Objective: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study... more
Objective: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study tested the value of somatosensory evoked potentials (SEP) for the functional identification of VIM and STN. Methods: Median nerve SEP were recorded from the final stimulation electrodes targeted
Research Interests: Deep Brain Stimulation, Multiple sclerosis, Electroencephalography, Low Frequency, Subthalamic Nucleus, and 14 moreMovement disorders, Brain Mapping, Humans, Female, Male, Aged, Middle Aged, Adult, Digital Filter Design, Basal ganglia, Essential Tremor, Median Nerve, Parkinson Disease, and Movement Disorder
Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy... more
Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disabilit...
Research Interests:
Stereotactic radiosurgery is related to the history of "radiotherapy" and "stereotactic neurosurgery". The concepts for neurosurgeons and radiooncologists have been changed during the last decade and have also... more
Stereotactic radiosurgery is related to the history of "radiotherapy" and "stereotactic neurosurgery". The concepts for neurosurgeons and radiooncologists have been changed during the last decade and have also transformed neurosurgery. The gamma knife and the stereotactically modified linear accelerator (LINAC) are radiosurgical equipments to treat predetermined intracranial targets through the intact skull without damaging the surrounding normal brain tissue. These technical developments allow a more precise intracranial lesion control and offer even more conformal dose plans for irregularly shaped lesions. Histological determination by stereotactic biopsy remains the basis for any otherwise undefined intracranial lesion. As a minimal approach, it allows functional preservation, low risk and high sensitivity. Long-term results have been published for various indications. The impact of radiosurgery is presented for the management of gliomas, metastases, brain ste...
Research Interests:
Deep Brain Stimulation (DBS, chronic high frequency stimulation) is well established for Parkinson's disease and tremordominant movement disorders. Generalized dystonia is known as a type of movement disorder in which therapeutic... more
Deep Brain Stimulation (DBS, chronic high frequency stimulation) is well established for Parkinson's disease and tremordominant movement disorders. Generalized dystonia is known as a type of movement disorder in which therapeutic options are very limited. A case of generalized dystonia is reported which was successfully treated by DBS in the Globus pallidus internus (GPI). A 26 years old male suffered from severe torsion dystonia of the lower limbs. The onset of symptoms was at age 7. It started with dystonia of the left foot. He very fast developed severe dystonia of the lower limbs. These complaints were initially treated by diazepam, later by baclofen (Lioresal ((R))) p.o em leader There was no L-DOPA response. Because of the rapid progression of the disease a cervical spinal cord stimulator was implanted with a transient success. Due to further progression of the disease the patient became wheelchair bounded and resistant for oral medication. Limited improvement of symptoms ...
Research Interests: Brain, Humans, Male, Baclofen, Adult, and 3 moreGlobus Pallidus, Basal ganglia, and X ray Computed Tomography
Research Interests:
Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Metastatic spread to the cerebral parenchyma is absolutely rare. This case report describes... more
Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Metastatic spread to the cerebral parenchyma is absolutely rare. This case report describes the clinical course in a 60-year-old man whose tumor came to medical attention because of a seizure. Magnetic resonance imaging demonstrated two intracerebral lesions. The symptomatic lesion was removed microneurosurgically and histology demonstrated a metastasis from a malignant peripheral nerve sheath tumor. Postoperatively, whole-brain irradiation was performed. The primary tumor was identified in the area of the sciatic nerve on the right. Follow-up 14 months after resection showed that there was no progression of the intracerebral lesions but an increase in size and number of distant metastases. There are no generally accepted guidelines for the treatment of malignant peripheral nerve sheath tumors with cerebral metastases. This case report pres...
Research Interests:
Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet... more
Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life.
Research Interests:
Spinal cord stimulation (SCS) for the treatment of chronic pain is a well-established therapy. However, the requirement that paresthesia be continually felt by the patient has important downsides. This study evaluated the effectiveness of... more
Spinal cord stimulation (SCS) for the treatment of chronic pain is a well-established therapy. However, the requirement that paresthesia be continually felt by the patient has important downsides. This study evaluated the effectiveness of a new paresthesia-free SCS paradigm, called burst stimulation, for the treatment of failed back surgery syndrome (FBSS) with a prospective, randomized, double-blind, placebo-controlled design. Twenty patients with FBSS and a preexisting SCS system each received three treatment allocations in random order for a period of one week: 500-Hz tonic stimulation, burst stimulation, and placebo stimulation. The primary outcome measure was pain intensity measured on a numerical rating scale (NRS). Secondary outcome measures were pain quality measured using the Short-Form McGill Pain Questionnaire (SFMPQ) and safety. Additional data were collected relating to pain-related disability measured using the Oswestry Disability Index (ODI). The lowest mean NRS and SFMPQ scores were observed under burst stimulation. For the burst stimulation treatment group, mean NRS and SFMPQ scores were significantly decreased compared with the other treatment groups. Mean NRS and SFMPQ scores were not significantly different between 500-Hz tonic stimulation and placebo stimulation. Although the lowest mean ODI score was observed under burst stimulation, no significant differences were found between the ODI categories. No adverse events occurred, and burst stimulation was significantly preferred by 16 patients (80%). Overall, burst stimulation resulted in significantly better pain relief and improved pain quality in the short term compared with 500-Hz tonic stimulation and placebo stimulation and was preferred by the majority of patients.
Research Interests:
Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment.... more
Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment. In this randomised, sham-controlled trial, we recruited patients with cervical dystonia from centres in Germany, Norway, and Austria. Eligible patients (ie, those aged 18-75 years, disease duration ≥3 years, Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score ≥15 points) were randomly assigned (1:1) to receive active neurostimulation (frequency 180 Hz; pulse width 120 μs; amplitude 0·5 V below adverse event threshold) or sham stimulation (amplitude 0 V) by computer-generated randomisation lists with randomly permuted block lengths stratified by centre. All patients, masked to treatment assignment, were implanted with a deep brain stimulation device and received their assigned treatment for 3 months. Neurostimulation was activat...
Research Interests:
Human somatosensory evoked potentials (SEP) contain a brief burst of high-frequency wavelets (>400 Hz) presumably reflecting rapidly repeated population spikes of as-yet undetermined origin. To study state-dependent response... more
Human somatosensory evoked potentials (SEP) contain a brief burst of high-frequency wavelets (>400 Hz) presumably reflecting rapidly repeated population spikes of as-yet undetermined origin. To study state-dependent response changes, SEP after electric median nerve stimulation were recorded in six Parkinson's disease patients perioperatively from intrathalamic electrode implants, and in five non-implanted patients from scalp electrodes, before and under propofol narcosis. In all intrathalamic recordings burst amplitude and intraburst frequency (approximately 950 Hz) proved to be almost stable under propofol administration. In strong contrast, the scalp burst (640 Hz) was significantly slowed (480 Hz) under propofol narcosis, and its amplitude reduced to 28% of the pre-propofol baseline. Low-frequency SEP components which underly the burst at thalamic (P16) and cortical level (N20) did not change significantly. This dissociation of bursts indicates neuronal generators showing different sensitivities to propofol narcosis, with a robust thalamic response and a state-dependent cortical contribution, possibly from pyramidal chattering cells and/or inhibitory interneurons.
Research Interests:
The pathophysiology of Parkinson's disease (PD) has been related to excessive beta band oscillations in the basal ganglia. Recent recordings from the subthalamic nucleus of PD patients showed that beta oscillations show strong... more
The pathophysiology of Parkinson's disease (PD) has been related to excessive beta band oscillations in the basal ganglia. Recent recordings from the subthalamic nucleus of PD patients showed that beta oscillations show strong cross-frequency coupling with high-frequency oscillations (>200 Hz). However, little is known about the characteristics and functional properties of these oscillations. We studied the spatial distribution of high-frequency oscillations and their relation to PD motor symptoms. We included 10 PD patients in medication OFF who underwent implantation of deep brain stimulation (DBS) electrodes. Intraoperative five-channel microelectrode recordings were performed at 9 to 10 recording sites within the subthalamic nucleus and its immediate surroundings. We found a focal spatial distribution of high-frequency oscillations with highest power 2 mm below the dorsolateral border of the subthalamic nucleus. Within the subthalamic nucleus, power peaked slightly anteri...
Research Interests:
Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson's disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS.... more
Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson's disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS. Thirty-eight patients have undergone surgery for advanced PD since 1996. They include 12 females and 26 males with a mean age of 55.6 years. The mean stage on the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes (Medtronic DBS 31389) were stereotactically implanted into the STN bilaterally. Targeting was performed using computerized tomography (CT) scans and ventriculography (VG). After 4 days of external stimulation, permanent neurostimulators were implanted. Patients were evaluated preoperatively and 1, 6, and 12 months postoperatively. Evaluations were performed in defined on and off states using the Unified Parkinson's Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr Scale, the dyskinesia scale, and the Activities of Daily Living (ADL) Scale. Significant improvement of all motor symptoms was found in all patients (UPDRS motor score 32/48 preoperatively versus 15/30 at 12-month follow-up, p < 0.001). Daily off-times were reduced by 35%. Dyskinesias also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3 at 12 months follow-up). Postoperative L-dopa medication was adjusted (mean reduction: 53%). Complications occurred in two patients (5%) who developed infections, leading to system removal. Systems were replaced after 6 months. Two patients (5%) had a permanent worsening of a previously known depressive state and developed progressive dementia. TN stimulation is a relatively safe procedure for treating advanced PD. The possibility of readjusting the stimulation parameters postoperatively improves the therapeutic outcome and reduces side effects in comparison to ablative methods.
Research Interests: Deep Brain Stimulation, Treatment Outcome, Subthalamic Nucleus, Humans, Female, and 13 moreMale, Follow-up studies, Ct Scan, Clinical Sciences, Rating Scale, Middle Aged, Computerized tomography, Side Effect, Neurosciences, Parkinson Disease, Movement Disorder, Postoperative Period, and Activity of Daily Living
Research Interests:
Tremor in Parkinson's disease... more
Tremor in Parkinson's disease (PD) is generated by an oscillatory neuronal network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus (STN) which is part of the basal ganglia is of particular interest, since deep brain stimulation of the STN is an effective treatment for PD including Parkinsonian tremor. It is controversial if and how the STN contributes to tremor generation. In this study, we analyze neuronal STN activity in seven patients with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain stimulation. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. After spike-sorting, spectral coherence was analyzed between spike activity of STN neurons and tremor activity. Significant coherence at the tremor frequency was detected between EMG and neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN activity was widely distributed over the STN being more frequent in its dorsal parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest that synchronous neuronal STN activity at the tremor frequency contributes to the pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of tremor-coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.
Research Interests: Neuroscience, Psychology, Cognitive Science, Deep Brain Stimulation, Skeletal muscle biology, and 18 moreSubthalamic Nucleus, Neuronal Network, Humans, Female, Male, Tremor, Electromyography, Microelectrodes, Neurons, Spatial Distribution, Aged, Middle Aged, Adult, Neuronal Activity, Basal ganglia, Neurosciences, Wrist, and Parkinson Disease
Somatosensory evoked potentials (SEP) were recorded in 11 awake patients from intrathalamic electrodes implanted for tremor treatment. A brief (7ms) polyphasic SEP burst (mean frequency > 1000 Hz, with occasional drops to 600 Hz)... more
Somatosensory evoked potentials (SEP) were recorded in 11 awake patients from intrathalamic electrodes implanted for tremor treatment. A brief (7ms) polyphasic SEP burst (mean frequency > 1000 Hz, with occasional drops to 600 Hz) was found to be superimposed onto the primary thalamic low-frequency response at 16 ms (tP16) and preceeded a scalp-derived 600 Hz burst by 4 ms. Thalamic burst and tP16 generators had a close intrathalamic co-localization. The thalamic burst strength varied more than and independently from tP16. High-frequency thalamic SEP bursts probably reflect a superposition of slightly asynchronously triggered population spikes, generated e.g. by bursting thalamocortical relay cells. The thalamic burst amplitude fluctuations independent from low-frequency responses suggest a peculiar role for thalamic burst coding in awake subjects.
Research Interests:
Human somatosensory evoked potentials (SEP) contain high-frequency (600 Hz) wavelet bursts possibly reflecting repetitive population spikes in thalamocortical axons and/or postsynaptic responses. To dissociate thalamic and cortical burst... more
Human somatosensory evoked potentials (SEP) contain high-frequency (600 Hz) wavelet bursts possibly reflecting repetitive population spikes in thalamocortical axons and/or postsynaptic responses. To dissociate thalamic and cortical burst components the recovery of intrathalamic SEP (derived from electrodes implanted for movement disorder therapy in seven patients) was compared with scalp SEP in six age-matched Parkinsonian patients and six healthy younger subjects. Upon electric median nerve double-pulse stimulation conditioned scalp bursts were found attenuated in both groups, more for 10ms than 20ms interstimulus intervals; moreover, intraburst frequencies decreased from 690Hz to 590Hz. By contrast, intrathalamic burst amplitudes and frequencies (around 1 kHz) remained largely stable. These dissociations indicate functionally distinct generator mechanisms for scalp and intrathalamic high-frequency SEP bursts.
Research Interests:
Spinal cord stimulation (SCS) is an established method for treatment of chronic pain. Cylindrical-type leads can be implanted percutaneously. In contrast, paddle leads (lamitrode) require more invasive surgery (i.e., laminotomy or... more
Spinal cord stimulation (SCS) is an established method for treatment of chronic pain. Cylindrical-type leads can be implanted percutaneously. In contrast, paddle leads (lamitrode) require more invasive surgery (i.e., laminotomy or laminectomy) for placement into the epidural space, thereby offering several advantages over percutaneous leads (octrode), including less lead migration and better paresthesia coverage. The goal of this study was to prospectively demonstrate the safety and efficacy of a percutaneous paddle lead for SCS. This prospective trial enrolled 81 patients. The mean age was 57 years (range 27-82 years) with an almost equal sex distribution (male 47%, female 53%). Most patients (90%) had failed back surgery syndrome combined with lower extremity pain and lower back pain. A percutaneous paddle lead was implanted using a novel introduction system for percutaneous implantation. All implantations were performed under local anesthesia. Prior to the final implantation of the impulse generator, all patients underwent seven days of trial stimulation with pain assessment using a visual analog scale (VAS). The median follow-up was 12 months. The data showed favorable clinical outcomes for paresthesia coverage and pain reduction (median VAS 8.4 vs. 2.3), with a risk profile comparable with known percutaneous techniques. Compared with the published data (2-22%), the lead migration rate in this study was low (2.5%). No perioperative complications occurred. This new, minimally invasive percutaneous paddle lead is effective and safe, with a low migration rate. Placement can be done under local anesthesia, allowing an intraoperative assessment of the paresthesia coverage in terms of pain relief. This approach is less invasive and offers a faster and more comfortable procedure compared with laminotomy or laminectomy.
Research Interests: Cognitive Science, Neuromodulation, Treatment Outcome, Pain Management, Low back pain, and 15 moreProspective studies, Humans, Female, Spinal Cord, Male, Follow-up studies, Clinical Sciences, General Anesthesia, Aged, Middle Aged, Adult, PARESTHESIA, Prosthesis Implantation, Neurosciences, and Pain Measurement
The aim of the study was to investigate the predictive value of percutaneous electrical nerve stimulation (PENS) in peripheral nerve stimulation (PNS) for chronic neuropathic pain. Twelve patients being evaluated for PNS for chronic... more
The aim of the study was to investigate the predictive value of percutaneous electrical nerve stimulation (PENS) in peripheral nerve stimulation (PNS) for chronic neuropathic pain. Twelve patients being evaluated for PNS for chronic neuropathic pain were included in this survey. Stimulation with acupuncture needles was applied with continuous high frequency stimulation. Position, polarity, frequency and amperage threshold of perception, and adverse effects were noted. Additional stimulation side effects were documented. A StimScore was developed to evaluate effects in a standardized manner. This StimScore comprises coverage of the painful area, therapeutic range, and amperage required for successful stimulation. StimScore was determined during PENS, during test stimulation, and under final stimulation. PNS was well tolerated by all patients. Seven of the 12 patients (58%) were classified as successfully treated, and 5/12 patients (42%) as unsuccessful. The mean overall pain reduction in the first group was 4.0 points (SD = 2.87, P = 0.010) and 2.4 points (SD = 1.29, P = 0.014), respectively, on the visual analogue scale. In the successful stimulation group, a mean StimScore of 13.14 (SD 11.19-15.0) was calculated vs. 10.4 (95% CI 8.52-12.28) in the unsuccessful stimulation group (P = 0.033, 95% CI = 0.265-5.220). Predicting response to PNS is crucial to reduce the number of patients implanted in vain. To adopt PENS via electroacupuncture needles as a percutaneous simulation method for PNS seemed to be feasible. The technique presented herein bears the potential to improve patient selection combined with reduced invasiveness. The presented results are encouraging and deliver a starting point for further trials.
Research Interests:
Research Interests:
Impaired generation of verbs relative to nouns has been reported in Parkinson's disease (PD) and has been associated with the frontal pathophysiology of PD. The aim of the present study was to measure noun/verb... more
Impaired generation of verbs relative to nouns has been reported in Parkinson's disease (PD) and has been associated with the frontal pathophysiology of PD. The aim of the present study was to measure noun/verb generation abilities in PD and to determine whether noun/verb generation is affected by stimulation of the subthalamic nucleus (STN). 8 participants who had been diagnosed with PD and had received surgery for deep brain stimulation (DBS) of the STN as well as 15 control participants completed a noun/verb generation task with four probe-response conditions-namely, noun-noun, verb-noun, noun-verb and verb-verb conditions. Patients with PD were assessed while receiving STN stimulation and without stimulation. During the off stimulation condition, patients with PD presented with a selective deficit in verb generation compared with control participants. However, when receiving STN stimulation, patients with PD produced significantly more errors than controls during the noun-noun and verb-verb conditions, supporting evidence from previous studies that STN stimulation modulates a frontotemporal network associated with word generation. Finally, errors during verb generation were significantly correlated with item selection constraint (ie, the degree to which a response competes with other response alternatives) in the on stimulation condition, but not the off stimulation condition. Our results suggest that STN stimulation affects the ability to select from many competing lexical alternatives during verb generation.
Research Interests:
Research Interests:
Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in... more
Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in other basal ganglia nuclei and cortical areas. In order to localize these cortical areas, we recorded local field potentials (LFPs) and magnetoencephalography (MEG) simultaneously in PD patients undergoing surgery for deep brain stimulation (DBS). Patients were withdrawn from antiparkinsonian medication and recorded at rest. We scanned the entire brain for oscillations coherent with LFPs recorded from the STN with a frequency domain beamformer. Coherent activity in the low (12-20 Hz) and high (20-35 Hz) beta range was found in the ipsilateral sensorimotor and the premotor cortex. Coherence in the alpha range (7-12 Hz) was observed at various locations in the ipsilateral temporal lobe. In a subset of subjects, the superior temporal gyrus consistently sh...