Instrument for spatially resolved simultaneous measurements of forces and currents in particle beams.

The article presents a device for spatially resolved and simultaneous measurements of forces and currents in particle beams, especially in beams composed of ions and neutral atoms. The forces are exerted by the impinging beam particles on a plane circular conductive target plate of 20 mm diameter mounted on a pendulum with electromagnetic force compensation. The force measurement in the micronewton range is achieved by electromagnetic compensation by means of static Helmholtz coils and permanent magnets attached to the pendulum. Exemplary measurements are performed in the 1.2 keV beam of a broad beam ion source. The simultaneous measurements of forces and currents onto the same target are compared with each other and with Faraday cup measurements.

Long-term effects of pallidal deep brain stimulation in tardive dystonia.

OBJECTIVE: High-frequency stimulation of the globus pallidus internus (GPi) is a highly effective therapy in primary dystonia. Recent reports have also demonstrated almost immediate improvement of motor symptoms in patients with tardive dystonia after pallidal deep brain stimulation (DBS). Here, we show the long-term effect of continuous bilateral GPi DBS in tardive dystonia on motor function, quality of life (QoL), and mood. METHODS: Nine consecutive patients undergoing DBS for tardive dystonia were assessed during continuous DBS at 3 time points: 1 week, 3 to 6 months, and last follow-up at the mean of 41 (range 18-80) months after surgery using established and validated movement disorder and neuropsychological scales. Clinical assessment was performed by a neurologist not blinded to the stimulation settings. RESULTS: One week and 3 to 6 months after pallidal DBS, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor scores were ameliorated by 56.4 +/- 26.7% and 74.1 +/- 15.8%, BFMDRS disability scores by 62.5 +/- 21.0% and 88.9 +/- 10.3%, and Abnormal Involuntary Movement Scale (AIMS) scores by 52.3 +/- 24.1% and 69.5 +/- 27.6%, respectively. At last follow-up, this improvement compared with the presurgical assessment was maintained as reflected by a reduction of BFMDRS motor scores by 83.0 +/- 12.2%, BFMDRS disability scores by 67.7 +/- 28.0%, and AIMS scores by 78.7 +/- 19.9%. QoL improved significantly in physical components, and there was a significant improvement in affective state. Furthermore, cognitive functions remained unchanged compared with presurgical status in the long-term follow-up. No permanent adverse effects were observed. CONCLUSION: Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.

Functional connectivity between motor cortex and globus pallidus in human non-REM sleep.

Recent evidence suggests that the motor system undergoes very specific modulation in its functional state during the different sleep stages. Here we test the hypothesis that changes in the functional organization of the motor system involve both cortical and subcortical levels and that these distributed changes are interrelated in defined frequency bands. To this end we evaluated functional connectivity between motor and non-motor cortical sites (fronto-central, parieto-occipital) and the globus pallidus (GP) in human non-REM sleep in seven patients undergoing deep brain stimulation (DBS) for dystonia using a variety of spectral measures (power, coherence, partial coherence and directed transfer function (DTF)). We found significant coherence between GP and fronto-central cortex as well as between GP and parieto-occipital cortex in circumscribed frequency bands that correlated with sleep specific oscillations in 'light sleep' (N2) and 'slow-wave sleep' (N3). These sleep specific oscillations were also reflected in significant coherence between the two cortical sites corroborating previous studies. Importantly, we found two different physiological activities represented within the broad band of significant coherence between 9.5 and 17 Hz. One component occurred in the frequency range of sleep spindles (12.5-17 Hz) and was maximal in the coherence between fronto-central and parieto-occipital cortex as well as between GP and both cortical sites during N2. This component was still present between fronto-central and parieto-occipital cortex in N3. Functional connectivity in this frequency band may be due to a common input to both GP and cortex. The second component consisted of a spectral peak over 9.5-12.5 Hz. Coherence was elevated in this band for all topographical constellations in both N2 and N3, but especially between GP and fronto-central cortex. The DTF suggested that the 9.5-12.5 Hz activity consisted of a preferential drive from GP to the fronto-central cortex in N2, whereas in N3 the DTF between GP and fronto-central cortex was symmetrical. Partial coherence supported distinctive patterns for the 9.5-12.5 and 12.5 and 17 Hz component, so that only coherence in the 9.5-12.5 Hz band was reduced when the effects of GP were removed from the coherence between the two cortical sites. The data suggest that activities in the GP and fronto-central cortex are functionally connected over 9.5-12.5 Hz, possibly as a specific signature of the motor system in human non-REM sleep. This finding is pertinent to the longstanding debate about the nature of alpha-delta sleep as a physiological or pathological feature of non-REM sleep.

The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease.

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications.

["Asleep-awake-asleep"-anaesthetic technique for awake craniotomy]. / "Schlaf-Wach-Schlaf"-Technik zur CS Wachkraniotomie.

Awake craniotomy in tumor and epilepsy surgery or for the implantation of electrodes for deep brain stimulation requires specific anesthesiological strategies. Propofol allows for quick emergence and has little effect on the respiratory function of the usually spontaneously breathing patient. Pain control may be instituted by hemiscalp block for trepanation or local infiltration for deep brain electrode implantation. In addition, low dose remifentanil is recommended for trepanation (i.e. tumor or epilepsy surgery). The airway may be secured by an ordinary Magill tube placed transnasally with its tip underneath the epiglottis. To protect the patient against vomiting an adequate antiemetic prophylaxis is required.

Oscillatory pallidal local field potential activity correlates with involuntary EMG in dystonia.

The pathophysiology of dystonia is unclear. The authors recorded local field potentials (LFPs) from deep brain stimulation electrodes implanted in the pallidum of 13 dystonic patients. LFP power correlated with the level of dystonic EMG in the sternocleidomastoid, with maximal positive correlations at the lower contacts of pallidal electrodes. The data suggest that the neuronal synchronization indexed by LFP oscillations in the globus pallidus may be mechanistically linked to dystonic EMG activity.

Pallidal stimulation in dystonia: effects on cognition, mood, and quality of life.

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) alleviates symptoms in patients with dystonia but its effects on cognition, neuropsychiatric status, and quality of life have not been examined. This is a case series report of 15 consecutive patients with different forms of dystonia who underwent bilateral implantation of DBS electrodes in the GPi. The patients were evaluated preoperatively and after 3-12 months of DBS with tests of cognition (Mattis Dementia Rating Scale, Stroop Test, Trail Making Test, Phonemic and Category Word Fluency, Digit Span, Rey Auditory Verbal Learning Test, Tonic and Phasic Alertness), neuropsychiatric status (Beck Depression and Anxiety Inventories, Montgomery Asberg Depression Rating Scale, Snaith-Hamilton Pleasure Scale, Brief Psychiatric Rating Scale), quality of life, and motor functions. GPi DBS significantly improved dystonic symptoms, functional abilities, and quality of life allowing for a significant reduction of antidystonic medications. No deterioration was observed in cognitive scores and neuropsychiatric measures. The present case series report thus provides preliminary evidence for the safety of GPi DBS regarding cognitive and neuropsychiatric functions in patients with dystonia.

Treatment of severe tardive dystonia with pallidal deep brain stimulation.

In five patients with medically refractory tardive dystonia, continuous bilateral high-frequency stimulation of the globus pallidus internus was associated with a rapid (within 12 to 72 hours) and substantial (mean 87%, 10.7 SD of the motor part of the Burke-Fahn-Marsden Dystonia Rating Scale) improvement of dystonia and functional disability without adverse events.

A randomized trial of botulinum toxin A for treatment of drooling.

The authors compared the efficacy of three different doses (18.75, 37.5, and 75 MU per parotid gland) of botulinum toxin A (BTX-A; Dysport, Ipsen Pharma, Germany) injections vs vehicle in patients with sialorrhea (n = 32) using a single-center, prospective, double-blind, placebo-controlled dose-finding study. The primary endpoint was achieved with 75 MU BTX-A without treatment-related adverse events, suggesting BTX-A is a safe and effective treatment for patients with sialorrhea.

The effects of frequency in pallidal deep brain stimulation for primary dystonia.

The effect of stimulation frequency for pallidal deep brain stimulation in five patients with either generalized or segmental dystonia was evaluated three to twelve months postoperatively via a randomized, double-blind paradigm. The quality of life and the severity of dystonic symptoms improved by approximately 60% and 43% respectively using a frequency of 130 Hz. Compared with 130 Hz a significant further clinical improvement was observed at frequencies of 180 and 250 Hz, which contrasted with a significant deterioration at lower frequencies (5, 50 Hz) compared to 130 Hz.

Modulation of motor cortex excitability by pallidal stimulation in patients with severe dystonia.

OBJECTIVE: To study the influence of continuous high-frequency electrical stimulation with electrodes implanted in the globus pallidus internus (GPi) on motor cortex excitability in nine patients with dystonia. METHODS: Short-term effects related to switching off and on the deep brain stimulator were investigated >3 months after electrode implantation. Activation of motor cortical excitatory and inhibitory neurons was examined with transcranial magnetic stimulation (TMS) by analysis of electromyographic activity in the hand muscles. Parameters of corticospinally mediated excitatory motor responses included latency, threshold, and response sizes with increasing stimulus intensities (stimulus-response curves). Other measures of motor cortex excitability comprised the duration of the contralateral silent period and intracortical inhibition and facilitation in a paired-pulse paradigm. RESULTS: Switching off GPi stimulation led to a decrease of motor cortex excitability, as reflected by an increase in motor thresholds (GPi stimulation on 37.5 +/- 6.1%, mean +/- SD; GPi stimulation off for 15 to 120 minutes, 40.5 +/- 6.7% of maximum stimulator output), and reduced the size of contralateral responses in the stimulus-response curves established for relaxed muscles. The changes were reversible within minutes after switching on GPi stimulation. They were associated with mild changes of dystonia. By contrast, measures of intracortical inhibition were not altered by switching off GPi stimulation. Spinal excitability did not change as assessed by H-reflex. CONCLUSION: GPi stimulation influences motor cortex excitability by a rapid modulation of thalamocortical outputs.

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators.

OBJECTIVES: In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses. METHODS: TMS and electrical stimulation of corticospinal fibres by the implanted electrodes were performed and the evoked hand motor potentials were analysed. RESULTS: In comparison with responses elicited by contralateral motor cortex stimulation, ipsilateral responses were smaller in amplitude (3.0+/-1.4 versus 5.8+/-1.5 mV), had shorter peak latencies (first negative peak: 20.9+/-0.8 versus 25.1+/-0.4 ms) and were followed by a shorter-lasting silent period (46+/-4 versus 195+/-35 ms). Ipsilateral responses following TMS had similar peak latencies to responses elicited subcortically by deep brain stimulation (DBS) (20.4+/-0.9 ms). CONCLUSIONS: Hand motor responses ipsilateral to TMS result from a subcortical activation of corticospinal fibres, via the implanted electrode in the other hemisphere, secondary to currents induced by TMS in subcutaneous wire loops that underlie the magnetic coil. Studies of TMS in patients with DBS have to take this potential source of confounding into account.

Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.

We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). Postoperatively, the patient improved by approximately 80% on the modified version of a myoclonus score without any significant change in the dystonic symptoms. This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.

Pallidal and thalamic neurostimulation in severe tardive dystonia.

A 70 year old woman presented with a 6 year history of medically refractory severe tardive dystonia. After informed consent, a bilateral stereotactic electrode placement targeting the ventral intermediate thalamic nucleus (VIM) and the globus pallidus internus (GPi) was performed. After bilateral stimulation of the GPi, the patient showed a clear and stable improvement of the painful dystonic syndrome within hours. Stimulation of the VIM did not improve the hyperkinetic movements and simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. The possible pathophysiological mechanisms are discussed.

[Apomorphine therapy versus deep rain stimulation. Clinical and economic aspects in patients with advanced Parkinson disease]. / Apomorphintherapie versus tiefe Hirnstimulation. Klinische und ökonomische Aspekte bei Patienten mit fortgeschrittenem Morbus Parkinson.

Long-term dopaminergic treatment of Parkinson's disease is complicated by the occurrence of dyskinesia and motor fluctuations and is responsible for increasing the costs of treatment. In these patients, continuous subcutaneous therapy with the dopamine agonist apomorphine or deep-brain stimulation represents a promising strategy. While the costs for the treatment with apomorphine are covered by health insurance, separate reimbursement for deep-brain stimulation does not exist in Germany. The case reports (n = 3) presented here emphasize that deep-brain stimulation is less cost-intensive than subcutaneous treatment with apomorphine in selected patients. Even in the first postoperative year costs for medication and hospital stays were reduced by approximately 60%. Moreover, in all three patients, motor complications improved after deep-brain stimulation in comparison to previous subcutaneous application of apomorphine. Thus, to further ensure deep-brain stimulation in parkinsonian patients it is mandatory to find a mode of reimbursement for the institutions concerned.

Interference of rhythmic constraint on gait in healthy subjects and patients with early Parkinson's disease: evidence for impaired locomotor pattern generation in early Parkinson's disease.

Patients in the early stages of Parkinson's disease have been shown to walk slower with smaller steps, resembling the gait of normal elderly subjects, but specific disorders of dynamic equilibrium or rhythmic gait patterning have not yet been identified. In the present study, gait control in 22 healthy subjects and 22 patients with early Parkinson's disease was challenged by means of a paradigm requiring subjects to decrease their step rate (cadence) by 20% in response to a metronome signal (rhythmic constraint). Control subjects and patients were matched for age, sex, and body height. Eleven patients were receiving standard antiparkinsonian therapy and were assessed under their ongoing medication, whereas the remaining 11 patients had not yet been started on dopaminergic therapy ("de novo" Parkinson's disease). Gait parameters reflecting dynamic equilibrium (double-support time) and locomotor patterning (step length, stride duration) were recorded by means of a mechanical device (locometer). Sixteen patients and 16 control subjects were able to accomplish the task. Whereas regulation of step length became irregular during rhythmic constraint in both patients and control subjects, irregular timing of steps was only observed in patients suggesting disturbance of periodic locomotor activity generation.