Hypoglossal Research Articles

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in a Young Child With Down Syndrome.

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.

Transoral robotic surgery with free flap reconstruction: Functional outcomes of 241 patients at a single institution.

Transoral robotic surgery (TORS) for oropharyngeal malignancy optimizes oncologic outcomes while preserving functionality. This study identifies patterns of functional recovery after TORS with free flap reconstruction (FFR). Retrospective cohort study at a tertiary care center of patients with primary oropharyngeal tumors treated with TORS with FFR between 2010 and 2022. Patients were categorized into: adjuvant chemoradiation or radiation, or no adjuvant therapy (NAT). Functional outcomes were measured by functional oral intake scale (FOIS). 241 patients were included. FOIS declined at first postoperative appointment (median = 7.0 to 2.0, IQR = [7.0, 7.0], [2.0, 4.0]), and progressively improved to 6.0 (5.0, 6.0) after 1 year, with NAT having the highest FOIS (7.0, p < 0.05). Predictors of poor long-term FOIS included RT and hypoglossal nerve (CN XII) involvement (p < 0.05). TORS with FFR leads to good long-term function with minimal intake restrictions. Radiation therapy and CN XII involvement increase risk of worse functional outcomes.

Isolated Unilateral Hypoglossal Nerve Palsy in a Man with Anterior Cervical Osteophyte (P9-4.008)

Isolated Unilateral Hypoglossal Nerve Palsy in a Man with Anterior Cervical Osteophyte (P9-4.008)

Hypoglossal Nerve Stimulation as a Treatment of Obstructive Sleep Apnea in Down Syndrome Patients: A Systematic Review and Meta-analysis (P7-11.007)

Hypoglossal Nerve Stimulation as a Treatment of Obstructive Sleep Apnea in Down Syndrome Patients: A Systematic Review and Meta-analysis (P7-11.007)

Gradenigo Syndrome With Facial and Hypoglossal Nerve Impairment Caused by Nontuberculous Mycobacteria Successfully Treated by Antibiotics Without Surgery.

Gradenigo Syndrome With Facial and Hypoglossal Nerve Impairment Caused by Nontuberculous Mycobacteria Successfully Treated by Antibiotics Without Surgery.

Response to Hypoglossal Nerve Stimulation Changes With Body Mass Index and Supine Sleep

Hypoglossal nerve stimulation (HGNS) is a potential alternative therapy for obstructive sleep apnea (OSA), but its efficacy in a clinical setting and the impact of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) on treatment response remain unclear. To investigate whether HGNS therapy is effective for patients with OSA, whether HGNS can treat supine OSA, and whether there are associations between BMI and treatment response. In this cohort study, adult patients with OSA implanted with HGNS at the Washington University Medical Center in St Louis from April 2019 to January 2023 were included. Data were analyzed from January 2023 to January 2024. HGNS. Multivariable logistic regression was performed to assess associations between HGNS treatment response and both BMI and supine sleep. Treatment response was defined as 50% reduction or greater in preimplantation Apnea-Hypopnea Index (AHI) score and postimplantation AHI of less than 15 events per hour. Of 76 included patients, 57 (75%) were male, and the median (IQR) age was 61 (51-68) years. A total of 59 patients (78%) achieved a treatment response. There was a clinically meaningful reduction in median (IQR) AHI, from 29.3 (23.1-42.8) events per hour preimplantation to 5.3 (2.6-12.3) events per hour postimplantation (Hodges-Lehman difference of 23.0; 95% CI, 22.6-23.4). In adjusted analyses, patients with BMI of 32 to 35 had 75% lower odds of responding to HGNS compared with those with a BMI of 32 or less (odds ratio, 0.25; 95% CI, 0.07-0.94). Of 44 patients who slept in a supine position, 17 (39%) achieved a treatment response, with a clinically meaningful reduction in median (IQR) supine AHI from 46.3 (33.6-63.2) events per hour preimplantation to 21.8 (4.30-42.6) events per hour postimplantation (Hodges-Lehman difference of 24.6; 95% CI, 23.1-26.5). In adjusted analysis, BMI was associated with lower odds of responding to HGNS with supine AHI treatment response (odds ratio, 0.39; 95% CI, 0.04-2.59), but the imprecision of the estimate prevents making a definitive conclusion. This study adds to the growing body of literature supporting the use of HGNS for OSA treatment. Sleep medicine clinicians should consider informing patients that higher BMI and supine sleeping position may decrease therapeutic response to HGNS. Future research is needed to replicate these findings in larger, more diverse cohorts, which would facilitate the optimization of treatment strategies and patient counseling for HGNS therapy.

Physician self-reported knowledge of and barriers to indication of alternative therapies for treatment of obstructive sleep apnea

Abstract Background Obstructive sleep apnea (OSA) is a common disease with significant implications for individual physical and mental wellbeing. Though in theory, OSA can be effectively treated with positive airway pressure therapy (PAP), many patients cannot adhere chronically and require alternative treatment. With sleep physicians being relevant stakeholders in the process of allocation of OSA treatments, this research aims to study their knowledge and perceptions of alternative therapies available in routine care in Germany. Methods This work is part of a larger research project which aims to assess the state of sleep medical care in Germany. Items relevant to this study included self-reported knowledge, indication volumes, and perceptions of five alternative treatments for OSA, which are available for routine care in Germany. Results A total of 435 sleep physicians from multiple medical disciplines and both care sectors participated in the study. Self-reported knowledge on alternative OSA treatments was moderate and correlated with the consultation volume. Self-reported adoption of alternative therapies was higher in nonsurgical methods, and only 1.1% of participants reported not utilizing any of the alternative treatments. The most relevant perceived barriers to indication were “reimbursement issues” for mandibular advancement devices and positional therapy; “evidence insufficient” for upper airway surgery, and “no demand from patients” for hypoglossal nerve stimulation and maxillomandibular Advancement. Conclusion Self-reported knowledge of alternative OSA treatments is moderate and indication of alternative OSA therapies varies substantially. Sleep physicians often perceive barriers that limit provision or referrals for provision of these treatments. Additional research is required to further understand barriers and factors influencing creation of those perceptions and decision-making among physicians.

454 Utilization of Adipose-Derived Stem Cells in Cranial Nerve Regeneration: A Systematic Review

INTRODUCTION: Large peripheral nerve injuries may require surgical reconnection. Cell-based therapies have also been investigated for nerve regeneration. METHODS: PubMed and Embase databases were used to search for primary studies reporting the use ADSCs in the regeneration of cranial nerves. A total of 12 studies were included which all presented data on specific neural injury, therapy, and functional outcomes. RESULTS: Eight studies focused on the facial nerve (66.7%), two on the optic nerve (16.7%), one on the olfactory nerve (8.3%), and one on the hypoglossal nerve (8.3%). One study applied ADSCs to human cranial nerve injuries, while the remainder studied animal models. In these studies, ADSC groups had higher numbers of myelinated fibers, increased myelin thickness and diameter of muscle fibers as well as greater magnitude of compound muscle action potentials (CMAP) when compared to controls. In studies focused on optic nerve regeneration, significant improvements across visual tests were observed. CONCLUSIONS: ADSCs demonstrate potential utility in regard to their ability to facilitate functional recovery of cranial nerves in humans as well as animal models. Further investigation into the use of ADSC should be pursued in both animal and early human studies to validate the findingsof previous literature.

Relationship of Nocturnal Insomnia Symptoms and Outcomes After Hypoglossal Nerve Stimulation.

In patients undergoing hypoglossal nerve stimulation (HGNS), we examined the Insomnia Severity Index (ISI) to understand how baseline sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), and early morning awakening (EMA) affected postsurgical outcomes. Observational. Multicenter registry. We included patients from the Adherence and Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea International Registry (ADHERE) with a baseline ISI from 2020 to 2023. Regression analysis examined the association of ISI question scores for SOI, SMI, and EMA and outcomes: Apnea-Hypopnea Index (AHI) reduction, device usage, changes in the Epworth Sleepiness Scale (ESS) and overall ISI score, final visit (FV) completion, and satisfaction. No relationship was noted between insomnia subtypes and AHI reduction or FV completion. In the subgroup of patients with baseline moderate/severe insomnia, patients with major impairment for SOI used their device 64 min/day longer than those with minimal impairment. Amongall patients, those with baseline major impairment for SOI had a 2.3 points greater improvement in ISI from baseline to FV compared to patients with minimal impairment, while patients with baseline major impairment for SMI had a 2.0 and 3.5 points greater improvement in the ESS and ISI than those with minimal impairment. Patients with EMA and moderate/severe baseline insomnia had decreased odds of being satisfied after surgery. In ADHERE, nocturnal symptoms of insomnia did not limit HGNS efficacy or therapy use. Conversely, those with worse insomnia subtype impairments at baseline had improved outcomes related to adherence, sleepiness, and insomnia at the FV.

Role of Facial Nerve Reconstruction With Anastomosis and Polyglycolic Acid Tube in Accelerating Functional Recovery After Axotomy in the Rat Facial Nucleus.

Facial nerve injuries stem from trauma or tumor surgery, triggering neurodegeneration and neuronal cell death in the facial nucleus, consequently inducing irreversible nerve paralysis. Following facial nerve transection, glial cells are activated and undergo proliferation, facilitating motor neuron survival, repair, and regeneration. Clinical approaches, including nerve anastomosis and hypoglossal nerve grafting, require delicate microscopic techniques. Recent advancements involve nerve reconstruction using polyglycolic acid (PGA) tubes, which yield nerve function improvement. However, the central pathophysiological effects of these procedures remain unclear. Therefore, using PGA tubes, we evaluated neurodegeneration and microglial inflammatory response in rats after facial nerve transection. Facial nerve functions were evaluated using vibrissae and blink reflex scores. In the end-to-end anastomosis and PGA tube reconstruction groups, a partial improvement in facial motor function was observed, with increased nerve fiber survival in the former. Approximately 90% of neurons survived in both groups, wherein gliosis exhibited increased microglial activation compared to that in the transection group. These results indicate that PGA tube-assisted nerve reconstruction post-facial nerve transection, although inferior to end-to-end anastomosis, improved certain functions and prevented neuronal cell death. Furthermore, the prolonged inflammatory response in the facial nerve nucleus underscored the correlation between neuronal function and survival and microglia.

Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy.

Differences in the pharyngeal site-of-collapse influences efficacy of non-CPAP therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site-of-collapse using overnight polysomnography. 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow-shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, N=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (N=22) versus absence (N=128) of CCCp (partial collapse and concurrent tongue-base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue-base, or epiglottis collapse. External validation was performed on a separate dataset (Ntotal=466). CCCp was characterised by greater scoopiness (β=1.5±0.6 per 2SD, multivariable estimate±se) and skewness (β=11.4±2.4) compared to non-CCCp. Odds ratio [95%CI] for CCCp in predicted positive versus negative subgroups was 5.0[1.9-13.1]. The same characteristics provided significant cross-validated prediction of lateral wall (OR=6.3[2.4-16.5]), tongue-base (3.2[1.4-7.3]), and epiglottis (4.4[1.5-12.4]) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue-base and epiglottis collapse characteristics. External validation confirmed model prediction. The current study provides a means to recognise patients with likely CCCp or other DISE-based site-of-collapse categories using routine polysomnography. Since site-of-collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.

Altered tongue muscle contractile properties coincide with altered swallow function in the adult Ts65Dn mouse model of down syndrome.

Down syndrome (DS) is a developmental disability associated with difficulties in deglutition. The adult Ts65Dn mouse model of DS has been previously shown to have differences in measures of swallowing compared with euploid controls. However, the putative mechanisms of these differences in swallowing function are unclear. This study tested the hypothesis that the Ts65Dn genotype is associated with atypical measures of tongue muscle contractile properties, coinciding with atypical swallow function. Adult (5-month-old) Ts65Dn (n = 15 female, 14 male) and euploid sibling controls (n = 16 female, 14 male) were evaluated through videofluoroscopy swallow studies (VFSS) to quantify measures of swallowing performance including swallow rate and inter-swallow interval (ISI). After VFSS, retrusive tongue muscle contractile properties, including measures of muscle fatigue, were determined using bilateral hypoglossal nerve stimulation. The Ts65Dn group had significantly slower swallow rates, significantly greater ISI times, significantly slower rates of tongue force development, and significantly greater levels of tongue muscle fatigue, with lower retrusive tongue forces than controls in fatigue conditions. Tongue muscle contractile properties are altered in adult Ts65Dn and coincide with altered swallow function.

Impact of Hypoglossal Nerve Stimulation on Consumer Sleep Technology Metrics and Patient Symptoms.

Obstructive sleep apnea (OSA) is usually assessed at discrete and infrequent timepoints. Wearable consumer sleep technologies (CST) may allow for more granular and longitudinal assessments of OSA therapy responses and OSA-related symptoms. In this case series, we enrolled hypoglossal nerve stimulator (HGNS) patients who had an effective treatment response for an 8-week study using a wearable CST. Participants started with "HGNS-on," were randomized to turn off HGNS therapy during either week 4 or 5 ("HGNS-off"), followed by a return to therapy, "HGNS-resume." Participants completed validated symptom questionnaires assessing sleepiness, insomnia symptoms, functional status, and overall sleep health (Satisfaction, Alertness, Timing, Efficiency, and Duration, SATED) each week. CST metrics and survey scores were compared between HGNS treatment phases. Associations between CST metrics and survey scores were assessed. Seven participants with a total of 304 nights of CST data showed no statistically significant changes in total sleep time (TST), wake time after sleep onset, or sleep efficiency (SE) across the study periods. During HGNS-off, survey scores indicated significantly worsened OSA-related symptom scores. Two participants had significantly higher heart rate variability (HRV) during HGNS-off (by 3.3 and 6.3 ms) when compared to HGNS active therapy periods. Amongst CST metrics, SATED scores correlated with TST (r = 0.434, p < 0.0001), HRV (r = -0.486, p < 0.0001), and SE (r = 0.320, = 0.0014). In addition, FOSQ-10 scores correlated with average HR during sleep (r = -0.489, p < 0.001). A 1-week HGNS therapy withdrawal period impacted OSA-related sleep symptoms. Sleep-related metrics measured by a wearable CST correlated with symptom scores indicating potential value in the use of CSTs for longitudinal sleep-tracking in OSA patients. 4 Laryngoscope, 134:3406-3411, 2024.

Solitary Fibrous Tumor of Nasal Cavity: A Case Report.

Solitary fibrous tumors (SFTs) belonging to a distinct group of mesenchymal tumors, was originally described by Klemper and Rabin in the pleura in year 1931. However, it can also be extra-pleural in origin. With tongue being the most common site involved in this region, epiglottis, larynx, thyroid, external auditory canal, lacrimal sac, hypoglossal nerve, parotid gland, sublingual gland, Para pharyngeal space, nasopharynx, scalp, gingiva, orbit and infratemporal fossa as well as paranasal sinuses and nasal cavities can also get involved. But SFTs involving nasal cavities and nasopharynx are quite uncommon, accounting for < 0.1% of all Sino-nasal neoplasms. Until now there have only been 40 cases of nasal SFT reported in literature. We report the case of an extraserosa solitary fibrous tumor arising from the nasal cavity with extension to the sphenoid sinus, a much rarer presentation of its type. Our case report is one of its type, emphasizing the need conducting further studies on the nature and management of the disease.

Epidemiology and risk factors for extension of necrotizing otitis externa.

Necrotizing otitis externa (OEN) is an aggressive and morbid infection of the external acoustic meatus. What are the risk factors for OEN extension? French monocentric retrospective study (2004-2021), including patients with OEN defined by the association of an inflamed EAM, a positive nuclear imaging, the presence of a bacteriological sample and the failure of a well-followed local and/or general antibiotic treatment. OEN was extensive if it was associated with vascular or neurological deficits, if nuclear imaging fixation and/or bone lysis extended beyond the tympanic bone. Our population (n = 39) was male (74%), type 2 diabetic (72%), aged 75.2years and pseudomonas aeruginosa was found in 88% of cases. Complications for 43% of patients were extensive fixation on nuclear imaging, for 21% of them the presence of extensive bone lysis, for 13% the appearance of facial palsy, for 5.3% the presence hypoglossal nerve palsy and for 2.5% the presence of thrombophlebitis or other nerves palsies. 59% of our population had extensive OEN. The diagnosis of the extensive OEN was made 22days later (p = 0.04). The clinical presentation was falsely reassuring due to easier identification of the tympanic membrane (70% vs 46%, p = 0.17) but associated with periauricular oedema (42% vs 0%), bone exposure (16% vs 0%) and a temporomandibular joint pain (41% vs 12%). Delayed treatment of OEN, identification of clinical bone lysis, especially when the tympanic membrane is easily visualized, and the presence of unbalanced diabetes are potential risk factors for extension of OEN.

Safety and Efficacy of Intravenous Thrombolysis for Ischemic Stroke in Elderly Patient with Thrombocytopenia

Introduction: Stroke remains as one of the diseases with a high mortality and morbidity which could be prevented by a prompt and concise treatment. Intravenous thrombolysis (IV-rTPA) is the mainstay treatment for hyperacute ischemic stroke with onset less than 4.5 hours. However, there are several contraindications that should be monitored, one of them being thrombocytopenia. We would like to report the use of IV-rTPA in geriatric patient with thrombocytopenia to highlight the efficacy and safety profile of the drug. Case Report: A 85-year-old woman was admitted to the emergency ward with weakness on the left extremities, slurred speech, and right-upward gaze of the eyes one hour prior to the admission in ER. Her history was significant for hypertension and type II diabetes mellitus. Physical examination revealed a muscle strength of +5/+1, left 7th and 12th cranial nerves palsy, a NIHSS score of 15, and a RACE score of 7. The laboratory result was significant for thrombocytopenia (96.000/μl). IV-rTPA was administered and two hours later, we noticed an improvement of the patient’s NIHSS score to 11. During the IV-rTPA administration, we noted a minor gum bleed, which was considered insignificant. The patient was admitted to the ICU and observed for the next 72 hours. No signs of bleeding or clinical deterioration were observed during that period. Discussion: Numerous studies have confirmed the efficacy of IV-rTPA in acute ischemic stroke if administered before 4,5 hours of onset. Thrombocytopenia is known as a contraindication of IV-rTPA which may increase the risk of bleeding. In this case, IV-rTPA is administered due to hyperacute onset and no known history of bleeding, even though the platelet count was low. Therefore, IV-rTPA may be considered if the benefits outweigh the risks with a thorough monitoring of the patient’s condition.

The Present and Future of the Clinical Use of Physiological Traits for the Treatment of Patients with OSA: A Narrative Review.

People with obstructive sleep apnea (OSA) are a heterogeneous group. While many succeed in the treatment of their OSA, many others struggle with therapy. Herein, we discuss how anatomical and physiological factors that cause sleep apnea (OSA traits) impact treatment response and may offer an avenue for more precise care. These OSA traits, including anatomical (upper-airway collapsibility) and physiological (loop gain, airway muscle responsiveness, and arousal threshold) factors, may help determine who can succeed with continuous positive airway pressure, oral appliances, hypoglossal nerve stimulation, or pharmacotherapy. In the future, identifying OSA traits before initiating treatment may help guide the selection of the most effective and tolerable therapy modalities for each individual.

Defining the Shape of the Mylohyoid Muscle: A Morphometric Imaging Study.

Implantable hypoglossal nerve stimulation (HNS) therapy is an evolving therapeutic alternative for patients with refractory obstructive sleep apnea (OSA). The muscular anatomy of this region has implications for surgical access through this zone as well as positioning and anchoring of hardware in this area. The purpose of this study was to radiologically describe the topography of the mylohyoid muscle and adjacent structures across a wide age spectrum. We retrospectively evaluated computed tomography scans of the neck in 102 patients who were imaged for reasons unrelated to the floor of mouth or submental space. Patients with prior surgery or pathology in the area of interest were excluded. Fourteen relevant muscle measurements were made on a midline sagittal image and a coronal image positioned at the midpoint between the hyoid bone and the mandible. We included 49 men and 53 women with an average age of 44 years (range 19-70). The average mylohyoid length was 42 mm; the average distance between the anterior digastric bellies was 17 mm. The average angle of the central mylohyoid was 174° in the sagittal plane and 164° in the coronal plane. Several measurements were significantly correlated with patient age, including the angle measurements and the distance between the digastric muscles. Aberrant digastric anatomy was common. The mylohyoid muscle has multiple radiologically distinct segments with predictable curvatures. An understanding of submental muscular anatomy, along with its variability between patients, may be beneficial to the development of bilateral implantable neurostimulation technology for the treatment of refractory OSA. N/A Laryngoscope, 134:2970-2975, 2024.

Ranula Plunging Cervical Approach a Case Report

Background: Ranulas are pseudocystic lesions resulting from an obstruction or disruption of the sublingual gland duct. They may be of congenital origin or occur secondary to immunological disorders, sialolithiasis, trauma or tumor lesions. The symptoms they cause may be pain or difficulty when speaking or swallowing. Treatment is removal or sclerosis of the pseudocyst. In the present work we present the case of a teenage patient with a ranula that extends to the right submandibular region. A cervicotomy was indicated that allowed the total resection of the ranula simultaneously with the sublingual and submandibular glands without affecting the hypoglossal and marginal nerves mandibular or lingual.

Extracranial transport of brain lymphatics via cranial nerve in human

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium.The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.