Florian Kopper

Two‐year follow‐up of subthalamic deep brain stimulation in Parkinson's disease

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN‐DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinsons Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow‐up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow‐up, STN‐DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN‐DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN‐DBS beyond the first year after surgical procedure. Complications of STN‐DBS comprise a wide range of psychiatric adverse events which, however, were temporary.

Introduction to the programming of deep brain stimulators.

The clinical success of deep brain stimulation (DBS) for treating Parkinsons disease, tremor, or dystonia critically depends on the quality of postoperative neurologic management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to optimally adapt stimulation parameters and medication after implantation of a DBS system. In clinical practice, the infinite number of possible parameter settings in DBS can be reduced to few relevant combinations. In this article, the authors describe a general scheme of selecting stimulation parameters in DBS and provide clinical and neurophysiological arguments for such a standardized algorithm. They also describe noninvasive technical trouble shooting by using programming features of the commercially available neurostimulation devices.

Neuronal Activity of the Human Subthalamic Nucleus in the Parkinsonian and Nonparkinsonian State

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinsons disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same (n = 30) or neighboring microelectrodes (n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinsons disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1-100 Hz. The distribution of significant oscillations across the theta (1-8 Hz), alpha (8-12 Hz), beta (12-35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fishers exact test (P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinsons disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinsons disease.

Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor.

SummaryBackground. The ventro-lateral thalamus is the stereotactic target of choice for severe intention tremor. Nevertheless, the optimal target area has remained controversial, and targeting of the subthalamic area has been suggested to be superior. Patients and methods. Eleven patients with disabling intention tremor of different etiology (essential tremor (n = 8), multiple sclerosis (n = 2) and one with, spinocerebellar ataxia) were implanted bilaterally with DBS electrodes targeted to the ventro-lateral thalamus using micro-recording and micro-stimulation. Among five tracks explored in parallel optimal tracks were chosen for permanent electrode implantation. Postoperative tremor suppression elicited by individual electrode contacts was quantified using a lateralised tremor rating scale at least 3 months (in most patients >1 year) after implantation. The position of electrode contacts was determined retrospectively from stereotactic X-ray exams and by correlation of pre- and postoperative MRI. Results. In all patients, DBS suppressed intention tremor markedly. On average, tremor on the left and right side of the body was improved by 68% (±19; standard deviation) and 73% (±21), respectively. In most patients, distal electrode contacts located in the subthalamic area proved to be more effective than proximal contacts in the ventro-lateral thalamus. In stereotactic coordinates, the optimal site was located 12.7 mm (±1.4; mean ± standard deviation) lateral, 7.0 (±1.6) mm posterior, and 1.5 (±2.0) mm ventral to the mid-commissural point. In general, the best contacts could be selected for permanent stimulation. Nevertheless, in some instances, more proximal contacts had to be chosen because of adverse effects (paraesthesiae, dysarthria, gait ataxia) which were more pronounced with bilateral stimulation resulting in slightly less tremor suppression on the left and right side of body (63 ± 18 and 68 ± 19%, respectively). Conclusion. Direct comparison of different stimulation sites in individual patients revealed that DBS in the subthalamic area is more effective in suppressing pharmacoresistant intention tremor than the ventro-lateral thalamus proper. Anatomical structures possibly involved in tremor suppression include cerebello-thalamic projections, the prelemniscal radiation, and the zona incerta.

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a therapy approaching evidence-based standards

Abstract. DBS of the STN is one of the most promising new therapies for the treatment of PD. However – like many other therapies for PD – the present stage of the scientific assessment does not yet suffice the rigid criteria of evidence-based medicine. Further studies should specifically address the questions of efficacy and side effects as well as the impact on quality of life.

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements

Deep brain stimulation of the subthalamic nucleus (STN‐DBS) reduces akinesia in Parkinsons disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L‐dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS‐items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L‐dopa test than in the pure STN‐DBS condition. Other akinesia items and the time for build‐up of lifting force were equally improved in both conditions. This suggests that routine STN‐DBS might not be equally effective on all aspects of fine motor functions.

Estimation of time delay by coherence analysis

Using coherence analysis (which is an extensively used method to study the correlations in frequency domain, between two simultaneously measured signals) we estimate the time delay between two signals. This method is suitable for time delay estimation of narrow band coherence signals for which the conventional methods cannot be reliably applied. We show, by analysing coupled Rossler attractors with a known delay, that the method yields satisfactory results. Then, we apply this method to human pathologic tremor. The delay between simultaneously measured traces of electroencephalogram (EEG) and electromyogram (EMG) data of subjects with essential hand tremor is calculated. We find that there is a delay of 11–27 milli-seconds (ms) between the tremor correlated parts (cortex) of the brain (EEG) and the trembling hand (EMG) which is in agreement with the experimentally observed delay value of 15ms for the cortico-muscular conduction time. By surrogate analysis we calculate error bars of the estimated delay.

Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus.

Deep‐brain stimulation of the subthalamic nucleus appears to reduce levodopa‐induced dyskinesias, but whether this effect is caused by the reduction of the total levodopa ingestion or represents a direct effect on the motor system is unknown. Precision grip force of grasping movements and levodopa‐induced dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of deep‐brain stimulation of the subthalamic nucleus. Peak grip force was abnormally increased before surgery in the off‐drug state and, particularly, in the on‐drug state (sensitization). This grip force upregulation normalized with chronic deep‐brain stimulation in both conditions (desensitization). Peak‐dose dyskinesias also improved, and off‐dystonia was completely abolished. Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction. Despite the same single levodopa test dose, force excess and levodopa‐induced dyskinesias were drastically reduced after 3 months of deep‐brain stimulation of the subthalamic nucleus. This indicates that direct effects of deep‐brain stimulation of the subthalamic nucleus on levodopa‐induced dyskinesias are likely to occur. Grip force overflow is a promising parameter to study the desensitizing effect of chronic deep‐brain stimulation on levodopa‐induced dyskinesias.

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Cortical correlates of the basic and first harmonic frequency of Parkinsonian tremor

OBJECTIVE It has been hypothesized that the basic and first harmonic frequency of Parkinsonian tremor are somewhat independent oscillations the biological basis of which remains unclear. METHODS We recorded 64-channel EEG in parallel with EMG of the forearm muscles most affected by rest tremor in 21 PD patients. EMG power spectrum, corticomuscular coherence spectra and EEG power spectra for each EEG electrode were calculated. The dynamics of the coherence and relative EMG and EEG power at the basic (tremor) frequency were calculated by a sliding, overlapping window analysis. Corticomuscular delays and direction of interaction were analysed by the maximizing coherence method for narrow band signals. RESULTS The contralateral EEG electrodes with maximal coherence were different for the basic and first harmonic frequency. The dynamical coherence curves showed non-parallel time courses for the two frequencies. The mean EEG-EMG and EMG-EEG delays were all around 15-20ms but significantly longer for the first harmonic than for the basic frequency. CONCLUSIONS Our data indicate different cortical representations and corticomuscular interaction of the basic and first harmonic frequencies of Parkinsonian tremor. SIGNIFICANCE Separate central generators seem to contribute to the tremor via different pathways. Further studies on this complex tremor network are warranted.