The full article may be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362302/Case Rep Neurol. 2012 Jan;4(1):47-53. Epub 2012 Mar 14.
A case of relapsing-remitting neuroborreliosis? Challenges in the differential diagnosis of recurrent myelitis.
Albrecht P, Henke N, Lehmann HC, Macht S, Hefter H, Goebels N, Mackenzie C, Rupprecht TA, Fingerle V, Hartung HP, Methner A.
Department of Neurology, Heinrich Heine University, Düsseldorf, Oberschleissheim, Germany.
We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case.
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I'm not questioning the authors' conclusions, however after reading many accounts of people who don't recall a tick bite or a rash, I don't think the possibility of re-infection should ever be ruled out without good reason(s):Introduction
Herein, we report a case with positive B. burgdorferi serology and 4 episodes of severe CNS manifestations with full recovery each time after sufficient antibiotic treatment. We illustrate the diagnostic steps and procedures which were valuable for posing the differential diagnosis in this unusual case, taking into account current state-of-the-art procedures for the diagnosis of Lyme borreliosis.
The differential diagnostic for the relapsing spinal syndromes of our patient comprises spinal lymphoma, a spinal manifestation of X-type histiocytosis, neuromyelitis optica, multiple sclerosis (MS) or a systemic autoimmune disease. As our patient presented with only spinal and brainstem symptoms and no supratentorial lesions were detectable in MRI, the diagnostic criteria for MS were not fulfilled . The long asymptomatic course between relapses, the absence of atypical cells in CSF, the positive response to antibiotic treatment (even without corticosteroids in 2008) and the serological findings argue against lymphoma. A relapse of X-type histiocytosis after 14 years without symptoms seems very improbable as the microscopic analysis of CSF revealed no evidence of histiocytes, and myelitis as a manifestation of histiocytosis is an extremely rare event, even though it has been previously reported . The severe pleocytosis and damage to the BBB argue against neuromyelitis optica, MS or vasculitis especially since the visual system was unaffected and aquaporin-4 antibodies, oligoclonal bands, MRZ reaction, supratentorial MRI and the laboratory screening for vasculitis were negative.
The fact that a positive B. burgdorferi CSF/serum AI was found in 3 out of 4 episodes and that CSF pleocytosis and clinical symptoms ameliorated in response to antibiotic treatment seems to suggest recurrent episodes of neuroborreliosis. However, recurrent episodes of borreliosis and even more so neuroborreliosis after sufficient antibiotic treatment such as in this case, are very uncommon. If relapses occur, they are attributed to reinfections or relapses after inadequate antibiotic therapy. Moreover, it needs to be considered that the patient did not recall any previous tick bite or erythema migrans nor does she belong to a part of the population with an increased risk for repeated tick bites. Further, it remains unclear why the AI was negative during the third episode while all other signs and symptoms were similar. All 4 episodes manifested with a spinal syndrome despite the fact that B. burgdorferi myelitis represents less than 5% of cases with neuroborreliosis in larger studies [9, 10, 11]. Positive CSF/serum IgG AI can be found after a successfully treated and no longer active neuroborreliosis. But we would expect continuously positive predominantly IgG AIs in the case of AI persistence after an acute infection or during a persisting or remitting infection involving the CNS. However, this was not the case during the episode in 2008 when the AI was normal or in the current episode when AIs returned to normal 3 months after the start of the episode.
AIs can change over time depending on the activation status of the immune system. Increasing AIs are not specific for an acute borreliosis as they can also be the result of an unspecific stimulation of the immune system, e.g. by an autoimmune manifestation or a yet unidentified infection in our patient. AIs are calculated as the ratio of specific to total immunoglobulins in CSF divided by the ratio of specific to total immunoglobulins in serum. It is therefore possible that low concentrations of total immunoglobulins in CSF give rise to positive AIs at rather low specific concentrations in CSF, like the Borrelia-specific IgG concentration of 1.3 U/ml observed in our patient. In line with this, a Reiber diagram gave no evidence of intrathecal IgG synthesis in our patient.
Therefore, further parameters were needed to resolve the diagnostic dilemma in this case. Real-time PCR-based results for B. burgdorferi in CSF are often negative, as are cultures, even in the case of active neuroborreliosis; however, positive results can serve to ascertain the diagnosis. Thus, negative PCR results do not exclude neuroborreliosis in this case.
The level of CXCL13 in CSF is a very sensitive parameter for neuroborreliosis and can be of great help, especially in complex cases like ours [12, 13]. In several studies using the same ready-made ELISA from R&D Systems as in our patient, untreated neuroborreliosis could be differentiated from other neurological disorders with a high sensitivity of above 90% using cutoff values of CXCL13 concentrations in CSF of 250 pg/ml , 100 pg/ml  or 142 pg/ml . In a prospective trial, where a self-made ELISA with different binding properties was used, a sensitivity of 94.1% and a specificity of 96.1% were obtained with a cutoff of 1,229 pg/ml, and sensitivity even reached 100% at a cutoff of 697 pg/ml . An important finding of this large trial was that the CXCL13 concentration in CSF could discriminate neuroborreliosis from MS. The CXCL13 levels found in MS were only moderately elevated, like in our case. A reanalysis of the data of this prospective study revealed a negative predictive value of 99% for acute untreated neuroborreliosis (A. Plate, pers. commun.).
This large body of evidence clearly indicates a good negative predictive value for the CXCL13 concentration of 35 pg/ml observed in our patient. Thus, the recurrence of episodes despite sufficient antibiotic therapy and the fact that she did not recall a tick bite or erythema migrans and did not belong to a risk group for repeated tick bites strongly argue against acute neuroborreliosis as the cause of our patient's current episode.
Instead, it seems most probable that our patient had suffered from neuroborreliosis in the past, e.g. when she had her first episodes of neurological symptoms in 1996 and/or 1999, which was effectively treated and cured back then. We interpret the subsequent episodes in 2008 and 2011 as post-infectious autoimmune-mediated transverse myelitis triggered by the preceding neuroborreliosis. Immune responses specific against CNS proteins or myelin have been reported in CSF of neuroborreliosis patients [17, 18, 19, 20, 21, 22], and post-infectious autoimmune mechanisms following Lyme borreliosis have been discussed for arthritis and autoimmune polyneuropathy [23, 24]. So an autoimmune mechanism caused by molecular mimicry seems a plausible explanation for the relapsing events of myelitis observed in our patient. The fact that she recovered in 2008 even without steroid treatment does not argue against an autoimmune transverse myelitis, as these disorders are also known to show spontaneous remissions, albeit with a slower recovery than with steroid treatment. Also, the fact that we did not observe more bands in the B. burgdorferi Western blot in CSF and serum argues against a persistent and relapsing neuroborreliosis, in which we would expect more bands, particularly IgG. The findings are in line with our assumption that our patient had contact with B. burgdorferi before, possibly even neuroborreliosis during one of the first episodes. Thus, the bands detectable in CSF and serum during the fourth episode would have been caused by a persistence of specific B cells, which are stimulated in the context of the presumed autoimmune event.
Taken together, our case highlights the diagnostic challenges that may occur in patients with inflammatory lesions of the spinal cord and/or positive B. burgdorferi serology.
Thus, the recurrence of episodes despite sufficient antibiotic therapy and the fact that she did not recall a tick bite or erythema migrans and did not belong to a risk group for repeated tick bites strongly argue against acute neuroborreliosis as the cause of our patient's current episode.