Brain stimulation in obesity.

Obesity is taking up epidemic proportions worldwide with significant impacts on the health of both the affected individual and on society as a whole. Treatment approaches consist of behavioural and pharmacological approaches, however, these are often found to be ineffective. In severe obesity, bariatric surgery is frequently performed. Unfortunately, 40% of patients show substantial weight gain over the long term or display the associated metabolic syndrome, making the development of novel therapies necessary. This review summarizes some of the current conceptual models, in particularly the 'food addiction' model, and then discusses specific therapeutic targets of brain stimulation, both non-invasive (transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcutaneous vagus nerve stimulation (VNS)) and invasive (deep brain stimulation and invasive VNS). As we will show, neuromodulatory approaches represent a promising tool for targeting specific brain structures implicated in the pathophysiology of obesity. Non-invasive techniques such as TMS, tDCS and transcutaneous VNS need further investigation before they may become ready for clinical usage. The currently available study data suggest that deep brain stimulation may become an effective and acceptable therapy for otherwise treatment-resistant obese patients. The results of the currently undergoing clinical trials are eagerly awaited.

EAN guidelines on central neurostimulation therapy in chronic pain conditions.

BACKGROUND AND PURPOSE: Our aim was to update previous European Federation of Neurological Societies guidelines on neurostimulation for neuropathic pain, expanding the search to new techniques and to chronic pain conditions other than neuropathic pain, and assessing the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. METHODS: A systematic review and meta-analysis of trials published between 2006 and December 2014 was conducted. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post-surgical chronic back and leg pain (CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE system was used to assess quality of evidence and propose recommendations. RESULTS: The following recommendations were reached: 'weak' for SCS added to conventional medical management in diabetic painful neuropathy, CBLP and CRPS, for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain; 'inconclusive' for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain. CONCLUSIONS: Given the poor to moderate quality of evidence identified by this review, future large-scale multicentre studies of non-invasive and invasive neurostimulation are encouraged. The collection of higher quality evidence of the predictive factors for the efficacy of these techniques, such as the duration, quality and severity of pain, is also recommended.

[SCS as a treatment option for failed back surgery syndrome]. / SCS als therapeutische Option beim Postnukleotomiesyndrom.

Unfortunately, 10-40 % of patients still experience pain after spinal surgery. There are many reasons for the patients' complaints. If no identifiable cause, such as a recurrent disc herniation, is visible, this is referred to as failed back surgery syndrome. However, this definition includes a variety of possible underlying causes of the pain, which result in just as many different therapeutic approaches. In addition to pharmacological, behavioral and physical therapy, also neuromodulation techniques can be offered; the best known method is spinal cord stimulation (SCS). The following article describes evidence-based studies with regard to the beneficial treatment of failed back surgery syndrome with conventional tonic SCS and new developments in spinal cord stimulation addressing the treatment of chronic refractory back pain.

[Neuromodulation for neuropathic pain]. / Neuromodulation bei neuropathischen Schmerzen.

In pain therapy neurostimulation procedures have replaced the previously used lesional methods with only very few exceptions. This is especially true for neuropathic pain, i.e. pain which occurs as a direct consequence of a lesion or disease of the somatosensory system. Nowadays, various stimulation procedures are included in the neurosurgical and anesthesiological armamentarium for pain therapy, depending on the site of damage. This article gives an overview of the currently used invasive stimulation procedures and the indications.

[Development of epidural spinal cord stimulation. Fortieth anniversary of the first implantation in Germany]. / Entwicklung der epiduralen Rückenmarkstimulation. 40 Jahre seit der Erstimplantation in Deutschland.

Spinal cord stimulation is nowadays an established therapy for various neuropathic and vasculopathic pain syndromes after more conservative measures have failed. However, 40 years ago, only 5 years after the first worldwide implantation in the US, this therapy was promoted in Germany. In 1972, the first devices were implanted in the Departments of Neurosurgery at the Universities Hannover and Freiburg. These pioneering efforts and the establishment of the therapy are intimately associated with three names: Jörg-Ulrich Krainick, Uwe Thoden, and Wolfhard Winkelmüller. Nowadays about 1700 spinal cord stimulation systems are implanted annually in Germany. The development of spinal cord stimulation from the beginnings up to now taking into special consideration the early years in Germany are presented.

Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex.

OBJECTIVES: Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. METHODS: Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. RESULTS: fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. CONCLUSION: Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time.

[Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines]. / Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen. Zusammenfassung der S3-Leitlinie.

Epidural spinal cord stimulation (SCS) is a reversible but invasive procedure which should be used for neuropathic pain, e.g. complex regional pain syndrome I (CRPS) and for mostly chronic radiculopathy in connection with failed back surgery syndrome following unsuccessful conservative therapy. Epidural SCS can also successfully be used after exclusion of curative procedures and conservative therapy attempts for vascular-linked pain, such as in peripheral arterial occlusive disease stages II and III according to Fontaine and refractory angina pectoris. Clinical practice has shown which clinical symptoms cannot be successfully treated by epidural SCS, e.g. pain in complete paraplegia syndrome or atrophy/injury of the sensory pathways of the spinal cord or cancer pain. A decisive factor is a critical patient selection as well as the diagnosis. Epidural SCS should always be used within an interdisciplinary multimodal therapy concept. Implementation should only be carried out in experienced therapy centers which are in a position to deal with potential complications.

[Subcutaneous peripheral stimulation of the greater occipital nerve for the treatment of chronic headache syndromes]. / Subkutane periphere Stimulation des N. occipitalis major zur Behandlung chronischer Kopfschmerzsyndrome.

Medical treatment for certain chronic headache syndromes such as hemicrania continua (HC), chronic migraine (CM) or chronic cluster headache (CCH) is challenging and in many cases does not lead to sufficient pain relief or is limited by severe side effects. In the last few years neuromodulatory treatments such as subcutaneous stimulation of the greater occipital nerve or deep brain stimulation (DBS) in the hypothalamus have evolved. This report focuses on current knowledge and the results of peripheral subcutaneous nerve stimulation (SPNS) in the literature of the described headache syndromes and presents our own long-term results in ten patients. Technical details of implantation and possible complications are reported. The results between the two different stimulation types are compared. In summary, peripheral nerve stimulation of the greater occipital nerve is less invasive but also less effective in comparison to hypothalamic stimulation. However, the severity and frequency of pain attacks is significantly reduced. For other intractable headache syndromes SPNS of the greater occipital nerve offers a reasonable addition to medical treatment.

[Artificial intelligence in neurosurgery]. / Künstliche Intelligenz in der Neurochirurgie.

BACKGROUND: Artificial intelligence (AI) in neurosurgery is becoming increasingly more important as the technology advances. This development can be measured by the increase of publications on AI in neurosurgery over the last years. OBJECTIVE: This article provides insights into the current possibilities of using AI in neurosurgery. MATERIAL AND METHODS: A review of the literature was carried out with a focus on exemplary work on the use of AI in neurosurgery. RESULTS: The current neurosurgical publications on the use of AI show the diversity of the topic in this field. The main areas of application are diagnostics, outcome and treatment models. CONCLUSION: The various areas of application of AI in the field of neurosurgery with a refined preoperative diagnostics and outcome predictions will significantly influence the future of neurosurgery. Neurosurgeons will continue to make the decisions on the indications for surgery but an optimized statement on diagnosis, treatment options and on the risk of surgery will be made by neurosurgeons with the help of AI in the future.

[Neuroablative procedures in pain therapy]. / Neurodestruktive Verfahren in der Schmerztherapie.

Although surgical ablative procedures can be effective in the management of chronic pain of malignant and non-malignant origin, they are often disregarded as treatment options due to the fact that in the past these procedures were associated with high complication rates. The complications include the development of new neurological deficits and in cases of long-term follow-up, the occurrence of the old or new pain syndromes by deafferentation. On the other hand there exist many less invasive, e.g. neuromodulatory procedures or non-invasive measures (systemic oral or transdermal opioids) which are able to considerably reduce chronic pain. Nevertheless, there remain certain very restricted indications for the use of neuroablative procedures for the treatment of chronic pain even today.

Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series.

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.

Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington's disease.

INTRODUCTION: Pharmacological treatment of chorea in Huntington's disease (HD) is often limited by poor efficacy or side effects. Pallidal deep brain stimulation (DBS) has been considered in these patients but experience is so far limited. METHODS: We prospectively evaluated the effects of bilateral DBS of the Globus pallidus internus (GPi) over one year in six severely affected HD patients with treatment refractory chorea in an advanced stage of the disease. Primary endpoint of the study was improvement in chorea. Additionally, we evaluated the effects of GPi DBS on the motor part of the Unified Huntington's Disease Rating Scale (UHDRS), bradykinesia, dystonia, functional impairment, psychiatric and cognitive symptoms. Side effects were systematically assessed. RESULTS: The chorea subscore was significantly reduced postoperatively (-47% six months, -40% twelve months postoperatively). The UHDRS total motor score was significantly reduced at six months postoperatively (- 17%) but the effect was not sustained twelve months after the operation (- 5%). Pallidal DBS did not improve other motor symptoms or functional impairment. There was no effect on psychiatric symptoms or cognition. A number of side effects were noted, especially spasticity in three of the patients. CONCLUSIONS: Pallidal DBS is a treatment option for HD patients with severe pharmacologically refractory chorea. Further studies are needed to define optimal candidates for this procedure.

[Trigeminal neuralgia: how often are trigeminal nerve-vessel contacts found by MRI in normal volunteers]. / Trigeminusneuralgie: Wie häufig gibt es einen Gefäss-Nerven-Kontakt bei schmerzfreien Probanden?

PURPOSE: To assess prospectively how often contacts are found between the trigeminal nerve and arteries or veins in the perimesencephalic cistern via MRI in normal volunteers. MATERIALS AND METHODS: 48 volunteers without a history of trigeminal neuralgia were examined prospectively (MRI at 1.5 T; T2-CISS sequence, coronal orientation, 0.9 mm slice thickness). Two radiologists decided by consensus whether there was a nerve-vessel contact in the perimesencephalic cistern. RESULTS: In 27 % of the volunteers, no contact was found between the trigeminal nerve and regional vessels, while in 73 %, such a contact was present. In 61 % of the cases, the offending vessel was an artery, in 39 %, it was a vein. In 2 volunteers, a deformation of the nerve was noted. CONCLUSION: Contrary to what has been suggested by retrospective studies, the majority of normal volunteers, if studied prospectively, do show a contact between the trigeminal nerve and local vessels. A close proximity between the nerve and regional vessels is thus normal and is not necessarily proof of a pathological nerve-vessel conflict.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

OBJECTIVE: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. RESULTS: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. CONCLUSIONS: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus.

We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Disappearance of central thalamic pain syndrome after contralateral parietal lobe lesion: implications for therapeutic brain stimulation.

At present there is hardly any appropriate therapy for central pain syndromes available. We report on a unique case of a central thalamic pain syndrome that did not respond to any therapy but disappeared after an additional contralateral parietal lobe lesion. This example indicates that lesions affecting the bilateral balance of thalamo-parietal circuits may lead to pain relief in patients with central pain syndrome, which probably constitutes a bilateral disorder of functional plasticity. This should be taken into account in chronic brain stimulation for persistent pain states.

Intraoperative MR imaging increases the extent of tumor resection in patients with high-grade gliomas.

BACKGROUND AND PURPOSE: MR is being used increasingly as an intraoperative imaging technique. The purpose of this study was to test the hypothesis that intraoperative MR imaging increases the extent of tumor resection, thus improving surgical results in patients with high-grade gliomas. METHODS: Thirty-eight patients with intracranial high-grade gliomas underwent 41 operations. Using a neuronavigation system, tumors were resected in all patients to the point at which the neurosurgeon would have terminated the operation because he thought that all enhancing tumor had been removed. Intraoperative MR imaging (0.2 T) was performed, and surgery, if necessary and feasible, was continued. All patients underwent early postoperative MR imaging (1.5 T). By comparing the proportions of patients in whom complete resection of all enhancing tumor was shown by intraoperative and early postoperative MR imaging, respectively, the impact of intraoperative MR imaging on surgery was determined. RESULTS: Intraoperative MR imaging showed residual enhancing tumor in 22 cases (53.7%). In 15 patients (36.6%), no residual tumor was seen, whereas the results of the remaining four intraoperative MR examinations (9.7%) were inconclusive. In 17 of the 22 cases in which residual tumor was seen, surgery was continued. Early postoperative MR imaging showed residual tumor in eight patients (19.5%) and no residual tumor in 31 cases (75.6%); findings were uncertain in two patients (4.9%). The difference in the proportion of "complete removals" was statistically highly significant (P = .0004). CONCLUSION: Intraoperative MR imaging significantly increases the rate of complete tumor removal. The rate of complete removal of all enhancing tumor parts was only 36.6% when neuronavigation alone was used, which suggests the benefits of intraoperative imaging.