The background occurrence of selected clinical conditions prior to the start of an extensive national vaccination program in Japan.

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has now affected tens of millions of people globally. It is the hope that vaccines against SARS-CoV-2 will deliver a comprehensive solution to this global pandemic; however, this will require extensive national vaccination programs. Ultimately, clinical conditions and even sudden unexplained death will occur around the time of vaccination, thus a distinction needs to be made between events that are causally related to the vaccine or temporally related to vaccination. This study aimed to estimate the background occurrence of 43 clinical conditions in the Japanese population. METHODS: A retrospective cohort study was conducted from 2013 to 2019 using data from two large healthcare claims databases (MDV and JMDC) in Japan. The estimated number of new cases and incidence were calculated based on the actual number of new cases identified in the databases. The PubMed and Ichushi-web databases, as well as grey literature such as guidelines and government statistics, were also searched to identify any publications related to incidence of these conditions in Japan. RESULTS AND CONCLUSION: The estimates of the number of total cases and incidence were similar for the MDV and JMDC databases for some diseases. In addition, some estimates were similar to those in the scientific literature. For example, from the MDV and JMDC databases, estimates of incidence of confirmed Bell's palsy in 2019 were 41.7 and 47.9 cases per 100,000 population per year, respectively. These estimates were of the same order from the scientific publication. Determining whether clinical conditions occurring around the time of vaccination are causally or only temporally related to vaccination will be critical for public health decision makers as well as for the general public. Comparison of background occurrence at the population level may provide some additional objective evidence for the evaluation of temporality or causality.

Electrical stimulation-based nerve location prediction for cranial nerve VII localization in acoustic neuroma surgery.

INTRODUCTION: Cranial nerve (CN) VII localization is a critical step during acoustic neuroma surgery because the nerve is generally hidden due to the tumor mass. The patient can suffer from Bell's palsy if the nerve is accidentally damaged during tumor removal. Surgeons localize CN VII by exploring the target area with a stimulus probe. Compound muscle action potentials (CMAPs) are elicited when the probe locates the nerve. However, false positives and false negatives are possible due to unpredictable tissue impedance in the operative area. Moreover, a single CMAP amplitude is not correlated with probe-to-nerve distance. OBJECTIVES: This paper presents a new modality for nerve localization. The probe-to-nerve distance is predicted by the proposed nerve location prediction model. METHODS: Input features are extracted from CMAP responses, tissue impedance, and stimulus current. The tissue impedance is calculated from the estimated resistance and capacitance of the tissue equivalent circuit. In this study, experiments were conducted in animals. A frog's sciatic nerve and gastrocnemius were used to represent CN VII and facial muscle in humans, respectively. Gelatin (2.8%) was used as a mock material to mimic an acoustic neuroma. The %NaCl applied to the mock material was used to emulate uncontrollable impedance of tissue in the operative area. RESULTS: The 10-fold cross-validation results revealed an average prediction accuracy of 86.71% and an average predicted error of 0.76 mm compared with the measurement data. CONCLUSION: The proposed nerve location prediction model could predict the probe-to-nerve distance across various impedances of the mock material.

The effect of total facial nerve decompression in preventing further recurrence of idiopathic recurrent facial palsy.

The objective is to study the role of total facial nerve decompression in preventing further episodes and promoting facial nerve recovery of idiopathic recurrent facial palsy. 24 cases with idiopathic recurrent facial palsy were involved in the study, among which 16 undergoing total facial nerve decompression were classified into the surgery group, and 8 who refused surgery and received prednisolone were included in the control group. The recurrence rate and facial nerve function recovery of the two groups were compared. The mean follow-up of surgery and control group was 4.9 years (range 3-7 years) and 5.0 years (range 3-8 years), respectively. Further attacks of facial palsy affected 1 of 16 cases (6.2 %) among surgery group in comparison to 4 of 8 cases (50 %) among control group, with statistical difference (p < 0.05). 15 of 16 cases (93.8 %) recovered to Grade I or Grade II in surgery group in contrast to 6 of 8 cases (75.0 %) in control group, without statistical difference (p > 0.05). In conclusion, total facial nerve decompression is effective to prevent further episodes of facial palsy in idiopathic recurrent facial palsy, but ineffective to promote facial nerve recovery.

Role of nitric oxide in the onset of facial nerve palsy by HSV-1 infection.

IMPORTANCE: Although herpes simplex virus type 1 (HSV-1) is a causative agent of Bell palsy, the precise mechanism of the paralysis remains unknown. It is necessary to investigate the pathogenesis and treatment of Bell palsy due to HSV-1 infection. OBJECTIVE: This study elucidated the role of nitric oxide (NO) in the incidence of facial nerve paralysis caused by HSV-1 in mice and to evaluate the possible role of edaravone, a free radical scavenger, in preventing the paralysis. DESIGN, SETTING, PARTICIPANTS: Sixty-two mice served as animal models of Bell palsy in this laboratory study conducted at an academic institution. INTERVENTIONS: Levels of NO in the facial nerve were measured using high-performance liquid chromatography and absorption photometry. The incidence of facial palsy was assessed following administration of edaravone immediately after HSV-1 inoculation and daily for 11 days thereafter. MAIN OUTCOMES AND MEASURES: The ratio of NO (inoculated side to control side) and incidence of facial palsy. RESULTS Before the onset of facial palsy, no substantial difference in the NO level was noted between the HSV-1-inoculated side and the control side. When facial palsy occurred, usually at 7 days after inoculation, the NO level was significantly higher on the inoculated side than on the control side. Following recovery from the palsy, the high NO level of the inoculated side decreased. No increase in the NO level was observed in animals without transient facial palsy. When edaravone was administered, the incidence of facial palsy decreased significantly. CONCLUSIONS AND RELEVANCE: These findings suggest that NO produced by inducible NO synthase in the facial nerve plays an important role in the onset of facial palsy caused by HSV-1 infection, which is considered a causative virus of Bell palsy. Hato and colleagues elucidate the role of nitric oxide in HSV-1­related facial nerve paralysis in mice and evaluate the role of edaravone, a free radical scavenger, in preventing the paralysis.

A cell culture model of facial palsy resulting from reactivation of latent herpes simplex type 1.

HYPOTHESIS: Reactivation of herpes simplex virus type 1 (HSV-1) in geniculate ganglion neurons (GGNs) is an etiologic mechanism of Bell's palsy (BP) and delayed facial palsy (DFP) after otologic surgery. BACKGROUND: Several clinical studies, including temporal bone studies, antibody, titers, and intraoperative studies, suggest that reactivation of HSV-1 from latently infected GGNs may lead to both BP and DFP. However, it is difficult to study these processes in humans or live animals. METHODS: Primary cultures of GGNs were latently infected with Patton strain HSV-1 expressing a green fluorescent protein-late lytic gene chimera. Four days later, these cultures were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1 in other neurons. Cultures were monitored daily by fluorescent microscopy. Titers of media from lytic, latent, and latent/TSA treated GGN cultures were obtained using plaque assays on Vero cells. RNA was harvested from latently infected GGN cultures and examined for the presence of viral transcripts using reverse transcription-polymerase chain reaction. RESULTS: Latently infected GGN cultures displayed latency-associated transcripts only, whereas lytically infected and reactivated latent cultures produced other viral transcripts, as well. The GGN cultures displayed a reactivation rate of 65% after treatment with TSA. Media from latently infected cultures contained no detectable infectious HSV-1, whereas infectious virus was observed in both lytically and latently infected/TSA-treated culture media. CONCLUSION: We have shown that cultured GGNs can be latently infected with HSV-1, and HSV-1 in these latently infected neurons can be reactivated using TSA, yielding infectious virus. These results have implications for the cause of both BP and DFP.