a useful, brief and easy instrument for identifying PD subjects with depression/dysthymia in daily practice.
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SUMMARY Ropinirole, a nonergoline dopamine agonist, has been used to treat the motor symptoms of Parkinson’s disease for more than 10 years. Owing to its moderate elimination half-life, the immediate-release formulation is administered... more
SUMMARY Ropinirole, a nonergoline dopamine agonist, has been used to treat the motor symptoms of Parkinson’s disease for more than 10 years. Owing to its moderate elimination half-life, the immediate-release formulation is administered three-times daily. Now, a prolonged-release form is also available, and despite administration in the morning, plasma level fluctuations are reduced over 24 h versus the immediate-release formulation, allowing for symptomatic treatment for the entire day with once-daily dosing. The prolonged-release formulation can be up-titrated more rapidly and simply, reaching clinical efficacy as early as the second week of therapy. In clinical studies, higher doses of ropinirole were achieved with the prolonged-release formulation compared with the immediate-release formulation. The results of a randomized, double-blind, head-to-head study of both formulations in patients with advanced Parkinson’s disease demonstrated significantly greater efficacy and a larger l...
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Safinamide is a highly selective, reversible MAO B-inhibitor recently marketed in European and North American countries. To better define clinical indications regarding motor and non-motor symptoms, targeted population and safety of this... more
Safinamide is a highly selective, reversible MAO B-inhibitor recently marketed in European and North American countries. To better define clinical indications regarding motor and non-motor symptoms, targeted population and safety of this compound, ten movement disorders specialists, experts in their field, convened and developed a panel of statements on: the role of glutamate in Parkinson’s disease, introduction to fluctuations, efficacy of safinamide on motor symptoms, motor complications and non-motor symptoms, quality of life, safety of safinamide and target population for use. Strong consensus was reached for all the statements on the efficacy of safinamide on motor symptoms, motor fluctuations, quality of life and safety. Among non-motor symptoms, a positive consensus was reached for the symptoms sleep/fatigue, mood, and pain while there was a lack of consensus for the statements regarding the efficacy of safinamide in improving cognition, urinary and sexual functions. The stat...
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Research Objectives Examine onabotulinumtoxinA utilization in patients with upper limb (UL) and lower limb (LL) spasticity from the Adult Spasticity International Registry (ASPIRE) study to gain real-world insights into the treatment of... more
Research Objectives Examine onabotulinumtoxinA utilization in patients with upper limb (UL) and lower limb (LL) spasticity from the Adult Spasticity International Registry (ASPIRE) study to gain real-world insights into the treatment of spastic hemiparesis. Design Prospective, observational registry (NCT01930786). Setting International clinical sites. Participants Adults with spasticity across multiple etiologies. Interventions OnabotulinumtoxinA at the clinician's discretion. Main Outcome Measures OnabotulinumtoxinA utilization and safety data were collected at each treatment session. Patients with spastic hemiparesis were defined as receiving ≥ 1 UL treatment and ≥ 1 LL treatment during the study. Results ASPIRE patients (N=730) were on average 53.6 years old, 52%; female, 77% Caucasian, 37% naive to botulinum toxin(s) for spasticity, and 56% post-stroke. Of N=730, n=284 patients were defined as hemiparetic. In hemiparetic patients treated for UL and LL at the same session (n=275), the mean total dose of onabotulinumtoxinA was 477 U for UL+LL, 257 U for UL, and 220 U for LL. Of n=275 hemiparetic patients, 56%; had a treatment interval of 10-15 weeks, 62% had 5-15 injections/session, and 82% had >5 muscles injected/session. Clenched fist was the most common UL presentation (n=219 patients), with 55% of sessions to the left side only. Equinovarus foot was the most common LL presentation (n=238 patients), with 52% of sessions to the left side only. Of the hemiparetic population (n=284), 115 patients (41%) reported 375 adverse events; 42 patients (15%) reported 80 serious adverse events. No new safety signals were identified. Conclusions This preliminary analysis from ASPIRE provides valuable, real-world evidence on the use of onabotulinumtoxinA to treat patients with combined upper limb and lower limb spasticity. OnabotulinumtoxinA was most frequently utilized to treat clenched fist (UL) and equinovarus foot (LL) in patients with spastic hemiparesis. Author(s) Disclosures Bavikatte: Consultant for Allergan(AbbVie); Francisco: Consulted/research grants from Allergan(AbbVie), Merz, and Ipsen; Esquenazi: Consulted for Allergan(AbbVie), Ipsen, and Merz. Received research grants from Allergan(AbbVie) and Ipsen; Dimyan: None reported; Ngo: None reported; Schwartz: Statistical consultant for Allergan(AbbVie); Zuzek: AbbVie employee; Jost: Speaker/consultant for Allergan(AbbVie), Ipsen, and Merz.
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ZusammenfassungDiabetes mellitus ist die häufigste Ursache einer Polyneuropathie bei Menschen in den Industrienationen. Besonders wichtig ist die Prophylaxe. Therapeutisch stehen Medikamente zur Verfügung, die zu einer symptomatischen... more
ZusammenfassungDiabetes mellitus ist die häufigste Ursache einer Polyneuropathie bei Menschen in den Industrienationen. Besonders wichtig ist die Prophylaxe. Therapeutisch stehen Medikamente zur Verfügung, die zu einer symptomatischen Besserung führen können. Hier sind besonders Schmerzen sowie schmerzhafte Dys- und Parästhesien zu nennen. Leider gibt es aber keine Substanz, welche die diabetische Polyneuropathie verhindert oder ursächlich positiv beeinflusst.Der Umfang der Diagnostik bei (poly-) neuropa-thischen Schmerzen richtet sich nach dem Ausmaß und dem Verlauf der klinischen Ausfälle. Die häufigsten Ursachen (Diabetes mellitus, Alkoholmissbrauch) sollten immer interdisziplinär abgeklärt werden, und nach Möglichkeit ist eine multimodale Schmerztherapie einzuleiten. Nach aktueller Studienlage besteht die höchste Evidenz (Level A) für trizyklische Antidepressiva, Gabapentin, Pre-gabalin, Opioide, Venlafaxin und Duloxetin.
Research Interests: Medicine and Gynecology
In pain therapy we are repeatedly faced with the problem that the available treatment methods are inadequate. For years we have also been using botulinum toxin especially for myofascial pain and chronic headaches. Unfortunately, the... more
In pain therapy we are repeatedly faced with the problem that the available treatment methods are inadequate. For years we have also been using botulinum toxin especially for myofascial pain and chronic headaches. Unfortunately, the assessment of its efficacy in both everyday clinical conditions and in studies is very variable. A final evaluation is not yet possible. Until the results of current studies are available, the use of botulinum toxin should be limited to clinical studies and to particular cases at specialized centres.
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Electroneurography of the pudendal nerve is extremely important in the diagnosis of neurogenic fecal incontinence and a pudendal canal syndrome. The aim of this study was to determine pudendal nerve motor latency of the overall distance... more
Electroneurography of the pudendal nerve is extremely important in the diagnosis of neurogenic fecal incontinence and a pudendal canal syndrome. The aim of this study was to determine pudendal nerve motor latency of the overall distance by stimulation of nerve root S3 by discharging a magnetic coil. This can be achieved by positioning an earth electrode between the site of stimulation and the registration electrode. We investigated 18 volunteers by this method. The average latency period was 2.51 milliseconds (SD = 0.32) on the right and 2.49 milliseconds (SD = 0.33) on the left side. This method enables precise diagnosis in neuropathies of the pudendal nerve more so than with conventional electric stimulation.
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Sphincterotomy still is considered the therapy of choice to eliminate sphincter spasm in the treatment of uncomplicated chronic anal fissure. The surgery is weighted with the possible surgical risk and the risk of subsequent fecal... more
Sphincterotomy still is considered the therapy of choice to eliminate sphincter spasm in the treatment of uncomplicated chronic anal fissure. The surgery is weighted with the possible surgical risk and the risk of subsequent fecal incontinence. This study reports the effect of botulin toxin injections within the first six months. One hundred patients were treated (43 females; average age, 34.7 years). The injection of botulin toxin (2.5-5 units of Botox each) was done bilaterally to the fissure, thereby causing paresis of the sphincters for approximately three months. Patients were re-examined after one week and three and six months. Within the first week, 78 percent of patients were free of pain. In 82 percent of patients, complete healing of the fissure occurred within the first three months. Eight patients experienced relapses within the first six months of therapy, three of whom needed surgical intervention. The healing rate after six months was 79 percent. No healing occurred in 21 patients, and they had to undergo surgery. Transitory fecal incontinence resulted in seven cases. Injection of botulin toxin enables us to treat chronic, uncomplicated anal fissures with increased sphincter tone. It is well tolerated, can be administered on an outpatient basis, does not cause any lesion of the continence organ, and subsequently, does not lead to any permanent latent or apparent fecal incontinence.
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Research Interests: Humans, Female, Male, Reaction Time, Clinical Sciences, and 4 moreMiddle Aged, Adult, Action Potentials, and Injections
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Urinary incontinence is the inability to willingly control bladder voiding. Stress urinary incontinence (SUI) is the most frequently occurring type of incontinence in women. No widely accepted or approved drug therapy is yet available for... more
Urinary incontinence is the inability to willingly control bladder voiding. Stress urinary incontinence (SUI) is the most frequently occurring type of incontinence in women. No widely accepted or approved drug therapy is yet available for the treatment of stress urinary incontinence. Numerous studies have implicated the neurotransmitters, serotonin and norepinephrine in the central neural control of the lower urinary tract function. The pudendal somatic motor nucleus of the spinal cord is densely innervated by 5HT and NE terminals. Pharmacological studies confirm central modulation of the lower urinary tract activity by 5HT and NE receptor agonists and antagonists. Duloxetine is a combined serotonin/norepinephrine reuptake inhibitor currently under clinical investigation for the treatment of women with stress urinary incontinence. Duloxetine exerts balanced in vivo reuptake inhibition of 5HT and NE and exhibits no appreciable binding affinity for receptors of neurotransmitters. The action of duloxetine in the treatment of stress urinary incontinence is associated with reuptake inhibition of serotonin and norepinephrine at the presynaptic neuron in Onuf's nucleus of the sacral spinal cord. In cats, whose bladder had initially been irritated with acetic acid, a dose-dependent improvement of the bladder capacity (5-fold) and periurethral EMG activity (8-fold) of the striated sphincter muscles was found. In a double blind, randomized, placebo-controlled, clinical trial in women with stress urinary incontinence, there was a significant reduction in urinary incontinence episodes under duloxetine treatment. In summary, the pharmacological effect of duloxetine to increase the activity of the striated urethral sphincter together with clinical results indicate that duloxetine has an interesting therapeutic potential in patients with stress urinary incontinence.