Two Cases of Peripheral Facial Palsy With Negative CSF Analysis Despite an Infectious Etiology

PRACTICAL IMPLICATIONS

Even in cases of the most common pathogens (i.e., Borrelia and VZV), basic CSF analysis as performed in the ER or “outside business hours” may not always rule out an infectious etiology.

Diagnosis and etiologic classification of peripheral facial palsy (PFP) can be challenging in acute clinical situations. Because most cases prove to be benign (i.e., Bell or idiopathic facial palsy), patients presenting to emergency departments with PFP are often sent home with steroid therapy after limited diagnostic testing. However, 10%–20% of cases have nonbenign etiologies, such as infection, with similar clinical presentation.^1–3 Common pathogens in these cases include Borrelia species, herpes simplex virus (HSV), and varicella zoster virus (VZV).^4,5 Infectious etiology not only has a therapeutic implication but also is of prognostic relevance because prognosis concerning recovery in viral cause of PFP is less favorable.

Besides a thorough history and physical examination, basic diagnostic tests include blood panel, C-reactive protein, and otoscopy. Additional measures comprise CSF assessment, ganglioside antibodies (i.e., GM1 and GQ1b), electrophysiology (facial nerve conduction studies, blink reflex, and electromyography), and cranial MRI with thin brain stem sections (containing the facial nerve nucleus and pathway).

Guidelines for testing CSF in patients with PFP are inconsistent (CSF analysis is recommended in German neurology guidelines,⁶ but not mentioned in US, Canadian, and British guidelines^7–10). The following 2 cases illustrate that even inconspicuous CSF parameters obtained in the emergency room (ER) (i.e., cell count, total protein, glucose, and lactate) are not sufficient to rule out an infectious etiology. Although routine CSF analysis in patients with simple PFP cannot be justified in light of the currently available data, CSF analysis should be carried out if certain “red flags” are present, and CSF should then be screened for typical causes of infection including Borrelia (i.e., pathogen-specific antibody index = ASI), HSV, and VZV (i.e., PCR). In some cases, empiric antiviral and antibiotic therapy (e.g., with acyclovir and doxycycline) may alternatively be discussed, the latter particularly in summer months and/or in Lyme disease-endemic areas when high Borrelia immunoglobulin M (IgM) titers are present (serology).

Cases

Case 1

A 57-year-old patient presented to the ER in November 2018 with acute-onset, right-sided PFP. A detailed history revealed right-sided periauricular pain 2 weeks before admission and mild headache. Basic CSF parameters were normal on day 1. Borrelia screening tests were positive (IgM enzyme-linked immunosorbent assay [ELISA] 23.95, normal < 5, immunoglobulin G [IgG] ELISA 89.11, normal < 16); however, because this could not be confirmed by western blot (IgM- and IgG-negative), ASI was not performed. Electrophysiologic results were consistent with PFP, whereas cranial MRI with thin brainstem sections to detect CNS pathology was unremarkable. The patient received steroid treatment and facial physiotherapy. Slight amelioration was found on clinical examination, and the patient reported fluctuating mild headaches. Discharge took place on day 5.

The patient presented to our ER again a fortnight later with refractory headache and general malaise. The PFP had improved, with only slight asymmetry of the nasolabial fold. Admission ensued for headache workup and treatment. Two days later, the patient developed additional contralateral PFP. Repeat cranial MRI was unremarkable; however, lumbar puncture revealed pleocytosis (314/μL), and triple therapy with ceftriaxone, ampicillin, and acyclovir was initiated. Renewed screening tests (serum) for Borrelia were again positive (IgM ELISA 9.66, IgG ELISA 98.77) and slightly positive on confirmation (slightly stronger band in CSF IgG western blot compared with serum). Further workup revealed intrathecal Borrelia-specific IgG antibodies (index 3.4; normal value ≤1.5). Therapy was reduced to ceftriaxone 2 g per day i.v. over 21 days, resulting in marked clinical improvement.

Case 2

A 52-year-old patient presented to our ER with acute onset of reduced brachiofacial sensitivity and right-sided PFP. In addition, hypersensitivity of the left scalp and increasing periauricular and unusually pronounced nuchal pain had been present for days. Primary admission to our stroke unit ruled out cranial artery dissection. In parallel, i.v. acyclovir was commenced to cover potential viral genesis. Cranial MRI did not show signs of ischemia or dissection but did show slight contrast enhancement of the facial nerve. Despite an inconspicuous CSF reading at day 2 postadmission (cell count, 4/μL; total protein, 467 mg/L), further virologic assessment revealed a highly positive (1000 copies/μL) VZV PCR at day 4 postadmission. Otoscopy did not detect local herpetic lesions, but audiometry and electronystagmography revealed inner ear involvement. Acyclovir treatment was hence continued, and 250 mg of prednisolone i.v. was transiently added. Renewed CSF analysis at day 16 postadmission revealed slight pleocytosis (cell count 10/μL, total protein 409 mg/L), but VZV PCR results were then negative, and acyclovir treatment was stopped after 21 days.

Discussion

These 2 case reports describe the occurrence of an infection-based PFP with inconspicuous CSF results in the acute situation. This highlights that even in cases of the most common pathogens (i.e., Borrelia and VZV), basic CSF analysis as performed in the ER or “outside business hours” may not always rule out an infectious etiology. Additional CSF workup (i.e., specific intrathecal antibody index for Borrelia, PCR for VZV and HSV) should be performed when “red flag” symptoms such as refractory headache, neuropathic pain, and bilateral PFP are present or when the emergency MRI is normal and/or patients are immunosuppressed.

German neurology guidelines deem CSF analysis obligatory in children presenting with PFP and recommend it in adults,⁶ whereas other guidelines do not mention CSF analysis at all in this context.^7–10 Routine CSF analysis in all patients with PFP is still a matter of controversy and may not be justified in light of the currently available data. Nonetheless, we recommend performing it in the presence of the abovementioned “red flag symptoms” or in specific patient subgroups that are at high risk of infection. Acute CSF analysis should not only cover the basic parameters but also include tests for Borrelia (i.e., ELISA, Western blot, and ASI) and HSV/VZV (i.e., PCR). Results of the latter must be followed up by the treating physician or general practitioner if patients are sent home from the ER (the turnaround time at our hospital is around 3 business days). Patients with “red flag” symptoms should be admitted. Furthermore, regardless of whether CSF analysis has been performed (and the results of specific pathogen tests are still outstanding), empiric antiviral and/or antibiotic treatment should be discussed in individual cases. The former has been suggested previously,⁷ whereas the latter may be considered in summer months in Lyme disease-endemic areas, particularly in patients with high IgM titers (serology).

Appendix. Authors

Study Funding

No targeted funding reported.

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