Randi Eikeland

• Franc, Strle,; Klemen, Strle,; Adriana, Marques,; J., Henningsson, Anna; Eikeland, Randi & E., Lemieux, Jacob [Vis alle 9 forfattere av denne artikkelen] (2026). Lyme borreliosis. Nature Reviews Disease Primers. 12. doi: 10.1038/s41572-026-00691-0. Fulltekst i vitenarkiv Vis sammendrag

  Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a zoonosis caused by several species of Borrelia burgdorferi sensu lato and transmitted by the bite of infected ticks of the Ixodes ricinus complex. Lyme borreliosis in North America and Europe differs in certain respects, likely reflecting the different Borrelia species that cause human disease in these locations. The earliest manifestation of Lyme borreliosis is the skin lesion erythema migrans, which develops at the tick bite site, typically 7–14 days after the bite. Some untreated patients will then (within the first few weeks or months after onset of the infection) develop additional erythema migrans skin lesions or other clinical manifestations such as borrelial lymphocytoma, nervous system involvement or carditis. Several months or even years after infection onset, Lyme arthritis or acrodermatitis chronica atrophicans may develop. The diagnosis of typical erythema migrans is clinical, whereas for all other manifestations the diagnosis is supported via serological testing. Treatment with an appropriate antibiotic will result in resolution of clinical symptoms in most patients; however, some patients experience prolonged subjective symptoms, which usually improve over time. Repeated courses of antimicrobials are not beneficial except in rare cases when there is objective evidence of treatment failure.

• Skarstein, Ingerid; Solheim, Anne Marit; Lorentzen, Åslaug Rudjord; Ljøstad, Unn; Mygland, Åse Daasvand & Eikeland, Randi [Vis alle 11 forfattere av denne artikkelen] (2026). Dynamics of IgM and IgG responses in Lyme neuroborreliosis – a Norwegian longitudinal study. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. doi: 10.1007/s10096-026-05632-z. Fulltekst i vitenarkiv Vis sammendrag

  Purpose We investigated longitudinal antibody responses against 13 different Borrelia burgdorferi (Bb) antigens in patients with Lyme neuroborreliosis (LNB) and explored whether antibody profiles were linked to length of symptoms and burden of symptoms prior to and after initiation of treatment. Methods A well-characterized cohort of 106 patients of whom 85% had definite LNB were followed for twelve months, with serum and cerebrospinal fluid (CSF) sampled at baseline, six- and twelve-months follow-up. Antibodies were measured by the recomBead Borrelia IgG and IgM assay, with a subgroup examined for oligoclonal IgG production restricted to CSF. Results Antibody levels in both serum and CSF declined gradually after antibiotic treatment, with most of the reduction occurring within the first six months after treatment. Higher baseline IgM reactivity against p18 in both serum and CSF was associated with higher symptom burden prior to treatment. We found no differences in CSF antibody reactivity between patients with short (< 42 days) and long (≥ 42 days) symptom duration prior to treatment. In serum, patients with short symptom duration prior to treatment had higher IgM reactivity against p58 and higher IgG reactivity against OspC and p18. At baseline, 68% exhibited oligoclonal IgG production, falling to 41% six months after treatment. There was no correlation between oligoclonal IgG production and symptom burden. Conclusion Both specific antibody production against a variety of antigens and intrathecal oligoclonal IgG production decreased after treatment for LNB, reflecting reduced antigenic load and thus reduced neuroinflammation. IgM and IgG reactivity against p18 were indicative of a shorter symptom duration and higher symptom burden prior to treatment.

• Skudal, Hilde Kristin; Lorentzen, Åslaug Rudjord; Stenstad, Tore; Paulsen, Else Quist; Fevang, Børre & Jaioun, Keson [Vis alle 10 forfattere av denne artikkelen] (2026). Long-term patient-reported neurocognitive and functional outcomes after tick-borne encephalitis: a prospective controlled multicenter cohort study. Journal of Neurology. ISSN 0340-5354. 273. doi: 10.1007/s00415-026-14095-3. Fulltekst i vitenarkiv Vis sammendrag

  Objective To characterize cognitive symptoms the first year after tick-borne encephalitis (TBE). Methods We conducted a controlled, multicenter cohort study of 109 hospitalized patients ≥16 years with confirmed TBE in Norway. At 3 and 12 months after admission, patients completed BRIEF-A (Global Executive Composite (GEC) and subscales), Everyday Memory Questionnaire-Revised (EMQ-R), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessing executive functioning, memory, and post-TBE symptoms (higher scores indicate more difficulties). The primary outcomes were within-patient change in questionnaire scores from 3 to 12 months, and 12-month scores in patients compared to controls. The secondary outcomes were BRIEF-A subscale scores and proportion with clinically significant impairment. Covariates included in the analyses were age, sex, comorbidities, acute disease severity, anxiety, and depression. Results There were no significant changes from 3 to 12 months. At 12 months, scores were within the normal range, but patients had higher EMQ-R and RPQ than controls ( p <0.001). BRIEF-A GECs did not differ, but patients had higher working memory subscale scores ( p =0.002). These differences persisted after adjustment for anxiety and depression. Clinically significant impairment was more frequent in patients (odds ratios 2.29–8.19). Comorbidities, acute disease burden, anxiety, depression and female sex were associated with unfavorable 12 month outcome. Conclusion TBE patients have an overall good one-year prognosis, but a minority—characterized by higher acute disease burden and comorbidities—have persistent cognitive difficulties that may warrant follow-up. Anxiety and depression were related to unfavorable prognosis but did not account for the cognitive differences between patients and controls.

• Berg, Kristine Karlsrud; Sarjomaa, Marjut; Tveten, Yngvar; Thilesen, Carina Merethe; Fell, Anne Kristin M. & Nordbø, Svein Arne [Vis alle 8 forfattere av denne artikkelen] (2026). Prevalence of severe fatigue after SARS-CoV-2 infection in Norway: a prospective 2-year follow-up study. BMJ Open. 16(3). doi: 10.1136/bmjopen-2025-104338. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: This study aims to estimate the prevalence of long-lasting severe fatigue and identify possible risk factors in a 2-year follow-up of patients with predominantly mild-to-moderate SARS-CoV-2 infection. Design: Prospective cohort study. Setting A community-based cohort from Telemark and Agder Counties, Norway. Participants A total of 159 PCR-confirmed SARS-CoV-2 positive individuals in the period between 28 February and 17 December 2020 were included at 12 months after SARS-CoV-2 infection, and 93 responded at 24 months follow-up. Outcome: measures Fatigue was assessed using the Fatigue Severity Scale (FSS), and health-related quality of life using the RAND version of health-related quality of life Short Form 36 (SF-36), developed by the RAND Corporation. SARS-CoV-2 antibodies were measured at 12 and 24 months. Results: Severe fatigue (FSS ≥5) was reported by 36% at 12 months and 31% at 24 months. A higher proportion of women than men reported severe fatigue at 12 months (p=0.08). The number of acute-phase symptoms was associated with severe fatigue. No association was found between severe fatigue and anti-SARS-CoV-2 antibody levels, demographic variables or reinfection status. The severe fatigue group scored significantly lower on all domains of SF-36. Conclusion: In this cohort, severe fatigue was common, greatly impacted quality of life and persisted for up to 2 years following SARS-CoV-2 infection. Fatigue severity was associated with symptom burden in the acute phase but not with antibody levels or other demographic variables. These findings underscore the need for long-term follow-up and support for affected individuals.

• Eikeland, Randi & Andreassen, Silje (2025). Lyme Neuroborreliosis - Cognitive Function and Medically Unexplained Symptoms. What Do We Know? I Halperin, John (Red.), Lyme Disease: An Evidence Based Approach. CABI Publishing. ISSN 9781800626201. s. 281–288. doi: https:/www.cabidigitallibrary.org/doi/10.1079/9781800626225.0015. Fulltekst i vitenarkiv
• Skudal, Hilde Kristin; Stenstad, Tore; Lorentzen, Åslaug Rudjord; Paulsen, Else Quist; Egeland, Jens & Fevang, Børre [Vis alle 12 forfattere av denne artikkelen] (2025). Tick-borne encephalitis in Norway: A cohort study of clinical course and health-related quality of life at three- and twelve-month follow-up. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. doi: 10.1007/s10096-025-05341-z. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Knowledge of tick-borne encephalitis (TBE) prognosis is limited. This study aimed to describe the disease course in the first year and assess one-year outcomes, focusing on clinical recovery and health-related quality of life (HR-QoL). Methods: In this cohort study, we recruited hospitalized patients ≥ 16 years with confirmed TBE from hospitals in Norway’s endemic area. A composite clinical score consisting of variables on symptoms and neurological findings was scored at baseline (during hospitalization), 3- and 12 months. HR-QoL at 12 months was measured using RAND 36-item short form health survey and compared to the Norwegian reference population. Results: Among the 93 patients included, clinical improvement from baseline to 3 months was 68%, increasing to 77% by 12 months. The proportion of patients with symptoms or neurological findings influencing daily life was 98% at baseline, 52% at 3 months, and 41% at 12 months. 14% required inpatient rehabilitation, and 4/56 (7%) of active workers were on full-time sick leave at 12 months. Severe disease and comorbidities were linked to poorer outcomes. Most common symptoms influencing daily life at 12 months were fatigue (28%), concentration issues (13%) memory and sleep difficulties (12% each), while 8% had clinical findings where impaired balance and tremor dominated. Patients scored lower in physical health and social functioning regarding HR-QoL than reference population. Conclusion: Most improvements occur during the first three months; however, 41% of patients experience ongoing complaints at 12 months, impacting HR-QoL regarding physical health. Severe disease and comorbidities correlate with poorer prognoses.

• Sarjomaa, Marjut Anneli; Berg, Kristine Karlsrud; Jaioun, Keson; Tveten, Yngvar; Kersten, Hege & Reiso, Harald [Vis alle 12 forfattere av denne artikkelen] (2025). SARS-CoV-2-specific humoral immunity in a Norwegian cohort between 2020 and 2023. BMC Medicine. 23, s. 1–14. doi: 10.1186/s12916-025-04171-2. Fulltekst i vitenarkiv Vis sammendrag

  Background: We have previously reported on natural humoral immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Norwegian cohort between 2020 and 2021. In this study, we evaluated long-term humoral (including vaccination-induced) immunity in the same cohort and assessed predictors of high antibody levels against spike protein, as well as the persistence of antibodies against the virus spike and nucleocapsid proteins. Methods: Vaccination data and antibody levels against the spike and nucleocapsid proteins were collected at 12 (only in infected participants) and 24 months (in both infected and uninfected participants) after the participants’ first polymerase chain reaction (PCR) tests for the virus. Antibody levels against spike protein at 24 months were categorized as high or low based on the 50th percentile. Possible predictors of high antibody levels against spike protein were examined using univariate and multivariate logistic regression models. Results: Of 1119 original participants (400 PCR + and 719 PCR −), 574 responded to our questionnaires and were invited to antibody measurements (median age: 51 years; women: 59%). Vaccination data showed that 11% were fully immunized, and 85% were booster-immunized at 24 months. Antibody levels were evaluated in 72% (287/400) of the PCR + participants at 12 months and 58% (233/400) at 24 months. At 12 and 24 months, we observed that 97% (278/287) and 100% (233/233), respectively, still had antibodies against the spike protein, and 86% (248/287) and 95% (221/233), respectively, against the nucleocapsid protein. Antibody levels were also evaluated in 34% (247/719) of those in the PCR − group, which revealed that 99.5% and 69% had detectable antibodies against spike and nucleocapsid proteins, respectively, at 24 months. Irrespective of pre-vaccination SARS-CoV-2 infection status, the boosterimmunized participants were 3.7 × more likely to have high antibody levels against spike protein vs the non-boosterimmunized ones. Those aged > 60 years had the highest median antibody levels against the spike protein and were more likely to be booster-immunized. Conclusions: Our findings highlight the benefits of booster vaccinations for humoral immune responses. Long-term antibody levels against the SARS-CoV-2 spike protein were higher in booster-immunized participants vs the nonbooster- immunized, irrespective of pre-vaccination infection status.

• Raffetin, Alice; Henningsson, Anna J.; Ornstein, Katharina; Arias, Pauline; Fingerle, Volker & Patrat-Delon, Solene [Vis alle 22 forfattere av denne artikkelen] (2025). Towards shortening the duration of antibiotic therapy for Lyme borreliosis: a systematic review and meta-analysis. Infection. ISSN 0300-8126. 53, s. 809–830. doi: 10.1007/s15010-025-02501-3. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Systematic review and meta-analysis on shortening antibiotic therapy for Lyme borreliosis (LB) patients. Methods Data sources: Medline, Google, and Google Scholar (queried from January 2022-February 2024), following the PRISMA method and the Cochrane Handbook. Eligibility criteria: Randomized clinical trials, comparative studies; clear definitions of LB, duration of antibiotics and outcome; follow-up ≥ 6–12 months. Meta-analysis included studies that examined three outcomes: treatment failure; residual symptoms; adverse events. Intervention: Short vs. extended antibiotic therapy for erythema migrans (≤ 10 days vs. > 10 days) and disseminated LB (≤ 21 days vs. > 21 days). Assessment of risk of bias. Independently, using the Cochrane Tools. Methods of data synthesis. Estimation of treatment effects based on a fixed-effect model (Mantel–Haenszel or Peto method), with odds ratio (OR) and 95% confidence intervals (CI). Results Thirty-eight full-text articles were examined (850 patients): 29 were included in the qualitative analysis; six in the meta-analysis. Heterogeneity was low (I2 = 0%). At 12 months, short-term treatment did not differ from long-term treatment in terms of failures (OR1.50, 95%CI[0.43–5.22]) and residual symptoms (OR0.95, 95%CI[0.66–1.37]), albeit with small samples. Conclusion This meta-analysis was underpowered to prove non-inferiority of shorter treatment, but suggests its safety for EM. Studies focusing on antibiotics duration, with sufficient sample sizes and clear outcomes, are warranted.

• Dessau, Ram Benny; Raffetin, Alice; Eikeland, Randi; Fingerle, Volker; Henningsson, Anna J. & Hunfeld, Klaus-Peter [Vis alle 14 forfattere av denne artikkelen] (2025). The choice of study designs of diagnostic accuracy using Borrelia specific IgG and IgM antibodies for the diagnosis of Lyme borreliosis. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 31(8), s. 1307–1312. doi: 10.1016/j.cmi.2025.04.001. Fulltekst i vitenarkiv Vis sammendrag

  Background Laboratory diagnosis of Lyme borreliosis (LB) is used in a variety of clinical settings where a range of other diagnoses may be considered. Therefore, it is essential that diagnostic accuracy studies and literature reviews consider information from different types of studies and choices of sample groups. The quality of patient selection is important to minimize the risk of misclassification. This narrative review was inspired by systematic reviews where nearly all studies on the diagnostic accuracy for LB tests were determined as biased and having low quality based solely on study design considerations—not the clinical relevance. Objectives To propose flexible design and interpretation of studies used to assess diagnostic accuracy in clinical microbiology. Sources Criteria for rating the quality of studies were discussed among the ESCMID study group for LB ESGBOR (The ESCMID study group for Lyme borreliosis). The literature was searched for similar methodological discussions. Content Knowledge of antibody reactivity in the background population across various clinical patient groups with and without infection should consider variations in clinical presentation and duration of disease. Case-control studies are the most frequently used design and were judged particularly instrumental in assessing serologic testing. However, clinical and epidemiological studies not specifically intended for diagnostic accuracy may also contribute estimates of sensitivity and specificity. Systematic reviews should focus on the application of the diagnostic assay for the individual patient in various clinical settings, rather than seeking an unbiased average. Different LB sample groups and controls for test panels are discussed. Implications Case-control (two-gate design) studies, case series, and seroprevalence studies representing the range of LB in different populations are necessary to assess the diagnostic accuracy of serological tests for LB. A broader range of studies should be considered for inclusion in systematic reviews of diagnostic accuracy.

• Dahlberg, Audun Olav; Aase, Audun; Reiso, Harald; Thortveit, Erik Thomas; Eikeland, Randi & Engstrøm, Morten [Vis alle 7 forfattere av denne artikkelen] (2025). Persistent self-reported health complaints in Norwegians who attribute their symptoms to tick bites or tick-borne disease– a cross-sectional controlled study. BMC Infectious Diseases. 25. doi: 10.1186/s12879-025-11104-0. Fulltekst i vitenarkiv Vis sammendrag

  Background: The frequency and mechanisms of persistent health complaints attributed to tick bites or tick-borne diseases are unknown. We evaluate such complaints in Norwegian cases and controls. Methods: People older than 18 years with persistent health complaints of six months or more attributed to tick bites or tick-borne diseases (cases) were recruited into a nationwide cross-sectional study between October 2016 and January 2021. Demographic data, tick bites, antibiotic use, and tick-borne pathogen serology were recorded. We evaluated somatic symptoms (PHQ-15), fatigue (Fatigue Severity Scale), mental and physical health (RAND-36), affective symptoms (HAD Scale) and modern health worries (MHW Scale) as outcome measures. Serological tests included IgG antibodies against B. burgdorferi (Bb) and other tick-borne pathogens. The control population (n = 2803) was recruited from a tick-endemic region in Søgne, southern Norway. Differences between cases and controls were evaluated. Results: A total of 500 responses were collected through general practitioners (n = 14), by invitation (n = 94), and by Short Message Service (SMS) (n = 392). The estimate of prevalence is based on 392 of 270.000 included by SMS (0.15%). The SMS cohort reported better physical health than those recruited by invitation. Cases had significantly more somatic and affective symptoms, fatigue, comorbidities, and reduced quality of life related to health than controls. The differences in fatigue and physical health between cases and controls were not related to previous tick exposures. Bb IgG and other antibodies against tick-borne pathogens were more prevalent in cases than controls. In multivariable analyses, cases that were never treated did not exhibit higher somatic symptom scores compared to those treated multiple times. Seropositive Bb cases had worse mental health (p < 0.001) and more depressive symptoms (p = 0.017) than seronegative cases. Conclusions: The crude prevalence of persistent health complaints in Norway attributed to tick bites or tick-borne diseases is 0.15%. The cases reported significantly poorer physical health, including increased fatigue, when compared to the controls. These relationships were not affected by tick exposures. However, poorer mental health in cases may be associated with Bb seropositivity, especially for the ones with comorbidities. In conclusion, no clear associations were found between tick bites, tick-borne diseases and persistent health complaints.

• Dias, Sara P.; Akhvlediani, Tamar; Bernard-Valnet, Raphael; Bigi, Sandra; Eikeland, Randi & Pal, Pramod K. [Vis alle 8 forfattere av denne artikkelen] (2025). Sex and gender differences in neurological infections. Current Opinion in Neurology. ISSN 1350-7540. 38(4), s. 429–435. doi: 10.1097/WCO.0000000000001389. Fulltekst i vitenarkiv Vis sammendrag

  Purpose of review Neurological infections are a significant cause of morbidity and mortality. This review aims to summarize current insights and developments for sex and gender differences in the epidemiology, clinical presentation, and prognosis of neurological infections. Recent findings Sex refers to the biological and physiological factors that define males and females. Gender, on the other hand, refers to characteristics that are socially constructed. Both aspects are central to infectious disease pathogenesis, and clinical and scientific evidence of their relevance in neuroinfections is emerging. Indeed, differences in exposure to pathogens and genetic and hormonal factors modulate immune responses and modify the susceptibility, clinical course, and response to the treatment of neurological infections. Summary Recognizing and addressing sex and gender differences in neurological infections is crucial for tailoring diagnostic, therapeutic, and preventive strategies. Our review underscores the importance of considering sex and gender in clinical practice and research to improve patient care and outcomes.

• Skarstein, Ingerid; Ulvestad, Elling; Solheim, Anne Marit; Vedeler, Christian; Ljøstad, Unn & Mygland, Åse [Vis alle 10 forfattere av denne artikkelen] (2024). Serum neurofilament light chain associates with symptom burden in Lyme neuroborreliosis patients: a longitudinal cohort study from Norway. Journal of Neurology. ISSN 0340-5354. 271, s. 2768–2775. doi: 10.1007/s00415-024-12237-z. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: Serum neurofilament light chain (sNfL), an indicator of neuronal damage, is increasingly recognized as a potential biomarker for disease activity in neurodegenerative disorders. In this study, we wanted to investigate sNfL as a prognostic marker in a large, well-defined population of 90 patients with Lyme neuroborreliosis (LNB). In addition, we sought to explore associations between symptoms and sNfL levels during the acute phase of LNB. Materials and methods: Patients diagnosed with definite or possible LNB were recruited from a double-blinded, placebo-controlled, multi-center trial, in which the participants were randomly assigned to 2 or 6 weeks of oral doxycycline treatment. The sNfL levels were measured using a single molecule array assay at both diagnosis and 6-month follow-up, and analysed against clinical parameters, variations in symptom burden and long-term complaints as assessed by a composite clinical score. Results: At the time of diagnosis, approximately 60% of the patients had elevated sNfL levels adjusted for age. Notably, mean sNfL levels were significantly higher at diagnosis (52 pg/ml) compared to 6 months after treatment (12 pg/ml, p < 0.001), when sNfL levels had normalized in the majority of patients. Patients with objective signs of spinal radiculitis had significantly higher baseline sNfL levels compared to patients without spinal radiculitis (p = 0.033). Conclusion: Our findings suggest that sNfL can serve as a biomarker for peripheral nerve tissue involvement in the acute phase of LNB. As found in an earlier study, we confirm normalization of sNfL levels in blood after treatment. We found no prognostic value of acute-phase sNfL levels on patient outcome.

• Quarsten, Hanne; Andreassen, Åshild Kristine; Paulsen, Katrine Mørk; Diekmann, Maria Juul; Eikeland, Randi & Helleren, Rita [Vis alle 9 forfattere av denne artikkelen] (2024). No detection of tick-borne encephalitis virus RNA in blood, urine or saliva of hospitalised immunocompetent tick-borne encephalitis patients. PLOS ONE. 19(6). doi: 10.1371/journal.pone.0305603. Fulltekst i vitenarkiv Vis sammendrag

  Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material.

• Sarjomaa, Marjut Anneli; Zhang, Chi; Tveten, Yngvar; Kersten, Hege; Reiso, Harald & Eikeland, Randi [Vis alle 14 forfattere av denne artikkelen] (2024). Risk factors for SARS-CoV-2 infection: A test-negative case-control study with additional population controls in Norway. BMJ Open. 14(1), s. 1–11. doi: 10.1136/bmjopen-2023-073766. Fulltekst i vitenarkiv Vis sammendrag

  Objectives This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. Design and setting Test-negative design (TND), multicentre case–control study with additional population controls in South-Eastern Norway. Participants Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. Primary outcome measures The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. Results In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). Conclusions Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case–control study designs during the pandemic.

• Solheim, Anne Marit; Skarstein, Ingerid; Quarsten, Hanne; Lorentzen, Åslaug Rudjord; Berg-Hansen, Pål & Eikeland, Randi [Vis alle 9 forfattere av denne artikkelen] (2024). Clinical and laboratory characteristics during a 1-year follow-up in European Lyme neuroborreliosis: A prospective cohort study. European Journal of Neurology. ISSN 1351-5101. 31(12). doi: 10.1111/ene.16487. Fulltekst i vitenarkiv Vis sammendrag

  Background and Purpose We need more knowledge on clinical presentations, time course, biomarkers, and prognosis in European Lyme neuroborreliosis (LNB). Methods A prospective 12-month follow-up of predetermined clinical and laboratory parameters was undertaken in 105 patients with LNB. Results At presentation, 79% had radiculopathy, 49% had facial palsy, and 13% had solely subjective symptoms (predominately pain). Intrathecally produced Borrelia burgdorferi (Bb) antibodies were demonstrated and cerebrospinal fluid (CSF) CXCL13 was positive in 85% and 82% pretreatment, in 73% and 10% at 6 months, and in 58% and 14% at 12 months, respectively. CSF Bb polymerase chain reaction (PCR) was positive in 40% pretreatment. In four patients who tested negative for Bb antibodies in both serum and CSF, the diagnosis was supported by typical clinical features, pleocytosis, CSF Bb-PCR (n = 1), or CSF CXCL13 (n = 2). The proportion with symptoms influencing daily life was 91% pretreatment, 25% at 10 weeks, 20% at 6 months, and 15% at 12 months. Fatigue was the most common complaint at 12 months. A high burden of symptoms before and after treatment was associated with residual complaints at 12 months, whereas background data, other clinical features, and laboratory features were not. Conclusions LNB can present with solely subjective symptoms, especially pain. Many LNB patients have persistent Bb antibodies in serum and CSF. In seronegative LNB, CSF Bb-PCR and CXCL13 may give diagnostic support. CXCL13 may be persistently positive after treatment in some patients. Most of the clinical improvement occurs during the first 10 weeks. High initial clinical score is associated with poorer outcome.

• Skudal, Hilde Kristin; Lorentzen, Åslaug Rudjord; Stenstad, Tore; Paulsen, Else Quist; Egeland, Jens & Fevang, Børre [Vis alle 13 forfattere av denne artikkelen] (2024). Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 43(7), s. 1355–1366. doi: 10.1007/s10096-024-04855-2. Fulltekst i vitenarkiv Vis sammendrag

  Purpose To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE). Methods This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified. Results Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease. Conclusion This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease.

• Eikeland, Randi; Henningsson, Anna J.; Lebech, Anne-Mette; Kerlefsen, Yvonne; Mavin, Sally & Vrijlandt, Amber [Vis alle 14 forfattere av denne artikkelen] (2024). Tick-borne diseases in the North Sea region–A comprehensive overview and recommendations for diagnostics and treatment. Ticks and Tick-borne Diseases. ISSN 1877-959X. 15(2). doi: 10.1016/j.ttbdis.2023.102306. Fulltekst i vitenarkiv
• Lindland, Elisabeth S.; Røvang, Martin S.; Solheim, Anne Marit; Andreassen, Silje; Skarstein, Ingerid & Dareez, Nazeer [Vis alle 17 forfattere av denne artikkelen] (2024). Are white matter hyperintensities associated with neuroborreliosis? The answer is twofold. Neuroradiology. ISSN 0028-3940. 67, s. 37–48. doi: 10.1007/s00234-024-03482-0. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Many consider white matter hyperintensities (WMHs) to be important imaging findings in neuroborreliosis. However, evidence regarding association with WMHs is of low quality. The objective was to investigate WMHs in neuroborreliosis visually and quantitatively. Materials and methods Patients underwent brain MRI within one month of diagnosis and six months after treatment. Healthy controls were recruited. WMHs were counted by visual rating and the volume was calculated from automatic segmentation. Biochemical markers and scores for clinical symptoms and findings were used to explore association with longitudinal volume change of WMHs. Results The study included 74 patients (37 males) with early neuroborreliosis and 65 controls (30 males). Mean age (standard deviation) was 57.4 (13.5) and 57.7 (12.9) years, respectively. Baseline WMH lesion count was zero in 14 patients/16 controls, < 10 in 36/31, 10–20 in 9/7 and > 20 in 13/11, with no difference between groups (p = 0.90). However, from baseline to follow-up the patients had a small reduction in WMH volume and the controls a small increase, median difference 0.136 (95% confidence interval 0.051–0.251) ml. In patients, volume change was not associated with biochemical or clinical markers, but with degree of WMHs (p values 0.002–0.01). Conclusion WMH lesions were not more numerous in patients with neuroborreliosis compared to healthy controls. However, there was a small reduction of WMH volume from baseline to follow-up among patients, which was associated with higher baseline WMH severity, but not with disease burden or outcome. Overall, non-specific WMHs should not be considered suggestive of neuroborreliosis.

• Tjernberg, Ivar; Lager, Malin; Jensen, Guro Furset; Eikeland, Randi; Nyman, Dag & Brudin, Lars [Vis alle 7 forfattere av denne artikkelen] (2023). Identification of potential biomarkers in active Lyme borreliosis. PLOS ONE. 18(6). doi: 10.1371/journal.pone.0287586. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Lyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous Borrelia infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to Borrelia. Methods Serum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink®) by which 92 different immune response-related human protein biomarkers were analysed simultaneously. Results In total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previously Borrelia exposed (n = 34) and not exposed (n = 41) based on anti-Borrelia antibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (p<0.1). Six proteins were statistically significantly different between LB patients and blood donors (p<0.05). These six proteins were then combined in an index and analysed using receiver-operating-characteristic curve analysis showing an area under the curve of 0.964 (p<0.001). Conclusions The results from this study suggest that there is an immunological protein pattern that can distinguish a present Borrelia infection from a previous exposure as well as anti-Borrelia antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.

• Akhvlediani, Tamar; Bernard-Valnet, Raphael; Dias, Sara; Eikeland, Randi; Pfausler, Bettina & Sellner, Johann (2023). Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2. European Journal of Neurology. ISSN 1351-5101. s. 3904–3912. doi: 10.1111/ene.16017. Fulltekst i vitenarkiv Vis sammendrag

  Background and purposeThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective.MethodsWe summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA).ResultsNirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4.ConclusionsNeurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

• Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Andreassen, Silje; Bugge, Robin Antony Birkeland; Eikeland, Randi & Reiso, Harald [Vis alle 10 forfattere av denne artikkelen] (2023). Dynamic contrast-enhanced MRI shows altered blood–brain barrier function of deep gray matter structures in neuroborreliosis: a case–control study. European Radiology Experimental. 7(1). doi: 10.1186/s41747-023-00365-6. Fulltekst i vitenarkiv Vis sammendrag

  Background Main aim was assessment of regional blood–brain barrier (BBB) function by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with neuroborreliosis. Secondary aim was to study the correlation of BBB function with biochemical, clinical, and cognitive parameters. Methods Regional ethical committee approved this prospective single-center case–control study. Within 1 month after diagnosis of neuroborreliosis, 55 patients underwent DCE-MRI. The patient group consisted of 25 males and 30 females with mean age 58 years, and the controls were 8 males and 7 females with mean age 57 years. Pharmacokinetic compartment modelling with Patlak fit was applied, providing estimates for capillary leakage rate and blood volume fraction. Nine anatomical brain regions were sampled with auto-generated binary masks. Fatigue, severity of clinical symptoms and findings, and cognitive function were assessed in the acute phase and 6 months after treatment. Results Leakage rates and blood volume fractions were lower in patients compared to controls in the thalamus (p = 0.027 and p = 0.018, respectively), caudate nucleus (p = 0.009 for both), and hippocampus (p = 0.054 and p = 0.009). No correlation of leakage rates with fatigue, clinical disease severity or cognitive function was found. Conclusions In neuroborreliosis, leakage rate and blood volume fraction in the thalamus, caudate nucleus, and hippocampus were lower in patients compared to controls. DCE-MRI provided new insight to pathophysiology of neuroborreliosis, and can serve as biomarker of BBB function and regulatory mechanisms of the neurovascular unit in infection and inflammation. Relevance statement DCE-MRI provided new insight to pathophysiology of neuroborreliosis, and can serve as biomarker of blood–brain barrier function and regulatory mechanisms of the neurovascular unit in infection and inflammation.

• Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Beyer, Mona K.; Solheim, Anne Marit; Ljøstad, Unn & Mygland, Åse Daasvand [Vis alle 13 forfattere av denne artikkelen] (2022). Assessment of cognitive function, structural brain changes and fatigue 6 months after treatment of neuroborreliosis. Journal of Neurology. ISSN 0340-5354. doi: 10.1007/s00415-022-11463-7. Fulltekst i vitenarkiv Vis sammendrag

  Background Complete recovery after adequately treated neuroborreliosis is common, but studies report that some patients experience persistent symptoms like self-reported cognitive problems and fatigue. Persisting symptoms are often termed post-Lyme disease syndrome, of which etiology is not clearly understood. The aim of this study was to investigate cognitive function, possible structural changes in brain regions and level of fatigue. We have not found previous studies on neuroborreliosis that use standardized neuropsychological tests and MRI with advanced image processing to investigate if there are subtle regional changes in cortical thickness and brain volumes after treatment. Methods We examined 68 patients treated for neuroborreliosis 6 months earlier and 66 healthy controls, with a comprehensive neuropsychological test protocol, quantitative structural MRI analysis of the brain and Fatigue Severity Scale. Results We found no differences between the groups in either cognitive function, cortical thickness or brain volumes. The patients had higher score on Fatigue Severity Scale 3.8 vs. 2.9 (p = 0.001), and more patients (25.4%) than controls (5%) had severe fatigue (p = 0.002), but neither mean score nor proportion of patients with severe fatigue differed from findings in the general Norwegian population. Conclusion The prognosis regarding cognitive function, brain MRI findings and fatigue after adequately treated neuroborreliosis is favorable.

• Bernardsjaw, Emilie; Gynthersen, Rosa; Bremell, Daniel; Mens, Helene; Stenør, Christian & Lorentzen, Åslaug Rudjord [Vis alle 9 forfattere av denne artikkelen] (2022). Antibiotic therapy of neuroborreliosis: A survey among infectious disease specialists and neurologists in Norway, Sweden, and Denmark. Ticks and Tick-borne Diseases. ISSN 1877-959X. 13(6). doi: 10.1016/j.ttbdis.2022.102051. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Neuroborreliosis (NB) is a prevalent tick-borne neuroinfection in Europe. To delineate current practice in antimicrobial management of adults with NB and to prioritize future trials needed to optimize treatment recommendations, a questionnaire-based survey was performed. Methods: A self-administered Internet-based survey of NB treatment practices among specialists in infectious diseases and neurology based in Norway, Sweden, and Denmark was carried out between October 2021 and February 2022. The participants were also asked to prioritize four pre-defined research questions for randomized controlled trials (RCTs) on therapy for NB. Results: In total, 290 physicians (45% female) from Norway (30%), Sweden (40%), and Denmark (30%) participated in the survey. Of the responders, 230 (79%) were infectious disease specialists and 56 (19%) were neurologists. The preferred antibiotic treatment for patients with early NB was oral doxycycline (n = 225, 78%). Intravenous (IV) penicillin, ceftriaxone, or cefotaxime for the full treatment course was favored by 12%. A preferred treat- ment duration of 10–14 days for patients with NB was reported by 245 respondents (85%), most common among participants from Sweden (97%). A total of 170 (59%) responders reported having local hospital guidelines on the treatment of NB, most often with recommendation of oral doxycycline (92%) for 10–14 days (90%) as first line treatment. The prioritization score for future RCTs was highest for adjunctive prednisone therapy in NB patients with facial palsy (median 5; IQR 4–6) and for placebo versus repeated antibiotics in patients with persistent symptoms after completed antibiotic therapy for NB (median 5, IQR 3–6). Conclusion: In Sweden, all respondents preferred treating NB with oral doxycycline for 10–14 days, whereas 5% in Norway and 19% in Denmark still treat NB with IV antibiotics for the entire treatment course. RCTs to define the role of adjunctive prednisolone in NB patients with facial palsy and repeated antibiotics in patients with persistent symptoms are prioritized for future research.

• Halperin, John; Eikeland, Randi; Branda, John & Dersch, Rick (2022). Lyme neuroborreliosis, known knowns, known unknowns. Brain. ISSN 0006-8950. 145(8), s. 2635–2647. doi: 10.1093/brain/awac206. Fulltekst i vitenarkiv Vis sammendrag

  Lyme borreliosis affects the nervous system in three principal ways—mononuclear cell meningitis, cranial neuropathies and radiculoneuropathies—the last a broad term encompassing painful radiculopathy, unifocal and multifocal peripheral nerve involvement. Diagnostic tools have been significantly refined—including improved peripheral blood and CSF serodiagnostics—and much has been learned about the interactions between the causative pathogen and the nervous system. Despite these advances in our understanding of this disease, a broad range of other disorders continue to be misattributed to nervous system Lyme borreliosis, supported by, at best, limited evidence. These misattributions often reflect limited understanding not only of Lyme neuroborreliosis but also of what constitutes nervous system disease generally. Fortunately, a large body of evidence now exists to clarify many of these issues, establishing a clear basis for diagnosing nervous system involvement in this infection and, based on well performed studies, clarifying which clinical disorders are associated with Lyme neuroborreliosis, which with non-neurologic Lyme borreliosis, and which with neither.

• Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Dareez, Muhammad Nazeer; Eikeland, Randi; Ljøstad, Unn & Mygland, Åse Daasvand [Vis alle 10 forfattere av denne artikkelen] (2022). Enhancement of cranial nerves in Lyme neuroborreliosis: incidence and correlation with clinical symptoms and prognosis. Neuroradiology. ISSN 0028-3940. 64, s. 2323–2333. doi: 10.1007/s00234-022-02957-2. Fulltekst i vitenarkiv Vis sammendrag

  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 fndings 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 afected. 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 afected. Enhancement of the facial nerve distal internal auditory canal and parotid segments correlate with degree of facial palsy.

• Andreassen, Silje; Solheim, Anne Marit; Ljøstad, Unn; Mygland, Åse Daasvand; Lorentzen, Åslaug Rudjord & Reiso, Harald [Vis alle 10 forfattere av denne artikkelen] (2022). Cognitive function in patients with neuroborreliosis: A prospective cohort study from the acute phase to 12 months post treatment. Brain and Behavior. 12(6). doi: 10.1002/brb3.2608. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Lie, Ingrid Anne; Wesnes, Kristin; Kvistad, Silje Agnethe Stokke; Brouwer, Iman; Wergeland, Stig & Holmøy, Trygve [Vis alle 20 forfattere av denne artikkelen] (2022). The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis. Neurology: Neuroimmunology and neuroinflammation. 9(5), s. 1–10. doi: 10.1212/NXI.0000000000200008. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives - The relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS). Methods - We included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months. Smoking status was decided for each patient by 2 separate definitions: by serum cotinine levels measured regularly for the first 2 years of the follow-up (during the clinical trial) and by retrospective patient self-reporting. At the 10-year follow-up visit, clinical tests were repeated, and brain atrophy measures were obtained from MRI using FreeSurfer. Differences in clinical and MRI measurements at the 10-year follow-up between smokers and nonsmokers were investigated by 2-sample t tests or Mann-Whitney tests and linear mixed-effect regression models. All analyses were conducted separately for each definition of smoking status. Results - After 10 years, smoking (defined by serum cotinine levels) was associated with lower total white matter volume (β = −21.74, p = 0.039) and higher logT2 lesion volume (β = 0.22, p = 0.011). When defining smoking status by patient self-reporting, the repeated analyses found an additional association with lower deep gray matter volume (β = −2.35, p = 0.049), and smoking was also associated with a higher score (higher walking impairment) on the log timed 25-foot walk test (β = 0.050, p = 0.039) after 10 years and a larger decrease in paced auditory serial addition test (attention) scores (β = −3.58, p = 0.029). Discussion - Smoking was associated with brain atrophy and disability progression 10 years later in patients with RRMS. The findings imply that patients should be advised and offered aid in smoking cessation shortly after diagnosis, to prevent long-term disability progression.

• Solheim, Anne Marit; Lorentzen, Åslaug Rudjord; Dahlberg, Audun Olav; Flemmen, Heidi Øyen; Brune, Synne & Forselv, Kristine Johanne Nordstrøm [Vis alle 12 forfattere av denne artikkelen] (2022). Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled trial. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 93(11), s. 1222–1228. doi: 10.1136/jnnp-2022-329724. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Sarjomaa, Marjut Anneli; Diep, Lien My; Zhang, Chi; Tveten, Yngvar; Reiso, Harald & Thilesen, Carina [Vis alle 14 forfattere av denne artikkelen] (2022). SARS-CoV-2 antibody persistence after five and twelve months: A cohort study from South-Eastern Norway. PLOS ONE. 17(8), s. 1–15. doi: 10.1371/journal.pone.0264667. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: To assess total antibody levels against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2) spike protein up to 12 months after Coronavirus Disease (COVID-19) infection in non-vaccinated individuals and the possible predictors of antibody persistence. Methods: This is the first part of a prospective multi-centre cohort study. Participants: The study included SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) positive and negative participants in South-Eastern Norway from February to December 2020. Possible predictors of SARS-CoV-2 total antibody persistence was assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR in 391 PCR-positive and 703 PCR-negative participants; 212 PCR-positive participants were included in follow-up measurements at 10 to 12 months. The participants completed a questionnaire including information about symptoms, comorbidities, allergies, body mass index (BMI), and hospitalisation. Primary outcome: The SARS-CoV-2 total antibody levels against spike protein three to five and 10 to 12 months after PCR positive tests. Results: SARS-CoV-2 total antibodies against spike protein were present in 366 (94%) non-vaccinated PCR-positive participants after three to five months, compared with nine (1%) PCR-negative participants. After 10 to 12 months, antibodies were present in 204 (96%) non-vaccinated PCR-positive participants. Of the PCR-positive participants, 369 (94%) were not hospitalised. The mean age of the PCR-positive participants was 48 years (SD 15, range 20-85) and 50% of them were male. BMI ≥ 25 kg/m2 was positively associated with decreased antibody levels (OR 2.34, 95% CI 1.06 to 5.42). Participants with higher age and self-reported initial fever with chills or sweating were less likely to have decreased antibody levels (age: OR 0.97, 95% CI 0.94 to 0.99; fever: OR 0.33, 95% CI 0.13 to 0.75). Conclusion: Our results indicate that the level of SARS-CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR-positive persons at least 10 to 12 months after mild COVID-19.

• Lie, Ingrid Anne; Kacar, Sezgi; Wesnes, Kristin; Brouwer, Iman; Kvistad, Silje Agnethe Stokke & Wergeland, Stig [Vis alle 24 forfattere av denne artikkelen] (2022). Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 93(8), s. 849–857. doi: 10.1136/jnnp-2021-328568. Fulltekst i vitenarkiv Vis sammendrag

  Background The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear. Objective Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years. Methods 85 patients, originally enrolled in a multicentre, randomised trial of ω−3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer. Results Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (β=−0.399, p=0.040) and deep (β=−0.556, p=0.010) GM volume, lower mean cortical thickness (β=−0.581, p=0.010) and higher T2 lesion count (β=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (β=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression. Conclusion Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

• Wesnes, Kristin; Myhr, Kjell-Morten; Riise, Trond; Kvistad, Silje Agnethe Stokke; Torkildsen, Øivind & Wergeland, Stig [Vis alle 17 forfattere av denne artikkelen] (2021). Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 50:102801, s. 1–7. doi: 10.1016/j.msard.2021.102801. Fulltekst i vitenarkiv Vis sammendrag

  Background: Low vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. Methods: In this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During 24 months, serum 25-hydroxyvitamin D (25 (OH)D), serum cotinine (nicotine metabolite), and BMI were repeatedly measured. In 2017, a follow-up study was conducted among 80 of the participants, including disability assessment by the Expanded Disability Status Scale (EDSS). Linear regression was used to explore associations between the lifestyle factors and the EDSS change over 10 years. Results: Higher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Further adjustments for potential confounders related to lifestyle and disease status gave similar results. The association was mainly driven by low 25(OH)D levels during spring, as well as seasonally adjusted levels below 80 nmol/L. No clear association was found for BMI and cotinine. Conclusion: Lower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS.

• Knudtzen, Fredrikke Christie; Eikeland, Randi; Bremell, Daniel; Paulsen, Else Quist; Johansen, Isik Somuncu & Solheim, Anne Marit [Vis alle 7 forfattere av denne artikkelen] (2021). Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. doi: 10.1016/j.cmi.2021.11.001. Fulltekst i vitenarkiv Vis sammendrag

  Background Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. Objectives To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. Data sources Medline, Embase, Scopus, Cochrane library. Study eligibility criteria There was no discrimination on study type, time of publication or language. Participants Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis. Methods Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. Results Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died. Conclusions This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.

• Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Beyer, Mona K.; Ljøstad, Unn & Mygland, Åse Daasvand [Vis alle 11 forfattere av denne artikkelen] (2021). Cognitive function, fatigue and Fazekas score in patients with acute neuroborreliosis. Ticks and Tick-borne Diseases. ISSN 1877-959X. 12(3), s. 1–5. doi: 10.1016/j.ttbdis.2021.101678. Fulltekst i vitenarkiv Vis sammendrag

  Long-term cognitive problems and fatigue after adequately treated neuroborreliosis has caused uncertainty and debate among patients and health care workers for years. Despite several studies, the prevalence, cause and severity of such complaints are still not clarified. More knowledge about cognitive function, fatigue and MRI findings in the acute phase of neuroborreliosis could possibly contribute to clarification. In the current study, we therefore aimed to address this. Patients with well-characterized acute neuroborreliosis (n = 72) and a matched control group (n = 68) were screened with eight subtests from three different neuropsychological test batteries assessing attention, working memory and processing speed, and with Fatigue Severity Scale. Fazekas score was used to grade white matter hyperintensities on MRI. We found no differences in mean scores on the neuropsychological tests between the groups. The patient group reported significantly higher level of fatigue (Fatigue Severity Scale: 4.8 vs. 2.9, p < .001). There was no significant difference in Fazekas score between the groups. Neuroborreliosis does not seem to affect cognitive functions in the acute state of the disease, while fatigue is common.

• Margos, Gabriele; Castillo-Ramírez, Santiago; Cutler, Sally; Dessau, Ram; Eikeland, Randi & Estrada-Peña, Agustin [Vis alle 19 forfattere av denne artikkelen] (2020). Rejection of the name Borreliella and all proposed species comb. nov. placed therein. International Journal of Systematic and Evolutionary Microbiology. ISSN 1466-5026. 70(5), s. 3577–3581. doi: 10.1099/ijsem.0.004149. Fulltekst i vitenarkiv
• Eikeland, Randi; Ljøstad, Unn; Helgeland, Geir; Sand, Geir; Flemmen, Heidi Øyen & Bø, Margrete Halvorsen [Vis alle 10 forfattere av denne artikkelen] (2020). Patient-reported outcome after treatment for definite Lyme neuroborreliosis. Brain and Behavior. 10(4), s. 1–7. doi: 10.1002/brb3.1595. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Quist-Paulsen, Else; Ormaasen, Vidar; Kran, Anne-Marte Bakken; Dunlop, Oona Borghild; Ueland, Per Magne & Ueland, Thor [Vis alle 9 forfattere av denne artikkelen] (2019). Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning. Scientific Reports. 9. doi: 10.1038/s41598-019-52570-2. Fulltekst i vitenarkiv Vis sammendrag

  For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.

• Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Andreassen, Silje; Paulsen, Else Quist; Eikeland, Randi & Ljøstad, Unn [Vis alle 12 forfattere av denne artikkelen] (2018). Imaging in Lyme neuroborreliosis. Insights into Imaging. 9(5), s. 833–844. doi: 10.1007/s13244-018-0646-x. Fulltekst i vitenarkiv Vis sammendrag

  Lyme neuroborreliosis (LNB) is a tick-borne spirochetal infection with a broad spectrum of imaging pathology. For individuals who live in or have travelled to areas where ticks reside, LNB should be considered among differential diagnoses when clinical manifestations from the nervous system occur. Radiculitis, meningitis and facial palsy are commonly encountered, while peripheral neuropathy, myelitis, meningoencephalitis and cerebral vasculitis are rarer manifestations of LNB. Cerebrospinal fluid (CSF) analysis and serology are key investigations in patient workup. The primary role of imaging is to rule out other reasons for the neurological symptoms. It is therefore important to know the diversity of possible imaging findings from the infection itself. There may be no imaging abnormality, or findings suggestive of neuritis, meningitis, myelitis, encephalitis or vasculitis. White matter lesions are not a prominent feature of LNB. Insight into LNB clinical presentation, laboratory test methods and spectrum of imaging pathology will aid in the multidisciplinary interaction that often is imperative to achieve an efficient patient workup and arrive at a correct diagnosis. This article can educate those engaged in imaging of the nervous system and serve as a comprehensive tool in clinical cases.

• Smaradottir, Berglind; Eikeland, Randi; Reiso, Harald & Fensli, Rune Werner (2018). User-centered design of a national medical registry for tick-borne diseases. Advances in Intelligent Systems and Computing. ISSN 2194-5357. 779, s. 99–108. doi: 10.1007/978-3-319-94373-2_11. Fulltekst i vitenarkiv Vis sammendrag

  Tick-borne diseases are increasing in a global perspective, with Lyme disease and tick-borne encephalitis as the most frequent. The Norwegian National Ad-visory Unit on Tick-borne Diseases is preparing the development of a national medical registry for clinical follow-up of patients with tick-borne diseases based on the best practice guidelines and for research purposes. This paper presents the methodological approach of a user-centered design process applied in the in-itial phase of the registry development. A user workshop identified user needs, requirements and proposed a service workflow for the registry operation. As the next step, a simulation of the proposed service workflow was performed in a clinical laboratory together with end-user groups. The main contribution of this paper lies on the methodological descriptions of the user-centered design pro-cess, and how to facilitate the active contribution of end-users in a technical de-velopment process within a health care context.

• Roaldsnes, Erlend; Eikeland, Randi & Berild, Dag (2017). Lyme-nevroborreliose ved uspesifikke nevrologiske symptomer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(2), s. 101–104. doi: 10.4045/tidsskr.15.1115. Fulltekst i vitenarkiv
• Lorentzen, Åslaug Rudjord; Forselv, Kristine Johanne Nordstrøm; Helgeland, Geir; Salvesen, Rigmor Elisabeth; Sand, Geir & Flemmen, Heidi Øyen [Vis alle 16 forfattere av denne artikkelen] (2017). Lyme neuroborreliosis: do we treat according to guidelines? Journal of Neurology. ISSN 0340-5354. 264(7), s. 1506–1510. doi: 10.1007/s00415-017-8559-z. Fulltekst i vitenarkiv Vis sammendrag

  Evidence-based guidelines, published in 2010, equate the efficacy of oral and intravenous antibiotics and recommend treatment duration of 2 weeks in early Lyme neuroborreliosis (LNB) without encephalitis or myelitis. Further, the Norwegian health authorities give a general advice to choose oral rather than intravenous administration when proven effective, due to lower costs, fewer risks, and reduced patient inconvenience. In this study we aimed to chart LNB treatment practice in Norway and compare it to these recommendations. Adult patients diagnosed with definite LNB between 2007 and 2013 in 11 different hospitals in the four health regions in Norway were invited to answer a questionnaire regarding duration and administration of antibiotic treatment. A total of 253 patients answered. Median age at diagnosis was 59 years (range 19–83), and 125 (49%) were women. Duration of treatment was 1 week in 7 (3%) patients, 2 weeks in 81 (32%), 3 weeks in 62 (25%), 4 weeks in 48 (19%), 5 weeks in 12 (5%), ≥6 weeks in 29 (12%), and unknown in 14 (6%). Treatment was given orally in 77 (30%) patients, intravenously in 110 (44%), both orally and intravenously in 65 (26%), and unknown in one. Treatment practices differed between the health regions (p = 0.002). During the study period, there were no significant time trend neither with respect to proportion of patients treated for only 2 weeks (OR 0.899, p = 0.109) nor with respect to proportion of patients treated exclusively with oral antibiotics (OR 1.131, p = 0.074). In conclusion, there seem to be a gap between evidence-based recommendations and treatment practice of LNB in Norway.

• Forselv, Kristine Johanne Nordstrøm; Lorentzen, Åslaug Rudjord; Ljøstad, Unn; Mygland, Åse; Eikeland, Randi & Kjelland, Vivian [Vis alle 8 forfattere av denne artikkelen] (2017). Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis? Infectious Diseases. ISSN 2374-4235. 50(4), s. 297–302. doi: 10.1080/23744235.2017.1399315. Fulltekst i vitenarkiv
• Fell, Anne Kristin Møller; Eikeland, Randi & Aaseth, Jan (2016). En kvinne i 30-årene med hoste, tremor, uro og synsforstyrrelser. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(14-15), s. 1233–1235. doi: 10.4045/tidsskr.15.0998. Fulltekst i vitenarkiv Vis sammendrag

  I 1970-årene kontaktet en kvinne som da var i 30-årene lege på grunn av intermitterende luftveisplager, økende tretthet, uro og synsforstyrrelser. Hun utviklet et sammensatt sykdomsbilde med symptomer fra flere organsystemer. Det skulle gå mer enn 30 år før den sannsynlige årsaken til plagene var identifisert.

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• Kjelland, Vivian; Andreassen, Åshild Kristine; Eikeland, Randi; Jenkins, Andrew & Stuen, Snorre (2026). Flåttforskere: Norge er ikke rustet til å håndtere dette flåttscenarioet. Fulltekst i vitenarkiv Vis sammendrag

  Flåtten øker i antall, sprer seg til nye områder, nye flåttarter ankommer landet, og stadig flere mennesker og dyr opplever flåttbitt og sykdom. Samtidig svekkes kunnskapsgrunnlaget vårt. Forskningen på flåtten er ikke bare på et minimum, men er i ferd med å tørke ut.

• Eikeland, Randi; J., Henningsson, Anna; E., Lemieux, Jacob; Adriana, Marques,; S., Mead, Paul & Franc, Strle, [Vis alle 9 forfattere av denne artikkelen] (2026). Author Correction: Lyme borreliosis | Nature Reviews Disease Primers. Nature Reviews Disease Primers. doi: 10.1038/s41572-026-00704-y. Fulltekst i vitenarkiv
• Aarøe, Anna; Kjelland, Vivian & Eikeland, Randi (2026). Forsker advarer mot flåttmyter: – Folk må beskytte seg. [Internet]. TV2. Fulltekst i vitenarkiv Vis sammendrag

  Det finnes mange myter om flåtten. Forsker Vivian Kjelland er redd desinformasjonen kan øke smitten av flåttbårne sykdommer.

• Skarstein, Ingerid; Solheim, Anne Marit; Quarsten, Hanne; Ljøstad, Unn; Mygland, Åse Daasvand & Lorentzen, Åslaug Rudjord [Vis alle 10 forfattere av denne artikkelen] (2026). Definite neuroborreliosis with atypical antibody-profiles: a case report. doi: 10.1186/s13256-026-05925-z. Fulltekst i vitenarkiv Vis sammendrag

  Background According to European Academy of Neurology guidelines, a positive Borrelia burgdorferi antibody index is required for diagnosing definite Lyme neuroborreliosis. Exceptions to the typical antibody production may be seen in the earlier phases of Lyme neuroborreliosis and in immunocompromised patients with Lyme neuroborreliosis, which can present diagnostic challenges. Case presentations We present four Norwegian immunocompetent patients (three male patients aged 52, 61 and 64 years old and one female patient aged 52 years) with neurological symptoms typical of Lyme neuroborreliosis and pleocytosis but a negative or incalculable Borrelia burgdorferi antibody index. A positive PCR for Borrelia burgdorferi DNA in cerebrospinal fluid confirmed the diagnosis of Lyme neuroborreliosis for all four patients. Conclusion Our cases demonstrate that Lyme neuroborreliosis patients with symptom duration for several weeks and a well-functioning immune system can present with atypical antibody profiles. Consequently, we suggest that in cases with pleocytosis and symptoms compatible with Lyme neuroborreliosis but negative Borrelia burgdorferi antibody index, one should consider supplementary laboratory testing to confirm the diagnosis.

• Eikeland, Randi (2024). Brukerorientert innovasjon på et norsk sykehus, veien til en web basert billedtjeneste som skal vurdere ditt utslett etter flåttbitt. Fulltekst i vitenarkiv
• Bos-Haugen, Steffan Daniel; Skarstein, Ingerid; Eikeland, Randi & Solheim, Anne Marit (2024). Serum neurofilament light chain associates with disease activity in Lyme neuroborreliosis patients-a longitudinal sohort study from Norway. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Infeksjonskurs for indremedisinere Borrelia og TBE. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Flått og flåttbårne sydkommer. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Flåttsykdommer i Norge. Fulltekst i vitenarkiv
• Eikeland, Randi; Barstad, Bjørn; Trønnes, Håvard & Døllner, Henrik (2024). Generell veileder i pediatri-borreliose. Helsebiblioteket.no. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Tick-Borne Encephalitis and Lyme Borreliosis, common and rare clinical presentations. Fulltekst i vitenarkiv
• Reiso, Harald; Eikeland, Randi; Kerlefsen, Yvonne; Omnes, Steinar & Ludvigsen, Ann-Elisabeth (2024). TickCheck-a web based application for assesing skin rashes after tick-bites. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Forskning på flåttbårne sydkommer i Agder. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Borreliose og TBE en oppdatering. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Flått og flåttbårne sydkommer. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Flått og flåttbårne sykdommmer-forekomst diagnostikk og behandling. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Min vei til professor. Fulltekst i vitenarkiv
• Eikeland, Randi (2024). Flått og flåttbårne sydkdommer. Fulltekst i vitenarkiv
• Grødeland, Gunnveig; Fossum, Even; Eikeland, Randi; Stiansen, Yngve & Sigurdsen, Ina Marie (2024). Stoppa sal etter skepsis – ny vaksine nærmar seg. [Internet]. NRK. Fulltekst i vitenarkiv
• Tveiten, Anne Cecilie; Løhaugen, Gro; Skranes, Jon Sverre; Gerstner, Thorsten Alfons & Eikeland, Randi (2024). Executive function deficits in Fetal Alcohol Spectrum Disorder (FASD) as key component in interventions for children and adolescents with FASD: A practical example. Fulltekst i vitenarkiv
• Tveiten, Anne Cecilie; Løhaugen, Gro; Gerstner, Thorsten Alfons; Eikeland, Randi & Skranes, Jon Sverre (2023). Presentation of a newly developed follow-up program based on psychoeducation of parents of children and adolescents with Fetal Alcohol Spectrum Disorder (FASD). Fulltekst i vitenarkiv
• Lindland, Elisabeth M.S.; Røvang, Martin Soria; Solheim, Anne Marit; Andreassen, Silje; Dareez, Muhammad Nazeer & Eikeland, Randi [Vis alle 7 forfattere av denne artikkelen] (2023). Brain White matter hyperintensities in neuroborreliosis. a case-control study. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Tick-borne diseases in the North Sea Region - a comprehensive overview and recommendations on diagnostic, treatment and management strategies. Fulltekst i vitenarkiv
• Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Ljøstad, Unn; Mygland, Åse Daasvand & Reiso, Harald [Vis alle 9 forfattere av denne artikkelen] (2023). Cognitive function in patients with neuroborreliosis: A prospective follow-up from the acute phase to 12 months after treatment. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Lyme Borreliosis recent progress and remaining challenges. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Nevroborreliose. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Covita studien. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Flåttbårne sykdommer, hva vet vi egentlig. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Flåttsituasjonen på Sørlandet, hva bør folk vite. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). TBE og Borreliose. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Flåtten våkner til liv, er du forberedt? Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Managment of tick-borne diseases. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Managment of tick-borne diseases. Fulltekst i vitenarkiv
• Eikeland, Randi (2023). Lyme Borreliosis: recent progress and remaining challhenges 2. Fulltekst i vitenarkiv
• Christiansen, Atle; Kjelland, Vivian & Eikeland, Randi (2023). Nå er det høysesong for flåtten. Blodsugeren spiser bare tre ganger i løpet av livet. [Internet]. Forskning.no. Fulltekst i vitenarkiv
• Kjelland, Vivian & Eikeland, Randi (2023). Nå er det høysesong for flåtten. [Internet]. Universitetet i Agder. Fulltekst i vitenarkiv
• Skisland, Anne Valen -Sendstad; Eikeland, Randi; Jeppestøl, Kristin & Øygarden, Halvor (2022). Våkn opp helseforetak, kommuner i Agder og sykepleiere. Fulltekst i vitenarkiv
• Eikeland, Randi (2022). Borrelia. Fulltekst i vitenarkiv
• Eikeland, Randi (2022). Post-Lyme Disease Syndrome: what is it and how to deal with it? Fulltekst i vitenarkiv
• Eikeland, Randi (2022). The different faces of borreliosis-in your brain? Fulltekst i vitenarkiv
• Eikeland, Randi (2022). Nevroborreliose. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Flått og flåttbårne sykdommer. [Radio]. Rikesdekkende Radio Plassen. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Et forskningseventyr med mange helter. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Nordic consensus on the assessment and follow-up of persons with long-term ailments after suspected tick-borne diseases. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Flått. [Radio]. Riksdekkende Radio Ekko. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Hva spør legene Flåttsenteret om? Fulltekst i vitenarkiv
• Eikeland, Randi (2021). choice of serological diagnostics in neuroinfections. Fulltekst i vitenarkiv
• Reiso, Harald; Kerlefsen, Yvonne; Aase, Audun; Aaberge, Ingeborg Aase S. & Eikeland, Randi (2021). What should be done in case of suspected tick-borne diseases? doi: 10.4045/tidskr.20.1006. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). flått i nord. [Journal]. altaposten. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Infalmmasjon og infeskjon i nervesystemet. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Nevroborreliose. [Internet]. db.no. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Misliker du flåtten? Nå kan det komme en løsning. [Internet]. nrk.viten. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Flåtten, hvor redde må vi være. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). flere blir syke av flåttbitt. [Journal]. Romedals budstikke. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). sykdommer som smitter ved flåttbitt. [Internet]. tv2.no. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). covita studien. [Journal]. fvn.no. Fulltekst i vitenarkiv
• Eikeland, Randi (2021). Bekymret for pasientene. [Journal]. askøyvøringen. Fulltekst i vitenarkiv
• Smaradottir, Berglind; Eikeland, Randi; Reiso, Harald & Fensli, Rune Werner (2018). User-Centered Design of a National Medical Registry for Tick-Borne Diseases. Fulltekst i vitenarkiv

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