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A 14-year-old spayed female Miniature Pinscher presented with tongue curling, dysphagia, hypersalivation, and sublingual gland swelling. Comprehensive evaluation, including neurologic and musculoskeletal examinations, blood work, and urinalysis, revealed no abnormalities other than tongue-related signs. Magnetic resonance imaging (MRI) revealed a multilobed cystic structure in the occipito-atlanto-axial joint, compressing the right hypoglossal canal. The lesion appeared cerebrospinal fluid (CSF)-like on T1-weighted and T2-weighted images, and hyperintense compared with CSF on fluid-attenuated inversion recovery T2-weighted images. The scans suggested mucinous content with enhanced peripheral areas on contrast-enhanced images. Surgical removal and drainage of this cyst were performed, and clinical signs improved markedly. The dorsal cyst was tentatively diagnosed as a ganglion cyst based on histopathologic and imaging findings. Ganglion cysts should be considered in the differential diagnosis for dogs with similar MRI findings and neurologic signs.

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OBJECTIVE: This review summarizes the approaches to pediatric sialorrhea management from least-to-most invasive: non-pharmacological management, anticholinergic medications, botulinum neurotoxin, non-invasive surgery, and invasive surgical intervention. REVIEW METHODS: An electronic literature review identified English-language articles on sialorrhea management in pediatric patients. Publications between 1982 and 2022 were used, with a focus on articles published from 2012 to 2022. Additional augmentation of pharmacologic information was obtained from the latest editions of medical textbooks supplemented with official package inserts of investigated medications. CONCLUSIONS: Sialorrhea is abnormal in patients greater than four years of age. Severe cases warrant intervention to improve patient quality of life and reduce caregiver burden. Management starts with conservative approaches. Viable candidates begin with non-pharmacological management options. Anticholinergic medications can decrease saliva production, but adverse side effects may outweigh benefits. Botulinum neurotoxin injection of the salivary glands decreases salivary flow rate; however, relief is transient and thus multiple treatments are required. Non-invasive sclerotherapy is an emerging treatment option showing promising results for sialorrhea. In contrast, surgical intervention is reserved as a last-resort treatment for patients with severe symptoms, due to its higher risk for adverse consequences. IMPLICATIONS FOR PRACTICE: Physicians should be familiar with the different pediatric sialorrhea management options, including advantages and disadvantages, to adequately facilitate shared decision making with caretakers of pediatric patients who require treatment.

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During the process of the multiple sclerosis (MS), persons with multiple sclerosis (PwMS) may experience drooling (sialorrhea) issues that are frequently disregarded. The exact cause of drooling in PwMS is poorly understood. This study aims to assess potential risk factors for drooling seen in PwMS. The study included 20 PwMS with drooling and 19 PwMS without drooling. The participants' sociodemographic data and clinical parameters were noted. To evaluate dysphagia, fatigue, and hypersalivation, the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS), the Fatigue Severity Scale (FSS), and objective saliva flow rate measurement with cottons placed in Stensen ducts and under the tongue (swab test) were used, respectively. The study employed univariate and multivariate logistic regression models to identify the risk factors linked to drooling. Gender, age, disease duration, MS type, and Expanded Disability Status Scale scores did not differ between the two groups. There was a significant increase in the DYMUS and submandibular/sublingual (SM/SL) saliva flow rate values in PwMS with drooling (p = 0.009 and p = 0.019, respectively). However, in our study, hypersalivation was not observed in PwMS with or without drooling. In the univariate model, DYMUS, SM/SL saliva flow rate, and FSS were found to be risk factors for drooling in PwMS. But only DYMUS was shown to be a significant risk factor in the multivariate model obtained by the backward (Wald) elimination method (p = 0.023). Finally, our research is the first to demonstrate the relationship between drooling and the presence of dysphagia symptoms in PwMS. This is a very important study to determine the nature of drooling in PwMS. This finding shows that our study will serve as a reference for choosing the best method for drooling treatment.

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Sialorrhea, defined as an excess flow of saliva or excessive secretions, is common in patients with cerebral palsy and other neurologic disorders and is associated with clinical complications such as increased risk of local skin reactions, infections, aspiration, pneumonia, and dehydration. Upon failure of non-pharmacologic measures, clinicians have several noninvasive pharmacologic options available to manage sialorrhea. This review of the literature provides detailed descriptions of medications used, efficacy, safety, and practical considerations for use of non-injectable pharmacologic agents. The literature search included published -human studies in the English language in PubMed and Google Scholar from 1997 to 2022. Relevant citations within articles were also screened. A total of 15 studies representing 719 pediatric patients were included. Glycopyrrolate, atropine, scopolamine, and trihexyphenidyl all have a potential role for sialorrhea management in children; however, glycopyrrolate remains the most studied option with 374 (n = 52.0%) of the 719 patients included in the systematic review receiving this medication. Overall, glycopyrrolate showed similar efficacy but higher tolerability than its comparators in 2 comparative studies and is often considered the first-line agent. Patient-specific (age, route of administration) and medication-specific (dosage formulation, medication strength) considerations must be weighed when initiating a new therapy or switching to another medication upon treatment failure. Owing to the high propensity of adverse events with all agents, clinicians should consider initiating doses at the lower end of the dosage range, as previous studies have noted a dose-dependent relationship.

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Introduction: Hypersalivation has been associated with Rolandic epilepsy and other childhood epilepsy syndromes. However, pure salivatory seizures are a rare type of focal seizure in which ictal hypersalivation is the dominant feature throughout the seizures. Case presentation: We present a case of pure salivatory seizures originating from the right post-central operculum cortex, confirmed by the favorable surgical outcome. We attempt to analyze the symptom from behavioral and neural network perspectives and propose a possible mechanism to generate ictal hypersalivation and pure salivatory seizures. Conclusion: Based on previous reports in the literature and our case, we emphasize the importance of the operculum in patients with ictal hypersalivation, particularly in patients with pure salivatory seizures.

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OBJECTIVES: Clozapine, an atypical antipsychotic used to treat people with schizophrenia, has been proposed as a possible treatment for salivary gland hypofunction. This scoping review investigated the available literature on clozapine's impact on salivary flow, in order to determine whether it could be used by dental practitioners in low doses as a treatment for dry mouth. DATA SOURCES: An electronic search was completed using Ovid MEDLINE (1996 to Nov 2021). Key MeSH search terms included "clozapine," "Clozaril," "salivation," "salivary flow rate," "sialorrhea," "hypersalivation," and "drooling." Two reviewers independently reviewed eligible articles and extracted the data based on the inclusion and exclusion criteria. RESULTS: The initial search identified 129 studies, six of which were included in this review. Four of them (one cross-sectional and three interventional) described salivary flow rates in schizophrenic patients taking clozapine, while one of those and two others focused on the mechanism of clozapine-induced sialorrhea, with one study covering both. There were mixed findings, with one study observing a moderate association between clozapine dose and salivary flow, and the others reporting no differences. Findings on the putative mechanisms for clozapine-induced sialorrhea (CIS) were inconclusive. CONCLUSION: There is insufficient high-quality information to justify using low-dose clozapine to increase salivary flow in dental patients with salivary gland hypofunction. Well-designed interventional studies and randomized control trials are required.

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Parkinson's disease (PD) is a chronic, progressive neurological disorder and the second most common neurodegenerative condition. We report three common but overlooked symptoms in PD-hiccups, hypersalivation, and hallucinations-in terms of their prevalence, pathophysiology, and up-to-date evidence-based treatment strategies. Whilst all these three symptoms do occur in many other neurological and non-neurological conditions, early recognition and treatment are paramount. Whilst hiccups affect 3% of healthy people, their rate of occurrence is higher (20%) in patients with PD. Hypersalivation (Sialorrhea) is another common neurological manifestation of many neurological and other neurodegenerative conditions such as motor neuron disease (MND), with a median prevalence rate of 56% (range: 32-74%). A 42% prevalence of sialorrhea is also reported in sub-optimally treated patients with PD. Hallucinations, especially visual hallucinations, are commonly reported, with a prevalence of 32-63% in PD, and a 55-78% prevalence is noted in patients with dementia with Lewy bodies (DLB), followed by tactile hallucinations, which are indicated by a sensation of crawling bugs or imaginary creatures across the skin surface. Whilst mainstay and primary management strategies for all these three symptoms are carried out through history taking, it is also essential to identify and treat possible potential triggers such as infection, minimise or avoid causative (such as drug-induced) factors, and especially carry out patient education before considering more definitive treatment strategies, such as botulinum toxin therapies for hypersalivation, to improve the quality of life of patients. This original review paper aims to provide a comprehensive overview of the disease mechanisms, pathophysiology, and management of hiccups, hypersalivation, and hallucinations in Parkinson's disease.

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BACKGROUND: Hypersalivation is a major side-effect of clozapine in patients with treatment-resistant schizophrenia. AIMS: We investigated the efficacy of topical anticholinergic formulation sofpironium bromide gel for improving hypersalivation in patients with treatment-resistant schizophrenia receiving clozapine. METHOD: A double-blind, controlled crossover study was conducted with sofpironium bromide gel and a placebo gel to treat clozapine-induced hypersalivation in 16 patients with treatment-resistant schizophrenia. Patients were randomly divided between groups A and B (each n = 8). Group A was treated with sofpironium bromide gel for 6 weeks, followed by a 2-week washout period and 6 weeks of placebo gel, after which they were observed for another 2 weeks. In contrast, group B was treated with placebo gel for 6 weeks, followed by a 2-week washout period, 6 weeks of sofpironium bromide gel and a 2-week observation period. One-minute saliva volume, objective salivation ratings (Drooling Severity and Frequency Scale and Nocturnal Hypersalivation Rating Scale) and subjective salivation ratings (Visual Analogue Scale) were assessed every 2 weeks. RESULTS: All patients completed the trials. Three patients reported mild, spontaneously resolved skin itching. Compared with baseline values, the 1-min saliva volumes of both groups were significantly decreased by approximately 30% at the second week of sofpironium bromide gel treatment (P < 0.001), and significantly decreased by >40% at the fourth and sixth weeks of treatment (P < 0.001). The effects were maintained for over 2 weeks even after the treatment was discontinued. CONCLUSIONS: We suggest that sofpironium bromide gel is effective in treating clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia.

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Dental sleep medicine as a discipline was first described about a quarter of a century ago. Snoring, obstructive sleep apnea, sleep bruxism, xerostomia, hypersalivation, gastroesophageal reflux disease, and orofacial pain were identified as dental sleep-related conditions. This scoping review aimed to: i) identify previously unidentified dental sleep-related conditions; and ii) identify the role of oral healthcare providers in the prevention, assessment, and management of dental sleep-related conditions in adults. A systematic literature search was conducted in PubMed, Embase.com, Web of Science, and Cochrane. Studies that reported an actual or likely role of oral healthcare providers in the prevention, assessment, and/or management of sleep-related conditions were included. Of the 273 included studies, 260 were on previously listed dental sleep-related conditions; the other 13 were on burning mouth syndrome. Burning mouth syndrome was therefore added to the list of dental sleep-related conditions for the first aim and categorized into sleep-related orofacial pain. For the second aim, the role of oral healthcare providers was found to be significant in the prevention, assessment, and management of obstructive sleep apnea and sleep bruxism; in the assessment and management of snoring, sleep-related orofacial pain, and oral dryness; and in the assessment of sleep-related gastroesophageal reflux condition.

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Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

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OBJECTIVES: Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation. METHODS: Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment ¼, « hypersalivation ¼, « induced ¼, « drug ¼, « clozapine ¼). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study. RESULTS: Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63). CONCLUSIONS: In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.

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Legalization/decriminalization of cannabis will increase the numbers of patients who have had recent exposure to recreational or medical cannabis. Currently, little has been reported about potential interactions between cannabis use and Propofol anesthesia e.g., for oropharyngeal procedures. We describe three cases of 'cannabis-induced hypersalivation after propofol' (CHAP) and present our institutions' experience with this unique pharmacological combination. Increased hypersalivation may complicate procedures and represent a procedural risk of suffocation. We evaluate possible pharmacological interactions that might underlie this phenomenon and consider management options going forward.

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OBJECTIVE: The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. METHOD: This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. RESULTS: Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. CONCLUSION: Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.

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PURPOSE: The purpose is to analyze the incidence of acute infectious supraglottitis in our center between 2010 and 2020, define the characteristics and trends of those patients and identify factors associated with the need of airway intervention. METHODS: A retrospective single-center observational study of a cohort of patients diagnosed with acute infectious supraglottitis between January 2010 and December 2020. Patients were stratified according to airway management. RESULTS: Eighty eight patients were included: 59 men (67%) and 29 women (33%). A significant upward trend of 9% in the annual incidence rate of supraglottitis was seen during 2010-2020, with an important increase in cases during 2019. Muffled voice (41%) and respiratory distress (38%) were the most common presenting symptoms; and the median duration of symptoms before hospital admission was 2 days [IQR 1; 3]. Airway intervention was performed in fifteen patients (17%). Nine patients (10%) were intubated and six required tracheotomy (7%). Comparing the patients who required airway intervention with those who received a conservative treatment, younger patients (p < 0.01) were more likely to need airway intervention. In logistic regression analysis, we found that epiglottic abscess (p = 0.015), hypersalivation (p = 0.027) and smoking (p = 0.036) were independent factors with a significant association with airway intervention. CONCLUSION: There was an important increase in cases and its severity in 2019, but due to COVID-19 pandemic, it was not possible to define if it was an isolate event or an upward trend. Epiglottic abscess, hypersalivation and smoking could be possible risk factors for airway intervention.

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(1) Background: Clozapine is the most effective antipsychotic. It is, however, associated with many adverse drug reactions. Nose-to-brain (N2B) delivery offers a promising approach. This study aims to develop clozapine-encapsulated thermosensitive sol-gels for N2B delivery. (2) Methods: Poloxamer 407 and hydroxypropyl methylcellulose were mixed and hydrated with water. Glycerin and carbopol solutions were added to the mixture and stirred overnight at 2-8 °C. Clozapine 0.1% w/w was stirred with polysorbate 20 (PS20) or polysorbate 80 (PS80) at RT (25 °C) before being added to the polymer solution. The final formulation was made to 10 g with water, stirred overnight at 2-8 °C and then adjusted to pH 5.5. (3) Results: Formulations F3 (3% PS20) and F4 (3% PS80) were selected for further evaluation, as their gelation temperatures were near 28 °C. The hydrodynamic particle diameter of clozapine was 18.7 ± 0.2 nm in F3 and 20.0 ± 0.4 nm in F4. The results show a crystallinity change in clozapine to amorphous. Drug release studies showed a 59.1 ± 3.0% (F3) and 53.1 ± 2.7% (F4) clozapine release after 72 h. Clozapine permeated after 8 h was 20.8 ± 3.0% (F3) and 17.8 ± 3.1% (F4). The drug deposition was higher with F4 (144.8 ± 1.4 µg/g) than F3 (110.7 ± 2.7 µg/g). Both sol-gels showed no phase separation after 3 months. (4) Conclusions: Binary PS80-P407 mixed micelles were more thermodynamically stable and rigid due to the higher synergism of both surfactants. However, binary mixed PS20-P407 micelles showed better drug permeation across the nasal mucosa tissue and may be a preferable carrier system for the intranasal administration of clozapine.

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Background: Sublingual atropine is an effective treatment of clozapine-induced hypersalivation. This study aims to investigate the pharmacokinetics of atropine after sublingual and oral administration and study the dose effect of atropine on saliva secretion. Methods: An interventional cross-over clinical trial where participants received 0.6 mg and 1.2 mg atropine sulfate sublingual solution and 0.6 mg oral tablet. Atropine plasma concentration was measured over 9 hours with validated LC-MS/MS method. Atropine effects on saliva secretion rate, visual acuity and accommodation, and vital signs were assessed. Results: Four clozapine-treated and three healthy participants were enrolled in the study. The area under the atropine plasma concentration-time curve (AUC0-∞) was highest after the 1.2 mg sublingual solution administration in comparison with 0.6 mg tablet or sublingual solution (8.58±1.66 µg.L-1.h vs. 4.65±1.29 vs. 2.98±0.73 µg.L-1.h, respectively). The Cmax for the 0.6 mg and 1.2 mg sublingual solutions was 1.11±0.99 and 1.76±0.62 µg.L-1, and tmax was 2.18±0.59 and 1.9±0.71 h, respectively. In comparison with the 0.6 mg sublingual solution dose, the saliva secretion reduction was larger after the oral tablet administration (-40% (-59, -22%) vs. -69% (-80, -57)) and largest after the 1.2 mg sublingual solution administration (-79% (-93,-64)). Conclusion: Both the sublingual and oral atropine are effective in reducing the saliva secretion however at a lower plasma concentration after sublingual administration, with a dose-dependent effect. Both have significantly reduced the blood pressure and pulse rate over 3 hours without significant changes in vision. No major safety concerns were reported.

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A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

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Pharyngeal foreign bodies are medical emergencies that require airway protection. Rapid diagnosis and adequate treatment are needed. However, in elderly patients with dementia, diagnosing foreign body aspiration sometimes seems difficult only from the medical history, so we should maintain a high degree of suspicion when treating patients with unexplained symptoms. We herein present a 95-year-old woman with hypersalivation and sore throat two hours after dinner. Due to her mild dementia, sufficient medical history could not be obtained. She could walk and talk, but could not swallow. Her vital signs were all within normal limits. There were no abnormal findings in the oral cavity. The neck x-ray images revealed the patent airway and foreign body in the hypopharynx. We used Macintosh laryngoscope and Magill forceps to remove the foreign body, which was a sliced lotus root with a diameter of 61 mm. After removal, she could swallow, and her symptoms rapidly improved. We should suspect this if the patient presents unexplained pharyngeal symptoms.

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INTRODUCTION: Sialorrhea, also known as hypersalivation, ptyalis, or drooling, results in physical and psychosocial complications that may have a significant negative impact on quality of life for both the patient and their caregiver. The goal of pharmacological treatment is to reduce excessive salivary flow, while maintaining a moist and healthy oral cavity; until recently, however, few of the agents used to treat chronic sialorrhea have been approved in pediatric patients. AREAS COVERED: This article summarizes early evidence for the use of botulinum neurotoxin A formulations in the treatment of children/adolescents with chronic sialorrhea, and findings of the recently completed phase III trial of incobotulinumtoxinA in this indication. Alternative therapies are also briefly discussed. EXPERT OPINION: IncobotulinumtoxinA is the first botulinum neurotoxin A to be approved for the treatment of chronic sialorrhea in children and adults, following the results of phase III trials that demonstrate the efficacy and safety of the drug in these patients. The authors expect that the positive findings will result in updates to clinical guidelines for the treatment of children with chronic sialorrhea. ABBREVIATIONS: AE, adverse event; AESI, adverse event of special interest; BoNT/A, botulinum neurotoxin A; CI, confidence interval; CP, cerebral palsy; DIS, drooling impact scale; DQ, drooling quotient; DSFS, Drooling Severity and Frequency Scale; GICS, Global Impression of Change Scale; LS, least squares; mTDS, modified Teacher's drooling scale; NR, not reported; PD, Parkinson's disease; SAE, serious adverse event; SE, standard error; SIAXI, Sialorrhea in Adults Xeomin Investigation; SIPEXI, Sialorrhea Pediatric Xeomin Investigation; SNAP-25, synaptosomal associated protein-25; TBI, traumatic brain injury; TDS, Teacher Drooling Scale; USA, United States of America; uSFR, unstimulated Salivary Flow Rate; VAS, visual analog scale.

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