Local anesthetics for brain tumor resection: Current perspectives

This review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local anesthesia or under local anesthesia only. Literature shows a large variation in the postoperative pain intensity ranging from no postoperative analgesia requirement in two-thirds of the patients up to a rate of 96% of the patients suffering from severe postoperative pain. The only identified causative factor predicting higher postoperative pain scores is infratentorial surgery. Postoperative analgesia can be achieved with multimodal pain management where local anesthesia is associated with lower postoperative pain intensity, reduction in opioid requirement and prevention of development of chronic pain. In awake craniotomy patients, sufficient local anesthesia is a cornerstone of the procedure. An awake craniotomy and brain tumor resection can be carried out completely under local anesthesia only. However, the use of sedative drugs is common to improve patient comfort during craniotomy and closure. Local anesthesia for craniotomy can be performed by directly blocking the six different nerves that provide the sensory innervation of the scalp, or by local infiltration of the surgical site and the placement of the pins of the Mayfield clamp. Direct nerve block has potential complications and pitfalls and is technically more challenging, but mostly requires lower total doses of the local anesthetics than the doses required in surgical-site infiltration. Due to a lack of comparative studies, there is no evidence showing superiority of one technique versus the other. Besides the use of other local anesthetics for analgesia, intravenous lidocaine administration has proven to be a safe and effective method in the prevention of coughing during emergence from general anesthesia and extubation, which is especially appreciated after brain tumor resection

The course of the radial nerve in the distal humerus: A novel, anatomy based, radiographic assessment

Iatrogenic nerve injury during fracture surgery of the upper arm is a well-known complication. Prevention of this type of injuries would be of great value. The literature describes several methods to reduce this type of injury, but no perfect solution is at hand. In this study we introduce a new radiographic evaluation of the course and variation of the radial nerve in the distal part of the humerus in relation to bony landmarks as observed on a plain (trauma) radiographs. Aim of this new approach is to reduce the chance of iatrogenic nerve injury by defining of a danger zone in the distal upper arm regarding the radial nerve and hence give an advise for future implant fabrication. Methods and findings: Measurements were done on both arms of ten specially embalmed specimens. Arms were dissected and radiopaque wires attached to the radial nerve in the distal part of the upper arm. Digital radiographs were obtained to determine the course of the radial nerve in the distal 20 cm of the humerus in relation to bony landmarks; medial epicondyle and capitellum-trochlea projection (CCT). Analysis was done with ImageJ and Microsoft Excel software. We also compared humeral nail specifications from different companies with the course of the radial nerve to predict possible radial nerve damage. Results: The distance from the medial epicondyle to point where the radial nerve bends from posterior to lateral was 142 mm on AP radiographs and 152 mm measured on the lateral radiographs. The average distance from the medial epicondyle to point where the radial nerve bends from lateral to anterior on AP radiographs was 66 mm. On the lateral radiographs where the nerve moves away from the anterior cortex 83 mm to the center of capitellum and trochlea (CCT). The distance from the bifurcation of the radial nerve into the posterior interosseous nerve (PIN) and superficial radial nerve was 21 mm on AP radiographs and 42 mm on the lateral radiographs (CCT). Conclusions: The course of the radial nerve in the distal part of the upper arm has great variety. Lateral fixation is relatively safe in a zone between the center of capitellum-trochlea and 48 mm proximal to this point. The danger zone in lateral fixation is in-between 48–122 mm proximal from CCT. In anteroposterior direction; distal fixation is dangerous between 21–101 mm measured from the medial epicondyle. The more distal, the more medial the nerve courses making it more valuable to iatrogenic damage. The IMN we compared with our data all show potential risk in case of (blind) distal locking, especially from lateral to medial direction

Use of the humeral head as a reference point to prevent axillary nerve damage during proximal fixation of humeral fractures: An anatomical and radiographic study

Introduction: Treatment of proximal humeral fractures with plate osteosynthesis or intramedullary nail fixation in humeral shaft fractures with a proximal locking bolt carries the risk of iatrogenic injury of the axillary nerve. The purpose of this anatomical study is to define a more reliable safe zone to prevent iatrogenic axillary nerve injury using the humeral head instead of the acromion as a (radiographic) reference point during operative treatment. Materials and methods: Anatomical dissection and labeling of the axillary nerve and branches was performed on 10 specially embalmed human specimens. Standard AP and straight lateral radiographs were made. The distances were measured indirectly from the cranial tip of the humerus to the axillary nerve on radiographs. Results: The median distance from the cranial tip of the humerus to the axillary nerve was 52 mm. The mean number of axillary nerve branches was 3. The distances from the cranial tip of the humerus to the nerve (branch) varied from 23 to 78 mm. The median distance from the proximal (anterior) branch was 36 mm, to the second branch 47 mm, 54 mm to the third branch and 73 mm to the fourth branch. The axillary nerve moves along with the humerus in cranial and caudal direction when the subacromial space varies. Conclusion: This study shows that the position of the axillary nerve can be better determent using the cranial tip of the humerus as a reference point instead of the acromion. Furthermore, it is unsafe to place the proximal locking bolts in the zone between 24 mm and 78 mm from the cranial tip of the humerus. The greatest chance to cause a lesion of the main branch of the axillary nerve is in the zone between 48 mm and 58 mm caudal from the tip of the humeral head

Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice

Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs). However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS)-related complex spike responses, and molecular layer interneuron (MLI) activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval. Purkinje cell simple spike suppression is a central driving mechanism in cerebellar conditioning. Here, ten Brinke etal. show how simple spike suppression, conditioned stimulus-related complex spikes, and molecular layer interneuron (MLI) activity correlate to conditioned eyelid behavior. Moreover, transgenic impairment of MLI input results in deficits in conditioned behavior

Cerebellar potentiation and learning a whisker-based object localization task with a time response window

Whisker-based object localization requires activation and plasticity of somatosensory and motor cortex. These parts of the cerebral cortex receive strong projections from the cerebellum via the thalamus, but it is unclear whether and to what extent cerebellar processing may contribute to such a sensorimotor task. Here, we subjected knock-out mice, which suffer from impaired intrinsic plasticity in their Purkinje cells and long-term potentiation at their parallel fiber-to-Purkinje cell synapses (L7-PP2B), to an object localization task with a time response window (RW). Water-deprived animals had to learn to localize an object with their whiskers, and based upon this location they were trained to lick within a particular period ("go" trial) or refrain from licking ("no-go" trial). L7-PP2B mice were not ataxic and showed proper basic motor performance during whisking and licking, but were severely impaired in learning this task compared with wild-type littermates. Significantly fewer L7-PP2B mice were able to learn the task at long RWs. Those L7-PP2B mice that eventually learned the task made unstable progress, were significantly slower in learning, and showed deficiencies in temporal tuning. These differences became greater as theRWbecame narrower. Trained wild-type mice, but not L7-PP2B mice, showed a net increase in simple spikes and complex spikes of their Purkinje cells during the task. We conclude that cerebellar processing, and potentiation in particular, can contribute to learning a whisker-based object localization task when timing is relevant. This study points toward a relevant role of cerebellum- cerebrum interaction in a sophisticated cognitive task requiring strict temporal processing

Cerebellar control of gait and interlimb coordination

Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Δγ2 and not significantly affected in α6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front–hind and left–right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements

Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning