WITHDRAWN: MS related employment and disease modifying treatment in the German working population: 1994-2009.

Ahead of Print article withdrawn by publisher.

Epilepsy-related employment prevalence and retirement incidence in the German working population: 1994-2009.

Epilepsy-related employment prevalence and retirement incidence were investigated in the German working population from 1994 to 2009. The overall mean prevalence of employment of people with epilepsy was 5.1±0.2 per 1000 workers. The employment rate among people with epilepsy increased from 63.5% in 1994 to 65.9% in 2000 (0.4% annually) and then more steeply from 66.8% in 2001 to 76.9% in 2009 (1.4% annually). A prominent increase in rate of employment of people with epilepsy since 2001 was temporarily associated with approval of leviteracetam in 2000 (P<0.001, OR=8.3, CI=6.45-10.12). The overall mean employment rate of people with epilepsy was lower than that of the general population (68.5% vs 90.1%, P<0.001). The overall mean incidence of epilepsy-related retirement (RI) during the study was 4.6±1.6/1000, similar to the RI for people with other illnesses (5.1±0.8/1000), and the risk of retiring because of epilepsy was not higher than that for other illnesses over the entire study period (P=0.52, OR=1.11, CI=0.86-1.43). The RI among workers with epilepsy, however, sharply declined from 8.3/1000 in 1994 to 2.9/1000 in 2000 (-65%, < 0.001), followed by a slight increase and stabilization at 3.9/1000 workers between 2001 and 2009. The decline in RI among people with epilepsy was temporarily associated with legislation of the Law on Support of Employment in 1996 (P=0.032, OR=2.15, CI=1.17-2.89) and approval of lamotrigine in 1993 (P=0.024, OR=2.64, CI=2.17-3.88). These patterns suggest that drug treatment and legislative laws may have led to increased employment and reduced retirement rates for people with epilepsy.

[When should we start medical treatment in Parkinson disease]. / Wann sollten wir mit der medikamentösen Therapie beim Morbus Parkinson beginnen?

There is still uncertainty when to start medical treatment in Parkinson disease (PD). Lack of availability of an unambiguous neuroprotective treatment and concern of potential short or long term adverse effects of medication often lead to an "wait and see" policy regarding initiation of medical treatment. This can result in insufficient symptom control and potentially reduced quality of life. There is increasing evidence of negative influence on disease progression by delayed onset of medical drug treatment in PD. It is under discussion whether symptomatic treatment in PD supports compensatory mechanisms of the cortico-basalganglionar system which might have been responsible for a physically intact motor function despite considerable and increasing nigro-striatal dopaminergic deficit during the preclinical phase of the disease. Therefore, symptomatic treatment might modify disease progression by supporting compensatory mechanisms within the basal ganglia. In this paper we discuss pro and contra of early medical treatment onset in PD under consideration of hitherto available scientific investigations.

Role of D1 and D2 receptors in the regulation of voluntary movements.

The effect of dopamine receptor agonist cabergoline on muscle tone and contractility was studied in healthy volunteers. Variations in muscle tone were evaluated by means of transcranial magnetic stimulation under resting conditions. Muscle contractility was estimated from kinematic parameters of voluntary movements. Oral administration of cabergoline in a dose of 2 mg was followed by a decrease in muscle tone and increase in muscle contractility. Our findings indicate that the brain dopaminergic system regulates voluntary movements by decreasing the tone and increasing contractility of skeletal muscles. Under resting conditions, prolonged exposure of D1 receptors to dopamine in a low concentration decreases excitability threshold of the motor cortex and reduces muscle tone. During voluntary movements, short-term stimulation of D2 receptors with dopamine in a high concentration increases excitability of the motor cortex and induces muscle contraction. The movement occurs when D2 receptor-mediated excitation of the cortex and induced muscle contraction exceed the decrease in muscle tone and excitability threshold caused by stimulation of D1 receptors.

TMS-assisted neurophysiological profiling of the dopamine receptor agonist cabergoline in human motor cortex.

Dopamine plays a broad role in motor control and practice-dependent plasticity. Here we tested, in eight healthy subjects, the effects of the dopamine receptor agonist cabergoline on motor cortical excitability because the state of motor cortex can strongly influence practice-dependent plasticity. Cabergoline enhances practice-dependent plasticity but the mechanisms are unknown. We used transcranial magnetic stimulation for testing of motor cortical excitability. A single dose of 2 mg of cabergoline increased short-interval intracortical inhibition, a measure of excitability of GABA-dependent inhibitory neural circuits, and decreased various excitatory measures (motor evoked potential amplitude and short-interval intracortical facilitation). Other measures of motor cortical (motor threshold, cortical silent period duration), spinal (peripheral silent period duration, F-wave) and neuromuscular excitability (maximum M-wave) remained unchanged. This shift in the balance from excitation to inhibition may assist, by improving the 'signal-to-noise ratio' in motor cortex, in the positive modulating effect of cabergoline on practice-dependent plasticity.

Differential effects of various treatment combinations on cardiovascular dysfunction in patients with Parkinson's disease.

OBJECTIVES: Patients with Parkinson's disease (PD) frequently suffer from cardiovascular dysfunction, which may be enhanced to various extents by different antiparkinsonian drugs. MATERIALS AND METHODS: We analysed electrocardiogram (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension (OH) in 148 patients with idiopathic PD assigned to five different combination therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP), selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy before and after a 1-week washout of the add-on drug. Patients were matched for age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular testing was performed at baseline, and following a 1-week washout period of the add-on drugs. RESULTS: We found that the incidence of cardiovascular dysfunction was generally higher in patients receiving a combination therapy compared with patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in combination therapy, but in only 20% of the patients receiving LD monotherapy. After discontinuation of BRO and SEL, there were significant improvements in ECG, OH and CVR. After washout of ACH and AMA, a significant improvement was found only in the CVR score. AMA and ROP were the add-on drugs with the least adverse cardiovascular effects. CONCLUSION: We conclude that pre-existing cardiovascular autonomic dysfunction should be investigated and taken into account when deciding which combination therapy to choose in the treatment of parkinsonian patients.

Autonomic dysfunction in Parkinson's disease assessed by sympathetic skin response: a prospective clinical and neurophysiological trial on 50 patients.

To verify possible dysfunction of sympathetic skin activity in Parkinson's disease (PD), we studied the electrically evoked sympathetic skin responses (SSR) bilaterally at hands and feet in a group of 50 PD patients and in normal subjects. SSR was present in all patients. Nevertheless, significant differences in the latency and amplitude values were noted. In the group of patients prolongation of latency as well as the reduction of SSR amplitude correlates with age. The longer the disease the more SSR abnormalities could be found. Gender, type of clinical manifestation of PD or medication had no statistically significant effects. However, motor symptom asymmetries evaluated separately for each body side correlated well with interside asymmetries of SSR.