| 1. |
- Kanberg, Nelly, et al.
(author)
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COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.
- 2024
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In: The Journal of infectious diseases. - 1537-6613. ; 229:2, s. 493-501
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Journal article (peer-reviewed)abstract
- To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC).Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed.SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, β2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies.We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.
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| 2. |
- Avellan, Sanna, 1990, et al.
(author)
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Adjunctive Corticosteroids for Lyme Neuroborreliosis Peripheral Facial Palsy-A Prospective Study With Historical Controls
- 2021
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:7, s. 1211-1215
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Journal article (peer-reviewed)abstract
- Background. Lyme neuroborreliosis peripheral facial palsy (LNB PFP) and idiopathic PFP, Bell's palsy (BP), are the most common causes of facial palsy in borrelia-endemic areas and are clinically similar. Early treatment with corticosteroids has been shown to be effective in Bell's palsy, and antibiotics improve the outcome in LNB. However, there is a lack of knowledge on how the addition of corticosteroids to standard antibiotic treatment affects the outcome in LNB PFP. Methods. This prospective, open trial with historical controls was conducted at 2 large hospitals in western Sweden between 2011 and 2018. Adults who presented with LNB PFP were included in the study group and were treated with oral doxycycline 200 mg twice daily for 10 days and prednisolone 60 mg once daily for 5 days, then tapered over 5 days. The historical controls were adult patients with LNB PFP included in previous studies and treated with oral doxycycline. Both groups underwent a follow-up lumbar puncture and were followed until complete recovery or for 12 months. Results. Fifty-seven patients were included, 27 in the study group and 30 in the control group. Two patients (7%) in the study group and 6 patients (20%) in the control group suffered from sequelae at the end follow-up. There was no statistically significant difference between the groups, either in the proportion of patients with sequelae or in the decline in cerebrospinal fluid mononuclear cell count. Conclusions. Adjunctive corticosteroids neither improve nor impair the outcome for patients with LNB PFP treated with doxycycline.
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| 3. |
- Avellan, Sanna, 1990, et al.
(author)
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Incidence of Lyme Carditis and Lyme Carditis as a Cause of Pacemaker Implantation: A Nationwide Registry-Based Case-Control Study
- 2024
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In: OPEN FORUM INFECTIOUS DISEASES. - 2328-8957. ; 11:2
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Journal article (peer-reviewed)abstract
- Background Lyme borreliosis (LB) of the heart is called Lyme carditis (LC), which often manifests with high-grade atrioventricular block (AVB) requiring pacemaker implantation. LC is treated with antibiotics, and most patients recover fully after treatment. The overall incidence of LC, and of LC as a cause of pacemaker implantation, has not previously been systematically studied.Methods This was a case-control study based on data from Swedish national registers. The study was divided into two parts; part 1 including all patients diagnosed with AVB between 2001 and 2018, and part 2 including all patients who had received a pacemaker due to AVB between 2010 and 2018. Patients diagnosed with LB 90 days before and 180 days after the AVB diagnosis were identified among the patients and compared to matched control groups generated from the general population.Results Of 81 063 patients with AVB, 102 were diagnosed with LB. In the control group, 27 were diagnosed with LB. The yearly incidence of LC was 0.056 per 100 000 adults and year. Of 25 241 patients who had received a pacemaker for AVB, 31 were diagnosed with LB. In the control group, 8 were diagnosed with LB. The yearly incidence of LC as a cause of pacemaker implantation was 0.033 per 100 000 adults and year. The estimated risk for patients with LC to receive a permanent pacemaker was 59%.Conclusions LC is a rare cause of AVB. Nevertheless, more than half of patients with LC receive a permanent pacemaker for a condition that is easily cured with antibiotics. In this nationwide registry-based study, we present data on the incidence of Lyme carditis, Lyme carditis as a cause of pacemaker implantation, and the risk for patients with Lyme carditis to receive a permanent pacemaker.
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| 4. |
- Bernardshaw, E., et al.
(author)
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Antibiotic therapy of neuroborreliosis: A survey among infectious disease specialists and neurologists in Norway, Sweden, and Denmark
- 2022
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In: Ticks and Tick-Borne Diseases. - : Elsevier BV. - 1877-959X. ; 13:6
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Journal article (peer-reviewed)abstract
- 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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| 6. |
- Bremell, Daniel, 1978, et al.
(author)
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Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
- 2013
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In: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
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Journal article (peer-reviewed)abstract
- Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
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| 7. |
- Bremell, Daniel, 1978, et al.
(author)
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Clinical characteristics and cerebrospinal fluid parameters in patients with peripheral facial palsy caused by Lyme neuroborreliosis compared with facial palsy of unknown origin (Bell's palsy).
- 2011
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In: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Bell's palsy and Lyme neuroborreliosis are the two most common diagnoses in patients with peripheral facial palsy in areas endemic for Borrelia burgdorferi. Bell's palsy is treated with corticosteroids, while Lyme neuroborreliosis is treated with antibiotics. The diagnosis of Lyme neuroborreliosis relies on the detection of Borrelia antibodies in blood and/or cerebrospinal fluid, which is time consuming. In this study, we retrospectively analysed clinical and cerebrospinal fluid parameters in well-characterised patient material with peripheral facial palsy caused by Lyme neuroborreliosis or Bell's palsy, in order to obtain a working diagnosis and basis for treatment decisions in the acute stage. METHODS: Hospital records from the Department of Infectious Diseases, Sahlgrenska University Hospital, for patients with peripheral facial palsy that had undergone lumbar puncture, were reviewed. Patients were classified as Bell's palsy, definite Lyme neuroborreliosis, or possible Lyme neuroborreliosis, on the basis of the presence of Borrelia antibodies in serum and cerebrospinal fluid and preceding erythema migrans. RESULTS: One hundred and two patients were analysed; 51 were classified as Bell's palsy, 34 as definite Lyme neuroborreliosis and 17 as possible Lyme neuroborreliosis. Patients with definite Lyme neuroborreliosis fell ill during the second half of the year, with a peak in August, whereas patients with Bell's palsy fell ill in a more evenly distributed manner over the year. Patients with definite Lyme neuroborreliosis had significantly more neurological symptoms outside the paretic area of the face and significantly higher levels of mononuclear cells and albumin in their cerebrospinal fluid. A reported history of tick bite was uncommon in both groups. CONCLUSIONS: We found that the time of the year, associated neurological symptoms and mononuclear pleocytosis were strong predictive factors for Lyme neuroborreliosis as a cause of peripheral facial palsy in an area endemic for Borrelia. For these patients, we suggest that ex juvantibus treatment with oral doxycycline should be preferred to early corticosteroid treatment.
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| 8. |
- Bremell, Daniel, 1978
(author)
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Lyme Neuroborreliosis - Diagnosis and Treatment
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Lyme neuroborreliosis, the infection of the nervous system by the tick-borne bacterium Borrelia burgdorferi, is a common infection in the temperate parts of the Northern hemisphere. Manifestations of the disease include facial palsy, radicular pain, sensory disturbances, and occasionally CNS symptoms such as confusion and paraparesis. The diagnosis of Lyme neuroborreliosis is based on medical history, clinical examination and cerebrospinal fluid (CSF) analysis. Recommended antibiotic treatment is oral doxycycline or intravenous ceftriaxone. The overall aims of this thesis were to improve the diagnosis and treatment of Lyme neuroborreliosis. In paper I, 102 patients with peripheral facial palsy were studied. Onset of symptoms in July to October, additional neurological symptoms and CSF pleocytosis were factors that discriminate patients with peripheral facial palsy caused by Lyme neuroborreliosis from patients with Bell’s palsy. In paper II, it was shown that CSF levels of the chemokine CXCL13 are highly elevated in Lyme neuroborreliosis and that levels decline after treatment, but high and overlapping CXCL13 levels were also seen in patients with asymptomatic HIV-infection and the decrease in CXCL13 is correlated to the decrease in CSF cell count. The additional diagnostic value of CXCL13 analysis is therefore limited. In paper III, new reference ranges for CSF cell counts when analyzed with automatic cell counters were determined, based on CSF sampling of 80 healthy volunteers. The differentiation of mononuclear cells into lymphocytes and monocytes was shown to be of limited value in the discrimination between Lyme neuroborreliosis and viral CNS infections. In paper IV, it was shown that treatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with peripheral nervous systems symptoms, and that all patients with CNS symptoms improved on treatment with no need for retreatment. Oral doxycycline can therefore be considered an effective treatment for Lyme neuroborreliosis, irrespective of the severity of symptoms.
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| 9. |
- Bremell, Daniel, 1978, et al.
(author)
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Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review.
- 2011
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In: Journal of medical case reports. - : Springer Science and Business Media LLC. - 1752-1947. ; 5:465
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Journal article (peer-reviewed)abstract
- ABSTRACT: INTRODUCTION: Lyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV) -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth case Case presentations: We present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis. CONCLUSION: Given the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with oral doxycycline with a good outcome, further proving the efficacy of this regime.
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| 10. |
- Bremell, Daniel, 1978, et al.
(author)
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Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis, myelitis, vasculitis or intracranial hypertension
- 2014
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In: European Journal of Neurology. - : Wiley. - 1351-5101. ; 21:9, s. 1162-1167
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Journal article (peer-reviewed)abstract
- Background and purpose: The treatment recommendation for Lyme neuroborreliosis with central nervous system (CNS) symptoms is intravenous ceftriaxone, according to current American and European guidelines. For Lyme neuroborreliosis with peripheral nervous system (PNS) symptoms, treatment with intravenous ceftriaxone and oral doxycycline is considered equally effective. The purpose of this study was to evaluate the efficacy of oral doxycycline in the treatment of Lyme neuroborreliosis with CNS symptoms. Methods: Patients with Lyme neuroborreliosis who had undergone cerebrospinal fluid (CSF) sampling before and after treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, during the period 1990-2012, were included in this retrospective study. The CSF mononuclear cell count was used as a surrogate marker of treatment outcome. Comparisons of CSF mononuclear cell counts were made between patients with CNS symptoms and patients with PNS symptoms before and after treatment with oral doxycycline. Results: Twenty-six patients classified as having CNS symptoms and 115 patients classified as having PNS symptoms were included. The decline in CSF mononuclear cell counts did not differ significantly between the two groups of patients. All patients with CNS disease showed a marked clinical improvement after treatment, even though 62% had remaining symptoms at the end of follow-up. Conclusion: Treatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with Lyme neuroborreliosis with PNS symptoms. The results indicate that oral doxycycline is an effective treatment for Lyme neuroborreliosis irrespective of the severity of symptoms.
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