The question of the aetiology of multiple sclerosis remains unresolved to this day. The disease is classically a chronic, immune-mediated, demyelinating disorder of the central nervous system, in which the current neurological perspective emphasises the combined role of autoimmune and environmental factors. At the same time, another idea has long been present: that, at least in some cases, a persistent infection, particularly Lyme borreliosis caused by Borrelia burgdorferi, may lie at the root of the condition. By now, a great deal of evidence has come to light that helps to fill in the gaps in the early theories.
Theory and evidence regarding the links between Lyme disease and MS
Markus Fritzsche’s article, published in 2005, presents the infectious hypothesis most forcefully. According to the author, chronic Lyme disease may even underlie multiple sclerosis, and he supports this with epidemiological, microbiological, immunological and therapeutic arguments. Fritzsche begins by noting that the geographical distribution of MS in many places parallels the spread of Borrelia burgdorferi and Ixodes ticks. He argues that this is not mere coincidence, but may indicate that the tick-borne spirochete triggers a chronic inflammatory process in the central nervous system in certain cases.
A key element of Fritzsche’s line of reasoning is that Borrelia can persist in the body for a long time, evade the immune system, and then reactivate later. This model would offer an explanation for the fluctuating, relapsing-remitting course of MS. The author therefore suggests that combined antibiotic treatment against Borrelia – for example, the use of minocycline, tinidazole and hydroxychloroquine – could represent a therapeutic option. Combined antibiotic treatment has led to remission or long-term recovery in numerous clinical cases of MS. It is important to note, however, that Fritzsche himself considers a randomised, prospective, double-blind clinical trial necessary to validate the theory.
In the Hungarian context, the work of Dr Béla Pál Bózsik deserves special mention; he is a key figure in domestic Lyme disease research and diagnostics and has particularly emphasised the significance of direct detection methods. He was the first, and to date the only one, to demonstrate the presence of Borrelia in archived samples from patients with multiple sclerosis using immunofluorescence testing, which has remained one of the strongest pillars of the infectious hypothesis ever since. In addition, he presented numerous clinical cases at conferences in which treatment with Borrelia resulted in the complete resolution of MS symptoms.
The counterpoint emphasises the distinct characteristics of the two syndromes;
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Schmutzhard’s 1989 study, by contrast, explicitly states that although tertiary Lyme disease affecting the central nervous system is a genuine entity, it is distinct from multiple sclerosis, and there is no proven aetiological link between the two diseases. According to the author, neuroborreliosis may be a ‘great mimic’, i.e. it may clinically mimic MS-like conditions, but this does not make it identical to MS. Schmutzhard’s main argument is that the age-related, clinical, cerebrospinal fluid, epidemiological and demographic characteristics of the two diseases differ from one another.
Schmutzhard considers cerebrospinal fluid findings to be particularly decisive. In his view, in MS, the elevation in cerebrospinal fluid protein and cell count is generally mild, whereas in progressive borreliotic encephalomyelitis, significantly higher protein levels and more pronounced pleocytosis may occur. Furthermore, the detection of Borrelia-specific intrathecal antibody production is crucial in the diagnosis of neurological complications of Lyme disease, whereas this is usually absent in MS. A subsequent study by Heller also emphasised that the two conditions may be clinically and cerebrospinal fluid-wise similar, but can be distinguished using immunological methods.
Schmutzhard’s theory, however, is based on circular reasoning, since although the diagnosis of neuroborreliosis is debatable, a mandatory component is the presence of positive anti-Borrelia antibody levels in serum-CSF pairs, as well as pleocytosis. The sensitivity of laboratory diagnosis of neuroborreliosis based on this principle is unknown, and it cannot be ruled out that these tests actually cover only a fraction of Borrelia infections of the nervous system. It is no coincidence that experts are advocating the use of newer diagnostic methods, such as CXCL13, which is elevated not only in neuroborreliosis but also in MS patients. Furthermore, the epidemiological and demographic references are also flawed, as total and severe Borrelia infections show a similar female predominance to that seen in MS cases.
Can the laboratory decide?
In his article outlining his theory, however, Fritzsche not only examines the statistical correlations but also lists the evidence from human and animal studies available up to that point regarding the presence of Borrelia in MS patients, which provides convincing arguments. Among the methods based on direct detection, he presents several that have confirmed the presence of the pathogen in sclerotic brain tissue or cerebrospinal fluid.
Other studies present a mixed picture. Some early serological studies found no convincing link between Borrelia infection and MS, whilst others reported higher Borrelia seropositivity in MS patient groups. However, most studies include in the borreliosis group only those patients who meet the strict criteria for neuroborreliosis and demonstrate an antibody response in the cerebrospinal fluid. If these strict criteria are not applied, the results show a stronger correlation. For example, a Polish seroepidemiological study published in 2000 found a statistical association between clinically confirmed MS and positive Borrelia serology. It is important to note here that the seroprevalence measured in the control group corresponds to the general Central European level determined in meta-analyses (19.4% versus 20.7%), whilst the data for MS patients corresponded to the general sensitivity typical of Lyme serological tests (38.5% versus 39–43%).
Summary and clinical conclusion
Overall, it can be stated that there is clinical and immunological overlap between Lyme borreliosis and multiple sclerosis, and that neurological involvement in Lyme disease may present with MS-like features in certain cases. Based on Fritzsche’s observations, it is worth keeping open the possibility that Borrelia may play a role in initiating or maintaining the demyelination process in certain patients. Schmutzhard’s critique, however, warns that classic MS and proven tertiary neuroborreliosis cannot be conflated as long as the diagnosis of neuroborreliosis is based on clinical, cerebrospinal fluid and immunological criteria. Direct detection tests and CXCL13 or similar new biomarkers, however, bring the two differing views closer together.
The final conclusion is therefore that a Lyme origin for MS cannot be regarded as a generally proven fact, nor can it simply be dismissed as an irrelevant hypothesis. Fritzsche’s hypothesis, Dr Béla Pál Bózsik’s immunofluorescence observations, correlations in CXCL13 levels, the significant matches in verified serum antibodies, the efficacy of combined Lyme treatments on MS symptoms, and the cases of neurological complications of Lyme disease mimicking MS, together justify further investigation into the link between MS and Borrelia. However, this would require not primarily serological comparisons, but direct pathogen detection, standardised immunofluorescence or molecular methods, as well as large-scale, controlled clinical trials.
A very important conclusion for clinicians is that a potential infectious background must be investigated in every case, not only in relation to neuroborreliosis—which involves strict criteria requiring tests of unknown sensitivity—but also in relation to infections that can be confirmed by general Lyme disease tests. MS is a condition of unknown origin that can only be treated symptomatically, whereas Lyme disease is, in most cases, a curable infection.
Sources:
https://pubmed.ncbi.nlm.nih.gov/15617845/
https://pubmed.ncbi.nlm.nih.gov/2686768/
https://pubmed.ncbi.nlm.nih.gov/2074447/
https://pubmed.ncbi.nlm.nih.gov/2725867/
https://pubmed.ncbi.nlm.nih.gov/11153045/
https://lymediagnostics.com/2019/04/16/interview-dr-bela-bozsik/
(C) Lyme Borreliosis Foundation
