Serum neurofilament light chain associates with symptom burden in Lyme neuroborreliosis patients: a longitudinal cohort study from Norway.

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.

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations.

INTRODUCTION: The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. OBJECTIVE: To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). METHODS: All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3-12 weeks after full vaccination, and compared with healthy subjects. RESULTS: 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. CONCLUSIONS: Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations.

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

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.

Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled 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. TRIAL REGISTRATION NUMBER: 2015-001481-25.

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.

Cognitive function in patients with neuroborreliosis: A prospective cohort study from the acute phase to 12 months post treatment.

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.

Web-based vestibular rehabilitation in persistent postural-perceptual dizziness.

OBJECTIVES: The aims of the study were to investigate the feasibility and preliminary outcome of a Norwegian web-based self-help application for vestibular rehabilitation (VR) among patients with high symptom burden of chronic dizziness fulfilling the criteria for persistent postural-perceptual dizziness (PPPD). MATERIALS AND METHODS: The web application consists of six weekly online sessions, with written information and video presentations. It is self-instructive and freely available on NHI.no (https://nhi.no/for-helsepersonell/vestibular-rehabilitering/). Ten consecutive patients referred to a neurologic outpatient clinic for chronic dizziness were included. They signed informed consent forms and were examined at inclusion and after three months. State of health and symptom burden were recorded using Vertigo symptom score (VSS), Niigata symptom score (NPQ), Patient Health Questionnaire (PHQ-9) and health-related quality of life score (EQ5D-5L). Experiences with the program were measured using a semi-structured interview at the end of the study. RESULTS: Nine out of ten patients completed the program. The findings suggest that the web application was easy to use, instructive and educatable. Challenges were the load of exercises, motivation to continue training during relapses and performing the body rolling on the floor. Participants had high symptom burden (VSS mean 32.9) and long duration of symptoms in years (mean 11.5). The participants improved on average 6.9 points on the VSS score. CONCLUSIONS: This web application for chronic dizziness appears to be feasible and may reduce symptoms in patients who have struggled with serious and long-lasting dizziness.

Cognitive function, fatigue and Fazekas score in patients with acute neuroborreliosis.

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.

Subjective health complaints and exposure to tick-borne infections in southern Norway.

OBJECTIVES: Whether tick-borne infections can cause chronic subjective health complaints is heavily debated. If such a causal connection exists, one would expect to find more health complaints among individuals exposed to tick-borne infections than among non-exposed. In this study, we aimed to assess if exposure to tick-borne infections earlier in life, evaluated by examination of serum for IgG antibodies to tick-borne microbes, was associated with self-reported somatic symptom load. MATERIALS & METHODS: All individuals with residential address in Søgne municipality in southern Norway, aged 18-69 years, were invited to participate in the study. Blood samples were analyzed for IgG antibodies to different tick-borne microbes, and somatic symptom load was charted by the Patient Health Questionnaire-15 (PHQ-15). RESULTS: Out of 7424 invited individuals, 2968 (40.0%) were included in the study. We detected IgG antibodies to Borrelia burgdorferi sensu lato (Bb) in 22.9% (95% CI 21.4-24.4). Bb seropositive individuals reported less frequently moderate to severe somatic symptom load (ie, PHQ-15 sum score ≥ 10) than seronegative individuals (12.5% versus 17.7%, difference 5.2% [95% 2.1-8.0]). However, when adjusting for several other variables in a multivariable linear regression model, presence of serum IgG antibodies to Bb was not associated with somatic symptom load. Presence of IgG antibodies to other tick-borne microbes than Bb, or seropositivity to at least two microbes, was also not associated with somatic symptom load. CONCLUSION: Presence of serum IgG antibodies to tick-borne microbes was not associated with self-reported somatic symptom load.

Patient-reported outcome after treatment for definite Lyme neuroborreliosis.

OBJECTIVE: To chart patient-reported outcome measures (PROMs) in Norwegian patients treated for definite neuroborreliosis (NB). MATERIAL AND METHODS: Adult patients treated for definite NB 1-10 years earlier supplied demographics, symptoms and treatment during NB, and answered validated questionnaires; Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), health-related quality of life questionnaire (RAND-36), and Patient Health Questionnaire (PHQ-15). RESULTS: A higher proportion of NB-treated persons reported severe fatigue, defined as FSS score ≥ 5, than in Norwegian normative data, but when removing persons with confounding fatigue associated comorbidities (n = 69) from the analyses, there was no difference between groups. Physical health-related quality of life (RAND-36 PCS), mean FSS score, proportions of persons reporting moderate or severe somatic symptom burden (PHQ-15 score ≥ 10), anxiety (HADS-A ≥ 8), or depression (HADS-D ≥ 8) did not differ between NB-treated persons and reference scores. Mental health-related quality of life (RAND-36 MCS) was poorer than in normative data (47.1 vs. 53.3), but associated with anxiety, depression and current moderate or severe somatic symptom burden, and not with NB characteristics. CONCLUSIONS: Results on validated PROM questionnaires measuring fatigue, anxiety, depression, self-reported somatic symptom burden, and physical health-related quality did not differ between persons treated for definite NB 1-10 years earlier and reference scores. NB-treated persons tended to report a slightly poorer mental health-related quality of life than found in normative data, but when adjusting for confounders the causative connection is questionable. Overall, the long-term prognosis of definite NB seems to be good.

Human seroprevalence of antibodies to tick-borne microbes in southern Norway.

The tick Ixodes ricinus is widespread along the coastline of southern Norway, but data on human exposure to tick-borne microbes are scarce. We aimed to assess the seroprevalence of IgG antibodies to various tick-borne microbes in the general adult population living in a Norwegian municipality where ticks are abundant. Søgne is a coastline municipality in the southernmost part of Norway, and has a high density of ticks. All individuals aged 18-69 years with residential address in Søgne municipality (n = 7424) were invited to give a blood sample and answer a questionnaire. Blood samples from 3568 individuals were available for analysis. All samples were analyzed for IgG antibodies to Borrelia burgdorferi sensu lato (Bbsl), and around 1500 samples for IgG antibodies to other tick-borne microbes. Serum IgG antibodies to Bbsl were present in 22.0% (785/3568) of the tested samples, tick-borne encephalitis virus (TBEV) in 3.1% (45/1453), Anaplasma phagocytophilum in 11.0% (159/1452), Babesia microti in 2.1% (33/1537), Bartonella henselae/B. quintana in 0.1% (2/1451) and Rickettsia helvetica/R. conorii in 4.2% (60/1445). Serum IgG antibodies to A. phagocytophilum and R. helvetica/R. conorii were significantly more prevalent (p = 0.010 and p = 0.016, respectively) among individuals with serum IgG antibodies to Bbsl than among individuals without. In conclusion, our study showed a high exposure to Bbsl in the general adult population living in a coastline municipality in the southernmost part of Norway. The population is also exposed to A. phagocytophilum, R. helvetica/R. conorii, B. microti and TBEV, but very rarely B. henselae/B. quintana.

Examination of patients with acute dizziness in a neurological department. / Utredning av pasienter med akutt svimmelhet ved en nevrologisk avdeling.

BACKGROUND: Acute dizziness may have a number of causes, including cerebrovascular stroke which can present as isolated acute vestibular syndrome. It is recommended that acute episodic dizziness be assessed using positioning tests, and acute persistent dizziness with a focus on the HINTS (Head Impulse, Nystagmus, Test of Skew) battery of tests, which can distinguish cerebrovascular stroke from vestibular neuritis. We wished to identify the prevalence, diagnostic spectrum and approach to acute dizziness in a neurological department. MATERIAL AND METHOD: We undertook a retrospective review of the medical records of all patients with acute dizziness as the primary symptom who where admitted to the department of neurology at Sørlandet Hospital, Kristiansand in 2015. RESULTS: Of 2 231 patients admitted to the department of neurology in 2015, altogether 243 (11 %) had dizziness as the primary symptom. A total of 106 patients (44 %) were examined using HINTS in its entirety. A cranial CT was performed in 213 (88 %) and MRI in 91 (37 %), and these showed relevant pathology in 1 and 4 patients, respectively. Upon discharge, 122 patients (50 %) were given a non-specific symptom diagnosis, 59 (24 %) received the diagnosis vestibular neuritis, 41 (17 %) benign paroxysmal positional vertigo, and 5 (2 %) were diagnosed with cerebrovascular stroke. Four out of five cases of cerebrovascular stroke could be classified retrospectively as acute vestibular syndrome, whereof three had typical findings determined by the HINTS test. INTERPRETATION: Acute dizziness is a frequent symptom in patients admitted to the department of neurology. Evidence-based diagnostic recommendations for the assessment of acute dizziness were not satisfactorily implemented in practice.

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. TRIAL REGISTRATION NUMBER: 2015-001481-25.

Persistent postural-perceptual dizziness / Persisterende postural-perseptuell svimmelhet.

Persistent symptoms of dizziness may be due to inappropriate compensatory strategies following an episode of acute dizziness. Common symptoms are dizziness in an upright position that is aggravated by visual stimuli and passive movement. In the World Health Organization's new disease classification, ICD-11, the condition has been named persistent postural-perceptual dizziness. It is important to recognise this condition in order to avoid unnecessary investigation and to initiate the correct treatment.

Somatic symptoms and fatigue in a Norwegian population with high exposure to ticks.

BACKGROUND: It is heavily debated whether tick-borne infections cause chronic subjective health complaints. If the hypothesis of a major causal connection is true, one would expect to find more subjective health complaints in a population with high exposure to ticks than in a population with less exposure. In the current study we aimed to assess somatic symptoms and fatigue in a Norwegian population with high exposure to ticks, compare our findings to normative data, and assess predictors of somatic symptom load. MATERIAL AND METHODS: All individuals aged 18-69 years with residential address in Søgne municipality in southern Norway were in the period June 2015 to June 2016 invited to participate in the study. Somatic symptoms were assessed by the Patient Health Questionnaire-15 (PHQ-15) and fatigue by the Fatigue Severity Scale (FSS). A multivariable regression analysis was performed to assess predictors of somatic symptom load. RESULTS: Out of 7424 invited individuals, 2971 (40.0%) returned the questionnaire. 85.1% of 2950 responders reported exposure to tick-bite. PHQ-15 mean sum score was 5.3, and 16.5% reported moderate to severe somatic symptom load (i.e. ≥ 10). FSS mean score was 3.2, and 29.8% scored above the cut-off value for fatigue (i.e. ≥ 4.0). All gender and age groups in our study population had equal or lower mean sum score on PHQ-15 than reported in Swedish normative data, and lower mean score on FSS than reported in Norwegian normative data. In multivariable regression the following factors were associated with higher somatic symptom load (listed in order of descending beta coefficient): Anxiety and depression, number of other diseases, female gender, younger age, recruitment when visiting general practitioner's office, ≤ 6 years education after primary school, tick-bite earlier in life, erythema migrans earlier in life, less physical activity, and modern health worries. CONCLUSION: The study population reported high exposure to tick-bites, but less or equal level of somatic symptoms and less fatigue than found in normative data. There was a weak association between somatic symptom load and exposure to tick-bite and erythema migrans, possibly related to selection bias. Our findings do not support the hypothesis of a major causal connection between tick-borne infections and subjective health complaints.

Screening for Fabry disease and Hereditary ATTR amyloidosis in idiopathic small-fiber and mixed neuropathy.

INTRODUCTION: In this study we assessed the value of genetic screening for Fabry disease (FD) and hereditary ATTR amyloidosis in patients with idiopathic small-fiber neuropathy (SFN) or mixed neuropathy in a clinical setting. METHODS: This was a Nordic multicenter study with 9 participating centers. Patients with idiopathic SFN or mixed neuropathy were included. Genetic sequencing of the TTR and GLA genes was performed. RESULTS: There were 172 patients enrolled in the study. Genetic screening was performed in 155 patients. No pathogenic mutations in the TTR gene were found. A single patient had a possible pathogenic variant, R118C, in the GLA gene, but clinical investigation showed no firm signs of FD. DISCUSSION: Screening for hereditary ATTR amyloidosis and FD in patients with idiopathic SFN or mixed neuropathy without any additional disease-specific symptoms or clinical characteristics in a Nordic population appears to be of little value in a clinical setting. Muscle Nerve 59:354-357, 2019.

Imaging in Lyme neuroborreliosis.

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. KEY POINTS: • Diagnostic criteria for LNB emphasise exclusion of an alternative cause to the clinical symptoms. • MRI makes a crucial contribution in the diagnosis and follow-up of LNB. • MRI may have normal findings, or show neuritis, meningitis, myelitis, encephalitis or vasculitis. • White matter lesions are not a prominent feature of LNB.

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

BACKGROUND: Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples. METHODS: Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls. RESULTS: Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases. CONCLUSION: We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.