High Mib-1-score correlates with new cranial nerve deficits after surgery for frontal skull base meningioma.

Postoperative new cranial nerve deficits comprise severe concomitant morbidity in skull base meningioma surgery. Therefore, long-term cranial nerve integrity represents an important outcome measure. In the current study, we analyzed our institutional database in order to identify risk factors for postoperative new cranial nerve morbidity in the course of frontobasal meningioma surgery. Between 2009 and 2017, 195 patients were surgically treated for frontobasal meningioma at the authors' institution. Postoperative cranial nerve function was assessed immediately after surgery as well as 12 months postoperatively. A univariate and multivariate analysis was performed to identify factors influencing favorable postoperative cranial nerve outcome. Tumors with histological Mib-1-labeling indices > 5% were associated with a significantly higher percentage of new cranial nerve deficits immediately after surgery compared with those with Mib-1-labeling indices ≤ 5% (39% versus 20%, p = 0.029). Elevated Mib-1-labeling indices could be correlated with high CD68-positive macrophage staining (54% for Mib-1 index > 5% versus 19% for Mib-1 index ≤ 5%, p = 0.001). Elevated Mib-1-labeling index correlates with initial new cranial nerve dysfunction after resection of frontal skull base meningioma. With regard to elevated CD68-positive macrophage staining in high Mib-1-positive meningiomas, initial postoperative new cranial nerve morbidity might partly reflect macrophage-based inflammatory immune responses.

Cranial nerve V2 and Vidian nerve trauma secondary to lateral pterygoid recess encephalocele repair.

BACKGROUND: The incidence of adverse sequelae related to trauma of cranial nerve V2 (V2) and the Vidian nerve (VN) during endoscopic pterygoid recess repair (PRR) of lateral sphenoid encephalocele is insufficiently reported in the medical literature. As part of our quality assessment and improvement program we sought to analyze the incidence and severity of V2 and VN injury during a 9-year experience (2010-2018) with PRR. METHODS: Hypoesthesia, paresthesia, and dry eye and their impact on patient quality of life were sought through chart review and a self-reported 0 to 5 Likert scale for each symptom. RESULTS: Thirty-five patients underwent repair of spontaneous cerebrospinal-fluid (CSF) rhinorrhea, with 11 consecutive patients undergoing endoscopic PRR. Mean follow-up for PRR was 32.5 months (range, 2.4 to 103.3 months). Although definitive management resulted in 100% success, 1 required secondary treatment. Eight patients were available for long-term follow-up (72.7%) and completed a symptom severity questionnaire using a Likert-scale. All patients observed either hypoesthesia, paresthesia, or dry eye of varying gradation (scale, 0 to 5). None described disabling symptoms, and some reported gradual improvement. Numbness, paresthesia, and dry eye were reported by 6 of 8 (75%), 5 of 8 (62.5%), and 4 of 8 (50%) patients, respectively. The mean Likert score among the 8 patients who completed this questionnaire noticing hypoesthesia, paresthesia, and dry eye was 2.6, 1.3, and 1.8, respectively. CONCLUSION: Meticulous surgical technique is paramount for successful PRR and minimizing nerve injury, yet the anatomic variation of the lateral pterygoid recess can be challenging, and neural injury is a real risk. Preoperatively, patients should be counseled that although V2 or VN injury is common, most patients describe resulting symptoms to be rarely bothersome.

Deoxycholic Acid and the Marginal Mandibular Nerve: A Cadaver Study.

BACKGROUND: One of the rare but serious complications observed with deoxycholic acid administration is damage to the marginal mandibular nerve. In this study, we evaluated if deoxycholic acid directly induces histologic damage to fresh cadaveric marginal mandibular nerve. METHODS: A segment of marginal mandibular nerve was harvested from 12 hemifaces of 6 fresh cadavers. The nerve specimen was exposed to either 0.9% sterile saline for 24 h, deoxycholic acid (10 mg/ml) for 20 min, or deoxycholic acid (10 mg/ml) for 24 h. The nerve specimens were then fixed in glutaraldehyde for a minimum of 24 h. Toluidine blue stained sections were evaluated for stain intensity using light microscopy and color deconvolution image analysis. Supraplatysmal fat was harvested as a positive control and exposed to the same treatments as the marginal mandibular nerve specimens, then evaluated using transmission electron microscopy. RESULTS: Toluidine blue staining was less in the marginal mandibular nerve exposed to deoxycholic acid when compared to saline. The specimen exposed to deoxycholic acid for 24 h showed less toluidine blue staining than that of the nerve exposed to deoxycholic acid for 20 min. Transmission electron microscopy of submental fat exposed to deoxycholic acid revealed disruption of adipocyte cell membrane integrity and loss of cellular organelles when compared to specimens only exposed to saline. CONCLUSIONS: Deoxycholic acid (10 mg/ml) damages the marginal mandibular nerve myelin sheath in fresh human cadaver specimens. Direct deoxycholic acid neurotoxicity may cause marginal mandibular nerve injury clinically. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Neuromonitoring Approach to Facial Nerve Preservation During Image-guided Robotic Cochlear Implantation.

HYPOTHESIS: A multielectrode probe in combination with an optimized stimulation protocol could provide sufficient sensitivity and specificity to act as an effective safety mechanism for preservation of the facial nerve in case of an unsafe drill distance during image-guided cochlear implantation. BACKGROUND: A minimally invasive cochlear implantation is enabled by image-guided and robotic-assisted drilling of an access tunnel to the middle ear cavity. The approach requires the drill to pass at distances below 1  mm from the facial nerve and thus safety mechanisms for protecting this critical structure are required. Neuromonitoring is currently used to determine facial nerve proximity in mastoidectomy but lacks sensitivity and specificity necessaries to effectively distinguish the close distance ranges experienced in the minimally invasive approach, possibly because of current shunting of uninsulated stimulating drilling tools in the drill tunnel and because of nonoptimized stimulation parameters. To this end, we propose an advanced neuromonitoring approach using varying levels of stimulation parameters together with an integrated bipolar and monopolar stimulating probe. MATERIALS AND METHODS: An in vivo study (sheep model) was conducted in which measurements at specifically planned and navigated lateral distances from the facial nerve were performed to determine if specific sets of stimulation parameters in combination with the proposed neuromonitoring system could reliably detect an imminent collision with the facial nerve. For the accurate positioning of the neuromonitoring probe, a dedicated robotic system for image-guided cochlear implantation was used and drilling accuracy was corrected on postoperative microcomputed tomographic images. RESULTS: From 29 trajectories analyzed in five different subjects, a correlation between stimulus threshold and drill-to-facial nerve distance was found in trajectories colliding with the facial nerve (distance <0.1  mm). The shortest pulse duration that provided the highest linear correlation between stimulation intensity and drill-to-facial nerve distance was 250  µs. Only at low stimulus intensity values (≤0.3  mA) and with the bipolar configurations of the probe did the neuromonitoring system enable sufficient lateral specificity (>95%) at distances to the facial nerve below 0.5  mm. However, reduction in stimulus threshold to 0.3  mA or lower resulted in a decrease of facial nerve distance detection range below 0.1  mm (>95% sensitivity). Subsequent histopathology follow-up of three representative cases where the neuromonitoring system could reliably detect a collision with the facial nerve (distance <0.1  mm) revealed either mild or inexistent damage to the nerve fascicles. CONCLUSION: Our findings suggest that although no general correlation between facial nerve distance and stimulation threshold existed, possibly because of variances in patient-specific anatomy, correlations at very close distances to the facial nerve and high levels of specificity would enable a binary response warning system to be developed using the proposed probe at low stimulation currents.

Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis.

Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

Galanin protects against nerve injury after shear stress in primary cultured rat cortical neurons.

The neuropeptide galanin and its receptors (GalR) are found to be up-regulated in brains suffering from nerve injury, but the specific role played by galanin remains unclear. This study aimed to explore the neuroprotective role of galanin after shear stress induced nerve injury in the primary cultured cortical neurons of rats. Our results demonstrated that no significant changes in cell death and viability were found after galanin treatment when subjected to a shear stress of 5 dyn/cm(2) for 12 h, after increasing magnitude of shear stress to 10 dyn/cm(2) for 12 h, cell death was significantly increased, while galanin can inhibit the nerve injury induced by shear stress with 10 dyn/cm(2) for 12 h. Moreover, Gal2-11 (an agonist of GalR2/3) could also effectively inhibit shear stress-induced nerve injury of primary cultured cortical neurons in rats. Although GalR2 is involved in the galanin protection mechanism, there was no GalR3 expression in this system. Moreover, galanin increased the excitatory postsynaptic currents (EPSCs), which can effectively inhibit the physiological effects of shear stress. Galanin was also found to inhibit the activation of p53 and Bax, and further reversed the down regulation of Bcl-2 induced by shear stress. Our results strongly demonstrated that galanin plays a neuroprotective role in injured cortical neurons of rats.

Axon degeneration and regeneration: insights from Drosophila models of nerve injury.

Axon degeneration is the pivotal pathological event of acute traumatic neural injury as well as many chronic neurodegenerative diseases. It is an active cellular program and yet molecularly distinct from cell death. Much effort is devoted toward understanding the nature of axon degeneration and promoting axon regeneration. However, the fundamental mechanisms of self-destruction of damaged axons remain unclear, and there are still few treatments for traumatic brain injury (TBI) or spinal cord injury (SCI). Genetically approachable model organisms such as Drosophila melanogaster, the fruit fly, have proven exceptionally successful in modeling human neurodegenerative diseases. More recently, this success has been extended into the field of acute axon injury and regeneration. In this review, we discuss recent findings, focusing on how these models hold promise for accelerating mechanistic insight into axon injury and identifying potential therapeutic targets for TBI and SCI.

Morphologic evaluation of the inferior alveolar nerve in patients with sensory disorders by high-resolution 3D volume rendering magnetic resonance neurography on a 3.0-T system.

OBJECTIVE: The objective of this study was to evaluate the inferior alveolar nerve (IAN) morphologically in patients with symptomatic posttraumatic sensory disorders using magnetic resonance imaging (MRI) on a high-field system. STUDY DESIGN: Sixteen patients who complained of persistent sensory disturbance attributed to unilateral IAN injury participated in the investigation. High-resolution 3-dimensional volume rendering magnetic resonance neurography was performed on a 3.0-T MRI system. RESULTS: In 15 (94%) of 16 patients, high-resolution 3-dimensional volume rendering magnetic resonance neurography demonstrated morphologic abnormalities of the IAN as well as connective tissue overgrowth. These findings were confirmed intraoperatively (6 patients) and histopathologically (5 patients). The duration of sensory disturbance correlated significantly with the pattern of morphologic deformity and connective tissue overgrowth. CONCLUSIONS: The current study clearly demonstrated that appropriate application of clinical MRI techniques can significantly improve the diagnosis and potential treatment of patients with orofacial peripheral nerve disorders.

Sphenoid sinus pneumatization and its relation to bulging of surrounding neurovascular structures.

OBJECTIVES: We investigated the bulging and dehiscence of neurovascular structures in the sphenoid sinus and their relationships to the pneumatization of the sphenoid sinus. METHODS: One hundred sagittally hemisected cadaveric heads were examined. The degree of pneumatization of the sphenoid sinus was determined. Bulging and dehiscence of the internal carotid artery (ICA), optic nerve, maxillary nerve, and vidian nerve were examined, and the distances between these structures and the anterior or superior wall of the sphenoid sinus were measured. Additionally, the degree of bony thickness over these structures was determined. RESULTS: The prevalences of bulging of the optic nerve, segments 1 and 3 of the ICA, and the maxillary and vidian nerves were 56%, 34%, 65%, 41%, and 52%, respectively. The greater the degree of pneumatization, the more frequently did the structures bulge into the sphenoid sinus. The optic nerve was found to be in close proximity to the anterior and superior walls of the sphenoid sinus. The bone over the surrounding structures was very thin, especially for the complete sellar type. CONCLUSIONS: The prevalence of bulging of the optic nerve, the ICA, and the maxillary and vidian nerves increased in proportion to the degree of sphenoid sinus pneumatization.

Does computed tomographic assessment of inferior alveolar canal cortical integrity predict nerve exposure during third molar surgery?

PURPOSE: To evaluate the association between computed tomographic (CT) assessment of inferior alveolar nerve (IAN) canal cortical integrity and intraoperative IAN exposure. MATERIALS AND METHODS: This was a retrospective cohort study. The study sample included patients considered at high risk for IAN injury based on panoramic findings. The primary predictor variable was IAN canal integrity (intact or interrupted) assessed on coronal CT images. The secondary predictor variable was length of the cortical defect, in millimeters. The primary outcome variable was intraoperative visualization of the IAN. Other variables were demographic and operative parameters. Bivariate and multiple logistic regression analyses were used to evaluate the unadjusted and adjusted associations between the cortical integrity and IAN exposure. Diagnostic test characteristics were computed for cortical integrity and threshold cortical defect size. A P value < or = 0.05 was statistically significant. RESULTS: The sample consisted of 51 subjects (57% female) with a mean age of 35.2 +/- 12.8 years. Of the 80 third molars available for evaluation, 52 third molars (64.1%) had evidence of loss of cortical integrity. The mean cortical defect length was 2.9 +/- 2.6 mm. Loss of cortical integrity had a high sensitivity (> or = 0.88) but low specificity (< or = 0.49) as a diagnostic test for IAN visualization. A cortical defect size > or = 3 mm was associated with an increased risk for intraoperative IAN visualization with a high sensitivity and specificity (> or = 0.82). CONCLUSION: Cortical defect size on a maxillofacial CT has a high sensitivity and specificity for predicting intraoperative IAN exposure during third molar removal.

Imaging of denervation in the head and neck.

Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

Removal of a chopstick out of the cavernous sinus, pons, and cerebellar vermis through the superior orbital fissure.

Penetrating non-missile orbito cranial injuries are rare in a civilian pediatric setting. We describe a case of a trans-orbital penetration by a wooden chopstick deep down into the cerebellar vermis detected at neuroradiological examination in a child presenting for head injury. The foreign body was successfully pulled out in one piece surgically.

Development of cranial nerve palsy shortly after endosaccular embolization for asymptomatic cerebral aneurysm: report of two cases and literature review.

CLINICAL DESCRIPTION: We report two cases of asymptomatic cerebral aneurysm in which cranial nerve palsy (CNP) developed shortly after symbolization. The CNP occurred immediately in case 1, but case 2 showed the CNP 30 h after symbolization. Although both aneurysms had increased in size on follow-up angiography, case 2 who showed dome re canalization resulted in progressive CNP deterioration. CONCLUSION: These findings suggest that the CNP may result not only from mechanical compression by coils but also from inflammation induced by perpendicular thrombosis, and that the prognosis of the CNP may be influenced by dome re canalization. This complication should be kept in mind in treatment for asymptomatic aneurysms adjacent to the cranial nerves.

Effect of SB-750364, a specific TRPV1 receptor antagonist, on injury-induced ectopic discharge in the lingual nerve.

Abnormal neural activity generated at a site of nerve injury is thought to contribute to the development of dysaesthesia. Vanilloid receptor 1 (TRPV1), a transducer of noxious stimuli, may be involved in the initiation of this abnormal activity and could provide a useful therapeutic target. We investigated the effect of a specific TRPV1 antagonist (SB-750364) on injury-induced discharge in the lingual nerve. In 12 anaesthetised adult ferrets the left lingual nerve was sectioned and animals were allowed to recover for 3-7 days. In terminal experiments under general anaesthesia, the nerve was re-exposed and electrophysiological recordings made from spontaneously active axons in fine filaments dissected from the nerve central to both the injury site and the junction with the chorda tympani. SB-750364 was infused via the cephalic vein in order to achieve three increasing but stable systemic blood levels of the compound (0.3, 1.0 and 3.0 microM). Twenty-eight spontaneously active units were studied, with discharge frequencies ranging from 0.02 to 4.9 Hz. There was a significant reduction in spontaneous activity in 17 units (61%) at 1.0 microM or less of SB-750364 (p<0.01; Friedman test with Dunn's multiple comparisons). A further 4 units (14%) showed a significant reduction in activity at 3.0 microM (p<0.01). In the remaining 7 units (25%) the discharge was unaffected (p>0.05). These data show that the TRPV1 antagonist SB-750364 can reduce the level of spontaneous activity initiated in some axons following lingual nerve injury.

[Extensive lower clivus chordomas. Removal using the unilateral transmandibular approach]. / Chordomes extensifs du clivus inférieur. Exérèse par voie transmandibulaire unilatérale.

BACKGROUND AND PURPOSE: Clival chordomas are rare skull-base tumors with local malignant behavior. Their control and removal remain difficult because of their anatomical location and because of their extensions. The goal of the treatment is complete surgical removal in a single stage if possible, with minimal deficits, followed by proton therapy. If the tumor remains extradural for a while, it finally progresses through the dura backwards to reach and displace the brain stem and upper cervical cord. Its anterior extension in the retropharyngeal space offers a logical opportunity and many advantages to use an anterior approach. METHODS: With three consecutive cases, we try to demonstrate that the unilateral transmandibular approach offers a large exposure of the lower clivus, the foramen magnum in its ventral part, the ipsilateral infratemporal fossa and C1 to C3. Surgical complications concern the lower cranial nerves, including the hypoglossal. Serous otitis media is possible in case of opened Eustachian tube. Tracheostomy is needed because of a transient tongue oedema. RESULTS: The unilateral transmandibular approach enabled to anatomical and physiological nasal preservation, large operative field facilitating dural closure and tumor removal, with acceptable cosmetic results and sequellae considering the natural course and prognosis of the tumor. CONCLUSIONS: This approach seems to be very useful to reach and removed extensive lower chordomas.

Etiology of lingual nerve injuries in the third molar region: a cadaver and histologic study.

PURPOSE: It has been suggested that different etiologies of lingual nerve damage in the third molar area will produce a different clinical and histologic appearance in the nerve. If the clinical and histologic pictures were different, it could result in different treatments being recommended. MATERIALS AND METHODS: Eight preserved cadavers (16 lingual nerves) were used for this study. As far as possible, the nerves were left in situ and damaged in a way that could be envisaged during third molar surgery. In each case, the damaged sections of nerve were photographed, resected, embedded in paraffin wax, sectioned in 5 mum sections, stained with hematoxylin-eosin, and examined histologically. RESULTS: The scalpel clinically produced a clean wound with sharply defined edges; this was confirmed histologically with minimal disruption to the fascicles. The 702 fissure bur produced a ragged stretch-type injury clinically, and histologically this was confirmed with an irregular-edged border to the lesion and stretching and internal damage to the fascicles immediately adjacent to the wound. The crush injury clinically caused considerable apparent damage to the nerve, which was confirmed histologically with crushing and disruption of the fascicles and reduction to approximately 25% of their preinjury thickness. The stretch injury clinically showed no damage, but histologically showed irregular internal disruption of the fascicles over the whole area subject to stretching movements. CONCLUSION: It does appear that different modalities in nerve injury produce a different type of injury both clinically and histologically. This information has implications for both natural clinical recovery and the indications for surgical intervention. Clinical recovery may occur best with close approximation of a sharp scalpel-type wound or excision of a crushed area of nerve with reapproximation of the nerve endings, but a ragged wound caused by a fissure bur may require excision back to healthy nerve with subsequent reapproximation, whereas with the stretching injury it may be difficult to ascertain the edges and limits of the wound, and difficult to repair, and it may be most appropriate to rely on a natural healing process for the best results.

The plasticity of the DRG neurons belonging to different subpopulations after dorsal rhizotomy.

1. The plasticity of sensory neurons following the injury to their axons is very important for prognosis of recovery of afferent fibers with different modality. It is evident that the response of dorsal root ganglion (DRG) neurons after peripheral axotomy is different depending on the deficiency in neurotrophic factors from peripheral region. The loss of cells appears earlier and is more severe in B-cells (small, dark cells with unmyelinated axons) than in A-cells (large, light cells with myelinated axons). 2. We studied using immunohistochemical methods the response of DRG neurons to dorsal rhizotomy and combined injury of central and peripheral neuronal processes. A quantitative analysis of DRG neurons tagged by the selective markers isolectin B4 (IB4) and the heavy molecular component of the neurofilament triplet (NF200) antibody, selective for subpopulations of small and large/medium DRG neurons, respectively, was performed after dorsal rhizotomy, peripheral axotomy, and their combination. 3. The number of NF200(+)-neurons is reduced substantially after both dorsal rhizotomy and peripheral axotomy, while the decrease of IB4(+)-neurons is observed only in combined injury, i.e., dorsal rhizotomy accompanied with sciatic nerve injury. 4. Our results show that distinct subpopulations of DRG neurons respond differently to the injury of their central processes. The number of NF200(+)-neurons decreases to greater degree following dorsal rhizotomy in comparison to IB4(+)-neurons.

Activation of c-Jun and ATF-2 in primate motor cranial nerve nuclei is not associated with apoptosis following axotomy.

Nerve transection induces complex changes in gene regulation and expression that can have profound phenotypic effects on the fate of axotomized neurons. The transcription factors c-Jun and ATF-2 (activating transcription factor-2) are components of a regulatory network that mediates survival, regeneration, and apoptosis following axotomy in rodents. The activation and function of c-Jun and ATF-2 after nerve injury have not been examined in primates. Using a novel model of cranial nerve injury in baboons, we have examined the temporality of c-Jun activation (phosphorylation) in cranial nerve (CN) III and CN VI neurons and ATF-2 activation in CN VI neurons at 2, 4, and 9 days post-injury by immunohistochemistry. Furthermore, we have addressed whether the activation of these factors is associated with apoptosis by the TUNEL assay. We report that activated c-Jun is present in CN III and CN VI neurons ipsilateral to axotomy at 2, 4, and 9 days post-injury, but not in neurons contralateral to injury. Additionally, CN VI neurons ipsilateral to injury at 4 and 9 days contain activated ATF-2. Furthermore, no evidence of TUNEL reactivity was observed in either nucleus, regardless of laterality, at any of the examined time points. These findings suggest that activation of both c-Jun and ATF-2 does not mediate apoptosis in axotomized primate CN III and CN VI neurons at time points up to 9 days. This report serves as a basic inquiry into the neuronal response to cranial nerve injury in primates.