Intrathecal Antibody Synthesis Research Articles

Results of Tick-Borne Encephalitis Virus (TBEV) Diagnostics in an Endemic Area in Southern Germany, 2007 to 2022.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted neurotropic flavivirus in Europe and Asia. Our analysis aimed to investigate the contribution of TBEV-specific antibody detection by serological assays and TBEV RNA detection by real-time PCR to the diagnosis of tick-borne encephalitis (TBE). We analyzed data from 3713 patients from 16 years of laboratory TBEV diagnostics in an endemic area in Southern Germany. During this period, 126 cases of TBE were diagnosed. TBEV-specific IgM ELISA tests showed a high clinical sensitivity (96.8%) and a very high clinical specificity (99.7%). In immunocompetent patients, TBE was reliably diagnosed by detection of TBEV IgM antibodies in serum. Intrathecal TBEV IgG antibody synthesis was detected in 46 of 84 (55%) cases by analysis of paired serum and cerebrospinal fluid (CSF) samples. None of the 87 immunocompetent TBE patients tested had detectable TBEV RNA in serum or CSF. In contrast, in two TBE patients without TBEV-specific antibodies, diagnosis could only be made by the detection of TBEV RNA in CSF. Both patients had previously been treated with the B cell-depleting antibody rituximab. Therefore, in patients with CNS infection and humoral immunodeficiency, it is necessary to include TBEV PCR in the diagnostic approach.

Probable Anti-Glutamate Decarboxylase 65 (Gad65) Antibody-Associated Cerebellar Ataxia. Clinical Case Report and Literature Review

Introduction. As more information about cerebellar ataxia induced by anti- GAD65 antibodies is accumulated, cerebellar dysfunction is increasingly associated with autoimmune causes. The prevalence of other neurological syndromes associated with anti- GAD65 antibodies has been estimated, but the occurrence of cerebellar ataxia of the same cause has not yet been reported. The clinical presentation and management of anti-GAD65 antibodies induced cerebellar ataxia are currently known only from single cases and small series reports.
 Case report. We present a clinical case of a 52-year-old woman who was admitted to the hospital due to dizziness, impaired coordination, occasional choking, and slurred speech. Diagnostic procedures were performed, in which anti-GAD65 antibodies and atrophic changes in the upper parts of the cerebellum were detected on brain MRI, which led to a possible diagnosis of anti-GAD65 antibody-associated cerebellar ataxia.
 Discussion and literature review. Patients tend to be women in their 60s with clinical symptoms such as gait and posture ataxia. Most patients present with nystagmus, dysarthria, and limb ataxia. To make the diagnosis, it is crucial to detect high titers of anti-GAD65 antibodies, do intrathecal anti-GAD65 antibody synthesis, and perform a brain MRI, which may reveal atrophy of the cerebellum as the disease progresses. Corticosteroids are one of the recommended treatment methods, which were effective in our case. Maintenance therapy is essential to prevent relapse of the disease.

Case report: Successive ipsilateral and contralateral laryngeal nerve palsy as probable manifestation of neuroborreliosis

Neuroborreliosis is part of advanced stage of Lyme disease and often characterized by damage to the cranial and/or peripheral nerves. Involvement of one or both recurrent nerves is rare. Diagnosis is often difficult and based on a set of clinical manifestations, biological arguments, and cerebrospinal fluid (CSF) analysis. A 70-year-old man was referred to our Voice Clinic with a 3-month history of dysphonia caused by right vocal fold paralysis (VFP) without any cutaneous symptoms of tick bite or erythema migrans in the previous weeks and normal initial radiological examination (neck and thorax CT). Methylprednisolone had already been prescribed but without any clinical improvement. Late biological investigation 3 months after initial symptoms of VFP showed high IgG (93 U/mL; reference <10 U/mL) against Borrelia burgdorferi (BB), which was confirmed by two immunoblot markers (VIsE, p39 antigens). Therefore, a possible manifestation of Lyme disease with involvement of the right inferior laryngeal nerve was suspected, namely Lyme neuroborreliosis. However, given the spontaneous recovery of the patient after 7 months without any adapted antimicrobial regimen treatment, the diagnosis of neuroborreliosis was not confirmed by a lumbar puncture. Nineteen months later, the patient presented again for the same symptomatology but as left VFP. High IgG (68 U/mL) and IgM (>6, reference <0.90) levels against BB were confirmed by immunoblot. Subsequently, lumbar puncture was performed and revealed IgG against BB at 46.1 UA/mL (reference<5.5 UA/mL) in the CSF, with an extremely high IgG intrathecal synthesis antibody index (281.33, positive if > 1.5). Intrathecal antibody synthesis is the gold standard for Lyme neuroborreliosis demonstrating a specific immune response to BB in the central nervous system, but with the limitation of persistence for years after eradication. Our patient did not exhibit pleocytosis in the CSF. Therefore, two criteria of the European Federation of Neurological Societies (EFNS) guidelines are fulfilled for possible neuroborreliosis. Doxycycline treatment led to rapid recovery in less than 8 weeks and normal mobility of the left vocal fold. Because of this very uncommon clinical presentation with two successive episodes of VFP for no other obvious reason and serological evidence from the serum and CSF during the second episode, we consider it possible that the first episode of VFP could also have been a manifestation of neuroborreliosis. This case is the first report of possible relapse of laryngeal palsy successively on the right, and then the left side as a manifestation of Lyme neuroborreliosis.

A-266 Evaluation of an Antibody Index Assay for Assessment of Intrathecal Anti-Treponema pallidum IgG Synthesis for the Diagnosis of Neurosyphilis

Abstract Background Diagnosis of neurosyphilis (NS) is challenging due to nonspecific clinical symptoms and the lack of a sensitive and specific laboratory test. The non-treponemal Venereal Disease Research Laboratory (VDRL-CSF) assay is a commonly used test in diagnosing NS. An important limitation of the VDRL-CSF is limited specificity, in part due to the inability to differentiate between intrathecally produced antibodies vs passive antibody diffusion into the CSF due to blood-brain barrier (BBB) disruption. Here, we compared the intrathecal synthesis antibody index (AI) of anti-Treponema pallidum IgG antibodies to results from the VDRL-CSF assay in routinely submitted clinical samples for evaluation of suspected NS. Methods Paired serum and CSF residual clinical samples from 98 patients with previous VDRL-CSF results were collected. For each pair, the serum and CSF were drawn within 24 h. No additional clinical information and limited supporting clinical test results were available. Thirty-one positive and 67 negative paired samples were tested by an anti-T. pallidum IgG ELISA (Euroimmun, Lübeck, Germany). The AI was calculated using Reiber’s method, with intrathecal total IgG synthesis corrected using the Reiber recommended albumin quotient calculation. Results were compared for positive, negative and overall agreement between methods. Results The anti-T. pallidum AI showed a positive, negative and overall agreement of 71.0% (22/31), 100% (67/67) and 90.8% (89/98), respectively, compared to VDRL-CSF. Of note, all nine discordant samples showed abnormally elevated albumin levels in CSF (range: 27.4 to 215 mg/dl; median = 41.7 mg/dl; normal value =&amp;lt;27 mg/dl), indicating a compromised BBB which likely resulted in false-positive VDRL-CSF results. The range and median value for CSF albumin in the 22 concordant samples was 12.4 to 168 mg/dl and 37.2 mg/dl, respectively. In total, 83.9% (26/31) of VDRL-CSF positive samples showed elevated CSF albumin levels which suggests a high percentage of BBB impairment in this patient population. This demonstrates the advantage in specificity that is offered by AI testing compared to use of the VDRL-CSF assay, given the ability of AI to differentiate intrathecally produced vs passively diffused syphilis-specific antibodies. No potential increase in sensitivity was observed in AI testing as 100% negative agreement was obtained. Conclusion Our data suggests that establishment of an AI using a treponemal assay to detect intrathecal antibody synthesis provides improved specificity compared to the current commonly performed VDRL-CSF antibody test as an aid in the diagnosis of NS. Further evaluation of sensitivity is warranted using samples from patients with clinically diagnosed NS.

Cerebrospinal fluid CXCL13 in non-borrelial central nervous system infections: contribution of CXCL13 to the differential diagnosis

Background The chemokine CXCL13 in cerebrospinal fluid (CSF) is used as a diagnostic marker of Lyme neuroborreliosis (LNB). However, the elevated levels in other non-borrelial CNS infections and the lack of a clearly defined cut-off value are limitations of the test. Methods In our prospective study, we evaluated CSF CXCL13 levels in patients with LNB (47 patients), tick-borne encephalitis (TBE; 46 patients), enteroviral CNS infections (EV; 45 patients), herpetic CNS infections (HV; 23 patients), neurosyphilis (NS; 11 patients) and controls (46 patients). The correlation of CXCL13 with CSF mononuclears was determined in all groups. Results Median CXCL13 was significantly higher in LNB group; however, the cut-off value of 162 pg/mL was also exceeded in 22% of TBE patients, 2% EV patients, 44% HV patients and in 55% patients with NS. Sensitivity and specificity were 0.83 and 0.78, respectively, with a Youden index of 0.62. CXCL13 was significantly correlated with CSF mononuclears (p = .0024), but the type of infectious agent had a greater influence on CXCL13 levels. Conclusions Increased CXCL13 levels are useful for LNB diagnostics, but other non-purulent CNS infections causes should be considered if intrathecal synthesis of borrelia specific antibodies is not confirmed or clinical manifestations are atypical.

Case report of neurosyphilis with intrathecal synthesis of oligoclonal antibodies

A clinical case is described which occurred in the practice of the Department of Neurology 1 of the Mechnikov Dnipropetrovsk Regional Clinical Hospital. Using the patient’s case history as an example, some possible difficulties in a differential diagnosis of neurosyphilis and demyelinating diseases are shown, peculiarities of laboratory diagnosis of the former are highlighted and reviewed, and also the diagnostic importance of identification of antibody synthesis type during a cerebrospinal fluid analysis for detecting oligoclonal bands is explained. The article contains a brief overview of the works related to modern views on the place and role of the cerebrospinal fluid analysis for a diagnosis and a differential diagnosis of diseases of the nervous system, for studying the types of antibody synthesis in the blood serum and in the cerebrospinal fluid, as well as to some aspects of diagnosing syphilis.

Teaching Video NeuroImages: Facial myokymia and myorhythmia in anti-IgLON5 disease

A 79-year-old woman presented with an 8-month history of parasomnia and progressive bulbar syndrome with dysarthria, dysphagia, facial myokymia, and mandibular myorhythmia (video 1) resulting in biting scars of her lower lip. Brain MRI and EEG were unremarkable. CSF analysis showed intrathecal antibody synthesis and elevated tau 372 pg/mL (0–320 pg/mL) and phospho-tau 54 pg/mL (0–50 pg/mL). Antibodies against IgLON5 were highly positive (1:1,000) in CSF and serum. Anti-IgLON5 disease was diagnosed.1 Recognition of bulbar symptoms with myokymia and myorhythmia as part of an anti-IgLON5 disease may be important to start early immunotherapy to prevent progression to neurodegeneration.2

Lesional Antibody Synthesis and Complement Deposition Associate With De Novo Antineuronal Antibody Synthesis After Spinal Cord Injury.

Spinal cord injury (SCI) disrupts the fine-balanced interaction between the CNS and immune system and can cause maladaptive aberrant immune responses. The study examines emerging autoantibody synthesis after SCI with binding to conformational spinal cord epitopes and surface peptides located on the intact neuronal membrane. This is a prospective longitudinal cohort study conducted in acute care and inpatient rehabilitation centers in conjunction with a neuropathologic case-control study in archival tissue samples ranging from acute injury (baseline) to several months thereafter (follow-up). In the cohort study, serum autoantibody binding was examined in a blinded manner using tissue-based assays (TBAs) and dorsal root ganglia (DRG) neuronal cultures. Groups with traumatic motor complete SCI vs motor incomplete SCI vs isolated vertebral fracture without SCI (controls) were compared. In the neuropathologic study, B cell infiltration and antibody synthesis at the spinal lesion site were examined by comparing SCI with neuropathologically unaltered cord tissue. In addition, the CSF in an individual patient was explored. Emerging autoantibody binding in both TBA and DRG assessments was restricted to an SCI patient subpopulation only (16%, 9/55 sera) while being absent in vertebral fracture controls (0%, 0/19 sera). Autoantibody binding to the spinal cord characteristically detected the substantia gelatinosa, a less-myelinated region of high synaptic density involved in sensory-motor integration and pain processing. Autoantibody binding was most frequent after motor complete SCI (grade American Spinal Injury Association impairment scale A/B, 22%, 8/37 sera) and was associated with neuropathic pain medication. In conjunction, the neuropathologic study demonstrated lesional spinal infiltration of B cells (CD20, CD79a) in 27% (6/22) of patients with SCI, the presence of plasma cells (CD138) in 9% (2/22). IgG and IgM antibody syntheses colocalized to areas of activated complement (C9neo) deposition. Longitudinal CSF analysis of an additional single patient demonstrated de novo (IgM) intrathecal antibody synthesis emerging with late reopening of the blood-spinal cord barrier. This study provides immunologic, neurobiological, and neuropathologic proof-of-principle for an antibody-mediated autoimmunity response emerging approximately 3 weeks after SCI in a patient subpopulation with a high demand of neuropathic pain medication. Emerging autoimmunity directed against specific spinal cord and neuronal epitopes suggests the existence of paratraumatic CNS autoimmune syndromes.

The repertoire of CSF antiviral antibodies in patients with neuroinflammatory diseases.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the etiology of MS remains unknown. Since intrathecal antibody synthesis is well documented in chronic viral infection and neuroinflammatory diseases, we hypothesized whether the patterns of antigen-specific antibody responses associated with various viral exposures may define patients with CNS chronic immune dysregulation. The pan-viral antibody profiling in cerebrospinal fluid (CSF) and serum of patients with MS showed significant differences from those in healthy volunteers and a pattern of antibody responses against multiple viruses, including the previously identified Epstein-Barr virus. These findings demonstrate that virus-specific antibody signatures might be able to reflect disease-associated inflammatory milieu in CSF of subjects with neuroinflammatory diseases.

Comparison of Treponema-specific immunoglobulin G (IgG) index with Treponema pallidum particle agglutination (TPPA) index for detection of intrathecal Treponema-specific antibody synthesis for serological diagnosis of neurosyphilis.

The determination of Treponema-specific intrathecal immunoglobulin synthesis with the Treponema pallidum particle agglutination (TPPA) index is a well-established method recommended in German guidelines for the diagnosis of neurosyphilis. However, the TPPA test is no longer available. The aim of this study was to evaluate whether the determination of a Treponema-specific immunoglobulin G (IgG) index can substitute the TPPA index. Serum and cerebrospinal fluid (CSF) samples from patients with confirmed (n=6) and probable (n=3) neurosyphilis as well as patients with adequately treated syphilis without neurosyphilis (n=4) were investigated. In addition to index calculation further CSF parameters were determined. The results of the Treponema IgG and the TPPA index were consistent in all patients with confirmed neurosyphilis and non-neurosyphilis patients. In two patients with probable neurosyphilis the IgG index appeared more plausible than the TPPA index when taking into account all available laboratory and clinical data of the patients. In conclusion, the determination of Treponema-specific intrathecal immunoglobulin synthesis with the IgG index appears to be a suitable alternative to the TPPA index.

Varicella Zoster Virus Aseptic Meningitis: A Misleading Clinical And Laboratory Presentation: Three Case Reports

Background: A septic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, Varicella-zoster virus is a neurotropic virus that remain dormant in dorsal root ganglion after primary infection, usually manifested as chickenpox which gets reactivated in immunocompromized state presented usually with vesicular rash complicated with multi-organ affection such as central nervous system. Rarely this characteristic skin rash can be absent initially requiring high clinical suspicion for diagnosis. When no skin lesions are present, a high clinical suspicion is required to reach the diagnosis. In this report we described three clinical of varicella-zoster virus reactivation presented in atypical way in terms of clinical presentation and cerebrospinal fluid analysis. Case presentation: Three patients otherwise healthy were admitted to the hospital with a chief complaint of headache, nausea, vomiting and symptoms suggestive of increased intracranial pressure (IIH). Resembling IIH but due to acute presentation and positive meningeal signs this was unlikely. The clinical examination did not show any neurological deficits or rash except lately in the first case. Lumbar puncture unexpectedly showed high opening pressure with markedly elevated CSF total and high total cell count with lymphocytic predominance which was misleading raising suspicion of tuberculous meningitis. Further CSF analysis, including polymerase chain reaction (PCR) and detection of intrathecal synthesis of antibodies, showed a VZV infection. Clinical follow-up examinations later on proved successful antiviral treatment. Conclusion: In conclusion, absence of typical vesicular rash of varicella zoster initially as well as high opening CSF pressure with high CSF protein even young and previously healthy patients should not rule out consideration of varicella zoster meningitis.

Femoral Nerve Injury during Neuroborreliosis — Nursing Care. Case Report

Introduction. Neuroborreliosis is an insidious disease. It is often confused with other neurological diseases. Diagnosis is possible when the following are present: neurological symptoms indicative of neuroborreliosis, pleocytosis in CSF, and production of antibodies to Borrelia burgdorferi in CSF.&#x0D; Aim. To assess the health situation and determine the nursing needs of a patient with femoral nerve damage during neuroborreliosis.&#x0D; Case Report. A 31-year-old woman was admitted to the Department of Neurology as an elective patient. On the basis of the clinical picture, elevated levels of protein and lymphocytic cells in the examination of cerebrospinal fluid and the demonstrated intrathecal synthesis of antibodies against Borrelia diagnosed neuroborreliosis with damage to the left femoral nerve. Observation, interview, and analysis of medical records were used to identify nursing problems correctly. The scales used were: the NRS Rating Scale (pain intensity), Lovett Scale (muscle strength assessment), Hospital Anxiety and Depression Scale Questionnaire (a modified version of the HADS scale to assess anxiety and depression), AIS Scale (to assess insomnia), Baxter Scale (to monitor and assess the risk of complications associated with venous cannulation).&#x0D; Conclusions. Dorothea Orem’s nursing theory is appropriate for a patient with neuroborreliosis. The patient’s main problems are: experiencing pain, difficulty in movement, and mental deterioration. The disease and related treatment and hospitalization influence bio-psycho-social deterioration. Holistic nursing management should be adapted to the patient’s changing condition. Care includes activities aimed at nullifying the effects of the disease, providing emotional support, and education regarding proper rehabilitation management and prevention of Lyme disease. (JNNN 2022;11(4):174–179)

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Varicella Zoster Virus Aseptic Meningitis: A Misleading Clinical and Laboratory Presentation: Three Cases Reports

Background: A septic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, Varicella-zoster virus is a neurotropic virus that remain dormant in dorsal root ganglion after primary infection, usually manifested as chickenpox which gets reactivated in immunocompromized state presented usually with vesicular rash complicated with multi-organ affection such as central nervous system. Rarely this characteristic skin rash can be absent initially requiring high clinical suspicion for diagnosis. When no skin lesions are present, a high clinical suspicion is required to reach the diagnosis. In this report we described three clinical of varicella- zoster virus reactivation presented in atypical way in terms of clinical presentation and cerebrospinal fluid analysis. Case presentation: Three patients otherwise healthy were admitted to the hospital with a chief complaint of headache, nausea, vomiting and symptoms suggestive of increased intracranial pressure (IIH). Resembling IIH but due to acute presentation and positive meningeal signs this was unlikely. The clinical examination did not show any neurological deficits or rash except lately in the first case. Lumbar puncture unexpectedly showed high opening pressure with markedly elevated CSF total and high total cell count with lymphocytic predominance which was misleading raising suspicion of tuberculous meningitis. Further CSF analysis, including polymerase chain reaction (PCR) and detection of intrathecal synthesis of antibodies, showed a VZV infection. Clinical follow-up examinations later on proved successful antiviral treatment.

Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders

IntroductionInfectious and immunological theories of schizophrenia have been discussed for over a century. Contradictory results for infectious agents in association with schizophrenia spectrum disorders (SSDs) were reported. The rationale of this study was to investigate intrathecal antibody synthesis of the most frequently discussed neurotropic pathogens using a pathogen-specific antibody index (AI) in patients with SSD in comparison to controls.MethodsIn 100 patients with SSD and 39 mentally healthy controls with idiopathic intracranial hypertension (IIH), antibodies against the herpesviruses EBV, CMV, and HSV 1/2 as well as the protozoan Toxoplasma gondii, were measured in paired cerebrospinal fluid (CSF) and serum samples with ELISA-kits. From these antibody concentrations the pathogen-specific AIs were determined with the assumption of intrathecal antibody synthesis at values > 1.5.ResultsNo significant difference was detected in the number of SSD patients with elevated pathogen-specific AI compared to the control group. In a subgroup analysis, a significantly higher EBV AI was observed in the group of patients with chronic SSD compared to patients with first-time SSD diagnosis (p = 0.003). In addition, two identified outlier EBV patients showed evidence for polyspecific immune reactions (with more than one increased AI).ConclusionsEvidence for the role of intrathecal EBV antibody synthesis was found in patients with chronic SSD compared to those first diagnosed. Apart from a possible infectious factor in SSD pathophysiology, the evidence for polyspecific immune response in outlier patients may also suggest the involvement of further immunological processes in a small subgroup of SSD patients.

Virus-specific antibody indices may supplement the total IgG index in diagnostics of multiple sclerosis

Intrathecal antibody synthesis to viruses is associated with multiple sclerosis (MS). Here, IgG levels to Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1), EBV nuclear antigen 1 (EBNA1), mumps virus (MuV) nucleoprotein (NuP), measles virus (MeV) NuP and rubella virus (RuV) capsid protein (CaP) were found to be elevated in serum and cerebrospinal fluid (CSF) of MS patients compared to healthy controls (HCs), whereas the opposite was found for cytomegalovirus (CMV) pp52. Strong correlations between serum and CSF IgG were seen for MeV, CMV and RuV in both MS patients and HCs. The antigen panel obtained high sensitivity (81%) and specificity (86%), demonstrating that antigen panels may supplement the total IgG index used in MS diagnosis.

Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting.

ABSTRACTLaboratory diagnosis of Lyme neuroborreliosis (LNB) is challenging, and validated diagnostic algorithms are lacking. Therefore, this retrospective cross-sectional study aimed to compare the diagnostic performance of seven commercial antibody assays for LNB diagnosis. Random forest (RF) modeling was conducted to investigate whether the diagnostic performance using the antibody assays could be improved by including several routine cerebrospinal fluid (CSF) parameters (i.e., leukocyte count, total protein, blood-CSF barrier functionality, and intrathecal total antibody synthesis), two-tier serology on serum, the CSF level of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13), and a Borrelia species PCR on CSF. In total, 156 patients were included who were classified as definite LNB (n = 10), possible LNB (n = 7), or non-LNB patient (n = 139) according to the criteria of the European Federation of Neurological Societies using a consensus strategy for intrathecal Borrelia-specific antibody synthesis. The seven antibody assays showed sensitivities ranging from 47.1% to 100% and specificities ranging from 95.7% to 100%. RF modeling demonstrated that the sensitivities of most antibody assays could be improved by including other parameters to the diagnostic repertoire for diagnosing LNB (range: 94.1% to 100%), although with slightly lower specificities (range: 92.8% to 96.4%). The most important parameters for LNB diagnosis are the detection of intrathecally produced Borrelia-specific antibodies, two-tier serology on serum, CSF-CXCL13, Reibergram classification, and pleocytosis. In conclusion, this study shows that LNB diagnosis is best supported using multiparameter analysis. Furthermore, a collaborative prospective study is proposed to investigate if a standardized diagnostic algorithm can be developed for improved LNB diagnosis.IMPORTANCE The diagnosis of LNB is established by clinical symptoms, pleocytosis, and proof of intrathecal synthesis of Borrelia-specific antibodies. Laboratory diagnosis of LNB is challenging, and validated diagnostic algorithms are lacking. Therefore, this retrospective cross-sectional study aimed to compare the diagnostic performance of seven commercial antibody assays for LNB diagnosis. Multiparameter analysis was conducted to investigate whether the diagnostic performance using the antibody assays could be improved by including several routine (CSF) parameters. The results of this study show that LNB diagnosis is best supported using the detection of intrathecally produced Borrelia-specific antibodies, two-tier serology on serum, CSF-CXCL13, Reibergram classification, and pleocytosis. Furthermore, we propose a collaborative prospective study to investigate the potential role of constructing a diagnostic algorithm using multiparameter analysis for improved LNB diagnosis.

Difficulties in differential diagnosis of chronic tick-borne encephalitis and progressive supranuclear palsy

The article presents two clinical cases of 51 and 57-year-old patients living in regions endemic for tick-borne encephalitis in which the differential diagnosis between progressive supranuclear palsy (PSP) and the extremely rare parkinsonian variant of chronic tick-borne encephalitis (CTBE) resulted in a diagnostic challenge. In both cases there was a clinical presentation of progressive symmetric levodopa-resistant parkinsonism with vertical gaze palsy, cognitive impairment of the executive type, frontal lobe signs, focal dystonia and in one case — early onset of postural instability, which corresponds to the diagnosis of probable PSP. The parkinsonian variant of CTBE was supported by the lack of tick-borne encephalitis virus IgG-antibodies negativity in the blood for several years, intrathecal oligoclonal antibody synthesis in one patient, the absence of typical neuroimaging signs of PSP, and delayed disease onset after a tick bite. Difficulties in diagnosis and possible mechanisms of the pathogenesis of primary progressive CTBE, as well as the similarity of the clinical and pathomorphological presentation of PSP, von Economo encephalitis lethargica, and postencephalitic parkinsonism are discussed.

Biomarkers related to the intrathecal humoral immune response as laboratory tools for multiple sclerosis diagnosis

In cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, the intrathecal synthesis (IS) of affinity-maturated IgG class antibodies secreted by transmigrated B cells, is considered as a hallmark of the disease. It is classically revealed by CSF isofocusing test (detection of IgG Oligoclonal bands (OCB) in CSF, considered as “the gold standard”), Total IgG Index and/or Reiber diagram. Our aim is to analyse the comparative performance of different CSF testing techniques for MS diagnosis.

Clinical and laboratory evidence of Lyme disease in North India, 2016–2019

BackgroundLyme disease is endemic to parts of the Americas, Europe and Asia. However, only a handful of sporadic cases have been reported from India. In this study, we systematically evaluated the clinical and epidemiological features of Lyme disease in North India. MethodAll samples were tested by using the standard two-tiered testing algorithm (STTA). Paired serum and cerebrospinal fluid (CSF) were used for demonstrating Borrelia burgdorferi specific intrathecal IgG antibody synthesis (AI). In addition, a commercial tick-borne bacterial flow chip (TBFC) system and a real-time PCR were also used to detect Borrelia species and Anaplasma phagocytophilum in patients who were positive by STTA. ResultsThe diagnosis of Lyme disease was confirmed in 18 (7.14%) of the 252 clinically suspected cases by STTA. Neurological involvement was reported in 14 (77.78%) patients, whereas joint and heart involvement was reported in five (27.78%) and three (16.67%) patients, respectively. Lymphocytic pleocytosis (median 37.5 cells/mm3; range 12–175 cells/mm3) in the CSF was seen in 11 of 14 Lyme neuroborreliosis (LNB) patients. Intrathecal production of Borrelia specific IgG antibodies was demonstrated in 9 (64.28%, n = 14) patients, a highly specific finding for neuroborreliosis. Two patients (11.11%) were also found to be co-infected with human granulocytic anaplasmosis. ConclusionsThe results of this study show clinical and laboratory evidence of endemic Lyme disease in North India and thus, highlight the importance for travel medicine practitioners and physicians to evaluate for Lyme disease in patients with compatible symptoms and a history of travel to tick risk areas.