[Brain Stem and Para-Brain Stem Lesions].

Surgeries for brainstem lesions and adjacent areas needs meticulous manipulation in the profoundly deep surgical field. Moreover, it is associated with a high risk of complications pertinent to resection. The opportunity for a surgeon to amass extensive surgical experience in these lesions is limited. Additionally, the reduced tissue mobility in the brainstem, compared to other lesions, makes selecting the optimal surgical approach critical. Preoperative simulation is pivotal in surmounting these challenges. However, the limitations of preoperative simulations should be recognized in accurately depicting diminutive vessels and cranial nerves around the brainstem. Incorporating intraoperative anatomical observations and data from intraoperative monitoring into a surgical strategy is imperative. Here, we present three cases in which we believe preoperative simulation was effective; a cavernous hemangioma of the brainstem, trochlear schwannoma, and diffuse midline glioma in the pons.

Cranial Nerve Thinning Distinguishes RFC1-Related Disorder from Other Late-Onset Ataxias.

BACKGROUND: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. OBJECTIVES: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. METHODS: Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. RESULTS: Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). CONCLUSION: MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.

The value of 3D high-resolution IR-prepared fast spoiled gradient-recalled MRI in the diagnosis of meningeal carcinomatosis involving the cranial nerves.

PURPOSE: The purpose of this study was to investigate the clinical utility of three-dimension (3D) high-resolution inversion recovery (IR)-prepared fast spoiled gradient-recalled (SPGR) magnetic resonance imaging (MRI) in the diagnosis of cranial nerve meningeal carcinomatosis (MC). METHODS: A total of 114 patients with MC from January 2015 to March 2020 were enrolled and their MRIs were analyzed retrospectively. All patients underwent MRIs before being administered a contrast agent. Both a 2D conventional MRI sequence and a 3D IR-prepared fast SPGR high-resolution T1-weighted (BRAVO) scan sequence were measured after contrast agent administration. The characteristics of MC and the involved cranial nerves were then examined. RESULTS: Among the 114 MC patients, 81 (71.05%) had cranial nerve enhancement on contrast-enhanced 3D-BRAVO imaging, while only 41 (35.96%) had image enhancement on conventional MRI. The contrast-enhanced 3D-BRAVO displayed stronger image contrast enhancement of the cranial nerves than the conventional MRI (P < 0.001). Furthermore, detection rates for the facial and auditory nerves, trigeminal nerve, oculomotor nerve, sublingual nerve, optic nerve, glossopharyngeal/vagal/accessory nerve, and abductor nerve on contrast-enhanced 3D-BRAVO imaging were 58.77%, 47.37%, 9.65%, 8.77%, 5.26%, 3.51%, and 0.88%, respectively. We found a statistically significant difference between the affected facial and auditory nerves, as well as the trigeminal nerve, oculomotor nerve, sublingual nerve, and optic nerve. CONCLUSION: In MC, contrast-enhanced 3D-BRAVO imaging displayed the cranial nerves more effectively than 2D conventional enhanced MRI. The facial, auditory, and trigeminal nerves are the primary nerves involved in MC, and improved scanning of these nerves would aid in the early detection and treatment of MC.

Predictors for postoperative cranial nerve complications in carotid body tumor resection: a retrospective cohort study.

INTRODUCTION: Carotid body tumors (CBTs) are slow-growing benign tumors. Therefore, surgical resection is considered in case of tumor growth. The timing of surgery is of the utmost importance as the risk of iatrogenic surgical complications increases when resecting larger tumors, whereas on the other hand, resections for asymptomatic small CBT should be prevented. The primary aim of this study was to identify which tumor size or dimension is most accurate to predict nerve injury in patients undergoing resection of a CBT. MATERIAL AND METHODS: This retrospective cohort study included patients who underwent surgical resection of CBT at the university hospital in South-Holland. Baseline patient characteristics and tumor measurements were retrieved from the medical records. The authors assessed how the different methods of measuring the size of the tumor were interrelated using Pearson correlation. Logistic regression was used to assess which variables were independently associated with nerve injury, including age at surgery, Shamblin classification, and those dimensions that captured different aspects of tumor size (rather than measuring the same as shown by high correlations) as possible independent variables. RESULTS: In 125 patients, 143 CBTs were resected whereof in 35 cases cranial nerve injury occurred, (transient in 16 cases and permanent in 19 cases). The risks for nerve injury increased with larger tumor size and the Shamblin classification. Logistic regression analysis showed that the anterior-posterior (AP) diameter significantly increased the odds of a nerve injury, a doubling for every 1 cm increase in AP diameter [odds ratio (95% CI) 2.12 (1.29-3.48), P =0.003]. CONCLUSION: This study shows that measured tumor size in the AP plane is a strong predictor for postoperative nerve injury of a CBT resection. This predictor can be used in the daily clinic to give insight in operative risks. More research is needed in order to select the most appropriate time window for CBT resection.

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].

Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.

Immunotherapy response in patients with cutaneous squamous cell carcinoma of head and neck with cranial nerve involvement.

BACKGROUND: Metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) can be treated with immunotherapy (IO). Cranial nerve involvement (CNI) is uncommon in cSCC and is a poor prognostic factor. Our aim is to describe how patients with CNI respond to IO monotherapy and/or as an adjunct to RT. METHODS: Under an IRB approved protocol, patients with histologically proven cSCC of the head and neck with CNI treated with IO were retrospectively reviewed. RESULTS: Twelve patients were included and received cemiplimab or pembrolizumab. Eight patients had CNI at diagnosis, and 4 at time of recurrence after non-IO therapy. Best responses were complete response (1), partial response (7), stable disease (1), progressive disease (2), and pending response (1). Nine patients are alive, 6 of which remain on IO. CONCLUSIONS: In this cohort, IO showed clinical response in 83% of patients, indicating IO can be an effective monotherapy, reserving RT for instances of local failure after IO.

Cranial nerve abnormalities in spontaneous intracranial hypotension and their clinical relevance.

BACKGROUND AND PURPOSE: Spontaneous intracranial hypotension (SIH) is a known cause of headaches and neurologic symptoms, but the frequency of cranial nerve symptoms and abnormalities on magnetic resonance imaging (MRI) has not been well described. The purpose of this study was to document cranial nerve findings in patients with SIH and determine the relationship between imaging findings and clinical symptoms. METHODS: Patients diagnosed with SIH with pre-treatment brain MRI at a single institution from September 2014 to July 2017 were retrospectively reviewed to determine the frequency of clinically significant visual changes/diplopia (cranial nerves 3 and 6) and hearing changes/vertigo (cranial nerve 8). A blinded review of brain MRIs before and after treatment was conducted to assess for abnormal contrast enhancement of cranial nerves 3, 6, and 8. Imaging results were correlated with clinical symptoms. RESULTS: Thirty SIH patients with pre-treatment brain MRI were identified. Sixty-six percent of patients had vision changes, diplopia, hearing changes, and/or vertigo. Cranial nerve 3 and/or 6 enhancement was present in nine patients on MRI, with 7/9 patients experiencing visual changes and/or diplopia (odds ratio [OR] 14.9, 95% confidence interval [CI] 2.2-100.8, p = .006). Cranial nerve 8 enhancement was present in 20 patients on MRI, with 13/20 patients experiencing hearing changes and/or vertigo (OR 16.7, 95% CI 1.7-160.6, p = .015). CONCLUSIONS: SIH patients with cranial nerve findings on MRI were more likely to have associated neurologic symptoms than those without imaging findings. Cranial nerve abnormalities on brain MRI should be reported in suspected SIH patients as they may support the diagnosis and explain patient symptoms.

Surgery for Pituitary Tumor Apoplexy Is Associated with Rapid Headache and Cranial Nerve Improvement.

Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (p < 0.01). At one year, 90% of CNDs affecting cranial nerves (CNs) 3, 4, and 6 had recovered, with no differences between early (<4 d), subacute (4−14 d), and delayed (>14 d) time-to-surgery cohorts. Remarkably, half recovered within three days. In total, 56% of CN2 deficits recovered, with the early surgery cohort including more severe deficits and recovering at a lower rate (p = 0.01). No correlation of time-to-surgery and rapidity of recovery of CNDs was observed (p = 0.65, 0.72). Surgery for PTA is associated with rapid recovery of CNDs in the early, subacute, and delayed time frames, and with rapid headache improvement in the early and subacute time frames in 50% or more of patients.

Surgical management of tympanojugular paragangliomas using the flexible CO2 laser.

PURPOSE: Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO2 laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO2 laser. METHODS: Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. RESULTS: The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. CONCLUSION: The flexible CO2 laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.

Artificial Intelligence-Based MRI in Diagnosis of Injury of Cranial Nerves of Premature Infant and Its Correlation with Inflammation of Placenta.

The study focused on the effects of artificial intelligence algorithms in magnetic resonance imaging (MRI) for diagnosing cranial nerve inflammation of placenta and the correlation between cranial nerve injury with placental inflammation was explored. The subjects were selected from 132 premature infants in the hospital. According to the pathological examination of placenta, 81 cases with chorioamnionitis were taken as the experimental group and 51 cases without chorioamnionitis were taken as the control group. The incidence of cranial nerve injury in different groups of premature infants was analyzed by MRI diagnosis based on the principal component analysis (PCA) artificial intelligence algorithm, so as to analyze the correlation between cranial nerve injury and placental inflammation in premature infants. It was found that when the PCA artificial intelligence algorithm was incorporated into MRI examination of cranial nerve injury of premature infant, the A (accuracy), P (precision), R (recall), and F1 values under the PCA algorithm were 92%, 93.75%, 90%, and 92.87%, respectively. The A, P, R, and F1 of the control group were 54%, 54.1%, 52%, and 53.03%, respectively; there were statistically significant differences between the two groups, P < 0.05. As for the correlation of placental inflammation and cranial nerve injury, the positive detection rate of the experimental group was 53.09%, and the positive detection rate of the control group was 15.69%, and the difference was statistically significant, P < 0.05. In conclusion, the PCA artificial intelligence algorithm has high effectiveness and high accuracy in auxiliary diagnosis of premature brain nerve injury, and placental inflammation greatly increases the chance of premature infant suffering from brain nerve injury.

Application of ABR in pathogenic neurovascular compression of the 8th cranial nerve in vestibular paroxysmia.

PURPOSE: To investigate the clinical value of electrophysiological tests in indicating pathogenic vascular contact of the 8th nerve in definite vestibular paroxysmia (VP) cases to provide a reference for decompression surgery. METHODS: We retrospectively analyzed patients who had vertigo, unilateral tinnitus, or hearing loss and exhibited vascular contact of the 8th cranial nerve by MRI. Participants were classified into the VP or non-VP group according to the criteria of the Bárány Society in 2016. The demographic characteristics and audiological and electrophysiological test results of the two groups were compared. Receiver operating characteristic (ROC) curves were calculated for ABR to determine the best parameters and cutoff values to predict the existence of pathological neurovascular contact in VP. RESULTS: Thirteen patients in the VP group and 66 patients in the non-VP group were included. VP patients had longer interpeak latency (IPL) I-III and wave III latency compared to non-VP patients (p < 0.001; p < 0.001). According to the ROC analyses, IPL I-III and wave III latency were the best indicators for the diagnosis of VP. The optimal cutoff for IPL I-III was 2.3 ms (sensitivity 84.6%, specificity 95.5%), and that for wave III latency was 4.0 ms (sensitivity 92.3%, specificity 77.3%). There were no differences in the PTA, caloric test, o-VEMP, or c-VEMP results between the two groups. CONCLUSION: Prolonged IPL I-III and the wave III latency of ABR strongly suggested that vascular contact of the 8th cranial nerve was pathological, which may provide some references for microvascular decompression surgery of VP.

Comparison of Lower Cranial Nerve Function Between Tympanojugular Paraganglioma Class C1/C2 With and Without Intracranial Extension: A Four-Decade Experience.

OBJECTIVE: To compare preoperative and postoperative lower cranial nerve (LCN) function between Class C1 and C2 tympanojugular paraganglioma (TJP) with/without intracranial intradural (Di)/extradural (De) extensions, according to the experience of a single surgeon over four decades. STUDY DESIGN: Retrospective review. SETTING: Quaternary referral center for otology and skull base surgery. MATERIAL AND METHODS: A chart review was conducted of all the patients operated for C1/C2 TJPs from September 1983 to December 2018. The tumors were classified as: Limited-Group (C1/C2 without Di/De extensions) and Extended-Group (C1/C2 with Di/De extensions). RESULTS: Of 159 patients, 107 (67.3%) were women; the mean age at surgery was 46.5 years. The Limited-Group (56.6%) comprised C1 (41.1%) and C2 (58.9%) tumors; the Extended-Group (43.4%) comprised C1+Di/De (14.5%) and C2+Di/De (85.5%) tumors. The prevalence of preoperative LCN palsy was 11.9 times higher in Extended than Limited tumors: 61.9% versus 4.9% (p < 0.05). The risk for postoperative LCN palsy was 4.7 times greater in Extended than Limited tumors: 29.2% versus 12.9%, p = 0.01. CONCLUSION: Especially in younger patients, complete removal of Limited C1/C2 tumors, before they extend intracranially, reduces the risk of dysfunctionality of LCNs and the burden of residual tumor. The incidence of new tumors increased over four decades. However, new-postoperative LCN palsy did not occur in any Limited C1/C2 tumors operated after the year 2000, and declined to less than 10% of Extended C1/C2 tumors.

Management of non-vestibular schwannomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section Part III: Lower cranial nerve schwannomas, jugular foramen (CN IX, X, XI) and hypoglossal schwannoma (XII).

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogenous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear, and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the third of a three-part series describing non-vestibular schwannomas (IX, X, XI, XII). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to preoperative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of non-vestibular schwannomas. For each of these tumours, the management paradigm is shifting towards the compromise between function preservation and progression free survival.

The Wandering Nerve: Positional Variations of the Cervical Vagus Nerve and Neurosurgical Implications.

BACKGROUND: The vagus ("wandering") nerve is the longest cranial nerve with the largest territory of innervation in the human body. Injury during various operative procedures involving the anterior or lateral neck may lead to serious complications. Per "textbook" descriptions, the cervical vagus nerve (CVN) commonly locates within the carotid sheath, in between the common carotid artery (CCA) and internal jugular vein (IJV). However, anatomic variations in its positioning may occur more often than expected and intraoperative identification may anticipate potential surgical pitfalls. METHODS: A literature review was conducted per PRISMA guidelines for all studies describing positional variations of the CVN within the carotid sheath. A rare and potentially dangerous variation, occurring in only 0.7% of all reported cases, is illustrated with a cadaveric case. RESULTS: Overall, 10 anatomic CVN variations have been described across 971 specimens. The non-textbook variations (26.5%) consist of: lateral (4.7%), anterolateral (8.7%), posteromedial (0.2%), posterior (5.8%), anterior (3.1%), medial (0.7%), and anteromedial (0.4%) to the CCA, as well as posterolateral (0.3%) and posterior (2.6%) to IJV. The "textbook" anatomic location is posterolateral to CCA (73.5%). Moreover, an increase in variability is reported on the left side (17.1%) compared with the right (11.3%). Our cadaveric dissection revealed a right-sided CVN directly medial to the CCA. CONCLUSIONS: Positional variations of the CVN occur in over 26% of patients and may add difficulty to an array of surgical procedures. Knowledge of these variations and their prevalence may aid the surgeon in conducting a more precise dissection possibly preventing significant potential adverse sequelae.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Remission of Mucosal Melanoma of the Middle Ear and Petrous Temporal Bone and Reversal of Cranial Nerve Paresis Following Radiation and Single Agent Nivolumab: Clinical Capsule and Review of the Literature.

OBJECTIVE: We report disease remission and recovery of fifth and seventh nerve paresis in a case of primary mucosal melanoma of the middle ear and petrous temporal bone. PATIENT: A 74-year-old man developed sudden, profound, right sided sensorineural hearing loss, disequilibrium, otalgia, and cranial nerve V and VII dysfunction. Imaging demonstrated an unresectable, osteolytic lesion involving the middle ear and anterior petrous apex. Melanoma was diagnosed via in-office biopsy; whole-body metabolic imaging revealed no other primary site. INTERVENTION: Multidisciplinary management included radiation therapy (30 Gy, 10 fractions) followed by induction (five cycles, q2w) and maintenance nivolumab (six cycles, q3w). MAIN OUTCOME MEASURE: Complete metabolic response of primary site and metastases on imaging, recovery of cranial neuropathies. RESULTS: Following palliative radiation therapy and induction nivolumab, cranial neuropathies resolved. With maintenance-dose nivolumab, primary site and metastases exhibited a complete response. Therapy was stopped at 16 months post-diagnosis. Complete remission was maintained until 22 months after diagnosis. The patient developed a solitary cerebral metastasis which was refractory to radiosurgery and biopsy confirmed melanoma. He expired 2 years, 8 months post-diagnosis. CONCLUSIONS: Mucosal melanoma of the middle ear and petrous temporal bone is exceedingly rare. Management is individualized and surgery is undertaken when possible. Key observations in this case are the complete metabolic response and reversal of cranial nerve neuropathies following radiation and anti-programed cell death receptor ligand 1 therapy. Non-surgical treatment is worthy of study as initial management for similar lesions.

Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles.

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p < 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.