Naoaki Yanagihara
Ehime University
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Annals of Internal Medicine | 1996
Shingo Murakami; Mutsuhiko Mizobuchi; Yuki Nakashiro; Takashi Doi; Naohito Hato; Naoaki Yanagihara
Bell palsy is the most common cause of facial paralysis worldwide; it has an incidence of 20 to 30 per 100 000 persons [1]. Although the second most frequent cause of facial paralysis, the Ramsay-Hunt syndrome, is known to be caused by reactivated varicella-zoster virus [2], the etiologic agent responsible for Bell palsy has not been identified. Many events, such as viral infection [1, 3, 4], ischemia [5], and autoimmune reaction [6], have been proposed as causes of Bell palsy. Viral infection is thought to be the most likely cause [7]. However, it is rare to find a diagnostic fourfold increase in specific viral antibody titer in the acute and convalescent serum specimens of patients with Bell palsy [3, 4, 7]. Postmortem histopathologic studies of the facial nerve suggest viral neuritis [8], but electron microscopic studies have failed to detect specific viral particles in the facial nerve [9]. Because the etiologic agent of Bell palsy is unknown, treatment of this condition is empiric, varying from observation alone to the use of steroids, surgical decompression, and antiviral agents. We analyzed the viral genomes of herpes simplex virus type 1 (HSV-1), varicella-zoster virus, and Epstein-Barr virus using polymerase chain reaction (PCR) on facial nerve endoneurial fluid specimens and specimens of posterior auricular muscle innervated by the facial nerve. Methods Patients and Specimens During a 4-year period, 14 of 170 patients with Bell palsy and 9 of 51 patients with the Ramsay-Hunt syndrome had decompression surgery 12 to 87 days after the onset of facial palsy. None had benefited from medical management. All patients and controls gave informed consent. Two types of clinical specimens were collected intraoperatively: endoneurial fluid from the facial nerve and tissue from the posterior auricular muscle. A piece of auricular muscle was resected after skin incision, and we obtained endoneurial fluid by absorbing it with a small, sterilized surgical sponge held at the mastoid segment immediately after the epineural sheath was incised. We stored both specimens immediately at 80 C and continued to store them at that temperature until PCR analysis was done. Control specimens of endoneurial fluid and posterior auricular muscle were collected during decompression surgery from four patients with temporal bone fracture or bacterial infection concomitant with otitis media. Posterior auricular muscle specimens were obtained during tympanoplasty from five patients with chronic otitis media who did not have facial paralysis. As an additional control, a piece of neural tissue was obtained from each of three patients with parotid tumors or facial neuroma whose facial nerves had already been affected (Table 1). Table 1. Clinical Data and Polymerase Chain Reaction Results in Patients with Bell Palsy, Patients with the Ramsay-Hunt Syndrome, and Controls* Polymerase Chain Reaction To amplify and identify the HSV, varicella-zoster virus, and Epstein-Barr virus genomes, five sets of virus-specific primers and internal oligonucleotide probes were synthesized for PCR and Southern blot analysis. Primer set 1 was prepared for amplification of the HSV-1 genome, which is located on the US6 gene [10]. Primer set 2 was designed to amplify both HSV-1 and HSV-2. A sense primer (5-CCACCGAGCGGCAGGTGATC-3) and an antisense primer (5-GCCGACCGCCTGCTCGTGCT-3) are located on the UL44-45 gene [11]. Using primer set 2, we discriminated between HSV-1 (578 base pairs) and HSV-2 (621 base pairs) on the basis of size. Nucleotide sequences of the HSV specific internal probe are 5-GAGGCGATCGAGTGGGT-3. Primer sets 3 and 4 were prepared for varicella-zoster virus amplification (genes 29 and 62, respectively) [12], and primer set 5 was prepared for Epstein-Barr virus amplification (latent cycle gene) [13]. The sensitivities of the primer sets were assessed by making serial 10-fold dilutions of each purified DNA sample. The limits of detection for primer sets 1, 2, 3, 4, and 5 were about 10, 100, 10, 100, and 10 femtograms, respectively. Samples of endoneurial fluid (about 10 L), posterior auricular muscle (2 mg to 5 mg), and nerve tissue (0.5 mg to 1 mg) were completely digested with proteinase K. Polymerase chain reaction amplification and subsequent hybridization with Southern blot analysis were done as described previously [14]. Rigid precautions against contamination in the sample processing included the use of water controls replacing the DNA samples in all amplifications. Serum Antibody Titers We examined serum antibody titers by using the complement fixation test for HSV-1 and varicella-zoster virus and by using fluorescent antibody methods for Epstein-Barr virus 8 to 38 days after the onset of facial paralysis. Results We amplified HSV-1-specific DNA fragments from the US6 and UL44-45 genes in both endoneurial fluid and posterior auricular muscle specimens obtained from patients with Bell palsy. The PCR-amplified products of the US6 gene were detected by Southern blot analysis in 10 of the 13 fluid specimens (77%) and 8 of the 14 muscle specimens (57%); the products of the UL44-45 gene were detected in 4 of the 13 fluid specimens (31%) and 7 of the 14 muscle specimens (50%). Neither varicella-zoster virus nor Epstein-Barr virus was detected in the same clinical specimens (Figure 1, top; (Table 1). We did not detect HSV-1 DNA in either the fluid or the muscle specimens of three patients with Bell palsy [patients 9, 12, and 13]. The PCR-amplified DNA fragments of the US6 gene from two patients with Bell palsy (patients 6 and 7) were sequenced directly after asymmetric PCR was done as described previously [14]. The nucleotide sequences of the amplified products (221 base pairs) were identical to those of the HSV-1 genome submitted to the GenBank (Mountain View, California [data bank with genetic information]) with accession numbers J02217 and K02372. Figure 1. Amplification of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) genomes from clinical samples. top bottom middle We detected varicella-zoster virus DNA from gene 29 or gene 62 in specimens obtained from patients with the Ramsay-Hunt syndrome only (Figure 1, middle; Table 1). Gene 29 was detected in 8 of the 9 patients (89%), and gene 62 was detected in 6 of the 9 patients (67%). On the other hand, we could not amplify HSV-1, varicella-zoster virus, or Epstein-Barr virus DNA from any specimens obtained from the other controls (Figure 1, bottom; Table 1). Serum antibody titer to HSV-1 was positive in 12 of 13 patients (92%) with Bell palsy, in 4 of 9 patients (44%) with the Ramsay-Hunt syndrome, and in 5 of 9 controls (56%) (Table 1). The prevalence of HSV-1 antibody in patients with Bell palsy was significantly higher than that in controls (P < 0.05, Fisher exact test). However, antibody titers to HSV-1 in patients with Bell palsy were not significantly higher than those of controls, as previously reported [3, 4]. Discussion We found HSV-1 DNA in 11 of 14 patients (79%) with Bell palsy, and we found varicella-zoster virus DNA in 8 of the 9 patients (89%) with the Ramsay-Hunt syndrome. The identification of viral DNA may not always be definitive evidence that a particular agent causes a disease process, because PCR can amplify viral DNA regardless of whether the virus is in the infective, lytic, or latent state. The presence of latent HSV-1 and varicella-zoster virus genomes has also been shown by PCR in the geniculate ganglion of human facial nerves at autopsy [15-17]. However, HSV-1 and varicella-zoster virus usually remain dormant in ganglia and would probably not be detected in the endoneurial fluid or auricular muscle unless they were reactivated. This hypothesis was supported by our inability to detect either HSV-1 or varicella-zoster DNA in controls. Cranial nerve surgery often reactivates latent HSV, causing labial and facial herpetic lesions 48 to 72 hours after surgery [18]. However, because we obtained specimens within 2 hours of beginning decompression surgery, reactivation of the virus in the muscle or fluid was probably not induced by surgery. If this surgery did reactivate latent HSV-1, viral DNA should also have been detected in patients with the Ramsay-Hunt syndrome and in other controls who were seropositive for HSV-1. Triggers known to be associated with Bell palsy are also known to reactivate HSV. Preceding stress, such as upper respiratory tract infection, fever, dental extraction, menstruation, or exposure to cold might reactivate latent HSV-1 in the geniculate ganglion. After the virus reactivates, it destroys ganglion cells and spreads into the endoneurial fluid. The virus also infects Schwann cells, leading to demyelinization and inflammation of the facial nerve [19]. This inflammatory response has been shown by gadolinium-enhanced magnetic resonance imaging in patients with Bell palsy and in patients with the Ramsay-Hunt syndrome [20]. Given the known neuropathogenicity of HSV-1 and the presence of HSV-1 DNA in the lesional site of the facial nerve specific to patients with Bell palsy, we conclude that HSV-1 infection in the facial nerve is directly related to the pathogenesis of Bell palsy just as the varicella-zoster virus is directly related to the pathogenesis of the Ramsay-Hunt syndrome. There are two possible explanations for our failure to detect HSV-1 in three of the patients with Bell palsy [patients 9, 12, and 13]: 1) the limited sensitivity of PCR analysis to detect small amounts of viral DNA and 2) the presence of an etiologic agent other than HSV-1. More data are required to determine the percentage of patients with Bell palsy in whom HSV-1 is the etiologic agent of Bell palsy, but our findings suggest that HSV-1 infection is the major cause of Bell palsy and that treatment with appropriate antiviral agents might benefit most patients with this condition. Drs. Mizobuchi, Nakashiro, and Doi: Department of Neuropsychiatry, Ehime Universit
Annals of Otology, Rhinology, and Laryngology | 1995
Toshiaki Sugita; Yasuo Fujiwara; Shingo Murakami; Yoshinari Hirata; Naoaki Yanagihara; Takeshi Kurata
We have been the first to succeed in producing an acute and transient facial paralysis simulating Bells palsy, by inoculating herpes simplex virus into the auricles or tongues of mice. The KOS strain of the virus was injected into the auricle of 104 mice and the anterior two thirds of the tongue in 30 mice. Facial paralysis developed between 6 and 9 days after virus inoculation, continued for 3 to 7 days, and then recovered spontaneously. The animals were painlessly sacrificed between 6 and 20 days after inoculation for histopathologic and immunocytochemical study. Histopathologically, severe nerve swelling, inflammatory cell infiltration, and vacuolar degeneration were manifested in the affected facial nerve and nuclei. Herpes simplex virus antigens were also detected in the facial nerve, geniculate ganglion, and facial nerve nucleus. The pathophysiologic mechanisms of the facial paralysis are discussed in light of the histopathologic findings, in association with the causation of Bells palsy.
Otology & Neurotology | 2003
Naohito Hato; Shuichi Matsumoto; Hisanobu Kisaki; Hirotaka Takahashi; Hiroyuki Wakisaka; Nobumitsu Honda; Kiyofumi Gyo; Shingo Murakami; Naoaki Yanagihara
Objective To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bells palsy. Study Design This was a retrospective study of 480 Bells palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases). Patients Patients met the after criteria: (1) severe or complete Bells palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60–40 mg/day) with or without oral acyclovir (2,000 mg/day). Main Outcome Measure Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis. Results The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent. Conclusion These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bells palsy.
Annals of Neurology | 2000
Naohito Hato; Hisanobu Kisaki; Nobumitsu Honda; Kiyofumi Gyo; Shingo Murakami; Naoaki Yanagihara
In a retrospective study, 52 children were diagnosed with Ramsay Hunt syndrome. The facial palsy was milder and complete recovery of the function was achieved in 78.6% of patients. Associated cranial neuropathies were less common in children than in adults. The timing of vesicle appearance tended to be delayed in children. In preschool children, Ramsay Hunt syndrome was rare, although the frequency has recently increased. The syndrome is relatively common in older children. This study suggested that vaccination can prevent or reduce the occurrence of Ramsay Hunt syndrome. Ann Neurol 2000;48:254–256
Laryngoscope | 1993
Naoaki Yanagihara; Masanori Asai
In our series of 111 patients operated on for acoustic neuroma from 1972 to 1990, 21 (18.9%) had sudden hearing loss. The 21 tumors involved were comprised of 9 small, 5 medium, and 7 large tumors. Emphasis is placed on the fact that even a small tumor has the potential to produce sudden hearing loss (SHL) and that the possibility of seeing patients with SHL is increasing thanks to advances in imaging diagnosis. Recognition of SHL as an initial symptom of acoustic tumor is considered essential to detect small acoustic neuroma.
Neuroscience Letters | 1997
Nobuhiro Hakuba; Kiyofumi Gyo; Naoaki Yanagihara; Akira Mitani; Kiyoshi Kataoka
Using a microdialysis technique followed by an enzyme cycling analysis, we measured changes in the glutamate levels in the perilymph of gerbil cochleae before, during and after transient ischemic insult. The basal glutamate level in perilymph was 0.35 +/- 0.22 pmol/microl. An almost immediate and continuous rise in the level of glutamate occurred after the ischemic insult, which advanced even further after recirculation; the average concentration was higher than 40 pmol/microl 55 min after recirculation. The compound action potentials (CAP) monitoring the auditory function totally disappeared after ischemic insult. However, CAP reappeared after recirculation; the threshold for acoustic stimulation was higher than that observed at the pre-ischemic state.
Otolaryngology-Head and Neck Surgery | 2001
Naoaki Yanagihara; Naohito Hato; Shingo Murakami; Nobumitsu Honda
OBJECTIVE: We sought to assess the efficacy of transmastoid decompression after steroid treatment. STUDY DESIGN: One hundred one adults with Bell palsy having denervation exceeding 95% after steroid treatment were divided into 2 groups. In 58 patients decompression from the labyrinthine segment to the stylomastoid foramen was performed, and the remaining 43 patients were only followed up. Using the Yanagihara score and House Brackmann grading system, the recovery from the palsy was assessed. RESULTS: There was a statistically significant difference in the final facial score of the 2 groups. Within 60 days after the onset, the chance of better recovery from the palsy was higher in the patients with decompression. CONCLUSION: In the era of steroid treatment, we cannot discard the transmastoid decompression of the facial nerve in the treatment of severe Bell palsy with profound denervation, although further effort is needed to obtain definitive evidence to show the benefit of the operation.
Auris Nasus Larynx | 2003
Jin Kanzaki; Yasuhiro Inoue; Kaoru Ogawa; Satoshi Fukuda; Kunihiro Fukushima; Kiyofumi Gyo; Naoaki Yanagihara; Tomoyuki Hoshino; Jun Ichi Ishitoya; Minoru Toriyama; Ken Kitamura; Kazuo Murai; Tsutomu Nakashima; Hideto Niwa; Yasuya Nomura; Hitome Kobayashi; Makoto Oda; Makito Okamoto; Tetuya Shitara; Masafumi Sakagami; Tetsuya Tono; Shin-ichi Usami
OBJECTIVES In order to evaluate the effect of a medical administration for the sudden deafness patients, single-drug treatment for idiopathic sudden sensorineural hearing loss (ISSHL) was assessed at multi-centers participating in the Acute Severe Hearing Loss Study Group sponsored by the Ministry of Health, Labor and Welfare of Japan. METHODS The subjects consisted of ISSHL patients who were (1) 20 years of age or older, (2) diagnosed within 2 weeks after the onset of hearing loss, (3) showing a mean hearing level of 40-90 dB at five frequencies from 250 to 4000 Hz, (4) previously untreated, and (5) with normal for age in hearing of the opposite ear. The drugs used in this study were ATP, alprostadil, hydrocortisone and amidotrizoate, which were administered intravenously, and beraprost sodium and betamethasone, which were given orally. Two drugs were assigned to each center, one of which was selected according to the code hidden in envelopes and administered for 1 week. The treatment after the single-drug administration was conducted at the discretion of each center. The hearing gain and recovery rate at 1 week after the initiation of single-drug treatment and at 1 month or over when the hearing level was fixed, were evaluated based on the criteria for hearing recovery prepared by the Acute Severe Hearing Loss Study Group. RESULTS There was no statistically significant difference in the recovery rate among drugs either at 1 week after the initiation of single-drug treatment or at the time of fixed hearing level. At the time when the hearing level was fixed, a statistically significant difference in the complete recovery rate was detected only between amidotrizoate and beraprost sodium. CONCLUSION From these results, we could not find any specific drugs recommended for ISSNHL. In evaluating the effect of the drugs, however, several problems in the clinical trial for ISSHL should be considered.
Otolaryngology-Head and Neck Surgery | 1984
Naoaki Yanagihara; Jun-Ichi Suzuki; Kiyofumi Gyo; Hisao Syono; Hironosuke Ikeda
A new, implantable hearing aid has been developed. An ultraminiature electret microphone placed under the skin of the external ear canal transduces sound waves into electrical impulses that are amplified with battery power. The amplified electrical impulses are fed into a piezoelectric vibrator directly in contact with the stapes. The vibrator transduces the electrical impulses into mechanical vibration with minimal consumption of electrical energy. Direct coupling of the vibrator to the stapes allows a high degree of fidelity in the perception of sound. The developmental process and the structure and function of each component are described together with clinical problems. Preliminary and tentative implantation of this new device during middle ear surgery indicated that it would be beneficial to patients who have suffered hearing loss from middle ear disease and whose condition does not lend itself to surgical correction.
Journal of Pediatric Ophthalmology & Strabismus | 1977
Katsuaki Kurihashi; Naoaki Yanagihara; Yoshihito Honda
Fine cotton thread is used instead of the filter paper of the Schirmer test. One end stained with fluorescein is inserted into the lateral upper conjunctival sac for 5-30 seconds. The length of the soaked portion is measured in millimeters and the two eyes are compared with each other. One test consists of several consecutive measurements. This new method has many advantages over the conventional Schirmer test: (1) It takes less time (5-30 seconds, compared to Schirmers method which takes five minutes); (2) It is less injurious to the eye than the stiff and rather large absorbing paper; (3) A diagnosis of lacrimal deficiency must be based on several consecutive measurements and the comparison between two eyes in each measurement (the lacrimation normally is very irregular in the same person). It is difficult to measure consecutively with filter paper; (4) The fine thread itself acts as a potent mechanical trigeminal stimulator and as absorbing agent; (5) The thread maintains a stable position in the eye, while the filter paper which hangs on the lower lid sometimes shifts out of place; (6) The fluorescein dye disappearance and dilution tests can be performed simultaneously; (7) This method can be applied to children.