Reactivation of type 1 herpes simplex virus and varicella zoster virus in an immunosuppressed patient with acute peripheral facial weakness

We describe a 26-year-old man treated with azathioprine for myasthenia gravis who developed acute left-sided peripheral facial weakness. Brain magnetic resonance imaging (MRI) revealed enhancement in the left geniculate ganglion and in the intracanalicular and tympanic segments of the facial nerve. Analysis of cerebrospinal fluid (CSF) and serum revealed intrathecal synthesis of anti-varicella zoster virus (VZV) IgG antibody. Although previous analyses of saliva, blood mononuclear cells, serum antibodies, middle ear fluid, and auricular and geniculate zone skin scrapings have shown that a small but definite proportion of patients with idiopathic peripheral facial palsy ("Bell's palsy") have the Ramsay Hunt syndrome zoster sine herpete (RHS ZSH), this is the first confirmation of RHS ZSH by intrathecal synthesis of anti-VZV IgG antibody. In addition, herpes simplex virus (HSV)-1 DNA was found in saliva of the patient on 3 consecutive days. Simultaneous reactivation of two alphaherpesviruses (HSV-1 and VZV) in our immunosuppressed patient underscores the need to consider opportunistic infection as a cause of facial weakness.     

Ramsay Hunt syndrome

The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth. J Ramsay Hunt, who described various clinical presentations of facial paralysis and rash, also recognised other frequent symptoms and signs such as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained these eighth nerve features by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of clinical variations of the syndrome now bearing his name led to his recognition of the general somatic sensory function of the facial nerve and his defining of the geniculate zone of the ear. It is now known that varicella zoster virus (VZV) causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken. In the only prospective study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy. Further, Bell's palsy is significantly associated with herpes simplex virus (HSV) infection. In the light of the known safety and effectiveness of antiviral drugs against VZV or HSV, consideration should be given to early treatment of all patients with Ramsay Hunt syndrome or Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for 3-5 days). Finally, some patients develop peripheral facial paralysis without ear or mouth rash, associated with either a fourfold rise in antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy.     

Successful response of non-recovering Ramsay Hunt syndrome to intravenous high dose methylprednisolone

Ramsay Hunt syndrome (RHS) is a frequent cause of facial palsy. It is a consequence of the infection of geniculate ganglion by herpes zoster or herpes simplex virus. In the lack of randomized controlled trials, RHS is empirically treated by a combination therapy of antiviral agents and steroids given orally. However, RHS has, per se, a poorer prognosis than idiopathic facial palsy (Bell's palsy). We describe a case series of two patients with RHS unsuccessfully treated with antiviral drugs and oral corticosteroids, showing an almost complete recovery after late administration of intravenous (i.v.) high dose methylprednisolone. Both patients had all recognized negative prognostic factors including age of onset, a high grade facial weakness, absence of R1 and R2 response at blink reflex test, and in the first case, the involvement of greater superficial petrosal nerve. We propose that i.v. high dose methylprednisolone should be considered, even as a late treatment option, in patients with RHS non recovering after standard antiviral and oral steroid therapy as well as presenting clinical features suggestive of a poor prognosis.     

EMG prognosis of facial palsy associated with herpes zoster oticus (Ramsay-Hunt's syndrome). A longitudinal study of 11 cases (author's transl

Eleven patients with peripheral facial palsy associated with geniculate herpes zoster (Ramsay-Hunt's syndrome) have been followed-up clinically and electromyographically. Each patient was examined three times: within the first week, at the end of the third week and 3-4 months after the onset of symptoms. Only in three cases the facial palsy evolved satisfactorily, with an almost total recovery within three weeks. In eight cases the recovery was delayed and incomplete, with residual, and often severe, hemifacial spasm. This study confirms the rather poor prognosis of peripheral facial palsy in Ramsay-Hunt's syndrome. The importance of detecting even slight signs of herpetic eruption in any case of apparently "idiopathic" peripheral facial palsy is emphasized.     

Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome

Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS‐ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S‐100β protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S‐100β protein and GFAp in CSF from patients with RHS (n = 15) and RHS‐ZSH (n = 13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n = 52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House‐Brackmann score. NFL and GFAp concentrations were increased compared with controls (P = 0.008 and P = 0.04), while S‐100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS‐ZSH (NS and P = 0.028). The amount of viral DNA in CSF correlated with increased GFAp (P = 0.003) and NFL (P = 0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.     

Treatment of ramsay hunt syndrome with acyclovir-prednisone: Significance of early diagnosis and treatment

Although the antiviral agent acyclovir is currently used for the treatment of Ramsay Hunt syndrome, its effects on facial nerve and hearing recovery remain controversial. We retrospectively analyzed the effects of acyclovir-prednisone treatment in 80 Ramsay Hunt patients. Of 28 patients for whom treatment was begun within 3 days of the onset of facial paralysis, the recovery from paralysis was complete in 21 (75%). By comparison, of 23 patients for whom treatment was begun more than 7 days after onset, recovery from facial paralysis was complete in only 7 (30%). A significant difference in facial nerve recovery was found between these groups. Early administration of acyclovir-prednisone was proved to reduce nerve degeneration by nerve excitability testing. Hearing recovery also tended to be better in patients with early treatment. There was no significant difference in facial nerve outcome between intravenous and oral acyclovir treatment.     

Abstracts

Bell’s palsy causes about two thirds of cases of acute peripheral facial weakness. Although the majority of cases completely recover spontaneously, about 30% of cases do not and are at risk from persisting severe facial paralysis and pain. It has been suggested that herpes simplex virus type 1 (HSV-1) may be the etiological agent that causes Bell’s palsy. Although corticosteroid therapy is now universally recognized as improving the outcome of Bell’s palsy, the question as to whether or not a combination of antiviral agents and corticosteroids result in a better rate of complete facial recovery compared with corticosteroids alone is now a highly contentious issue. The evidence obtained from laboratory studies of animals and humans that HSV-1 may be linked to facial nerve paralysis is first outlined. The discussion then focuses on the results of different clinical trials of the efficacy of antiviral agents combined with corticosteroids in increasing the rate of complete recovery in Bell’s palsy. These have often given different results leading to opposite conclusions as to the efficacy of antivirals. Of three recent meta-analyses of previous trials, two concluded that antivirals produce no added benefit to corticosteroids alone in producing complete facial recovery, and one concluded that such combined therapy may be associated with additional benefit. Although it is probably not justified at the present time to treat patients with Bell’s palsy with antiviral agents in addition to corticosteroids, it remains to be shown whether antivirals may be beneficial in treating patients who present with severe or complete facial paralysis.     

Bell's palsy in children: analysis of clinical findings and course

To evaluate treatment of Bell's palsy (acute idiopathic peripheral facial nerve paralysis) of children, the authors analyzed 38 cases (18 females, 20 males) of Bell's palsy in children aged below 16 years old. The mean age of all cases was 6.8 +/- 6.2 years old. All cases resulted in complete recovery within 6 months. Clinical score of facial motor functions were adapted to 17 patients who were more than 5 years old. They were divided into two groups: early recovery group (clinical symptoms recovered within 3 months; 10 cases) and later recover group (over 3 months; 7 cases). Clinical scores evaluated in the first week from the onset were not significantly different. Steroid therapy was used for 9 patients of early group and 6 patient of later group. All patients of this study were recovered, thus we could not evaluate effect of steroid therapy for Bell's palsy in children. Use of steroid therapy for Bell's palsy needs more concretely administration. We consider how the region locates near to the center is an important prognostic factor.     

Ramsay Hunt syndrome with multiple cranial neuropathies in a liver transplant recipient

Ramsay Hunt syndrome is an infection of the head and neck caused by varicella zoster virus involving the facial nerve; less commonly, other cranial nerves might be involved. We report a case of Ramsay Hunt syndrome in an immune compromised patient, with classic facial nerve palsy and ipsilateral ear vesicles, which rapidly evolved to involve multiple cranial neuropathies, and improved dramatically with antiviral therapy and corticosteroids. Varicella zoster virus should be considered as a cause of multiple cranial neuropathies in an immune compromised patient, and abrupt treatment with acyclovir should be initiated once this diagnosis is suspected.     

Acyclovir responsive brain stem disease after the Ramsay Hunt syndrome

We report an immunocompetent patient with the Ramsay Hunt syndrome (RHS) followed days later by brainstem disease. Extensive virological studies proved that varicella zoster virus (VZV) was the causative agent. Treatment with intravenous acyclovir resulted in prompt resolution of all neurological deficits except peripheral facial palsy. This case demonstrates that after geniculate zoster, brainstem disease may develop even in an immunocompetent individual and effective antiviral therapy can be curative.     

A case of multiple cranial nerve palsy with severe dysphagia due to herpes zoster infection]

A case of multiple cranial nerve palsy by herpes zoster was reported. A 79-year-old man showed fever, sore throat, and dysphagia. No vesicle was noted at ear and pharynx. The patient developed, later, left peripheral facial nerve palsy. The cerebrospinal fluid revealed pleocytosis with increased protein. The viral antibody titer of herpes zoster was significantly elevated both in cerebrospinal fluid and in serum. The left facial palsy was slightly improved. But his dysphagia didn't improve during at least 10 months after the onset. Among the cranial nerves, trigeminal and facial nerves are the most commonly affected by herpes zoster. But there are a few cases of the 9th and 10th cranial nerve involvement in the literature. However, dysphagia has rarely been reported in these previous cases, only four cases developed severe dysphagia like the present patient. All of these cases including our case were over sixty years old, while cases with slight dysphagia were under sixty years old. No other differentiating factor is noted between these two groups with regard to sites of vesicles, findings of cerebrospinal fluid and mode of therapy.     

Cerebrospinal fluid immunoglobulins and virus-specific antibodies in disorders affecting the facial nerve

Summary Sixty-two patients with acute idiopathic peripheral facial nerve palsy (AIPFP) and 31 patients with lymphocytic meningoradiculitis (Garin-Bujadoux or Bannwarth's syndrome) are described. Results of cerebrospinal fluid (CSF) analysis, including the measurement of immunoglobulins (Ig) G, A, and M, indicate that pleocytosis and/or disturbance of the blood-CSF barrier (BCB) and/or local immunoglobulin synthesis within the central nervous system (CNS) do occur in about 25% of patients with AIPFP. The commonest finding is a slight to moderate breakdown of BCB function without evidence of intrathecal immunoglobulin synthesis. In only about 10% of patients, further support for an inflammatory process within the CNS is found by intrathecal synthesis of oligoclonal IgG and/or localized synthesis of IgG and/or IgA. The majority of cases (75%) do not show any signs of an inflammatory process within the CNS. In contrast, lymphocytic meningopolyradiculitis (LMR) has a characteristic CSF profile with early impairment of BCB permeability as well as with rapid and predominant intrathecal IgM synthesis, which helps to distinguish monosymptomatic LMR from AIPFP. By applying a sensitive enzyme-linked immunosorbent assay to identical concentrations of IgG in serum and CSF, evidence of intrathecal synthesis of virus-specific antibodies was found only in 2 of 13 patients with AIPFP. In contrast, all 4 patients with herpes zoster oticus and peripheral facial palsy (Ramsay Hunt syndrome) showed an intrathecal IgG synthesis to varicella zoster virus lasting for up to 4 months after onset of disease.     

Diagnostic relevance of transcranial magnetic and electric stimulation of the facial nerve in the management of facial palsy.

OBJECTIVE: Earlier investigations have suggested that isolated conduction block of the facial nerve to transcranial magnetic stimulation early in the disorder represents a very sensitive and potentially specific finding in Bell's palsy differentiating the disease from other etiologies. METHODS: Stimulation of the facial nerve was performed electrically at the stylomastoid foramen and magnetically at the labyrinthine segment of the Fallopian channel within 3 days from symptom onset in 65 patients with Bell's palsy, five patients with Zoster oticus, one patient with neuroborreliosis and one patient with nuclear facial nerve palsy due to multiple sclerosis. RESULTS: Absence or decreased amplitudes of muscle responses to early transcranial magnetic stimulation was not specific for Bell's palsy, but also evident in all cases of Zoster oticus and in the case of neuroborreliosis. Amplitudes of electrically evoked muscle responses were more markedly reduced in Zoster oticus as compared to Bell's palsy, most likely due to a more severe degree of axonal degeneration. The degree of amplitude reduction of the muscle response to electrical stimulation reliably correlated with the severity of facial palsy. CONCLUSIONS: Transcranial magnetic stimulation in the early diagnosis of Bell's palsy is less specific than previously thought. While not specific with respect to the etiology of facial palsy, transcranial magnetic stimulation seems capable of localizing the site of lesion within the Fallopian channel. SIGNIFICANCE: Combined with transcranial magnetic stimulation, early electrical stimulation of the facial nerve at the stylomastoid foramen may help to establish correct diagnosis and prognosis.     

Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients. METHODS: In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263. FINDINGS: Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1.40, 95% CI 1.18 to 1.64; p<0.0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1.01, 0.85 to 1.19; p=0.90). The number of patients with adverse events was similar in all treatment arms. INTERPRETATION: Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery.     

Altered axonal excitability properties in facial palsy

Introduction: Axonal excitability measures give insight into the biophysical properties of peripheral nerve axons. In this study we applied these techniques to the study of facial palsy. Methods: Thirty patients with established facial palsy due to unresolved Bell's palsy or herpes zoster (>6 months duration), tumor invasion of the facial nerve, or traumatic facial nerve injury were assessed using facial nerve excitability techniques. Results: Full recordings were obtained in 23 patients (15 unrecovered Bell's palsy or herpes zoster, 5 trauma, 3 tumor‐related). Compared with normal controls, the facial palsy group demonstrated changes in stimulus response properties, threshold electrotonus, refractoriness, superexcitability, and I/V slope. Depolarizing threshold electrotonus distinguished between viral and non‐viral etiologies on subgroup analysis. Discussion: In this cross‐sectional study, established facial palsy demonstrated findings similar to those seen in studies of regenerated axons. The improved understanding of underlying axonal characteristics offered by the technique may guide future treatment. Muscle Nerve 57 : 268–272, 2018     

Peripheral facial paralysis and HIV infection: report of four African cases and review of the literature

Summary Four cases of infranuclear facial palsy associated with infection by the human immunodeficiency virus in young heterosexual African patients are reported. Two cases were healthy HIV carriers, one patient manifested AIDS-related complex, and one case fulfilled the CDC criteria for AIDS. Two patients had a typical Bell's palsy, one presented with manifest cephalic Herpes zoster infection and one, who suffered from facial diplegia, could be considered to have a cephalic form of Guillain-Barré syndrome. A review of the literature confirmed that peripheral facial palsy can occur at any stage of HIV infection and in various clinical contexts. In stages I and II of the HIV infection, patients may develop either Bell's palsy or Guillain-Barré syndrome. In stages III and IV, when the cellular immunity has begun to decline, Herpes zoster-related facial paralysis, seventh cranial nerve involvement secondary to meningeal lymphomatosis, and peripheral facial paralysis as one aspect of widespread chronic peripheral neuropathy may also occur.     

Investigation of unilateral facial weakness: magnetic stimulation of the proximal facial nerve and of the face-associated motor cortex

Summary Twenty-four patients with unilateral facial weakness of various aetiologies were investigated using a magnetic stimulator to stimulate the proximal segment of the facial nerve directly (short latency response) and also to activate the facial motoneurons bilaterally via corticonuclear pathways by placing the stimulating coil over the motor cortex (long latency responses). Electromyographic recordings were taken from both mentalis muscles using concentric needle electrodes. Seventeen patients were investigated at various times after onset of idiopathic facial palsy (Bell's palsy). In the acute stage (less than 5 days after onset) short and long latency responses on the paretic side were abnormal, being absent in all but one patient, in whom the short latency response was delayed. These abnormal responses were the earliest neurographic correlate for nerve conduction block. In 4 out of 9 patients seen up to 30 days after onset of palsy, trans-synaptically evoked long latency responses were absent. In patients examined more than 2 months after onset, long latency responses could always be obtained and, in 5 of 8 patients, short latency responses could also be elicited, indicating a return of the direct excitability of the nerve. Five patients with cerebral hemisphere lesions causing mild unilateral facial weakness had absent long latency responses when stimulating over the affected hemisphere, but normal bilateral long latency responses following stimulation over the unaffected cerebral hemisphere; short latency responses were normal. Magnetic stimulation of the brain and of the facial nerve can differentiate between central and peripheral causes of unilateral facial weakness and may prove useful in the early assessment of the degree of conduction block in Bell's palsy.Supported by the Deutsche Forschungsgemeinschaft     

Orbicularis oculi-Reflexe und Summenpotentiale des Orbicularis oris bei idiopathischer Facialislähmung

In 84 patients with idiopathic, clinically complete Bell's palsy the electrically induced blink reflexes with their two components (OOR I and II) were electromyographically recorded on both sides using skin electrodes. In 67 of these patients the evoked responses of the orbicularis oris muscle were also studied. The latencies and amplitudes were measured and related to the clinical outcome of the facial paralysis. The patients were divided into two groups, one with good recovery of the palsy (46 patients), the other with significant residual paresis and/or strong associated movements of the facial musculature (38 patients). In the group with good recovery the following results were obtained: 1. the OOR I remained elicitable or reappeated during the first 12 days after the onset of palsy; 2. the OOR II began to rise during the first 10 days of palsy; 3. the amplitude of the orbicularis oris response did not decrease to below 10%. In the group with poor recovery: 1. both components of the OOR were absent or diminished to below 4% for more than 12 days after the onset of palsy; 2. the latency difference of the OOR I exceeded 8 msec; 3. the amplitude of the orbicularis oris responses decreased to below 10%. Using these criteria it appears to be possible in about 85% of patients to make a prognosis between the 3rd to 5th and the 10th to 12th day after the onset of Bell's palsy.     

Facial palsy in multiple sclerosis

Facial palsy occurred in 21 (19.6%) of 107 Japanese patients with multiple sclerosis (MS) during a mean follow-up period of 4.3 years. We observed residual signs of facial palsy in five other patients in whom acute onset was confirmed from medical records. Facial palsy began on average 7.6 years after the onset of MS but in five patients (4.7%) was the first symptom of MS, preceding the next MS symptom by 0.5–3 years. Facial palsy was usually associated with other brainstem signs, while two patients showed only facial palsy 1 and 3 years after the onset of MS. Twenty-one (84.0%) of the 25 patients who underwent brain magnetic resonance imaging (MRI) showed brainstem lesions in the pontine tegmentum ipsilateral to the facial palsy. However, the two patients without other symptoms or signs had no apparent causal lesion on MRI, which suggests difficulty in differentiating idiopathic Bell’s palsy from MS- associated facial palsy by MRI, although it has an excellent capacity to detect causal lesions of facial palsy associated with MS. Received: 6 March 1997 Received in revised form: 25 July 1997 Accepted: 12 August 1997     

Electrophysiologic findings and prognosis in Bell's palsy

Electrophysiologic investigations were carried out on 45 patients with Bell's palsy at periodic intervals after the onset of paralysis. It was found that there was a good correlation between prognosis in Bell's palsy and the amplitude of evoked motor response obtained after six or more days of clinical paresis. When the average amplitude of evoked motor response was within normal limits (i.e., 504μV or greater), complete recovery with no residual deficits took place two to six weeks after the onset of facial palsy. When the evoked motor response was absent in all three major branches of the facial nerve, indicating complete nerve degeneration, electromyographic signs of recovery were apparent by the third or fourth month after the onset of paralysis. In these cases, recovery was relatively slow and incomplete, with some degree of residual deficit and synkinesis. Maximal return of voluntary facial movement was established 8 to 12 months after the initial symptom. When the mean amplitude of evoked motor response was below the lower limit of normal (i.e., less than 504μV), electromyographic signs of recovery were noted within 1 to 3 months, depending on the amplitude values. The final outcome of this intermediate group was similar, but not identical, to that of the previous group. The prognosis of facial paralysis in Bell's palsy was thus found to be directly related to the mean amplitude of evoked motor response, regardless of the extent of clinical paralysis.