Neurofilament Light in Cerebrospinal Fluid is Associated With Disease Staging in European Lyme Neuroborreliosis

BACKGROUND: Drivers of differences in disease presentation and symptom duration in Lyme neuroborreliosis (LNB) are currently unknown. OBJECTIVES: We hypothesized that neurofilament light (NfL) in cerebrospinal fluid (CSF) would predict disease location and sequelae in a historic LNB cohort. DESIGN: Using a cross-sectional design and archived CSF samples from 185 patients diagnosed with LNB, we evaluated the content of NfL in the total cohort and in a subgroup of 84 patients with available clinical and paraclinical information. METHODS: Individuals were categorized according to disease location: a. Central nervous system (CNS) with stroke (N=3), b. CNS without stroke (N=11), c. Peripheral nervous system (PNS) with cranial nerve palsy (CNP) (N=40) d. PNS without CNP (N=30). Patients with hospital follow-up more than 6 months after completed antibiotic therapy were categorized as having LNB associated sequelae (N=15). RESULTS: At diagnosis concentration of NfL exceeded the upper reference level in 60% (105/185), especially among individuals above 30 years. Age-adjusted NfL was not found to be associated with symptom duration. Age-adjusted NfL was significantly higher among individuals with CNS involvement. Category a. (stroke) had significantly higher NfL concentrations in CSF compared to all other categories, category b. (CNS involvement without stroke) had significantly higher values compared to the categories of PNS involvement. We found no significant difference between the categories with PNS involvement (with or without CNP). Significantly higher NfL was found among patients with follow-up in hospital setting. CONCLUSION: Comparison of NfL concentrations between the 4 groups of LNB disease manifestations based on clinical information revealed a hierarchy of neuron damage according to disease location and suggested evolving mechanisms with accelerated injury especially when disease is complicated by stroke. Higher values of NfL among patients with need of follow-up in hospital setting suggest NfL could be useful to identify rehabilitative needs

Long-Term Mortality in Patients with Tuberculous Meningitis: A Danish Nationwide Cohort Study

Background: With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. Methods: A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death. Findings: A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. Conclusion: Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems fro

Plasma neurofilament light significantly decreases following treatment in Lyme neuroborreliosis and not associated with persistent symptoms

BACKGROUND: Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15-20%), variable clinical course and the long-lasting B. burgdorferi antibodies. We therefore wanted to evaluate plasma NfL as a marker for disease activity in LNB. METHODS: Prospective included cohort of definite LNB (N=36) with blood samples and clinical evaluation including Glasgow Outcome Score (GOS) at treatment initiation, 3- and 6-months follow-up. Consecutive plasma was retrospectively analyzed for the content of NfL by Quanterix® kits (Simoa® NF-light Kit). RESULTS: pNfL significantly decreased between treatment initiation and 3-months follow-up (median 83 pg/ml vs median 14 pg/ml (25 pairs), p<0.0001). No significant change was observed between 3- and 6-months follow-up (median 14 pg/ml vs median 12 pg/ml (21 pairs), p=0.33). At treatment initiation 90% had pNfL above the age defined reference compared to only 23% and 7% respectively at 3- and 6-months follow-up. Decreases in pNfL were mirrored by increasing GOS. Reporting persistent symptoms at the 6 months follow-up was not associated with plasma NfL (relative change from reference or actual values) at baseline or at 6 months follow-up CONCLUSION: pNfL decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. We therefore speculate that it may prove useful as a treatment response biomarker in LNB

Serum 25(OH)D in 1250 pulmonary TB patients and 355 neighbourhood controls by categories of sex, age, body mass index, pulmonary TB and HIV status and elevated acute phase reactants¹.

1<p>Pulmonary TB status was based on culture, except where culture data were not available. For 355 consecutively recruited sputum positive TB patients a control was randomly selected among individuals with same sex and age from the neighbourhood. Serum 25(OH)D data were available on 1570, but n may sum up to less, due to missing data.</p>2<p>Based on sex-specific percentiles among the neighbourhood controls.</p

Correlates of serum 25(OH)D in 1250 pulmonary TB patients and 355 neighbourhood with regression coefficient B, 95% confidence interval (CI) and P-values¹.

1<p>Pulmonary TB status was based on culture, except where culture data were not available. For 355 consecutively recruited sputum positive TB patients a control was randomly selected among individuals with same sex and age from the neighbourhood. Age, and quarter and year of recruitment were adjusted for in both models.</p>2<p>Model 1: N = 1540, adjusted R2 = 0.206 and intercept = 112.1 (95% CI: 105.1; 119.2).</p>3<p>Model 2: N = 1537, adjusted R2 = 0.212 and intercept = 110.4 (95% CI: 103.3; 117.5).</p

Mean serum 25(OH)D among 355 neighbourhood controls (NHc) and 1250 pulmonary tuberculosis (PTB) patients at the year and quarter (Q) of examination.

<p>Two cases from first quarter of 2006 and seven from 2009 not shown.</p