Bell’s palsy, or idiopathic facial paralysis (IFP), accounts for approximately 60–80% of lower motor neuronal facial palsies [
A 58-year-old Hispanic woman with no significant past medical history presented to a county hospital in 2007 due to the sudden onset of peripheral left facial weakness preceded by an upper respiratory tract infection. She received acyclovir and a course of prednisone with a partial response documented 4 weeks later. Three months after the initial episode, she returned to the emergency department due to relapse of the left peripheral facial weakness. A second cycle of acyclovir and prednisone was prescribed, and she underwent brain magnetic resonance imaging (MRI) and Lyme serology testing. Brain MRI without contrast was unremarkable and her Lyme IgG/IgM antibodies were equivocal with negative a Western Blot (WB). In early 2010, the patient was seen yet again in an outpatient clinic for a 2-day history of left facial palsy; this time she declined steroids. Concerns were raised regarding the equivocal serology for Lyme and recurrence of facial palsy, and the patient was empirically treated with doxycycline for 2 weeks. A WB for Lyme disease was repeated and returned positive. She was evaluated by the infectious disease service and provided a second course of antibiotics. In June 2011, the patient presented to the emergency department with sudden onset of right facial weakness and was admitted for further workup. Results were significant for negative WB for Lyme disease, cerebrospinal fluid (CSF), analysis revealed WBC 2, RBC 1, glucose 95 mg/dL, and protein 31 mg/dL. CSF polymerase chain reaction (PCR) for Lyme, varicella zoster virus (VZV), and herpes simplex virus (HSV) was negative. The IgG synthesis rate was 3.6, which was slightly elevated but there were no oligoclonal bands (OGB). Rheumatologic panel included positive antinuclear antibodies (ANA) 1 : 80 speckled, double stranded ANA was negative, and antiribonucleoprotein was borderline positive. Upon reviewing her clinical history, the patient mentioned having 6 relatives with histories consistent with peripheral Bell’s palsy, including her mother, one cousin, and 4 of her sisters. One of the patient’s sisters also had recurrent episodes of facial nerve paralysis. The familial pedigee is displayed in Figure
Pedigree of patient’s family with 7 affected individuals across 2 generations.
Since David McCormicks’s landmark study published in Lancet in 1972, the most commonly cited mechanism for IFP involves reactivation of latent herpes simplex virus in the seventh nerve ganglion [
While a firm hereditary basis for IFP has yet to be uncovered, familial clustering has long been noted in the literature. Since the first reported case series of familial Bell
Numerous studies have attempted to provide objective evidence of a genetic basis for IFP. Much of the attention thus far has centered on the human leukocyte antigen (HLA) system, which has strong objective associations with a variety of autoimmune diseases. One Mexican study of 92 patients with IFP found a significant decrease in the HLA class 2 DR antigen and acutely decreased levels of CD3/CD4 T cells at the onset of facial paralysis, suggesting the possibility that an HLA-DR linked “resistance gene” may exist [
Ultimately, these studies have yielded a convoluted and mixed understanding of the role of HLA antigens in IFP. We feel these studies provide evidence of, if nothing else, a state of immune dysregulation that often accompanies IFP. Specifically, there seems to be a repeated theme of HLA-DR antigen positivity and the subsequent development of IFP. Rather than a simple inflammatory response to reactivation of HSV in the nerve ganglion, IFP may very well represent a secondary autoimmune disease induced by infection. Many studies have postulated that familial IFP is, thus, an autoimmune disease with genetic predisposition. While an interesting theory, it has little experimental backing. All the current evidence exists in the form of retrospective genetic analyses, all of which have produced possible associations with various antigens and nothing more. Additional, more extensive, rigorous retrospective analyses are needed to further characterize this possible genetic component to IFP.
Among mechanisms posed for IFP, a structural predisposition has long been mentioned as a potential contributor. Knowledge of the pathophysiology of this disease, with the exception of the proven association with HSV, has been historically been limited to edema and swelling of the facial nerve. This has been objectively documented both on MRI contrast enhancement and direct observation during decompression operations. Contrast enhancement, interestingly, has been often noted bilaterally and not simply restricted to the side of facial nerve dysfunction [
Though a paucity of evidence exists with regard to this question, the few imaging-based studies to date have found evidence that seems to support the validity of this hypothesis. One retrospective computed-tomography-based study of 25 patients with IFP found a statistically significant asymmetry in diameter of the facial canal at the meatal foramen between clinically involved and uninvolved sides [
Bell’s palsy remains a complex and mysterious entity from a pathophysiologic perspective. Seropositivity to HSV is a clearly established risk factor in the development of IFP. However, the clear discord between the incidence of HSV seropositivity and the incidence of IFP suggests the progression of disease from infection with HSV to facial nerve paralysis is a very multifactorial process dependent on several host factors.
The sheer number of case studies to date suggests that familial clustering of IFP is a real, noncoincidental phenomenon. Our case represents a unique and perplexing example of one such family. Our patient had recurrent episodes of paralysis that occurred in the absence of an obvious precipitant. Her workup revealed no evidence of hyperglycemia to suggest diabetic neuropathy, unremarkable imaging, and negative serologic studies for infection. Her facial palsy was thus felt to be due to an underlying genetic predisposition, though we were unable to obtain HLA testing of this individual. Whether this family’s history represents common exposure to similar environmental influences or a discrete genetic or anatomic predisposition is ultimately unknown, but the current body of evidence seems to strongly support a possible hereditary basis.