Enhancement of cranial nerves in Lyme neuroborreliosis: incidence and correlation with clinical symptoms and prognosis

Purpose Symptoms of cranial neuritis are a common presentation of Lyme neuroborreliosis (LNB). Imaging studies are scarce and report contradictory low prevalence of enhancement compared to clinical studies of cranial neuropathy. We hypothesized that MRI enhancement of cranial nerves in LNB is underreported, and aimed to assess the prevalence and clinical impact of cranial nerve enhancement in early LNB. Methods In this prospective, longitudinal cohort study, 69 patients with acute LNB were examined with MRI of the brain. Enhancement of cranial nerves III–XII was rated. MRI enhancement was correlated to clinical findings of neuropathy in the acute phase and after 6 months. Results Thirty-nine of 69 patients (57%) had pathological cranial nerve enhancement. Facial and oculomotor nerves were most frequently affected. There was a strong correlation between enhancement in the distal internal auditory canal and parotid segments of the facial nerve and degree of facial palsy (gamma = 0.95, p < .01, and gamma = 0.93, p < .01), despite that 19/37 nerves with mild-moderate enhancement in the distal internal auditory canal segment showed no clinically evident palsy. Oculomotor and abducens nerve enhancement did not correlate with eye movement palsy (gamma = 1.00 and 0.97, p = .31 for both). Sixteen of 17 patients with oculomotor and/or abducens nerve enhancement had no evident eye movement palsy. Conclusions MRI cranial nerve enhancement is common in LNB patients, but it can be clinically occult. Facial and oculomotor nerves are most often affected. Enhancement of the facial nerve distal internal auditory canal and parotid segments correlate with degree of facial palsy.publishedVersio

Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, noninferiority, double-blinded, randomised and placebocontrolled trial

Background There is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme neuroborreliosis (LNB). Methods The trial had a randomised, double-blinded, placebo-controlled, non-inferiority design. Patients with LNB were recruited from eight Norwegian hospitals and randomised to doxycycline 200 mg once daily for 2 weeks, followed by 4 weeks of placebo, or doxycycline 200 mg once daily for 6 weeks. The primary endpoint was clinical improvement as measured by difference in a Composite Clinical Score (0–64 points) from baseline to 6 months. The non-inferiority margin was predetermined to 0.5 points. Results One hundred and twenty-one patients were included. Fifty-two treated for 2 weeks and 53 for 6 weeks were included in the intention-to-treat analyses, and 52 and 51 in per-protocol analysis. Mean difference in clinical improvement between the groups was 0.06, 95% CI −1.2 to 1.2, p=0.99 in the intention-to-treat population, and −0.4, 95% CI −1.4 to 0.7, p=0.51 in the per-protocol population and non-inferiority could not be established. There were no treatment failures and no serious adverse events. The groups did not differ in secondary outcomes including clinical scores at 10 weeks and 12 months, cerebrospinal fluid data and patient-reported outcome measures. Patients receiving 6 weeks doxycycline reported slightly more side effects in week 5. Conclusion Our results strongly indicate that there are no benefits of doxycycline treatment beyond 2 weeks in European LNB.publishedVersio

Assessment of cognitive function, structural brain changes and fatigue 6 months after treatment of neuroborreliosis

publishedVersionPaid Open Acces

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.publishedVersio

Human seroprevalence of antibodies to tick-borne microbes in southern Norway

The tick Ixodes ricinus is widespread along the coastline of southern Norway, but data on human exposure to tick-borne microbes are scarce. We aimed to assess the seroprevalence of IgG antibodies to various tick-borne microbes in the general adult population living in a Norwegian municipality where ticks are abundant. Søgne is a coastline municipality in the southernmost part of Norway, and has a high density of ticks. All individuals aged 18-69 years with residential address in Søgne municipality (n = 7424) were invited to give a blood sample and answer a questionnaire. Blood samples from 3568 individuals were available for analysis. All samples were analyzed for IgG antibodies to Borrelia burgdorferi sensu lato (Bbsl), and around 1500 samples for IgG antibodies to other tick-borne microbes. Serum IgG antibodies to Bbsl were present in 22.0% (785/3568) of the tested samples, tick-borne encephalitis virus (TBEV) in 3.1% (45/1453), Anaplasma phagocytophilum in 11.0% (159/1452), Babesia microti in 2.1% (33/1537), Bartonella henselae/B. quintana in 0.1% (2/1451) and Rickettsia helvetica/R. conorii in 4.2% (60/1445). Serum IgG antibodies to A. phagocytophilum and R. helvetica/R. conorii were significantly more prevalent (p = 0.010 and p = 0.016, respectively) among individuals with serum IgG antibodies to Bbsl than among individuals without. In conclusion, our study showed a high exposure to Bbsl in the general adult population living in a coastline municipality in the southernmost part of Norway. The population is also exposed to A. phagocytophilum, R. helvetica/R. conorii, B. microti and TBEV, but very rarely B. henselae/B. quintana

Subjective health complaints and exposure to tick-borne infections in southern Norway

Objectives Whether tick‐borne infections can cause chronic subjective health complaints is heavily debated. If such a causal connection exists, one would expect to find more health complaints among individuals exposed to tick‐borne infections than among non‐exposed. In this study, we aimed to assess if exposure to tick‐borne infections earlier in life, evaluated by examination of serum for IgG antibodies to tick‐borne microbes, was associated with self‐reported somatic symptom load. Materials & Methods All individuals with residential address in Søgne municipality in southern Norway, aged 18‐69 years, were invited to participate in the study. Blood samples were analyzed for IgG antibodies to different tick‐borne microbes, and somatic symptom load was charted by the Patient Health Questionnaire‐15 (PHQ‐15). Results Out of 7424 invited individuals, 2968 (40.0%) were included in the study. We detected IgG antibodies to Borrelia burgdorferi sensu lato (Bb) in 22.9% (95% CI 21.4‐24.4). Bb seropositive individuals reported less frequently moderate to severe somatic symptom load (ie, PHQ‐15 sum score ≥ 10) than seronegative individuals (12.5% versus 17.7%, difference 5.2% [95% 2.1‐8.0]). However, when adjusting for several other variables in a multivariable linear regression model, presence of serum IgG antibodies to Bb was not associated with somatic symptom load. Presence of IgG antibodies to other tick‐borne microbes than Bb, or seropositivity to at least two microbes, was also not associated with somatic symptom load. Conclusion Presence of serum IgG antibodies to tick‐borne microbes was not associated with self‐reported somatic symptom load

Selective intrathecal enrichment of G1m1-positive B cells in multiple sclerosis

Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF). However, how these variants are implicated in disease mechanisms remains unknown. Here, we show that proliferating plasmablasts expressing the G1m1 allotype of IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients, whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme neuroborreliosis displayed oligoclonal IgG1 of both allotypes. This points to a disease-specific mechanism involved in B-cell establishment within the central nervous system in MS

Patient-reported outcome after treatment for definite Lyme neuroborreliosis

Objective To chart patient‐reported outcome measures (PROMs) in Norwegian patients treated for definite neuroborreliosis (NB). Material and Methods Adult patients treated for definite NB 1–10 years earlier supplied demographics, symptoms and treatment during NB, and answered validated questionnaires; Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), health‐related quality of life questionnaire (RAND‐36), and Patient Health Questionnaire (PHQ‐15). Results A higher proportion of NB‐treated persons reported severe fatigue, defined as FSS score ≥ 5, than in Norwegian normative data, but when removing persons with confounding fatigue associated comorbidities (n = 69) from the analyses, there was no difference between groups. Physical health‐related quality of life (RAND‐36 PCS), mean FSS score, proportions of persons reporting moderate or severe somatic symptom burden (PHQ‐15 score ≥ 10), anxiety (HADS‐A ≥ 8), or depression (HADS‐D ≥ 8) did not differ between NB‐treated persons and reference scores. Mental health‐related quality of life (RAND‐36 MCS) was poorer than in normative data (47.1 vs. 53.3), but associated with anxiety, depression and current moderate or severe somatic symptom burden, and not with NB characteristics. Conclusions Results on validated PROM questionnaires measuring fatigue, anxiety, depression, self‐reported somatic symptom burden, and physical health‐related quality did not differ between persons treated for definite NB 1–10 years earlier and reference scores. NB‐treated persons tended to report a slightly poorer mental health‐related quality of life than found in normative data, but when adjusting for confounders the causative connection is questionable. Overall, the long‐term prognosis of definite NB seems to be good

Cognitive function in patients with neuroborreliosis: A prospective cohort study from the acute phase to 12 months post treatment

Background Long-term cognitive problems after neuroborreliosis treatment remain a subject of debate. We have previously shown that cognitive problems are not present in the acute phase of neuroborreliosis, although fatigue is common. The aim of this study was to re-assess the same patient cohort and evaluate long-term outcomes. Methods In this follow-up, we re-assessed 58 patients with well-characterized neuroborreliosis 12 months after completing treatment. The same protocol with eight subtests measuring attention and processing speed and the Fatigue Severity Scale (FSS) were used to compare the results from the acute phase to 12 months post treatment. Results We found no changes in attention or processing speed but a reduction in the level of fatigue (median score on FSS: 4.9 vs. 3.9, p < .001) from the acute phase to 12 months post treatment. Conclusion The patient group did not develop problems with attention or processing speed post treatment, while the level of fatigue decreased