OBJECTIVE: To systematically report and document Trigeminal Trophic Syndrome (TTS), characterize its clinical presentation, diagnostic tests performed, outline management strategies, outcomes; and highlight the role of otolaryngologists in the tissue diagnosis of this rare syndrome.
METHODS: PubMed/Medline, Scopus, and Cochrane databases.
METHODS: PubMed/Medline, Scopus, and Cochrane databases were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all cases of TTS published with an English translation from inception to December 2020.
RESULTS: A total of 142 articles describing 214 patients with TTS were included in the analysis. There was a female predominance (62.9 %) and a median age of 57 (range 1-93) years at presentation. A trigeminal neurological insult was identified in 200 (93.5 %) cases. The most common triggers for TTS were treatment for trigeminal neuralgia (35.7 %) and cerebrovascular accident (21.6 %). Self-inflicted trauma occurred in 137 (64 %) patients. Biopsy was done in 123 (57.5 %) patients. Patient education, barrier devices, and medications to address parasthesias were the most common treatment strategies. The majority of patients (72.5 %) received multimodal therapy. Surgery was performed in 35 (22.7 %) patients. Treatment outcomes were discussed in 120 (56.1 %) patients.
CONCLUSIONS: TTS is a rare condition with poorly understood pathophysiology. It should be suspected in a patient with non-healing facial ulceration and altered sensation within the trigeminal nerve distribution. Biopsy of the ulcer is important to confirm the diagnosis and exclude malignancy. Treatment options include conservative and pharmacologic measures, and less frequently surgery.

Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care. Protocol registration: PROSPERO ID: CRD42022348475.

Trigeminal schwannoma is an uncommon tumor in pediatric patients. Several surgical approaches have been described in the literature.
The case of an 11-year-old boy with a giant dumbbell-shaped trigeminal schwannoma removed through a 2-stage approach was presented with an intraoperative video. Using PubMed and Scopus, the literature on trigeminal schwannoma in pediatric patients was searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
The search strategy yielded 312 titles, of which 13 were included in the review. Cases of trigeminal schwannoma were described, with a highly variable clinical presentation and anatomical arrangement in cranial fossae. Two-stage approaches were reported, although most studies described single-stage approaches. Common postoperative outcomes were a range of disturbances of cranial nerve V.
The surgical approach varies based on the tumor conformation. However, a 2-stage pterional subtemporal and semisitting retrosigmoid approach is a safe, practical, and effective strategy for the removal of dumbbell-shaped trigeminal schwannoma in a pediatric patient.

OBJECTIVE: Chronic headache remains a major cause of disability and pain worldwide. Although the literature has extensively described pharmacologic options for headache treatment and prophylaxis, there remains a paucity of data on the efficacy of neuromodulation interventions for treatment of headache unresponsive to conventional pharmacologic therapy. The primary aim of this review was to appraise the literature for the efficacy of cervical spinal cord stimulation (cSCS) in treating any intractable chronic headache, including migraine headaches (with or without aura), cluster headache, tension headache, and other types of headaches.
METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed a systematic review by identifying studies in PubMed, Embase (Scopus), Web of Science, and Cochrane Central Register of Controlled Trials that assessed cSCS to treat chronic headache. Data were synthesized qualitatively, with primary outcomes of headache intensity and frequency. The secondary outcome was adverse effects.
RESULTS: In total, 16 studies comprising 107 patients met the inclusion criteria. Findings were presented based on type of headache, which included migraine headache with or without aura, cluster headache, trigeminal neuropathy, occipital neuralgia, posttraumatic headache, cervicogenic headache, short-lasting unilateral neuralgiform headache with autonomic symptoms, and poststroke facial pain. Per the Grading of Recommendations, Assessment, Development and Evaluations criteria, there was very low-quality evidence that cSCS is associated with a decrease in migraine headache frequency, migraine headache intensity, and trigeminal neuropathy intensity. Placement for cSCS leads ranged from C1 to C4.
CONCLUSIONS: Our review suggests promising data from observational studies that cSCS may be helpful in decreasing frequency and intensity of chronic intractable headache. Future well-powered, randomized controlled trials are needed.

Neurotrophic keratopathy (NK) is a rare degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia or anesthesia. Neurotrophic corneal ulcers are notoriously difficult to treat and can lead to blindness. Corneal neurotization (CN) is a recent surgical technique aimed at restoring corneal sensation and may offer a definitive treatment in the wake of NK. Herein, we review the surgical techniques utilized in direct and indirect CN. Technical considerations, outcomes, current limitations and future perspectives are also discussed. This article highlights the key points of this promising procedure and biological aspects that will help provide the best treatment options for patients with severe NK.

OBJECTIVE: The purpose of this study was to report the use of bilateral corneal neurotization for neurotrophic keratitis in the setting of Ramos-Arroyo syndrome.
METHODS: The case report and surgical technique are described in detail in this article, as well as a review of the literature on corneal neurotization for congenital corneal anesthesia.
RESULTS: We report a 17-year-old patient who underwent bilateral corneal neurotization for neurotrophic keratitis secondary to corneal anesthesia in Ramos-Arroyo syndrome. Corneal neurotization was performed with great auricular nerve transfers extended by sural nerve autografts.
CONCLUSIONS: We present the treatment of neurotrophic keratopathy with corneal neurotization in a patient with Ramos-Arroyo syndrome. We describe how bilateral corneal neurotization using the great auricular nerve technique is a safe and effective procedure for patients with congenital/developmental corneal anesthesia.

BACKGROUND Bell\'s palsy, also called facial nerve palsy, occasionally co-occurs with trigeminal neuropathy, which presents as additional facial sensory symptoms and/or neck pain. Bell\'s palsy has a proposed viral etiology, in particular when occurring after dental manipulation. CASE REPORT A 52-year-old Asian woman presented to a chiropractor with a 3-year history of constant neck pain and left-sided maxillary, eyebrow, and temporomandibular facial pain, paresis, and paresthesia, which began after using a toothpick, causing possible gum trauma. She had previously been treated with antiviral medication and prednisone, Chinese herbal medicine, and acupuncture, but her recovery plateaued at 60% after 1 year. The chiropractor ordered cervical spine magnetic resonance imaging, which demonstrated cervical spondylosis, with no evidence of myelopathy or major pathology. Treatment involved cervical and thoracic spinal manipulation, cervical traction, soft-tissue therapy, and neck exercises. The patient responded positively. At 1-month follow-up, face and neck pain and facial paresis were resolved aside from residual eyelid synkinesis. A literature review identified 12 additional cases in which chiropractic spinal manipulation with multimodal therapies was reported to improve Bell\'s palsy. Including the current case, 85% of these patients also had pain in the face or neck. CONCLUSIONS This case illustrates improvement of Bell\'s palsy and concurrent trigeminal neuropathy with multimodal chiropractic care including spinal manipulation. Limited evidence from other similar cases suggests a role of the trigeminal pathway in these positive treatment responses of Bell\'s palsy with concurrent face/neck pain. These findings should be explored with research designs accounting for the natural history of Bell\'s palsy.

UNASSIGNED: 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.

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.

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.