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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. TRIAL REGISTRATION: Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.
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Encefalite Transmitida por Carrapatos , Hospitalização , Índice de Gravidade de Doença , Humanos , Encefalite Transmitida por Carrapatos/epidemiologia , Encefalite Transmitida por Carrapatos/diagnóstico , Masculino , Noruega/epidemiologia , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Hospitalização/estatística & dados numéricos , Vírus da Encefalite Transmitidos por Carrapatos , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective. METHODS: We summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA). RESULTS: Nirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4. CONCLUSIONS: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.
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COVID-19 , SARS-CoV-2 , Humanos , Ritonavir/efeitos adversos , Pandemias , Citocromo P-450 CYP3A , Antivirais/efeitos adversos , Interações MedicamentosasRESUMO
Lyme borreliosis affects the nervous system in three principal ways-mononuclear cell meningitis, cranial neuropathies and radiculoneuropathies-the last a broad term encompassing painful radiculopathy, unifocal and multifocal peripheral nerve involvement. Diagnostic tools have been significantly refined-including improved peripheral blood and CSF serodiagnostics-and much has been learned about the interactions between the causative pathogen and the nervous system. Despite these advances in our understanding of this disease, a broad range of other disorders continue to be misattributed to nervous system Lyme borreliosis, supported by, at best, limited evidence. These misattributions often reflect limited understanding not only of Lyme neuroborreliosis but also of what constitutes nervous system disease generally. Fortunately, a large body of evidence now exists to clarify many of these issues, establishing a clear basis for diagnosing nervous system involvement in this infection and, based on well performed studies, clarifying which clinical disorders are associated with Lyme neuroborreliosis, which with non-neurologic Lyme borreliosis, and which with neither.
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Neuroborreliose de Lyme , Humanos , Meningite , PolineuropatiasRESUMO
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. TRIAL REGISTRATION NUMBER: 2015-001481-25.
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BACKGROUND: The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear. OBJECTIVE: Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years. METHODS: 85 patients, originally enrolled in a multicentre, randomised trial of ω-3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer. RESULTS: Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (ß=-0.399, p=0.040) and deep (ß=-0.556, p=0.010) GM volume, lower mean cortical thickness (ß=-0.581, p=0.010) and higher T2 lesion count (ß=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (ß=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression. CONCLUSION: Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.
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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 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.
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Doenças dos Nervos Cranianos , Paralisia Facial , Neuroborreliose de Lyme , Humanos , Neuroborreliose de Lyme/diagnóstico por imagem , Neuroborreliose de Lyme/complicações , Incidência , Estudos Prospectivos , Estudos Longitudinais , Nervos Cranianos/diagnóstico por imagem , Doenças dos Nervos Cranianos/diagnóstico por imagem , PrognósticoRESUMO
Rejection (nomen rejiciendum) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes).
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Filogenia , Spirochaetales/classificação , Terminologia como AssuntoRESUMO
Lyme borreliosis (LB), caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, is the most common tick-borne infection in Europe. Laboratory diagnosis of LB is mainly based on the patients' medical history, clinical signs and symptoms in combination with detection of Borrelia-specific antibodies where indirect enzyme-linked-immunosorbent assay (ELISA) is the most widely used technique. The objective of the study was to evaluate and compare the diagnostic accuracy (sensitivities and specificities) of serological tests that are currently in use for diagnosis of LB in clinical laboratories in Northern Europe, by use of a large serum panel. The panel consisted of 195 serum samples from well-characterized and classified patients under investigation for clinically suspected LB (n = 59) including patients with Lyme neuroborreliosis, Lyme arthritis, acrodermatitis chronica atrophicans, erythema migrans or other diseases (n = 112). A total of 201 serum samples from healthy blood donors were also included. The panel (396 serum samples altogether) was sent to 12 clinical laboratories (using five different ELISA methods) as blinded for group affiliation and the laboratories were asked to perform serological analysis according to their routine procedure. The results from the study demonstrated high diagnostic concordance between the laboratories using the same diagnostic assay and lower diagnostic concordance between laboratories using different diagnostic assays. For IgG, the results were in general rather homogenous and showed an average sensitivity of 88% (range 85-91%) compared to IgM which showed lower average sensitivity of 59% (range 50-67%) and more heterogeneous results between assays and laboratories.
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Grupo Borrelia Burgdorferi/imunologia , Doença de Lyme/diagnóstico , Testes Sorológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Analysis of cerebrospinal fluid is required in order to diagnose Lyme neuroborreliosis. We investigated the symptoms of patients in a highly endemic area who were referred for evaluation of possible Lyme neuroborreliosis, and explored whether cerebrospinal fluid analysis confirmed or ruled out the diagnosis. METHOD: We reviewed the medical records of all patients who underwent lumbar puncture at Sørlandet Hospital Arendal in the period 1 January 2013 to 31 December 2013. RESULTS: A total of 140 patients were referred with suspected Lyme neuroborreliosis. Of these, 110 patients had non-specific neurological symptoms (e.g. fatigue, dizziness and headache), only one of whom received a diagnosis of possible Lyme neuroborreliosis. Thirty patients had symptoms typical of the condition (such as radiculitis or peripheral facial nerve palsy). Six of these were diagnosed with definite Lyme neuroborreliosis, and one with possible Lyme neuroborreliosis. None of those diagnosed with Lyme neuroborreliosis had had symptoms lasting more than six months. INTERPRETATION: The probability of Lyme neuroborreliosis is low in the absence of typical symptoms of the condition, even when anti-Borrelia antibodies are detected in serum and especially when the symptoms are of long duration.
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Neuroborreliose de Lyme , Anticorpos Antibacterianos/sangue , Borrelia burgdorferi/imunologia , Borrelia burgdorferi/isolamento & purificação , Doenças dos Nervos Cranianos/etiologia , Humanos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/diagnóstico , Prontuários Médicos , Mialgia/etiologia , Parestesia/etiologia , Radiculopatia/etiologia , Punção Espinal , Cefaleia do Tipo Tensional/etiologiaAssuntos
Encefalite Transmitida por Carrapatos , Doenças Transmitidas por Carrapatos , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Humanos , Doenças Transmitidas por Carrapatos/diagnóstico , Doenças Transmitidas por Carrapatos/epidemiologiaRESUMO
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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Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Imunoglobulina M , RNA Viral , Saliva , Humanos , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/urina , Encefalite Transmitida por Carrapatos/sangue , Encefalite Transmitida por Carrapatos/virologia , Encefalite Transmitida por Carrapatos/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/genética , Saliva/virologia , RNA Viral/urina , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Imunoglobulina M/sangue , Imunoglobulina M/urina , Imunoglobulina G/sangue , Imunoglobulina G/urina , Anticorpos Antivirais/sangue , Idoso de 80 Anos ou mais , Imunocompetência , HospitalizaçãoRESUMO
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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Biomarcadores , Neuroborreliose de Lyme , Proteínas de Neurofilamentos , Humanos , Neuroborreliose de Lyme/sangue , Neuroborreliose de Lyme/tratamento farmacológico , Neuroborreliose de Lyme/diagnóstico , Masculino , Feminino , Proteínas de Neurofilamentos/sangue , Pessoa de Meia-Idade , Noruega , Adulto , Biomarcadores/sangue , Idoso , Estudos Longitudinais , Método Duplo-Cego , Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Estudos de Coortes , Carga de SintomasRESUMO
OBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway. PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic.
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COVID-19 , Adulto , Humanos , Masculino , COVID-19/diagnóstico , COVID-19/epidemiologia , Controle da População , Estudos de Casos e Controles , SARS-CoV-2 , Fatores de Risco , Noruega/epidemiologiaRESUMO
As part of the NorthTick project, co-funded by the European Union through the European Regional Development Fund and the North Sea Region Programme, specialists in the field of tick-borne diseases from seven North Sea countries co-operated with patient organisations and governmental health care institutions to provide this comprehensive overview of diagnostics and treatment recommendations in the region for Lyme borreliosis, Borrelia miyamotoi infection, tick-borne encephalitis, human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis and babesiosis. The main conclusion is that the recommendations in these northern countries are essentially the same, with very few differences. This overview presents the current diagnostics and provides useful clinical guidance.
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Babesiose , Infecções por Borrelia , Encefalite Transmitida por Carrapatos , Doença de Lyme , Doenças Transmitidas por Carrapatos , Animais , Humanos , Mar do Norte , Doenças Transmitidas por Carrapatos/diagnóstico , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/terapia , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Doença de Lyme/terapia , Babesiose/diagnóstico , Babesiose/epidemiologia , Babesiose/terapiaRESUMO
OBJECTIVES: Lyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous Borrelia infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to Borrelia. METHODS: Serum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink®) by which 92 different immune response-related human protein biomarkers were analysed simultaneously. RESULTS: In total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previously Borrelia exposed (n = 34) and not exposed (n = 41) based on anti-Borrelia antibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (p<0.1). Six proteins were statistically significantly different between LB patients and blood donors (p<0.05). These six proteins were then combined in an index and analysed using receiver-operating-characteristic curve analysis showing an area under the curve of 0.964 (p<0.001). CONCLUSIONS: The results from this study suggest that there is an immunological protein pattern that can distinguish a present Borrelia infection from a previous exposure as well as anti-Borrelia antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.
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Borrelia burgdorferi , Borrelia , Doença de Lyme , Adulto , Humanos , Doença de Lyme/diagnóstico , Doadores de Sangue , Técnicas de Laboratório Clínico , Biomarcadores , Anticorpos AntibacterianosRESUMO
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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Neuroborreliose de Lyme , Doenças do Sistema Nervoso , Humanos , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Cognição , Fadiga/diagnóstico por imagem , Fadiga/etiologia , Fadiga/epidemiologiaRESUMO
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. KEY POINTS: ⢠Neuroborreliosis is an infection with disturbed BBB function. ⢠Microvessel leakage can be studied with DCE-MRI. ⢠Prospective case-control study showed altered microvessel properties in thalamus, caudate, and hippocampus.
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Barreira Hematoencefálica , Substância Cinzenta , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Barreira Hematoencefálica/diagnóstico por imagem , Estudos de Casos e Controles , Fadiga , Inflamação , Imageamento por Ressonância MagnéticaRESUMO
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.
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Encefalite , Neuroborreliose de Lyme , Idoso , Ataxia , Estudos de Coortes , Encefalite/diagnóstico , Encefalite/epidemiologia , Humanos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/epidemiologia , Estudos RetrospectivosRESUMO
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 treatment 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.