Facial Grimacing Research Articles

Focal negative motor seizures: Multimodal evaluation.

This case report shows the importance of multimodal evaluation to formulate a proper diagnosis of negative motor seizures (NMSs). Only few reports in literature document NMSs with video-electroencephalographic (EEG) and electromyographic coregistration. A multimodal evaluation is crucial to exclude common mimics and propose correct therapy. We describe a case of a 62-year-old man with drug-resistant focal epilepsy and NMSs, evaluated with video-EEG recording with polygraphy, magnetoencephalography (MEG), and brain magnetic resonance imaging (MRI). Video-EEG monitoring showed 182 focal NMSs, with preserved awareness and comprehension. The patient reported complex paresthesia of the left hand followed by left facial grimace, left arm flaccid paralysis, and bradycardia. EEG showed ictal discharges in the right frontocentral region associated with sudden electromyographical silence in left limb muscles consistent with loss of tonic contraction from distal to proximal muscles of the arm. MEG localized the epileptic zone in the right opercular region, consistent with MRI evidence of type II cortical dysplasia in the right inferior frontal gyrus. Multimodal evaluation is essential to document the temporal relationship between ictal discharges, clinical onset of limb paresis, and electrophysiologic evidence of loss of tonic muscular contraction. It allows definition of the specific cortical area involved in NMSs, offering new insight into physiological brain functioning.

Speech Assessments in Hypoplastic Cleft Maxilla Treated by Anterior Segmental Distraction Osteogenesis

Introduction: Cleft lip and palate (CLP) affect the craniofacial region, with significant implications for speech, hearing, feeding, and facial aesthetics. This study aimed to evaluate the impact of anterior maxillary segmental distraction osteogenesis (AMSDO) using an internal distractor on speech outcomes in CLP patients, assessed using the Pittsburgh Weighted Speech Scale (PWSS).Methodology: A single-center prospective study was conducted between March 2022 and April 2024. Twelve CLP patients with maxillary hypoplasia, aged 17.8 to 32.6 years, were included. Purposive sampling was done to include patients with complete unilateral or bilateral CLP who exhibited Class III skeletal relationships with reverse overjet greater than 7 mm. Speech assessments were conducted preoperatively (1-3 months before surgery) and postoperatively (5-7 months after distraction). Speech samples were recorded and evaluated by a licensed speech-language pathologist using the PWSS. Statistical analysis was performed using paired t-tests and Chi-square tests.Results: Significant improvements were observed in the total PWSS score (p = 0.03), nasality (p < 0.001), phonation (p < 0.001), and articulation errors (p = 0.004) postoperatively. No significant changes were seen in nasal emission and facial grimace. No correlation was found between the amount of distraction and speech outcomes. Unilateral cleft patients showed better outcomes than bilateral cleft patients, though not statistically significant.Conclusion: AMSDO significantly improves speech outcomes in CLP patients with maxillary hypoplasia. The PWSS is a reliable tool for assessing these changes. Further research with larger samples and longer follow-ups is warranted to confirm these findings.

Speech Outcomes After Primary Palatoplasty and Presurgical Cleft Characteristics: Is There a Predictive Association?

Speech disorders related to cleft lip and palate exhibit different degrees of involvement and can occur even after primary palate repair. Hypernasality can be present as a result of velopharyngeal insufficiency, as well as nasal emission, weak pressure, articulatory errors and facial grimace, affecting speech intelligibility. Palatoplasty outcomes can be variable, and among the influencing factors are the surgical technique, the surgeon's experience, the postoperative care, and the patient/cleft characteristics. The aim of this study was to correlate speech results after primary palate repair with surgical technique and cleft characteristics, using anthropometric measurements and speech assessment in patients diagnosed with cleft lip and palate. A longitudinal, retrospective study with patients who underwent primary palatoplasty between 2015 and 2019 and still attend Craniomaxillofacial Surgery Outpatient Clinic was conducted. Patients were operated on by a single surgeon using the intravelar technique veloplasty with maximal retropositioning of the soft palate elevator muscle. Patients who underwent primary palatoplasty after 2018 had the measurements before and immediately after palatoplasty recorded: length of palate, and the distances from cleft and uvula to posterior pharyngeal wall, and uvula to adenoid. Considering the total of 39 patients, 30 (76.9%) were male, with a mean age of 20.9 months (9-53mo). All patients had their speech recorded between ages of 60 and 120 months. Speech samples were assessed by 3 different speech pathologists experienced in cleft speech, with an intrarater and inter-rater reliability >80%. The most frequent cleft type was unilateral complete cleft lip and palate (59%). One patient had mild hyponasality, 1 isolated obligatory disorder (nasal turbulence), and 3 patients presented compensatory articulation (2 isolated and 1 also presented obligatory disorder). Only 1 patient had marginal velopharyngeal insufficiency. Postoperatively, there was a mean increase in palate length from 5.4 to 5.6cm, and a statistically significant decrease in the distance from the uvula to the pharynx wall, with a mean of 1.7 to 1.1cm (P<0.001). In general, patients analyzed did not have significant alterations in speech assessment, which did not allow further comparisons and correlation. Therefore, regardless of the anatomic characteristics of the palate, it is possible to achieve good results depending on the handling experience and the technique used.

Speech Outcomes after Delayed Hard Palate Closure and Synchronous Secondary Alveolar Bone Grafting in Patients with Cleft Lip, Alveolus and Palate.

Background The best timing of closure of the hard palate in individuals with cleft lip, alveolus, and palate (CLAP) to reach the optimal speech outcomes and maxillary growth is still a subject of debate. This study evaluates changes in compensatory articulatory patterns and resonance in patients with unilateral and bilateral CLAP who underwent simultaneous closure of the hard palate and secondary alveolar bone grafting (ABG). Methods A retrospective study of patients with nonsyndromic unilateral and bilateral CLAP who underwent delayed hard palate closure (DHPC) simultaneously with ABG at 9 to 12 years of age from 2013 to 2018. The articulatory patterns, nasality, degree of hypernasality, facial grimacing, and speech intelligibility were assessed pre- and postoperatively. Results Forty-eight patients were included. DHPC and ABG were performed at the mean age of 10.5 years. Postoperatively hypernasal speech was still present in 54% of patients; however, the degree of hypernasality decreased in 67% ( p < 0.001). Grimacing decreased in 27% ( p = 0.015). Articulation disorders remained present in 85% ( p = 0.375). Intelligible speech (grade 1 or 2) was observed in 71 compared with 35% of patients preoperatively ( p < 0.001). Conclusion This study showed an improved resonance and intelligibility following DHPC at the mean age of 10.5 years, however compensatory articulation errors persisted. Sequential treatments such as speech therapy play a key role in improvement of speech and may reduce remaining compensatory mechanisms following DHPC.

Impaired amygdala astrocytic signaling worsens neuropathic pain-associated neuronal functions and behaviors.

Introduction: Pain is a clinically relevant health care issue with limited therapeutic options, creating the need for new and improved analgesic strategies. The amygdala is a limbic brain region critically involved in the regulation of emotional-affective components of pain and in pain modulation. The central nucleus of amygdala (CeA) serves major output functions and receives nociceptive information via the external lateral parabrachial nucleus (PB). While amygdala neuroplasticity has been linked causally to pain behaviors, non-neuronal pain mechanisms in this region remain to be explored. As an essential part of the neuroimmune system, astrocytes that represent about 40-50% of glia cells within the central nervous system, are required for physiological neuronal functions, but their role in the amygdala remains to be determined for pain conditions. In this study, we measured time-specific astrocyte activation in the CeA in a neuropathic pain model (spinal nerve ligation, SNL) and assessed the effects of astrocyte inhibition on amygdala neuroplasticity and pain-like behaviors in the pain condition. Methods and Results: Glial fibrillary acidic protein (GFAP, astrocytic marker) immunoreactivity and mRNA expression were increased at the chronic (4weeks post-SNL), but not acute (1week post-SNL), stage of neuropathic pain. In order to determine the contribution of astrocytes to amygdala pain-mechanisms, we used fluorocitric acid (FCA), a selective inhibitor of astrocyte metabolism. Whole-cell patch-clamp recordings were performed from neurons in the laterocapsular division of the CeA (CeLC) obtained from chronic neuropathic rats. Pre-incubation of brain slices with FCA (100µM, 1h), increased excitability through altered hyperpolarization-activated current (Ih) functions, without significantly affecting synaptic responses at the PB-CeLC synapse. Intra-CeA injection of FCA (100µM) had facilitatory effects on mechanical withdrawal thresholds (von Frey and paw pressure tests) and emotional-affective behaviors (evoked vocalizations), but not on facial grimace score and anxiety-like behaviors (open field test), in chronic neuropathic rats. Selective inhibition of astrocytes by FCA was confirmed with immunohistochemical analyses showing decreased astrocytic GFAP, but not NeuN, signal in the CeA. Discussion: Overall, these results suggest a complex modulation of amygdala pain functions by astrocytes and provide evidence for beneficial functions of astrocytes in CeA in chronic neuropathic pain.

USING SHEEP FACIAL GRIMACE SCALE, INFRARED THERMOGRAPHY AND CORTISOL HORMONE TO MEASURE PAIN IN SHEEP INFECTED WITH MASTITIS DISEASE

The purpose of this study was to apply sheep pain facial expression scales (SPFES) to sheep infected with mastitis, measuring peripheral temperatures and serum cortisol hormone. Twenty-three healthy ewes and 23 infected ewes with clinical mastitis were included in this research from January 2022 to April 2023. Images were taken from each ewe to detect facial grimace scales of ewes. Nasal, eye and ear temperatures were collected using infrared thermal imaging camera. Moreover, serum cortisol hormone was collected from the blood. It was found that there was a significant decrease (p&lt;0.01) in nasal, eye and ear temperatures of infected ewes in comparison to healthy ewes. Additionally, cortisol hormone was found significantly (p&lt;0.01) higher in infected ewes at day 1 and day 7 compared to non-infected animals. The changes in facial expressions for all the determined five regions were significantly (p&lt;0.01) different than healthy ewes. The total pain score was significantly (p&lt;0.05) higher on day 1 and day 7, compared to healthy ewes. It was concluded that sheep facial grimace scale was a useful and practical tool for measuring pain in sheep. In addition, cortisol from the serum and peripheral temperatures were found to be useful pain indicators.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.

Universal scoring system for assessing speech function in patients with cleft palate at the stages of surgical treatment

To develop a universal system for assessing the speech function in patients with congenital palatal cleft in the postoperative period. A universal system for assessing the speech function for patients with a palatal cleft can be applied both after the primary operation of uranoplasty and for patients diagnosed with velopharyngeal insufficiency (VPI). The patient's speech is assessed according to the following criteria: defects in the pronunciation of consonants by place of articulation: labial, labiodental, lingual-dental, lingual-palatal, lingual-alveolar; speech breathing; tongue position; directed air stream; voicing disorders; The patient's is also evaluated for the following findings: hypernasality (reflected speech); hypernasality (spontaneous speech); hyponasality; pharyngeal reflex; audible nasal emission/turbulence; facial grimaces; speech intelligibility. The speech therapy and dental assessments are added to obtain a value characterizing the patient's condition: from 0 to 10 scoring indicates than only speech therapy correction is needed; from 11 to 18 - the decision on the necessity of surgical treatment is made by the surgeon together with the speech therapist, from 18 to 25 - surgical treatment is necessary with subsequent sessions with a speech therapist. With the help of this questionnaire, the operating surgeon can more accurately and objectively assess in dynamics the result of the surgical treatment, regardless of the results of speech therapy treatment in the postoperative period. The creation of this scoring system for speech assessment is aimed at objectivizing the results of uranoplasty and speech-improving operations. It allows the surgeon to compare the effectiveness of different surgical methods. The universal scoring system for assessing the state of speech function can be applied in the diagnosis of a patient with a palatal cleft both after the primary operation on the palate and after corrective surgical interventions. It allows monitoring progress and identifying dynamics in surgical and speech therapy treatment.

Ochoa Syndrome: A Comprehensive Exploration

Objective: Ochoa Syndrome, also recognized as Urofacial Syndrome, presents an intricate confluence of urological anomalies and distinctive facial expressions during micturition. This article endeavors to meticulously dissect the genetic underpinnings and clinical intricacies that define this rare genetic disorder, providing a comprehensive overview for clinicians, geneticists, and researchers. Methods: A thorough review of existing literature, genetic studies, and clinical case reports was conducted to synthesize the current understanding of Ochoa Syndrome. Molecular pathways implicated in the pathogenesis of Ochoa Syndrome, with a focus on the HPSE2 gene, were elucidated, providing a foundation for the exploration of potential therapeutic interventions. Results: Ochoa Syndrome emerges as a consequence of mutations in the HPSE2 gene, unraveling a cascade of molecular events intricately linked to neurogenic bladder dysfunction and unique facial grimacing during voiding. The clinical spectrum encompasses a range of urological challenges, necessitating a nuanced approach to patient management and care. Conclusion: This article illuminates the complexities of Ochoa Syndrome, offering a roadmap for clinicians and researchers to navigate the intricate genetic landscape. By elucidating the molecular labyrinth that underlies this syndrome, we aim to not only enhance diagnostic precision but also pave the way for targeted therapeutic interventions, thereby advancing our collective understanding and management of this rare genetic enigma. Through this exploration, we endeavor to foster a deeper appreciation for the intricacies of Ochoa Syndrome and underscore the imperative for continued research in the pursuit of optimal patient outcomes.

Diagnosing and Managing Velopharyngeal Insufficiency in Patients With Cleft Palate After Primary Palatoplasty

Velopharyngeal insufficiency (VPI) after palatoplasty is caused by improper anatomy preventing velopharyngeal closure and manifests as a hypernasal resonance, audible nasal emissions, weak pressure consonants, compensatory articulation, reduced speech loudness, and nostril or facial grimacing. A multidisciplinary team using multimodal instruments (speech analysis, nasoendoscopy, videofluoroscopy, nasometry, and magnetic resonance imaging) to evaluate velopharyngeal function should manage these patients. Careful monitoring of velopharyngeal function by a speech pathologist remains paramount for early identification of VPI and the perceptual assessment should follow a standardized protocol. The greatest methodology problem in CLP studies has been the use of highly variable speech samples making comparison of published results impossible. It is hoped that ongoing international collaborative efforts to standardize procedures for collection and analysis of perceptual data will help this issue. Speech therapy is the mainstay treatment for velopharyngeal mislearning and compensatory articulation, but it cannot improve hypernasality, nasal emissions, or weak pressure consonants, and surgery is the definitive treatment for VPI. Although many surgical methods are available, there is no conclusive data to guide procedure choice. The goal of this review article is to present a review of established diagnostic and management techniques of VPI.

Elevated Heme Drives Evoked and Ongoing Pain Behaviors in WT Mice By Sensitization of Dorsal Root Ganglia Neurons

Individuals with sickle cell disease (SCD) suffer from complex stimulus-evoked and ongoing pain that is mediated in part by the hyperexcitability of their peripheral sensory neurons. However, it is unclear whether acute or chronic elevation of cell free heme, a key pathological feature of SCD, contributes to the aberrant activity of sensory neurons. Thus, determining whether heme drives pain behavior and enhanced excitability of dorsal root ganglia (DRG) primary sensory neurons involved in pain signal transduction is critical for the development of targeted pain therapies for SCD. In the current experiments, we use evoked and ongoing pain behavior assays and in vitro calcium imaging to evaluate the hypothesis that acute increases in heme causes direct sensitization of nociceptive DRG neurons in wildtype (WT) mice. Our preliminary data reveal that similar to pain behaviors in the mouse model of SCD, hind paw injection of heme into WT mice induces mechanical hypersensitivity (Figure 1). We also observed increased aversive responses to dynamic paintbrush and noxious needle stimulation as well as the onset of paw licking behavior suggesting that heme also drives ongoing, non-evoked pain. These data suggest that axon terminals in the skin become rapidly sensitized when exposed to elevated heme. We next administered heme to primary cultured DRG neurons in vitro and observed calcium flux across the neuronal cell membrane that was dependent on extracellular calcium. To determine if heme directly triggers action potentials or enhances spontaneous activity of sensory neurons, we conducted electrophysiological recordings of neuronal activity in neurons held at resting membrane potential at physiological temperature. Our preliminary data indicate that exposure to heme may directly enhance neuronal action potential firing frequency (Figure 2). Together, these data suggest that heme opens calcium channels on sensory neurons to initiate pain signal transduction and drive acute pain behaviors. We plan to conduct additional non-evoked pain behavior assays including facial grimace analysis and conditioned place aversion to determine whether heme injection is sufficient to drive ongoing pain. We will further determine whether exposure to heme enhances the intrinsic excitability of mechanical and cold sensitive neurons as heme-dependent hyperactivity of these neurons may lead to our observed acute onset mechanical and cold hypersensitivity in heme-injected mice. Completion of these experiments will shed light on the contributions of cell free heme to SCD pain and illuminate downstream effectors that may be targeted to provide analgesic relief for this historically understudied and debilitating disease.

Speech and Burden of Secondary Surgical Interventions Following One-Stage Repair of Unilateral Cleft Lip and Palate and Alveolar Bone Grafting Performed at Different Timings.

A comprehensive assessment of the treatment outcome in cleft lip and palate involves evaluating speech and the impact of speech-correcting surgical interventions. This retrospective case-control study compared the speech outcomes of 37 boys and 19 girls with unilateral cleft lip and palate (UCLP) who underwent one-stage cleft repair at an average age of 8.1 months and alveolar bone grafting either before or after 6 years of age, with a non-cleft control group at an average age of 10 years. Two experienced speech and language pathologists conducted perceptual speech assessments using a specialized test of 27 sentences designed for Polish-speaking cleft patients. The results revealed that 5.3% had severe hypernasality, 1.8% had severely impaired speech intelligibility, 10.7% exhibited retracted compensatory articulations, and 7.1% displayed facial grimacing. Mild hyponasality was observed in 12.3% of patients, while 16.1% exhibited voice abnormalities. Additionally, 12.5% of patients required orofacial fistula repairs, 3.6% underwent pharyngoplasties, and 28.6% received ear ventilation tube insertions. The study indicates that speech abnormalities in UCLP patients were relatively infrequent and not highly severe, suggesting that the primary UCLP repair method presented effectively reduced the need for further surgical interventions, leading to positive speech outcomes.

Protease-Activated Receptor 2 (PAR2) Expressed in Sensory Neurons Contributes to Signs of Pain and Neuropathy in Paclitaxel Treated Mice

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice. PAR2 knockout/wildtype (WT) mice and mice with PAR2 ablated in sensory neurons were treated with PTX administered via intraperitoneal injection. In vivo behavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. The pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781. Mechanical allodynia caused by PTX treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the DRG of the PTX-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the PTX-treated control mice had a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG, where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia. PerspectiveOur work demonstrates that PAR2 expressed in sensory neurons plays a key role in PTX-induced mechanical allodynia, spontaneous pain, and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of PTX CIPN.

Foramen lacerum impingement of trigeminal nerve root as a rodent model for trigeminal neuralgia.

Trigeminal neuralgia (TN) is a classic neuralgic pain condition with distinct clinical characteristics. Modeling TN in rodents is challenging. Recently, we found that a foramen in the rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root. Using this access, we developed a foramen lacerum impingement of trigeminal nerve root (FLIT) model and observed distinct pain-like behaviors in rodents, including paroxysmal asymmetric facial grimaces, head tilt when eating, avoidance of solid chow, and lack of wood chewing. The FLIT model recapitulated key clinical features of TN, including lancinating pain-like behavior and dental pain-like behavior. Importantly, when compared with a trigeminal neuropathic pain model (infraorbital nerve chronic constriction injury [IoN-CCI]), the FLIT model was associated with significantly higher numbers of c-Fos-positive cells in the primary somatosensory cortex (S1), unraveling robust cortical activation in the FLIT model. On intravital 2-photon calcium imaging, synchronized S1 neural dynamics were present in the FLIT but not the IoN-CCI model, revealing differential implication of cortical activation in different pain models. Taken together, our results indicate that FLIT is a clinically relevant rodent model of TN that could facilitate pain research and therapeutics development.

Efficacy of dual enkephalinase inhibition in a preclinical migraine model is mediated by activation of peripheral delta opioid receptors.

The aim of this study was to evaluate whether elevating levels of enkephalin by inhibiting their degradation can attenuate stress-induced migraine-like behaviors in mice. Previous studies in animals have suggested the delta opioid receptor (DOR) as a novel migraine target. The primary endogenous ligands for DOR are enkephalins and their levels can be increased by pharmacological inhibition of enkephalinases; however, it is not clear whether enkephalinase inhibition can be efficacious in preclinical migraine models through activation of DOR or whether other opioid receptors might be involved. Further, it is not clear whether opioid receptors in the central nervous system are necessary for these effects. This study used a model of repetitive restraint stress in mice that induces periorbital hypersensitivity and priming to the nitric oxide donor sodium nitroprusside (SNP; 0.1 mg/kg). Von Frey filaments were used to measure periorbital mechanical thresholds and grimace scores were evaluated by observing mouse facial features. Animals were treated with the dual enkephalinase inhibitor (DENKI) PL37. On day two post-stress, PL37 given to mice via either intravenous injection (10 mg/kg) or oral gavage (20 mg/kg) significantly attenuated stress-induced periorbital hypersensitivity and facial grimace responses. Additionally, both intravenous (10 mg/kg) and oral gavage (20 mg/kg) of PL37 prior to SNP (0.1 mg/kg) administration on day 14 post-stress significantly reduced SNP-induced facial hypersensitivity. Injection of the DOR antagonist naltrindole (0.1 mg/kg) but not the mu-opioid receptor antagonist CTAP (1 mg/kg) prior to PL37 treatment blocked the effects. Finally, pretreatment of mice with the peripherally restricted opioid receptor antagonist naloxone methiodide (5 mg/kg) blocked the effects of PL37. These data demonstrate that inhibiting enkephalinases, and thus protecting enkephalins from degradation, attenuates stress-induced migraine-like behavior via activation of peripheral DOR. Peripheral targeting of endogenous opioid signaling may be an effective therapeutic strategy for migraine.

Dystonia as Presenting Feature of Compound Heterozygous PMPCA Gene Variants.

Video 1. This video shows the patient at 24 years. Dystonia is generalized, particularly severe at cranio-cervical level, but also involving the upper limbs. Speech is severely impaired. The clip shows involuntary orofacial movements, jaw-opening and tongue protrusion dystonia. At cervical level, there are abnormal postures and torsional movements relieved by a sensory trick (touching the chin with the left hand). Upper limb involvement is prevalent in the right arm with writer's cramp and evidence of mirror dystonia. Gait is broad-based with evident right foot dystonia accentuated by walking. Video 2. Video taken at home at age 29, three months after bilateral GPi implant. Dystonia has progressed. Facial grimaces are continuous, there is constantly flexed neck posture with head tilt to the right and rotational movements. Speech is not intelligible. Dystonic slowing is evident upon repetitive finger and foot tapping. There is bilateral dysmetria in the upper limbs. Sensory tricks (touching of eyelids) provides inconstant relief. The patient is unable to write. Diffuse muscle atrophy is evident, with normal strength. Deep tendon reflexes are brisk bilaterally. The patient is able to stand-up unassisted and uses a walker due to severe gait ataxia. Standing posture is characterized by severe neck and trunk flexion. Gait is wide-based with cock-walk appearance. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

PAR2 activation in the dura causes acute behavioral responses and priming to glyceryl trinitrate in a mouse migraine model

BackgroundMigraine is a severely debilitating disorder that affects millions of people worldwide. Studies have indicated that activation of protease-activated receptor-2 (PAR2) in the dura mater causes headache responses in preclinical models. It is also well known that vasodilators such as nitric oxide (NO) donors can trigger migraine attacks in migraine patients but not controls. In the current study we examined whether activation of PAR2 in the dura causes priming to the NO donor glyceryl trinitrate (GTN).MethodsA preclinical behavioral model of migraine was used where stimuli (PAR2 agonists: 2at-LIGRL-NH2 (2AT) or neutrophil elastase (NE); and IL-6) were applied to the mouse dura through an injection made at the intersection of the lamdoidal and sagittal sutures on the skull. Following dural injection, periorbital von Frey thresholds and facial grimace responses were measured until their return to baseline. GTN was then given by intraperitoneal injection and periorbital hypersensitivity and facial grimace responses observed until they returned to baseline.ResultsWe found that application of the selective PAR2 agonist 2at-LIGRL-NH2 (2AT) onto the dura causes headache-related behavioral responses in WT but not PAR2−/− mice with no differences between sexes. Additionally, dural PAR2 activation with 2AT caused priming to GTN (1 mg/kg) at 14 days after primary dural stimulation. PAR2−/− mice showed no priming to GTN. We also tested behavioral responses to the endogenous protease neutrophil elastase, which can cleave and activate PAR2. Dural neutrophil elastase caused both acute responses and priming to GTN in WT but not PAR2−/− mice. Finally, we show that dural IL-6 causes acute responses and priming to GTN that is identical in WT and PAR2−/− mice, indicating that IL-6 does not act through PAR2 in this model.ConclusionsThese results indicate that PAR2 activation in the meninges can cause acute headache behavioral responses and priming to an NO donor, and support further exploration of PAR2 as a novel therapeutic target for migraine.

Teaching Neuro Images : Facial grimacing and sensorineural hearing loss in a woman with cirrhosis of the liver

A 29-year-old woman presented with 5-year history of gait instability and hearing loss. Medical history disclosed cirrhosis of the liver and polycythemia. Examination showed bradykinesia, facial grimacing, cervical dystonia, and ataxia. Neuroimaging showed hyperintense signal in basal ganglia on T1-weighted images (figure). Blood tests showed 18.5 g/dL of hemoglobin and 1,500 nmol/L of serum manganese (reference <320 nmol/L). Genetic analysis revealed previously described pathogenic1,2 homozygous mutation c.266T>C(p.Leu89Pro) in the SLC30A10 gene.

Clinical Findings of Sydenham Chorea in Pediatric Patients: A Single-Center Retrospective Study

Purpose: Sydenham chorea is known for its rapid, irregular, and aimless involuntary movements and is considered a benign and self-limiting condition among the major manifestations of rheumatic fever. The current study reviewed the demographic, clinical, and paraclinical findings of pediatric patients with Sydenham chorea.Methods: This cross-sectional study was conducted among 22 patients with Sydenham chorea who were admitted to the pediatric wards of Mashhad Imam Reza and Ghaem Hospitals between 2006 and 2016. Data from these patients’ medical records were extracted, organized using checklist forms, and analyzed.Results: Eight patients were male and 14 were female. The average age was 10.09±3.53 years. In 31.8% of patients, chorea was the only sign of rheumatic fever. Chorea was unilateral in 21.1% of patients. The most common clinical findings were, in descending order, jerky movements, facial grimacing, gait disorders, mental disorders, speech disorders, muscle weakness, and milkmaid’s grip. Cardiac auscultation was normal in 76.2% of patients, while a holosystolic murmur was heard in 23.8%. In laboratory exams, 50% of patients were erythrocyte sedimentation rate (ESR)-positive, 31.2% were C-reactive protein (CRP)-positive, and 53.3% were anti-streptolysin O (ASO)-positive. Echocardiography showed the prevalence of mitral regurgitation (63.6%), aortic regurgitation (45.5%), tricuspid regurgitation (22.7%), pulmonary regurgitation (4.5%), and pericardial effusion (4.5%).Conclusion: This study showed that Sydenham chorea can be the only sign of rheumatic fever. This disease typically occurs in children between the ages of 7 and 12. ESR, CRP, and ASO can be the most effective laboratory tests for diagnosis.

Amantadine augmentation in electroconvulsive therapy-resistant catatonia: a case report.

IntroductionCatatonia is a syndrome characterized by physical symptoms ranging from immobility to excessive motor activity. Besides being historically associated mainly with schizophrenia, it is widely known that it can be the expression of different psychiatric, neurological or medical conditions. The treatment of choice is benzodiazepines, indicating electroconvulsive therapy in refractory cases. Amantadine is considered a second-line therapy in setting when electroconvulsive therapy is not available.ObjectivesTo describe the case of a patient with treatment-resistant catatonic schizophrenia. Not having responded to benzodiazepines or electroconvulsive therapy, potentiation with amantadine was subsequently started.MethodsOur patient presented at a psychopathological level; psychomotor inhibition, a perplexing attitude, and mute speech. At the motor level; ambitendency, indecision, automatic obedience, motor stereotypes, and facial grimaces. He did not present other alterations at the neurological level. Regarding complementary explorations, we performed neuroimaging and blood tests, which resulted all anodyne. With an alternative diagnosis, we considered that sequelae of a neuroleptic malignant syndrome could have produced the symptoms that he had suffered. Due to the persistence of the symptoms and their typical characteristics, catatonia was our first diagnostical impression. As treatment with benzodiazepines was ineffective, electroconvulsive therapy was started. No clinical improvement was observed. Given the refractoriness of the case, a review of the existing literature was carried out. We found reports of a good response to amantadine in similar cases. Amantadine was introduced up to a dose of 200mg.ResultsAfter four weeks of treatment with amantadine at a dose of 200mg, the patient showed meager improvement at both psychopathological and motor level.ConclusionsWe find the case of a patient with long-term schizophrenia who is nowadays dependent on all daily living activities and requires sustained care.Disclosure of InterestNone Declared