Aberrant reinnervation following hypoglossal nerve damage

Hypoglossal nerve damage is a known complication of carotid endarterectomy, occurring in approximately 5% of endarterectomies. The vast majority of these patients recover without functional disability from this injury even if the tongue remains hemiplegic. We report 2 patients who suffered hypoglossal nerve section during neck surgery. Although they were initially mildly symptomatic, they developed increasingly severe dysarthria and dysphagia beginning 4 months after surgery. EMG revealed abnormal coactivation of the genioglossus and styloglossus muscles on the affected side, suggesting aberrant reinnervation. Aberrant reinnervation is a well-known complication of facial nerve injury, but has not been previously recognized in hypoglossal nerve injury. Like the face, the tongue is composed of many muscles that must perform complex movements. Normally, injury to one hypoglossal nerve causes little or no disability, but when aberrant reinnervation occurs, the tongue no longer moves in a coordinated manner, and significant dysarthria ensues.     

Developmental modulation of mouse hypoglossal nerve inspiratory output in vitro by noradrenergic receptor agonists

The ontogeny of the noradrenergic receptor subtypes modulating hypoglossal (XII) nerve inspiratory output was characterized. Noradrenergic agents were locally applied over the XII nucleus of rhythmically active medullary slice preparations isolated from mice between zero and 13 days of age (P0-P13) and the effects on XII inspiratory burst amplitude quantified. The alpha1 receptor agonist phenylephrine (PE, 0.1-10 microM) produced a dose-dependent, prazosin-sensitive (0.1-10 microM) increase in XII nerve inspiratory burst amplitude. The magnitude of this potentiation increased steadily from a maximum of 15+/-8% in P0 mice to 134+/-4% in P12-P13 mice. The beta receptor agonist isoproterenol (0.01-1.0 mM) produced a prazosin-insensitive, propranolol-sensitive potentiation of XII nerve burst amplitude. The isoproterenol-mediated potentiation increased with development from 27+/-5% in P0-P1 slices, to 37+/-3% in P3 slices and 45+/-4% in P9-P10 slices. The alpha2 receptor agonist clonidine (1 mM) reduced XII nerve inspiratory burst amplitude in P0-P3 slices by 29+/-5%, but had no effect on output from P12-P13 slices. An alpha2 receptor-mediated inhibition of inspiratory activity in neonates (P0-P3) was further supported by a 19+/-3% reduction in XII nerve burst amplitude when norepinephrine (NE, 100 microM) was applied in the presence of prazosin (10 microM) and propranolol (100 microM). Results indicate that developmental increases in potentiating alpha1 and, to a lesser extent, beta receptor mechanisms combine with a developmentally decreasing inhibitory mechanism, most likely mediated by alpha2 receptors, to determine the ontogenetic time course by which NE modulates XII MN inspiratory activity.     

Role of GABAB receptors in the control of hypoglossal motoneurons in vivo

There is little information on GABAB receptor-mediated effects on orofacial motoneurons. We recorded the inspiratory activity from both hypoglossal (XII) nerves in urethane-anesthetized, paralyzed, vagotomized and artificially ventilated rats. A GABAB receptor agonist, baclofen, or antagonist, CGP-35348, was microinjected into one XII nucleus. Baclofen rapidly reduced the XII nerve activity in a dose-dependent manner by over 50%. The antagonist caused a delayed suppression of activity by 40%. We conclude that: (1) GABAB receptors within the XII nucleus may suppress the activity of inspiratory XII motoneurons, but they are not tonically active under the conditions of our experiment; (2) there is a net endogenous excitatory effect in XII motoneurons that is mediated by GABAB receptors located in the reticular formation surrounding the XII nucleus.     

Oral manifestations and differential diagnosis of isolated hypoglossal nerve palsy: report of two cases

Isolated hypoglossal nerve palsy is rare, but occasionally it appears as the initial or solitary sign of an intracranial or extracranial space-occupying lesion, a head and neck injury, or a vascular abnormality of the internal carotid artery. Therefore it should be considered in differential diagnosis. We report two cases of isolated unilateral hypoglossal nerve palsy. In Case 1 the cause of the palsy appeared to be hypoglossal nerve neurilemmoma within the hypoglossal canal, whereas in Case 2 the cause could not be identified. Neither patient complained of any disability other than slight dysarthria. The tongue deviated toward the healthy side at rest and toward the affected side on protrusion. Hemiatrophy of the tongue with fatty displacement was demonstrated by means of T1-weighted magnetic resonance imaging. Dentists who might at times see patients with isolated hypoglossal nerve palsy should be aware of the significance of its oral manifestation, and they should be able to perform differential diagnosis of patients with the condition who appear for treatment.     

Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis

The classic hypoglossal transfer to the facial nerve is invariably followed by complications caused by tongue atrophy. In 1984, Terzis introduced the "baby-sitter" procedure which involved a formal cross-facial procedure, in addition to partial neurectomy of the hypoglossal nerve, and an end-to-side coaptation with the ipsilateral facial nerve. This reported study provides, for the first time, quantification of the number of hypoglossal motor fibers needed to successfully restore eye sphincter function, using an end-to-side coaptation with preservation of the tongue. Thirty adult Sprague-Dawley rats were divided into six groups: control, denervated, perineurial window, 20 percent partial neurectomy (PN), 40 percent PN, and 80 percent PN. The procedure involves interposing a nerve graft (saphenous) between the partially severed XII nerve and the upper zygomatic branch of the facial nerve. Evaluation of the behavioral data (blink reflex) revealed good-to-superb return of the blinking mechanism in the 40 percent group, without significant tongue atrophy. Electrophysiologic data in the 40 percent neurectomy group demonstrated superiority to the other groups. Quantitative axonal morphometry of the coaptation sites and graft, as well as motor end-plates of the orbicularis oculi muscle and tongue showed the 40 percent partial neurectomy group to be the optimal group.     

NMR study of virenose and dihydrohydroxystreptose isolated from Coxiella burnetii phase I lipopolysaccharide

Expression of Shc family protein (Shc/ShcA, SCK/ShcB and N-Shc/ShcC) and Grb2 mRNAs in the hypoglossal motoneurons after axotomy was examined by in situ hybridization. In normal hypoglossal motor neurons, N-Shc mRNA was expressed predominantly, whereas the Shc mRNA level is very low. Rat hypoglossal nerve injury reversed the expressions of these two molecules in hypoglossal motoneurons. Shc mRNA expression was up-regulated markedly whereas N-Shc was down-regulated after nerve injury. Expression levels of SCK, another Shc family member, and Grb2 were unaffected by nerve injury. These results suggest that, whereas the N-Shc-mediated pathway dominates under normal conditions, an alternative Shc-mediated pathway is utilized in the event of nerve injury. By changing the expression of the Shc family members, the signaling pathway can be altered and various responses induced for nerve regeneration.     

A motor neuron-specific epitope and the low-affinity nerve growth factor receptor display reciprocal patterns of expression during development, axotomy, and regeneration

Somatic motor neurons begin to express the transmitter synthesizing enzyme, choline acetyltransferase (ChAT) and the low-affinity nerve growth factor receptor (NGFR) during embryonic development. However, as motor neurons mature in postnatal life, they lose immunoreactivity for NGFR and acquire a motor neuron-specific epitope that is recognized by the monoclonal antibody, MO-1. The present study was undertaken to examine the effect of nerve injury in adult rats on these three developmentally regulated markers in two populations of somatic motor neurons. Unilateral transection, ligation, or crushing of the sciatic nerve resulted in a loss of MO-1 binding and a concomitant rise in immunoreactivity for NGFR within axotomized motor neurons in lumbar levels of the spinal cord. These changes, detectable within 5 days following nerve injury, are reversed with reinnervation, but persist if reinnervation is prevented by chronic axotomy. Thus, regulation of the expression of NGFR and the MO-1 epitope appears to be critically dependent upon interactions between motor neurons and target muscles. These observations are also consistent with the idea that during regeneration, neurons may revert to a developmentally immature state; in motor neurons, this state is characterized by the presence of NGFRs and the absence of the MO-1 epitope. Transection of the hypoglossal nerve, a purely motor nerve, resulted in a similar loss of MO-1 binding and a selective rise in NGFR immunoreactivity in neurons within the ipsilateral hypoglossal motor nucleus. In addition, immunoreactivity for ChAT was also lost in axotomized hypoglossal motor neurons. In contrast, injury to the sciatic nerve, which bears both sensory and motor axons, did not result in any detectable change in ChAT immunoreactivity in spinal motor neurons.     

Effects of bilateral hypoglossal and glossopharyngeal nerve blocks on epiglottic and soft palate position in exercising horses

OBJECTIVE: To determine the effect of bilateral hypoglossal and and glossopharyngeal nerve block on epiglottic and soft palate position and tracheal and pharyngeal pressures in exercising horses. ANIMALS: 5 Standardbreds. PROCEDURE: Tracheal and pharyngeal pressures were measured in 5 Standardbreds exercising at the speed at which the horses achieved 50, 75, and 100% of maximal heart rate after bilateral hypoglossal and glossopharyngeal nerve block and without nerve block. Nerve block was achieved by injection of 1 to 2 ml of 2% mepivicaine hydrochloride between the glossopharyngeal and hypoglossal nerves, as they coursed through the medial compartment of the diverticulum of the auditory tube (guttural pouch), using videoendoscopic guidance and an injection apparatus. RESULTS: Compared with control values, peak inspiratory tracheal pressure was significantly (P = 0.02) more negative, and peak pharyngeal inspiratory pressure was less negative (P = 0.004) after bilateral hypoglossal and glossopharyngeal nerve block. Respiratory frequency was significantly (P = 0.024) lower after nerve block, compared with control values. The epiglottis was unstable and retroflexed through the rima glottis during inspiration after bilateral hypoglossal and glossopharyngeal nerve block. Despite loss of contact between the epiglottis and the caudal free margin of the soft palate, dorsal displacement of the soft palate did not occur. CONCLUSIONS AND CLINICAL RELEVANCE: Loss of contact of the epiglottis with the soft palate did not affect soft palate position, suggesting that when the soft palate is normal, the epiglottis does not function as a support, holding the soft palate in a ventral position. Therefore, epiglottic dysfunction is not solely responsible for intermittent dorsal displacement of the soft palate in horses, and neuromuscular dysfunction involving the hyoepiglotticus muscle, geniohyoideus muscle, or the hypoglossal nerve may cause epiglottic retroflexion in horses.     

Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients

BACKGROUND: It has been theorized that fetal myelomeningocele repair may reduce ongoing intrauterine injury and perhaps allow healing and regeneration of dysplastic neural tissue. We report on the postnatal imaging studies of the first 4 patients to have undergone intrauterine myelomeningocele repair at our institution. METHODS: Each of the 4 patients underwent postnatal sonographic and MRI. In addition, the postnatal ultrasounds of these 4 were compared to a group of retrospective controls. RESULTS: MRI scans of the 4 experimental subjects revealed no evidence of hindbrain herniation while other stigmata of the Chiari-II malformation persisted. In comparison to the retrospective controls this absence of herniation was distinctly unusual. CONCLUSION: Intrauterine myelomeningocele repair may reduce the degree of hindbrain herniation normally seen in patients with myelomeningocele. This raises the possibility that intrauterine repair may decrease the morbidity associated with the Chiari type-II malformation including brainstem dysfunction, hydrocephalus and syringomyelia.     

Calcitonin gene-related peptide and alpha-CGRP mRNA expression in cranial motoneurons after hypoglossal nerve injury during postnatal development

Changes in calcitonin gene-related peptide (CGRP) immunoreactivity and alpha-CGRP mRNA expression were determined in the hypoglossal nucleus after the nerve was crushed or transected in rats at 10, 14 and 21 days postnatal. alpha-CGRP mRNA expression was determined in normal, noninjured, hypoglossal nuclei at the three ages and after both injuries in 10 and 21 days postnatal rats. Reinnervation and neuronal survival were assayed. Although the three age groups expressed comparable levels of alpha-CGRP mRNA and its peptide in intact, hypoglossal nuclei, axonal injury produced age-dependent alterations in alpha-CGRP mRNA and CGRP. In the 21 days postnatal rats, changes in alpha-CGRP mRNA and peptide mimicked those reported in adult motoneurons after the same injuries. CGRP was elevated until reinnervation after nerve crush, whereas biphasic elevations occurred after nerve transection. In 21 days postnatal rats, increases in alpha-CGRP mRNA preceded elevations of the peptide but a greater increase resulted initially after nerve transection. An upregulation of alpha-CGRP mRNA also developed initially after both injuries in 10 days postnatal rats but subsequent elevations of alpha-CGRP mRNA did not materialize. In contrast, CGRP immunoreactivity did not increase after either injury in 10 days postnatal rats and, in fact decreased. Levels of CGRP immunoreactivity did not differ from normal amounts after either nerve injury in 14 days postnatal rats. Substantial neuronal cell loss occurred after each injury in 10 and 14 days postnatal rats but was not found in 21 days postnatal rats. Tongue reinnervation by surviving motoneurons was established after all injury paradigms except 10 days postnatal transection. The current findings demonstrate an age-dependent correlation between injury-induced expression of CGRP and hypoglossal motoneuron survival.     

Unilateral hypoglossal nerve paralysis following the use of the laryngeal mask airway

We report a unilateral hypoglossal nerve paralysis following the use of a laryngeal mask airway in a 62-year-old woman with rheumatoid arthritis undergoing a shoulder joint replacement. Cervical epidural anaesthesia was combined with general anaesthesia using nitrous oxide administered via a laryngeal mask airway with the patient in the right lateral decubitus position. The next morning, the patient was noted to have a right hypoglossal nerve palsy. Compression of the nerve between the laryngeal mask airway cuff, distended with nitrous oxide, and the hyoid bone, was considered to be the cause of the nerve paralysis.     

Minimally invasive surgery in the management of Mirizzi syndrome]

BACKGROUND: Evidence accumulating over the last 10 years suggests that the exposed spinal cord tissue in a myelomeningocele sustains a secondary injury as the result of prolonged exposure to the intrauterine environment. These data suggest that early closure of the myelomeningocele sac might prevent such injury and in turn improve the neurologic outcome in the affected infant. METHODS: Three patients with fetuses carrying the ultrasonic diagnosis of myelomeningocele elected to enter a study of the feasibility of repairing myelomeningocele in utero. At approximately 28 weeks of gestation each patient underwent laparotomy and hysterotomy, thus exposing the myelomeningocele defect. The defect was closed in a routine surgical fashion, and the hysterotomy was then closed. RESULTS: The 3 patients recovered from surgery without incident. Early premature contractions subsided, and they were discharged by the 5th postoperative day. At between 33 and 36 weeks of gestation, each infant was delivered via cesarean section. The observed neurologic deficits were within the range expected from the anatomic level of the defects. Two of the infants have not required ventriculoperitoneal shunting. CONCLUSIONS: This limited series of patients suggests that myelomeningocele can be repaired in utero with minimal morbidity to either the mother or her fetus. A larger study will be needed to substantiate this low morbidity and to determine the extent of any neurologic benefit of early surgery.     

Construction and performance of a scanning, photon-counting spectrofluorometer

The authors report on their treatment of 32 young patients with severe anorexia nervosa who had lost an average of 37% of their original body weight. The therapeutic approach, conceived to meet both the physiological and the psychological needs of the patients, was carried out in a psychiatric unit for adolescents in a general hospital and involved separation of the patient from his or her family, treatment of the malnutrition, individually planned psychotherapy, and concurrent work with the family. The importance of accepting the patient's uniqueness, maintaining long-term contact, and encouraging the patient's striving toward constructive growth and autonomy is emphasized.     

Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma

In this study we aimed to examine a role for interleukin 6 (IL-6) and its receptor (IL-6R) in peripheral nerve regeneration in vivo. We first observed that cultured mouse embryonic dorsal root ganglia exhibited dramatic neurite extension by simultaneous addition of IL-6 and soluble IL-6R (sIL-6R), a complex that is known to interact with and activate a signal transducing receptor component, gp130. After injury in the hypoglossal nerve in adult mice by ligation, immunoreactivity to IL-6 was upregulated in Schwann cells at the lesional site as well as in the cell bodies of hypoglossal neurons in the brain stem. In the latter, upregulation of the immunoreactivity to IL-6R was also observed. Regeneration of axotomized hypoglossal nerve in vivo was significantly retarded by the administration of anti-IL-6R antibody. Surprisingly, accelerated regeneration of the axotomized nerve was achieved in transgenic mice constitutively expressing both IL-6 and IL-6R, as compared with nontransgenic controls. These results suggest that the IL-6 signal may play an important role in nerve regeneration after trauma in vivo.     

Organization of motoneurons in the dorsal hypoglossal nucleus that innervate the retrusor muscles of the tongue in the rat

This anatomical investigation was prompted by the incomplete knowledge of the myotopic organization of the dorsal subdivison of the hypoglossal nucleus. Intrinsic muscle motoneurons were not segregated and labeled previously with regard to the lateral division of the hypoglossal nerve. Also, motoneuron number and cell size, in relation to the individual retrusor tongue musculature, were rarely addressed previously. Retrograde labeling ofretrusor muscle motoneurons in the dorsal subdivision of the rat hypoglossal nucleus was done. Cholera toxin conjugate horseradish peroxidase (CTHRP) was injected into the retrusor tongue muscles with only the lateral division of the hypoglossal nerve intact. The dorsal subdivision of the hypoglossal nucleus contained approximately 800 motoneurons ranging in cell body size from 19 to 41 microm. When either the styloglossus, hyoglossus, superior longitudinal, or inferior longitudinal muscle was isolated and injected with CTHRP, a separate motoneuron pool for each muscle was seen. The extrinsic muscle motoneurons, styloglossus and hyoglossus, were found rostrolateral and caudolateral respectively. In contrast, the intrinsic superior and inferior longitudinal muscle motoneurons were found more central and medial in the nucleus. Extrinsic muscle motoneurons were larger (approximately 30 microm) than intrinsic muscle motoneurons (approximately 26 microm; P < .0001). Intrinsic muscle motoneurons account for a great majority of the motoneurons in the dorsal aspect of the hypoglossal nucleus and their axons have been shown to be contained in the lateral (retrusor) division of the hypoglossal nerve. This study revealed the myotopic organization of the retrusor subdivision of the rat hypoglossal nucleus.     

Nutrient content of tomatoes and tomato products

We report nine patients with hypoglossal nerve palsy as the sole neurological manifestation, without simultaneous involvement of other cranial nerves or long-tract signs. In four patients, no cause was found and the outcome was excellent. The next common cause proved to be metastatic disease at the base of the skull in three patients. Two exceptional causes were Chiari malformation in one case and dural arteriovenous fistula of the transverse sinus in another. Although the aetiological importance and ominous prognosis of neoplasia has been emphasized by others, our study suggests that an isolated hypoglossal nerve palsy may be benign and idiopathic.     

Temperature dependence on the recovery of electrical activities in brain slice during incubation

Four cases of suprascapular neuropathy treated by nonoperative means have been presented. Complete recovery occurred in all four. The anatomy of the suprascapular nerve and probable mechanisms of injury secondary to traction have been discussed. The importance of electromyography in diagnosis has been stressed. Longer periods of nonoperative treatment are recommended here than by previous authors. Since the lesion is felt not to be an entrapment phenomenon but, rather, a traction injury, operative treatment should consist of release of the nerve at the notch to reduce the possibility of further traction injury, and a neurolysis should be done as well.     

Six antimicrobial peptide genes of the cathelicidin family map to bovine chromosome 22q24 by fluorescence in situ hybridization

Seven patients with acute or chronic unilateral hypoglossal nerve lesions were evaluated by magnetic resonance imaging and computed tomography. In patients with acute to subacute tongue paralysis, the base of the ipsilateral side of the tongue appeared expanded and showed increased signal intensity on T2-weighted images. This appearance was suggestive of an infiltrative mass lesion within the tongue. These radiographic findings are due to the pathophysiological process of nerve injury and muscle denervation.     

Strategies to enhance internal validity in multi-center longitudinal research

A 64-year-old former civil servant consulted his general practitioner because of severe fatigue. Later he began to lose weight and gradually developed chronic sensorimotor polyneuropathy characterized by sensory nerve loss which started in his legs. After a year he needed a wheel chair and developed cachexia. IgG paraprotein was detected. Morbid-anatomical examination of enlarged supraclavicular lymph nodes revealed plasma cell angiofollicular hyperplasia, characteristic of Castleman's disease. Treatment with corticosteroids led to marked improvement of the patient's condition. He was able to walk again, using an ankle orthosis on both legs.     

Developmental changes in the hypoxic response of the hypoglossus respiratory motor output in vitro

The transverse brain stem slice of mice containing the pre-B?tzinger complex (PBC), a region essential for respiratory rhythm generation in vitro, was used to study developmental changes of the response of the in vitro respiratory network to severe hypoxia (anoxia). This preparation generates, at different postnatal stages [postnatal day (P)0-22], spontaneous rhythmic activity in hypoglossal (XII) rootlets that are known to occur in synchrony with periodic bursts of neurons in the PBC. It is assumed that this rhythmic activity reflects respiratory rhythmic activity. At all examined stages anoxia led to a biphasic response: the frequency of rhythmic XII activity initially increased ("primary augmentation") and then decreased ("secondary depression"). In neonates (P0-7), anoxia did not significantly affect the amplitude of integrated XII bursts. Secondary depression never led to a cessation of rhythmic activity. In mice older than P7, augmentation was accompanied by a significant increase in the amplitude of XII bursts. A significant decrease of the amplitude of XII bursts occurred during secondary depression. This depression led always to cessation of rhythmic activity in XII rootlets. The anoxia-induced response of the respiratory rhythmic XII motor output is biphasic and changes during development in a similar way to the in vivo respiratory network. Whether this biphasic response is due to a biphasic response of the respiratory rhythm generator and/or to a biphasic modulation of the XII motor nucleus remains unresolved and needs further cellular analysis. We propose that the transverse slice is a useful model system for examination of the mechanisms underlying the hypoxic response.