Targeted neurotechnology restores walking in humans with spinal cord injury.

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

Unilateral prefrontal lobotomy for epilepsy: technique and surgical anatomy.

OBJECTIVE: Surgery for frontal lobe epilepsy remains a challenge because of the variable seizure outcomes after surgery. Disconnective procedures are increasingly applied to isolate the epileptogenic focus and avoid complications related to extensive brain resection. Previously, the authors described the anterior quadrant disconnection procedure to treat large frontal lobe lesions extending up to but not involving the primary motor cortex. In this article, they describe a surgical technique for unilateral disconnection of the prefrontal cortex, while providing an accurate description of the surgical and functional anatomy of this disconnective procedure. METHODS: The authors report the surgical treatment of a 5-month-old boy who presented with refractory epilepsy due to extensive cortical dysplasia of the left prefrontal lobe. In addition, with the aim of both describing the subcortical intrinsic anatomy and illustrating the different connections between the prefrontal lobe and the rest of the brain, the authors dissected six human cadaveric brain hemispheres. These dissections were performed from lateral to medial and from medial to lateral to reveal the various tracts sectioned during the three different steps in the surgery, namely the intrafrontal disconnection, anterior callosotomy, and frontobasal disconnection. RESULTS: The first step of the dissection involves cutting the U-fibers. During the anterior intrafrontal disconnection, the superior longitudinal fasciculus in the depth of the middle frontal gyrus, the uncinate fasciculus, and the inferior frontooccipital fasciculus in the depth of the inferior frontal gyrus at the level of the anterior insular point are visualized and sectioned, followed by sectioning of the anterior limb of the internal capsule. Once the frontal horn is reached, the anterior callosotomy can be performed to disconnect the genu and the rostrum of the corpus callosum. The intrafrontal disconnection is deepened toward the falx, and at the medial surface, the cingulum is sectioned. The frontobasal disconnection involves cutting the anterior limb of the anterior commissure. CONCLUSIONS: This technique allows selective isolation of the epileptogenic focus located in the prefrontal lobe to avoid secondary propagation. Understanding the surface and white matter fiber anatomy is essential to safely perform the procedure and obtain a favorable seizure outcome.

A New Combined Technique Reducing the Risk of Paraplegia during Thoracoabdominal Aorta Replacement.

Acute spinal cord ischemia during thoracoabdominal aorta replacement is a dreadful complication. Existing tools (motor evoked potential [MEP] and somatosensory evoked potential [SSEP]) do not allow differentiating between central and peripheral paraplegia. Therefore, the surgeon often performs unnecessary reimplantation of intercostal arteries: this is time consuming, and significantly increases bleeding complications. We present a simple technique combining MEP and peripheral compound muscle action potential induced by posterior tibialis nerve stimulation, enabling the surgeon to quickly discriminate between central and peripheral neurologic injury. The surgeon has one more tool to drive in real time the optimal surgical strategy. This strategy guides the decision as to which side branches ought to be reimplanted, thus minimizing the risk of paraplegia.

Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach: planned subtotal resection followed by gamma knife radiosurgery.

OBJECTIVE: To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves. METHODS: Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up. RESULTS: A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4-78). Mean presurgical tumor volume was 12.5 cm3 (range 1.47-34.9). Postoperative status showed normal facial nerve function (House-Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner-Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8-13.9). Mean tumor volume at GKRS was 3.5 cm3 (range 0.5-12.8), corresponding to mean residual volume of 29.4% (range 6-46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11-12). Mean follow-up after GKRS was 24 months (range 3-60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time. CONCLUSION: Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.

Deep Brain Stimulation of the Ventroposteromedial (VPM) Thalamus 10 Years after VPM Thalamotomy to Treat a Recurrent Facial Pain.

We report the successful treatment of recurrent facial pain by deep brain stimulation (DBS) of the ventroposteromedial thalamic nucleus (VPM-DBS), 10 years after VPM thalamotomy. A 62-year-old woman who suffered from an atypical right-sided trigeminal neuralgia of the V1 and V2 branches was successfully treated a decade ago with a radiofrequency VPM thermocoagulation. Ten years later, the same burning right-sided trigeminal pain progressively recurred and was resistant to medical treatments. A DBS procedure was proposed to the patient aiming to stimulate the vicinity of the preexisting stereotactic lesion. Intraoperatively, the pain relief was immediate at low stimulation intensities. Eleven months later, the patient remains pain free. This case report suggests that DBS targeting an area of the VPM close to the previous stereotactic lesion is possible as a salvage therapy, and can successfully achieve relief of facial pain 10 years after VPM thalamotomy.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND: Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES: The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS: We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS: There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION: There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

[Operative and perioperative aspects of deep brain stimulation]. / Aspects opératoires et péri-opératoires de la stimulation cérébrale profonde.

Deep brain stimulation (DBS) requires the surgical implantation of a system including brain electrodes and impulsion generator(s). The nuclei targeted by the stereotaxic implantation methodology have to be visualized at best by high resolution imaging. The surgical procedure for implanting the electrodes is performed if possible under local anaesthesia to make electro-physiological measurements and to test intra-operatively the effect of the stimulation, in order to optimize the position of the definitive electrode. In a second step, the impulsion generator(s) are implanted under general anaesthesia. DBS for movement disorders has a very good efficacy and a low albeit non-zero risk of serious complications. Complications related to the material are the most common.

A CT-based study investigating the relationship between pedicle screw placement and stimulation threshold of compound muscle action potentials measured by intraoperative neurophysiological monitoring.

PURPOSE: Neurophysiological monitoring aims to improve the safety of pedicle screw placement, but few quantitative studies assess specificity and sensitivity. In this study, screw placement within the pedicle is measured (post-op CT scan, horizontal and vertical distance from the screw edge to the surface of the pedicle) and correlated with intraoperative neurophysiological stimulation thresholds. METHODS: A single surgeon placed 68 thoracic and 136 lumbar screws in 30 consecutive patients during instrumented fusion under EMG control. The female to male ratio was 1.6 and the average age was 61.3 years (SD 17.7). Radiological measurements, blinded to stimulation threshold, were done on reformatted CT reconstructions using OsiriX software. A standard deviation of the screw position of 2.8 mm was determined from pilot measurements, and a 1 mm of screw-pedicle edge distance was considered as a difference of interest (standardised difference of 0.35) leading to a power of the study of 75 % (significance level 0.05). RESULTS: Correct placement and stimulation thresholds above 10 mA were found in 71 % of screws. Twenty-two percent of screws caused cortical breach, 80 % of these had stimulation thresholds above 10 mA (sensitivity 20 %, specificity 90 %). True prediction of correct position of the screw was more frequent for lumbar than for thoracic screws. CONCLUSION: A screw stimulation threshold of >10 mA does not indicate correct pedicle screw placement. A hypothesised gradual decrease of screw stimulation thresholds was not observed as screw placement approaches the nerve root. Aside from a robust threshold of 2 mA indicating direct contact with nervous tissue, a secondary threshold appears to depend on patients' pathology and surgical conditions.

Direct cochlear nerve stimulation monitoring through evoked muscle responses during retrosigmoid vestibular schwannoma resection surgery: technical note.

OBJECTIVE: Cochlear nerve preservation during surgery for vestibular schwannoma (VS) may be challenging. Brainstem auditory evoked potentials and cochlear compound nerve action potentials have clearly shown their limitations in surgeries for large VSs. In this paper, the authors report their preliminary results after direct electrical intraoperative cochlear nerve stimulation and recording of the postauricular muscle response (PAMR) during resection of large VSs. METHODS: The details for the electrode setup, stimulation, and recording parameters are provided. Data of patients for whom PAMR was recorded during surgery were prospectively collected and analyzed. RESULTS: PAMRs were recorded in all patients at the ipsilateral vertex-earlobe scalp electrode, and in 90% of the patients they were also observed in the contralateral electrode. The optimal stimulation intensity was found to be 1 mA at 1 Hz, with a good cochlear response and an absent response from other nerves. At that intensity, the ipsilateral cochlear response had an initial peak at a mean (± SEM) latency of 11.6 ± 1.5 msec with an average amplitude of 14.4 ± 5.4 µV. One patient experienced a significant improvement in his audition, while that of the other patients remained stable. CONCLUSIONS: PAMR monitoring may be useful in mapping the position and trajectory of the cochlear nerve to enable hearing preservation during surgery.

Central quadrantotomy for intractable childhood epilepsy: operative technique and functional neuroanatomy.

Refractory subhemispheric epilepsy has been traditionally treated by resection. The last few decades have seen the emergence of disconnective techniques, for both hemispheric and subhemispheric disease. The aim of this study was to describe the technique for a disconnective surgery for large epileptogenic lesions involving the central (perirolandic cortices), parietal, and occipital lobes. This junctional cortex within the hemisphere (in contrast to anterior and posterior quadrantotomies) presents unique challenges when contemplating a complete disconnection of the region. The surgical technique is achieved through six distinct steps: fronto-central, inferior frontoparietal, lateral temporo-occipital, medial frontal, basal temporo-occipital, and posterior parasagittal callosal disconnections. The functional neuroanatomy of each step is described, along with cadaveric dissections. The authors describe this technique and include a case description of a young girl who presented with childhood-onset intractable epilepsy associated with cognitive stagnation. The postoperative seizure outcome in this patient remains excellent at 2 years' follow-up, with gains in cognition and behavior. Excellent seizure outcomes can be achieved if the network encompassing the entire epileptogenic cortex is disconnected while ensuring preservation of fiber systems that link functionally eloquent uninvolved cortices adjacent to the central quadrant.

Cadaveric White Matter Dissection Study of the Telencephalic Flexure: Surgical Implications.

Neurosurgery has traditionally been overtly focused on the study of anatomy and functions of cortical areas with microsurgical techniques aimed at preserving eloquent cortices. In the last two decades, there has been ever-increasing data emerging from advances in neuroimaging (principally diffusion tensor imaging) and clinical studies (principally from awake surgeries) that point to the important contribution of white matter tracts (WMT) that influence neurological function as part of a brain network. Major scientific consortiums worldwide, currently working on this human brain connectome, are providing evidence that is dramatically altering the manner in which we view neurosurgical procedures. The development of the telencephalic flexure, a major landmark during the human embryogenesis of the central nervous system (CNS), severely affects the cortical/subcortical anatomy in and around the sylvian fissure and thus the different interacting brain networks. Indeed, the telencephalic flexure modifies the anatomy of the human brain with the more posterior areas becoming ventral and lateral and associative fibers connecting the anterior areas with the previous posterior ones follow the flexure, thus becoming semicircular. In these areas, the projection, association, and commissural fibers intermingle with some WMT remaining curved and others longitudinal. Essentially the ultimate shape and location of these tracts are determined by the development of the telencephalic flexure. Five adult human brains were dissected (medial to lateral and lateral to medial) with a view to describing this intricate anatomy. To better understand the 3D orientation of the WMT of the region we have correlated the cadaveric data with the anatomy presented in the literature of the flexure during human neuro-embryogenesis in addition to cross-species comparisons of the flexure. The precise definition of the connectome of the telencephalic flexure is primordial during glioma surgery and for disconnective epilepsy surgery in this region.

Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue.

Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca2+ spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

Anterior peri-insular quadrantotomy: a cadaveric white matter dissection study.

OBJECTIVE: Anterior quadrant disconnection represents a safe surgical option in well-selected pediatric patients with a large frontal lobe lesion anterior to the motor cortex. The understanding of the anatomy of the white matter tracts connecting the frontal lobe with the rest of the cerebrum forms the basis of a safe and successful disconnective surgery. The authors explored and illustrated the relevant white matter tracts sectioned during each surgical step using fiber dissection techniques. METHODS: Five human cadaveric hemispheres were dissected to illustrate the frontal connections in the 3 planes. The dissections were performed from lateral to medial, medial to lateral, and ventral to dorsal to describe the various tracts sectioned during the 4 steps of this surgery, namely the anterior suprainsular window, intrafrontal disconnection, anterior callosotomy, and frontobasal disconnection. RESULTS: At the beginning of each surgical step, the U fibers were cut. During the anterior suprainsular window, the superior longitudinal fasciculus (SLF), the uncinate fasciculus, and the inferior fronto-occipital fasciculus (IFOF) were visualized and sectioned, followed by sectioning of the anterior limb of the internal capsule. During the intrafrontal disconnection, the SLF was cut, along with the corona radiata. At the medial surface the cingulum was sectioned. The anterior callosotomy disconnected the anterior third of the body of the callosum, the genu, and the rostrum. The frontobasal disconnection addressed the last remaining fibers connecting the frontal lobe with the rest of the hemisphere, namely the anterior limb of the anterior commissure. CONCLUSIONS: The anterior peri-insular quadrantotomy aims at effectively treating children with large lesions of the frontal lobe anterior to the motor cortex. A precise understanding of the gyral anatomy of this lobe along with the several white matter connections is crucial to avoid motor complications and to ensure complete disconnection.

Do intra-operative neurophysiological changes predict functional outcome following decompressive surgery for lumbar spinal stenosis? A prospective study.

BACKGROUND: To analyse the relation between immediate intraoperative neurophysiological changes during decompression and clinical outcome in a series of patients with lumbar spinal stenosis (LSS) undergoing surgery. METHODS: Twenty-four patients with neurogenic intermittent claudication (NIC) due to LSS undergoing decompressive surgery were prospectively studied. Intra operative trans-cranial motor evoked potentials (tcMEPs) were recorded before and immediately after surgical decompression. Lower limb normalised tcMEP improvement was used as primary neurophysiological outcome. Clinical outcome was assessed using the Zurich Claudication Questionnaire (ZCQ) self-assessment score, before surgery (baseline) and at an average of 8 and 29 months post-operatively. RESULTS: We found a moderate positive correlation between tcMEP changes and ZCQ at early follow-up (R=0.36). At late follow-up no correlation was found between intra-operative tcMEP and ZCQ changes. Dichotomizing the data showed a statistically significant relationship between tcMEP improvement and better functional outcome at early follow-up (P=0.013) but not at later follow-up (P=1). CONCLUSIONS: Our findings suggest that intra-operative neurophysiological improvement during decompressive surgery may predict a better clinical outcome at early follow-up although this is not applicable to late follow-up possibly due to the observed erosion of functional improvement with time.

Periinsular anterior quadrantotomy: technical note.

Refractory frontal lobe epilepsy has been traditionally treated through a frontal lobectomy. A disconnective technique may allow similar seizure outcomes while avoiding the complications associated with large brain resections. The aim of this study was to describe a new technique of selective disconnection of the frontal lobe that can be performed in cases of refractory epilepsy due to epileptogenic foci involving 1 frontal lobe (anterior to the motor cortex), with preservation of motor function. In addition to the description of the technique, an illustrative case is also presented. This disconnective procedure is divided into 4 steps: the suprainsular window, the anterior callosotomy, the intrafrontal disconnection, and the frontobasal disconnection. The functional neuroanatomy is analyzed in detail for each step of the surgery. It is important to perform cortical and subcortical electrophysiological mapping to guide this disconnective procedure and identify eloquent cortices and intact neural pathways. The authors describe the case of a 9-year-old boy who presented with refractory epilepsy due to epileptogenic foci localized to the right frontal lobe. MRI confirmed the presence of a focal cortical dysplasia of the right frontal lobe. A periinsular anterior quadrant disconnection (quadrantotomy) was performed. The postoperative period was uneventful, and the patient was in Engel seizure outcome Class I at the 3-year follow-up. A significant cognitive gain was observed during follow-up. Periinsular anterior quadrantotomy may thus represent a safe technique to efficiently treat refractory epilepsy when epileptogenic foci are localized to 1 frontal lobe while preserving residual motor functions.

The Changing Paradigm for the Surgical Treatment of Large Vestibular Schwannomas.

Objective Planned subtotal resection followed by Gamma Knife surgery (GKS) in patients with large vestibular schwannoma (VS) has emerged during the past decade, with the aim of a better functional outcome for facial and cochlear function. Methods We prospectively collected patient data, surgical, and dosimetric parameters of a consecutive series of patients treated by this method at Lausanne University Hospital during the past 8 years. Results A consecutive series of 47 patients were treated between July 2010 and January 2018. The mean follow-up after surgery was 37.5 months (median: 36, range: 0.5-96). Mean presurgical tumor volume was 11.8 mL (1.47-34.9). Postoperative status showed normal facial nerve function (House-Brackmann I) in all patients. In a subgroup of 28 patients, with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 26 (92.8%) retained serviceable hearing. Nineteen had good or excellent hearing (Gardner-Robertson class 1) before surgery, and 16 (84.2%) retained it after surgery. Mean duration between surgery and GKS was 6 months (median: 5, range: 3-13.9). Mean residual volume as compared with the preoperative one at GKS was 31%. Mean marginal dose was 12 Gy (11-12). Mean follow-up after GKS was 34.4 months (6-84). Conclusion Our data show excellent results in large VS management with a combined approach of microsurgical subtotal resection and GKS on the residual tumor, with regard to the functional outcome and tumor control. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.

Differential contributions of subthalamic beta rhythms and 1/f broadband activity to motor symptoms in Parkinson's disease.

Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings. Here we propose a data-driven, automatic and individualized mathematical model that disentangles beta activity and 1/f broadband activity in the STN power spectrum, and investigate the link between these individual components and motor symptoms in thirteen Parkinsonian patients. We show, using both modeled and actual data, how beta oscillatory activity significantly correlates with motor symptoms (bradykinesia and rigidity) only when broadband activity is not considered in the biomarker estimations, providing solid evidence that oscillatory beta activity does correlate with motor symptoms in untreated PD states as well as the significant impact of broadband activity. These findings emphasize the importance of data-driven models and the identification of better biomarkers for characterizing symptom severity and closed-loop applications.