Lyme Neuroborreliosis Presenting as Multiple Cranial Neuropathies

ABSTRACT

Neuroborreliosis can manifest with cranial nerve (CN) palsies, commonly CN VII. Rarely have isolated or multiple palsies been reported. We describe a case of a young female from a Lyme endemic region who presented with bilateral CN VI palsies and a dilated right pupil, possibly a partial CN III palsy. She later developed CN VII palsy and bilateral enhancement of multiple cranial nerves on neuroimaging. She was diagnosed with Lyme disease by serological testing, with gradual improvement on antibiotics. Our case illustrates that neuroborreliosis can present as any or multiple CN palsies, and should be considered particularly in endemic areas.

Introduction

Lyme disease is caused by the bacterial spirochaete Borrelia burgdorferi and is transmitted by the Ixodes tick in the United States. It is the most frequently transmitted tick-borne infection in the United States, with a high prevalence in the Northeastern and upper Midwestern regions. In such regions, the incidence is approximately 40 per 100,000 people, with most infections occurring during the late spring, summer, and early fall.¹ The diagnosis of Lyme disease is largely clinical, and requires a likely exposure, a clinical finding with a high positive predictive value (such as erythema migrans) and positive laboratory testing (typically, positive enzyme-linked immunosorbent assay [ELISA], and Western blot).²

The disease is classified into three stages, namely, localised, disseminated, and persistent. The localised and disseminated stages are part of early infection, while the persistent stage is indicative of chronic infection. In the first stage, the disease often presents with an erythema migrans rash. This rash is found in 70% to 80% of cases and appears at the site of the tick bite as an enlarging, erythematous skin lesion that may be homogenous or targetoid. In addition to the rash, patients may experience flu-like symptoms, such as fever, myalgias, or headache. However, nearly 30% of patients with the erythema migrans rash will have no additional symptoms.¹

The second stage of Lyme disease develops 3–12 weeks following the initial infection. Common features include neurological symptoms, such as dizziness and headache, and cardiac symptoms, such as chest pain and palpitations. The third stage of Lyme disease can occur months to years later, with the key feature of late-stage disease being severe arthritis, which tends to affect the knee. Cognitive abnormalities in third-stage Lyme are also common.¹ Patients may initially present in any stage of disease.³

With regard to neuroborreliosis, approximately 20% of patients with Lyme disease have some degree of neurological involvement, and this tends to occur in the second or third stages.¹ The Borrelia bugdorferi spirochaete can produce symptomatic neurological disease or remain dormant in the central nervous system for long periods of time.⁴ Central nervous system involvement can present as meningitis, encephalitis, cranial neuritis, and radiculoneuropathy early on. Thereafter, encephalomyelitis and encephalopathy may occur. Lyme has also been associated with the development of psychiatric conditions, including bipolar, major depression, and schizophrenia, among others.⁵ Neuroborreliosis can be treated with oral or parenteral antibiotics, such as doxycycline, amoxycillin, or a cephalosporin.²

Cranial nerve (CN) VII is the most common cranial nerve palsy associated with Lyme disease. There are few reports of different CN palsies as the presenting feature. Furthermore, there are few reports of multiple simultaneous CN palsies secondary to Lyme disease.³ Here, we present a case of a patient who initially presented with bilateral CN VI palsies and a dilated right pupil (possibly representing a partial CN III palsy), and was then found to have involvement of multiple cranial nerves secondary to Lyme disease.

Case report

A 48-year-old healthy white Caucasian female with a past ocular history of myopia, with no known tick bites or previous diagnosis of Lyme disease, presented with 1 week of binocular horizontal diplopia and also noted that her right eye had started to turn in. These symptoms were associated with right-sided headache, retrobulbar pain, blurry vision, and vomiting. Other than headache, she had no other neurological complaints, such as dizziness or hearing loss, and she had no other symptoms related to stage 1 or 2 of Lyme disease. On examination, her visual acuity was 20/20 with correction in both eyes. Her right pupil was 5 mm and minimally reactive, and the left pupil was 3 mm and briskly reactive, without a relative afferent pupillary defect on either side. She had significant limitation of abduction of the right eye and a mild limitation of abduction of the left eye. A week later, she reported an inability to close her right eye and was noted to have 5 mm of lagophthalmos. She had also developed a significant limitation in abduction in the left eye. By this time, she had also developed back pain and weakness of her neck and upper extremities. Magnetic resonance imaging (MRI) of her brain showed enhancement of CN III, V, VI, VII, VIII, IX, and X symmetrically (Figures 1a and 2a). MRI of the spine also showed diffuse enhancement of the cauda equina nerve roots and enhancement of nerve roots throughout the cervical spine (Figure 3a). The differential diagnoses included inflammatory, infectious, or neoplastic aetiologies, such as sarcoidosis, Lyme disease, tuberculosis, and bartonellosis, among others. A laboratory work-up demonstrated elevated erythrocyte sedimentation rate, C reactive protein, and Lyme IgG and IgM by ELISA and Western blot. Cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis and detection of Lyme IgM and IgG bands by Western blot. Serological studies for other inflammatory or infectious aetiologies were negative. She began antibiotic treatment with intravenous (IV) ceftriaxone. On a return visit, the CN VII palsy on the right side had improved, while her bilateral CN VI palsy was unchanged. A few months later, her lagophthalmos had completely resolved, but she still had some right-sided abduction deficit. On repeat MRI, all cranial nerve enhancement had diminished, as had the enhancement along the cervical cord and cauda equina (Figures 1b, 2b, and 3b).

Figure 1.

(a) Axial T1-weighted magnetic resonance image after administration of intravenous gadolinium contrast at the level of the internal auditory canals demonstrating enhancement along with the 7th and 8th cranial nerves (solid arrows). There is also enhancement of the right 5th cranial nerve (arrowhead) within Meckel’s cave and bilateral VI nerve enhancement (dashed arrows). (b) Repeat imaging 4 months later showing resolution of the enhancement along the 7th and 8th cranial nerves (solid arrows). There is mild residual enhancement along the right VI nerve (dotted arrow). The 5th nerve is not clearly visualised on this slice due to differences in angulation.

Figure 2.

(a) Obliqued axial T1-weighted magnetic resonance image after administration of intravenous gadolinium contrast at the level of the midbrain demonstrating enhancement along with the 3rd cranial nerves (solid arrows). (b) Repeat imaging 4 months later showing significantly decreased enhancement.

Figure 3.

(a) Sagittal T1-weighted fat saturated magnetic resonance image after administration of intravenous gadolinium contrast demonstrating thin enhancement along the surface of the spinal cord and exiting cervical nerve roots (arrows). (b) Repeat examination 4 months later showing resolution of these findings.

Discussion

Lyme disease can affect the central nervous system and cause neurological abnormalities in both the second and third stages, with 20% of patients with Lyme disease developing neurological abnormalities. More specifically, 5% develop a CN VII palsy, and in such cases, lagophthalmos and exposure keratopathy may be initial presenting signs.¹ Lyme disease is thought to account for nearly 25% of new onset CN VII palsies in endemic areas.⁶

Rarely, patients may also present with other isolated CN palsies or combined palsies. A case report by Moynagh and McNamar described an isolated CN VI palsy following a bull’s eye rash. The patient had no flu-like symptoms, facial weakness, or any other neurological signs.⁷ Another report by Sharma and Biswas described a 16-year-old female with isolated CN IV and VI palsies suspected to be from Lyme disease.⁸ In addition, a report by Dabiri and Burakgazi documented a case of isolated CN VI palsy with optic neuritis in a patient with Lyme disease.⁹

Patients may also present with several simultaneous CN palsies, or may be found to have multiple cranial nerves enhancing on imaging. A report by Chaturvedi and colleagues described a patient who presented with simultaneous palsies of CN II, V, VI, IX, and X, associated with flu-like symptoms and an erythema migrans rash. The patient had positive Lyme IgG and IgM antibodies by ELISA and Western blot, and had full resolution of all cranial neuropathies after antibiotic treatment.³ Another case report by Piché-Renaud and colleagues described a patient who presented with bilateral CN VII palsy and was found to have symmetric enhancement of CN III, V, VI, VII, VIII, X and XII on MRI. The patient had experienced fever and rash, and had a confirmed diagnosis of Lyme disease by lumbar puncture and serology. The patient then had a complete resolution of symptoms after treatment with IV ceftriaxone.¹⁰ Furthermore, in a study examining Lyme disease-related intracranial hypertension in seven patients, six had an MRI and were all found to have enhancement of various cranial nerves.¹¹

As opposed to the more common presentation of a CN VII palsy, our patient presented initially with CN VI palsies and a possible partial CN III palsy, given her limitation in abduction and pupil abnormality. To our knowledge, our case is the first ever reported of these two palsies as the initial presentation of neuroborreliosis. The patient then developed a clinical CN VII palsy with lagophthalmos, along with enhancement of multiple cranial nerves bilaterally on imaging. She also developed back pain and weakness of her neck and upper extremities, corresponding to the enhancement of the cervical cord and cervical nerve roots on MRI.

In addition to the clinical presentation and imaging, the diagnosis of Lyme disease was made based on serological and CSF studies. For serological testing, a two-tiered approach is recommended: immunofluorescence assay or ELISA, followed by reflexive immunoblotting. This screening test (and confirmatory blot testing) can be falsely negative in early stages of Lyme disease. When positive, however, patients must undergo confirmatory testing. For the two-tiered approach, the sensitivity is 30–40% in early infection and 70–100% in disseminated disease, and the specificity is >95% in all stages.¹² Our patient initially had elevated Lyme antibodies by ELISA. Western blot was then performed, which detected two out of three IgM bands, indicating acute infection. The blot also detected 2 out of 10 positive IgG bands. At least 5 of the 10 IgG bands must be detected to be considered positive, but detection of fewer IgG bands can occur in acute infection as the IgG response usually appears after 30 days.¹² IgM positivity and IgG negativity a month after symptom onset may be false positive; however, in our case, the testing was performed 1 week after symptom onset. Notably, but rarely, a positive immunoblot can represent exposure to other spirochaetes.

In addition to serologies, our patient’s CSF studies revealed one positive IgG band and two positive IgM bands. There are no specific criteria for the interpretation of a CSF immunoblot, and positivity can indicate transudation from plasma or compartmental antibody production. To assess if intrathecal antibodies are not transferred from serum, CSF and serum should be collected on the same day and the ratio of IgG compared; if the CSF to serum ratio of IgG is more than 1, then the IgG is likely to have been made intrathecally. CSF testing can be useful in regions with high background seroprevalence, but generally, serological testing in the appropriate clinical setting is sufficient for the diagnosis of Lyme disease.¹²

This case illustrates the importance of having a high suspicion for Lyme disease in various CN palsies, particularly in patients from endemic areas. Our patient lived in a Lyme endemic region, and her presentation required a high degree of suspicion for Lyme disease, despite no recollection of a previous tick bite. Lyme disease can cause a host of ocular manifestations, including conjunctivitis, keratitis, intraocular inflammation, and papilloedema,¹³ further emphasising the need for a high degree of suspicion for Lyme disease in ophthalmology practices in endemic areas. Lyme disease is considered to be a great imitator and is often misdiagnosed as other conditions, which can undoubtedly occur in cases of neuroborreliosis.⁴ Thus, one’s clinical suspicion for Lyme disease should remain high in patients who present with multiple CN palsies in endemic areas.

Declaration of interest statement

The authors report no conflict of interest.