Tickborne Encephalitis Virus, Norway and Denmark

Serum from 2 Norwegians with tickborne encephalitis (TBE) (1 of whom was infected in Denmark) and 810 Norwegian ticks were tested for TBE virus (TBEV) RNA by reverse transcription–polymerase chain reaction. Sequencing and phylogenetic analysis were performed. This is the first genome detection of TBEV in serum from Norwegian patients

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

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

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

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

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

publishedVersionPaid Open Acces

Genetic epidemiology of amyotrophic lateral sclerosis in Norway - a 2-year population based study

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.publishedVersio

Risk factors for a non-favourable outcome after treated European Neuroborreliosis

Aim: To identify risk factors for a non-favourable long term outcome with respect to Health Related Quality of Life (HRQoL) and fatigue after treated Lyme Neuroborreliosis (LNB). Methods: We followed 50 LNB patients, and assessed outcome by the self-report questionnaires Short Form-36 (SF-36) and Fatigue Severity Scale (FSS) 30 months after treatment. We analyzed associations between these outcomes and demographical, clinical and laboratory data by univariate analyses and linear regression. Clinical status was assessed by a composite score based on subjective complaints and objective findings. Results: Pre-treatment symptom duration > 6 weeks (B=-10.2, P=0.002) and non-complete recovery at 12 months (B=-5.6, P=0.033) were associated with lower scores in the SF-36 domain Physical Component Summary (R2=0.59). Non-complete recovery at 4 months was associated with lower scores in the SF-36 domain Mental Component Summary (B=-8.9, P=0.01 (R2= 0.37)). Pre-treatment symptom duration > 6 weeks (B=1.3, P= 0.028), high scores on the composite clinical score pre-treatment (B=0.1, P=0.019) and non-complete recovery at 12 months (B=1.7, P=0.001) were associated with higher FSS scores (R2=0.70). No laboratory test results were associated with these outcomes. Conclusions: Delayed treatment start, more symptoms and findings before and non-complete recovery at 4 and 12 months after treatment seem to predict a non-favourable outcome regarding HRQoL and fatigue 30 months after treated LNB. Age, gender, educational level involvement of the central nervous system pre-treatment, coexisting diseases and cerebrospinal fluid findings before treatment and during follow-up, were not long term HRQoL and fatigue

First Human Cases of Tickborne Encephalitis, Norway

The first reported case of tickborne encephalitis (TBE) in Norway occurred in 1997. From 1997 to 2003, from zero to two cases of human TBE have been diagnosed per year in Norway; a total of eight cases have been diagnosed. Clinical TBE cases in dogs are not reported in Norway

Quality of multiple sclerosis out-patient health care services with focus on patient reported experiences

Abstract Background To investigate multiple sclerosis (MS) patients’ satisfaction with out-patient follow-up in a general neurological hospital department. Patients with definite MS living in Vest-Agder county, Norway were invited to answer a questionnaire comprising one question regarding overall satisfaction, and 24 questions regarding demographics, disease characteristics, and experiences with different aspects of the health care services. Results Out of 330 invited patients, 159 responded (48%). Mean overall satisfaction with health care was 3.5 (SD = 1.03) on a 1–5 Likert scale (1 = not at all, 5 = to a very large extent). The best sub scores were given on confidence in the physician’s competence (mean = 4.01), the physician speaks in an understandable way (mean = 4.07), expectation of good treatment (mean = 3.72), and perception of being submitted to wrong treatment (mean = 1.5). The worst scores were given on satisfaction with frequency of outpatient appointments (mean = 2.89) and delay of outpatient appointments (mean = 3.07). Four factors were associated with high overall satisfaction; receiving the disease modifying drug natalizumab (B = 0.549, p = 0.004), satisfaction with frequency of outpatient appointments (B = 0.242, p < 0.001), experience that the physician facilitates talking about what the patient finds important (B = 0.218, p = 0.001), and confidence with the physician’s competence (B = 0.453, p < 0.001). Conclusion The patients were rather satisfied with the content of follow-up, and less satisfied with the structure. Regular and predictable contact with a trustworthy physician that facilitates that the patient is able to talk about what is important was associated with higher overall satisfaction

Six versus two weeks treatment with doxycycline in Lyme neuroborreliosis: the protocol of a multicentre, non-inferiority, double-blinded and randomised controlled trial

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