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Lyme optic neuritis
Journal of the Neurological Sciences 295 (2010) 117–119
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Lyme optic neuritis Frédéric Blanc a,b,c,⁎, Laurent Ballonzoli b,d, Christophe Marcel a, Sylvie De Martino b,e, Benoît Jaulhac b,e, Jérôme de Seze a,b,c a
Department of Neurology, University Hospital of Strasbourg, Strasbourg, France GEBLY, Study Group for Lyme Borreliosis, Strasbourg, France Laboratoire d'Imagerie et de Neuroscience Cognitives (LINC, UMR7191), University of Strasbourg and Centre National de la Recherche Scientifique (CNRS), Strasbourg, France d Ophthalmology, University Hospital of Strasbourg, Strasbourg, France e National Reference Centre for Borrelia, Laboratory of Bacteriology, University Hospital of Strasbourg, Strasbourg, France b c
a r t i c l e
i n f o
Article history: Received 1 February 2010 Received in revised form 8 May 2010 Accepted 17 May 2010 Available online 8 June 2010 Keywords: Lyme disease Neuroborreliosis Optic neuritis Multiple sclerosis
a b s t r a c t Lyme optic neuritis (ON) is a rare disease and only a few cases have been reported. We describe two cases of isolated Lyme ON, one with recurrence 9 months after the appearance of initial symptoms. Diagnosis criteria for multiple sclerosis and neuromyelitis optica were not met. The etiological diagnosis was based on European case definition criteria for neuroborreliosis. Both patients had positive serum and cerebrospinal fluid serology, a positive intrathecal anti-Borrelia antibody index, and a good outcome on ceftriaxone. Specific diagnosis of Lyme ON is important since improvement of visual acuity is possible with specific antibiotherapy, even after many months. © 2010 Elsevier B.V. All rights reserved.
1. Introduction The first case of confirmed ocular Lyme borreliosis was described in 1985 by Steere et al. [1]. Although ocular involvement is rare in Lyme borreliosis, various ocular manifestations have been described including conjunctivitis, keratitis, various types of ocular inflammatory syndrome, and optic neuritis (ON) [2]. Cranial neuropathy, including ON, is a classical manifestation of Lyme neuroborreliosis in Europe. ON has been described in association with meningoradiculitis and chronic encephalomyelitis in two large neuroborreliosis cohorts [3,4], using European criteria for the diagnosis of neuroborreliosis [5]. Isolated forms – without any other neurological symptoms – of Lyme ON are rare, but at least four cases have been described [6–8]. We describe two new cases and discuss this rare clinical entity.
2. Methods The diagnosis of Lyme ON in our two patients was made according to the European criteria for neuroborreliosis, including the major biological criterion, the detection of intrathecally produced specific antibodies. ⁎ Corresponding author. Service of Neuropsychology, Department of Neurology, University Hospital of Strasbourg, 1, Place de l'Hôpital, 67091 Strasbourg Cedex, France. Tel.: +33 388116892; fax: +33 388116343. E-mail address: [email protected] (F. Blanc). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.05.009
Clinical data were recorded for both patients including: sex, age, tick bite history, erythema migrans history, arthralgia, myalgia, neurological data, and visual acuity. Both patients underwent biological and immunological tests including measurement of blood cell count, erythrocyte sedimentation rate, and serum analysis including total gammaglobulins, protein electrophoresis, C-reactive protein, complement factors, antinuclear antibodies, anticardiolipin antibodies, rheumatoid factor, venereal disease research laboratory testing, Treponema pallidum ELISA, and two tier-testing Lyme serology (ELISA, and Western blot as confirmatory analysis). Ocular fundus, visual evoked potential, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis including blood cell count, protein level, and oligoclonal band (OCB) evaluation by isoelectrofocusing, and intrathecal anti-Borrelia antibody index (AI) were also determined. Borrelia burgdorferi ELISA was performed for the detection of serum IgG and IgM, and CSF IgG, using a commercial kit (Enzygnost borreliosis; Dade Behring, Germany) [9]. Western blotting was performed on both serum and CSF samples using a local B. garinii strain isolated from CSF as the antigen source [10]. The interpretation criteria used for the serum immunoblots were selected from European rules validated in a multicenter study (two bands from p41 and OspC for IgM, or from p83/100, p39, p41, p17 for IgG) [11]. The B. burgdorferi AI was determined as the ratio: (ELISA titer in CSF/ELISA titer in serum) to (total IgG in CSF/total IgG in serum), as described previously [10,12]. The specific AI was considered to be positive when the ratio was ≥2, negative when b1.5, and intermediate when between 1.5 and 1.9.
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F. Blanc et al. / Journal of the Neurological Sciences 295 (2010) 117–119
Table 1 Summary of the two cases of Lyme optic neuritis. CSF protein (g/l)
Patient
Other symptoms
Serum IgG/IgM ELISA (AU)
Serum IgG Western blot bands
Western blot positivity11
1
Headache, arthralgia Arthralgia
26/0
32, 41, 60, 66, 75, 83
Yes
0.49
100/0 b 10
32, 41, 60, 100 –
Yes No
0.64 b0.45
2 Normal values
CSF white cell count (/mm3)
CSF IgG ELISA (AU)
CSF Western blot bands
AI/OCB
Visual outcome after ceftriaxone
0
16
None
2/0
++ (× 2.5)
0 b5
65 b4
41, 60, 100 –
2.2/0 b1.5/0
+++ (× 4.5)
AI: intrathecal anti-Borrelia antibody index; AU: arbitrary unit; CSF: cerebrospinal fluid; ELISA: enzyme-linked immunosorbent assay; IgG: immunoglobulin G; IgM: immunoglobulin M; OCB: oligoclonal bands.
3. Results
3.2. Patient 2
3.1. Patient 1
A 48 year-old female presented with left ON, headache, diffuse arthralgia, and bilateral optic papilla edema. She had no previous history of erythema migrans but had been exposed to tick bites. Left visual acuity was 20/100. Visual evoked potential showed a left P100 latency of 147 ms and a normal right latency of 99 ms. Brain MRI showed two non-specific subcortical FLAIR-lesions in the left frontal lobe, b3 mm in diameter. CSF analysis showed a raised protein level of 0.64 g/l without any white cells or OCBs. Anti-Borrelia IgG was positive in both serum and CSF and was confirmed by Western blotting. B. burgdorferi sensu lato AI was also positive (Table 1). Ceftriaxone (2 g/day for 3 weeks) plus methylprednisolone (for 3 days) followed by prednisolone (1 mg/kg/day for 2 months) were administered simultaneously. Left visual acuity improved to 20/20. Six years after the original ON, the patient has had no new neurological symptoms and her visual acuity remains unchanged.
A 63 year-old female developed right ON with a loss of visual acuity (20/200) but without any pain, 9 months before the current episode. She had no headache, no history of erythema migrans and no myalgia, but had discrete diffuse arthralgia. Later questioning of the patient revealed a history of tick bite a few months earlier. No treatment was given. Nine months later she developed left ON without any pain, with a loss of visual acuity (20/200). Visual evoked potential showed delayed P100 latency of 181 ms for the right eye and 154 ms for the left. AntiBorrelia IgG was detected in both serum and CSF and was confirmed by Western blotting. Specific intrathecal AI was also positive (Table 1). CSF analysis revealed a raised protein level of 0.49 g/l without any white cells or OCBs. Brain MRI showed three non-specific lesions on T2-FLAIR- and T2-weighted images (Fig. 1). Because of the nonconsecutive and bilateral nature of her ON, recurrent ON of inflammatory origin was suspected. Anti-neuromyelitis optica antibodies and medullar MRI were negative. Intravenous methylprednisolone (1 g/day for 3 days) was given initially because the AI result was not known at that time. As the patient had not improved after 3 weeks treatment, ceftriaxone (2 g/day for 3 weeks) was introduced. The patient improved after 2 weeks treatment and final visual acuity in each eye was 20/80. Four years after the first symptoms, the patient has had no other neurological symptoms and visual acuity remains unchanged.
4. Discussion These two cases support previous reports in the literature and confirm the occurrence of isolated cases of Lyme ON. Both of our patients had anti-Borrelia antibodies in serum and CSF and a favorable outcome after treatment with ceftriaxone, even when this treatment was initiated 9 months after the appearance of initial symptoms, as in patient 1. Both patients also had arthralgia and a history of tick bite exposure — as previously reported, the majority of patients with Lyme ON had the non-specific symptoms usually encountered in Lyme
Fig. 1. Axial brain MRI of patients 1 (A) and 2 (B) using T2-FLAIR (Fluid-Attenuated Inversion Recovery) sequences. Brain lesions for the two patients are non-specific. Patient 1 has two juxtacortical lesions of the frontal lobe and one periventricular lesion of the parietal lobe. Patient 2 has two juxtacortical lesions of the frontal lobe. No other abnormalities have been detected on brain MRI.
F. Blanc et al. / Journal of the Neurological Sciences 295 (2010) 117–119
borreliosis such as arthralgia and myalgia [8]. Finally, they also satisfied positive European criteria for neuroborreliosis including a positive intrathecal anti-Borrelia AI [5]. The AI has been demonstrated to be highly specific (N95%) for neuroborreliosis [13–15]. However, one study demonstrated the positivity of AI in 26.2% in a cohort of 42 MS patients, using a commercial kit of sandwich enzyme immunoassay (Test-Line Ltd, Clinical Diagnostics) different from the kit used for the two patients here [21]. In two previous studies of ON, with systematic screening for Lyme disease, four patients also had strong arguments in favor of isolated Lyme ON [6,7]. In the first study, 25 out of 440 patients with ON had positive Lyme serology and two of these patients had a positive specific AI [6], giving an overall prevalence of Lyme ON of 0.5%. In the second study, four patients had positive Lyme serology. Two of these patients had a negative specific AI and subsequently developed multiple sclerosis, and the other two had specific AI and Lyme ON [7]. In these two studies, the four patients with Lyme ON were treated with antibiotics with a good outcome. Other studies including suspected cases of Lyme ON, but without measurement of the AI, showed a positive outcome with specific antibiotics [16]. Among 20 patients with suspected isolated or non-isolated Lyme ON in the literature including ours, 13 had a positive response to antibiotherapy [8,16]. Furthermore, all six patients with a positive AI had a good outcome with antibiotherapy [6,7]. Corticosteroid treatment seems to be only partially effective [8]. The two patients described here have had the two treatment: steroids and ceftriaxone, and we cannot affirm which one of the two was efficient. The Optic Neuritis Treatment Trial (ONTT) is a randomized study evaluating the efficacy of corticosteroids in the treatment of acute ON and the risk of developing multiple sclerosis after ON. Patients have been followed up for 15 years. In the ONTT, only patients with brain MRI lesions N3 mm in diameter and without optic disc swelling developed multiple sclerosis [17]. Furthermore, the absence of pain, age N60 years (as in patient 1), and the absence of OCBs in CSF were protective factors for multiple sclerosis. In the ONTT, 37% of patients without evolution to multiple sclerosis had a poor visual outcome. Some of these patients probably had other chronic inflammatory diseases of the central nervous system such as neuromyelitis optica [18]. However, a few of these patients may have had Lyme ON. We describe a unique case of recurrent ON or, more precisely, manifestations in the other optic nerve secondary to Lyme disease in an untreated patient (patient 1). Few cases of recurrent ON of infectious origin have been described previously. However, in each case specific treatment, usually antibiotherapy, was effective [19]. In a cohort of 81 patients with neuroborreliosis, 42% reported blurred vision or diplopia and 27% had a delayed visual evoked potential [20]. Involvement of the optic nerve in neuroborreliosis seems to be more common than previously thought. It is extremely important to diagnose Lyme ON because of the availability of an effective treatment approach. Systematic question-
119
ing about tick bite exposure, non-specific associated symptoms such as arthralgia, Lyme serology (serum and CSF), and intrathecal antiBorrelia AI are useful in the diagnosis of these difficult cases.
References [1] Steere AC, Duray PH, Kauffmann DJ, Wormser GP. Unilateral blindness caused by infection with the Lyme disease spirochete, Borrelia burgdorferi. Ann Intern Med 1985;103(3):382–4. [2] Lesser RL. Ocular manifestations of Lyme disease. Am J Med 1995;98(4A):60S–2S. [3] Hansen K, Lebech AM. The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985–1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production. Brain 1992;115 (Pt 2):399–423. [4] Oschmann P, Dorndorf W, Hornig C, Schafer C, Wellensiek HJ, Pflughaupt KW. Stages and syndromes of neuroborreliosis. J Neurol 1998;245(5):262–72. [5] Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect 2010 Feb 2. Electronic publication ahead of print. [6] Sibony P, Halperin J, Coyle PK, Patel K. Reactive Lyme serology in optic neuritis. J Neuroophthalmol 2005;25(2):71–82. [7] Jacobson DM. Lyme disease and optic neuritis: long-term follow-up of seropositive patients. Neurology 2003;60(5):881–2. [8] Krim E, Guehl D, Burbaud P, Lagueny A. Retrobulbar optic neuritis: a complication of Lyme disease? J Neurol Neurosurg Psychiatry 2007;78(12):1409–10. [9] Hauser U, Krahl H, Peters H, Fingerle V, Wilske B. Impact of strain heterogeneity on Lyme disease serology in Europe: comparison of enzyme-linked immunosorbent assays using different species of Borrelia burgdorferi sensu lato. J Clin Microbiol 1998;36(2):427–36. [10] Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology 2007;69(10): 953–8. [11] Robertson J, Guy E, Andrews N, et al. A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis. J Clin Microbiol 2000;38 (6):2097–102. [12] Kaiser R, Lucking CH. Intrathecal synthesis of specific antibodies in neuroborreliosis. Comparison of different ELISA techniques and calculation methods. J Neurol Sci 1993;118(1):64–72. [13] Stiernstedt GT, Granstrom M, Hederstedt B, Skoldenberg B. Diagnosis of spirochetal meningitis by enzyme-linked immunosorbent assay and indirect immunofluorescence assay in serum and cerebrospinal fluid. J Clin Microbiol 1985;21(5):819–25. [14] Hansen K, Cruz M, Link H. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1990;161(6): 1194–202. [15] Steere AC, Berardi VP, Weeks KE, Logigian EL, Ackermann R. Evaluation of the intrathecal antibody response to Borrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis. J Infect Dis 1990;161(6):1203–9. [16] Rothermel H, Hedges 3rd TR, Steere AC. Optic neuropathy in children with Lyme disease. Pediatrics 2001;108(2):477–81. [17] Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 2008;65(6):727-32. [18] de Seze J, Arndt C, Jeanjean L, et al. Relapsing inflammatory optic neuritis: is it neuromyelitis optica? Neurology 2008;70(22):2075–6. [19] Pohl D, Rostasy K, Gieffers J, Maass M, Hanefeld F. Recurrent optic neuritis associated with Chlamydia pneumoniae infection of the central nervous system. Dev Med Child Neurol 2006;48(9):770–2. [20] Kubova Z, Szanyi J, Langrova J, Kremlacek J, Kuba M, Honegr K. Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis. J Clin Neurophysiol 2006;23(5):416–20. [21] Bednarova J, Stourac P, Adam P. Relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scand 2005;112(2):97–102.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Lyme optic neuritis Frédéric Blanc a,b,c,⁎, Laurent Ballonzoli b,d, Christophe Marcel a, Sylvie De Martino b,e, Benoît Jaulhac b,e, Jérôme de Seze a,b,c a
Department of Neurology, University Hospital of Strasbourg, Strasbourg, France GEBLY, Study Group for Lyme Borreliosis, Strasbourg, France Laboratoire d'Imagerie et de Neuroscience Cognitives (LINC, UMR7191), University of Strasbourg and Centre National de la Recherche Scientifique (CNRS), Strasbourg, France d Ophthalmology, University Hospital of Strasbourg, Strasbourg, France e National Reference Centre for Borrelia, Laboratory of Bacteriology, University Hospital of Strasbourg, Strasbourg, France b c
a r t i c l e
i n f o
Article history: Received 1 February 2010 Received in revised form 8 May 2010 Accepted 17 May 2010 Available online 8 June 2010 Keywords: Lyme disease Neuroborreliosis Optic neuritis Multiple sclerosis
a b s t r a c t Lyme optic neuritis (ON) is a rare disease and only a few cases have been reported. We describe two cases of isolated Lyme ON, one with recurrence 9 months after the appearance of initial symptoms. Diagnosis criteria for multiple sclerosis and neuromyelitis optica were not met. The etiological diagnosis was based on European case definition criteria for neuroborreliosis. Both patients had positive serum and cerebrospinal fluid serology, a positive intrathecal anti-Borrelia antibody index, and a good outcome on ceftriaxone. Specific diagnosis of Lyme ON is important since improvement of visual acuity is possible with specific antibiotherapy, even after many months. © 2010 Elsevier B.V. All rights reserved.
1. Introduction The first case of confirmed ocular Lyme borreliosis was described in 1985 by Steere et al. [1]. Although ocular involvement is rare in Lyme borreliosis, various ocular manifestations have been described including conjunctivitis, keratitis, various types of ocular inflammatory syndrome, and optic neuritis (ON) [2]. Cranial neuropathy, including ON, is a classical manifestation of Lyme neuroborreliosis in Europe. ON has been described in association with meningoradiculitis and chronic encephalomyelitis in two large neuroborreliosis cohorts [3,4], using European criteria for the diagnosis of neuroborreliosis [5]. Isolated forms – without any other neurological symptoms – of Lyme ON are rare, but at least four cases have been described [6–8]. We describe two new cases and discuss this rare clinical entity.
2. Methods The diagnosis of Lyme ON in our two patients was made according to the European criteria for neuroborreliosis, including the major biological criterion, the detection of intrathecally produced specific antibodies. ⁎ Corresponding author. Service of Neuropsychology, Department of Neurology, University Hospital of Strasbourg, 1, Place de l'Hôpital, 67091 Strasbourg Cedex, France. Tel.: +33 388116892; fax: +33 388116343. E-mail address: [email protected] (F. Blanc). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.05.009
Clinical data were recorded for both patients including: sex, age, tick bite history, erythema migrans history, arthralgia, myalgia, neurological data, and visual acuity. Both patients underwent biological and immunological tests including measurement of blood cell count, erythrocyte sedimentation rate, and serum analysis including total gammaglobulins, protein electrophoresis, C-reactive protein, complement factors, antinuclear antibodies, anticardiolipin antibodies, rheumatoid factor, venereal disease research laboratory testing, Treponema pallidum ELISA, and two tier-testing Lyme serology (ELISA, and Western blot as confirmatory analysis). Ocular fundus, visual evoked potential, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis including blood cell count, protein level, and oligoclonal band (OCB) evaluation by isoelectrofocusing, and intrathecal anti-Borrelia antibody index (AI) were also determined. Borrelia burgdorferi ELISA was performed for the detection of serum IgG and IgM, and CSF IgG, using a commercial kit (Enzygnost borreliosis; Dade Behring, Germany) [9]. Western blotting was performed on both serum and CSF samples using a local B. garinii strain isolated from CSF as the antigen source [10]. The interpretation criteria used for the serum immunoblots were selected from European rules validated in a multicenter study (two bands from p41 and OspC for IgM, or from p83/100, p39, p41, p17 for IgG) [11]. The B. burgdorferi AI was determined as the ratio: (ELISA titer in CSF/ELISA titer in serum) to (total IgG in CSF/total IgG in serum), as described previously [10,12]. The specific AI was considered to be positive when the ratio was ≥2, negative when b1.5, and intermediate when between 1.5 and 1.9.
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F. Blanc et al. / Journal of the Neurological Sciences 295 (2010) 117–119
Table 1 Summary of the two cases of Lyme optic neuritis. CSF protein (g/l)
Patient
Other symptoms
Serum IgG/IgM ELISA (AU)
Serum IgG Western blot bands
Western blot positivity11
1
Headache, arthralgia Arthralgia
26/0
32, 41, 60, 66, 75, 83
Yes
0.49
100/0 b 10
32, 41, 60, 100 –
Yes No
0.64 b0.45
2 Normal values
CSF white cell count (/mm3)
CSF IgG ELISA (AU)
CSF Western blot bands
AI/OCB
Visual outcome after ceftriaxone
0
16
None
2/0
++ (× 2.5)
0 b5
65 b4
41, 60, 100 –
2.2/0 b1.5/0
+++ (× 4.5)
AI: intrathecal anti-Borrelia antibody index; AU: arbitrary unit; CSF: cerebrospinal fluid; ELISA: enzyme-linked immunosorbent assay; IgG: immunoglobulin G; IgM: immunoglobulin M; OCB: oligoclonal bands.
3. Results
3.2. Patient 2
3.1. Patient 1
A 48 year-old female presented with left ON, headache, diffuse arthralgia, and bilateral optic papilla edema. She had no previous history of erythema migrans but had been exposed to tick bites. Left visual acuity was 20/100. Visual evoked potential showed a left P100 latency of 147 ms and a normal right latency of 99 ms. Brain MRI showed two non-specific subcortical FLAIR-lesions in the left frontal lobe, b3 mm in diameter. CSF analysis showed a raised protein level of 0.64 g/l without any white cells or OCBs. Anti-Borrelia IgG was positive in both serum and CSF and was confirmed by Western blotting. B. burgdorferi sensu lato AI was also positive (Table 1). Ceftriaxone (2 g/day for 3 weeks) plus methylprednisolone (for 3 days) followed by prednisolone (1 mg/kg/day for 2 months) were administered simultaneously. Left visual acuity improved to 20/20. Six years after the original ON, the patient has had no new neurological symptoms and her visual acuity remains unchanged.
A 63 year-old female developed right ON with a loss of visual acuity (20/200) but without any pain, 9 months before the current episode. She had no headache, no history of erythema migrans and no myalgia, but had discrete diffuse arthralgia. Later questioning of the patient revealed a history of tick bite a few months earlier. No treatment was given. Nine months later she developed left ON without any pain, with a loss of visual acuity (20/200). Visual evoked potential showed delayed P100 latency of 181 ms for the right eye and 154 ms for the left. AntiBorrelia IgG was detected in both serum and CSF and was confirmed by Western blotting. Specific intrathecal AI was also positive (Table 1). CSF analysis revealed a raised protein level of 0.49 g/l without any white cells or OCBs. Brain MRI showed three non-specific lesions on T2-FLAIR- and T2-weighted images (Fig. 1). Because of the nonconsecutive and bilateral nature of her ON, recurrent ON of inflammatory origin was suspected. Anti-neuromyelitis optica antibodies and medullar MRI were negative. Intravenous methylprednisolone (1 g/day for 3 days) was given initially because the AI result was not known at that time. As the patient had not improved after 3 weeks treatment, ceftriaxone (2 g/day for 3 weeks) was introduced. The patient improved after 2 weeks treatment and final visual acuity in each eye was 20/80. Four years after the first symptoms, the patient has had no other neurological symptoms and visual acuity remains unchanged.
4. Discussion These two cases support previous reports in the literature and confirm the occurrence of isolated cases of Lyme ON. Both of our patients had anti-Borrelia antibodies in serum and CSF and a favorable outcome after treatment with ceftriaxone, even when this treatment was initiated 9 months after the appearance of initial symptoms, as in patient 1. Both patients also had arthralgia and a history of tick bite exposure — as previously reported, the majority of patients with Lyme ON had the non-specific symptoms usually encountered in Lyme
Fig. 1. Axial brain MRI of patients 1 (A) and 2 (B) using T2-FLAIR (Fluid-Attenuated Inversion Recovery) sequences. Brain lesions for the two patients are non-specific. Patient 1 has two juxtacortical lesions of the frontal lobe and one periventricular lesion of the parietal lobe. Patient 2 has two juxtacortical lesions of the frontal lobe. No other abnormalities have been detected on brain MRI.
F. Blanc et al. / Journal of the Neurological Sciences 295 (2010) 117–119
borreliosis such as arthralgia and myalgia [8]. Finally, they also satisfied positive European criteria for neuroborreliosis including a positive intrathecal anti-Borrelia AI [5]. The AI has been demonstrated to be highly specific (N95%) for neuroborreliosis [13–15]. However, one study demonstrated the positivity of AI in 26.2% in a cohort of 42 MS patients, using a commercial kit of sandwich enzyme immunoassay (Test-Line Ltd, Clinical Diagnostics) different from the kit used for the two patients here [21]. In two previous studies of ON, with systematic screening for Lyme disease, four patients also had strong arguments in favor of isolated Lyme ON [6,7]. In the first study, 25 out of 440 patients with ON had positive Lyme serology and two of these patients had a positive specific AI [6], giving an overall prevalence of Lyme ON of 0.5%. In the second study, four patients had positive Lyme serology. Two of these patients had a negative specific AI and subsequently developed multiple sclerosis, and the other two had specific AI and Lyme ON [7]. In these two studies, the four patients with Lyme ON were treated with antibiotics with a good outcome. Other studies including suspected cases of Lyme ON, but without measurement of the AI, showed a positive outcome with specific antibiotics [16]. Among 20 patients with suspected isolated or non-isolated Lyme ON in the literature including ours, 13 had a positive response to antibiotherapy [8,16]. Furthermore, all six patients with a positive AI had a good outcome with antibiotherapy [6,7]. Corticosteroid treatment seems to be only partially effective [8]. The two patients described here have had the two treatment: steroids and ceftriaxone, and we cannot affirm which one of the two was efficient. The Optic Neuritis Treatment Trial (ONTT) is a randomized study evaluating the efficacy of corticosteroids in the treatment of acute ON and the risk of developing multiple sclerosis after ON. Patients have been followed up for 15 years. In the ONTT, only patients with brain MRI lesions N3 mm in diameter and without optic disc swelling developed multiple sclerosis [17]. Furthermore, the absence of pain, age N60 years (as in patient 1), and the absence of OCBs in CSF were protective factors for multiple sclerosis. In the ONTT, 37% of patients without evolution to multiple sclerosis had a poor visual outcome. Some of these patients probably had other chronic inflammatory diseases of the central nervous system such as neuromyelitis optica [18]. However, a few of these patients may have had Lyme ON. We describe a unique case of recurrent ON or, more precisely, manifestations in the other optic nerve secondary to Lyme disease in an untreated patient (patient 1). Few cases of recurrent ON of infectious origin have been described previously. However, in each case specific treatment, usually antibiotherapy, was effective [19]. In a cohort of 81 patients with neuroborreliosis, 42% reported blurred vision or diplopia and 27% had a delayed visual evoked potential [20]. Involvement of the optic nerve in neuroborreliosis seems to be more common than previously thought. It is extremely important to diagnose Lyme ON because of the availability of an effective treatment approach. Systematic question-
119
ing about tick bite exposure, non-specific associated symptoms such as arthralgia, Lyme serology (serum and CSF), and intrathecal antiBorrelia AI are useful in the diagnosis of these difficult cases.
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