Publications
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Skarstein, Ingerid; Solheim, Anne Marit; Lorentzen, Åslaug Rudjord; Ljøstad, Unn; Mygland, Åse Daasvand & Eikeland, Randi
[Show all 11 contributors for this article]
(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.
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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.
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Skudal, Hilde Kristin; Lorentzen, Åslaug Rudjord; Stenstad, Tore; Paulsen, Else Quist; Fevang, Børre & Jaioun, Keson
[Show all 10 contributors for this article]
(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.
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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.
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Torkildsen, Øivind; Brustad, Hilde Kjelgaard; Høgestøl, Einar August; Alstadhaug, Karl Bjørnar; Bhan, Alok & Flemmen, Heidi Øyen
[Show all 22 contributors for this article]
(2026).
Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis.
New England Journal of Medicine.
ISSN 0028-4793.
395(1),
p. 44–53.
doi:
10.1056/nejmoa2600993.
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BACKGROUND
Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking.
METHODS
In this phase 3, multicenter, double-blind, noninferiority trial, we randomly assigned adults with newly diagnosed relapsing multiple sclerosis and recent disease activity
in a 3:2 ratio to receive rituximab or ocrelizumab every 6 months for 24 months. The primary end point was the absence of new or enlarging lesions on T2-weighted
magnetic resonance imaging (MRI) from month 6 to month 24. Noninferiority was defined as a lower limit of the 95% confidence interval for the risk difference (ritux-
imab minus ocrelizumab) of greater than or equal to −10 percentage points. Secondary end points included efficacy and safety.
RESULTS
A total of 218 participants underwent randomization; 216 received treatment (132 assigned to the rituximab group and 84 assigned to the ocrelizumab group). Between
months 6 and 24, the estimated probability of having no new or enlarging lesions detected on T2-weighted MRI was 92.2% with rituximab and 94.8% with ocrelizumab,
corresponding to a risk difference of –2.6 percentage points (95% confidence interval, –9.4 to 4.3), which met the prespecified noninferiority criterion. Relapse rates, dis-
ability outcomes, and cognitive-performance profiles appeared to be similar in the two groups. Infections were more common in the rituximab group than in the ocreliz-
umab group (in 82% vs. 69% of participants), although the percentage of participants with serious adverse events was similar in the two groups (8% and 7%, respectively).
CONCLUSIONS
In participants with newly diagnosed relapsing multiple sclerosis and recent disease activity, rituximab was noninferior to ocrelizumab in suppressing disease activity as
detected by MRI from 6 to 24 months, with a similar incidence of serious adverse events.
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Rasmussen, Tilde Harridsleff; Schikora-Rustad, Stine; Lorentzen, Åslaug Rudjord; Tran, Trung; Øverås, Mathias Herstad & Myhr, Kjell-Morten
[Show all 22 contributors for this article]
(2026).
Low risk of severe COVID-19 in vaccinated people with multiple sclerosis: a nationwide Norwegian study.
BMJ Neurology Open.
8(1).
doi:
10.1136/bmjno-2026-001556.
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Background: We aimed to assess antibody responses and COVID-19 outcomes after vaccination in people with multiple sclerosis (pwMS) receiving disease-modifying therapies.
Methods: NevroVAX is a Norwegian multicentre cohort study including 3559 pwMS and 449 healthy controls (HCs) who received at least one dose of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or ChAdOx1 (AstraZeneca/Oxford) between January 2021 and December 2022. Data from records, registries, questionnaires and blood samples collected June 2021–November 2023 were analysed. Primary outcomes were humoral immune responses assessed by seroconversion (anti-spike and anti-receptor-binding domain (RBD) IgG ≥5 binding antibody units/mL). Secondary outcomes included quantitative anti-RBD IgG levels, breakthrough SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Associations with breakthrough infection were evaluated using multivariable logistic regression.
Results: Among 3559 pwMS, 1201 received anti-CD20 monoclonal antibodies and 324 sphingosine-1-phosphate receptor (S1PR) modulators. After three vaccine doses, seroconversion was observed in 43.0% of anti-CD20-treated patients and 48.4% of S1PR-treated patients. In multivariable analysis, seroconversion was associated with lower risk of breakthrough infection (OR 0.67, 95% CI 0.58 to 0.78). During follow-up, 58 pwMS (1.6%) were hospitalised for COVID-19; 4 (0.1%) required non-invasive ventilatory support, no patients required invasive ventilation and no deaths occurred.
Conclusions: Humoral vaccine responses were impaired in pwMS receiving anti-CD20 or S1PR therapies, but severe COVID-19 was rare. These findings support continued vaccination programmes and tailored protective measures for immunomodulated populations.
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Skudal, Hilde Kristin; Stenstad, Tore; Lorentzen, Åslaug Rudjord; Paulsen, Else Quist; Egeland, Jens & Fevang, Børre
[Show all 12 contributors for this article]
(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.
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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.
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Skarstein, Ingerid; Ulvestad, Elling; Solheim, Anne Marit; Vedeler, Christian; Ljøstad, Unn & Mygland, Åse
[Show all 10 contributors for this article]
(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,
p. 2768–2775.
doi:
10.1007/s00415-024-12237-z.
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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.
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Lorentzen, Åslaug Rudjord; Berg, Kristine Karlsrud & Ljøstad, Unn
(2024).
Rituximab leading to an atypical presentation of neuroborreliosis and false negative serology.
Practical Neurology.
ISSN 1474-7758.
24(3),
p. 215–218.
doi:
10.1136/pn-2023-003976.
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Quarsten, Hanne; Andreassen, Åshild Kristine; Paulsen, Katrine Mørk; Diekmann, Maria Juul; Eikeland, Randi & Helleren, Rita
[Show all 9 contributors for this article]
(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.
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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.
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Kvistad, Christopher Elnan; Lehmann, Anne Kristine; Stokke, Silje Agnethe; Holmøy, Trygve; Lorentzen, Åslaug Rudjord & Trovik, Linn
[Show all 9 contributors for this article]
(2024).
Autologous hematopoietic stem cell transplantation for multiple sclerosis: Long-term follow-up data from Norway.
Multiple Sclerosis.
ISSN 1352-4585.
30(6),
p. 751–754.
doi:
10.1177/13524585241231665.
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Background: Autologous hematopoietic stem cell transplantation (HSCT) is a potent treatment option for patients with aggressive relapsing-remitting multiple sclerosis (RRMS). Objective: To evaluate long-term outcomes of HSCT in MS. Methods: National retrospective single-center observational study of patients with aggressive RRMS that underwent HSCT in Norway from January 2015 to January 2018. Criteria for receiving HSCT included at least two clinical relapses the last year while on disease modifying treatment (DMT). Results: In total, 29 patients, with a mean follow-up time of 70 months (standard deviation:14.3), were evaluated. Twenty patients (69%) had sustained no evidence of disease activity (NEDA-3) status, 24 (83%) were relapse-free, 23 (79%) free of magnetic resonance imaging (MRI) activity, and 26 (90%) free of progression. Number of patients working full-time increased from 1 (3%), before HSCT, to 10 (33%) after 2 years and 15 (52%) after 5 years. Conclusion: HSCT offers long-term disease-free survival with successively increasing work participation in patients with aggressive MS resistant to DMTs.
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Solheim, Anne Marit; Skarstein, Ingerid; Quarsten, Hanne; Lorentzen, Åslaug Rudjord; Berg-Hansen, Pål & Eikeland, Randi
[Show all 9 contributors for this article]
(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.
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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.
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Skudal, Hilde Kristin; Lorentzen, Åslaug Rudjord; Stenstad, Tore; Paulsen, Else Quist; Egeland, Jens & Fevang, Børre
[Show all 13 contributors for this article]
(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),
p. 1355–1366.
doi:
10.1007/s10096-024-04855-2.
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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.
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Lindland, Elisabeth S.; Røvang, Martin S.; Solheim, Anne Marit; Andreassen, Silje; Skarstein, Ingerid & Dareez, Nazeer
[Show all 17 contributors for this article]
(2024).
Are white matter hyperintensities associated with neuroborreliosis? The answer is twofold.
Neuroradiology.
ISSN 0028-3940.
67,
p. 37–48.
doi:
10.1007/s00234-024-03482-0.
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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.
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Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Andreassen, Silje; Bugge, Robin Antony Birkeland; Eikeland, Randi & Reiso, Harald
[Show all 10 contributors for this article]
(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.
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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.
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Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Beyer, Mona K.; Solheim, Anne Marit; Ljøstad, Unn & Mygland, Åse Daasvand
[Show all 13 contributors for this article]
(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.
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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.
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Bernardsjaw, Emilie; Gynthersen, Rosa; Bremell, Daniel; Mens, Helene; Stenør, Christian & Lorentzen, Åslaug Rudjord
[Show all 9 contributors for this article]
(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.
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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.
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Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Dareez, Muhammad Nazeer; Eikeland, Randi; Ljøstad, Unn & Mygland, Åse Daasvand
[Show all 10 contributors for this article]
(2022).
Enhancement of cranial nerves in Lyme neuroborreliosis: incidence and correlation with clinical symptoms and prognosis.
Neuroradiology.
ISSN 0028-3940.
64,
p. 2323–2333.
doi:
10.1007/s00234-022-02957-2.
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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.
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Andreassen, Silje; Solheim, Anne Marit; Ljøstad, Unn; Mygland, Åse Daasvand; Lorentzen, Åslaug Rudjord & Reiso, Harald
[Show all 10 contributors for this article]
(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.
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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.
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Solheim, Anne Marit; Lorentzen, Åslaug Rudjord; Dahlberg, Audun Olav; Flemmen, Heidi Øyen; Brune, Synne & Forselv, Kristine Johanne Nordstrøm
[Show all 12 contributors for this article]
(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),
p. 1222–1228.
doi:
10.1136/jnnp-2022-329724.
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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.
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Eid, Karine; Torkildsen, Øivind Fredvik Grytten; Aarseth, Jan Harald; Flemmen, Heidi Øyen; Holmøy, Trygve & Lorentzen, Åslaug Rudjord
[Show all 15 contributors for this article]
(2021).
Perinatal Depression and Anxiety in Women with Multiple Sclerosis: A Population-Based Cohort Study.
Neurology.
ISSN 0028-3878.
96(23),
p. e2789–e2800.
doi:
10.1212/WNL.0000000000012062.
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Objective: To assess the occurrence of perinatal depression and anxiety in women before and after diagnosis of multiple sclerosis (MS).
Methods: 114,629 pregnant women were included in the Norwegian Mother, Father and Child Cohort study 1999-2008. We assessed depression and anxiety by questionnaires during and after pregnancy. Women with MS were identified from national health registries and hospital records and grouped into 1) MS diagnosed before pregnancy (n = 140), MS diagnosed after pregnancy with 2) symptom onset before pregnancy (n = 98) and 3) symptom onset after pregnancy (n = 308). Thirty-five women were diagnosed with MS in the postpartum period. The reference group (n = 111,627) consisted of women without MS.
Results: Women with MS diagnosed before pregnancy had an adjusted odds ratio of 2.0 (95% confidence interval 1.2-3.1) for depression in the third trimester. Risk factors were adverse socioeconomic factors, history of psychiatric disease and physical/sexual abuse. The risk of anxiety was not increased. Women diagnosed with MS in the postpartum period had especially high risk of postpartum depression. Women with MS symptom onset within 5 years after pregnancy had increased risk of both depression and anxiety during pregnancy, whereas women with more than 5 years until symptom onset did not.
Conclusion: Women diagnosed with MS have increased risk of perinatal depression. Women with MS symptom onset within 5 years after pregnancy have increased risk of both depression and anxiety during pregnancy.
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König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, Trung; Schikora-Rustad, Stine & Vaage, Eline Benno
[Show all 22 contributors for this article]
(2021).
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.
Journal of Neurology, Neurosurgery and Psychiatry.
ISSN 0022-3050.
doi:
10.1136/jnnp-2021-327612.
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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.
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Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Beyer, Mona K.; Ljøstad, Unn & Mygland, Åse Daasvand
[Show all 11 contributors for this article]
(2021).
Cognitive function, fatigue and Fazekas score in patients with acute neuroborreliosis.
Ticks and Tick-borne Diseases.
ISSN 1877-959X.
12(3),
p. 1–5.
doi:
10.1016/j.ttbdis.2021.101678.
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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.
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Eikeland, Randi; Ljøstad, Unn; Helgeland, Geir; Sand, Geir; Flemmen, Heidi Øyen & Bø, Margrete Halvorsen
[Show all 10 contributors for this article]
(2020).
Patient-reported outcome after treatment for definite Lyme neuroborreliosis.
Brain and Behavior.
10(4),
p. 1–7.
doi:
10.1002/brb3.1595.
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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.
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Thortveit, Erik Thomas; Aase, Audun; Petersen, Lizette Balle; Lorentzen, Åslaug Rudjord; Mygland, Åse & Ljøstad, Unn
(2020).
Subjective health complaints and exposure to tick-borne infections in southern Norway.
Acta Neurologica Scandinavica.
ISSN 0001-6314.
142(3),
p. 260–266.
doi:
10.1111/ane.13263.
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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.
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Thortveit, Erik Thomas; Aase, Audun; Petersen, Lizette Balle; Lorentzen, Åslaug Rudjord; Mygland, Åse & Ljøstad, Unn
(2020).
Human seroprevalence of antibodies to tick-borne microbes in southern Norway.
Ticks and Tick-borne Diseases.
ISSN 1877-959X.
11(4),
p. 1–6.
doi:
10.1016/j.ttbdis.2020.101410.
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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.
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Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Andreassen, Silje; Paulsen, Else Quist; Eikeland, Randi & Ljøstad, Unn
[Show all 12 contributors for this article]
(2018).
Imaging in Lyme neuroborreliosis.
Insights into Imaging.
9(5),
p. 833–844.
doi:
10.1007/s13244-018-0646-x.
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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.
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Thortveit, Erik Thomas; Lorentzen, Åslaug Rudjord; Ljøstad, Unn & Mygland, Åse
(2018).
Somatic symptoms and fatigue in a Norwegian population with high exposure to ticks.
Ticks and Tick-borne Diseases.
ISSN 1877-959X.
10(1),
p. 156–161.
doi:
10.1016/j.ttbdis.2018.09.012.
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Lorentzen, Åslaug Rudjord; Forselv, Kristine Johanne Nordstrøm; Helgeland, Geir; Salvesen, Rigmor Elisabeth; Sand, Geir & Flemmen, Heidi Øyen
[Show all 16 contributors for this article]
(2017).
Lyme neuroborreliosis: do we treat according to guidelines?
Journal of Neurology.
ISSN 0340-5354.
264(7),
p. 1506–1510.
doi:
10.1007/s00415-017-8559-z.
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Show summary
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.
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Lossius, Peter Andreas Vold; Tomescu-Baciu, Alina; Holmøy, Trygve; Vedeler, Christian A.; Røsjø, Egil Rørvik & Lorentzen, Åslaug Rudjord
[Show all 8 contributors for this article]
(2017).
Selective intrathecal enrichment of G1m1-positive B cells in multiple sclerosis.
Annals of clinical and translational neurology.
4(10),
p. 756–761.
doi:
10.1002/acn3.451.
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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.
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Maniaol, Angelina; Elsais, Ahmed; Lorentzen, Åslaug Rudjord; Owe, Jone Furulund; Viken, Marte K & Sæther, Hanne Skarpodde
[Show all 17 contributors for this article]
(2012).
Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population.
PLOS ONE.
7(5).
doi:
10.1371/journal.pone.0036603.
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Background: Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. Methodology/Principal Findings: This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥60years) (OR 2.38, pc7.4×10−5). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, pc 4.71×10−4), a finding not previously described. No significant association was found to the DRB1*07:01 allele (pnc = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. Conclusion: The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG.
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Harbo, Hanne Flinstad; Lorentzen, Åslaug Rudjord; Lie, Benedicte Alexandra; Celius, Elisabeth Gulowsen & Spurkland, Anne
(2011).
Nytt genkart for multippel sklerose.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
131(21),
p. 2126–2130.
doi:
10.4045/tidsskr.10.0823.
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Ban, Maria; Booth, David R; Heard, Robert N; Stewart, Graeme J; Goris, An & Dobosi, Rita
[Show all 33 contributors for this article]
(2009).
The expanding genetic overlap between multiple sclerosis and type I diabetes.
Genes and Immunity.
ISSN 1466-4879.
10(1),
p. 11–14.
doi:
10.1038/gene.2008.83.
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Familial clustering of autoimmune disease is well recognized and raises the possibility that some susceptibility genes may predispose to autoimmunity in general. In light of this observation, it might be expected that some of the variants of established relevance in one autoimmune disease may also be relevant in other related conditions. On the basis of this hypothesis, we tested seven single nucleotide polymorphisms (SNPs) that are known to be associated with type I diabetes in a large multiple sclerosis data set consisting of 2369 trio families, 5737 cases and 10,296 unrelated controls. Two of these seven SNPs showed evidence of association with multiple sclerosis; that is rs12708716 from the CLEC16A gene (P=1.6 x 10(-16)) and rs763361 from the CD226 gene (P=5.4 x 10(-8)). These findings thereby identify two additional multiple sclerosis susceptibility genes and lend support to the notion of autoimmune susceptibility genes.
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Harbo, Hanne Flinstad; Ekstrom, PO; Lorentzen, Åslaug Rudjord; Gjerstad, Vibeke Sundvold; Celius, EG & Sawcer, Stephen
[Show all 7 contributors for this article]
(2006).
Coding region polymorphisms in T cell signal transduction genes. Prevalence and association to development of multiple sclerosis.
Journal of Neuroimmunology.
ISSN 0165-5728.
177,
p. 40–45.
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Lorentzen, Åslaug Rudjord; Celius, Elisabeth Gulowsen; Ekstrøm, Per Olaf; Wiencke, Kristine; Lie, Benedicte Alexandra & Myhr, KM
[Show all 11 contributors for this article]
(2005).
Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients.
Journal of Neuroimmunology.
ISSN 0165-5728.
166.
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Harbo, Hanne Flinstad; Lie, Benedicte Alexandra; Sawcer, Stephen; Celius, EG; Dai, Kezheng & Oturai, Anette
[Show all 22 contributors for this article]
(2004).
Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.
Tissue Antigens.
ISSN 0001-2815.
63,
p. 237–247.
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In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.
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Smerdel, Anna; Dai, Kezheng; Lorentzen, Åslaug Rudjord; Flatø, Berit; Maslinski, S & Thorsby, Erik
[Show all 8 contributors for this article]
(2004).
Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene.
Genes and Immunity.
ISSN 1466-4879.
5(4),
p. 310–312.
Full text in Research Archive
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T-cell-specific adapter protein (TSAd) involved in the negative control of T-cell activation is encoded by the SH2D2A gene. Our recent studies indicate that homozygosity for short (ie GA(13) and GA(16)) alleles of the SH2D2A gene promoter is associated with development of multiple sclerosis. To study whether the same SH2D2A promoter polymorphism also contributes to the genetic susceptibility to develop juvenile rheumatoid arthritis (JRA), we examined 210 JRA patients and 558 healthy unrelated controls from Norway. The frequency of the short allele GA(13) was increased among the JRA patients compared to control (0.098 vs 0.05; P(n=8)=0.042). There was a significant increased frequency of HLA-DRB1(*)08-positive patients carrying two copies of 'short' alleles GA(13) and/or GA(16) compared to healthy controls (16% vs 6%; P(n=4)=0.016). Our data indicate that the 'short' alleles of the SH2D2A promoter could contribute to the genetic susceptibility to JRA.
View all works in NVA
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Skarstein, Ingerid; Solheim, Anne Marit; Quarsten, Hanne; Ljøstad, Unn; Mygland, Åse Daasvand & Lorentzen, Åslaug Rudjord
[Show all 10 contributors for this article]
(2026).
Definite neuroborreliosis with atypical antibody-profiles: a case report.
doi:
10.1186/s13256-026-05925-z.
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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.
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Lorentzen, Åslaug Rudjord; Ban, Maria; Booth, David; Heard, Robert; Stewart, Graeme & Goris, An
[Show all 33 contributors for this article]
(2008).
The expanding genetic overlap between multiple sclerosis and type 1 diabetes.
Full text in Research Archive
Show summary
A familial clustering of autoimmune disease is well recognised and suggests that some susceptibility genes may predispose to autoimmunity in general whereas other genes lead to specific disease. On the basis of this hypothesis it may be expected that variants of established relevance in one autoimmune disease might also be relevant in other related conditions.
To investigate this we tested seven single nucleotide polymorphisms (SNPs) that are known to be associated with type I diabetes in a large multiple sclerosis dataset consisting of 2,369 trio families, 5,737 cases and 10,296 unrelated controls. Samples were recruited from across six countries: Australia, Belgium, Norway, Sweden, United Kingdom (UK) and the United States of America (USA) within the IMSGC.
Two of these seven SNPs emerged as also being associated with multiple sclerosis; rs12708716 from the C-type lectin domain family 16, member A (CLEC16A) gene (p=1.6x10-15) and rs763361 from the CD226 gene (p=5.4x10-8). In each case the allele associated with increased risk for multiple sclerosis was identical to that showing evidence for association with T1D.
These findings thereby confirm two additional multiple sclerosis susceptibility genes and lend support to the notion of commonality amongst autoimmune susceptibility genes.
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Lorentzen, Åslaug Rudjord; Karlsen, Tom Hemming; Olsson, Marita; Smestad, Cathrine; Mero, Inger-Lise & Woldseth, Bente
[Show all 13 contributors for this article]
(2008).
Protection against multiple sclerosis conferred by carriage of the inhibitory killer immunoglobulin-like receptors (KIRs) ligand HLA-Bw4.
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Background: Combinations of killer immunoglobulin-like receptors (KIRs) and HLA class I ligands that reduce natural killer (NK) cells inhibition may increase the risk of autoimmune diseases.
Multiple sclerosis (MS) is affecting the central nervous system and is presumed to be an autoimmune disease. There are significant genetic associations to genes in the HLA class II region (DRB1*1501-haplotype),but associations to genes in the HLA class I region have also been reported (for instance A2, A3 and Cw*05).
We investigated whether there might be associations to given KIRs and/or their HLA class I ligands .
Materials and methods: 631 Norwegian MS patients and 555 Norwegian controls were typed for the presence or absence of genes encoding inhibiting KIRs (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, KIR3DL1, KIR3DL2 and KIR3DL3) and activating KIRs (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5 and KIR2DL4) using sequence specific primers. HLA-A, -B, -C and –DRB1 typing was performed by direct sequencing or sequence specific primers.
Results: We found no significant differences in gene carrier frequencies of inhibitory and activating KIRs in MS patients as compared to controls when p-values were adjusted for number of KIR genes investigated. However, the frequency of the HLA-Bw4 specificity was significantly reduced in MS patients as compared to controls (41.5% vs. 55.1%, p=4.9*10-6), even in individuals who did not carry any of the known HLA class II risk alleles (DRB1*1501,DRB1*03 and DRB1*01, p=0.002). No HLA class II independent associations were observed to genes at the HLA-C or HLA -A loci.
Conclusion: The presence of the HLA-Bw4 specificity seems to protect against MS in an HLA class II independent manner. Ongoing analyses aim to characterize possible interaction effects between HLA-Bw4 and KIR3DL1 and KIR3DS1, as well as between HLA-C1 and C2 groups and their corresponding receptors.
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Harbo, Hanne Flinstad; Utsi, E; Lorentzen, Åslaug Rudjord; Kampman, M T; Celius, EG & Myhr, KM
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(2006).
Low prevalence of multiple sclerosis in a Sami population is related to low frequency of the disease-associated HLA DR15-DQ6 haplotype.
Tissue Antigens.
ISSN 0001-2815.
67,
p. 523–523.
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