Search

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurological disorder caused by deleterious CAG repeat expansion in the coding region of the ataxin 7 gene (polyQ-ataxin-7). Infantile-onset SCA7 leads to severe clinical manifestation of respiratory distress, but the exact cause of respiratory impairment remains unclear. Using the infantile-SCA7 mouse model, the SCA7266Q/5Q mouse, we examined the impact of pathological polyQ-ataxin-7 on hypoglossal (XII) and phrenic motor units. We identified the transcript profile of the medulla and cervical spinal cord and investigated the XII and phrenic nerves and the neuromuscular junctions in the diaphragm and tongue. SCA7266Q/5Q astrocytes showed significant intranuclear inclusions of ataxin-7 in the XII and putative phrenic motor nuclei. Transcriptomic analysis revealed dysregulation of genes involved in amino acid and neurotransmitter transport and myelination. Additionally, SCA7266Q/5Q mice demonstrated blunted efferent output of the XII nerve and demyelination in both XII and phrenic nerves. Finally, there was an increased number of neuromuscular junction clusters with higher expression of synaptic markers in SCA7266Q/5Q mice compared with WT controls. These preclinical findings elucidate the underlying pathophysiology responsible for impaired glial cell function and death leading to dysphagia, aspiration, and respiratory failure in infantile SCA7.

Background: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors., Case Report: We report the diagnostic imaging, surgical treatment, and histopathological findings of a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years., Conclusion: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

CT and MRI findings of tongue ptosis and atrophy should alert radiologists to potential pathology along the course of the hypoglossal nerve (cranial nerve XII), a purely motor cranial nerve which supplies the intrinsic and extrinsic muscles of the tongue. While relatively specific for hypoglossal nerve pathology, these findings do not accurately localize the site or cause of denervation. A detailed understanding of the anatomic extent of the nerve, which crosses multiple anatomic spaces, is essential to identify possible underlying pathology, which ranges from benign postoperative changes to life-threatening medical emergencies. This review will describe key imaging findings of tongue denervation, segmental anatomy of the hypoglossal nerve, imaging optimization, and comprehensive imaging examples of diverse pathology which may affect the hypoglossal nerve. Armed with this knowledge, radiologists will increase their sensitivity for detection of pathology and provide clinically relevant differential diagnoses when faced with findings of tongue ptosis and denervation., (© 2023. The Author(s).)

The hypoglossal nerve is the 12th cranial nerve, exiting the brainstem in the preolivary sulcus, passing through the premedullary cistern, and exiting the skull through the hypoglossal canal. This is a purely motor nerve, responsible for the innervation of all the intrinsic tongue muscles (superior longitudinal muscle, inferior longitudinal muscle, transverse muscle, and vertical muscle), 3 extrinsic tongue muscles (styloglossus, hyoglossus, and genioglossus), and the geniohyoid muscle. Magnetic resonance imaging (MRI) is the best imaging exam to evaluate patients with clinical signs of hypoglossal nerve palsy, and computed tomography may have a complementary role in the evaluation of bone lesions affecting the hypoglossal canal. A heavily T2-weighted sequence, such as fast imaging employing steady-state acquisition (FIESTA) or constructive interference steady state (CISS) is important to evaluate this nerve on MRI. There are multiple causes of hypoglossal nerve palsy, being neoplasia the most common cause, but vascular lesions, inflammatory diseases, infections, and trauma can also affect this nerve. The purpose of this article is to review the hypoglossal nerve anatomy, discuss the best imaging techniques to evaluate this nerve and demonstrate the imaging aspect of the main diseases that affect it., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the diagnostic value of the Yin-Yang tongue sign in patients with tongue deviation., Methods: According to the presence of the Yin-Yang tongue sign on CT/MR, 107 patients with tongue deviation were divided into a positive group and a negative group. The involvement categories of the hypoglossal canal (HC) in the positive group were evaluated and classified as HC dilation and HC erosion. The correlations between HC involvement categories and the presence of the sign were analysed., Results: There were 55 cases (55/107, 51.4%) in the positive group and 52 cases (52/107, 48.6%) in the negative group. Hypoglossal nerve (HN) involvement mainly occurred in the skull base (61.8%), skull base and carotid space (10.9%), and carotid space segment (12.7%). Neurogenic (50.9%), squamous cell carcinoma (14.5%), and metastases (12.7%) were the predominant aetiologies. The sensitivity, specificity, and accuracy of this sign for suggesting skull base lesions around HC were 72.4%, 80.8%, and 76.6%, respectively. In the positive group, HC dilation was seen in 21 patients (21/55, 38.2%) and 21 cases were all benign. HC erosion were noted in 19 patients (19/55, 34.5%), of whom 12 cases were malignant., Conclusion: The Yin-Yang tongue sign is formed by unilateral tongue atrophy and fat infiltration caused by lesions in the HN pathway, especially compressive or invasive lesions involving the skull base segment.

Background: Schwannomas or neurilemmomas are well-encapsulated, benign, solitary, and slow-growing tumors that originate from Schwann cells of the nerve sheath. Extracranial schwannoma is reported to have a relatively high incidence in the tongue while an extremely low incidence in the floor of mouth. In the current study, we presented the first case series of hypoglossal nerve-derived schwannoma in the floor of mouth in Asia., Methods: A retrospective study of 9 surgical cases of hypoglossal nerve-derived schwannoma in the floor of mouth was performed. The patient and tumor characteristics were evaluated by physical, radiological and pathological examination. Details of operation and complications were also recorded., Results: Hypoglossal nerve-derived schwannoma in the floor of mouth showed a well-defined boundary with a firm texture, smooth surface and good mobility on palpation. The median maximum diameter of the tumors was 4.3 cm (range 2.8-7.0 cm). The median operative time and bleeding volumes were 89.4 min (range 47-180 min) and 99.2 mL (range 15-200 mL), respectively. All cases received complete surgical excision., Conclusion: In this study, we presented the diagnosis and management of hypoglossal nerve-derived schwannoma in the floor of mouth for the first time in Asia. The study provided us with a recommendation for consideration of the diagnosis of hypoglossal schwannoma when a patient presents with a mass in the floor of mouth., (© 2022. The Author(s).)

The hypoglossal nerve is a pure motor nerve. It provides motor control to the intrinsic and extrinsic tongue muscles thus being essential for normal tongue movement and coordination. In order to design a useful imaging approach and a working differential diagnosis in cases of hypoglossal nerve damage one has to have a good knowledge of the normal anatomy of the nerve trunk and its main branches. A successful imaging evaluation to hypoglossal diseases always requires high resolution studies due to the small size of the structures being studied. MRI is the preferred modality to directly visualize the nerve, while CT is superior in displaying the bony anatomy of the neurovascular foramina of the skull base. Also, while CT is only able to detect nerve pathology by indirect signs, such as bony expansion of the hypoglossal canal, MRI is able to visualize directly the causative pathological process as in the case of small tumors, or infectious/inflammatory processes affecting the nerve. The easiest way to approach the study of the hypoglossal nerve is to divide it in its main segments: intra-axial, cisternal, skull base and extracranial segment, tailoring the imaging technique to each anatomical area while bearing in mind the main disease entities affecting each segment. [Copyright &y& Elsevier]

A 4 yr old male Maltese dog presented with a 1 wk history of intermittent neck pain and progressive difficulty walking. Neurologic evaluation was consistent with a left-sided brainstem lesion. On oral examination, left lingual hemiatrophy was evident suggesting hypoglossal nerve involvement. A dumbbell-shaped extra-axial mass in the left side of the caudal fossa extending extracranially through the hypoglossal canal was detected by MRI. At postmortem histologic examination, the hypoglossal nerve was diffusely infiltrated by fusiform neoplastic cells arranged in Antoni A and Antoni B patterns. This is the first description of a malignant nerve sheath tumor selectively involving the hypoglossal nerve in a dog., (© 2022 by American Animal Hospital Association.)

The total motor neuron (MN) somato-dendritic surface area is correlated with motor unit type. MNs with smaller surface areas innervate slow (S) and fast fatigue-resistant (FR) motor units, while MNs with larger surface areas innervate fast fatigue-intermediate (FInt) and fast fatigable (FF) motor units. Differences in MN surface area (equivalent to membrane capacitance) underpin the intrinsic excitability of MNs and are consistent with the orderly recruitment of motor units (S > FR > FInt > FF) via the Size Principle. In amyotrophic lateral sclerosis (ALS), large MNs controlling FInt and FF motor units exhibit earlier denervation and death, compared to smaller and more resilient MNs of type S and FR motor units that are spared until late in ALS. Abnormal dendritic morphologies in MNs precede neuronal death in human ALS and in rodent models. We employed Golgi-Cox methods to investigate somal size-dependent changes in the dendritic morphology of hypoglossal MNs in wildtype and SOD1 G93A mice (a model of ALS), at postnatal (P) day ~30 (pre-symptomatic), ~P60 (onset), and ~P120 (mid-disease) stages. In wildtype hypoglossal MNs, increased MN somal size correlated with increased dendritic length and spines in a linear fashion. By contrast, in SOD1 G93A mice, significant deviations from this linear correlation were restricted to the larger vulnerable MNs at pre-symptomatic (maladaptive) and mid-disease (degenerative) stages. These findings are consistent with excitability changes observed in ALS patients and in rodent models. Our results suggest that intrinsic or synaptic increases in MN excitability are likely to contribute to ALS pathogenesis, not compensate for it., (© 2020 American Association for Anatomy.)

Background and Purpose: To assess a 3D high-resolution IR-prepped fast SPGR high-resolution MRI sequence for evaluating hypoglossal nerve lesions., Methods: The clinical data of 8 patients with hypoglossal nerve lesions admitted from December 2011 to February 2016 were retrospectively analyzed. MRI included contrast-enhanced conventional sequences and a 3D IR-prepped fast SPGR high-resolution T1-weighted (BRAVO) MRI sequence at 3T., Results: Eight patients had hypoglossal lesions detected by MRI. Conventional enhanced scanning could not clearly display the hypoglossal nerve and canal, while the enhanced 3D high-resolution sequence could. In addition, multiple planar reconstruction clearly displayed the hypoglossal nerve, hypoglossal canal, and lesions in multiple planes., Conclusions: Compared with conventional MRI, we show superior results from an advanced sequence to improve image quality in characterizing hypoglossal nerve lesions., (© 2020 American Society of Neuroimaging.)

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that results in death due to respiratory failure. Many genetic defects are associated with ALS; one such defect is a mutation in the gene encoding optineurin (OPTN). Using an optineurin null mouse (Optn -/- ), we sought to characterize the impact of optineurin deficiency on respiratory neurodegeneration. Respiratory function was assessed at 6 and 12 mo of age using whole body plethysmography at baseline during normoxia (FiO 2 : 0.21; N 2 balance) and during a respiratory challenge with hypoxia and hypercapnia (FiCO 2 : 0.07, FiO 2 : 0.10; N 2 balance). Histological analyses to assess motor neuron viability and respiratory nerve integrity were performed in the medulla, cervical spinal cord, hypoglossal nerve, and phrenic nerve. Minute ventilation, peak inspiratory flow, and peak expiratory flow are significantly reduced during a respiratory challenge in 6 mo Optn -/- mice. By 12 mo, tidal volume is also significantly reduced in Optn -/- mice. Furthermore, 12mo Optn -/- mice exhibit hypoglossal motor neuron loss, phrenic and hypoglossal dysmyelination, and accumulated mitochondria in the hypoglossal nerve axons. Overall, these data indicate that Optn -/- mice display neurodegenerative respiratory dysfunction and are a useful model to study the impact of novel therapies on respiratory function for optineurin-deficient ALS patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by deleterious mutations in the DMD gene which encodes the dystrophin protein. Skeletal muscle weakness and eventual muscle degradation due to loss of dystrophin are well-documented pathological hallmarks of DMD. In contrast, the neuropathology of this disease remains understudied despite the emerging evidence of neurological abnormalities induced by dystrophin loss. Using quantitative morphological analysis of nerve sections, we characterize axonopathies in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe dysfunction in these nerves - which innervate the diaphragm and genioglossus respectively - that we propose contributes to respiratory failure, the most common cause of death in DMD. These observations highlight the importance in the further characterization of the neuropathology of DMD. Additionally, these observations underscore the necessity in correcting both the nervous system pathology in addition to skeletal muscle deficits to ameliorate this disease.

Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment., Materials and Methods: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation., Results: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP., Conclusion: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: A variant of the innervation of the infrahyoid neck musculature is reported in which the typical looped ansa cervicalis structure is absent. In this variant, the infrahyoid muscles (sternohyoid, sternothyroid omohyoid and thyrohyoid) were innervated by a presumptive superior root of "ansa cervicalis" traveling with vagus nerve (CN X) and not branching from hypoglossal nerve (CN XII). The omohyoid muscle, typically innervated by the inferior root of ansa cervicalis, is instead innervated by nerve fibers branching from the accessory nerve (CN XI). This formation created a non-looping variant of ansa cervicalis. Furthermore, the omohyoid muscle did not attach to the hyoid bone but instead attached to the mastoid process of the temporal bone by merging its fibers superiorly and posteriorly with the clavicular portion of the sternocleidomastoid muscle, creating a "sternocleidoomomastoid" muscle innervated by a branch of accessory nerve., Materials and Methods: This variation was found in one black male cadaver from a cohort of 25 male and female cadavers., Results: Only one variation of ansa cervicalis was observed., Conclusions: As neck dissections and surgical procedures of this region are performed for a variety of conditions-including coronary artery bypass grafting and metastatic neck disease-variations of this type are of broad clinical surgical importance.

Background: The "post-paralytic syndrome" after facial nerve reconstruction has been attributed to (i) malfunctioning axonal guidance at the fascicular (branches) level, (ii) collateral branching of the transected axons at the lesion site, and (iii) intensive intramuscular terminal sprouting of regenerating axons which causes poly-innervation of the neuromuscular junctions (NMJ)., Objective: The first two reasons were approached by an innovative technique which should provide the re-growing axons optimal conditions to elongate and selectively re-innervate their original muscle groups., Methods: The transected facial nerve trunk was inserted into a 3-way-conduit (from isogeneic rat abdominal aorta) which should "guide" the re-growing facial axons to the three main branches of the facial nerve (zygomatic, buccal and marginal mandibular). The effect of this method was tested also on hypoglossal axons after hypoglossal-facial anastomosis (HFA). Coaptational (classic) FFA (facial-facial anastomosis) and HFA served as controls., Results: When compared to their coaptation (classic) alternatives, both types of 3-way-conduit operations (FFA and HFA) promoted a trend for reduction in the collateral axonal branching (the proportion of double- or triple-labelled perikarya after retrograde tracing was slightly reduced). In contrast, poly-innervation of NMJ in the levator labii superioris muscle was increased and vibrissal (whisking) function was worsened., Conclusions: The use of 3-way-conduit provides no advantages to classic coaptation. Should the latter be impossible (too large interstump defects requiring too long interpositional nerve grafts), this type of reconstruction may be applied. (230 words).

A 40-year-old woman presented with insidious onset, gradually progressive dysarthria and inability to manoeuvre bolus of food in her mouth while eating. The duration of her symptoms was 3 months. On evaluation, the left half of her tongue was wasted. The tongue deviated to the left on protrusion. There were no clinical features suggestive of involvement of the ipsilateral 9th, 10th or 11th cranial nerves. MRI of the brain showed a large, fusiform lesion in the left hypoglossal canal, extending into the jugular canal. The lesion was surgically excised and found to be a schwannoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to degeneration of motor neurons and skeletal muscles, including those required for swallowing. Tongue weakness is one of the earliest signs of bulbar dysfunction in ALS, which is attributed to degeneration of motor neurons in the hypoglossal nucleus in the brainstem, the axons of which directly innervate the tongue. Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to preserve swallowing function have seldom been studied in ALS models. It is difficult to study dysphagia in ALS models since the amount and rate at which hypoglossal motor neuron death occurs cannot be controlled, and degeneration is not limited to the hypoglossal nucleus. Here, we report a novel experimental model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to study the impact of only hypoglossal motor neuron death without the many complications that are present in ALS models. Hypoglossal motor neuron survival, swallowing function, and hypoglossal motor output were assessed in Sprague-Dawley rats after intralingual injection of either CTB-SAP (25 g) or unconjugated CTB and SAP (controls) into the genioglossus muscle. CTB-SAP treated rats exhibited significant (p ≤ 0.05) deficits vs. controls in: (1) lick rate (6.0 ± 0.1 vs. 6.6 ± 0.1 Hz; (2) hypoglossal motor output (0.3 ± 0.05 vs. 0.6 ± 0.10 mV); and (3) hypoglossal motor neuron survival (398 ± 34 vs. 1018 ± 41 neurons). Thus, this novel, inducible model of hypoglossal motor neuron death mimics the dysphagia phenotype that is observed in ALS rodent models, and will allow us to study strategies to preserve swallowing function., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Hypoglossal nerve injury may result in swallowing and speech problems. To reduce this morbidity and allow the performance of the hypoglossal-facial nerve anastomosis bilaterally, a technique that includes partial splitting of the hypoglossal nerve and skeletonization of the facial nerve within the mastoid process has been applied. The aim of this study is to present clinical results regarding the facial and hypoglossal nerves after the procedure., Methods: Prospectively collected data from 56 consecutive patients who underwent hemihypoglossal-facial nerve anastomosis (HHFA) were analyzed. The outcome was correlated with epidemiologic data, initial disease, the presence of neurofibromatosis type 2, previous radiosurgery, and the time between nerve injury and reconstructive surgery., Results: Forty-eight (84%) patients achieved satisfactory outcomes; 8 of them (14%) showed some improvement, and in 1 patient (2%) there was no improvement during long-term observation. The result at follow-up was not related to the time interval between the 2 procedures. However, recovery times for facial tonicity were statistically significantly longer if the procedure was performed after 12 months (P = 0.044). There was no statistically significant association between patient age (P = 0.96) or sex (P = 0.13) and facial nerve function. HHFA resulted in no or minimal tongue atrophy without deviation in 53 patients (93%), and the remainder had mild hemiatrophy with tongue deviation <30 degrees., Conclusions: HHFA is an effective technique for facial nerve reanimation with acceptable morbidity related to tongue function. Patients with a longer duration of facial palsy still have a good chance for restoration of facial movement but require longer recovery periods., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Occipital condyle syndrome consists of the presence of unilateral occipital headache exacerbated by moving the head and is accompanied by paralysis of the ipsilateral hypoglossal nerve. One of its causes is infiltration of the base of the skull by bone metastases, especially those affecting the hypoglossal nerve due to infiltration as it passes through the osseous canal., Case Reports: We report two clinical cases of occipital condyle syndrome secondary to metastatic hepatocarcinoma. The first is that of a 52-year-old male with liver cirrhosis secondary to liver pathology caused by hepatitis C virus with occipital condyle syndrome as the presenting symptom in disseminated hepatocarcinoma. The second case is that of a 56-year-old male after recurrence of hepatocarcinoma following a liver transplant, despite not fulfilling the Milan criteria., Conclusion: Occipital condyle syndrome is an alarm symptom and requires a thorough study by means of imaging tests, since it may be the first symptom of an undetected hepatocarcinoma.

Spinocerebellar ataxia type 1 (SCA1) is characterized by adult-onset cerebellar degeneration with attendant loss of motor coordination. Bulbar function is eventually impaired and patients typically die from an inability to clear the airway. We investigated whether motor neuron degeneration is at the root of bulbar dysfunction by studying SCA1 knock-in ( Atxn1 154Q/+ ) mice. Spinal cord and brainstem motor neurons were assessed in Atxn1 154Q/+ mice at 1, 3 and 6 months of age. Specifically, we assessed breathing physiology, diaphragm histology and electromyography, and motor neuron histology and immunohistochemistry. Atxn1 154Q/+ mice show progressive neuromuscular respiratory abnormalities, neurogenic changes in the diaphragm, and motor neuron degeneration in the spinal cord and brainstem. Motor neuron degeneration is accompanied by reactive astrocytosis and accumulation of Atxn1 aggregates in the motor neuron nuclei. This observation correlates with previous findings in SCA1 patient tissue. Atxn1 154Q/+ mice develop bulbar dysfunction because of motor neuron degeneration. These findings confirm the Atxn1 154Q/+ line as a SCA1 model with face and construct validity for this understudied disease feature. Furthermore, this model is suitable for studying the pathogenic mechanism driving motor neuron degeneration in SCA1 and possibly other degenerative motor neuron diseases. From a clinical standpoint, the data indicate that pulmonary function testing and employment of non-invasive ventilator support could be beneficial in SCA1 patients. The physiological tests used in this study might serve as valuable biomarkers for future therapeutic interventions and clinical trials.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the brainstem and spinal cord. Clinical studies have indicated that there is a distinct region-dependent difference in the vulnerability of motor neurons. For example, the motor neurons in the facial and hypoglossal nuclei are more susceptible to neuronal death than those in the oculomotor nucleus. To understand the mechanism underlying the differential susceptibility to cell death of the neurons in different motor nuclei, we compared the effects of chemical anoxia on the membrane currents and postsynaptic currents in different motor nuclei. The membrane currents were recorded from neurons in the oculomotor, facial and hypoglossal nuclei in brain slices of juvenile Wistar rats by using whole-cell recording in the presence of tetrodotoxin that prevents action potential-dependent synaptic transmission. NaCN consistently induced an inward current and a significant increase in the frequency of spontaneous synaptic inputs in neurons from these three nuclei. However, this increase in the synaptic input frequency was abolished by strychnine, a glycine receptor antagonist, but not by picrotoxin in neurons from the hypoglossal and facial nuclei, whereas that in neurons from the oculomotor nucleus was abolished by picrotoxin, but not by strychnine. Blocking ionotropic glutamate receptors did not significantly affect the NaCN-induced release facilitation in any of the three motor nuclei. These results suggest that anoxia selectively facilitates glycine release in the hypoglossal and facial nuclei and GABA release in the oculomotor nucleus. The region-dependent differences in the neurotransmitters involved in the anoxia-triggered release facilitation might provide a basis for the selective vulnerability of motor neurons in the neurodegeneration associated with ALS., (Copyright © 2017. Published by Elsevier Inc.)

We report a case of anesthetic management of a 43-year-old patient with Eagle's syndrome (ES) in whom post-extubation acute airway obstruction occurred due to bilateral hypoglossal nerve paralysis. After an accurate examination, elongated bilateral stylohyoid ligament was observed and surgical resection was planned. After completion of the surgery following extubation, significant dysfunction in swallowing, speech function, and tongue motion was observed. The clinical situation was evaluated as bilateral hypoglossal nerve paralysis related to the procedure. The patient was closely observed over 48 h in the intensive care unit. After 2 days, the patient was discharged to a surgical ward. Following clinical assessment, the patient was discharged from hospital for monthly return. At the 6-month follow-up, there were no further episodes of paresthesia and other symptoms. In conclusion, patients with ES represent a real challenge for physicians from diagnosis to treatment, especially regarding perioperative complications, and close collaboration between surgeons and anesthesiologists is of crucial importance.

Objective: To describe the ocular motor abnormalities in 9 patients with a lesion involving the nucleus prepositus hypoglossi (NPH), a key constituent of a vestibular-cerebellar-brainstem neural network that ensures that the eyes are held steady in all positions of gaze., Methods: We recorded eye movements, including the vestibulo-ocular reflex during head impulses, in patients with vertigo and a lesion involving the NPH., Results: Our patients showed an ipsilesional-beating spontaneous nystagmus, horizontal gaze-evoked nystagmus more intense on looking toward the ipsilesional side, impaired pursuit more to the ipsilesional side, central patterns of head-shaking nystagmus, contralateral eye deviation, and decreased vestibulo-ocular reflex gain during contralesionally directed head impulses., Conclusions: We attribute these findings to an imbalance in the NPH-inferior olive-flocculus-vestibular nucleus loop, and the ocular motor abnormalities provide a new brainstem localization for patients with acute vertigo., (© 2016 American Academy of Neurology.)

Background The clinical application of end-to-side (ETS) neurorrhaphy is under debate partly due to a lack of consensus on the source of axonal sprouting. Methods In this study, 24 rats were divided into three groups: sham operation, facial-hypoglossal ETS neurorrhaphy, and end-to-end (ETE) neurorrhaphy. Electrophysiological tests were employed to detect the evoked compound muscle action potentials (CMAPs) in different situations, and the latencies and maximal amplitudes of the CMAPs recorded were compared. Fluorescence retrograde tracing studies, hematoxylin and eosin (HE) staining, and immunohistochemical staining of growth-associated protein 43 (GAP-43) were performed. The number and the diameter of myelinated axons proximal and distal to the coaptation sites were measured. Results Twelve weeks after the surgeries, reinnervation of whisker pad muscles by hypoglossal nerves in both the ETS and ETE groups were confirmed via electrophysiological study. The maximal amplitudes of the CMAPs recorded in different situations and the quantification of myelinated axons supported the coexistence spontaneous collateral sprouting and regenerative sprouting of axons. Double-labeled neurons were found within the hypoglossal nuclear areas in the ETS neurorrhaphy group and HE staining illustrated the axons crossed the coaptation site into the facial acceptor nerve. Although immunohistochemical staining of GAP-43 revealed different timeframes between ETS and ETE neurorrhaphy groups, no significant difference on latency or diameters of the myelinated axons distal to the coaptation sites was noted between ETE and ETS groups. Conclusion Both spontaneous collateral sprouting and regenerative sprouting of axons coexisted following ETS neurorrhaphy, which represents an alternative approach to peripheral nerve reconstruction., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Maternal smoking or use of other products containing nicotine during pregnancy can have significant adverse consequences for respiratory function in neonates. We have shown, in previous studies, that developmental nicotine exposure (DNE) in a model system compromises the normal function of respiratory circuits within the brainstem. The effects of DNE include alterations in the excitability and synaptic interactions of the hypoglossal motoneurons, which innervate muscles of the tongue. This study was undertaken to test the hypothesis that these functional consequences of DNE are accompanied by changes in the dendritic morphology of hypoglossal motoneurons. Hypoglossal motoneurons in brain stem slices were filled with neurobiotin during whole-cell patch clamp recordings and subjected to histological processing to reveal dendrites. Morphometric analysis, including the Sholl method, revealed significant effects of DNE on dendritic branching patterns. In particular, whereas within the first five postnatal days there was significant growth of the higher-order dendritic branches of motoneurons from control animals, the growth was compromised in motoneurons from neonates that were subjected to DNE. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1125-1137, 2016., (© 2016 Wiley Periodicals, Inc.)

The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n=12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n=12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n=17) cohort that presented with pure bvFTD, 35% (n=6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)

The runt-related transcription factor Runx1 contributes to cell type specification and axonal targeting projections of the nociceptive dorsal root ganglion neurons. Runx1 is also expressed in the central nervous system, but little is known of its functions in brain development. At mouse embryonic day (E) 17.5, Runx1-positive neurons were detected in the ventrocaudal subdivision of the hypoglossal nucleus. Runx1-positive neurons lacked calcitonin gene-related peptide (CGRP) expression, whereas Runx1-negative neurons expressed CGRP. Expression of CGRP was not changed in Runx1-deficient mice at E17.5, suggesting that Runx1 alone does not suppress CGRP expression. Hypoglossal axon projections to the intrinsic vertical (V) and transverse (T) tongue muscles were sparser in Runx1-deficient mice at E17.5 compared to age-matched wild-type littermates. Concomitantly, vesicular acetylcholine transporter-positive axon terminals and acetylcholine receptor clusters were less dense in the V and T tongue muscles of Runx1-deficient mice. These abnormalities in axonal projection were not caused by a reduction in the total number hypoglossal neurons, failed synaptogenesis, or tongue muscles deficits. Our results implicate Runx1 in the targeting of ventrocaudal hypoglossal axons to specific tongue muscles. However, Runx1 deficiency did not alter neuronal survival or the expression of multiple motoneuron markers as in other neuronal populations. Thus, Runx1 appears to have distinct developmental functions in different brain regions., (© 2015 Wiley Periodicals, Inc.)

Importance: Improvements in endoscopic technology and reconstructive techniques have made the endoscopic endonasal approach (EEA) a viable option to approach ventromedial lesions in the region of the hypoglossal canal. Prior to contemplating this surgical corridor, a thorough understanding of anatomic relationships and landmarks is essential to safely approach this region of the posterior skull base through an EEA., Objective: To describe the surgical technique and anatomic landmarks in the EEA to the hypoglossal canal through referencing nasopharyngeal and posterior skull base anatomy., Design, Setting, and Participants: Study of latex-injected cadaveric heads at the North Carolina Eye Bank Multidisciplinary Surgical Skills Laboratory at the University of North Carolina., Interventions: An EEA to the hypoglossal canal was carried out bilaterally in 5 embalmed, latex-injected cadaver heads., Main Outcomes and Measures: Cadaveric measurements of anatomic landmarks and relationships in the approach were obtained using a 10-cm surgical ruler and were reported as mean distances. Additionally, high-quality endoscopic images demonstrating the operative technique and anatomic relationships were obtained., Results: The distance between the lacerum segment of the internal carotid arteries, the superolateral boundary, was 23.6 mm (SD, 11.8 mm). The distance between the anterolateral edge of the occipital condyles, the inferolateral boundary, was 19 mm (SD, 0.80 mm). The supracondylar groove was identified in the same anteroposterior plane as the nasopharyngeal orifice of the eustachian tube, and the anterior-most edge of the occipital condyle was 14 mm (SD, 0.82 mm) from the posterosuperior edge of the salpingopharyngeal fold. Additionally, the transtubercular corridor was on the same plane as the superior edge of the torus tubarius in the anteroposterior axis. The distance to the hypoglossal canal from midline was 10 mm, which was found after completing drilling in the transcondylar and transtubercular corridors. Last, the hypoglossal nerve rootlets were identified entering the canal 6 mm inferiorly and 8 mm laterally from the vertebrobasilar junction., Conclusions and Relevance: The eustachian tube and other elements of nasopharyngeal anatomy are fixed landmarks that provide important points of reference when approaching the hypoglossal canal through an EEA. A thorough understanding of these anatomic relationships is vital in safely navigating this direct, surgical corridor to the posterior fossa.

Parkinson's disease (PD) is a common neurodegenerative disorder that is often associated with weak tongue motility. However, the link between the degenerated dopaminergic neurons in the substantia nigra (SN) and lingual dysfunction remains unclear. In the present study, we investigated the localization of dopamine receptor 1 (D1) and dopamine receptor 2 (D2) and alternations in their expression in cholinergic motoneurons of the hypoglossal nucleus (HN) using double-label immunofluorescence, Western blotting and semi-quantitative reverse transcription and polymerase chain reaction (SqRT-PCR) in rats that received microinjections of 6-hydroxydopamine bilaterally into the SN (6-OHDA rats). The results revealed that a large population of choline acetyltransferase immunoreactive (ChAT-IR) neurons was distributed throughout HN and that almost all of the ChAT-IR motoneurons were also D1-IR and D2-IR. Several tyrosine hydroxylase (TH)-IR profiles were observed in a nonuniform pattern near the ChAT-IR, D1-IR or D2-IR somas, suggesting potent dopaminergic innervation. In the 6-OHDA rats, TH immunoreactivity in the SN was significantly decreased, but food residue was increased and treadmill occupancy time was shortened. In the HN, protein expression of TH and D2 was increased, whereas that of ChAT and D1 was decreased. A similar pattern was observed in mRNA levels. The present study suggests that dopamine may modulate the activity of cholinergic neurons via binding with D1 and D2 in the HN. Changes in the expression of ChAT, TH, D1 and D2 in the HN of 6-OHDA rats might be associated with the impaired tongue motility in PD. These findings should be further investigated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The aim of this retrospective study is to assess the rate at which glomus jugulare tumors invade the hypoglossal canal (HC) and to correlate computed tomography (CT) and magnetic resonance imaging (MRI) findings with the clinical evidence of cranial nerve (CN) XII dysfunction. CT and MRI imaging modalities of 31 patients were blindly reviewed by an attending neuroradiologist. Imaging studies identified involvement in 22 tumors (22/31, 71.0%). Thirteen of 22 patients (59.1%) had clinically evident CN XII symptoms. Accuracy rate was 76.7% (23/30) for MRI and 78.6% (11/14) for CT. MRI showed 100% sensitivity but had only 59% specificity and the specificity for CT was 66.7%. When radiologists elucidate HC involvement, it may alter the surgical approach and may lead to more focused/accurate clinical evaluation of tongue function., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This cross-sectional study of acute ischemic stroke patients examined relationships between hypoglossal nerve conduction, sleep-disordered breathing (SDB), and its severity., Methods: Patients within 7 days of stroke underwent nocturnal respiratory monitoring with the ApneaLink device and hypoglossal nerve conduction studies., Results: Eighteen of 52 subjects (35% [95% confidence interval: 22%, 49%]) had an abnormal hypoglossal amplitude and 23 (44% [95% confidence interval: 30%, 59%]) had an abnormal hypoglossal latency. No differences were identified in hypoglossal nerve latency or amplitude between those with (n = 26) and without (n = 26) significant SDB, defined by an apnea-hypopnea index ≥ 15. However, hypoglossal nerve conduction latency was associated (linear regression p < 0.05) with SDB severity as reflected by the apnea-hypopnea index., Conclusions: Acute ischemic stroke patients have a high prevalence of hypoglossal nerve dysfunction. Further studies are needed to explore whether hypoglossal nerve dysfunction may be a cause or consequence of SDB in stroke patients and whether this association can provide further insight into the pathophysiology of SDB in this population.

Although the aberrant assembly of mutant superoxide dismutase 1 (mSOD1) is implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS), the molecular basis of superoxide dismutase 1 (SOD1) oligomerization remains undetermined. We investigated the roles of transglutaminase 2 (TG2), an endogenous cross-linker in mSOD1-linked ALS. TG2 interacted preferentially with mSOD1 and promoted its oligomerization in transfected cells. Purified TG2 directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a substrate of TG2. Moreover, the non-cell-autonomous effect of extracellular TG2 on the neuroinflammation was suggested, since the TG2-mediated soluble SOD1 oligomers induced tumor necrosis factor-α, interleukin-1β, and nitric oxide in microglial BV2 cells. TG2 was up-regulated in the spinal cord of pre-symptomatic G93A SOD1 transgenic mice and in the hypoglossal nuclei of mice suffering nerve ligation. Furthermore, inhibition of spinal TG2 by cystamine significantly delayed the progression and reduced SOD1 oligomers and microglial activation. These results indicate a novel role of TG2 in SOD1 oligomer-mediated neuroinflammation, as well as in the involvement in the intracellular aggregation of misfolded SOD1 in ALS., (© 2013 International Society for Neurochemistry.)

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone.

The lower cranial nerves innervate the pharynx and larynx by the glossopharyngeal (CN IX) and vagus (CN X) (mixed) nerves, and provide motor innervation of the muscles of the neck by the accessory nerve (CN XI) and the tongue by the hypoglossal nerve (CN XII). The symptomatology provoked by an anomaly is often discrete and rarely in the forefront. As with all cranial nerves, the context and clinical examinations, in case of suspicion of impairment of the lower cranial nerves, are determinant in guiding the imaging. In fact, the impairment may be located in the brain stem, in the peribulbar cisterns, in the foramens or even in the deep spaces of the face. The clinical localization of the probable seat of the lesion helps in choosing the adapted protocol in MRI and eventually completes it with a CT-scan. In the bulb, the intra-axial pathology is dominated by brain ischemia (in particular, with Wallenberg syndrome) and multiple sclerosis. Cisternal pathology is tumoral with two tumors, schwannoma and meningioma. The occurrence is much lower than in the cochleovestibular nerves as well as the leptomeningeal nerves (infectious, inflammatory or tumoral). Finally, foramen pathology is tumoral with, outside of the usual schwannomas and meningiomas, paragangliomas. For radiologists, fairly hesitant to explore these lower cranial pairs, it is necessary to be familiar with (or relearn) the anatomy, master the exploratory technique and be aware of the diagnostic possibilities., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Perinatal alcohol exposure (AE) has multiple detrimental effects on cognitive and various behavioral outcomes, but little is known about its impact on the autonomic functions. In a rat model of fetal alcohol spectrum disorders (FASD), we investigated neurochemical and neuroanatomical alterations in two brainstem nuclei, the hypoglossal nucleus (XIIn) and the dorsal nucleus of the vagus nerve (Xdn). One group of male Sprague-Dawley rats (n=6) received 2.625 g/kg ethanol intragastrically twice daily on postnatal days (PD) 4-9, a period equivalent to the third trimester of human pregnancy, and another group (n=6) was sham-intubated. On PD 18-19, the rats were perfused and medullary sections were immunohistochemically processed for choline acetyltransferase (ChAT) or two aminergic receptors that mediate excitatory drive to motoneurons, α₁-adrenergic (α₁-R) and serotonin 2A (5-HT(2A)-R), and c-Fos. Based on ChAT labeling, AE rats had reduced numbers of motoneurons in the ventral XIIn (XIIn-v; 35.4±1.3 motoneurons per side and section vs. 40.0±1.2, p=0.022), but not in the dorsal XIIn or Xdn. Consistent with ChAT data, both the numbers of α₁-R-labeled motoneurons in the XIIn-v and the area of the XIIn-v measured using 5-HT(2A)-R staining were significantly smaller in AE rats (19.7±1.5 vs. 25.0±1.4, p=0.031 and 0.063 mm² ±0.002 vs. 0.074±0.002, p=0.002, respectively). Concurrently, both 5-HT(2A)-R and c-Fos staining tended to be higher in AE rats, suggesting an increased activation. Thus, postnatal AE causes motoneuronal loss in the XIIn-v. This may compromise upper airway control and contribute to increased risk of upper airway obstructions and sudden infant death in FASD victims., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Once the rabies virus has spread through the central nervous system (CNS), the virus is also transported centrifugally along axons, especially of the autonomic nervous system, to a wide range of organs including the heart. In this case report of a 49-year-old man who had been bitten by a dog in Asia, the rabies infection of cardiac nerves and cardiac muscle fibres is shown by immunohistochemistry. The neuritis cordis and rabies myocarditis can have important clinical effects on the heart rate and myocardial function and lead to blood pressure crises which are typical for the clinical course of rabies in humans.

S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to exert various functions, e.g., cell proliferation and differentiation, calcium homeostasis, and neuronal degeneration. In this study, we aimed to investigate whether S100A6 might be linked to glutamate toxicity using three animal models and pharmacological interventions. We first examined the age-related changes in S100A6 immunoreactivity in the mouse hippocampus, considering that an important negative aspect of brain aging is linked to increased extracellular glutamate. The surface area of S100A6-positive (+) astrocytes was significantly larger in aged mice than in young mice, while the numbers of S100β+ astrocytes did not change with age. In the second experiment, we examined the alterations in S100A6 immunoreactivity in the injured hypoglossal nucleus, because glutamate toxicity is considered to contribute to neuronal death after axotomy. There was no apparent S100A6 immunoreactivity in the hypoglossal nucleus of sham control animals. However, intense labeling for S100A6 in activated astrocytes was observed in the axotomized hypoglossal nucleus of mice. Administration of ceftriaxone, an astrocyte glutamate transporter enhancer, to axotomized mice significantly decreased the immunoreactivity for S100A6. In the third experiment, we tested an animal model of epilepsy using kainic acid (KA), a glutamate analog. In the mouse hippocampus after KA injection, S100A6 immunoreactivity was significantly increased in astrocytes, and pyknotic changes were observed in CA3 pyramidal neurons. Treatment of MK-801, an N-methyl-d-aspartate receptor antagonist, counteracted the KA-induced increase in S100A6 immunoreactivity, and reduced the numbers of pyknotic neurons. Our results indicate that upregulation of astrocytic S100A6 in response to extracellular glutamate may be involved in neuronal damage under pathophysiological conditions., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: Dysarthria and tongue swelling may be seen with hypoglossal nerve palsy, and on cross-sectional imaging studies, tongue denervation can be misinterpreted as a primary base-of-tongue mass. Understanding radiological patterns of tongue denervation is important to prevent misinterpretation. Close evaluation of the skull base is critical as hypoglossal palsies resulting from pathology here are often overlooked., Methods: Neck and brain magnetic resonance imaging studies obtained in 7 adult patients referred to our institution with clinically and/or radiologically suspected tongue base masses were retrospectively reviewed. Outside imaging evaluations were misinterpreted as base-of-tongue tumors in 3 patients, incorrectly read as normal in 2, and skull base pathologies were missed in 5., Results: All 7 patients showed magnetic resonance imaging findings typical of tongue denervation: T2-weighted hyperintensity of involved hemitongue, protrusion of the tongue into oropharynx, variable fatty infiltration. All 5 skull base masses involved hypoglossal canal (4 metastases, 1 multiple myeloma; 4 newly diagnosed cancers). Two patients had internal carotid artery dissections at the skull base., Conclusions: To avoid misinterpretation of tongue denervation for tongue base mass, understanding of tongue innervations and classic imaging findings of hypoglossal denervation are essential. Careful inspection of skull base is paramount to avoid overlooking these hidden pathologies.

Objective: Posteroinferior cerebellar artery (PICA) aneurysms are uncommon and have not been well investigated previously. We report our series of 29 ruptured PICA aneurysms with surgical treatment along with the description of the surgical anatomy of the PICA to the lower cranial nerves in cadaveric specimen., Methods: All patients with ruptured PICA aneurysms who were surgically treated at the First Affiliated Hospital of Soochow University during the period from January 1995 to December 2008 were reviewed retrospectively. Data relating to clinical, radiological, and intraoperative findings were analyzed. Forty formalin-fixed cerebellar hemispheres provided the material for the study of describing the detailed surgical anatomic relationship of the PICA to the lower cranial nerves., Results: In our series, ruptured PICA aneurysms reached an incidence of 2.35% of all ruptured intracranial aneurysms. There were 13 aneurysms (44.8%) located in the proximal segment, and 16 (55.2%) located in the distal segment. Of these, 89.7% were saccular, 6.9% fusiform, and 3.4% dissecting aneurysms. Usually, the surgical outcome was influenced by Poor admission grade, the presence of obstructive hydrocephalus and associated distal AVM. In cadaveric specimen, 17.5% of PICAs passed between the glossopharyngeal and vagus nerves, 7.5% between the vagus and accessory nerves, and 62.5% through the rootlets of the accessory nerve., Conclusion: This report summarizes the presentation and outcome of a large series of 29 patients with ruptured PICA aneurysms, and we conclude that ruptured PICA with surgical treatment usually gets well recovered. The study does, however, also demonstrate that the anatomic relationship of the PICA and lower cranial nerves is somehow variable and irregular. Recognition of the findings in cadaveric dissection is essential in treating lesions of this region., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: We report a patient with a malignant carotid body paraganglioma treated with surgery and adjuvant radiotherapy. We discuss her treatment and outcome in the light of the published literature., Case Report: A 26-year-old woman presented with a 12-month history of a painless, left-sided neck lump. Ultrasound, computed tomography and magnetic resonance imaging revealed a carotid body tumour, which at surgical excision was found to be adherent to the vagus and hypoglossal cranial nerves (X and XII). The tumour was resected from the surrounding structures. Two local lymph nodes were removed to allow access. The internal carotid artery was also involved and had to be repaired with a synthetic graft. Histology and immunohistochemistry confirmed malignant carotid body paraganglioma. There were positive resection margins, and cervical lymph node metastasis was reported in one of the two nodes. Post-operatively, she had left Horner's syndrome, left vocal fold palsy and right upper limb weakness, all of which resolved spontaneously. She underwent adjuvant radiotherapy and remained recurrence free after 30 months., Conclusion: Malignant carotid body paraganglioma can affect young adults, with an insidious onset of symptoms. In this patient, local excision (without neck dissection) and adjuvant radiotherapy were well tolerated and resulted in satisfactory local disease control.

Non-cell-autonomous motor neuronal death is suggested in a mutant Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) model, in which microglia and T cells play significant roles in disease progression. However, it remains unknown whether these cells are toxic or protective. The present study aimed to clarify the developmental age-related alterations of neuronal, glial and T cell responses to acute neuron injury in non-transgenic (N-Tg) mice, and the in vivo effects of mSOD1 on these changes by studying N-Tg and mSOD1-Tg mice subjected to unilateral hypoglossal nerve axotomy at young (8 weeks) and adult (17 weeks) ages. Adult N-Tg mice showed increased neuronal viability on day 21 after axotomy and trends toward increased numbers of recruited microglia on day 3 and T cells on day 7, in the hypoglossal nucleus, compared with young N-Tg mice. Quantitative comparisons between mSOD1-Tg and N-Tg mice at the same ages, on day 3 after axotomy, showed that microglial recruitment was significantly lower in mSOD1-Tg mice than in 17-week-old N-Tg mice (the disease progression stage), but the same difference was not seen in 8-week-old mice (the presymptomatic stage), despite good preservation of hypoglossal neurons. Infiltration of CD3-positive T cells, mostly CD4-positive, on day 7 and the viability rate of hypoglossal neurons on the operated side compared with the contralateral side on day 21 were significantly decreased in mSOD1-Tg mice compared with N-Tg mice aged 17 weeks, but the same difference was not seen in mice aged 8 weeks. On day 3 after axotomy, expression levels of IGF-1 mRNA in the operated hypoglossal nucleus were significantly lower in mSOD1-Tg mice than N-Tg mice at 17 weeks of age. The observation that depressed microglial and T cell responses and expression of neurotrophic factors coincided with reduced neuronal viability in adult mSOD1-Tg mice suggests that diminished neuroprotective functions of mSOD1 microglia and T cells may contribute to exaggerated neuronal death., (Copyright © 2012 Elsevier Inc. All rights reserved.)