Anatomy and Function of the Nervus Intermedius in Stereotactic Radiosurgery for Vestibular Schwannoma

Seong-Hyun Park, MD, PhD Department of Neurosurgery, Kyungpook National University Hospital, Daegu, Korea

Complete resection of vestibular schwannomas often presents a major surgical challenge because of the relationship of the tumor to critical neurovascular structures. Stereotactic radiosurgery plays a important role in the management of vestibular schwannomas. Some patients undergoing stereotactic radiosurgery (SRS) for vestibular schwannoma experience various disturbances of non-motor components of the facial nerve as a result of the SRS. In this brief review, the author described the anatomy of the nervus intermedius, the non-motor component of the facial nerve, and evaluate its dysfunction following stereotactic radiosurgery for the treatment of vestibular schwannoma.

KEY WORDS: Gamma Knife radiosurgery · Nervus intermedius · Stereotactic radiosurgery · Vestibular schwannoma.

INTRODUCTION vus intermedius during microsurgery or SRS for vestibular schwannoma is necessary to provide better functional out- Stereotactic radiosurgery (SRS) has become an impor- comes and to evaluate various disturbances of non-motor tant alternative option for small to moderate-sized vestibular components of the facial nerve. The facial nerve is a mixed schwannomas since the 1990s. Attention has been usually nerve with both motor and sensory components (nervus in- paid to the excellent rate of tumor control and the preserva- termedius) : motor, parasympathetic, and special sensory tion of the hearing and motor components of the facial nerve (taste). The facial nerve carries motor nerves to muscles of following SRS.1)4)5)8)9) However, several studies have re- facial expression, parasympathetics to lacrimal, subman- ported various disturbances to non-motor functions result- dibular, and sublingual glands and taste from the anterior ing from modern SRS, including lacrimal, salivary, nasal, two-thirds of the tongue.7)12) Nervus intermedius takes its and taste disturbances.7)10)11) name from its intermediate portion between motor root of The nervus intermedius is the sensory component of the facial and superior portion of vestibular nerves. Inside the facial nerve and carries parasympathetic secretomotor (lac- meatus, the motor root of the facial nerve and the nervus in- rimal, nasal, submandibular, and sublingual glands) and termedius are usually bound together as a single structure. special sense (taste) fibers (Fig. 1). This brief review consid- The special sensory fibers originate from the nucleus of the ered the anatomy and function of the nervus intermedius and solitary tract, which innervate parts of taste buds of the pal- provides information about the dysfunction of the nervus ate and anterior two-thirds of the tongue and some mucous intermedius following Gamma Knife® SRS for vestibular membranes of the nasopharynx. The parasympathetic fibers schwannoma. originate from a scattered group of cells called the superior salivatory nucleus, which innervate submandibular and sub- ANATOMY OF THE NERVUS INTERMEDIUS lingual salivary glands, nasal and palatine glands, and lacrimal glands. An understanding of the anatomical features of the ner- SRS FOR VESTIBULAR SCHWANNOMA Address for correspondence: Seong-Hyun Park, MD, PhD Department of Neurosurgery, Kyungpook National University Hos- SRS has become alternative frequent management for pital, 130 Dongduk-ro, Jung-gu, Daegu 700-721, Korea Tel: +82-53-200-5652, Fax: +82-53-423-0504 vestibular schwannomas and is reported to lead to high tu- 1)4)5)8)9) E-mail: [email protected] mor control rates and low complications. SRS is con- This study was accepted by 2014 Korean society of stereotactic sidered in the following groups of patients : those with re- and functional neurosurgery award. current or residual tumors after primary surgical resection ;

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terioration ; 2) no change ; 3) improvement compared with the preradiosurgical status ; and 4) normal function. Fifty-five consecutive patients underwent SRS for unilat- eral vestibular schwannoma at our institute between 2005 and 2010 were enrolled in our previous study.7) The author evaluated patients with a functional questionnaire before and after SRS to evaluate the function of nervus intermedius. Eighteen of 50 patients (36%) presented at least one disturbance of the nervus intermedius following SRS with dysfunctions of lacrimation, salivation, nasal secretion, and taste. Fig. 1. Schematic diagram showing the nuclei and course of the facial nerve. Nine of the 50 patients had preradiosurgical disturbances. A lacrimal disturbance before SRS was reported in 5 of those with symptomatic primary tumors in locations associ- 50 patients (10%) and in 10 patients (20%) after SRS. Five ated with a high risk for complete resection ; those with medi- out of 45 patients (11.1%) had a new lacrimal dysfunction af- cal comorbidities or advanced age ; and younger patients ter SRS. Salivary disturbances after SRS were reported in who decline microsurgery or continued observation. 5 of 50 patients (10%). Two patients had preradiosurgical symptoms, while 3 of 48 patients had an onset of a salivary Radiosurgical technique disturbance. In one patient (2%), increased nasal secretion The Gamma Knife radiosurgical technique has been de- was reported after SRS. A taste disturbance was experienced scribed in detail in previous reports.6)7) Patients underwent by three patients (6%) prior to SRS and by eight (16%) af- application of a Model G Leksell stereotactic frame under ter SRS. Five of 47 patients (10.6%) without a preradiosur- local anesthesia. After attaching an imaging compatible fi- gical taste disturbance experienced the symptom after SRS. ducial system to the frame, all patients underwent either high New onset of various disturbances occurred on average 15 resolution computed tomography (CT) or magnetic reso- months after SKS (range, 1-48 months). nance imaging (MRI). The three-dimensional reconstruc- Stripf, et al.10) reported that more than 50% of patients tions and treatment planning were made with T1-, T2-, who underwent microsurgery for vestibular schwannoma and enhanced T1-weighted MR images with 2mm axial removal presented with symptoms potentially caused by in- slices, and CISS (constructive interference in steady-state) jury of the nervus intermedius, which suggests insufficient images with 1mm slices. The CISS imaging helped iden- knowledge about anatomy of the nerve. Postoperatively, 70 tify the facial and vestibulocochlear nerves in the CPA cis- patients (45%) experienced crocodile tears and 62 (40%) tern ; it provided a good contrast between the cerebrospinal had dry eyes. Disturbances in taste were noted in 52 patients fluid and the nerves, with a focus on T2-weighted sequenc- (33%) after microsurgery. Increased nasal secretion was not- es. The MR images were transferred to a workstation for ed postoperatively in 68 patients (44%). The high incidence post-processing and analysis. of these symptoms seems to correlate with an increased risk of damage to the nervus intermedius during microsurgery DYSFUNCTION OF THE NERVUS because between the brainstem and the porus acousticus INTERMEDIUS this nerve is found to have no perineurium and is generally covered with just a thin arachnoid membrane.3) A normal In order to evaluate the function of nervus intermedius nervus intermedius contains 20% unmyelinated fibers.14) from the patient’s point of view, a functional questionnaire Therefore, the non-motor component of the nerve fiber is proposed by Stripf, et al.10) has been usually used. It is com- more vulnerable to mechanical damage, as compared to the posed of four parts assessing lacrimation, salivation, nasal thicker motor portion of the facial nerve. secretion, and taste. Each part of the questionnaire is divid- Tamura, et al.11) demonstrated that radiosurgery can in- ed into pre- and post-treatment occurrences, with each sec- duce nervus intermedius injury in a small proportion of the tion contains questions related to the presence of symptoms, patients (14%). In this study the Gamma Knife group expe- their character, and the time of onset and duration. Each dis- rienced a significant decrease in symptoms due to nervus turbance after SRS is classified into four categories : 1) de- intermedius injury, compared to microsurgery group. Park,

2 Seong-Hyun Park : Nervus Intermedius in Radiosurgery

Table 1. Comparison of nervus intermedius dysfunction after stereotactic radiosurgery (SRS) published in the literature

Population New disturbances after SRS (%) Authors & Year (no. of patients) Lacrimation Taste Salivation Nasal secretion Regis, et al.,9) 2002 104 27 - - - Tamura, et al.,11) 2008 064 12.8 08.1 - -

Park, et al.,7) 2013 055 11.1 10.6 10 2 et al.7) found 9 of 41 patients (22%) experienced a new on- increase after radiosurgery for vestibular schwannoma might set of a postradiosurgical nervus intermediate dysfunction. cause nervus intermedius dysfunction. Cranial nerve neu- Even though the nervus intermedius is anatomically less pro- ropathy may be related to tumor volume increase which in tected from radiation compared to the motor component, turn induces the risk of cranial nerve demyelination. How- a radiosurgical technique using a low marginal dose and a ever, there was no strong association between cranial nerve highly conformal dosage plan decreased the incidence of neuropathy and change in tumor volume after SRS.6) Ad- postradiosurgical dysfunction of both the non-motor and mo- verse radiation effect, defined as new neurological symp- tor fibers of the facial nerve, when compared to microsur- toms or signs in the absence of measurable tumor volume gery. change also might be one of the main causes of nervus in- In Park’s study, 11.1% of patients without a preradiosur- termedius dysfunction. gical lacrimal disturbance had a new lacrimal symptom With microsurgery, the risk of the facial nerve injury ris- after SRS and a postradiosurgical onset of a taste distur- es with tumor size, with the incidence of facial neuropa- bance occurred in 10.6% of patients (Table 1).7) Regis, et thy ranging from 0 to 6% in small tumors and from 8 to 24% al.9) reported that 27% of patients who underwent SRS ex- in moderate-sized tumors.2)8)15) Tamura, et al.11) suggested perienced a lacrimal disturbance. However, the risk of the that if one suffers injuries of the lacrimal component of the lacrimal disturbance was much higher in the patients treat- nervus intermedius before SRS, one will have also a high- ed by microsurgery due to a high incidence of facial palsy. er possibility to suffer from lacrimal disturbance after SRS. Tamura, et al.11) reported a taste disturbance in 8.1% patients However, factors related to the dysfunction of the nervus after SRS and in 45.5% of the patients after microsurgery. intermedius following SRS were not identified in our per- Watanabe, et al.13) reported that a taste disturbance occurred vious study.7) An analysis of the correlation between the postoperatively in 28.6% of patients having no preopera- tumor size and nervus intermedius dysfunction revealed no tive taste disturbance. Compared to lacrimal and taste dis- relationship to development of symptoms after SRS (p= turbances, nasal and salivary disturbances were rare after 0.305). Both the margin dose and the patient’s age were not SRS. In the literature review, no one has reported these related to the disturbance after SRS (p=0.352, 0.768, respec- symptoms to date, because patients may recover via a quick tively). Park, et al.6) reported SRS for cerebellopontine an- adaptation and not experience much discomfort. gle meningioma, and they found that there was no signifi- Nervus intermedius dysfunction in patients with vestib- cant relationship between cranial nerve neuropathy and ular schwannoma rarely occurs by tumor itself before treat- tumor volume, marginal dose. Reduction of marginal dose ment. The incidence of these disturbances after SRS in- in modern radiosurgical period could allow a decrease in creases by radiation injury. The physicians should consider facial nerve injury. However, there are still facial sensory that delayed onset of a nervus intermedius dysfunction could nerve deficits after SRS. It is import to find the way to re- occur in many cases, and the potential causes are transient duce the related morbidity because of high postradiosurgi- volume increase and radiation induced neuropathy. In cal quality of life. Park’s study, new onset of a lacrimal disturbance occurred on average 16 months after SRS (range, 8-36 months), a CONCLUSIONS salivary disturbance within 12 months after SRS (range, 6-12 months), and a taste disturbance on average 19 months It is true that the nervus intermedius dysfunction follow- after SRS (range, 1-48 months).7) Increased nasal secretion ing SRS for vestibular schwannoma is not as severe as was reported one year after SRS. A transient tumor volume hearing loss and facial palsy, but nervus intermedius dys-

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