Facial Grimacing Research Articles

Models for Predicting Velopharyngeal Competence Based on Speech and Resonance Errors and Velopharyngeal Area Estimation.

To develop tools for predicting velopharyngeal competence (VPC) based on auditory-perceptual assessment and its correlation with objective measures of velopharyngeal orifice area. Methodological study. Sixty-two patients with repaired cleft palate, aged 6 to 45 years, underwent aerodynamic evaluation by means of the pressure-flow technique and audiovisual recording of speech samples. Three experienced speech-language pathologists analysed the speech samples by rating the following resonance, visual, and speech variables: hypernasality, audible nasal air emission, nasal turbulence, weak pressure consonants, facial grimacing, active nonoral errors, and overall velopharyngeal competence. The correlation between the perceptual speech variables and velopharyngeal orifice area estimates was analysed with Spearman's correlation coefficient. Two statistical models (discriminant and exploratory) were used to predict VPC based on the orifice area estimates. Sensitivity and specificity analyses were performed to verify the clinical applicability of the models. There was a strong correlation between VPC (based on the orifice area estimates) and each speech variable. Both models showed 88.7% accuracy in predicting VPC. The sensitivity and specificity for the discriminant model were 92.3% and 97.2%, respectively, and 96.2% and 94.4% for the exploratory model. Two predictor models based on ratings of resonance, visual, and speech variables and a simple calculation of a composite variable, SOMA (Eng. "sum"), were developed and found to be efficient in predicting VPC defined by orifice estimates categories based on aerodynamic measurements. Both tools may contribute to the diagnosis of velopharyngeal dysfunction in clinical practice.

Optimal lameness induction model development using amphotericin B in meat goats.

Lameness continues to be a critical health and welfare concern associated with goat production. Amphotericin B (amp B) is an antimicrobial successful in inducing transient lameness for research purposes previously in livestock animals. The objectives of this study were to (1) identify which of three varying doses of amp B would be most effective in inducing lameness in meat type goats and (2) develop a facial grimace scale for goats. Lameness was produced by an intra-articular injection of amphotericin B into the left hind lateral claw distal interphalangeal joint with either a 5 mg/0.25 mL (high-low, 5 mg of amphotericin B in a volume of 0.25 mL), 5 mg/0.5 mL (high-high, 5 mg of amphotericin B in a volume of 0.5 mL), or a 2.5 mg/0.25 mL (low-low, 2.5 mg of amphotericin B in a volume of 0.25 mL). A saline treatment of 0.5 mL was used as control (0.9% sterile saline solution). Lameness response was analyzed by infrared thermography (IRT) at the induced joint, mechanical-nociception threshold (MNT), visual lameness scoring (VLS), a visual analogue scale (VAS), kinetic gait analysis (KGA), plasma cortisol (CORT), substance P (Sub P), and behavior scoring. The IRT and MNT values differed by timepoint (P ≤ 0.0001). Results from VLS showed the HL treatment was the most effective at inducing lameness (6/6 goats became lame compared to HH 4/6 and LL 2/6). At 24, 48, and 72 h, VAS scores were significantly higher when comparing HL to all other treatment groups (P = 0.0003). Both behavior observers (1 and 2) reported a significant time effect (P = 0.05), with goats exhibiting more facial grimacing at 24 h post-lameness induction. From these data, an optimal dose for a repeatable lameness induction model in goats was aquired. An effective Goat Grimace Scale (GGS) was also developed to evaluate pain responses in goats.

Comparison of assessment of vocal cord mobility following thyroid surgery using Macintosh Laryngoscope and Airtraq

Introduction: Vocal cord assessment after thyroidectomy, routinely performed by anaesthesiologist by direct laryngoscopy in the immediate postoperative period is associated with significant haemodynamic changes and patient discomfort. Aim: Comparison of patient comfort, haemodynamic response and accuracy of assessment of vocal cord mobility between Airtraq and Macintosh laryngoscope. Methodology: In a prospective, randomised controlled study, 82 euthyroid patients, ASA PS 1-2, aged 20-60 years, of either gender undergoing thyroidectomy under general anaesthesia were randomised to one of two groups, Group M and Group A. Anaesthesia was induced with propofol and fentanyl, maintained with morphine, vecuronium, nitrous oxide and isoflurane in oxygen to maintain a MAC of 1-1.3%. At the end of surgery, patients were extubated after complete reversal of neuromuscular blockade and when fully awake. Vocal cord movement and haemodynamic changes were assessed three minutes later using either Airtraq (Group A) or Macintosh laryngoscope (Group M). Patient reactivity score (Favourable - No grimace or facial grimace; Unfavourable – Any head, neck and limb movements or cough). Vocal cord movements were again assessed by an ENT surgeon 48 hours later. Results: Demographic data, type and duration of surgery were similar in both groups. 63.4% of patients in Group A had favourable scores compared to 29.3% in Group M even though duration of laryngoscopy was longer in Group A. There was no significant difference in haemodynamic changes between the groups. Conclusion: Patients are more comfortable during vocal cord assessment with Airtraq laryngoscopy even though duration of laryngoscopy is longer when compared to Macintosh laryngoscope.

A Systematic Approach to Developing Virtual Patient Vignettes for Pediatric Health Equity Research.

The aim of this study was to describe a systematic approach to developing virtual patient (VP) vignettes for health equity research in pediatric pain care. VPs were initially developed to depict the body posture and movements of actual children experiencing pain. Researchers and clinicians with expertise in pediatric pain worked closely with a professional animator to portray empirically supported pain expression in four, full-motion, virtual male characters of two races (i.e., White and Black). Through an iterative process, VPs were refined to (1) appear realistic in a clinical setting and (2) display archetypal pain behavior and expression during a 1-min video clip without sound. Text vignettes were developed with consultation from experts in pain care and presented alongside VPs to assess clinical decision-making. VP vignettes were piloted in a sample of pediatric providers (N=13). Informed by the literature and expertise of stakeholders, several revisions were made to improve VPs' facial grimacing and realism before piloting. VPs appeared to accurately capture important aspects of pain expression and behavior common among pediatric patients with pain disorders. Additional refinements to the text vignettes were made based on provider feedback to improve clarity and clinical relevance. This article presents a working framework to facilitate a systematic approach to developing VP vignettes. This framework is a first step toward advancing health equity research by isolating psychosocial and interpersonal factors affecting provider behavior and decision-making. Future research is needed to validate the use of VP vignettes for assessing provider behavior contributing to health inequities for youth with pain disorders.

Evaluating the utility of a CO2 surgical laser for piglet tail docking to reduce behavioral and physiological indicators of pain and to improve wound healing: A pilot study

In the U.S. millions of commercially raised piglets are routinely tail docked. Human and veterinary medical patients experienced reduced inflammation, healing time and post-procedural pain using a CO2 surgical laser compared to standard surgical instruments. Refinement of the tail docking procedure using a laser may improve piglet welfare by reducing tail docking-associated pain compared to cutting pliers. The objectives of this pilot study were to evaluate the ability of a CO2 surgical laser to 1) reduce pain and 2) improve wound healing of piglets after tail docking. Thirty piglets (male and female; 2 days old) were randomly allocated to one of three treatments (n = 10 piglets/treatment): tail docking with side pliers (SP), tail docking with a CO2 surgical laser (LA) or sham-tail docking (control; CON). Piglet vocalizations were recorded during the tail docking procedure and the maximum frequency, amplitude and energy were quantified. Piglet behavior was recorded for 30 min at baseline and at 0, 1, 2, 6, 7, 8, and 24 h post-procedure. Facial images were collected at the same time points to assess facial grimacing using the Piglet Grimace Scale (PGS). Digital images of the tail tip were taken at baseline and up to 168 h post-procedure for wound healing assessment. Infrared thermography (IRT) images of the tail tip and its surrounding tissues were taken at baseline, 0, 0.5, 8, and 24 h post-procedure to assess inflammation. Blood samples were collected from each piglet at baseline and 0.5 h and saliva samples at baseline, 0.5 and 8 h post-procedure for cortisol analysis. The LA and CON groups elicited calls of higher energy than the SP group (P < 0.0001). Across the assessment period, the SP group had higher grimace scores than the LA group (P = 0.03). Additionally, male piglets grimaced more than female piglets (P = 0.009). A treatment effect was observed for both wound scores and IRT (P < 0.0001). At 0 h the SP group had significantly higher wound scores than the LA and CON group (P < 0.0001). At 0 h, the SP group had a greater temperature difference between the tail tip and surrounding tissue compared to the LA group (P = 0.02). Behavioral indicators of pain were not different between the SP and LA piglets. In conclusion, LA piglets had less tail damage immediately post-procedure and lower facial grimace scores throughout the assessment period, suggesting it may have the utility as a less painful alternative to traditional tail docking with cutting pliers in piglets.

Facial Nerve Anomalies as an Obscure Co-occurrence With External Ear Malformations: A Case Report

This study reports an infant with a rare triad of congenital facial palsy, bilateral aural atresia, and middle ear malformations. We highlight the audiological test battery in detail that led to identifying this obscure co-occurrence in a 6-month-old infant. The challenges associated with identifying such rare conditions, especially in infants, can be overcome only by incorporating a meticulous and vigilant approach. The infant was subjected to a series of subjective and objective audiological evaluations, through which rare asymmetric facial grimaces were vigilantly observed. This observation warranted radiologic investigation, which confirmed the suspicion that the anomaly may not be restricted to auditory structures alone. As facial nerve anomalies were confirmed, diversified recommendations, including speech, language, and swallow evaluation, were made apart from the auditory management. Hence in cases of external ear anomalies, although rare, it is essential to rule out facial nerve abnormalities as they can be a concealed problem.

Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide-induced migraine-like pain behaviors in mice.

Migraine is a complex neurovascular disorder that is one of the leading causes of disability and a reduced quality of life. Even with such a high societal impact, our understanding of the cellular and molecular mechanisms that contribute to migraine headaches is limited. To address this complex disorder, several groups have performed genome-wide association studies to elucidate migraine susceptibility genes, with many identifying transient receptor potential melastatin 8 (TRPM8), a cold-sensitive cation channel expressed in peripheral afferents innervating the trigeminovascular system, and the principal mediator of cold and cold pain associated with injury and disease. Interestingly, these migraine-associated single-nucleotide polymorphisms reside in noncoding regions of TRPM8, with those correlated with reduced migraine risk exhibiting lower TRPM8 expression and decreased cold sensitivity. Nonetheless, as a role for TRPM8 in migraine has yet to be defined, we sought to address this gap in our knowledge using mouse genetics and TRPM8 antagonism to determine whether TRPM8 channels or neurons are required for migraine-like pain (mechanical allodynia and facial grimace) in inducible migraine models. Our results show that both evoked and spontaneous pain behaviors are dependent on both TRPM8 channels and neurons, as well as required in both acute and chronic migraine models. Moreover, inhibition of TRPM8 channels prevented acute but not established chronic migraine-like pain. These results are consistent with its association with migraine in genetic analyses and establish that TRPM8 channels are a component of the underlying mechanisms of migraine.

Facial grimace during speech in cleft lip and palate: a proposal for classification.

To investigate the effectiveness of a proposal for classification of facial grimace (FG) and its correlation with objective evaluation of velopharyngeal closure (VPC). Twenty individuals with repaired cleft lip and palate underwent velopharyngeal area measurement by means of rhinomanometry and speech sample recording. The FG was rated in two steps, by three speech-language pathologists. First the evaluators rated the FG using their own criteria as: 1= absent FG; 2=mild; 3=moderate; 4=severe. Subsequently, they were submitted to a training session that established the following FG rating criteria: 1=absent FG; 2=movement only of the nose or upper third of the face; 3=strong movement of the nose or upper third of the face; 4=movement of the nose and upper third of the face. The evaluators rated the FG using the established criteria. Intra- and inter-rater agreement were calculated using weighted Kappa coefficient. Correlation between the two stage ratings with the VPC was calculated by Spearman's correlation coefficient. In the first stage inter-rater agreement ranged from fair to substantial; in the second stage, from substantial to almost perfect. Intra-rater agreement ranged from moderate to almost perfect in the first stage, and from moderate to substantial in the second stage. The correlation between FG and velopharyngeal area was positive and significant in both stages. The proposed FG judgement proved to be effective in determining the symptom and reliable in diagnosing the severity of velopharyngeal dysfunction. The significant correlation between perceptual and instrumental methods suggests that FG can be used in predicting VPC.

Factors influencing postoperative pain management among nurses in selected district hospitals in Ghana.

Poorly managed postoperative pain is linked to numerous postoperative complications worldwide and in Ghana. This is due to the myriad of physical and psychological problems, such as lifelong chronic pain syndromes, impaired functionality and death. The aim of this study was to assess the barriers and factors influencing postoperative pain management by Ghanaian nurses working in four hospitals. A quantitative descriptive cross-sectional design was employed for this study. Participants were recruited using a multistage sampling technique by which 146 returned their questionnaires out of 194 participants. The statistical analysis of data was done with the Statistical Package of Social Sciences (SPSS) 20.0 version. Findings revealed that some verbal and non-verbal cues from patients such as facial grimacing, restlessness, irritability and distress, lack of concentration and moaning or crying (verbalisation) influenced how nurses controlled postoperative pain with analgesia. The participants also identified several barriers to influence postoperative pain management by nurses. In conclusion, postoperative pain control by nurses is influenced by several factors, and hence, nurses need to manage patients' pain effectively in Ghana and abroad using multiple approaches.

Speech Outcome Analysis after Primary Cleft Palate Repair: Interim Siriraj Hospital Audit

Objective: To evaluate the speech outcomes after primary cleft palate repair in a single tertiary medical institution of Thailand.Materials and Methods: A prospective cohort study was performed. Patients who had cleft palate with/without cleft lip and underwent primary cleft palate repair were included. Speech assessment was performed using the Pittsburgh weighted speech score (PWSS) by a speech-language pathologist.Results: Forty patients (21 males and 19 females) who underwent primary cleft palate repair at Siriraj Hospital were included. The median age at the time of speech evaluation was 7 years. The median age at primary cleft palate surgery was 12 months. The predominant cleft palate type was Veau 3 (47.5%). Oronasal fistula occurred 40%. Two-flap palatoplasty and intravelar veloplasty were the most common procedures. Median PWSS was 7, in which the competence velopharyngeal mechanism was found 5%, borderline competence 10%, borderline incompetence 32.5%, and incompetence velopharyngeal mechanism 52.5%. Among the velopharyngeal incompetence group, articulation disorder was the most common disorder with median score of 3. Besides, the median scores for hypo/hyper-nasality, nasal emission, phonation, and facial grimace disorder were 1, 2, 0 and 0, respectively. There was no statistically significant association between velopharyngeal incompetence and cleft types, age at primary surgery, type of operation, the width of cleft palate and prevalence of postoperative oronasal fistula or otitis media effusion.Conclusion: Velopharyngeal incompetence has been commonly identified after cleft palate repair in our institute. The articulation disorder is the most common characteristic.

COMPARATIVE STUDY BETWEEN DEXMEDETOMIDINE AND MAGNESIUM SULPHATE AS SEDATIVES IN AWAKE FIBEROPTIC INTUBATION IN CONTROLLED HYPERTENSIVE ADULT PATIENTS

Background: Flexible bronchoscopy has become the “gold standard” for managing the expected and unexpected difficult airway. Several drugs have been used to provide adequate sedation to optimize adequate fiberoptic intubation. Objective: To compare the sedative effects of dexmedetomidine and magnesium sulphate during awake fiberoptic nasal intubation in controlled hypertensive adults undergoing elective surgeries. Patients and methods: Sixty controlled hypertensive patients intubated using awake fiberoptic. They were divided into 2 equal groups: Patients received dexmedetomidine infusion at dose of 1ug/kg, and the other patients received magnesium sulphate at dose of 30mg/kg. Topicalization of airway was done using lidocaine “spray as you go technique”. After completing the loading dose, Ramsay score was assessed before intubation. The 2 groups were compared according to Ramsay score, cough score, facial grimace and hemodynamic changes. This study was done at Al-Azhar University Hospitals after approval of the medical ethical committee, from May 2019 till November 2020. Results: Ramsay score, cough score and facial grimace were favorable with less hemodynamic effects in dexmedetomidine group than magnesium group. Conclusion: Dexmedetomidine was effective sedative agent for awake fiberoptic intubation in controlled hypertensive patients in comparison with magnesium sulphate.

S2755 Subclinical Liver Involvement in Wilson's Disease

Introduction: Wilson’s disease is an autosomal recessive disorder resulting in defective cellular copper transport. End-organ damage due to copper accumulation in the liver and brain disease (hepatolenticular degeneration) is the most common clinical manifestation. Case Description/Methods: A 29 year old woman was evaluated at the emergency department for a suicidal gesture. During the initial evaluation, she admitted she did not want to kill herself but was rather seeking immediate help for issues that she felt had been unattended to. Her complaints included bilateral leg pain associated with muscle cramps, stiffness, weakness, symmetric resting and intentional tremors, ataxia and depressed mood evolving over the previous six months. The patient had been diagnosed with a variety of psychiatric disorders. The patient stated she had moved to Indiana shortly after Hurricane Maria and returned to PR at the onset of the present illness. No family history of neurologic or liver disease. The physical exam revealed an unaltered mental status, flat affect, facial grimacing, cogwheel rigidity of the upper extremities with mild muscle weakness, bradykinesia, dystonia, fasciculations, muscle wasting, choreoathetosis and a Parkinsonian gait. Hepatomegaly or stigmata of cirrhosis were not found. Initial laboratories were negative for anemia, thrombocytopenia, coagulopathy or hyperbilirubinemia, as was serology for Lyme disease, syphilis, hepatitis and HIV. Moreover, transaminases, inflammatory markers, ANA, ASMA, ammonia and aldolase levels were also all normal. Brain MRI suggested encephalopathy. CSF revealed no pleocytosis. The working diagnosis was encephalitis, possibly infectious or autoimmune, and the patient was initially treated with antibiotics & intravenous glucocorticoids. An elevated AFP was reported which led to an abdominal CT scan that revealed hepatomegaly with heterogeneous enhancement throughout the liver parenchyma and surface nodularity. Ophthalmology evaluation showed Kaysher-Fleischer rings. Low ceruloplasmin levels, high urine copper levels and liver biopsy were all confirmatory of Wilson’s disease, and the patient was treated with penicillamine. Discussion: This case report emphasizes the importance of ruling out organic disease before diagnosing a psychiatric illness. A young patient with neurological symptoms in the absence of evident liver disease at presentation should prompt evaluation for uncommon disorders such as Wilson’s disease.

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Voluntary Wheel Running Partially Attenuates Early Life Stress-Induced Neuroimmune Measures in the Dura and Evoked Migraine-Like Behaviors in Female Mice.

Migraine is a complex neurological disorder that affects three times more women than men and can be triggered by endogenous and exogenous factors. Stress is a common migraine trigger and exposure to early life stress increases the likelihood of developing chronic pain disorders later in life. Here, we used our neonatal maternal separation (NMS) model of early life stress to investigate whether female NMS mice have an increased susceptibility to evoked migraine-like behaviors and the potential therapeutic effect of voluntary wheel running. NMS was performed for 3 h/day during the first 3 weeks of life and initial observations were made at 12 weeks of age after voluntary wheel running (Exercise, -Ex) or sedentary behavior (-Sed) for 4 weeks. Mast cell degranulation rates were significantly higher in dura mater from NMS-Sed mice, compared to either naïve-Sed or NMS-Ex mice. Protease activated receptor 2 (PAR2) protein levels in the dura were significantly increased in NMS mice and a significant interaction of NMS and exercise was observed for transient receptor potential ankyrin 1 (TRPA1) protein levels in the dura. Behavioral assessments were performed on adult (>8 weeks of age) naïve and NMS mice that received free access to a running wheel beginning at 4 weeks of age. Facial grimace, paw mechanical withdrawal threshold, and light aversion were measured following direct application of inflammatory soup (IS) onto the dura or intraperitoneal (IP) nitroglycerin (NTG) injection. Dural IS resulted in a significant decrease in forepaw withdrawal threshold in all groups of mice, while exercise significantly increased grimace score across all groups. NTG significantly increased grimace score, particularly in exercised mice. A significant effect of NMS and a significant interaction effect of exercise and NMS were observed on hindpaw sensitivity following NTG injection. Significant light aversion was observed in NMS mice, regardless of exercise, following NTG. Finally, exercise significantly reduced calcitonin gene-related peptide (CGRP) protein level in the dura of NMS and naïve mice. Taken together, these findings suggest that while voluntary wheel running improved some measures in NMS mice that have been associated with increased migraine susceptibility, behavioral outcomes were not impacted or even worsened by exercise.

Assessment of Monoacyglycerol Lipase Inhibition for Acute and Chronic Antinociception in a Behavioral Battery for Testing Candidate Analgesics in Mice

Objective and Hypothesis There is a pressing need for discovery of novel, safe, and effective analgesics with improved preclinical-to-clinical translation. This study addressed these issues by evaluating the antinociceptive effectiveness of the monoacylglycerol lipase (MAGL)-selective inhibitors MJN110 and JZL184 in a battery of pain-stimulated, pain-depressed, and pain-independent behaviors in male and female mice. Ketoprofen (cyclooxygenase1/2 inhibitor) was used as a clinically-effective analgesic positive control, and ∆9-tetrahydrocannabinol (THC; cannabinoid 1/2 receptor (CB1/2­R) agonist) as a negative control that is not clinically effective to treat acute pain. We hypothesized that ketoprofen and MAGL-selective inhibitors would produce antinociception on endpoints of pain-stimulated and pain-depressed behaviors at doses that did not alter pain-independent behaviors, whereas THC would not. Methods Intraperitoneal dilute lactic acid (IP acid) served as an acute noxious stimulus in male and female ICR mice to produce two IP acid-stimulated behaviors (stretching and facial grimace) and two IP acid-depressed behaviors (rearing and nesting). Pain-independent drug effects were assessed in nesting and locomotion in the absence of IP acid. All test drugs were delivered subcutaneously and evaluated for effectiveness to alleviate pain-related behaviors at doses below those that altered pain-independent behaviors. The assay of IP acid-depressed nesting was also used to assess MJN110 time course, sensitivity to blockade by the CB1R- and CB2R-selective antagonists rimonabant and SR144528, and effects of repeated dosing for 7 consecutive days. Results and Significance Ketoprofen (0.1-10 mg/kg) produced robust antinociception without general behavioral disruption on all IP acid-stimulated and IP acid-depressed behaviors. MJN110 (0.1-3.2 mg/kg) and JZL184 (1.0-32 mg/kg) produced antinociception without motor disruption on endpoints of stretching (MJN110 only), grimace, and nesting, but not rearing. THC (1-10 mg/kg) attenuated IP acid-stimulated stretching and facial grimace at doses that did not produce general motor disruption; however, THC did not alleviate IP acid-induced depression of either nesting or rearing. MJN110 (1.0 mg/kg) antinociception in the assay of IP acid-induced nesting depression showed a long duration (40min – 6hr) mediated by CB1R but not CB2R and tended to be stronger in females. Chronic MJN110 (1.0 mg/kg/day × 7 days) showed sex-dependent antinociception and tolerance, with females showing tolerance by Day 7 and males showing no significant antinociceptive effect across all 7 days. These results provide modest support for further consideration of MAGL-selective inhibitors, especially MJN110, as candidate analgesics, with future work needed to assess sex-dependent effects. However, it should be noted that none of the cannabinoids were as effective in this behavioral battery as ketoprofen.

Tourette’s syndrome: Alternative approaches to a clinical case refractory to conventional therapy

IntroductionTourette’s syndrome is a neuropsychiatric disorder marked by motor and phonic tics frequently associated with psychiatric comorbidities, beginning in childhood. While most cases improve or resolve with age, some are refractory.ObjectivesTo review new strategies for the management of Tourette’s Syndrome, following an outpatient clinical vignette.MethodsWe performed a review based on the PubMed® database.ResultsA 50-years-old female patient with a long-term outpatient psychiatric follow-up presented with motor tics appearing in adolescence, including winking and facial grimacing, as well as episodes of coprolalia. Over the years, she developed an anxiety disorder and social isolation. In addition to psychological therapy, pharmacological therapy had already been approached with the use alpha-adrenergic agonists and several antipsychotics, such as risperidone and aripiprazole, with the patient showing only partial response to pimozide. In Tourette’s syndrome, the therapy must be adequate to the patient’s individual needs. Emerging treatments for refractory cases, such as anticonvulsants, cannabinoids or antiglutamatergic drugs have been the target of several studies. Botulinum toxin injections are particularly effective in patients with focal motor tics and complex phonic tics. Non-pharmacological treatment options, such as electroconvulsive therapy and deep brain stimulation may prove effective in some cases.ConclusionsA significant proportion of patients fail to respond to conventional strategies. Thus, new pharmacological and non-pharmacological therapies are on the horizon and may represent an important step in treatment algorithms for refractory cases in the future.

EEG changes reflecting pain: is alpha suppression better than gamma enhancement?

ObjectiveSuppression of alpha and enhancement of gamma electroencephalographic (EEG) power have both been suggested as objective indicators of cortical pain processing. While gamma activity has been emphasized as the best potential marker, its spectral overlap with pain-related muscular responses is a potential drawback. Since muscle contractions are almost universal concomitants of physical pain, here we investigated alpha and gamma scalp-recorded activities during either tonic pain or voluntary facial grimaces mimicking those triggered by pain. MethodsHigh-density EEG (128 electrodes) was recorded while 14 healthy participants either underwent a cold pressor test (painful hand immersion in 10 °C water) or produced stereotyped facial/nuchal contractions (grimaces) mimicking those evoked by pain. The scalp distribution of spectral EEG changes was quantified via vector-transformation of maps and compared between the pain and grimacing conditions by calculating the cosine of the angle between the two corresponding topographies. ResultsPainful stimuli significantly enhanced gamma power bilaterally in fronto-temporal regions and decreased alpha power in the contralateral central scalp. Sustained cervico-facial contractions (grimaces) gave also rise to significant gamma power increase in fronto-temporal regions but did not decrease central scalp alpha. While changes in alpha topography significantly differed between the pain and grimace situations, the scalp topography of gamma power was statistically indistinguishable from that occurring during grimaces. ConclusionGamma power induced by painful stimuli or voluntary facial-cervical muscle contractions had overlapping topography. Pain-related alpha decrease in contralateral central scalp was less disturbed by muscle activity and may therefore prove more discriminant as an ancillary pain biomarker.

Comparison of intra− and postoperative variables between laparoscopic and open ovariectomy in rabbits (Oryctolagus cuniculus)

To compare intraoperative and short-term postoperative variables pertaining to laparoscopic ovariectomy (LapOVE) and open ovariectomy (OVE) in rabbits (Oryctolagus cuniculus). Twelve 4- to 5-month-old female New Zealand White rabbits. Rabbits were randomly assigned to undergo LapOVE (n = 6) or OVE (6), with a vessel-sealing device used to seal and transect the ovarian pedicles. Laparoscopic ovariectomy was performed with a 3-port approach. Variables were measured during surgery (surgery and anesthesia times and incision lengths) and for up to 7 days after surgery (food consumption, feces production, body weight, vital parameters, blood glucose and cortisol concentrations, abdominal palpation findings, facial grimace scale scores, and ethograms). Mean surgery (43.2 vs 21.7 minutes) and anesthesia (76.2 vs 48.8 minutes) times were longer and mean incision length was shorter (24.0 vs 41.5 mm) for LapOVE versus OVE. No significant differences in postoperative variables were identified between groups. During LapOVE, small intestinal perforation occurred in 1 rabbit, which was then euthanized. Postoperative complications for the remaining rabbits included superficial incisional dehiscence (LapOVE, 1/5; OVE, 2/6), subcutaneous emphysema (LapOVE, 1/5; OVE, 0/6), and seroma formation (LapOVE, 1/5; OVE, 0/6). Surgery time for LapOVE was twice that of OVE, and LapOVE resulted in unique complications in rabbits. No evidence of a reduction in pain or faster return to baseline physiologic status was found for LapOVE. Further evaluation of LapOVE in rabbits is warranted, with modification to techniques used in this study or a larger sample size.

A prospective randomized controlled study comparing intravenous dexmedetomidine plus ketamine combination with intravenous dexmedetomidine alone for awake fibreoptic nasotracheal intubation

BackgroundThe purpose of this study was to compare the efficacy and safety of dexmedetomidine versus dexmedetomidine and ketamine for sedation during awake fibreoptic intubation (FOI) in patients posted for elective surgeries. Ninety-eight American Society of Anesthesiologists Physical Status (ASA-PS) I–II patients with difficult airway and scheduled for elective surgeries were enrolled in this study after institutional ethics committee approval. Patients were randomly allocated into 2 groups, i.e. 49 patients in each group. Group D patients received 1 μg/kg dexmedetomidine IV over 10 min in 100-mL normal saline followed by a continuous infusion at 0.5 μg/kg/h till FOI and 5-mL normal saline followed by saline infusion. Group DK patients received 1 μg/kg dexmedetomidine IV over 10 min in 100-mL normal saline. Further, they received IV ketamine 15 mg as a bolus of 5 mL, followed by continuous infusion of ketamine at 20 mg/h until the end of intubation. The primary objective was to compare the efficacy of the combination of IV dexmedetomidine and ketamine with IV dexmedetomidine alone as sedation for FOI. Vocal cord movement, sedation, coughing, facial grimace score, recall of procedure, and haemodynamics were also compared in both groups.ResultsDemographic data, vocal cord movement, cough score, facial grimace score, total drugs used, hoarseness, sore throat and level of recall were comparable in both groups. Haemodynamics were significantly better in group DK at 2, 3, 4 and 5 min compared to group D.ConclusionsAddition of ketamine to dexmedetomidine did not improve intubating conditions, reduce cough or improve recall of FOI. However, patients remain sedated when ketamine was used with dexmedetomidine. The study was not registered prospectively in any clinical trial registry.

Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls

This study evaluated a battery of pain-stimulated, pain-depressed, and pain-independent behaviors for preclinical pharmacological assessment of candidate analgesics in mice. Intraperitoneal injection of dilute lactic acid (IP acid) served as an acute visceral noxious stimulus to produce four pain-related behaviors in male and female ICR mice: stimulation of 1) stretching, 2) facial grimace, 3) depression of rearing, and 4) depression of nesting. Additionally, nesting and locomotion in the absence of the noxious stimulus were used to assess pain-independent drug effects. These six behaviors were used to compare effects of two mechanistically distinct but clinically effective positive controls (ketoprofen and oxycodone) and two negative controls that are not clinically approved as analgesics but produce either general motor depression (diazepam) or motor stimulation (amphetamine). We predicted that analgesics would alleviate all IP acid effects at doses that did not alter pain-independent behaviors, whereas negative controls would not. Consistent with this prediction, ketoprofen (0.1-32 mg/kg) produced the expected analgesic profile, whereas oxycodone (0.32-3.2 mg/kg) alleviated all IP acid effects except depression of rearing at doses lower than those that altered pain-independent behaviors. For the negative controls, diazepam (1-10 mg/kg) failed to block IP acid-induced depression of either rearing or nesting and only decreased IP acid-stimulated behaviors at doses that also decreased pain-independent behaviors. Amphetamine (0.32-3.2 mg/kg) alleviated all IP acid effects but only at doses that also stimulated locomotion. These results support utility of this model as a framework to evaluate candidate-analgesic effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behavioral endpoints. SIGNIFICANCE STATEMENT: Preclinical assays of pain and analgesia often yield false-positive effects with candidate analgesics. This study used two positive-control analgesics (ketoprofen, oxycodone) and two active negative controls (diazepam, amphetamine) to validate a strategy for distinguishing analgesics from nonanalgesics by profiling drug effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behaviors in male and female mice.