Neuroborreliosis in a patient with Multiple Sclerosis on Ocrelizumab, a case report

doi:10.21203/rs.3.rs-2874360/v1

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Neuroborreliosis in a patient with Multiple Sclerosis on Ocrelizumab, a case report

https://doi.org/10.21203/rs.3.rs-2874360/v1

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Introduction

Borreliosis is one of the most common vector-borne diseases in Europe that can affect the central nervous system.

Case Presentation

A 41-jears old female MS-Patient presented to our emergency department with Nausea and Headache that did not respond to painkillers. She was on Therapy with Ocrelizumab for two years without noticing disease activity. The results from both the lumbar puncture and laboratory tests confirmed an active infection with Borrelia burgdorferi. The patient was treated with Ceftriaxon intravenously for one week and Doxycyclin for another week with complete resolution of the symptoms.

Conclusion

We report the first case of neuroborreliosis in a patient under CD-20 depletion. Neuroborreliosis was treated with antibiotics with complete remission of the symptoms. The diagnosis of neuroborreliosis could be challenging in clinical practice and should be considered in MS patients with fatigue, especially in endemic areas.

Neroborreliosis

Ocrelizumab

case report

Borreliosis is one of the most common vector-borne diseases in Europe, is caused by Borrelia burgdoferi and is transmitted by ticks of the Ixodes Ricinus complex. It is characterized by different neurologic, dermatologic, rheumatologic, and cardiac symptoms; the immune response to borreliosis is complex and includes the participation of a variety of cell types and molecules based on the organ system affected by infection with this pathogen.

Ocrelizumab is an FDA-approved CD20-depleting therapy with remarkable efficacy against active MS and a favorable way of administration every six months (Montalban et al., 2023). Since it is a relatively new treatment option in the market, it is important to understand its safety profile. It is believed that this treatment will play a significant role in managing MS in the future. In this report, we present a case of Neuroborreliosis in a patient under CD20 depletion with Ocrelizumab.

The presentation of the 41-year-old female patient was due to headaches with nausea and vomiting, which have been present for about 2 weeks. The headaches began from the cervical spine area and radiated to both temples, with initial pain intensity of 4–5/10 on the Numeric Rating Scale (NRS). In addition to their other complaints, the patient reported experiencing pressure behind both eyes. She sought medical attention from her family doctor and was prescribed ibuprofen 600 mg up to 3 times a day and metamizole 500mg up to 3 times a day. Due to known problems with her cervical spine, the patient also consulted an outpatient orthopedist, who recommended adapted analgesics as needed. Despite a daily intake of ibuprofen 600mg 3 times a day and metamizole 500mg 3 times, the headaches did not improve. Multiple sclerosis had been known since 2006 and is currently being treated with ocrelizumab. Her previous DMT was Interferon but she switched to Ocrelizumab 2 years ago. A couple of years ago, a tick bit her, and weeks after that, she developed a rash.

On magnetic resonance imaging (MRI) of the head, several older MS-typical lesions were found supratentorially, periventricularly, and juxta-cortically. A lesion measuring up to approximately 1.5 cm was found right periventricularly. After contrast agent administration, we were unable to objectively demonstrate any active lesions.

In the cerebrospinal fluid, we saw a significant increase in cell count (573 cells) accompanied by lactate and protein increases, so we treated the patient with aciclovir and ceftriaxone intravenously as an urgent suspicion of meningoencephalitis with a subacute course. The Reiber diagram showed a barrier disturbance with intrathecal IgM synthesis; the IgG and IgM antibodies for Borrelia were positive in both the serum and the cerebrospinal fluid. The PCR panel in the cerebrospinal fluid showed no evidence of viral infection. JC virus DNA was not detected in the cerebrospinal fluid.

After ruling out herpes infection, intravenous aciclovir therapy was discontinued. Ceftriaxone was given for a total of 7 days. During the course of treatment, the patient's symptoms improved significantly. By the second day of hospitalization, the patient no longer experienced headaches or dizziness. After 7 days (with clinical improvement, no symptoms, and confirmed Borrelia infection in the serum and cerebrospinal fluid) we decided to switch from ceftriaxone to doxycycline (which can be taken orally) and discharge the patient to home care.

To our knowledge, this is the first case report that describes neuroborreliosis in a patient under Ocrelizumab. A narrative review for this adverse event in Pubmed did not yield any relevant works. Some case reports describe neuroborreliosis in Patients treated with Rituximab, another CD-20 depleting therapy. In these two cases, Neuroborreliosis was seronegative, the diagnosis was secured after PCR testing for B.burgdoferi in cerebrospinal fluid (Wagemakers et. al 2018, van Dop et. al 2013). According to the latest EFNS guidelines, the diagnosis of Lyme neuroborreliosis requires neurological symptoms suggestive of Neuroborreliosis, pleocytosis in cerebrospinal fluid, and intrathecal antibody production against Borrelia burgdorferi (Mygland et. al 2010). However, in immunocompromised patients, such as MS patients under Ocrelizumab, the diagnosis could be challenging and should also include PCR testing in cerebrospinal fluid.

Moreover, Lyme neuroborreliosis can have a chronic course and this may affect the level of the plasma neurofilaments light chain levels, as treatment with antibiotics significantly decreases the level of the neurofilaments in patients with Lyme disease without persistent symptoms (Mens et al., 2023). Nowadays this may influence clinical practice as the level of neurofilaments plays an important role in decisions about treatment and disease activity (Benkert et al., 2022). Moreover, even after treating Borreliosis, the patients report more fatigue and severe fatigue (Andreassen et al., 2023). Early diagnosis of Neuroborelliosis in patients with multiple sclerosis can prevent the development of fatigue. It is possible that an underlying Neuroborelliosis could be a contributing factor to the fatigue experienced by many multiple sclerosis patients. Contrarily to most viral infections of the central nervous system, antibiotic therapy with ceftriaxone or doxycycline is effective against an acute infection with Borrelia. Regarding our patient, we must consider the possibility of a reactivation of Borrelia since she was bitten by a tick and developed a rash two years ago. It is likely that she was infected at that time.

Infections are one of the most common serious adverse events, according to the long-term follow-up of the ORATORIO study with 4.13 (95% CI 3·45–4·91) per 100 patient-years (Wolinsky et. al 2020). In the OPERA I, OPERA II and ORATORIO phase 3 clinical trials the most common adverse events are infusion-related reactions (Mayer et. al 2019). More evidence with longitudinal data is needed to establish the safety profile of Ocrelizumab in patients with MS (Ng et. al 2020).

Funding

No funding was received.

Conflicts of interest/Competing interests (include appropriate disclosures)

The authors declare that there is no potential conflict of Interest.

Ethics approval (include appropriate approvals or waivers)

Not applicable

Consent to participate

The patient was hospitalized in our hospital and provided an informed consent to publish this case.

Written Consent for publication (include appropriate statements)

The patient was hospitalized in our hospital and provided an informed consent to publish this case.

Data availability statement

No aplicable

Code availability

Not applicable

Authors' contributions

All the authors contributed to the diagnosis and treatment of the patient. Stamatellos VP has written the present manuscript, the other authors have contributed to manuscript editing .

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Neuroborreliosis in a patient with Multiple Sclerosis on Ocrelizumab, a case report

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Introduction

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