The presence of herpes simplex-1 and varicella zoster viruses is not related with clinical outcome of Bell's Palsy.

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

Typical or Atypical Ramsay-Hunt Syndrome in Delayed Facial Palsy After Stapedectomy?

OBJECTIVES: The aim of this study was to define the typical pattern for varicella zoster virus (VZV) reactivation in delayed facial palsy (DFP) after stapedectomy for otosclerosis. MATERIALS AND METHODS: Review of the relevant literature, personal casistics, and case-report. RESULTS: In total, 48 cases of DFP after stapes surgery have been described so far, including the reported case with exclusive manifestation of atypical Ramsay Hunt syndrome (RH); in the personal series of 1253 stapedectomies, DFP occurred in only one case (0.08%). Complete DFP (House-Brackmann grade VI) rapidly developed 12 days after surgery; RH appeared 2 days later, confirming the role of VZV. The DFP started improving after 8 weeks and completely recovered 6 months later. CONCLUSION: Acute otalgia prior to DFP should raise the suspicion of VZV reactivation. Atypical RH is the most frequent pattern that occurs in DFP after stapedectomy.

Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection.

BACKGROUND: Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis. CASE DESCRIPTION: A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery. CONCLUSION: Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.

[Comparative study of several methods for producing experimental animal model of viral facial palsy].

OBJECTIVE: To select the optimal method for developing experimental animal model of viral facial paralysis by comparing several inoculation methods. METHOD: One hundred and twenty Balb/c mice were divided into 4 groups, with each group having 30 mice. Group A, the posterior auricular branch of right facial nerve were incised and inoculated with 25 microl HSV-1; group B, 25 microl HSV-1 were inoculated into the posterior aspect of the right auricle by cutaneous scarification; group C, 25 microl HSV-1 were injected into subcutaneous tissue of the posterior aspect of the right auricle; group D, 100 microl HSV-1 were inoculated in the way similar to that of group C. The symmetry of mouse face was observed, and the incidence of paralysis and death were analyzed. The temporal bones of paralyzed mice were serially sectioned and stained with hematoxylin and eosin. RESULT: Thirteen (43.33%) mice developed the right facial paralysis and recovered from it 3-7 days later in group A. Six (20%) mice developed the paralysis and recovered from it 2-9 days later in group B. Group C had no signs of facial paralysis and group D had 1 paralyzed animal. Except for 12 mice in group D, there was no death in the other groups. Nerve swelling was observed in right temporal facial nerve of paralyzed mice. Facial nerve to facial canal cross-sectional area ratio (FN/FC) of the right side was much higher than that of the left side. CONCLUSION: Inoculating HSV-1 into the posterior auricular branch of facial nerve can produce an acute and transient facial paralysis in mice. With the advantage of higher morbidity of facial paralysis and lower mortality in comparison to the other methods, it is an optimal method.

Delayed facial nerve palsy following tympano-mastoid surgery: incidence, aetiology and prognosis.

OBJECTIVE: To establish the frequency of occurrence of delayed facial nerve paralysis following tympano-mastoid surgery in our department and to determine the aetiological factors and long term prognosis. SETTING: Tertiary care academic centre. MATERIALS AND METHODS: A retrospective review of all patients who had undergone tympano-mastoid surgery in our department over the previous five years was carried out. A total of 219 patients were included in the study. Only two patients were identified as having delayed onset facial nerve palsy over this period of time. The patients' medical records were reviewed and the patients clinically assessed. RESULTS: The frequency of delayed onset facial nerve palsy following tympano-mastoid surgery in our series was 0.91 per cent. Facial weakness set in on day eight and day 14 in the two patients. Serological investigations in both patients revealed raised titres of immunoglobulin (Ig) M and IgG to varicella-zoster virus, confirming the presence of varicella-zoster infection. In our experience, the combined use of prednisone and acyclovir was an effective form of treatment for both patients, whose facial nerve function fully recovered within six months of onset. CONCLUSION: The incidence of delayed facial nerve palsy following tympano-mastoid surgery is low. It can occur up to two weeks after the surgery. Our two cases confirm viral reactivation to be an important aetiological factor in the development of delayed onset facial nerve palsy. The overall prognosis for delayed facial nerve palsy following tympano-mastoid surgery appears to be good.

[Animal model of facial neuritis induced by herpes simplex virus].

OBJECTIVE: To study the role of herpes simplex virus type 1 ( HSV-1 ) in facial paralysis by developing an experimental animal model of viral facial paralysis. METHODS: Both sides of posterior auricular branch of facial nerve were anatomies and incised in 66 mice. The HSV-1 was inoculated into right ear branch and fetal bovine serum was inoculated into left ear branch as control. The symmetry of mouse face was observed and scored. The temporal bones were serially sectioned and stained with hematoxylin and eosin. The extratemporal facial nerves were stained with osmium tetroxide. HSV-1 DNA in bilateral facial nerve, brain stem, trigeminal ganglion and spinal cord was detected by the polymerase chain reaction. RESULTS: Twenty-eight (42. 42%) mice developed right facial paralysis between 2 and 5 days after inoculation. Continuing 3-6 days, the facial paralysis recovered spontaneously. Thirty-eight mice had no signs of facial paralysis. Compared with the left, nerve swelling, inflammatory cell infiltration were manifested in right temporal facial nerve of paralyzed mice. The ratio of the cross-sectional area of the facial nerve to the facial canal ( FN/FC ) was significantly higher than that on the control side (P < 0.01). Demyelinated nerve fibers were seen in the right extratemporal facial nerve. Not only in paralyzed mice, but also in non-paralyzed mice, HSV DNA was detected in some nerve tissues. CONCLUSIONS: Inoculating HSV-1 into posterior auricular branch of facial nerve can produce an acute and transient facial paralysis in mice. The possible pathophysiologic mechanism of the facial paralysis is viral invasion and transportation from distal branch to main trunk. Then the viral facial neuritis causes facial paralysis.

Bell's palsy and Herpes simplex virus: fact or mystery?

HYPOTHESIS AND BACKGROUND: In recent years, progress has been made in the understanding of Bell's palsy, the most common form of acute facial weakness. Herpes simplex virus (HSV) reactivation within the geniculate ganglion with subsequent inflammation and entrapment of the nerve at the meatal foramen has been proposed to be the pathogenetic mechanism. We challenged its accuracy by analyzing our own data on the presence of viral genomic DNA of HSV-1 and 2, human herpes virus (HHV)-6A/B, as well as varizella zoster virus (VZV) in patients with Bell's palsy and in control patients without the disease. METHODS: Polymerase chain reaction was performed with primer sets specific for viral genomic DNA of HSV-1, HSV-2, and VZV in facial muscle biopsy specimens from patients with Bell's palsy. As control specimens, the Scarpa's ganglion of patients with Meniere's disease and the geniculate ganglion harvested at autopsy from patients without history of facial palsy. In a second study, we used polymerase chain reaction with primers specific for HSV-1, -2, and HHV-6A, -6B to analyze for the presence of these viruses in tear fluid samples from control patients and patients with acute Bell's palsy. RESULTS: HSV-1 and VZV genomic DNA were detected in 86 and 43%, respectively, of geniculate ganglion preparations from control specimen. We were not able to detect the presence of HSV-1, HSV-2, or VZV genomic DNA in ganglion scarpae or muscle biopsy results in control and Bell's palsy patients. HHV-6A could be detected in tear fluid samples in 40% of control patients and 30% of Bell's palsy patients. CONCLUSIONS: The sole presence of HSV genomic DNA within the sensory ganglion along the facial nerve does not explain the direct association with Bell's palsy. The missing link would be the identification of an active replicating virus, an investigation that has not yet been carried out.

Ultrastructure of cranial nervs of rats inoculated with rabies virus

The V and VII cranial nerves of rats inoculated with rabies virus were studied by electron microscopy. The results were compared with the same cranial nerves of rats inoculated with rabies virus but vaccinated against the disease. The findings are those of axonal degeneration and intense demyelination of the nerves of the group of rats not vaccinated. The vaccinated rats showed some ultrastructural irrelevant alterations when compared with the other group. The degreee of ultrastructural alterations found in the group of rats not vaccinated suggests that in rabies severe damage of the cranial nerves occurs and that this may be closely related to the clinical picture of the disease (hydrophobia). Furthermore, as far as the authors know, this has not been considered in the classic descriptions of rabies and it is possible that an immunologic process may take part in the demyelination observed in the present study.

Adenoviral vector-mediated gene expression in the nervous system of immunocompetent Wistar and T cell-deficient nude rats: preferential survival of transduced astroglial cells in nude rats.

In the present paper, we examined the effect of the adenoviral vector dosage, the role of T cells, and the influence of the presence of replication-competent adenovirus (RCA) in adenoviral vector stocks, on the efficacy of adenoviral vector-directed transgene expression in the facial nucleus of immunocompetent Wistar and athymic nude rats. A small number of motor neurons and glial cells was transduced at low dosages of viral vector (1 x 10(6) pfu) and in the absence of RCA, and transgene-expressing cells persisted throughout the 3-week period of observation. Intraparenchymal infusion of 2 x 10(7) pfu of a recombinant adenoviral vector free of RCA was required for optimal transduction of facial motor neurons. In Wistar rats, a biphasic immune response occurred at higher dosages of the vector (5 x 10(6) and 2 x 10(7) pfu) that was characterized by early infiltration of macrophages and the occurrence of T cells during the second week after injection of the vector. The immune response was associated with the loss of transduced neural cells. In nude rats, administration of an adenoviral vector free of RCA resulted in a macrophage response comparable to that in the Wistar rat and long-term survival of transduced astroglial cells. However, transduced motor neurons degenerated according to a similar time course as observed in Wistar rats. Small amounts of RCA (2 x 10(5) pfu) injected with 2 x 10(7) pfu recombinant viral vector particles resulted in an accelerated T cell response and a rapid elimination of transduced cells within 1 week in Wistar rats, whereas in nude rats transgene expression continued during this period. Taken together, these observations suggest that at the high viral vector loads necessary to achieve optimal transduction of the facial nucleus, T cells play a role in the degeneration of adenoviral vector-transduced astroglial cells. The adverse effects on neurons appear to be due to the observed inflammatory response or to direct adenoviral vector toxicity.

Adenovirus-mediated gene transfer in neurons: construction and characterization of a vector for heterologous expression of the axonal cell adhesion molecule axonin-1.

By homologous recombination, a first-generation adenovirus-based gene transfer vector, AdCMVax-1, was constructed as a means of manipulating the expression level of the axonal cell adhesion molecule axonin-1 in neurons and glial cells. AdCMVax-1 harbours the entire coding region of the chicken axonin-1 cDNA under the transcriptional control of the Cytomegalovirus enhancer/promoter in the early-region 1 of the viral genome. Characterization of AdCMVax-1 in vitro revealed highly efficient gene transfer and expression of recombinant axonin-1 in neurons and glial cells of dissociated rat dorsal root ganglia. Similar to its native counterpart, virus-derived axonin-1 was detected on the cell body, neurites, and growth cones of transduced neurons, occurred in a secreted and membrane-associated form, and could be cleaved from the membrane with phosphatidylinositol-specific phospholipase C. Functional characterization of recombinant axonin-1 revealed the same binding properties as previously reported for native axonin-1 isolated from the vitreous fluid of chicken embryos. In vivo gene transfer was studied by stereotactic injection of AdCMVax-1 in the dentate gyrus of the hippocampus and the facial nucleus in the brainstem of adult Wistar rats and revealed high level expression of recombinant axonin-1 in a subset of hippocampal neurons and motor neurons in the facial nucleus.