Facial Nucleus Research Articles

The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series.

This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.

MORPHOMETRIC PARAMETERS OF THE HUMAN FETUS PONS 17-18 WEEKS OF INTRAUTERINE DEVELOPMENT

Relevance. Currently, increased interest is observed in the early stages of postnatal ontogenesis in research of age-related changes in the systems of the human body.
 Aim: To define the macrometric parameters of the pons of human fetuses of 17-18 weeks of fetal development, the sizes and area of the cranial nerve nuclei contained in pons, as well as the size and area of the nerve cells that form these nuclei.
 Materials and methods: We performed an anatomical and histological examination of 10 human fetuses at the stage of 17-18 weeks of intrauterine development.
 Results: The boundaries of the nucleus of the abductor nerve are unclear, the neurons of the nucleus are spherical or rounded in shape. The vestibular nucleus of the vestibulocochlear nerve has an indeterminate shape, the boundaries of the nucleus are not clear, neurons with different areas of the nucleus are noted, from large to small. The motor nucleus of the facial nerve has an elongated shape, with not clear outer edges, the nerve cells are dome-shaped. The principal nucleus of the trigeminal nerve has a rounded shape.
 Conclusions: We established that at 17-18 weeks of intrauterine development of human fetuses, the nucleus of the abductor nerve, the motor nucleus of the facial nerve, the principal nucleus of the trigeminal nerve, and the vestibular nucleus of the vestibulocochlear nerve were visualized. Nucleus of the abductor nerve has the largest area, the smallest -has the vestibular nucleus of the vestibulocochlear nerve. The largest area of neurons of the vestibular nucleus was established in comparison with the area of the nucleus of the facial, trigeminal and abductor nerves. The diameter and area of the nuclei of the cells of the abductor nerve, the motor nucleus of the facial nerve, and the principal nucleus of the trigeminal nerve have almost the same size, while the area of the neurons of the vestibulocochlear nerve is different, there is a group of neurons with a large area, and there is a group with a much smaller area of neurons.

Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity.

The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.

Dense reconstruction of elephant trunk musculature

The elephant trunk operates as a muscular hydrostat1,2 and is actuated by the most complex musculature known in animals.3,4 Because the number of trunk muscles is unclear,5 we performed dense reconstructions of trunk muscle fascicles, elementary muscle units, from microCT scans of an Asian baby elephant trunk. Muscle architecture changes markedly across the trunk. Trunk tip and finger consist of about 8,000 extraordinarily filigree fascicles. The dexterous finger consists exclusively of microscopic radial fascicles pointing to a role of muscle miniaturization in elephant dexterity. Radial fascicles also predominate (at 82% volume) the remainder of the trunk tip, and we wonder if radial muscle fascicles are of particular significance for fine motor control of the dexterous trunk tip. By volume, trunk-shaft muscles6 comprise one-third of the numerous, small radial muscle fascicles; two-thirds of the three subtypes of large longitudinal fascicles (dorsal longitudinals, ventral outer obliques, and ventral inner obliques);7,8,9 and a small fraction of transversal fascicles. Shaft musculature is laterally, but not radially, symmetric. A predominance of dorsal over ventral radial muscles and of ventral over dorsal longitudinal muscles may result in a larger ability of the shaft to extend dorsally than ventrally10 and to bend inward rather than outward. There are around 90,000 trunk muscle fascicles. While primate hand control is based on fine control of contraction by the convergence of many motor neurons on a small set of relatively large muscles, evolution of elephant grasping has led to thousands of microscopic fascicles, which probably outnumber facial motor neurons.

Facial expressions of pain: the role of the serotonergic system

RationaleAlthough interest in the neurobiology of facial communication of pain has increased over the last decades, little is known about which neurotransmitter systems might be involved in regulating facial expressions of pain.ObjectivesWe aim to investigate whether the serotonergic system (5-HT), which has been implicated in various aspects of pain processing as well as in behavioral response inhibition, might play a role in facial expressions of pain. Using acute tryptophan depletion (ATD) to manipulate 5-HT function, we examined its effects on facial and subjective pain responses.MethodsIn a double-blind, placebo-controlled within-subject design, 27 participants received either an ATD or a control drink in two separate sessions. Approximately 5-h post-oral consumption, we assessed pain thresholds (heat, pressure) as well as facial and subjective responses to phasic heat pain. Moreover, situational pain catastrophizing and mood were assessed as affective state indicators.ResultsATD neither influenced pain thresholds nor self-report ratings, nor catastrophizing or mood. Only facial responses were significantly affected by ATD. ATD led to a decrease in pain-indicative as well as in pain-non-indicative facial responses to painful heat, compared to the control condition.ConclusionsDecrease in brain 5-HT synthesis via ATD significantly reduced facial responses to phasic heat pain; possibly due to (i) diminished disposition to display social behavior or due to (ii) decreased facilitation of excitatory inputs to the facial motor neuron.

A brainstem circuit for the expression of defensive facial reactions in rat

The brainstem houses neuronal circuits that control homeostasis of vital functions. These include the depth and rate of breathing1,2 and, critically, apnea, a transient cessation of breathing that prevents noxious vapors from entering further into the respiratory tract. Current thinking is that this reflex is mediated by two sensory pathways. One known pathway involves vagal and glossopharyngeal afferents that project to the nucleus of the solitary tract.3,4,5 Yet, apnea induced by electrical stimulation of the nasal epithelium or delivery of ammonia vapors to the nose persists after brainstem transection at the pontomedullary junction, indicating that the circuitry that mediates this reflex is intrinsic to the medulla.6 A second potential pathway, consistent with this observation, involves trigeminal afferents from the nasal cavity that project to the muralis subnucleus of the spinal trigeminal complex.7,8 Notably, the apneic reflex is not dependent on olfaction as it can be initiated even after disruption of olfactory pathways.9 We investigated how subnucleus muralis cells mediate apnea in rat. By means of electrophysiological recordings and lesions in anesthetized rats, we identified a pathway from chemosensors in the nostrils through the muralis subnucleus and onto both the preBötzinger and facial motor nuclei. We then monitored breathing and orofacial reactions upon ammonia delivery near the nostril of alert, head-restrained rats. The apneic reaction was associated with a grimace, characterized by vibrissa protraction, wrinkling of the nose, and squinting of the eyes. Our results show that a brainstem circuit can control facial expressions for nocifensive and potentially pain-inducing stimuli.

Mechanisms of Microglia Proliferation in a Rat Model of Facial Nerve Anatomy.

Although microglia exist as a minor glial cell type in the normal state of the brain, they increase in number in response to various disorders and insults. However, it remains unclear whether microglia proliferate in the affected area, and the mechanism of the proliferation has long attracted the attention of researchers. We analyzed microglial mitosis using a facial nerve transection model in which the blood-brain barrier is left unimpaired when the nerves are axotomized. Our results showed that the levels of macrophage colony-stimulating factor (M-CSF), cFms (the receptor for M-CSF), cyclin A/D, and proliferating cell nuclear antigen (PCNA) were increased in microglia in the axotomized facial nucleus (axotFN). In vitro experiments revealed that M-CSF induced cFms, cyclin A/D, and PCNA in microglia, suggesting that microglia proliferate in response to M-CSF in vivo. In addition, M-CSF caused the activation of c-Jun N-terminal kinase (JNK) and p38, and the specific inhibitors of JNK and p38 arrested the microglial mitosis. JNK and p38 were shown to play roles in the induction of cyclins/PCNA and cFms, respectively. cFms was suggested to be induced through a signaling cascade of p38-mitogen- and stress-activated kinase-1 (MSK1)-cAMP-responsive element binding protein (CREB) and/or p38-activating transcription factor 2 (ATF2). Microglia proliferating in the axotFN are anticipated to serve as neuroprotective cells by supplying neurotrophic factors and/or scavenging excite toxins and reactive oxygen radicals.

Establishment of a facial nerve trunk crush injury model and evaluation of facial nerve self-healing in rats.

To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.

Brainstem Modulates Parkinsonism-Induced Orofacial Sensorimotor Dysfunctions.

Parkinson's Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.

Interchangeable Role of Motor Cortex and Reafference for the Stable Execution of an Orofacial Action.

Animals interact with their environment through mechanically active, mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability or prehension would be profoundly impeded. The nervous system may keep track of the position of a sensorimotor organ via two complementary feedback mechanisms-peripheral reafference (external, sensory feedback) and efference copy (internal feedback). Yet, the potential contributions of these mechanisms remain largely unexplored. By training male rats to place one of their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, except in the absence of peripheral reafference to maintain motor stability. Finally, the red nucleus, which receives descending inputs from motor cortex and cerebellum and projects to facial motoneurons, is critically involved in the execution of the vibrissa positioning task. All told, our results point toward the existence of an internal model that requires either peripheral reafference or motor cortex to optimally drive voluntary motion.SIGNIFICANCE STATEMENT How does an animal know where a mechanically active, mobile sensor lies relative to its body? We address this basic question in sensorimotor integration using the motion of the vibrissae in rats. We show that rats can learn to reliably position their vibrissae in the absence of sensory feedback or in the absence of motor cortex. Yet, when both sensory feedback and motor cortex are absent, motor precision is degraded. This suggests the existence of an internal model able to operate in closed- and open-loop modes, requiring either motor cortex or sensory feedback to maintain motor stability.

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

Drop-off in axonal regeneration along the length of a cross-face nerve graft: An experimental study in rats.

The average nerve graft length utilized in cross-face nerve grafting for reconstruction of facial nerve palsy is 20-22 cm. While the graft length is thought to be one of the greatest determinants of muscle strength, the mechanism through which this happens remains unknown. We studied changes in axonal regeneration along the length of a 2 cm cross-face nerve graft in a rat model. The hypothesis was that axon count would decrease along the length of the graft. A 2 cm nerve graft (sciatic nerve) was used as a cross-face nerve graft in 16 adult female, 210-250 g, Sprague Dawley rats. Thirteen weeks later, 5 mm nerve biopsies were taken at four sites: the facial nerve trunk (control), proximal graft, midpoint of graft (1 cm distal to coaptation) and distal graft (2 cm distal to coaptation). Retrograde nerve labeling with FluoroGold was performed at the biopsied nerve site and the facial motor nucleus was taken 1 week later. Microscopic imaging and manual counting of axons and labeled motor nuclei was performed. Retrograde-labeled motor neuron counts were decreased at the midway point of the graft compared to the facial trunk (1517 ± 335 axons, Δ% = 92.5, p = .01) and even further decreased at the distal end of the graft (269 ± 293 axons, Δ% = 175.5, p = .006). Analysis of the nerve biopsies demonstrated no significant differences in myelinated axon count between the nerve trunk and over the length of the nerve graft (range 6207-7179 axons, Δ% = 14.5, p = .07). In a rat model, the number of regenerating motor neurons drops off along the length of the graft and axon count is preserved due to axon sprouting. How this pattern correlates to ultimate muscle strength remains unknown, but this study provides insight into why shorter grafts may afford better outcomes.

Efferent network of Neuromedin B neurons in the retrotrapezoid nucleus in mice

In the parafacial region of the medulla, the peptide Neuromedin B (NMB) is expressed in retrotrapezoid nucleus (RTN) neurons that are proposed to be central respiratory chemoreceptors. The efferent network of RTN Nmb neurons has been established in rats, but has not been examined in mice in detail. To map the downstream connections of RTN Nmb neurons we performed genetically-targeted tracing using novel Nmb-Cre knock-in mice. Adult Nmb-Cre mice were injected in the RTN unilaterally with a Cre-dependent AAV producing expression of red fluorescent protein (AAV-Cre ON -mScarlet). Expression of Nmb was identified by fluorescent in situ hybridization (FISH). Injections of AAV-Cre ON -mScarlet in the RTN (N=3) transduced 58 ± 11 % of Nmb-expressing neurons with a selectivity for Nmb neurons of 98 ± 1 %. Intensely labelled axons and terminals were observed in regions overlapping with the medullary and pontine respiratory network. We observe an intra-RTN network of fibers with close appositions between RTN Nmb neurons, as well as moderate projections to areas dorso-medial to the facial nucleus and medially adjacent to the locus coeruleus. There was a modest contralateral projection to the medullary respiratory network, but none to the pontine respiratory network. No labelled fibers were found rostral of the parabrachial nucleus. Anterograde tracing of RTN Nmb neurons was complemented using retrograde transport of Cre-recombinase (AAVrg-Cre) in R26-loxSTOPlox-L10-GFP mice (eGFP-reporter) mice combined with labelling of transcript for Nmb by FISH. Small volumes (3-6 nL) of AAVrg-Cre were unilaterally injected in the Pre-Bötzinger complex (PreBöt), lateral parabrachial nucleus (LPB), caudal ventral respiratory group (cVRG), and the nucleus of the solitary tract (NTS). We determined the proportion of total RTN Nmb neurons that were retro-labelled from each target (PreBöt- 75 ± 3%, n=3; LPB- 65 ± 3%, n=4; cVRG- 54 ± 6%, n=3; NTS- 38 ± 3%, n=3). This result suggests that RTN neurons have a high degree of collateralization within the medullary and pontine respiratory network. Injections of AAVrg-Cre in the PreBöt labelled 16 ± 11% of RTN Nmb neurons contralateral to the injection site. Collectively, these neuroanatomical observations show that the efferent network of RTN Nmb neurons broadly innervate and selectively the central respiratory network in alignment with prior descriptions in rat. Furthermore, we provide evidence for novel connectivity between RTN Nmb neurons. This anatomy supports the idea that RTN neurons generate a coordinated widespread excitation of the respiratory rhythm and pattern generating network in order to promote alveolar ventilation. Funding from NIH-HLBI #HL148004 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An Atypical Manifestation of Lateral Medullary Syndrome (P12-5.011)

<h3>Objective:</h3> To describe a case of lateral medullary syndrome (LMS) presenting with ipsilateral hemiparesis and upper motor neuron (UMN)-type facial palsy. <h3>Background:</h3> LMS is a classical vascular syndrome involving the posterior inferior cerebellar artery, which presents typically with ipsilateral Horner syndrome, ipsilateral ataxia, and contralateral hemianesthesia. Motor weakness and facial palsy are not traditionally presented in LMS. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 62-year-old male with poorly controlled hypertension presented with sudden onset left hemiparesis. On presentation, initial blood pressure was 178/95 mmHg. The neurological exam showed dysarthria, left facial palsy sparing the forehead, left facial hypoesthesia, and left hemiparesis (NIHSS 8). Diffusion-weighted MR Brain showed acute infarct in the left lateral medulla. FLAIR sequence showed chronic infarct in the right thalamus. CT arteriogram revealed non-opacification of the left vertebral artery at the level of C2–C3 with opacification of the distal left V4 via retrograde flow, severe stenosis of the right M1 segment, and multifocal atherosclerosis of the bilateral internal carotid arteries. Initial labs showed elevated LDL (213 mg/dl) and normal hemoglobin A1c. Right hemianesthesia was reported during his hospitalization; dysphagia, frequent hiccups, and left dysmetria out of proportion to weakness were noted during the recovery. After acute interventions, he was started on dual antiplatelet treatments for 90 days and a single antiplatelet afterward given concerns of large vessel disease as stroke etiology. <h3>Conclusions:</h3> Atypical clinical presentation in this LMS case included the combination of ipsilateral hemiparesis and ipsilateral UMN-type facial palsy. LMS with ipsilateral hemiparesis is known as Opalski’s syndrome, which is explained by involving the post-decussating pyramidal tract at the lower medulla and upper cervical spine. The explanation of ipsilateral UMN-type facial palsy in our case remains unclear. One possible explanation is the aberrant caudal looping of facial corticobulbar fibers into medulla oblongata prior to synapsing with the pontine facial nucleus. <b>Disclosure:</b> Dr. Yu has nothing to disclose. Mr. Bluntson has nothing to disclose. Dr. Sharma has nothing to disclose.

Beneficial Effect of Bee Venom and Its Major Components on Facial Nerve Injury Induced in Mice.

Peripheral nerve injury (PNI) is a health problem that affects many people worldwide. This study is the first to evaluate the potential effect of bee venom (BV) and its major components in a model of PNI in the mouse. For that, the BV used in this study was analyzed using UHPLC. All animals underwent a distal section-suture of facial nerve branches, and they were randomly divided into five groups. Group 1: injured facial nerve branches without any treatment. Group 2: the facial nerve branches were injured, and the normal saline was injected similarly as in the BV-treated group. Group 3: injured facial nerve branches with local injections of BV solution. Group 4: injured facial nerve branches with local injections of a mixture of PLA2 and melittin. Group 5: injured facial nerve branches with local injection of betamethasone. The treatment was performed three times a week for 4 weeks. The animals were submitted to functional analysis (observation of whisker movement and quantification of nasal deviation). The vibrissae muscle re-innervation was evaluated by retrograde labeling of facial motoneurons in all experimental groups. UHPLC data showed 76.90 ± 0.13%, 11.73 ± 0.13%, and 2.01 ± 0.01%, respectively, for melittin, phospholipase A2, and apamin in the studied BV sample. The obtained results showed that BV treatment was more potent than the mixture of PLA2 and melittin or betamethasone in behavioral recovery. The whisker movement occurred faster in BV-treated mice than in the other groups, with a complete disappearance of nasal deviation two weeks after surgery. Morphologically, a normal fluorogold labeling of the facial motoneurons was restored 4 weeks after surgery in the BV-treated group, but no such restoration was ever observed in other groups. Our findings indicate the potential of the use of BV injections to enhance appropriate functional and neuronal outcomes after PNI.

The widespread action observation/execution matching system for facial expression processing.

Observing and understanding others' emotional facial expressions, possibly through motor synchronization, plays a primary role in face-to-face communication. To understand the underlying neural mechanisms, previous functional magnetic resonance imaging (fMRI) studies investigated brain regions that are involved in both the observation/execution of emotional facial expressions and found that the neocortical motor regions constituting the action observation/execution matching system or mirror neuron system were active. However, it remains unclear (1) whether other brain regions in the limbic, cerebellum, and brainstem regions could be also involved in the observation/execution matching system for processing facial expressions, and (2) if so, whether these regions could constitute a functional network. To investigate these issues, we performed fMRI while participants observed dynamic facial expressions of anger and happiness and while they executed facial muscle activity associated with angry and happy facial expressions. Conjunction analyses revealed that, in addition to neocortical regions (i.e., the right ventral premotor cortex and right supplementary motor area), bilateral amygdala, right basal ganglia, bilateral cerebellum, and right facial nerve nucleus were activated during both the observation/execution tasks. Group independent component analysis revealed that a functional network component involving the aforementioned regions were activated during both observation/execution tasks. The data suggest that the motor synchronization of emotional facial expressions involves a widespread observation/execution matching network encompassing the neocortex, limbic system, basal ganglia, cerebellum, and brainstem.

Morphofunctional regeneration by mesenchymal stem cell and IGF-1 inoculation in a model of facial nerve crush injury in rats.

To analyze the morphofunctional regeneration process of facial nerve injury in the presence of insulin-like growth factor-1 and mesenchymal stem cells. Fourteen Wistar rats suffered unilateral facial nerve crushing and were randomly divided into two groups. All received insulin-like growth factor-1 inoculation, but only half of the animals received an additional inoculation of mesenchymal stem cells. The animals were followed for 90 days and facial nerve regeneration was analyzed via spontaneous facial motor function tests and immunohistochemistry in the nerve motor nucleus. The group that received the growth factor and stem cells showed a statistically superior mean in vibrissae movements (p < 0.01), touch reflex (p = 0.05) and eye closure (p < 0.01), in addition to better immunohistochemistry reactivity. There was a statistically significant difference in the mean number of cells in the facial nerve nucleus between the experimental groups (p = 0.025), with the group that received the growth factor and stem cells showing the highest mean. The association between growth factor and stem cells potentiates the morphofunctional regeneration of the facial nerve, occurring faster and more effectively. 4, degree of recommendation C.

Abstract Number ‐ 226: Pontine Stroke Presenting as 1.5 Syndrome Evolving to 9 Syndrome over 72 Hours.

Introduction A 75 year old woman with a past medical history of hypertension developed sudden‐onset vertigo, nausea and vomiting. She did not immediately seek medical care, thinking she was suffering from food poisoning. The following day her symptoms improved however she developed new right sided weakness and gait imbalance, prompting her presentation to the ED. Her neurologic exam noted complete loss of adduction of the right eye and loss of horizontal extraocular movements of the left eye. She also displayed right upper extremity paresis, right upper extremity dysmetria and mild dysarthria. MRI of the brain disclosed acute pontine infarcts in the ventral and dorsal left paramedian regions. Over the next three days, her horizontal gaze palsy improved with some return of adduction of the right eye and horizontal movements of the left eye. However right sided paresis worsened, and in addition, progressed to include complete left facial palsy (lower motor neuron lesion). She was able to be discharged to rehab, placed on Aspirin 81 mg daily and Ezetimibe (due to elevated liver function enzymes) and 30 day Cardiac Event Monitor follow up. Methods Case report and review of literature. Results Due to the combination of multiple cranial nuclei and white matter tracts in the brainstem, ischemia can lead to several clinical manifestations. There are various presenting clinical syndromes, named numerically by structures involved and/or the clinical deficit. One‐and‐a‐half (1.5) syndrome, first reported by Fischer in 1967, is an uncommon entity caused by a lesion (most commonly infarction) in the pontine tegmentum [1]. It consists of complete ipsilateral horizontal gaze palsy (due to involvement of ipsilateral Paramedian Pontine Reticular Formation/Abducens Nucleus and Medial Longitudinal Fasciculus) and loss of adduction of the contralateral eye (due to involvement of the contralateral Medial Longitudinal Fasciculus). Extension of the lesion to the facial nucleus can produce ipsilateral lower motor neuron type facial palsy, leading to an even more uncommon 8.5 syndrome (7 + 1.5), described by Eggenberger in 1998 [2]. When the lesion involves the corticospinal tracts and/or the medial lemniscus, it can lead to contralateral hemiparesis and/or hemisensory deficits; the so called “9 syndrome” first proposed by Rosini et al in 2013 [3]. This rare entity has been reported in only a handful of cases. Conclusions The awareness of complex brainstem neuroanatomy enables precise localization of the clinical deficits. The noted slow progression of the clinical syndrome from 1.5 to 8.5 and finally 9 syndrome over 72 hours in this case highlights the complexity of small vessel brainstem ischemia.

Bilateral Facial Nerve Palsy as a Rare Presentation of Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE), a disease of the immune system, has a relapsing-remitting course. It is known to affect multiple organ systems of the body, including the nervous system. Cranial neuropathy, particularly facial neuropathy, is an unusual complication of SLE whose pathogenic mechanism is still not understood. Cardiac involvement, like myocarditis and papilledema, is another rare presentation of SLE. A 23-year-old male had bilateral lower motor neuron type of facial palsy which on a thorough investigation was found to be as a manifestation of SLE confirmed by antinuclear antibodies and double-stranded DNA antibody positive test. Electrocardiogram and echocardiography were suggestive of myocarditis. Fundus examination revealed Grade 2 papilledema. The patient was managed with symptomatic treatment along with corticosteroids, to which he responded gradually. Bilateral facial nerve lower motor neuron type palsy is a rare manifestation of SLE which should be diagnosed promptly and can be managed with corticosteroids. The clinician should also keep an eye on infrequent manifestations like myocarditis and papilledema.

Neurocircuitry underlying the antidepressant effect of retrograde facial botulinum toxin in mice

BackgroundsBotulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized.ResultsHere, we modeled MDD using mice subjected to chronic restraint stress (CRS). By pre-injecting BoNT/A into the unilateral whisker intrinsic musculature (WIM), and performing behavioral testing, we showed that pre-injection of BoNT/A attenuated despair- and anhedonia-like phenotypes in CRS mice. By applying immunostaining of BoNT/A-cleaved SNAP25 (cl.SNAP25197), subcellular spatial localization of SNAP25 with markers of cholinergic neurons (ChAT) and post-synaptic membrane (PSD95), and injection of monosynaptic retrograde tracer CTB-488-mixed BoNT/A to label the primary nucleus of the WIM, we demonstrated that BoNT/A axonal retrograde transported to the soma of whisker-innervating facial motoneurons (wFMNs) and subsequent transcytosis to synaptic terminals of second-order neurons induced central effects. Furthermore, using transsynaptic retrograde and monosynaptic antegrade viral neural circuit tracing with c-Fos brain mapping and co-staining of neural markers, we observed that the CRS-induced expression of c-Fos and CaMKII double-positive neurons in the ventrolateral periaqueductal grey (vlPAG), which sent afferents to wFMNs, was down-regulated 3 weeks after BoNT/A facial pre-administration. Strikingly, the repeated and targeted silencing of the wFMNs-projecting CaMKII-positive neurons in vlPAG with a chemogenetic approach via stereotactic injection of recombinant adeno-associated virus into specific brain regions of CRS mice mimicked the antidepressant-like action of BoNT/A pre-treatment. Conversely, repeated chemogenetic activation of this potential subpopulation counteracted the BoNT/A-improved significant antidepressant behavior.ConclusionWe reported for the first time that BoNT/A inhibited the wFMNs-projecting vlPAG excitatory neurons through axonal retrograde transport and cell-to-cell transcytosis from the injected location of the WIM to regulate depressive-like phenotypes of CRS mice. For the limited and the reversibility of side effects, BoNT/A has substantial advantages and potential application in MDD.