Evaluation of the Rotational Stability of Directional Deep Brain Stimulation Leads: A Case Series and Systematic Review.

BACKGROUND: The rotational stability of directional deep brain stimulation leads is a major prerequisite for sustained clinical effects. Data on directional lead stability are limited and controversial. METHODS: We aimed to evaluate the long-term rotational stability of directional leads and define confounding factors in our own population and the current literature. We retrospectively evaluated the orientation of directional leads in patients with available postoperative computed tomography (CT; T1; day of surgery) and an additional postoperative image (T2; CT or rotational fluoroscopy) performed more than 7 days after the initial scan. The potential impact of intracranial air was assessed. We also reviewed the literature to define factors impacting stability. RESULTS: Thirty-six leads were evaluated. The mean follow-up between T1 and T2 was 413.3 (7-1,171) days. The difference in rotation between T1 and T2 was 2.444 ± 2.554 degrees (range: 0-9.0 degrees). The volume of intracranial air did not impact the rotation. The literature search identified one factor impacting the stability of directional leads, which is the amount of twist applied at implantation. CONCLUSION: Directional leads for deep brain stimulation show stable long-term orientation after implantation. Based on our literature review, large amounts of twist during implantation can lead to delayed rotation and should thus be avoided.

Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper. Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery. Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential. Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland.

Facilitatory rTMS over the Supplementary Motor Cortex Impedes Gait Performance in Parkinson Patients with Freezing of Gait.

Freezing of gait (FOG) in Parkinson's disease (PD) occurs frequently in situations with high environmental complexity. The supplementary motor cortex (SMC) is regarded as a major network node that exerts cortical input for motor control in these situations. We aimed at assessing the impact of single-session (excitatory) intermittent theta burst stimulation (iTBS) of the SMC on established walking during FOG provoking situations such as passing through narrow spaces and turning for directional changes. Twelve PD patients with FOG underwent two visits in the off-medication state with either iTBS or sham stimulation. At each visit, spatiotemporal gait parameters were measured during walking without obstacles and in FOG-provoking situations before and after stimulation. When patients passed through narrow spaces, decreased stride time along with increased stride length and walking speed (i.e., improved gait) was observed after both sham stimulation and iTBS. These effects, particularly on stride time, were attenuated by real iTBS. During turning, iTBS resulted in decreased stride time along with unchanged stride length, a constellation compatible with increased stepping frequency. The observed iTBS effects are regarded as relative gait deterioration. We conclude that iTBS over the SMC increases stepping frequency in PD patients with FOG, particularly in FOG provoking situations.

Do directional deep brain stimulation leads rotate after implantation?

BACKGROUND: The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. METHODS: We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). RESULTS: In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. CONCLUSION: D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

ABSTRACT: Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

Evaluation of Automatic Segmentation of Thalamic Nuclei through Clinical Effects Using Directional Deep Brain Stimulation Leads: A Technical Note.

Automatic anatomical segmentation of patients' anatomical structures and modeling of the volume of tissue activated (VTA) can potentially facilitate trajectory planning and post-operative programming in deep brain stimulation (DBS). We demonstrate an approach to evaluate the accuracy of such software for the ventral intermediate nucleus (VIM) using directional leads. In an essential tremor patient with asymmetrical brain anatomy, lead placement was adjusted according to the suggested segmentation made by the software (Brainlab). Postoperatively, we used directionality to assess lead placement using side effect testing (internal capsule and sensory thalamus). Clinical effects were then compared to the patient-specific visualization and VTA simulation in the GUIDE™ XT software (Boston Scientific). The patient's asymmetrical anatomy was correctly recognized by the software and matched the clinical results. VTA models matched best for dysarthria (6 out of 6 cases) and sensory hand side effects (5/6), but least for facial side effects (1/6). Best concordance was observed for the modeled current anterior and back spread of the VTA, worst for the current side spread. Automatic anatomical segmentation and VTA models can be valuable tools for DBS planning and programming. Directional DBS leads allow detailed postoperative assessment of the concordance of such image-based simulation and visualization with clinical effects.

Altered activation and connectivity of the supplementary motor cortex at motor initiation in Parkinson's disease patients with freezing.

OBJECTIVE: Motor initiation failure is a key feature of freezing of gait (FOG) due to Parkinson's disease (PD). The supplementary motor cortex (SMC) plays a central role in its pathophysiology. We aimed at investigating SMC activation, connectivity and plasticity with regard to motor initiation in FOG. METHODS: Twelve patients with FOG and eleven without FOG underwent a multimodal electrophysiological evaluation of SMC functioning including the Bereitschaftspotential and movement-related desynchronisation of cortical beta oscillations. SMC plasticity was modulated by intermittent theta burst stimulation (iTBS) and its impact on gait initiation was assessed by a three-dimensional gait analysis. RESULTS: Prior to volitional movements the Bereitschaftspotential was smaller and beta power was less strongly attenuated over the SMC in patients with FOG compared to those without. Pre-motor coherence between the SMC and the primary motor cortex in the beta frequency range was also stronger in patients with FOG. iTBS resulted in a relative deterioration of gait initiation. CONCLUSIONS: Reduced activation of the SMC along with increased SMC connectivity in the beta frequency range hinder a flexible shift of the motor set as it is required for gait initiation. SIGNIFICANCE: Altered SMC functioning plays an important role for motor initiation failure in PD-related FOG.

Decreased grey matter in the postural control network is associated with lateral flexion of the trunk in Parkinson's disease.

BACKGROUND: Disruption of central networks, particularly of those responsible for integrating multimodal afferents in a spatial reference frame, were proposed in the pathophysiology of lateral trunk flexion in Parkinson's disease (PD). Knowledge about the underlying neuroanatomical structures is limited. OBJECTIVE: To investigate if decreased focal grey matter (GM) is associated with trunk flexion to the side and if the revealed GM clusters correlate with a disturbed perception of verticality in PD. METHODS: 37 PD patients with and without lateral trunk flexion were recruited. Standardized photos were taken from each patient and trunk orientation was measured by a blinded rater. Voxel-based morphometry (VBM) was used to detect associated clusters of decreased GM. The subjective visual vertical (SVV) was assessed as a marker for perception of verticality and SVV estimates were correlated with GM clusters. RESULTS: VBM revealed clusters of decreased GM in the right posterior parietal cortex and in the right thalamus were associated with lateral trunk flexion. The SVV correlated with the extent of trunk flexion, and the side of the SVV tilt correlated with the side of trunk flexion. GM values from the thalamus correlated with the SVV estimates. CONCLUSIONS: We report an association between neurodegenerative changes within the posterior parietal cortex and the thalamus and lateral trunk flexion in PD. These brain structures are part of a network proposed to be engaged in postural control and spatial self-perception. Disturbed perception of verticality points to a shifted egocentric spatial reference as an important pathophysiological feature.

[Focused ultrasound ablation as tremor treatment]. / Fokussierter Ultraschall in der Behandlung von Tremor.

BACKGROUND: The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data. OBJECTIVES: This article encompasses a description of the technological basis and typical course of MRIgFUS interventions, a comparison to alternative open or incisionless surgical techniques as well as a review of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor. MATERIAL AND METHODS: Narrative literature review and comparison. RESULTS: Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report a reduction of tremor intensity of up to 80% after 6-12 months follow-up without the disadvantages of open brain surgery. CONCLUSION: The MRIgFUS functional neurosurgery is conducted only at a limited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is a significant addition to the interventional armamentarium for functional stereotactic neurosurgery and a potentially valuable alternative to established interventional therapy options for tremor disorders.

Functional lesional neurosurgery for tremor: back to the future?

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article.

Sodium Oxybate for Excessive Daytime Sleepiness and Sleep Disturbance in Parkinson Disease: A Randomized Clinical Trial.

Importance: Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce. Objective: To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale [ESS] score >10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12). Interventions: Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed. Main Outcomes and Measures: Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale-2), and objective variables of nighttime sleep (polysomnography). Results: Among 12 patients in the intention-to-treat population (10 men, 2 women; mean [SD] age, 62 [11.1] years; disease duration, 8.4 [4.6] years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, -4.2 points ; 95% CI, -5.3 to -3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P < .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment. Conclusions and Relevance: This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation. Trial Registration: clinicaltrials.gov Identifier: NCT02111122.

Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound.

OBJECTIVE: To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET). METHODS: This was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS. Motor symptoms, manual dexterity, cognition, and quality of life were assessed before intervention and at 48 hours and 1, 3, and 6 months after intervention. Rating of standardized video recordings was blinded for evaluation time points. Primary outcome was the change in unilateral hand tremor score of the treated hand. RESULTS: Six patients received MRIgFUS ablation of the CTT contralateral to the treated hand. Repeated-measures comparison determined a statistically significant 83% reduction (before vs 6 months after intervention mean ± SD; absolute reduction; 95% confidence interval) in the unilateral treated hand subscore (14.3 ± 4.9 vs 2.5 ± 2.6; 11.8; 8.4-15.2; p < 0.001), while quality of life improved by 52% (50.5 ± 19.4 vs 24.8 ± 11.4; 25.7; 3.5-47.28; p = 0.046). Measures for manual dexterity, attention and coordination, and overall cognition were unchanged. Transient side effects (n = 3) were ipsilateral hand clumsiness and mild gait instability for up to 3 months. CONCLUSIONS: Unilateral MRIgFUS lesioning of the CTT was highly efficacious in reducing contralateral hand tremor in ET without affecting fine motor function and dexterity over 6 months of follow-up. Adverse effects were mild and transient. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with ET, transcranial MRIgFUS ablation of the cerebellothalamic tract improves tremor.

[Neurological complications of anticancer treatments]. / Complications neurologiques des traitements anticancéreux.

After bone marrow toxicity, neurological toxicities are the second most common complications of cancer. They can be observed throughout the course of the disease or even after the end of treatment. Establishing the correct diagnosis may be a challenge but is of outmost importance to minimize the risk of long-term neurological deficits and to improve the quality of life of the patients. This review will focus on neurological complications induced by chemotherapeutic agents. As the life expectancy and number of treatment lines used in cancer patients increases, these complications are bound to become more frequent and should be aware to neurologists.

Spinal Cord Disorders.

BACKGROUND: The spinal cord is the main pathway for information, connecting the brain and the peripheral nervous system. Any disorder that results in spinal cord dysfunction will have a dramatic impact on the patient's quality of life. This review focusses on myelopathy, specifically, on the acute and subacute clinical presentations and the inflammatory and vascular etiology of this widespread disorder. SUMMARY: Myelopathy following spinal cord injury is a generic term referring to a lesion that affects the spinal cord following traumatic injury, or autoimmune, infectious, neoplastic, vascular and hereditary degenerative diseases. Depending on the patient's medical history, the underlying clinical syndrome and the temporal course of the manifestation, the clinician must account for a wide range of possible differential diagnoses. KEY MESSAGES: Spinal cord disorders pose a tremendous challenge for the clinician, as they show great variability in clinical presentation but can have potentially devastating sequelae. The acute and sometimes urgent nature of therapeutic management is highly dependent on the underlying disorder, often necessitating a combination of approaches including surgical or conservative therapies (including immunomodulatory therapy) and an interdisciplinary approach to achieve the best outcomes.

Do executive dysfunction and freezing of gait in Parkinson's disease share the same neuroanatomical correlates?

Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.

[Nerve sonography of intraneural ganglia as cause painful peroneal palsies: a case series]. / Nervensonographie intraneuraler Ganglien als Ursache schmerzhafter N.-peronaeus-Paresen: eine Fallserie.

In selected cases acquired peroneal palsy is caused by intraneural ganglia. In contrast to the much more frequent "loco typico" lesion which is caused by external pressure, intraneural ganglia can be treated by microscopic nerve surgery as part of primary treatment strategy. A careful clinical history as well as a profound clinical and electrophysiological examination is required to disclose unusual findings. These are common in non-typical peroneal palsy. In this situation high resolution nerve sonography is a fast and sensitive method to detect intraneural ganglia. We report a case series of three patients with peroneal palsy caused by intraneural ganglia and give a review of the literature.

Rarement la lésion du nerf péronier au niveau de la tête fibulaire suivie par une parésie des muscles innervés par ce nerf est causée par un ganglion appuyant sur les structures nerveuses. En ce cas une intervention chirurgicale peut souvant résondre le problème. Une anamnèse soigneusement menée, l'examen neurologique et des investigations neuromusculaires sont essentielles mais souvent atypiques comparés à la lésion péronière «loco typico¼. L'ultrasonographie à haute résolution est procédée facilement et plus sensible qu'une MRI. Nous allons décrire dans ce papier trois cas de parèsie du nerf péronier pour lesquels la diagnostic final a été posé par ultrasonographie.