Anne Marit Solheim

• 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. Full text in Research Archive Show summary

  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; 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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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 [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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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 [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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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 [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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive Show summary

  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.

• Knudtzen, Fredrikke Christie; Eikeland, Randi; Bremell, Daniel; Paulsen, Else Quist; Johansen, Isik Somuncu & Solheim, Anne Marit [Show all 7 contributors for this article] (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. Full text in Research Archive Show summary

  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 [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. Full text in Research Archive Show summary

  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.

• Solheim, Anne Marit; Ljøstad, Unn & Mygland, Åse (2019). Six versus two weeks treatment with doxycycline in Lyme neuroborreliosis: the protocol of a multicentre, non-inferiority, double-blinded and randomised controlled trial. BMJ Open. 9:e027083(6), p. 1–5. doi: 10.1136/bmjopen-2018-027083. Full text in Research Archive Show summary

  Introduction: Current treatment guidelines for European Lyme neuroborreliosis (LNB) recommend cephalosporins, penicillin or doxycycline for 14–28 days but evidence for optimal treatment length is poor. Treatment lengths in clinical practice tend to exceed the recommendations. Most patients experience a rapid improvement of symptoms and neurological findings within days of treatment, but some report long-term complaints. The underlying mechanisms of remaining complaints are debated, and theories as ongoing chronic infection with Borrelia burgdorferi, dysregulated immune responses, genetic predisposition, coinfection with multiple tick-borne pathogens, structural changes in CNS and personal traits have been suggested. The main purpose of our trial is to address the hypothesis of improved outcome after long-term antibiotic treatment of LNB, by comparing efficacy of treatment with 2 and 6 weeks courses of doxycycline. Methods and analysis: The trial has a multicentre, non-inferiority, double-blinded design. One hundred and twenty patients diagnosed with LNB according to European Federation of Neurological Societies (EFNS)guidelines will be randomised to 6 or 2 weeks treatment with oral doxycycline. The patients will be followed for 12 months. The primary endpoint is improvement on a composite clinical score (CCS) from baseline to 6 months after inclusion. Secondary endpoints are improvements in the CCS 12 months after inclusion, fatigue scored on Fatigue Severity Scale, subjective symptoms on the Patient Health Questionnaire-15 scale, health-related quality of life scored on RAND 36-item short form health survey and safety as measured by side effects of the two treatment arms. Blood and cerebrospinal fluid (CSF) are collected from inclusion and throughout the follow-up and a biobank will be established. The study started including patients in November 2015 and will continue throughout December 2019. Ethics and dissemination: The study is approved by the Norwegian regional committees for medical and health research ethics and the Norwegian Medicines Agency. Data from the study will be published in peer-reviewed medical journals.

• 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. Full text in Research Archive Show summary

  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.

• Solheim, Anne Marit; Mygland, Åse & Ljøstad, Unn (2017). Quality of multiple sclerosis out-patient health care services with focus on patient reported experiences. BMC Research Notes. 10:250, p. 1–5. doi: 10.1186/s13104-017-2568-y. Full text in Research Archive

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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. Full text in Research Archive Show summary

  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.

• 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. Full text in Research Archive
• Lindland, Elisabeth M.S.; Røvang, Martin Soria; Solheim, Anne Marit; Andreassen, Silje; Dareez, Muhammad Nazeer & Eikeland, Randi [Show all 7 contributors for this article] (2023). Brain White matter hyperintensities in neuroborreliosis. a case-control study. Full text in Research Archive
• Andreassen, Silje; Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Ljøstad, Unn; Mygland, Åse Daasvand & Reiso, Harald [Show all 9 contributors for this article] (2023). Cognitive function in patients with neuroborreliosis: A prospective follow-up from the acute phase to 12 months after treatment. Full text in Research Archive
• Solheim, Anne Marit (2025). European neuroborreliosis in adults : Clinical course, treatment outcomes and diagnostic considerations. Universitetet i Bergen. ISSN 9788230897782. Full text in Research Archive Show summary

  Nevroborreliose (NB) er den nevrologiske manifestasjonen av Borrelia burgdorferi (Bb) infeksjon og kan gi et bredt spekter av symptomer. Vanligst er smertefull radikulitt og kranial nevropati, ofte kjent som Bannwarths syndrom. Langvarige plager etter behandling rapporteres hos opptil 45 % av pasientene. Da det ikke finnes en diagnostisk gullstandard, baseres diagnosen på klinisk presentasjon, utelukkelse av andre årsaker, samt funn i cerebrospinalvæsken (CSF) – pleocytose og analyse av Bb-spesifikke antistoffer. Denne avhandlingen hadde tre mål: (1) Å undersøke om en 2-ukers kur med doksysyklin er like effektiv som en 6-ukers kur ved NB, (2) å kartlegge sykdomsforløp og prognostiske markører ved NB, og (3) å undersøke parakliniske funn med relevans for diagnostiske vurderinger. Det ble utført en randomisert, placebokontrollert, dobbeltblindet, ikke-underlegenhetsstudie hvor 121 voksne pasienter med sikker eller mulig NB ble inkludert ved åtte sykehus i Sør-Norge (2015–2020). Pasientene ble randomisert til enten 2 eller 6 ukers behandling med doksysyklin-tabletter. Klinisk effekt ble vurdert med en klinisk score (CCS), pasientrapporterte spørreskjemaer (PROMS), og analyser av CSF ved inklusjon, samt etter 10 uker, 6 måneder og 12 måneder. Resultatene viste ingen signifikant forskjell i klinisk bedring mellom behandlingsgruppene ved 6 måneder selv om ikke-underlegenhet for 2-ukersbehandlingen ikke kunne fastslås statistisk. Det ble ikke observert behandlingssvikt hos noen av pasientene. Seks ukers behandling ga flere bivirkninger, men forskjellen mellom gruppene hva gjaldt bivirkninger var kun signifikant ved uke 5 av behandlingen. Ved inklusjon hadde 79 % radikulopati, 49 % facialisparese og 13 % hadde kun subjektive symptomer, hovedsakelig smerter uten objektive funn. I CSF hadde 85 % Bb-spesifikk IgG antistoffproduksjon og 82% hadde positiv CXCL13 før behandling. Ved 12 måneder hadde 58% vedvarende IgG antistoffproduksjon i CSF. Vedvarende symptomer etter 12 måneder var assosiert med høy symptombyrde før behandling. Det ble ikke funnet assosiasjon med demografiske eller parakliniske variabler. Konklusjonen er at en 2-ukers doksysyklinkur har sammenlignbar klinisk effekt som en 6-ukers kur ved NB, og har færre bivirkninger. Diagnostikken av NB bør bygge på pleocytose i CSF, og i noen tilfeller er det nyttig å supplere med CSF Bb-PCR eller CXCL13, særlig tidlig i sykdomsforløpet eller ved negative antistoffer. Vedvarende symptomer denne pasientkohorten synes å være relatert til symptombyrde før behandling.

• Fitjar, Rune Dahl; Leknes, Einar & Solheim, Anne Marit (2008). Interreg-prosjektenes betydning for norsk regionalpolitikk. International Research Institute of Stavanger. Full text in Research Archive

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