Borrelioosiin sairastuneiden henkilökohtaisia kokemuksia taudista ja sen hoidosta.

Valvojat: Bb, Sailairina, maranoma, Tiina


ViestiKirjoittaja soijuv » To Marras 26, 2009 12:04

Borreliabakteeri aiheutti 33-vuotiaalle miehelle silmäoireita; näkökenttäpuutos, näkökyvyn heikentyminen, vähäinen näköhermon turvotus.

Neurol Sci

DOI 10.1007/s10072-009-0175-y


Borrelia burgdorferi, a great chameleon: know it to recognize it!

Iolanda Santino ? Paola Comite ? Giuseppe Maria Gandolfo

Received: 11 December 2008 / Accepted: 13 October 2009

Springer-Verlag 2009


Borrelia burgdorferi is a spirochaete that can penetrate the blood?brain barrier in early infection and can cause endothelial damage other than central nervous system lesions. We describe a clinical case of neuroborreliosis that occurred in the absence of classical erythema migrans or arthralgia. Magnetic resonance imaging findings compatible with simil-vasculitis and demyelinating lesions associated with the presence of anti-B. burgdorferi antibodies in the plasma or cerebrospinal liquid is an indication for antimicrobial treatment against B. burgdorferi. An early diagnosis and a prompt establishment of an adequate antibiotic treatment is needed for a successful recovery.

Keywords Neuroborreliosis  Multiple sclerosis  Vasculitis  Borrelia burgdorferi


Lyme borreliosis (LB) is a well recognized multisystem disorder caused by spirochaetes belonging to the genospecies complex Borrelia burgdorferi sensu lato. Borrelia is transmitted to humans by the bite of infected ticks belonging to the genus Ixodes spp. [1].

The infection begins as a cutaneous lesion followed, weeks or months later, by arthritic, cardiac or neurological manifestations [1]. Neurologic disorders may occur in early disseminated or late chronic Lyme borreliosis. In particular, persisting borreliosis often affects the central nervous system with demyelinating lesions which may be misdiagnosed as multiple sclerosis (MS).

In addition, Lyme disease can cause a variety of neuro-ophthalmologic manifestations [2, 3].

LB is the most common tick-borne infection in Europe and it is also present in Italy where it is endemic in some regions of the northern part of the country, although is known to occur also in other Italian regions. In Latium, clinical cases of Lyme disease in humans have been reported and Borrelia species have been identified in ticks [4?8].

In this report, we describe a clinical case of neuroborreliosis that occurred in the absence of classical erythema migrans or arthralgia. The diagnosis of Borrelia infections was achieved through a meticulous evaluation of the clinical, radiological and laboratory data.

Case report

The patient was a 33-year-old male living in the centre of Italy. He presented a central scotoma in right eye in May. On ophthalmologic examination, visual acuity was decreased to 4/10 in the right eye and 10/10 in the left. No fundus? alteration was observed, except a light papilloedema.

The neurological examination showed no alteration. Neither extra signs nor symptoms were found. The motor and somatosensory evoked potentials were normal. The visual evoked potentials were lightly decreased.

I. Santino (&) Department of Public Health Sciences, Sapienza University of Rome, P.le Aldo Moro, 5, 00185 Rome, Italy e-mail: P. Comite  G. M. Gandolfo Department of Experimental Medicine and Pathology, Sapienza University of Rome, P.le Aldo Moro, 5, 00185 Rome, Italy 123

Neurol Sci

DOI 10.1007/s10072-009-0175-y

Blood count, serum inflammatory markers, thyroid profile, autoimmunity screening (ANA, ENA, anti-DNA, C3, C4, circulating immunocomplexes), thrombophilia screening (antithrombin, protein C and protein S, factor V Leiden, homocysteine, lupus anticoagulant, anti-cardiolipin, anti-beta2 glycoprotein) were within normal limits.

IgG and IgM anti-B. burgdorferi antibodies were found in blood. The differential diagnosis included TPHA test for Treponema pallidum, Parvovirus B, EBV, CMV, HIV, hepatitis viruses were negative. No fever was present.

In addition, examination of the cerebrospinal fluid (CSF) showed the presence of white blood cells with lymphocytic predominance without any malignant cells. CSF glucose levels were normal, CSF total proteins were increased and no oligoclonal IgGs were observed.

Eventual presence of demyelinating lesions or neoplasms affecting the nervous system was investigated by magnetic resonance imaging (MRI) scan of the brain and cervical spine with and without contrast.

Bilateral multifocal cerebral lesions, apparently consistent with a possible simil-vasculitic involvement of cerebral parenchyma were observed in the brain. Moreover, an area of altered signal intensity was described in supraventricular area. Altered signal intensity was observed in T2-weighted sequence at C3?C5. No enhancement of the cerebral and spinal lesions occurred upon injection of mean of contrast.

An electrocardiogram (ECG) was performed and it was normal. The patient did not have a prior history of infection or vaccination, neither any evidence of typical signs and symptoms of acute disseminated encephalomyelitis [9].

None of the diagnostic criteria of fibromyalgia was present [10]. There was also no history, symptoms or imaging findings to suggest a granulomatous-type process like neurosarcoidosis.

The initial diagnosis was then monolateral optic neuritis with demyelinating lesions.

Upon corticosteroid therapy (5 days intravenous methylprednisolone, 1 g/daily) neuritis symptoms disappeared with recovery of the visual acuity on the right eye (10/10 in the right eye and 10/10 in the left).

We decided to make another serum sample to assess the further evaluation of antibodies titre to B. burgdorferi and for the detection of Borrelia antigens by Western Blot. At this stage, the presence of IgG and IgM antibodies to B. burgdorferi was investigated using a commercially available immunoenzymatic assay (ELISA) (recomWell IgM/IgG, Mikrogen, Neuried, Germany) and Western blot (ViraBlot IgM/IgG, Viramed Biotech AG) tests according to the manufacturer?s instructions. ELISA tests were considered negative, positive or borderline when values were lower than 20, higher than 24 or between 20 and 24 U/ml, respectively as suggested by the manufacturer. Western Blot IgM test was considered positive for the presence of 2/3 significant bands: 24 kDa (OspC), 39 kDa (BmpA), and 41 kDa (Fla). Western Blot IgG test was considered positive for the presence of 5/10 significant bands: 18, 21 kDa (OspC), 28, 30, 39 kDa (BmpA), 41 kDa (Fla), 45, 58 kDa (not GroEL), 66, and 93 kDa.

Elisa test showed evidence of specific IgM and IgG antibodies to B. burgdorferi. Western blot analysis showed four bands (60, 58, 41, 24 kDa) for IgM and six (60, 58, 41, 30, 24, 18 kDa) for IgG.

Finally, the serum of the patient was further analysed with the technique of polymerase chain reaction (PCR) developed in our laboratory [8] that has confirmed the positivity to B. burgdorferi s.l.

Based on clinical picture and microbiological data, an active Borrelia infection with involvement of the nervous system, i.e. neuroborreliosis, was identified. This patient fulfilled the European clinical case definitions for Lyme borreliosis [11].

Accordingly an antibiotic therapy was started with i.v. ceftriaxone for 3 weeks. Two months after treatment, another sample of serum showed a decrease of IgM and IgG by Elisa (a reduction from 72 to 14 ng/ml). Eight months after the initial treatment there was no evidence of IgM and a mild improvement of IgG.

MRI with and without contrast were performed to monitor the potential evolution of demyelinating lesions at 3, 6, 12, 24, 36 months. No evidence of progression was found.

In the subsequent 3 years the patient has been well, he regularly underwent clinical and instrumental checkup and there were no recurrence of visual or other symptoms.


Lyme disease is known to cause intermittent neurologic events, include Bell?s palsy [12], nonspecific symptoms of numbness, fatigue, amnesia, headache, stroke-like syndromes, central nervous system vasculitis [13], encephalitis, myelitis, neuritis [14], nervous tumour-like lesions [15].

Most importantly, in this case report, demyelinating disease which mimics multiple sclerosis can also occur [16].

Essentially, Lyme disease is characterized from a phenotypic variability depending on stage. The prevalence has a seasonal incidence and disease manifestations are influenced by genetic diversity and differential distribution of spirochaete species. Arthritis appears to be more frequent in America, while encephalomyelitis occurs more often in Europe [17]. Furthermore, encephalomyelitis or myelitis is a relatively common complication in adults, rarely seen in children, while facial palsy is the most common paediatric neurological manifestation [18].

Neurol Sci


Because of limitations of laboratory tests the diagnosis is essentially clinical and one must be mindful that the laboratory testing is recommended if there is a clear evidence of the characteristic symptoms and signs of this disease. Nevertheless, the laboratory data and a correct interpretation of them are supportive to the clinical diagnosis.

The characteristic erythema migrans rash, the host reaction to the bite and the hallmark of the disease, is not often present [19].

Several studies have revealed than less than 50% of the patients recalled a tick bite [20, 21].

In addition, in some cases, especially those with involvement of central nervous system, signs and symptoms overlapping with several pathological conditions can occur and an accurate differential diagnosis must be done.

Although already shown as an emerging problem, Borrelia infection is often misdiagnosed: only one out of ten cases of Lyme disease is reported to the Control Disease Center (CDC).

In our case, according to criteria of International Lyme and Associated Diseases Society, we have searched for Lyme disease in a patient living in a area where the Borrelia is present [4?6], with systemic signs and symptoms compatible with Borrelia infection and that, subsequently, has shown the seropositivity, the seroconversion on paired sera, the antigen and DNA recovery, and finally the response to prescribed treatment. They are sufficient data to consider the diagnosis compatible with a ??borreliosis?? [22].

In the case we report hereby, the laboratory analysis has a crucial role in confirming the diagnosis of Lyme disease. In fact, in primary and in secondary stage, especially in the case of neuroborreliosis, the antibody profile of the patient is often unclear and hard to distinguish from the profile of a healthy subject previously exposed to Borrelia. Additionally, the laboratory test might be untruthfully negative (the so-called ??seronegative Lyme disease??), as it might the case for those clinical reports of patients with equivocal serology tests and neurological symptoms and MRI findings consistent with MS, treated successfully with antibiotic therapy [23].

However, in our case the strong positivity of IgM and IgG in the serum associated to other reported clinical and instrumental data of the patient suggested the final diagnosis.

Spinal taps are not routinely recommended, as a negative tap does not rule out Lyme. Especially, not all patients with neuroborreliosis have CSF abnormalities. Most patients with neuroborreliosis have specific antibodies in serum and testing for CSF antibodies is usually not necessary [24]. Specific antibodies in the CSF are present in 40?85% of cases. Furthermore, in neuroborreliosis the oligoclonal bands may be present, but they are not typically expressed [24, 25].

Although the mechanism underlying the involvement of nervous system in Lyme disease remains unclear, it is speculated that it may be a direct or an indirect action of the spirochaete on neural cell, which may explain development of vasculitis associated with opthalmo-neuropathy [26].

Most likely B. burgdorferi can act as a trigger for T-cell mediated autoimmune reactions within the CNS, exhibiting a molecular mimicry with human nervous tissue, especially for myelinated fibres of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells, joint synovial and heart muscle cells [27].

In conclusion, our report confirms that in daily clinical neurological practice Borrelia microbiological investigation is a crucial step for identification of neuroborreliosis and for optimal therapy. The successful follow-up after 3 years demonstrates the importance of systematic investigation of these bacteria in several neurological conditions to promptly establish an adequate antibiotic treatment. In particular it is recommended to investigate possible exposure to Lyme disease even when classical symptoms could be missing.


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3. Stricker RB, Lautin A (2003) Lyme disease and optic neuritis: long-term follow-up of seropositive patients. Neurology 61:1162

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Neurol Sci


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Neurol Sci
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