Acta Oto-Laryngologica. 2014; 134: 221–226
ORIGINAL ARTICLE
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Evidence for bilateral endolymphatic hydrops in ipsilateral delayed endolymphatic hydrops: preliminary results from examination of five cases HIROSHI NONOYAMA1, TOHRU TANIGAWA1, TSUNEO TAMAKI2, HIROKAZU TANAKA1, OSAMU YAMAMURO2 & HIROMI UEDA1 1
Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi and 2Department of Radiology, East Nagoya Imaging Diagnisis Center, Jiyugaoka, Nagoya, Japan
Abstract Conclusion: After the administration of a standard dose of gadodiamide, an intravenous gadolinium-based contrast agent (GBCA), magnetic resonance imaging (MRI) evaluation of endolymphatic hydrops (EH) became possible in patients with ipsilateral delayed endolymphatic hydrops (DEH). We found that patients with ipsilateral DEH may also have bilateral EH. Objective: MRI evaluation contributes to understanding of the pathological conditions in patients with EH. However, double or triple the standard dose of GBCA is often required to obtain images of high quality. We attempted to examine EH bilaterally in patients with ipsilateral DEH after routine administration of an intravenous GBCA. Methods: GBCA (gadodiamide, 0.2 ml/kg) was administered intravenously to five patients with ipsilateral DEH. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR) MRI was performed with a 3-T MRI scanner 4 h after GBCA administration. Results: In all five patients, EH was observed in the affected vestibules. Moreover, EH was observed bilaterally in four (80%) of five patients with ipsilateral DEH. The region of the deaf ear affected by EH was considerably larger compared with the normal ear in three patients. However, observed regions of EH were of approximately the same size in both ears in patients 4 and 5.
Keywords: 3 T magnetic resonance imaging, three-dimensional fluid attenuated inversion recovery, intravenous administration, standard dose, gadolinium-based contrast agent, gadodiamide, better-hearing ear
Introduction Ipsilateral delayed endolymphatic hydrops (DEH) occurs in patients who have sustained a profound hearing loss in one ear, and then, after a prolonged period, develop episodic vertigo from the same ear [1]. Endolymphatic hydrops (EH) is a typical pathological alteration underlying DEH. Evidence of EH in the affected ear has been found at autopsy in patients with ipsilateral DEH [2]. Magnetic resonance imaging (MRI)-based analysis of patients with EH is valuable because MRI is more sensitive for detecting EH compared with other approaches, such as vestibular evoked myogenic potential measurement and electrocochleography
[3]. Recently, Kasai et al. reported that MRI following intratympanic gadolinium-based contrast agent (GBCA) injection can resolve EH in patients with DEH [4]. However, evaluation of endolymphatic spaces in the better-hearing ear of patients with DEH has not been reported. GBCA is administered via direct intratympanic injection or via intravenous delivery to visualize EH [5]. The intravenous delivery involves a simple procedure and can be used to evaluate the endolymphatic space in both ears simultaneously. Direct intratympanic injection of GBCAs has been found to induce mild ototoxicity in animal model studies [6]. Direct injections of GBCAs into the better-hearing ear are necessary if we
Correspondence: Tohru Tanigawa, Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan. Tel: +81 561 62 3311. Fax: +81 561 63 3403. E-mail: [email protected]
(Received 8 August 2013; accepted 26 September 2013) ISSN 0001-6489 print/ISSN 1651-2251 online Ó 2014 Informa Healthcare DOI: 10.3109/00016489.2013.850741
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want to check the bilateral conditions of the inner ear. Transmastoid labyrinthectomy is sometimes performed for patients with intractable ipsilateral DEH [7], but this treatment would be ineffective if the vertigo attacks were caused by a problem in the other ear. Routine GBCA dosages are frequently associated with poor MRI quality, because the signal-to-noise ratio is insufficient [8]. In 2006, the US Food and Drug Administration (FDA) warned that a severe reaction termed nephrogenic systemic fibrosis (NSF) may occur after exposure to a GBCA [9]. Broome et al. reported that 12 of 207 patients (5.8%) who underwent MR examinations with a double dose of GBCA developed NSF, but none of the 94 patients with a single dose developed NSF [10]. Therefore, we had to decide between obtaining images of higher quality and excessive GBCA administration. In 2011, we successfully visualized bilateral vestibular EH in patients with Meniere’s disease using three-dimensional fluid attenuated inversion recovery (3D-FLAIR) MRI performed 4 h after intravenous administration of a standard dose of a GBCA [5]. In this report, we describe the examination of bilateral vestibular EH using a 3 T MRI scanner, in patients with ipsilateral DEH 4 h after administration of a single dose of an intravenous GBCA. Material and methods Patients Five patients with ipsilateral DEH, diagnosed according to the 1987 criteria of the Japan Society for Equilibrium Research [11], were enrolled in this study (Table I). Patient 1 was a 28-year-old woman complaining of recurrent episodic vertigo and left-sided hearing impairment. The hearing loss (average threshold at 500, 1000, 2000 Hz is 110 dB) was first noticed and diagnosed in the patient at 8 years of age. Audiogram results for the better-hearing ear (right ear) showed no
hearing change (Figure 1, lower panel). Patient 1 had experienced vertigo attacks for the last 8 years and had consulted us because the frequent episodes could not be controlled during the previous 3 months. She had not used medication because vertigo attacks had not occurred since her first visit to our hospital. She had also not received any surgical treatment for her condition. The time period between patient 1’s last vertigo attack and the MRI examination was 120 days. Patient 2 was a 44-year-old man complaining of recurrent episodic vertigo and severe right-sided hearing loss (110 dB). When he was 8 years old, he contracted a mumps virus infection, leaving him with profound, fixed hearing loss in the right ear. The patient’s left ear exhibited a normal hearing profile (Figure 2A, lower panel). He had experienced episodic vertigo attacks for 8 years before our examination. Patient 2 was not taking any medication and had not undergone any surgical treatment for his condition. The time period between patient 2’s last vertigo attack and the MRI examination was 21 days. Patient 3 was an 18-year-old woman who had been referred to our hospital with a complaint of vertigo attacks 18 months earlier. The attacks had occurred approximately twice every month over the last 6 months before our MRI examination. Hearing loss in the right ear was apparent in patient 3 from 2 years of age. An audiogram of the left ear showed no degenerative hearing change (Figure 2B, lower panel). Patient 3 was not receiving any medication or surgical treatment for her condition. The time period between patient 3’s last vertigo attack and the MRI examination was 14 days. Patient 4 was a 75-year-old man who had experienced episodes of severe vertigo for 3 months before our MRI examination. The patient had a history of hearing loss in the right ear with age of onset being 2 years. He complained of feeling dizzy even when vertigo attacks did not occur. An audiogram of the better-hearing ear (left side) showed no hearing change (Figure 3A, lower panel). He received betahistine at a daily dose of 18 mg but had not undergone
Table I. Characteristics of patients with delayed endolymphatic hydrops (DEH).
Patient no
Age (years), sex
1
28, F
Left
15/110
8
Unknown
8
120
2
44, M
Right
113.3/20
8
Mumps
7
21
3
18, F
Right
115/15
2
Unknown
1.5
14
4
75, M
Right
115/31.7
2
Unknown
0.5
30
5
20, M
Right
111.7/11.7
Sudden deafness
0.25
7
Ear
Hearing level (dB): right/left
Age (years) at onset of hearing loss
11
Etiology of hearing loss
Duration of disease (years)
Time (days) between last attack and MRI
Endolymphatic hydrops in ipsilateral DEH A Patient 2
CBT
CBT
223
3D-FLAIR
250
Frequency in Hz 500 1000 2000
4000
8000
250
Frequency in Hz 500 1000 2000
4000
8000
3D-FLAIR –20
125
–10 0
3D-FRFSE
Frequency in Hz –20
125
250
500
1000
2000
4000
8000
–10
Hearing level in dB
3D-FRFSE
50
40 50 60 70
100
20
40
30
90
10
30
20
80
0
Hearing level in dB
110 120 B Patient 3
60 70 80 90 100 110
–20
120
–10
125
0 Figure 1. MRI in a patient with ipsilateral delayed endolymphatic hydrops (DEH) (patient 1). On 3D-FLAIR MRI, the EH of the vestibule was significantly larger on the left side (upper right panel, white arrow) than on the right side (upper left panel, black arrow). MRI of the right ear was similar to images obtained from a normal volunteer. No EH was observed in the cochlear basal turn (CBT) of either side. For anatomic reference, 3D-FRFSE MRI (middle panels) was also performed. The lower panel shows the audiogram for patient 1. The hearing loss (average threshold at 500, 1000, 2000 Hz is 110 dB) was first noticed and diagnosed in the patient at 8 years of age. Audiogram results for the better-hearing ear (right ear) showed no change in hearing.
any surgical treatment. The time period between patient 4’s last vertigo attack and the MRI examination was 30 days. Patient 5 was a 20-year-old man who was referred to our hospital with a history of frequent vertigo attacks for several months before our MRI examination. When he was 11 years old, he experienced sudden idiopathic sensorineural hearing loss in the right ear. The left ear exhibited a normal hearing
10 Hearing level in dB
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10
20 30 40 50 60 70 80 90
100 110 120 Figure 2. MRI in patients with ipsilateral delayed endolymphatic hydrops (DEH): (A) patient 2, (B) patient 3. On 3D-FLAIR MRI, the area of EH was enlarged in the affected (right side) ears compared with that in the better-hearing ears (white arrows). Superimposed audiograms are shown in the lower panels of A and B. In patient 3 (B), hearing levels of low frequency in the unaffected (left-sided) ear were slightly impaired, but the fluctuation was not identified.
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A Patient 4
Frequency in Hz –20
125
250
500
1000
2000
4000
8000
–10
profile (Figure 3B, lower panel), but the patient complained of left-sided tinnitus. He received betahistine at a daily dose of 18 mg but had not undergone any surgical treatment for vertigo symptoms. The time period between patient 5’s last vertigo attack and the MRI examination was 7 days. All patients gave informed consent to participate in this study. The study protocol was approved by the Ethics Review Committee of Aichi Medical University.
0
Hearing level in dB
Intravenous GBCA injection
20
All subjects received standard (single) intravenous doses (0.2 ml/kg) of gadodiamide (OmniscanTM, Daiichi Sankyo Pharmaceutical Co. Ltd, Tokyo, Japan). Gadodiamide is commonly administered intravenous MRI contrast agent [12]. According to previous reports [5], the gadolinium concentration in the perilymph reaches a maximal level 4 h after intravenous administration of a GBCA, therefore MRI was performed 4 h post-infusion for all patients in our study.
30 40 50 60 70 80 90
100 110 120
MRI
B Patient 5
Frequency in Hz –20
125
250
500
1000
2000
4000
8000
–10 0 10 Hearing level in dB
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10
20 30 40 50 60 70 80 90
All scans were performed with a 3 T MRI scanner (GE Healthcare Japan, Hino, Japan) using a 12-channel head-neck-spine coil to obtain a high signal-to-noise ratio [5]. Three-dimensional fast recovery fast spin echo (FRFSE) imaging was performed for anatomic reference data and 3D-FLAIR imaging was then performed to detect the EH. The running parameters for 3D-FRFSE were as follows: repetition time (TR), 2000 ms; echo time, 150 ms; echo train length, 39; receiver bandwidth, ± 41.67 kHz; matrix size, 384 384 (ZIP512), and 2 mm thick slices (ZIP2) covering the labyrinth with an 18 cm2 field of view. The number of excitations was one, and the scan time was 8 min 3 s. The parameters for 3D-FLAIR were as follows: TR, 9000 ms; echo time, 160 ms, echo train length, 132; receiver bandwidth, ± 31.25 kHz; matrix size, 320 192; and 1.8 mm thick slices (ZIP2) covering the labyrinth with a 20 cm2 field of view. The number of excitations was one, and the scan time was 9 min 31 s.
100 110
Image evaluation of EH
120 Figure 3. MRI in patients with ipsilateral delayed endolymphatic hydrops (DEH): (A) patient 4, (B) patient 5. On 3D-FLAIR MRI, the observed regions of EH were of approximately the same size (white arrows). Superimposed audiograms are shown in the lower panels of A and B. In patient 4 (A), age-related hearing impairment of the left-sided ear was observed.
EH was classified into one of three categories according to the gadolinium distribution, as follows: not visible, absence of high signal contrast medium; partially visible, interrupted high signal images of vestibulae; completely visible, all vestibular structure is completely visible. The degree of vestibular hydrops
225
Endolymphatic hydrops in ipsilateral DEH is rated as per the scoring system proposed by Fang et al. [13].
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Results In all patients, partially visible (including partial, but largely absent) or interrupted high signal images were observed in the affected vestibulae (Table II). Thus, we concluded that EH could be visualized with the administration of a standard dose of an intravenous GBCA for all patients in the study. The degree of vestibular hydrops is summarized in Table II. In four (80%) of five ipsilateral DEH patients, EH was also observed in the other ear not affected by DEH. In three patients, the area of EH was enlarged in the affected ear compared with that of the betterhearing ear (patients 1–3, representative MRIs are shown in Figures 1 and 2). In patients 4 and 5 (Figure 3), observed regions of EH were of approximately the same size in both ears. The relation between duration of the disease (vertigo period) and increased severity of the EH could not be found in both ears (Tables I and II). Discussion We successfully visualized EH after administration of a standard dose of an intravenous GBCA in patients with ipsilateral DEH. To our knowledge, this is the first report of EH being successfully visualized in patients with ipsilateral DEH after administration of a single dose of a GBCA. Previous studies indicated that the results of functional tests were positive in 75–82% of affected ears of patients with ipsilateral DEH [14,15]. Our imaging evaluation detected EH in all five patients for the study described herein. Intravenous administration of GBCA is therefore useful in imaging affected ears of patients with DEH. Our results show that EH was observed bilaterally in four (80%) of five patients with ipsilateral DEH. Tagaya et al. reported that bilateral (both affected and unaffected ear) EH was observed in patients with
unilateral Meniere’s disease [16]. Takeda et al. observed that higher SP/AP amplitude ratios were observed in the better-hearing ears of patients with ipsilateral DEH examined by electrocochleography, and speculated that EH was manifested in the betterhearing ears alongside the ear with confirmed DEH [17]. These features are consistent with our imaging results indicating that MRI-detectable EH is present in better-hearing ears of patients with ipsilateral DEH, although more studies are needed to confirm these imaging results. In the present study, EH regions of the affected ears were considerably larger than those of the unaffected ears in three patients. Observed regions of EH were of approximately the same size in the other two patients (patients 4 and 5). We could not find a relationship between the duration of the disease and the severity of the EH. We speculate that the extent of EH, as indicated by MRI, is less severe in affected ears for ‘recent onset’ patients (patients 4 and 5). However, progression of EH in the better-hearing ear may occur, possibly causing the episodes of vertigo [18]. Mizuta et al. reported that they had diagnosed some patients as having ipsilateral-type DEH, but afterwards they noticed their misdiagnosis because patients suffered from fluctuating hearing loss in the better-hearing ear [19]. GBCAs administered intravenously enter the perilymph but not the endolymph [4,5,16]. Therefore, 3D-FLAIR images in patients with EH fail to show complete high signal images of vestibulae [13]. Previous studies have focused on assessing the endolymphatic space in patients with EH [4,16]. Fang et al. noticed that evaluation of the MRI appearance of the perilymphatic space is an easier and more effective approach in patients with Meniere’s disease [13]. The present study found that determining gadodiamide distribution in the perilymphatic space is an important consideration in optimizing the MRI examination of DEH patients. This study has a few limitations. We reported on a relatively small number of patients, therefore we could not evaluate each EH quantitatively. The results we
Table II. 3D-FLAIR MRI findings in patients with delayed endolymphatic hydrops (DEH). High signal images in vestibulae Patient no
Clinical diagnosis
Right
Left
1
Left DEH
Completely visible
Partially visible
2
Right DEH
Not visible
Partially visible
3
Right DEH
Partially visible
Partially visible
4
Right DEH
Partially visible
Partially visible
5
Right DEH
Partially visible
Partially visible
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have reported are preliminary and further studies are essential to determine the prevalence of bilateral EH in patients with ipsilateral DEH, in addition to optimizing GBCA dosing regimens to improve the diagnostic utility of MRI data. In conclusion, we successfully visualized EH in all five patients after an intravenous administration of single-dose GBCA. EH was observed in the betterhearing ears in four of five patients with ipsilateral DEH, indicating that bilateral EH may be a subsequent pathological manifestation. Further large-scale studies are essential to fully understand the results. Findings of this study will be useful in developing better diagnostic and clinical approaches for the treatment of patients affected with DEH. In the near future, we intend to visualize the inner ear in patients with contralateral-type DEH. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
[7]
[8]
[9]
[10]
[11]
[12] [13]
References [1] Schuknecht HF. Delayed endolymphatic hydrops. Ann Otol Rhinol Laryngol 1978;87:743–8. [2] Schuknecht HF, Suzuka Y, Zimmermann C. Delayed endolymphatic hydrops and its relationship to Meniere’s disease. Ann Otol Rhinol Laryngol 1990;99:843–53. [3] Fukuoka H, Takumi Y, Tsukada K, Miyagawa M, Oguchi T, Ueda H, et al. Comparison of the diagnostic value of 3 T MRI after intratympanic injection of GBCA, electrocochleography, and the glycerol test in patients with Meniere’s disease. Acta Otolaryngol 2012;132:141–5. [4] Kasai S, Teranishi M, Katayama N, Sugiura M, Nakata S, Sone M, et al. Endolymphatic space imaging in patients with delayed endolymphatic hydrops. Acta Otolaryngol 2009;129: 1169–74. [5] Tanigawa T, Tamaki T, Yamamuro O, Tanaka H, Nonoyama H, Shiga A, et al. Visualization of endolymphatic hydrops after administration of a standard dose of an intravenous gadolinium-based contrast agent. Acta Otolaryngol 2011;131:596–601. [6] Katahira N, Tanigawa T, Tanaka H, Nonoyama H, Ueda H. Diluted gadoteridol (ProHanceÒ) causes mild
[14]
[15]
[16]
[17]
[18] [19]
ototoxicity in cochlear outer hair cells. Acta Otolaryngol 2013;133:788–95. Hashimoto S, Furukawa K, Sasaki T. Treatment of ipsilateral delayed endolymphatic hydrops. Acta Otolaryngol Suppl 1997;528:113–15. Nakashima T, Naganawa S, Teranishi M, Tagaya M, Nakata S, Sone M, et al. Endolymphatic hydrops revealed by intravenous gadolinium injection in patients with Ménière’s disease. Acta Otolaryngol 2010;130:338–43. Food and Drug Administration. Public health advisory: gadolinium containing contrast agents for magnetic resonance imaging (MRI): Omniscan, OptiMARK, Magnecist, ProHance, and MultiHance. Rockville, MD: FDA. 2006. Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007;188:586–92. Komatsuzaki A, Futaki T, Harada Y, Hozawa J, Ishii T, Kamei T, et al. Delayed endolymphatic hydrops. The guideline for standardization of diagnostic criteria in vertiginous diseases. The Committee for Standardization of Diagnostic Criteria in 16 Vertiginous Diseases. Equilib Res 1987;47:249–50; in Japanese. Nunn AD. The cost of developing imaging agents for routine clinical use. Invest Radiol 2006;41:206–12. Fang ZM, Chen X, Gu X, Liu Y, Zhang R, Cao DR, et al. A new magnetic resonance imaging scoring system for perilymphatic space appearance after intratympanic gadolinium injection, and its clinical application. J Laryngol Otol 2012; 126:454–9. Egami N, Ushio M, Yamasoba T, Murofushi T, Iwasaki S. Indication of the side of delayed endolymphatic hydrops by vestibular evoked myogenic potential and caloric test. ORL J Otorhinolaryngol Relat Spec 2010;72:242–6. Ohki M, Matsuzaki M, Sugasawa K, Murofushi T. Vestibular evoked myogenic potentials in ipsilateral delayed endolymphatic hydrops. ORL J Otorhinolaryngol Relat Spec 2002;64: 424–8. Tagaya M, Yamazaki M, Teranishi M, Naganawa S, Yoshida T, Otake H, et al. Endolymphatic hydrops and blood-labyrinth barrier in Ménière’s disease. Acta Otolaryngol 2011;131:474–9. Takeda N, Koizuka I, Nishiike S, Kitahara T, Horii A, Uno A, et al. Clinical features in patients with delayed endolymphatic hydrops. Nihon Jibiinkoka Gakkai Kaiho 1998;101:1385–9. Kamiei T. Delayed endolymphatic hydrops – comparison with Meniere’s disease. Pract Otol 2009;102:395–401. Mizuta K, Ito Y, Ushida J, Mori M, Kuze B, Hayakawa K, et al. Clinical characteristics of delayed endolymphatic hydrops. Equilib Res 1998;57:328–34.
ORIGINAL ARTICLE
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Evidence for bilateral endolymphatic hydrops in ipsilateral delayed endolymphatic hydrops: preliminary results from examination of five cases HIROSHI NONOYAMA1, TOHRU TANIGAWA1, TSUNEO TAMAKI2, HIROKAZU TANAKA1, OSAMU YAMAMURO2 & HIROMI UEDA1 1
Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi and 2Department of Radiology, East Nagoya Imaging Diagnisis Center, Jiyugaoka, Nagoya, Japan
Abstract Conclusion: After the administration of a standard dose of gadodiamide, an intravenous gadolinium-based contrast agent (GBCA), magnetic resonance imaging (MRI) evaluation of endolymphatic hydrops (EH) became possible in patients with ipsilateral delayed endolymphatic hydrops (DEH). We found that patients with ipsilateral DEH may also have bilateral EH. Objective: MRI evaluation contributes to understanding of the pathological conditions in patients with EH. However, double or triple the standard dose of GBCA is often required to obtain images of high quality. We attempted to examine EH bilaterally in patients with ipsilateral DEH after routine administration of an intravenous GBCA. Methods: GBCA (gadodiamide, 0.2 ml/kg) was administered intravenously to five patients with ipsilateral DEH. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR) MRI was performed with a 3-T MRI scanner 4 h after GBCA administration. Results: In all five patients, EH was observed in the affected vestibules. Moreover, EH was observed bilaterally in four (80%) of five patients with ipsilateral DEH. The region of the deaf ear affected by EH was considerably larger compared with the normal ear in three patients. However, observed regions of EH were of approximately the same size in both ears in patients 4 and 5.
Keywords: 3 T magnetic resonance imaging, three-dimensional fluid attenuated inversion recovery, intravenous administration, standard dose, gadolinium-based contrast agent, gadodiamide, better-hearing ear
Introduction Ipsilateral delayed endolymphatic hydrops (DEH) occurs in patients who have sustained a profound hearing loss in one ear, and then, after a prolonged period, develop episodic vertigo from the same ear [1]. Endolymphatic hydrops (EH) is a typical pathological alteration underlying DEH. Evidence of EH in the affected ear has been found at autopsy in patients with ipsilateral DEH [2]. Magnetic resonance imaging (MRI)-based analysis of patients with EH is valuable because MRI is more sensitive for detecting EH compared with other approaches, such as vestibular evoked myogenic potential measurement and electrocochleography
[3]. Recently, Kasai et al. reported that MRI following intratympanic gadolinium-based contrast agent (GBCA) injection can resolve EH in patients with DEH [4]. However, evaluation of endolymphatic spaces in the better-hearing ear of patients with DEH has not been reported. GBCA is administered via direct intratympanic injection or via intravenous delivery to visualize EH [5]. The intravenous delivery involves a simple procedure and can be used to evaluate the endolymphatic space in both ears simultaneously. Direct intratympanic injection of GBCAs has been found to induce mild ototoxicity in animal model studies [6]. Direct injections of GBCAs into the better-hearing ear are necessary if we
Correspondence: Tohru Tanigawa, Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan. Tel: +81 561 62 3311. Fax: +81 561 63 3403. E-mail: [email protected]
(Received 8 August 2013; accepted 26 September 2013) ISSN 0001-6489 print/ISSN 1651-2251 online Ó 2014 Informa Healthcare DOI: 10.3109/00016489.2013.850741
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want to check the bilateral conditions of the inner ear. Transmastoid labyrinthectomy is sometimes performed for patients with intractable ipsilateral DEH [7], but this treatment would be ineffective if the vertigo attacks were caused by a problem in the other ear. Routine GBCA dosages are frequently associated with poor MRI quality, because the signal-to-noise ratio is insufficient [8]. In 2006, the US Food and Drug Administration (FDA) warned that a severe reaction termed nephrogenic systemic fibrosis (NSF) may occur after exposure to a GBCA [9]. Broome et al. reported that 12 of 207 patients (5.8%) who underwent MR examinations with a double dose of GBCA developed NSF, but none of the 94 patients with a single dose developed NSF [10]. Therefore, we had to decide between obtaining images of higher quality and excessive GBCA administration. In 2011, we successfully visualized bilateral vestibular EH in patients with Meniere’s disease using three-dimensional fluid attenuated inversion recovery (3D-FLAIR) MRI performed 4 h after intravenous administration of a standard dose of a GBCA [5]. In this report, we describe the examination of bilateral vestibular EH using a 3 T MRI scanner, in patients with ipsilateral DEH 4 h after administration of a single dose of an intravenous GBCA. Material and methods Patients Five patients with ipsilateral DEH, diagnosed according to the 1987 criteria of the Japan Society for Equilibrium Research [11], were enrolled in this study (Table I). Patient 1 was a 28-year-old woman complaining of recurrent episodic vertigo and left-sided hearing impairment. The hearing loss (average threshold at 500, 1000, 2000 Hz is 110 dB) was first noticed and diagnosed in the patient at 8 years of age. Audiogram results for the better-hearing ear (right ear) showed no
hearing change (Figure 1, lower panel). Patient 1 had experienced vertigo attacks for the last 8 years and had consulted us because the frequent episodes could not be controlled during the previous 3 months. She had not used medication because vertigo attacks had not occurred since her first visit to our hospital. She had also not received any surgical treatment for her condition. The time period between patient 1’s last vertigo attack and the MRI examination was 120 days. Patient 2 was a 44-year-old man complaining of recurrent episodic vertigo and severe right-sided hearing loss (110 dB). When he was 8 years old, he contracted a mumps virus infection, leaving him with profound, fixed hearing loss in the right ear. The patient’s left ear exhibited a normal hearing profile (Figure 2A, lower panel). He had experienced episodic vertigo attacks for 8 years before our examination. Patient 2 was not taking any medication and had not undergone any surgical treatment for his condition. The time period between patient 2’s last vertigo attack and the MRI examination was 21 days. Patient 3 was an 18-year-old woman who had been referred to our hospital with a complaint of vertigo attacks 18 months earlier. The attacks had occurred approximately twice every month over the last 6 months before our MRI examination. Hearing loss in the right ear was apparent in patient 3 from 2 years of age. An audiogram of the left ear showed no degenerative hearing change (Figure 2B, lower panel). Patient 3 was not receiving any medication or surgical treatment for her condition. The time period between patient 3’s last vertigo attack and the MRI examination was 14 days. Patient 4 was a 75-year-old man who had experienced episodes of severe vertigo for 3 months before our MRI examination. The patient had a history of hearing loss in the right ear with age of onset being 2 years. He complained of feeling dizzy even when vertigo attacks did not occur. An audiogram of the better-hearing ear (left side) showed no hearing change (Figure 3A, lower panel). He received betahistine at a daily dose of 18 mg but had not undergone
Table I. Characteristics of patients with delayed endolymphatic hydrops (DEH).
Patient no
Age (years), sex
1
28, F
Left
15/110
8
Unknown
8
120
2
44, M
Right
113.3/20
8
Mumps
7
21
3
18, F
Right
115/15
2
Unknown
1.5
14
4
75, M
Right
115/31.7
2
Unknown
0.5
30
5
20, M
Right
111.7/11.7
Sudden deafness
0.25
7
Ear
Hearing level (dB): right/left
Age (years) at onset of hearing loss
11
Etiology of hearing loss
Duration of disease (years)
Time (days) between last attack and MRI
Endolymphatic hydrops in ipsilateral DEH A Patient 2
CBT
CBT
223
3D-FLAIR
250
Frequency in Hz 500 1000 2000
4000
8000
250
Frequency in Hz 500 1000 2000
4000
8000
3D-FLAIR –20
125
–10 0
3D-FRFSE
Frequency in Hz –20
125
250
500
1000
2000
4000
8000
–10
Hearing level in dB
3D-FRFSE
50
40 50 60 70
100
20
40
30
90
10
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any surgical treatment. The time period between patient 4’s last vertigo attack and the MRI examination was 30 days. Patient 5 was a 20-year-old man who was referred to our hospital with a history of frequent vertigo attacks for several months before our MRI examination. When he was 11 years old, he experienced sudden idiopathic sensorineural hearing loss in the right ear. The left ear exhibited a normal hearing
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100 110 120 Figure 2. MRI in patients with ipsilateral delayed endolymphatic hydrops (DEH): (A) patient 2, (B) patient 3. On 3D-FLAIR MRI, the area of EH was enlarged in the affected (right side) ears compared with that in the better-hearing ears (white arrows). Superimposed audiograms are shown in the lower panels of A and B. In patient 3 (B), hearing levels of low frequency in the unaffected (left-sided) ear were slightly impaired, but the fluctuation was not identified.
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profile (Figure 3B, lower panel), but the patient complained of left-sided tinnitus. He received betahistine at a daily dose of 18 mg but had not undergone any surgical treatment for vertigo symptoms. The time period between patient 5’s last vertigo attack and the MRI examination was 7 days. All patients gave informed consent to participate in this study. The study protocol was approved by the Ethics Review Committee of Aichi Medical University.
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All scans were performed with a 3 T MRI scanner (GE Healthcare Japan, Hino, Japan) using a 12-channel head-neck-spine coil to obtain a high signal-to-noise ratio [5]. Three-dimensional fast recovery fast spin echo (FRFSE) imaging was performed for anatomic reference data and 3D-FLAIR imaging was then performed to detect the EH. The running parameters for 3D-FRFSE were as follows: repetition time (TR), 2000 ms; echo time, 150 ms; echo train length, 39; receiver bandwidth, ± 41.67 kHz; matrix size, 384 384 (ZIP512), and 2 mm thick slices (ZIP2) covering the labyrinth with an 18 cm2 field of view. The number of excitations was one, and the scan time was 8 min 3 s. The parameters for 3D-FLAIR were as follows: TR, 9000 ms; echo time, 160 ms, echo train length, 132; receiver bandwidth, ± 31.25 kHz; matrix size, 320 192; and 1.8 mm thick slices (ZIP2) covering the labyrinth with a 20 cm2 field of view. The number of excitations was one, and the scan time was 9 min 31 s.
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120 Figure 3. MRI in patients with ipsilateral delayed endolymphatic hydrops (DEH): (A) patient 4, (B) patient 5. On 3D-FLAIR MRI, the observed regions of EH were of approximately the same size (white arrows). Superimposed audiograms are shown in the lower panels of A and B. In patient 4 (A), age-related hearing impairment of the left-sided ear was observed.
EH was classified into one of three categories according to the gadolinium distribution, as follows: not visible, absence of high signal contrast medium; partially visible, interrupted high signal images of vestibulae; completely visible, all vestibular structure is completely visible. The degree of vestibular hydrops
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Endolymphatic hydrops in ipsilateral DEH is rated as per the scoring system proposed by Fang et al. [13].
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Results In all patients, partially visible (including partial, but largely absent) or interrupted high signal images were observed in the affected vestibulae (Table II). Thus, we concluded that EH could be visualized with the administration of a standard dose of an intravenous GBCA for all patients in the study. The degree of vestibular hydrops is summarized in Table II. In four (80%) of five ipsilateral DEH patients, EH was also observed in the other ear not affected by DEH. In three patients, the area of EH was enlarged in the affected ear compared with that of the betterhearing ear (patients 1–3, representative MRIs are shown in Figures 1 and 2). In patients 4 and 5 (Figure 3), observed regions of EH were of approximately the same size in both ears. The relation between duration of the disease (vertigo period) and increased severity of the EH could not be found in both ears (Tables I and II). Discussion We successfully visualized EH after administration of a standard dose of an intravenous GBCA in patients with ipsilateral DEH. To our knowledge, this is the first report of EH being successfully visualized in patients with ipsilateral DEH after administration of a single dose of a GBCA. Previous studies indicated that the results of functional tests were positive in 75–82% of affected ears of patients with ipsilateral DEH [14,15]. Our imaging evaluation detected EH in all five patients for the study described herein. Intravenous administration of GBCA is therefore useful in imaging affected ears of patients with DEH. Our results show that EH was observed bilaterally in four (80%) of five patients with ipsilateral DEH. Tagaya et al. reported that bilateral (both affected and unaffected ear) EH was observed in patients with
unilateral Meniere’s disease [16]. Takeda et al. observed that higher SP/AP amplitude ratios were observed in the better-hearing ears of patients with ipsilateral DEH examined by electrocochleography, and speculated that EH was manifested in the betterhearing ears alongside the ear with confirmed DEH [17]. These features are consistent with our imaging results indicating that MRI-detectable EH is present in better-hearing ears of patients with ipsilateral DEH, although more studies are needed to confirm these imaging results. In the present study, EH regions of the affected ears were considerably larger than those of the unaffected ears in three patients. Observed regions of EH were of approximately the same size in the other two patients (patients 4 and 5). We could not find a relationship between the duration of the disease and the severity of the EH. We speculate that the extent of EH, as indicated by MRI, is less severe in affected ears for ‘recent onset’ patients (patients 4 and 5). However, progression of EH in the better-hearing ear may occur, possibly causing the episodes of vertigo [18]. Mizuta et al. reported that they had diagnosed some patients as having ipsilateral-type DEH, but afterwards they noticed their misdiagnosis because patients suffered from fluctuating hearing loss in the better-hearing ear [19]. GBCAs administered intravenously enter the perilymph but not the endolymph [4,5,16]. Therefore, 3D-FLAIR images in patients with EH fail to show complete high signal images of vestibulae [13]. Previous studies have focused on assessing the endolymphatic space in patients with EH [4,16]. Fang et al. noticed that evaluation of the MRI appearance of the perilymphatic space is an easier and more effective approach in patients with Meniere’s disease [13]. The present study found that determining gadodiamide distribution in the perilymphatic space is an important consideration in optimizing the MRI examination of DEH patients. This study has a few limitations. We reported on a relatively small number of patients, therefore we could not evaluate each EH quantitatively. The results we
Table II. 3D-FLAIR MRI findings in patients with delayed endolymphatic hydrops (DEH). High signal images in vestibulae Patient no
Clinical diagnosis
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Partially visible
Partially visible
4
Right DEH
Partially visible
Partially visible
5
Right DEH
Partially visible
Partially visible
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have reported are preliminary and further studies are essential to determine the prevalence of bilateral EH in patients with ipsilateral DEH, in addition to optimizing GBCA dosing regimens to improve the diagnostic utility of MRI data. In conclusion, we successfully visualized EH in all five patients after an intravenous administration of single-dose GBCA. EH was observed in the betterhearing ears in four of five patients with ipsilateral DEH, indicating that bilateral EH may be a subsequent pathological manifestation. Further large-scale studies are essential to fully understand the results. Findings of this study will be useful in developing better diagnostic and clinical approaches for the treatment of patients affected with DEH. In the near future, we intend to visualize the inner ear in patients with contralateral-type DEH. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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[8]
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[12] [13]
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