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Purpose Stellate ganglion block (SGB) is effective in treating head and neck pain and neuropathic diseases by increasing tissue blood flow through its sympatholytic effect. This study aimed to investigate the relationship between duration of cervical sympathetic nerve block by SGB and its therapeutic efficacy against trigeminal neuropathy after orthognathic surgery. Methods Twenty-eight patients with trigeminal neuropathy were randomly assigned to two groups (mepivacaine and levobupivacaine) according to the drug used for SGB. Increased blood flow, which is a symptom of sympathetic blockade, was recorded for 180 min after SGB. Current perception threshold, warm or cool detection threshold, and tactile detection threshold were measured preoperatively, postoperatively, on day 10 after initiation of SGB, and 3 months postoperatively to compare therapeutic efficacy between the groups. Results The levobupivacaine group had a significantly longer duration of increased blood flow compared with the mepivacaine group. Values of current perception threshold, warm and cool detection threshold, and tactile detection threshold significantly improved in the levobupivacaine group on day 10 after initiation of SGB and 3 months postoperatively. Conclusion A prolonged increase in blood flow due to long-term sympatholytic effects accelerates the therapeutic efficacy of SGB in trigeminal neuropathy.

PURPOSE The purpose of this study was to describe an indirect corneal neurotization (CN) technique for congenital bilateral trigeminal anesthesia using the greater auricular nerve (GAN) as a donor. METHOD CN was performed to preserve the integrity of the only seeing eye in a 4-year-old boy with pontine tegmental cap dysplasia and bilateral trigeminal anesthesia. He had recurrent corneal ulceration and scarring despite full medical treatment. The GAN was used as a donor, and the sural nerve was harvested and used as a bridge which was tunneled to the sub-Tenon space in the inferior fornix. The fascicles were distributed into the 4 quadrants and sutured to the sclera near the limbus. RESULT This technique resulted in providing corneal sensation and improving stability of the epithelium. Corneal opacity gradually decreased allowing significant visual improvement evidenced in the early postoperative months. CONCLUSIONS Using the GAN technique for CN bypasses trigeminal innervation and has the potential to improve corneal sensation. The GAN is a large caliber nerve and provides a large amount of axons and robust neurotization. This technique would be desirable for cases with bilateral congenital trigeminal anesthesia, such as pontine tegmental cap dysplasia.

PURPOSE: To illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort. A subset of these patients may also present with neuropathic corneal pain (NCP). METHOD: Retrospective case series of 7 stage 1 NK patients who presented with concurrent ocular pain, as confirmed by clinical examination, proparacaine challenge test and in vivo corneal confocal microscopy (IVCM). Records were assessed for results of ocular surface disease index (OSDI), pain on visual analog scale (VAS), ocular pain assessment survey (OPAS), best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, and IVCM findings. IVCM findings were compared to that of 20 healthy reference controls. RESULTS: Mean age of patients was 63.7±11.6 (range 44–76) years and 56.9±8.6 (range 42–74) years in reference controls (p=0.11). At presentation, ocular discomfort was 8.0±1.3 (range 7–10) on VAS and mean OSDI scores were 72.26±6.81 (range 62.50–79.54). Mean BCVA was 20/40, and mean CFS scores were 3.43±0.79 (range 2–4) on the Oxford scale. IVCM analysis showed significant decrease in mean total, main and branch nerve densities in ranges consistent with NK as compared to normal controls (p

PURPOSE The purpose of this study was to evaluate the clinical outcome of patients with refractory neurotrophic keratopathy (NK) in stages 2 and 3 treated with topical insulin. METHODS Retrospective analysis of eyes with NK in stages 2 and 3 refractory to standard medical and/or surgical treatment which were treated with topical insulin (1 unit per mL). This treatment was applied 4 times per day and was continued until the persistent epithelial defect (PED) or ulcer resolved. The primary outcome of the study was the complete reepithelialization of the PED or persistent ulcer. "Best-corrected visual acuity" pretreatment and posttreatment, "days until complete reepithelialization" data, and anterior segment photographs were obtained. Outcome measures were compared before and after treatment in both groups using paired and independent samples t tests. RESULTS Twenty-one eyes were included in this study, and 90% achieved complete reepithelialization of the PED and/or persistent ulcer within 7 to 45 days of follow-up. The mean number of days until complete reepithelialization was significantly lower in NK stage 2 (18 ± 9 days) when compared with NK stage 3 (29 ± 11 days) (P = 0.025). The best-corrected visual acuity improved significantly in both NK stage 2 (P < 0.001) and NK stage 3 (P = 0.004). No side effects were reported during the follow-up. CONCLUSIONS Our results suggest that topical insulin drops may be an effective therapeutic in refractory NK. This therapy may prove extremely useful because of its low cost and high accessibility.

Neurosensory disturbances (NSDs) caused by injury to the trigeminal nerve can affect many aspects of daily life. However, factors affecting the persistence of NSDs in patients with posttraumatic trigeminal neuropathies (PTTNs) remain largely unknown. The identification of such risk factors will allow for the phenotyping of patients with PTTNs, which is crucial for improving treatment strategies. We therefore aimed to identify the prognostic factors of NSD persistence, pain intensity, and quality of life (QoL) in patients with PTTNs and to use these factors to create a prognostic prediction model. We first performed a bivariate analysis using retrospective longitudinal data from 384 patients with NSDs related to posttraumatic injury of the trigeminal nerve (mean follow-up time: 322 ± 302 weeks). Bivariate and multivariate analyses were performed. The multivariable prediction model to predict persistent NSDs was able to identify 76.9% of patients with persistent NSDs, with an excellent level of discrimination (area under the receiver operating characteristic curve: 0.84; sensitivity: 81.8%; specificity: 70.0%). Furthermore, neurosensory recovery was significantly associated with sex; injury caused by local anesthesia, extraction, third molar surgery, or endodontic treatment; and the presence of thermal hyperesthesia. Pain intensity and QoL analysis revealed several factors associated with higher pain levels and poorer QoL. Together, our findings may aid in predicting patient prognosis after dental, oral, and maxillofacial surgery and might lead to personalized treatment options and improved patient outcomes. ispartof: PAIN vol:163 issue:4 pages:E557-E571 ispartof: location:United States status: published

Painful post-traumatic trigeminal neuropathy (PPTTN) is a distinctive facial pain syndrome characterized by facial and/or oral pain along the sensory distribution of the fifth cranial nerve with a clear history of a traumatic event. To our knowledge, PPTTN after endoscopic sinus surgery (ESS) has not been reported in the literature. We present a case of an elderly woman who experienced unilateral neuralgic pain after undergoing ESS. Following ESS of the left sphenoid sinus to remove suspicious fungus balls, the patient complained of intermittent facial pain occurring in the left periorbital and forehead area. Clinical diagnosis of PPTTN was established after a comprehensive multidisciplinary assessment. The pain disappeared completely after a 5-week medical treatment with gabapentin. Since PPTTN cases associated with ESS are extremely rare, our case demonstrates that PPTTN should be considered in the differential diagnosis of facial pain developing after ESS and can be successfully treated with medical therapy.

Neurotrophic keratopathy is a degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia. Injuries to neurotrophic corneas are notoriously difficult to treat and have traditionally been approached with supportive management. However, recent progress in the field of corneal neurotization has given new direction for addressing nerve loss directly by stimulating new nerve growth onto the cornea from nearby sensory nerves transferred to the perilimbal region. Herein, we review the surgical techniques utilized in corneal neurotization, including direct transfers and the use of nerve grafts. Considerations in surgical approach, as well as factors that influence prognosis and outcomes of the surgical intervention are also discussed.

Background: Trigeminal neuralgia is a chronic disease characterized by intense facial pain that is caused by trigeminal nerve affectation. It usually affects adults from 50 years of age, and is more frequent in women. Additionally, it presents serious psychological effects that often lead to depression, which is why it is considered highly disabling. The therapeutic approach is based on the modification of nerve activity through electrical, surgical or chemical stimulation in specific regions of the nervous system. Objective: To perform a meta-analysis of the scientific literature related to invasive and non-invasive electrical neuromodulation of trigeminal neuralgia, in order to assess their effects over pain and adverse effects. Methods: A literature search was conducted in 4 databases, followed by a manual search of articles on invasive or non-invasive electrical neuromodulation to control the pain of trigeminal neuralgia, including the last 15 years. Results: Regarding non-invasive methods, clinical trials did not present enough results in order to perform a meta-analysis. Regarding invasive methods, clinical trials meta-analysis showed no statistical differences between different treatment methods. In all cases, improvements in patients' pain were reported, although results regarding adverse effects were variable. Conclusion: In the treatment of trigeminal neuralgia, the continuous radiofrequency provides better short and medium-term results, but pulsed radiofrequency shows less adverse effects after treatment, and has better results in the long-term.

Background Soft tissue filler injections are frequently performed with a relatively low number of severe adverse events reported. While venous complications have been described, the majority of adverse events are generally associated with the arterial vascular system. Intra-arterial product application can present with pain, skin discoloration, and potential tissue loss and/or injection related visual compromise. Aim We present the clinical case and the consecutive symptomology of a 39-year-old woman injected with calcium hydroxylapatite at the zygomatic arch with five perpendicular needle (27G 12mm) supraperiosteal bolus injections of 0.2 cc per site. Methods Immediately after the injections, weakness, nausea, vomiting, and loss of consciousness occurred. Additionally, left-sided loss of sensation of her face, scalp, oral, and nasal mucosa occurred, with absence of left corneal reflex and ipsi-lateral ear congestion. Subsequently, left-sided masseteric atrophy and dysphagia occurred. Results One year after the injection procedure the sensory loss of her facial skin and scalp persisted, while the other symptoms improved. Medications involved in the symptomatic (not causal) partial recovery process were Dexamethasone, Vitamin B complex, Vinpocetine, Pentoxifyllin, and Thioctic acid. Conclusion The symptoms presented and the time-related relationship to the injection procedure increases the likeliness of an association between the administration of the calcium hydroxylapatite product and a lesion of the trigeminal ganglion. The resulting symptoms can altogether be related to the functions of the ganglion. The connecting pathway between the injection site and the ganglion can be explained by the arterial vascular pathway.

Purpose To characterize corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (SIV)-infected macaques by combining in vivo corneal confocal microscopy (IVCM) with automated assessments using deep learning-based methods customized for macaques. Methods IVCM images were collected from both male and female age-matched rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including preinfection and 10-day post-SIV infection time points. All IVCM images were analyzed using a deep convolutional neural network architecture developed specifically for macaque studies. Results Deep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of human immunodeficiency virus, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P = 0.01 and P = 0.008, respectively). Conclusions The combination of IVCM and robust objective deep learning analysis is a powerful tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting deep learning analyses to clinical corneal nerve assessments will improve monitoring of small sensory nerve fiber damage in numerous clinical settings including human immunodeficiency virus.

Purpose To characterize patients with neurotrophic keratopathy (NK) and describe treatment outcomes. Methods Setting: Two institutional tertiary cornea clinics. Patients: Medical record review of 37 consecutive patients (37 eyes) with NK. Intervention: Management of NK. Main Outcome Measures: Best-corrected visual acuity (BCVA), epithelial defects (ED), re-epithelialization time, number of perforations, need for penetrating keratoplasty and tarsorrhaphy. Results Average age was 64.4 ± 15.0 years, with 59.5% male patients. Average follow up time was 20.8 ± 32.6 months. Moderate to severe NK (Mackie Stage) was present in 62.1% of patients. Herpetic, neurosurgical and pars plana vitrectomy were the top three causes in each Mackie Stage. 72.9% used topical steroids to treat inflammatory ocular disease. Mean number of EDs was 1.6 per patient averaging 85 days to heal. Persistent EDs affected 56.7%. Corneal perforation (18.9%) was more likely with advanced age, herpetic cause and Stage 3 presentation. Tarsorrhaphy was performed in 35% of patients and were more likely with Stage 3 presentation. Referral for neurotization occurred in 10.8%. Evisceration was required in 2 eyes. BCVA of 20/40 or better was achieved in 21.6% of eyes at last follow up. Conclusions NK is chronic, frequently visually disabling with multiple contributing factors requiring different treatment modalities. Herpetic, pars plana vitrectomy and neurosurgical causes constitute a significant proportion of NK. Persistent epithelial defects should be rapidly managed as corneal perforation is a serious complication. Advanced age, herpetic cause and Mackie Stage 3 at diagnosis are significant risk factors for corneal perforation.

Neurotrophic keratopathy (NK) is a degenerative corneal disease produced by different factors, including infection, trauma, and neurogenesis, that lead to trigeminal nerve damage and impaired corneal sensitivity. Extensive epithelial breakdown, impaired corneal epithelial healing and corneal ulceration, stromal melting, and perforation are main NK features. The proliferation of the corneal epithelium is endogenously regulated by a balance between adrenergic cAMP-dependent and cholinergic cGMP-dependent pathways. A careful balance of epitheliotropic neuromediators and neurotrophic factors expressed by corneal nerves and epithelial cells, respectively, is required to maintain corneal homeostasis. Even in its early stages, NK can cause reduced vision secondary to epithelial disturbance. Diagnosing NK is challenging, requiring the acquisition of a thorough clinical history and a comprehensive neurological and ophthalmic examination. Following suspicion of a clinical NK diagnosis, corneal sensitivity must be assessed qualitatively with the wisp of the cotton-tipped applicator and quantitatively through Cochet-Bonnet esthesiometry (CBE). A myriad of therapies is used for NK, and new, more specific modalities are being developed and investigated. Medical treatment with topical recombinant human nerve growth factor and surgical treatment through corneal neurotization are promising therapies aiming to target NK pathophysiology. Coexistent ocular surface disorders must be managed concomitantly to improve its prognosis. This review describes the up-to-date knowledge of the molecular basis regarding the pathogenesis of NK, and the novel target-specific therapeutic approaches based on this molecular mechanism.

Significance Ocular tilt reaction (OTR) is an abnormal eye-head postural reaction that consists of skew deviation, head tilt, and bilateral ocular torsion. Understanding of the pathway of the vestibulo-ocular reflex (VOR) is essential because this will help to localize the pathology. Purpose The aim of this study was to report a case of OTR with contralateral internuclear ophthalmoplegia (INO) and fifth and seventh cranial nerve palsies. Case report A 51-year-old gentleman with underlying diabetes mellitus presented with sudden onset of diplopia for 3 days. On examination, his visual acuity was 20/30 bilaterally without a relative afferent pupillary defect. He had a right OTR consisting of a right head tilt, a skew deviation with a left eye hypertropia, and bilateral ocular torsion (right excyclotorsion and left incyclotorsion) with nystagmus. He also had a left adduction deficit and right abduction nystagmus consistent with a left INO. Ocular examination revealed evidence of proliferative diabetic retinopathy bilaterally. Two days after the initial presentation, the patient developed left seventh and fifth cranial nerve palsies. MRI showed left pontine infarction and multiple chronic lacunar infarctions. There was an incidental finding of a vascular loop compression on cisternal portions of the left trigeminal, facial, and vestibulocochlear nerves. Antiplatelet treatment was started on top of a better diabetic control. The diplopia was gradually resolved with improved clinical signs. In this case, the left pontine infarction had likely affected the terminal decussated part of the vestibulocochlear nerve from the right VOR pathway, medial longitudinal fasciculus, and cranial nerve nuclei in the left pons. Conclusions The OTR can be ipsilateral to the lesion if the lesion is before the decussation of the VOR pathway in the pons, or it can be contralateral to the lesion if the lesion is after the decussation. In case of an OTR that is associated with contralateral INO and other contralateral cranial nerves palsy, a pathology in the pons that is contralateral to the OTR should be considered. Neuroimaging study can hence be targeted to identify the possible cause.

Neurotrophic keratopathy (NK) occurs because of disruption of corneal sensory innervation. There are many etiologies that can lead to NK, such as infection, trauma, topical medication use, cornea surgery, and intracranial tumors among others. We review the current available treatment options and provide a stage-based approach to its management.

Objective To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 anti‐neurofascin 155 antibody‐positive (NF155+) chronic inflammatory demyelinating polyneuropathy (CIDP). Methods Thirteen IgG4 NF155+ CIDP patients with mean onset age of 34 years (11 men) were subjected to neurological examination, blink reflex, and visual‐evoked potential (VEP) testing, and axial and/or coronal T2‐weighted head magnetic resonance imaging (MRI). Results Among 13 patients, facial sensory impairment, facial weakness, and apparent visual impairment were observed in three (23.1%), two (15.4%), and two (15.4%) patients, respectively. All 12 patients tested had blink reflex abnormalities: absent and/or delayed R1 in 11 (91.7%), and absent and/or delayed R2 in 10 (83.3%). R1 latencies had strong positive correlations with serum anti‐NF155 antibody levels (r = 0.9, P ≤ 0.0001 on both sides) and distal and F wave latencies of the median and ulnar nerves. Absent and/or prolonged VEPs were observed in 10/13 (76.9%) patients and 17/26 (65.4%) eyes. On MRI, hypertrophy, and high signal intensity of trigeminal nerves were detected in 9/13 (69.2%) and 10/13 (76.9%) patients, respectively, whereas optic nerves were normal in all patients. The intra‐orbital trigeminal nerve width on coronal sections showed a significant positive correlation with disease duration. Interpretation Subclinical demyelination frequently occurs in the optic, trigeminal, and facial nerves in IgG4 NF155+ CIDP, suggesting that both central and peripheral myelin structures of the cranial nerves are involved in this condition, whereas nerve hypertrophy only develops in myelinated peripheral nerve fibers.

Simultaneous multi-slice (SMS) imaging with short repetition time (TR) accelerates diffusion tensor imaging (DTI) acquisitions. However, its impact when combined with readout-segmented echo planar imaging (RESOLVE) on the cranial nerves given the challenging skull base/posterior fossa terrain is unexplored. We evaluated the reliability of trigeminal nerve DTI metrics using SMS with RESOLVE-DTI. Eight healthy controls and six patients with unilateral trigeminal neuralgia (TN) underwent brain MRI scan. Three different RESOLVE-DTI protocols were performed on a 3-T MRI system: non-SMS (TR = 4330 ms), SMS with identical TR (4330 ms), and SMS with short TR (2400 ms). Pontine signal-to-noise ratio (SNR) and DTI metrics of the trigeminal nerve streamlines tracked by two independent raters using deterministic tractography and standardized tracking protocol were obtained. These were statistically analyzed and compared across the three protocols using intra-rater and inter-rater intraclass correlation coefficients (ICCs), one-way analysis of variance (ANOVA), post hoc analysis, and linear regression. On visual screening, there were no artifacts across the trigeminal nerves. All data also cleared objective image quality assurance analysis. Pontine SNR was similar for the two SMS protocols and higher for the non-SMS RESOLVE-DTI (F(2,36) = 4.40, p = 0.02). Intra-rater and inter-rater ICCs were very good (> 0.85). Trigeminal nerve DTI metrics were consistently measured by the three protocols, revealing significant linear relationships between non-SMS- and SMS-derived DTI metrics. SMS RESOLVE-DTI enables fast and reliable evaluation of microstructural integrity of the trigeminal nerve, with potential application in the clinical management of TN. • Readout-segmented diffusion-weighted echo planar imaging (RESOLVE-DTI) reduces image distortion artifacts in the posterior fossa but its long acquisition time limits clinical utility. • Simultaneous multi-slice (SMS) imaging combined with RESOLVE-DTI provides reliable trigeminal nerve tractography with potential applications in trigeminal neuralgia. • Two-fold-accelerated RESOLVE-DTI yields comparable trigeminal nerve streamlines and DTI metrics while near-halving acquisition time.

OBJECTIVETrigeminal schwannomas are rare neoplasms with an incidence of less than 1% that require a comprehensive surgical strategy. These tumors can occur anywhere along the path of the trigeminal nerve, capable of extending intradurally into the middle and posterior fossae, and extracranially into the orbital, pterygopalatine, and infratemporal fossa. Recent advancements in endoscopic surgery have suggested a more minimally invasive and direct route for tumors in and around Meckel’s cave, including the endoscopic endonasal approach (EEA) and endoscopic transorbital superior eyelid approach (ETOA). The authors assess the feasibility and outcomes of EEA and ETOA for trigeminal schwannomas.METHODSA retrospective multicenter analysis was performed on 25 patients who underwent endoscopic surgical treatment for trigeminal schwannomas between September 2011 and February 2019. Thirteen patients (52%) underwent EEA and 12 (48%) had ETOA, one of whom underwent a combined approach with retrosigmoid craniotomy. The extent of resection, clinical outcome, and surgical morbidity were analyzed to evaluate the feasibility and selection of surgical approach between EEA and ETOA based on predominant location of trigeminal schwannomas.RESULTSAccording to predominant tumor location, 9 patients (36%) had middle fossa tumors (Samii type A), 8 patients (32%) had dumbbell-shaped tumors located in the middle and posterior cranial fossae (Samii type C), and another 8 patients (32%) had extracranial tumors (Samii type D). Gross-total resection (GTR, n = 12) and near-total resection (NTR, n = 7) were achieved in 19 patients (76%). The GTR/NTR rates were 81.8% for ETOA and 69.2% for EEA. The GTR/NTR rates of ETOA and EEA according to the classifications were 100% and 50% for tumors confined to the middle cranial fossa, 75% and 33% for dumbbell-shaped tumors located in the middle and posterior cranial fossae, and 50% and 100% for extracranial tumors. There were no postoperative CSF leaks. The most common preoperative symptom was trigeminal sensory dysfunction, which improved in 15 of 21 patients (71.4%). Three patients experienced new postoperative complications such as vasospasm (n = 1), wound infection (n = 1), and medial gaze palsy (n = 1).CONCLUSIONSETOA provides adequate access and resectability for trigeminal schwannomas limited in the middle fossa or dumbbell-shaped tumors located in the middle and posterior fossae, as does EEA for extracranial tumors. Tumors predominantly involving the posterior fossa still remain a challenge in endoscopic surgery.

Painful traumatic trigeminal neuropathy (PTTN) may occur following major craniofacial or oral trauma, or may be subsequent to relatively minor dental interventions. Following injury, pain may originate from a peripheral nerve, a ganglion, or from the central nervous system. In this review, we focus on molecular mechanisms of pain resulting from injury to the peripheral branch of the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy (PTTN) by the International Headache Society and replaces previous terms including atypical odontalgia, deafferentation pain, traumatic neuropathy and phantom toothache. We emphasize the scientific evidence supporting the events purported to lead to PTTN by reviewing the pathophysiology of PTTN based on relevant animal models. Additionally, we briefly overview clinical correlates and pathophysiological manifestations of PTTN.

PURPOSE To investigate the effect of multiple sclerosis (MS) on corneal and retinal nerve fiber by quantifying corneal subbasal nerve fibers and retinal ganglion cells. METHODS A total of 46 eyes of 23 patients with MS and 42 eyes of 21 healthy subjects were included in the study. All patients and healthy subjects underwent a comprehensive ocular examination. In vivo confocal microscopy with Heidelberg Retina Tomograph in association with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) and a swept-source optical coherence tomography (Topcon Corporation) were performed in all patients and healthy subjects. The number of subbasal nerve fibers and the nerve fiber density were calculated. Student t test was used to compare eyes with MS with control eyes. The normal distribution was first confirmed with the Shapiro-Wilk test. RESULTS A statistically significant (P < 0.05) decrease was found for nerve fiber number, ganglion cell-inner plexiform layer, and retinal nerve fiber layer in patients with MS compared with those of healthy subjects. Moreover, an inverse correlation was found between retinal nerve fiber layer (r = -0.32), nerve fiber number (r = -0.47), and ganglion cell-inner plexiform layer (r = -0.51) and Expanded Disability Status Scale. A direct correlation between Expanded Disability Status Scale and optic neuritis frequency was found (r = 0.322). CONCLUSIONS In vivo confocal microscopy showed a difference in corneal morphological parameters and retinal damage; moreover, these changes seemed to be related to the degree of neurological disability. Both retinal ganglion and trigeminal cell atrophy measurements could become affordable and accessible biomarkers for clinical trials in progressive disease.

Purpose To determine neurotrophic keratitis (NK) frequency, etiologies and prognostic factors, and evaluate the outcome of its management. Methods In this retrospective epidemiologic study, we reviewed the electronic records of all patients consulting our tertiary referral eye hospital between November 2009 and October 2017. NK was defined as corneal hypoesthesia or anesthesia associated with epithelial irregularities. Results Among the 305,351 patients’ files screened for eligibility, 335 (354 eyes) were included, yielding an NK frequency of 11/10,000 (0.11%). Their mean ± SD age was 63.1 ± 21.0 years. Eyes were equally divided among the Mackie classification 3 stages. The most frequent etiology was herpetic eye disease (114 eyes; 32.2%). A multifactorial cause was found for 121 (34.2%) eyes. Surgery required for 118 eyes (33.3%). Respective success rates for amniotic membrane transplantation (AMT) or matrix-regeneration of stages 2 and 3, and autologous serum of stage 1 were 57.2%, 63.6% and 21.7%, with mean healing times of 15.0, 16.3 and 85 days. The overall healing rate was 79.5%, with a mean of 44.8 days to healing. Advanced initial stage, diminished corrected-distance visual acuity (CDVA) and advanced age correlated with worse final CDVA. Conclusions NK was more frequent than previously reported in the literature. Delayed diagnoses indicated we must increase ophthalmologists’ awareness of this disease for patients with decreased corneal sensitivity and abnormal epithelium. To improve prognosis and final CDVA, NK-specific treatment should be initiated as soon as the diagnosis is suspected. Patient-centered combinations of different therapeutic components and close monitoring achieved promising results.

Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief. This is peer-reviewd wersion of the foloving article: Pecikoza, U.; Tomić, M.; Micov, A.; Vuković, M.; Stepanović-Petrović, R. Eslicarbazepine Acetate Interacts in a Beneficial Manner with Standard and Alternative Analgesics to Reduce Trigeminal Nociception. Psychopharmacology 2020. [https://doi.org/10.1007/s00213-020-05470-7.]

PURPOSE The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization. METHODS A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms "corneal neurotization," "corneal neurotisation," "corneal reinnervation," and "neurotrophic keratopathy" was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed. RESULTS A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6-10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0-17 years) as compared with adults (ages 18-82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011). CONCLUSIONS Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

Herein, the authors report an unusual case of a 6-year-old boy with right-sided Goldenhar syndrome and trigeminal nerve aplasia who developed neurotrophic keratopathy (NK). Despite the use of therapeutic contact lenses and multiple temporary tarsorrhaphy, NK worsened showing a central corneal scar, neovascularization, and significant stromal thinning, with risk of corneal perforation. Cochet-Bonnet esthesiometry revealed complete corneal anesthesia. To minimize additional corneal complications, the patient underwent indirect corneal neurotization by a sural nerve autograft anastomosed to the contralateral supratrochlear nerve. At 24-month follow up, no epithelial defects, complications, or recurrence were observed. Significant improvements in corneal sensitivity with esthesiometry score of 20 mm and reflex blinking were achieved. This case highlights corneal anesthesia should be suspected among Goldenhar syndrome ophthalmologic abnormalities and monitored before corneal changes become irreversible. Since corneal neurotization can successfully improve corneal sensation, it could be considered as an early therapeutic option to avoid refractory NK.

Corneal neurotization is a fast-evolving surgical procedure for sensory reinnervation in neurotrophic keratopathy. After neurotization, prior reports document return of corneal sensation on average 8 months after surgery with 38 mm of sensation gain measured via cochet bonnet esthesiometer testing. Here, the authors describe a dual nerve grafting approach via simultaneous parallel sural nerve grafts from both the supratrochelar and supraorbital nerves to the affected contralateral cornea with return of sensation by postoperative week 11.

This report describes the successful treatment of two patients with trigeminal neuropathy by using gasserian ganglion stimulation. Case reports: The first case report deals with a 53‐year‐old woman suffering from right‐sided facial pain after a gamma knife lesion for schwannoma of the right inner ear. For 9 years, several interventions with the aim of relieving the pain were unsuccessful; in fact, they had aggravated the symptoms. A trial with a neurostimulator at the level of the Gasser ganglion had an immediately positive effect on her score for facial pain, which decreased from 7.3 to 0 on a visual analog scale, assessed during a period of 2 months. Additionally, the patient had weaned off all her medication by the end of the period. The second case report describes a 64‐year‐old man suffering from trigeminal neuropathy, which mainly manifested itself as an itch. For a period of 15 years, neither medication nor several interventions were effective. A trial with an electrode at the level of the Gasser ganglion reduced his pain score from 7.0 to 1.5 on a visual analog scale, assessed during a period of three months. His medication could be limited to pregabalin 150 mg bidaily. In contrast, prior to the implantation, his oral medication consisted of pregabalin 75 mg up to five times a day. Conclusion: These case reports show that stimulation of the gasserian ganglion is a successful, minimally invasive, and non‐destructive treatment in refractory trigeminal neuropathy and should be considered earlier in the treatment algorithm of trigeminal neuropathy., The manuscript reports two case reports on the use of neuromodulation in trigeminal neuropathy. Both patients had an extensive history of interventions that had no effect on their symptoms, which in fact aggravated their complaints. Our case reports show the successful result of stimulation of the gasserian ganglion in trigeminal neuropathy.

Trigeminal anesthesia may yield blindness and facial disfigurement, secondary to neurotrophic keratopathy and trigeminal trophic syndrome. This article summarizes contemporary medical and emerging surgical approaches for the therapeutic management of this rare and devastating disease state.

Purpose of review Trigeminal anesthesia causes neurotrophic keratopathy, which may yield facial disfigurement and corneal blindness. Recent findings We summarize approaches and evidence for corneal neurotization. Summary Regional sensory nerve transfer appears safe and effective for therapeutic management of neurotrophic keratopathy. Prospective randomized clinical trials are necessary to confirm the utility of corneal neurotization.

Background Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. Methods An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. Results There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. Conclusions These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.

Dumbbell-shaped trigeminal schwannoma afflicts the middle and posterior cranial fossa. Surgical approach for gross total resection remains highly challenging. The authors present a case of dumbbell-shaped trigeminal schwannoma treated successfully by using frontotemporal intradural approach with the removal of temporal pole. Subtotal resection was achieved as the schwannoma was closely adhered to trigeminal nerve. As a postoperative complication, abducens paralysis recovered significantly within the 3-month follow-up. No severe complication was observed. The authors suggest that frontotemporal intradural approach is optimal surgical approach as it is particularly convenient and safe.

Background and importance Hypertrophic interstitial neuropathy (HIN) is an uncommon, non-neoplastic lesion typically affecting peripheral nerves. Cranial nerve (CN) involvement is exceedingly rare. We present a case of isolated trigeminal nerve HIN manifesting with V3 distribution neuralgia. Clinical presentation A 50-yr-old male presented with left sided trigeminal neuralgia refractory to medical management. The patient underwent retromastoid craniectomy for possible microvascular decompression. Intra-operatively, the trigeminal nerve appeared to be focally enlarged with a sausage-like configuration. We selectively resected 1 fascicle which was predominantly involved. Histopathological examination revealed onion bulb formations composed of Schwann cells around centrally placed axons. A diagnosis of HIN was made. Postoperatively, the patient experienced complete resolution of symptoms. Conclusion This is the third case of isolated trigeminal nerve HIN in the literature. We performed a selective resection in a patient presenting with trigeminal neuralgia, resulting in complete resolution of symptoms. It is reported here with intraoperative microscope images, along with a review and analysis of this topic as it related to CN.

Background Several therapeutics have been proposed for neurotrophic keratitis, but no direct comparison among different approaches is available. Objective To compare treatment-related problems and outcomes of both traditional and novel therapeutics for neurotrophic keratopathy, focusing on resolution rate, healing time, and recurrence rate. Data sources Literature search of published studies between 1980 and 2019 on neurotrophic keratopathy available on PubMed was made without any language constraints but limited to human study participants. Study selection All published peer-reviewed open, blinded and randomized clinical trials, case series and case reports, divided according to evidence level, were reviewed and resolution rate, healing time, relapses of the disease, and visual outcomes were evaluated. Data extraction and synthesis Single observer data extraction. Main outcomes and measures resolution rate, healing time, recurrence rate. Results Human recombinant Nerve Growth Factor eye drops, Serum Tears and Substance P showed comparable resolution rate in patients with neurotrophic keratopathy. Amniotic membrane transplantation and Nerve Growth Factor eye drops are associated with a faster healing time among available treatments. Nerve Growth Factor eye drops clinical trial are the only study with evidence level 1, hence randomized and controlled. Conclusions and relevance Several new treatment options are available for patients with neurotrophic keratitis with adequate safety.

Background Trigeminal schwannomas are fifth cranial nerve tumors that originate from the nerve sheath. They rarely occur within the pediatric population and can cause dysfunction of the trigeminal nerve and surrounding structures. When patients become symptomatic, neurosurgeons should consider resection. Case Desription We report the case of a 14-year-old adolescent boy who presented with an isolated sixth nerve palsy manifested by diplopia. The patient was found to have a trigeminal schwannoma involving the ophthalmic and maxillary branches of the trigeminal nerve. A modified mini-pterional craniotomy was performed for an extended middle fossa approach with an anterior petrosectomy to gain access to the inferior aspect of the posterior fossa tumor component. Intraoperatively, the sixth nerve was compressed within Dorello's canal. Postoperatively, the patient's sixth nerve palsy resolved, and magnetic resonance imaging demonstrated near-total resection with residual enhancement along the superior orbital fissure near the oculomotor nerve entry zone and foramen rotundum. Conslusions We present a rare case of pediatric trigeminal schwannoma type Mp treated surgically with a near-total resection via a novel mini-pterional approach and use of cranial nerve diffusion tensor imaging.

Trigeminal nerve pathology can lead to sensory and motor dysfunction to structures of the head that are easily recognized. The trigeminal nerve is a conduit for the distribution of postganglionic parasympathetic innervation to structures of the head. Parasympathetic innervation to the salivary glands is provided by preganglionic parasympathetic neurons of the facial and glossopharyngeal nerves. Postganglionic axons course with branches of the mandibular branch of the trigeminal nerve to reach the salivary glands. Denervation of the salivary glands impacts glandular function, leading to a reduction in the volume and composition of the saliva produced. Saliva plays an important role in oral health. Poor oral health has widespread systemic implications. This article describes a group of dogs with unilateral or bilateral dysfunction of the trigeminal nerve and/or its branches. In all dogs, an accumulation of thick, foamy saliva was observed accumulating in the dorsal aspect of the caudal oral cavity on the ipsilateral side to the affected nerve. In dogs with magnetic resonance imaging (MRI), there was a reduction in size based on the largest cross-sectional area measurement and an increase in mean signal intensity of the salivary glands ipsilateral to the affected nerves compared to the glands on the normal side. The authors hypothesize that the abnormal saliva and MRI changes observed were consequent to parasympathetic denervation of the salivary glands. The recognition of this clinical observation is the first step in understanding the impact that denervation has on salivation and ultimately on overall oral and systemic health in dogs.

Purpose The aim of this study was to report a case of central neurotrophic keratopathy (NK) in Wallenberg syndrome (WS) and its successful management with topical recombinant nerve growth factor (rNGF). Methods A 47-year-old man with WS caused by a stroke in the territory of the left vertebrobasilar artery complained of progressive visual loss in his left eye (OS). Examination showed corneal anesthesia associated with a corneal epithelial ulceration consistent with a diagnosis of NK grade 3 of central origin. Topical treatment with rNGF, 1 drop 6 times daily, was started for 8 weeks, and the patient was followed up for 1 year. Results Topical treatment with rNGF was successful in promoting complete epithelial corneal healing. No recurrence was seen at 1-year follow-up. Conclusions Clinicians should be aware that visual loss can also occur from NK of central origin. To the best of our knowledge, this is the first case report of NK caused by WS successfully treated with rNGF reported in the literature.

Background Both the pterygopalatine fossa (PPF) and the infratemporal fossa (ITF) lie outside the midline of the skull base. Lesions in the PPF or ITF include trigeminal schwannoma (trigeminal schwannoma, TS), which originates from the second or third branch of the trigeminal nerve (maxillary nerve or mandibular nerve). Due to their typically deep anatomic location, lesions in the PPF or ITF can be difficult to treat using traditional surgical approaches. In recent years, because of their advantages, which include the fact that they allow the problem to be observed close up, neuroendoscopic techniques are increasingly being applied in skull base surgery, especially in treatment of lesions around the midline of the base of the skull. This study aims to 1) evaluate the neuroendoscopic treatment of lesions in PPF or ITF via the transnasal palate bone perpendicular plate or transnasal maxillary sinus approach and 2) analyze the clinical significance of this approach. Methods We retrospectively analyzed 3 cases of PPF TSs and 1 case of ITF TS treated between January 2015 and May 2017. All of the cases underwent neuroendoscopic resection of TSs located in the PPF via the nasal perpendicular plate palatine bone (or nasal maxillary sinus) approach. Results Two cases of PPF TSs were characterized by a thin palate bone perpendicular plate due to oppressed absorption of the tumor. Therefore the endoscopic transnasal palate bone perpendicular plate approach was employed. Additionally, 1 case of PPF TSs and 1 case of ITF TS were resected via the transnasal maxillary sinus approach. All 4 patients received total resection under endoscopy and recovered well after their respective operations without cerebrospinal fluid leakage, although 1 patient experienced postoperative dry eye symptoms and 1 other patient showed no improvement in facial numbness before and after the operation. Conclusions Neuroendoscopic surgery performed via the transnasal perpendicular plate palatine bone or transnasal maxillary sinus approach has its own unique advantages in removing TSs in PPF and in ITF: Notably, the tumor can be exposed and dealt with under direct vision, which prevents damage to important structures, such as the internal carotid and maxillary nerves, while at the same time helping to achieve total removal of TSs. Furthermore, by adopting this approach versus traditional skull base surgery, postoperative trauma can be reduced significantly, which should be advocated for in this time of minimal invasive surgery.

Objective To assess outcomes and complications of stereotactic radiosurgery treatment for trigeminal schwannoma (TS). Methods A retrospective analysis was performed to describe the presentation and outcomes of patients undergoing Gamma Knife radiosurgery (GKRS) for TS. Clinical, radiographic, and stereotactic radiosurgery dose plans were reviewed. Descriptive statistics and univariate analysis were performed to identify factors associated with poor tumor control. Results A total of 22 patients with TS were treated with GKRS between 1990 and 2018. One patient had a history of neurofibromatosis type II. Of the study population, 81% underwent GKRS as a first-line treatment. The average tumor volume was 3.3 cm3 and the average margin treatment dose was 14.1 Gy. The median clinical and radiographic follow-up period were 18.5 and 27 months, respectively. Tumor control was achieved in 17 patients (77.3%). Symptomatic improvement was noted in 8 patients (42.1%). Tumor expansion was observed in 7 patients (31.8%) and was associated with poor tumor control at last follow-up (P Conclusions GKRS provides effective control for most TS. Increased margin doses are associated with tumor expansion, which was a poor prognostic event associated with progression and clinical decline. Based on these results, combined with analysis of available data from other series of TS treated with GKRS, we believe that margin dose between 13 and 14 Gy offers a high probability of tumor control, yet minimizing risk of adverse radiation effects.

Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Treatment of the infraorbital nerve with neutralizing antibody HMGB1 (anti-HMGB1 nAb) before dIoN-CCI prevented both facial grooming and hyper-responsiveness to cooling. Pretreatment with anti-HMGB1 nAb also blocked immune cell activation associated with trigeminal nerve injury including the accumulation of macrophage around the injured IoN and increased microglia activation in the ipsilateral spinal trigeminal nucleus caudalis. The current findings demonstrated that blocking of HMGB1 prior to nerve injury prevents the onset of pain-related behaviors, possibly through blocking the activation of immune cells associated with the nerve injury, both within the CNS and on peripheral nerves. The current findings further suggest that blocking HMGB1 before tissue injury could be a novel strategy to prevent the induction of chronic pain following orofacial surgeries.

Purpose: This review provides an overview of the causes and treatment of neurotrophic keratopathy in the pediatric population.Methods: A thorough review of the current literature discussing neurotr...

Neurotrophic Keratitis (NK) is a degenerative disorder of the cornea characterized by decreased or absent sensory corneal innervation, corneal epitheliopathy and impaired healing.The clinical presentation of NK can range from persistent epithelial defects to corneal perforation and management is often both challenging and protracted. Historically, the management of NK has consisted of non-specific strategies to facilitate corneal epithelial healing such as lubrication, bandage contact lenses and tarsorrhaphy. Recent advances in the development of therapeutics for NK have provided new and efficacious targeted strategies for its management.In this article, we review recombinant human nerve growth factor (Cenegermin), currently approved for clinical use in the United States and Europe, as well as other promising therapeutic options that are in pre-clinical development such as thymosine beta 4, connexin43 inhibitors, and artificial extracellular matrix components.

Neurotrophic keratopathy is characterized by decreased corneal sensitivity, decreased reflex tearing, and poor corneal healing resulting in corneal injury. Without proper sensory innervation, the cornea undergoes continuous epithelial injury, ulceration, infection and eventually results in vision loss. In situations where patients have concomitant facial paralysis, such as after resection of a large vestibular schwannoma, the ocular health is further impaired by paralytic lagophthalmos with decreased eye closure and blink reflex, decreased tearing, and potential lower eyelid malposition. In patients with a dual nerve injury, the ocular surface is in significant danger, as there is increased environmental exposure in conjunction with the inability to sense damage when it occurs. Immediate recognition and care of the eye are critical for maintaining ocular health and preventing irreversible vision loss. The first modern corneal neurotization procedure was described in 2009. The ultimate goal in corneal neurotization is to establish sub-basal plexus regeneration via transferring a healthy nerve to the corneo-limbal region. Corneal neurotization can be achieved either via a direct transfer of healthy nerve (direct approach) or via nerve graft interpositions (indirect approach). This is an emerging concept in the treatment of neurotrophic/exposure keratitis and over the past decade multiple direct and indirect approaches have been described in the attempt to restore corneal sensation and to prevent the devastating outcomes of neurotrophic keratitis. Knowledge of these techniques, their advantages, and disadvantages is required for proper management of patients suffering from neurotrophic keratitis in the setting of facial paralysis.

Purpose To report a case of neurotrophic keratopathy (NK) in a patient with complex regional pain syndrome (CRPS) with ipsilateral facial involvement. Methods Case report. Results An 18-year old woman with a 5-year history of CRPS type I, a systemic disorder with a neuropathic component with associated limb and right facial involvement, presented with an insidious onset of blurred vision and pain in the right eye. Ocular examination revealed decreased corneal sensation, as measured by Cochet-Bonnet testing, associated with recurrent epithelial defects and whorl-like superficial corneal epitheliopathy. NK was suspected and confirmed by in vivo confocal microscopy (IVCM), which revealed rarefaction of the subbasal nerve plexus in the affected eye. To enhance corneal nerve health, plasma rich in growth factors drops were used. Persistence of NK prompted a superficial keratectomy with placement of an amniotic membrane graft and a course of cenegermin 0.002% (Oxervate; Dompe Farmaceutici SpA, Italy) in the postoperative period. This combination therapy resulted in successful epithelial closure and vision improvement after 8 weeks of therapy with no recurrence of disease for 11 months. Importantly, at that final visit, IVCM demonstrated growth of corneal nerves for the first time in this patient. Conclusions This is the first case report of NK occurring in the context of CRPS, a neuropathy with ipsilateral facial pain involvement. IVCM was important in the diagnosis of NK, which responded successfully to ocular surface treatments focused on nerve health stimulation that ultimately resulted in corneal nerve growth.

Purpose The aim of this study is to describe techniques, results, and open issues of corneal neurotization (CN) for the treatment of neurotrophic keratopathy (NK). Methods An overview of the most important studies of CN is provided. The 2 main surgical approaches (namely, direct CN and indirect CN) with specific advantages and disadvantages are described. The results regarding changes of corneal sensitivity and clarity, visual acuity, and in vivo confocal microscopy metrics are summarized. Ex vivo studies with histopathology of the neurotized cornea are reported. Intraoperative and early and late postoperative complications are described along with current open issues to be further clarified. Results Corneal sensitivity improves after both direct and indirect CN. Corneal reinnervation allows the healing of NK in almost the totality of the operated eyes, determining a corresponding improvement of corneal clarity and visual acuity. Regeneration of corneal nerve fibers is confirmed by means of either in vivo confocal microscopy or ex vivo histopathology. Few self-limiting complications are reported during the postoperative course. Current open issues concern the identification of the technique of choice, the use of autograft or allograft, and the timing of CN either when performed alone or when combined with other surgeries. Conclusions CN represents a game-changing surgical procedure for NK, which has the potential to restore corneal sensitivity in all stages of the disease regardless of the mechanism of denervation. Further long-term results are needed to confirm its efficacy over time. The design of randomized clinical trials comparing CN with noninterventional therapies could further validate the adoption of this technique.

Rationale: Treatment of chronic neuropathic pain in the head and face regions presents a challenge for pain specialists due to the lack of reliable medical and surgical approaches. Patient concerns: A 62-year-old patient came to our attention for an intense facial pain secondary to a lesion of the right trigeminal nerve (all branches) due to a petroclival meningioma. Diagnoses: The patient also presented with gait impairment as well as a deficit of the right facial, auditory, trochlear and abducens cranial nerves. Interventions: Conventional medical management (CMM) as well as tonic SCS were already adopted but they all dramatically failed. We intervened with the use of high-frequency (10 kHz) spinal cord stimulation (HFSCS) at the cervicomedullary junction (CMJ). The patient was thus provided with HFSCS at the CMJ. Pain and quality of life (QoL) were assessed 1 and 3 months after implantation. We also tested the trigeminal-facial reflex responses. Outcomes: HFSCS led to a full relief from the debilitating electric shocks like pain in the right hemiface, even though a background dull pain appeared. The gradual addition of pregabalin helped in fully relieving the painful symptomatology, with a significant improvement in QoL. Moreover, sensitivity amelioration on the inner portion of the mouth allowed the patient to start feeding again also using that side of the mouth. These findings were paralleled by a significant reshape of trigeminal-facial reflex responses suggesting an inhibition of nociceptive sensory inputs at brainstem level following HFSCS. Lessons: This is the first report suggesting the usefulness of HFSCS at the CMJ in neuropathic pain due to trigeminal nerve neuropathy non-responsive to tonic SCS and CMM.

Purpose We present a challenging case of a 9-year-old patient with refractory neurotrophic keratopathy (NK) who was successfully treated with cenegermin eye drops. Methods A 7-year-old boy developed an ocular infection after a visit to a public swimming pool. After having been unsuccessfully treated for 2 years with antibiotics, steroids, and artificial tears, the patient presented to our clinic with a therapy-refractory NK. We initiated treatment with autologous serum eye drops that showed only weak response. Therefore, treatment with cenegermin eye drops was started. Results After cenegermin therapy, a complete restoration of the corneal surface and an increase in visual acuity were achieved. Conclusions The use of cenegermin is effective in treating pediatric NK.

Objective The pattern of recurrence of large trigeminal neurinomas is analyzed on the basis of experience with 7 cases. Methods This is a report of 7 cases of large trigeminal neurinomas that were operated on an average of 11 years earlier. After being relatively asymptomatic over the years, these patients worsened relatively suddenly in their neurologic symptoms and were reoperated. Results Imaging showed massive recurrence with tumor having cystic and solid components with sizes ranging from 4.5–11 cm. In 4 cases, the cysts at the time of initial presentation and at the time of recurrence showed a well-defined fluid level within the fluid content of the cyst. During operation it was seen that the tumor contained “hemorrhagic” fluid that was under significant pressure. The solid component in the circumferential periphery of the cyst fluid was soft, necrotic, and vascular. The entire recurrence in the middle and posterior cranial fossa and in the extracranial compartment was “interdural” or within the dural confines. Radical tumor resection within the dural confines by deploying relatively small surgical exposure resulted in “unusually” rapid recovery in the symptoms. Histological examination of the tumor did not reveal any malignant transformation. Conclusions The cases add further insight to the growth pattern and characteristics of large trigeminal neurinomas.

Epidermoid cysts (ECs) are benign extraaxial tumors. They frequently occur at the cerebellopontine angle and parasellar regions. However, they rarely occur in the Meckel's cave. Typically, ECs appear as a hypointense mass on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI. However, ECs may occasionally present as hyperintense on T1-weighted imaging and hypointense on T2-weighted imaging. When this occurs, they are known as white epidermoid cysts. We present a case of a 25-year-old woman with a 3-month history of hypoesthesia in the distribution of the right trigeminal nerve. MRI showed a lesion located within the Meckel's cave. The MRI signal was heterogeneous, with hyperintense areas on T1-weighted images, being hypointense on T2-weighted imaging. Preoperative suspicion was trigeminal schwannoma with unusual radiologic features. Finally, the pathologic diagnosis was epidermoid cyst. Therefore to establish a proper preoperative diagnosis, one should be aware that ECs can occur in Meckel's cave and with unusual radiologic features, as occurred in the case described earlier.