The ptotic tongue-imaging appearance and pathology localization along the course of the hypoglossal nerve.

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.

Malignant Nerve Sheath Tumor of the Hypoglossal Nerve in a Maltese Dog.

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.

Diagnosis and management of hypoglossal nerve-derived schwannoma in the floor of mouth: a case series.

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.

Gradient subthalamic neurodegeneration and tau pathology in the hypoglossal nucleus as essential pathological markers of progressive supranuclear palsy - Richardson syndrome.

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.

Report of a non-looped variant of ansa cervicalis with omohyoid innervation from accessory nerve branch and omohyoid attachment to mastoid process.

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.

Isolated hypoglossal nerve palsy due to a jugular foramen schwannoma.

Introduction - Although the involvement of the hypoglossal nerve together with other cranial nerves is common in several pathological conditions of the brain, particularly the brainstem, isolated hypoglossal nerve palsy is a rare condition and a diagnostic challenge. Case presentation - The presented patient arrived to the hospital with a history of slurred speech and an uncomfortable sensation on his tongue. Neurological examination showed left-sided hemiatrophy of the tongue with fasciculations and deviation towards the left side during protrusion. Based on the clinical and MRI findings, a diagnosis of hypoglossal nerve schwannoma was made. Discussion - Hypoglossal nerve palsy may arise from multiple causes such as trauma, infections, neoplasms, and endocrine, autoimmune and vascular pathologies. In our case, the isolated involvement of the hypoglossal nerve was at the skull base segment, where the damage to the hypoglossal nerve may occur mostly due to metastasis, nasopharyngeal carcinomas, nerve sheath tumors and glomus tumors. Conclusion - Because of the complexity of the region's anatomy, the patient diagnosed with hypoglossal nerve schwannoma was referred for gamma knife radiosurgery.

Facial-Hypoglossal End-To-Side Neurorrhaphy: Exploration of the Source of Axonal Sprouting.

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.

Bilateral hypoglossal nerve paralysis following elongated styloid process resection: case report.

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.

Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through interaction with misfolded superoxide dismutase 1.

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-1ß, 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.

Altered expression of dopamine receptors in cholinergic motoneurons of the hypoglossal nucleus in a 6-OHDA-induced Parkinson's disease rat model.

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.

Extracranial Hypoglossal Schwannoma: Case Report and Literature Review.

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.

[Neuritis cordis and myocarditis in rabies]. / Neuritis cordis und Myokarditis bei Tollwut.

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.

Yin-Yang tongue sign: An imaging clue of lesions involving the skull base segment in the hypoglossal pathway.

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.

The Hypoglossal Nerve.

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.

Hypoglossal nerve palsy missed and misinterpreted: the hidden skull base.

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.

Isolated Hypoglossal Nerve Palsy as an Early Symptom of a Granular Cell Tumor.

BACKGROUND: Hypoglossal nerve palsy (HNP) is rather common as a neurological disease. However, as an isolated nerve palsy it is an exceedingly rare phenomenon and points at local pathologies along the peripheral course of the nerve. In this communication we report a granular cell tumor (GCT) arising in the submandibular segment of the hypoglossal nerve. CASE-REPORT: Spontaneous isolated HNP was recognized in a female patient. First line MR-imaging identified a clivus-chordoma. However, involvement of the hypoglossal nerve was highly unlikely according to MR-findings. Finally, ultrasonographic investigation revealed a small submandibular mass which, at histological examination, turned out to be a granular cell tumor arising within the hypoglossal nerve. CONCLUSIONS: This is the report of an extremely rare GCT originating within the 12th cranial nerve. The case illustrates that isolated motoric cranial nerve palsy may result from this rare tumor entity. This report also points out the diagnostic value of a simple ultrasonographic investigation to depict pathologic lesions of the submandibular space.

Endoscopic transoral approach for extracranial hypoglossal schwannoma.

OBJECTIVE: Hypoglossal nerve schwannoma, especially when inside the extracranial region, is extremely rare. This report describes a new endoscopic transoral approach for the removal of extracranial hypoglossal schwannoma. PATIENTS AND METHODS: Three patients (1 male and 2 females, aged 58-63 years) with extracranial hypoglossal schwannoma in the paroccipital condyle and the jugular foramen were treated solely by an endoscopic transoral approach. All patients presented signs of hypoglossal nerve paresis with hemiatrophy of the tongue. In addition, one of them had glossopharyngeal nerve paresis, and vagus nerve paresis was found in another patient. RESULTS: In all patients, tumors underwent successful radical intracapsular removal by the endoscopic transoral approach, as confirmed by the postoperative examinations and MRI. No complications occurred during or after surgery, except that 1 patient had swallowing difficulties and a temporary right vagus palsy during the first day after surgery. All patients were followed up for 6 months, and the lack of any recurrence has been confirmed. Muscle bulk, motor and swallowing functions, and the vagus palsy improved in all patients. CONCLUSION: The endoscopic transoral approach is a safe and useful surgical technique for the removal of intracapsular tumors, including extracranial hypoglossal schwannomas, which involves minimal invasion.

Hemihypoglossal-facial nerve anastomosis for facial nerve palsy.

BACKGROUND AND PURPOSE: Commonly used classic hypoglossal (CN XII) to facial nerve (CN VII) anastomosis has the disadvantage of tongue hemiatrophy. Thus, various attempts have been made to modify this method to reduce the tongue damage. The aim of this report was to present the results of hemihypoglossal-facial nerve anastomosis (HHFA) technique in relation to facial muscles reanimation and hemitongue atrophy. MATERIAL AND METHODS: The first 7 consecutive patients who underwent CN VII anastomosis with half of the CNXII, for which the follow-up period exceeded 12 months, were analysed. During the procedure, CN VII was transected as proximally as possible after drilling the mastoid process. CN XII was separated longitudinally into two parts at a short distance to allow suture of the stumps without any tension. One half of CN XII was transected and sutured to the distal stump of CN VII. Recovery from facial palsy was quantified with the House-Brackmann grading system (HB). Tongue function was assessed according to the scale proposed by Martins. RESULTS: Features of initial reinnervation of facial muscles were visible after 6 months in all 7 patients. All patients achieved satisfactory outcome of CN VII regeneration (HB grade III) until the last control examination (12-27 months after surgery, mean 16). No or minimal tongue atrophy without deviation (grades I-II according to the Martins scale) was found in 4 patients. Mild hemiatrophy with tongue deviation < 30 degrees (grade III) was visible in 3 patients. CONCLUSIONS: In our experience, HHFA is effective treatment of facial palsy and gives a chance to reduce damage of the tongue.

Size-dependent dendritic maladaptations of hypoglossal motor neurons in SOD1G93A mice.

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 SOD1G93A 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 SOD1G93A 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.

Hypoglossal Nerve Lesions: The Role of a 3D IR-Prepped Fast SPGR High-Resolution 3T MRI Sequence.

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.