Yasushi Furuta

Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.

Objective: To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bells palsy, excluding zoster sine herpete. Study Design: Prospective, multicenter, randomized placebo-controlled study. Setting: Six academic tertiary referral centers. Patients: Ultimately, 221 patients with Bells palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bells palsy from zoster sine herpete. Intervention: The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally. Main Outcome Measure: Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis. Results: The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p < 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p < 0.05). Conclusion: The valacyclovir and prednisolone therapy was more effective in treating Bells palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bells palsy cases based on an etiologic background.

Reactivation of herpes simplex virus type 1 in patients with Bell's palsy

Reactivation of herpes simplex virus type 1 (HSV‐1) has been implicated in the pathogenesis of idiopathic peripheral facial palsy (Bells palsy). The present study used the polymerase chain reaction (PCR) to analyze the saliva of patients with Bells palsy for the presence of shed HSV‐1. The study involved 47 patients with Bells palsy, 24 patients with Ramsay Hunt syndrome, and 16 healthy HSV‐seropositive volunteers. HSV‐1 DNA was not detected in the saliva samples from HSV‐seronegative patients. The prevalence of shed HSV‐1 in patients with Bells palsy (50%) was significantly higher than that in healthy volunteers (19%, p<0.05). When saliva samples were tested within 7 days after the onset of palsy, the prevalence of shed HSV‐1 in patients with Bells palsy (40%) was significantly higher than that in patients with Ramsay Hunt syndrome (7%, p<0.05). Furthermore, HSV‐1 usually became undetectable by the second week after the onset of Bells palsy when HSV‐1 was detected during the acute phase of the disease. These findings strongly suggest that reactivation of HSV‐1 is involved in the pathogenesis Bells palsy, and indicate that PCR is a useful tool for early diagnosis of HSV‐1 reactivation in patients with Bells palsy. J. Med. Virol. 54:162–166, 1998.

Otologic Manifestations of Wegener's Granulomatosis

Objective/Hypothesis To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegeners granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan.

High Prevalence of Varicella-Zoster Virus Reactivation in Herpes Simplex Virus-Seronegative Patients with Acute Peripheral Facial Palsy

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are considered to be the major causes of acute peripheral facial palsy (APFP). One hundred and forty-two patients with APFP were analyzed by serological assays and polymerase chain reaction analysis. Ramsay Hunt syndrome was diagnosed in 21 patients. Of the remaining 121 patients clinically diagnosed with Bells palsy, VZV reactivation without zoster (zoster sine herpete) was detected in 35 patients (29%). The prevalence of antibodies to HSV among patients with Bells palsy was significantly higher than the prevalence among those with VZV reactivation (Ramsay Hunt syndrome or zoster sine herpete). In contrast, a high incidence (88%) of VZV reactivation among HSV-seronegative patients with APFP was observed. Our data indicate that VZV is one of the major etiologic agents of clinically diagnosed Bells palsy and that VZV reactivation causes APFP in most patients who lack antibodies to HSV.

Varicella-zoster virus reactivation is an important cause of acute peripheral facial paralysis in children.

Background: Reactivation of herpes simplex virus type 1 is thought to be a major cause of adult idiopathic peripheral facial paralysis or Bells palsy. However, few studies have examined the pathogenesis of this condition in children. Serologic assays and polymerase chain reaction (PCR) analysis of paired sera and saliva samples were used here to investigate the causes of acute peripheral facial paralysis in pediatric patients. Methods: A total of 30 children with acute peripheral facial paralysis were recruited. Paired sera were assayed for evidence of herpesvirus, mumps virus or Borrelia infection. PCR was used to detect herpes simplex virus type 1 and varicella-zoster virus (VZV) DNA in saliva samples. Results: Ramsay Hunt syndrome with accompanying zoster lesions was diagnosed clinically in 2 patients, and VZV reactivation was confirmed serologically. VZV reactivation in the absence of zoster (zoster sine herpete) was diagnosed in 9 patients with either serologic assays or PCR. Thus VZV reactivation was demonstrated in 11 of 30 (37%) patients. The prevalence of VZV reactivation among patients between 6 and 15 years of age was significantly higher than in those younger than 5 years of age (53% versus 9%, P = 0.023). Conclusions: Our data indicate that VZV reactivation is an important cause of acute peripheral facial paralysis in children, especially those between 6 and 15 years of age.

Detection of Latent Herpes Simplex Virus DNA and RNA in Human Geniculate Ganglia by the Polymerase Chain Reaction

By using the polymerase chain reaction (PCR) we detected latent herpes simplex virus type 1 (HSV-1) in human geniculate and trigeminal ganglia obtained from autopsy cases. A pair of primers which were specific for a part of the HSV-1 thymidine kinase domain were used for detection of HSV DNA. We also examined the latency-associated transcript (LAT), known as latency-specific RNA, by means of reverse transcription-PCR with a pair of LAT-specific primers. HSV-1 DNA was detected in 16 of 17 (94%) trigeminal ganglia and in 15 to 17 (88%) geniculate ganglia of adults. We also demonstrated HSV-1 RNA derived from the LAT in both types of ganglia. These findings suggest that HSV-1 latently infects the majority of geniculate and trigeminal ganglia of adults, and that PCR and reverse transcription-PCR are useful tools for analysis of HSV latency.

Latent herpes simplex virus type 1 in human geniculate ganglia

SummaryViral infection, especially by reactivation of herpes simplex virus (HSV) has been considered to be a possible explanation for the pathogenesis of idiopathic peripheral facial nerve palsy (Bells palsy). We investigated whether the geniculate ganglia of man contain latent HSV type 1 (HSV-1), and compared the frequency of HSV-infected ganglia and that of latently infected neurons in human geniculate ganglia and in trigeminal ganglia. From autopsy specimens of eight adults 15 geniculate ganglia and 16 trigeminal ganglia were examined by means of in situ hybridization and immunohistochemical staining. The HSV-1 genome was detected in 11 of the 15 (71%) geniculate ganglia and in 13 of the 16 (81%) trigeminal ganglia. No HSV antigen was noted in any of the ganglia. The incidence of latently infected neurons was 0.9% in the trigeminal ganglia and 5.3% in the geniculate ganglia. The difference in percentages between the two types of ganglia was significant. Our results suggest that reactivation of latent HSV in the geniculate ganglia is a probable cause of some cases of herpetic stomatitis and of idiopathic peripheral facial nerve palsy.

Early diagnosis of zoster sine herpete and antiviral therapy for the treatment of facial palsy

Article abstract The effect of antiviral agents on recovery from facial palsy in patients with zoster sine herpete (ZSH; varicella zoster virus reactivation without zoster) has not been evaluated because ZSH is difficult to diagnose early after onset. In this study, all 13 patients who received acyclovir-prednisone treatment within 7 days of onset, as confirmed by a positive PCR result, showed complete recovery. PCR-based early diagnosis of ZSH and antiviral therapy elicited an excellent outcome for recovery from facial palsy due to ZSH.

Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction, and its use for early diagnosis of zoster sine herpete

Varicella‐zoster virus (VZV) reactivation without cutaneous vesicles (zoster sine herpete) has been demonstrated in 8 to 25% of patients with acute peripheral facial palsy (APFP) by serological methods. To make an early diagnosis of zoster sine herpete, VZV DNA in oropharyngeal swabs from patients with APFP was examined by the polymerase chain reaction (PCR). VZV DNA was detected in oropharyngeal swabs from 6 of 36 (17%) patients with APFP by PCR. VZV DNA was detected in the oropharyngeal swabs from the six patients at their initial visit (2 to 4 days after the onset of APFP), while the anti‐VZV IgM and IgG antibody titers were not increased significantly. In contrast, VZV DNA was undetectable in the oropharyngeal swabs at the time when the VZV specific antibody response appeared. These results indicate that detection of VZV DNA in oropharyngeal swabs by PCR is more useful than currently available serological assays for the early diagnosis of zoster sine herpete in patients with APFP. J. Med. Virol. 52:316–319, 1997.

Latent Herpes Simplex Virus Type 1 in Human Vestibular Ganglia

Viral infection has been considered to be a possible pathogenesis of vestibular neuronitis, and reactivation of the herpes simplex virus (HSV) is one of the most likely causes. However, it remains unknown whether the human vestibular ganglia contain latent HSV. We examined 26 vestibular ganglia from autopsied adults in search of HSV type 1 (HSV-1). To detect HSV-1, we used polymerase chain reaction (PCR), in situ hybridization and immunohistochemical staining. HSV DNA was detected in 6 of 10 vestibular ganglia using the PCR method. However, the latency-associated transcript (LAT) of HSV-1 was negative in all of the 16 vestibular ganglia examined. No HSV antigen was detected in any of the ganglia. These results indicate that HSV-1 is latently infected in the human vestibular ganglia, and that LAT is transcribed weakly or not at all.