Thoracic Outlet Syndrome Part II: Consensus on the Management of Neurogenic Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: In the first part of this report, the European Association of Neurosurgical Societies' section of peripheral nerve surgery presented a systematic literature review and consensus statements on anatomy, classification, and diagnosis of thoracic outlet syndrome (TOS) along with a subclassification system of neurogenic TOS (nTOS). Because of the lack of level 1 evidence, especially regarding the management of nTOS, we now add a consensus statement on nTOS treatment among experienced neurosurgeons. OBJECTIVE: To document consensus and controversy on nTOS management, with emphasis on timing and types of surgical and nonsurgical nTOS treatment, and to support patient counseling and clinical decision-making within the neurosurgical community. METHODS: The literature available on PubMed/MEDLINE was systematically searched on February 13, 2021, and yielded 2853 results. Screening and classification of abstracts was performed. In an online meeting that was held on December 16, 2021, 14 recommendations on nTOS management were developed and refined in a group process according to the Delphi consensus method. RESULTS: Five RCTs reported on management strategies in nTOS. Three prospective observational studies present outcomes after therapeutic interventions. Fourteen statements on nonsurgical nTOS treatment, timing, and type of surgical therapy were developed. Within our expert group, the agreement rate was high with a mean of 97.8% (± 0.04) for each statement, ranging between 86.7% and 100%. CONCLUSION: Our work may help to improve clinical decision-making among the neurosurgical community and may guide nonspecialized or inexperienced neurosurgeons with initial patient management before patient referral to a specialized center.

Psychiatric mimics of neurosurgical disorders.

Every year there are about 22.6 million people in need of neurosurgical care around the world, and one or several interventions are required to save lives and restore functional losses in more than half of these cases (13.8 million). Most neurosurgical interventions are performed in patients with traumatic brain and spinal cord injuries, strokes, central nervous system (CNS) tumors, hydrocephalus, and epilepsy. In addition to neurological symptoms, many CNS disorders are often accompanied by cognitive and/or behavioral changes. Physical and psychological symptoms can be intertwined as follows: 1) neurological symptoms may be manifested as a result of complex psychological processes; 2) psychological disorders may be manifested as neurological symptoms; 3) neurological disorders commonly cause secondary psychological responses; 4) psychological disorder may be induced more or less directly by an organic brain disease. In the present paper, we focus on the psychiatric conditions occurring in the patients with neurosurgical disorders who either get prepared for surgery or have already received it.

Thoracic Outlet Syndrome Part I: Systematic Review of the Literature and Consensus on Anatomy, Diagnosis, and Classification of Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: Although numerous articles have been published not only on the classification of thoracic outlet syndrome (TOS) but also on diagnostic standards, timing, and type of surgical intervention, there still remains some controversy because of the lack of level 1 evidence. So far, attempts to generate uniform reporting standards have not yielded conclusive results. OBJECTIVE: To systematically review the body of evidence and reach a consensus among neurosurgeons experienced in TOS regarding anatomy, diagnosis, and classification. METHODS: A systematic literature search on PubMed/MEDLINE was performed on February 13, 2021, yielding 2853 results. Abstracts were screened and classified. Recommendations were developed in a meeting held online on February 10, 2021, and refined according to the Delphi consensus method. RESULTS: Six randomized controlled trials (on surgical, conservative, and injection therapies), 4 "guideline" articles (on imaging and reporting standards), 5 observational studies (on diagnostics, hierarchic designs of physiotherapy vs surgery, and quality of life outcomes), and 6 meta-analyses were identified. The European Association of Neurosurgical Societies' section of peripheral nerve surgery established 18 statements regarding anatomy, diagnosis, and classification of TOS with agreement levels of 98.4 % (±3.0). CONCLUSION: Because of the lack of level 1 evidence, consensus statements on anatomy, diagnosis, and classification of TOS from experts of the section of peripheral nerve surgery of the European Association of Neurosurgical Societies were developed with the Delphi method. Further work on reporting standards, prospective data collections, therapy, and long-term outcome is necessary.

Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson Disease with Prior Pallidotomy or Thalamotomy.

Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic nucleus (STN DBS) in patients with Parkinson disease (PD) who previously underwent lesioning of the basal ganglia. Material and methods. The study included 22 patients who underwent STN DBS. Eleven patients had undergone prior unilateral pallidotomy (n = 6) or VL/VIM thalamotomy (n = 5) while the other 11 patients had not. The primary outcome was the change from baseline in the motor subscore of the Unified Parkinson Disease Rating Scale (UPDRS-III) 12 months after STN DBS. Secondary outcomes included change in motor response complications (UPDRS-IV) and change in levodopa equivalent daily dose (LEDD). Results. In the group with prior lesioning UPDRS-III improved by 45%, from 51.5 ± 9.0% (range, 35–65) to 26.5 ± 8.4 (range, 21–50) (p < 0.01) and UPDRS-IV by 75%, from 8.0 ± 2.01 (range, 5–11) to 2.1 ± 0.74 (range, 1–3) (p < 0.01). In the group without prior lesioning UPDRS-III improved by 61%, from 74.2% ± 7.32 (range, 63–82) to 29.3 ± 5.99 (range, 20–42) (p < 0.01) and UPDRS-IV by 77%, from 9.1 ± 2.46 (range, 5–12) to 2.0 ± 1.1 (range, 1–4) (p < 0.01). Comparing the two groups (with and without lesioning) no significant differences were found either in UPDRS-III (p > 0.05) or UPDRS-IV scores (p > 0.05) at 12 months post-DBS. The LEDD was reduced by 51.4%, from 1008.2 ± 346.4 to 490.0 ± 194.3 in those with prior surgery (p < 0.01) and by 55.0%, from 963.4 ± 96.2 to 433.3 ± 160.2 in those without (p < 0.01).UPDRS-III improved by 51.8%, from 53.7 ± 4.6 (range, 50–62) to 25.0 ± 3.8 (range, 21–31) in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8 ± 12.6 (range, 35–65) to 29.8 ± 13.6 (range, 22–50) in those with prior thalamotomy (p < 0.01). This numerical difference in improvement was not statistically significant (p > 0.05). Conclusion. Our comparative study indicates that bilateral STN DBS is effective and can be used in patients with Parkinson disease with prior unilateral stereotactic destructive operations on subcortical structures. The results in our patient cohort are generally consistent with previously published reports of smaller series from multiple centers worldwide.

Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking.

Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing involves gamma oscillations, which support memory, attention, cognitive flexibility and sensory responses. These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food-seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma-rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.

Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway.

Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.

The potential of microvessel density in prediction of infarct growth: a two-month experimental study in vessel size imaging.

OBJECTIVES: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth. METHODS: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia. RESULT: The median values of Q and VSI were: for INF 0.29 s(-1/3) and 15.8 µm, for IPE 0.33 s(-1/3) and 20.6 µm and for HEA 0.36 s(-1/3) and 17.4 µm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s(-1/3) predicted the final infarction with a sensitivity of 69% and a specificity of 64%. CONCLUSIONS: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization.

Vitamin K and sphingolipid metabolism: evidence to date.

The brain is enriched with sphingolipids, which are important membrane constituents and major lipid signaling molecules that have a role in motor and cognitive behavior. Vitamin K has been implicated in brain sphingolipid metabolism for more than 30 years. The in vitro and in vivo studies to date suggest a role of vitamin K in the regulation of multiple enzymes involved in sphingolipid metabolism within the myelin-rich regions in the brain. However, the precise mechanisms of action are not well understood. Further, the physiological consequences of the observed effects of vitamin K on sphingolipid metabolism have not been systematically studied.

The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of the EGF receptor/ERK pathway.

The nitrone spin trap PBN has been shown to protect neuronal cells from reactive oxygen species both in culture and in vivo. As an approach to understanding the molecular mechanisms by which PBN may function to protect cells, we examined whether PBN alters the cellular response to reactive oxygen species. H(2)O(2) stimulation of PC-12 cells results in weak activation of both the ERK and JNK signal transduction pathways. PBN pretreatment of PC-12 cells, followed by H(2)O(2) stimulation, results in strong and selective activation of the pro-survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN-pretreated cells results in only 30% of the increase in intracellular Ca(+2) as compared to untreated cells following H(2)O(2) stimulation. These data suggest a model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK pathway.