Hisanobu Kisaki

Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone

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.

Ramsay Hunt syndrome in children

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

Pathophysiology of Facial Nerve Paralysis Induced by Herpes Simplex Virus Type 1 Infection

Herpes simplex virus type 1 (HSV-1) has been proven to be a cause of Bells palsy; however, the underlying pathophysiology of the facial nerve paralysis is not fully understood. We established a mouse model with facial nerve paralysis induced by HSV-1 infection simulating Bells palsy and investigated the pathophysiology of the facial nerve paralysis. The time course of the R1 latency in the blink reflex tests paralleled the recovery of the facial nerve paralysis well, whereas electroneurographic recovery tended to be delayed, compared to that of the paralysis; these responses are usually seen in Bells palsy. On histopathologic analysis, intact, demyelinated, and degenerated nerves were intermingled in the facial nerve in the model. The similarity of the time course of facial nerve paralysis and the electrophysiological results in Bells palsy and the model strongly suggest that the pathophysiological basis of Bells palsy is a mixed lesion of various nerve injuries.

Demyelination Associated with HSV-1-Induced Facial Paralysis

In 1995, we developed an animal model of transient homolateral facial nerve paralysis by inoculating Herpes simplex virus type 1 (HSV-1) into the auricle of mice. This study examined the mechanism of facial nerve paralysis in this model histopathologically. Using the immunofluorescence technique with anti-HSV-1 antibody, the time course of viral spread and the site of viral replication were investigated over the entire course of the facial nerve. Furthermore, viral replication and nerve degeneration at the site of viral replication were observed by electron microscopy. On the 7th day after inoculation, facial paralysis was observed in more than 60% of mice. Immunofluorescence study revealed HSV-1 in the geniculate ganglion, the descending root, and the facial nucleus at this stage. On the 9th day, the descending root in the sections stained with osmium looked pale, because prominent demyelination had occurred in this region; electron micrographs showed many degenerated oligodendrocytes and large naked axons. In contrast, the facial nucleus neurons showed no remarkable degeneration, despite HSV-1 particles in their cytoplasm. From these findings, we concluded that facial nerve paralysis in this model is caused mainly by facial nerve demyelination in the descending root.

Effects of acyclovir on facial nerve paralysis induced by herpes simplex virus type 1 in mice

OBJECTIVES Bells palsy has recently been claimed to be caused by herpes simplex virus type 1 (HSV-1) infection. The anti-viral agent acyclovir is a specific inhibitor of herpesvirus replication, and the most effective agent for the treatment herpesvirus infection. The purpose of this experiment was to assess the effect of acyclovir on the facial nerve paralysis included by HSV-1 infection. METHODS We succeeded in producing an animal model of acute and transient facial nerve paralysis induced with HSV-1 neuritis simulating human Bells palsy. In this study, acyclovir administration was performed before and after facial nerve paralysis, and continued for 5 days. Controls were given phosphate-buffer saline (PBS) instead of acyclovir, and the incidence and duration of facial nerve paralysis was compared in the acyclovir groups and controls. RESULTS The incidence of facial nerve paralysis was significantly lower in the group given acyclovir before the paralysis than in the controls, and the duration of facial nerve paralysis was shorter. CONCLUSIONS Administration of acyclovir before the paralysis reduced the incidence and duration of facial nerve paralysis. Administration of acyclovir after the paralysis improved the duration of facial nerve paralysis.

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1

Conclusion. Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4+ T cells play a more important role in host defense against virus replication. Objective. To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. Material and methods. Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n=69) were given an i.p. injection of either anti-CD4 (n=46) or anti-CD8 (n=23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. Results. Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.

CLINICAL ASPECT OF VIRAL ETIOLOGY OF BELL'S PALSY

within the ganglion cells; latent HSV-1 has been detected in geniculate ganglia at autopsy of unselected cadavers; PCR studies of the endoneurial fluid of the facial nerve and of the posterior auricle muscle have shown the presence of HSV-1 DNA only in Bell’s Palsy patients as well as viral genomes of Varicella-Zoster Virus (VZV) being found only in patients with Ramsay-Hunt’s Syndrome; patients treated with early association of steroids and acyclovir presented better results than those only treated with steroids. After a primary infection, the virus subsides to latency in cranial and spinal ganglia. When a transient immune depression condition is produced, the virus is reactivated and replicates within the ganglion cells, where is protected from any response from the immune system and produces a local damage to the ganglia. The clinical result of this ganglionitis is hyposthesia of the face, pharynx, and head and neck. Afterwards, the virus passes down and up to the axons inducing radiculitis and local meningoencephalitis, evidenced by increased protein and lymphocytic pleocytosis in the CSF, also T-2 gadolinium-enhanced MRI indicates inflammation of the brain stem and the intratemporal course of the facial nerve. At this point, the virus infects Schwann cells where it produces some changes on the antigens of the Schwann cell membrane, inducing an inflammatory response from the immune system: antibody and lymphocytic infiltration, which leads to fragmentation of myelin and causes chromatolisis of facial nucleus nerve cells. This impairs the nerve cells but leaves them potentially retrievable, provided the distal disease process resolves. The result is a segmental and horizontal demyelination, with a random affectation of motor sensory and secretory fibers, clinically presented as nerve paralysis. Once the viral reactivation is controlled by the immune system, remyelination ensues and functional innervation is re-established. The degree and rate of recovery depends directly on the degree and rate of damage.

A Seriological Study of HIV, HTLV-1, and HSV-1 in Bellʼs Palsy

group was compared. Furthermore, utilizing RT-PCR technique, we analyzed the expression of latency associated transcripts (LAT) in the geniculate ganglion which is a marker of latent infection of HSV1. The mice treated with an auricular scratch and an anti-CD4 mAb injection were subjected to the latter experiment because of high incidence of the paralysis. Statistical comparison of incidence of facial paralysis was performed with Fisher’s exact probability test.