Paretic complications of tick-borne encephalitis and Lyme neuroborreliosis in the Czech Republic: Characteristics and clinical outcome.

Tick-borne encephalitis (TBE) and Lyme neuroborreliosis (LNB), the most common tick-borne diseases of the central nervous system in Central Europe, are frequently associated with pareses. The aim of this study was to characterise paretic complications in patients with TBE and LNB, including their severity, persistence and impact on the patients' quality of life. Our retrospective observational study included patients with aseptic CNS infection due to TBE virus or Borrelia burgdorferi sensu lato. Paretic complications were evaluated in the acute phase and the patients were followed up until complete regression or long-term stabilisation of any neurological deficit. The severity of the neurological deficit was graded according to the modified Rankin Scale (mRS). A total of 823 patients (582 with TBE, 241 with LNB) was included. Paretic complications were diagnosed in 63 TBE patients (10.8 %) and in 147 LNB patients (61.0 %). In TBE, the most common neurological deficit was brachial plexus paresis in 21 patients (33 %) and bulbar symptoms in 18 patients (29 %). In LNB patients, facial nerve palsy was the most frequent neurological deficit (117patients; 79.6 %), followed by lower limb paresis in 23 patients (15.6 %). Forty-nine TBE patients and 134 LNB paretic patients completed follow-up. Paresis resolved within 3 weeks in 16 TBE patients (33 %) and 53 LNB patients (39.5 %), but the proportion of patients with paresis persisting for more than 12 months was significantly higher in TBE (34.7 vs. 3.7 %, p < 0.001). The mean mRS was significantly higher in TBE paretic patients compared to LNB (p < 0.001). Paretic complications are significantly more common in LNB than in TBE but pareses associated with TBE last longer than in LNB and considerably reduce the quality of life of patients. Prevention remains the only way to influence the long-term motor deficits of TBE.

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.

Neurotoxic side effects of acyclovir: two case reports.

Acyclovir is an antiviral drug frequently used in clinical practice. It is indicated for the treatment of infections caused by herpes simplex virus and varicella zoster virus. The drug has a good safety profile; however, severe side effects may rarely occur during therapy. These include renal failure as a major risk factor for neurotoxic side effects potentially developing within 24-48 hours of therapy initiation. The paper presents the cases of two patients developing neurotoxic side effects while treated for herpes zoster. The aim of the authors is to highlight the potential for developing neurotoxic side effects in high-risk groups such as the elderly, patients with impaired renal function or multiple comorbidities on polypharmacy, or those using nephrotoxic drugs. Acyclovir use could lead to renal impairment and an increase in its plasma and CNS concentrations with severe neuropsychiatric side effects. The neurotoxic side effects are reversible after therapy withdrawal. Thus, in patients developing mental impairment or showing other neurological symptoms during acyclovir therapy, the patient should be promptly assessed for potential drug neurotoxicity, their therapy should be discontinued and drug elimination with forced diuresis or hemodialysis considered. Early recognition of acyclovir neurotoxic side effects can significantly improve a patient's prognosis.

Acute Urinary Retention in Aseptic Meningitis: Meningitis-retention Syndrome.

Here we present the case of a 50-year-old woman with acute urinary retention who was treated by the insertion of a permanent catheter. For associated headaches, fever and muscle and joint pain, the patient underwent neurologic examination, including lumbar puncture and magnetic resonance of head and spine. The results confirmed aseptic meningitis. Subsequently, the patient was hospitalized at the infectious disease clinic, where the permanent catheter was extracted after 5 days, with spontaneous micturition recovery and no post-void residual volume. The combination of aseptic meningitis and urinary retention is called meningitis-retention syndrome. This is a rare disease, which has been described only a few times in the literature.

Serological Diagnostics of Lyme Borreliosis: Comparison of Universal and Borrelia Species-Specific Tests Based on Whole-Cell and Recombinant Antigens.

The study compares diagnostic parameters of different commercial serological kits based on three different antigen types and correlates test results with the status of the patient's Borrelia infection. In total, 8 IgM and 8 IgG kits were tested, as follows: enzyme-linked immunosorbent assay (ELISA) (Euroimmun) based on whole-cell antigen, 3 species-specific enzyme immunoassays (EIAs) (TestLine), Liaison chemiluminescence (DiaSorin), ELISA-Viditest (Vidia), EIA, and Blot-Line (TestLine) using recombinant antigens. All tests were performed on a panel of 90 samples from patients with clinically characterized borreliosis (53 with neuroborreliosis, 32 with erythema migrans, and 5 with arthritis) plus 70 controls from blood donors and syphilis patients. ELISA based on whole-cell antigens has superior sensitivity and superior negative predictive value and serves as an excellent screening test, although its specificity and positive predictive values are low. Species-specific tests have volatile parameters. Their low sensitivity and low negative predictive value handicap them in routine diagnostics. Tests with recombinant antigens are characterized by high specificity and high positive predictive value and have a wide range of use in diagnostic practice. Diagnostic parameters of individual tests depend on the composition of the sample panel. Only a small proportion of contradictory samples giving both negative and positive results is responsible for discrepancies between test results. Correlation of test results with the patient's clinical state is limited, especially in the erythema migrans group with high proportions of negative and contradictory results. In contrast, IgG test results in the neuroborreliosis group, which are more concordant, show acceptable agreement with Borrelia status.

[Guideline for the diagnosis and treatment of Lyme borreliosis].

The national guideline aims to highlight the latest knowledge about clinical manifestations of the infection, to summarize the diagnostic algorithm and to recommend the appropriate antibiotic therapy with respect to evidence-based medicine. The recommendations are consistent with most European guidelines as well as those published by the IDSA. The guideline provides the most recent information on the epidemiology, etiology and pathogenesis of Lyme borreliosis, dermatological, neurological and musculoskeletal involvement, the appropriate diagnostic procedure and prevention. Some information is also provided about post-treatment Lyme disease syndrome. Recommended oral and intravenous antimicrobials are listed in a table showing the doses and duration of therapy. The guideline also mentions diagnostic methods to be avoided or whose results should be interpreted with caution. Although the guideline cannot account for all individual variations among patients, it may provide instructions to physicians in typical and frequent clinical situations.

Presence of herpesvirus DNA in cerebrospinal fluid of patients with tick-borne encephalitis and enteroviral meningoencephalitis.

Reactivation of HHVs in the CNS due to inflammation has not been well described yet. The primary aim of this study was to investigate the frequency of HHV DNA detection in the cerebrospinal fluid (CSF) of immunocompetent patients with meningoencephalitis of other than HHV origin. The secondary aim of this study was to evaluate the impact of herpesvirus co-infection on the clinical course and patient outcome. Ninety-six patients with clinically and laboratory proven tick-borne encephalitis (TBE) and 77 patients with a confirmed diagnosis of enteroviral meningitis (EVM), along with a control group of 107 patients without evidence of inflammation in the CSF were retrospectively tested by nested PCR for the presence of DNA of the neurotropic herpesviruses HSV1, HSV2, VZV, and HHV6 in the CSF. The clinical course, laboratory tests, antiviral treatment, and neurological complications in a 6-month follow-up were compared between the groups positive or negative for HHV DNA in the CSF. HHV DNA was found in the CSF of 12 (6.9%) patients (6.3% and 7.8% in the TBE and EVM groups, respectively) and in 1 (0.9%) control patient. None of the patients had recent blisters or rash. The clinical course was comparably mild in all patients. No permanent neurological sequelae were observed. Only the CSF total protein level was significantly higher in HHV DNA-positive than in HHV-negative patients.

[Detection of borrelia DNA from patients with neuroborreliosis and erythema migrans]. / Prukaz boreliové DNA u pacientu s neuroboreliózou.

AIM: Assessment of PCR procedure for proving of the Borrelia burgdorferi sensu lato DNA in nerve and skin forms of Lyme borreliosis. METHODS: DNA from plasma, urine and CSF was isolated by QIAamp DNA mini kit. PCR was designed as two-step amplification (nested-PCR). Each sample was tested in PCR for five target sequences: two were specific for plasmide genes encoding OspA and OspC proteins and three correlated with genes for 16SrDNA, flagellin and p66 protein. RESULTS: Borrelial DNA was proved in 41 patients suffering from neuroborreliosis out of 56 (77.4 %), among 48 patients with erythema migrans (EM) were found 26 positive (54.2 %). After treatment the specific DNA was detected in 22 patients with neuroborreliosis (41.5 %) and 16 patients with EM (38.1 %). Three months after the treatment 23 patients were positive in both of groups (28.7 %) and next 3 months later the specific DNA was found in 6 (9.5 %). The highest rate of positive results was manifested by 16SrDNA target, lower and comparable results were obtained by OspA, C and flagellin primers, the lowest rate was in p66 system. CONCLUSION: The tested PCR proved specific DNA in all tested biological fluids in both of the clinical forms of Lyme borreliosis with a relatively high sensitivity. The proving of DNA can not be used for the assessment of the effect of treatment due to the long persistence of PCR positivity after antibiotic treatment. To achieve a sufficient diagnostic sensitivity of PCR it is desirable to use minimally two amplification systems in parallel.

Examination of specific DNA by PCR in patients with different forms of Lyme borreliosis.

BACKGROUND: Borrelial specific DNA was examined in a group of 62 patients with different forms of Lyme borreliosis (LB) (32 patients suffered from neuroborreliosis, 19 manifested erythema migrans, and 11 joint involvement). METHODS: Nested-PCR system with five newly derived primers was used in parallel. The study was organized prospectively, the presence of DNA was tested for plasma, CSF, joint fluid and urine before treatment, and plasma, joint fluid and urine were examined after treatment. RESULTS: Before therapy, 36 patients (58.1%) were DNA positive on the whole; 21 positive patients (65.6%) were found in the group of neuroborreliosis, 8 (42.1%) showed signs of skin involvement, and 7 (63.6%) were positive in arthritis. After treatment, 11 patients (36.7%) were positive in neuroborreliosis, 3 (17.6%) in skin form, and 6 (54.5%) in joint form of LB. Among 97 positive amplifications the most frequent target was found in primer corresponding with 16S rDNA (50 samples, 51.5%). Lower but very similar results were obtained with primers for OspA (18 positive amplifications; 18.6%), OspC (13 positive amplifications; 13.4%), and flagellin (13 positive amplifications; 13.4%). There were 11 patients in whom only DNA and no specific antibodies were found. CONCLUSIONS: Specific DNA was found in all clinical groups of LB with similar sensitivity. Examination of the borrelial DNA in urine displayed the same sensitivity as in CSF and had a two times higher sensitivity than in plasma.

[First experience with detecting bacterial DNA in the cerebrospinal fluid of patients with purulent meningitis using broad spectrum multiplex nested PCR]. / První zkusenosti s prukazem DNA bakterií v mozkomísním moku u pacientu s hnisavou pomocí sirokospektré multiplex nested PCR.

OBJECTIVES: To propose and verify a PCR assay for detecting Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Staphylococcus species, Streptococcus pneumoniae and Neisseria meningitidis serogroups B and C in a single sample of the cerebrospinal fluid of patients with purulent meningitis. MATERIAL AND METHODS: DNA from the cerebrospinal fluid was isolated using the QIAamp DNA Mini Kit. PCR was performed as two-step amplification (nested PCR). For E. coli, H. influenzae, L. monocytogenes, S. species and S. pneumoniae, universal and species-specific primers encoding bacterial 16S rDNA were used in the first and second reaction, respectively. For N. meningitidis serogroups B and C, an amplification system with primers for the SiaD gene was utilized. RESULTS: Of 25 patients examined at the beginning of their treatment, bacterial DNA was detected in the cerebrospinal fluid of 17 (68 %) of them. Those were six cases of N. meningitidis serogroup B, four of N. meningitidis serogroup C, five of S. pneumoniae, one of H. influenzae and one of L. monocytogenes. Of 7 patients in whom antibiotic therapy was initiated prior to diagnostic lumbar puncture, PCR was positive in four cases. CONCLUSIONS: The proposed nested PCR approach is faster than traditional culture methods and suitable for early laboratory diagnosis of infectious agents. When compared to culture methods, the technique offers slightly higher positivity (by 16 %). This is similar in samples analyzed after the initiation of antibiotic therapy. The PCR method never detected other bacteria than the cultured ones.

[Detection of anti-Ehrlichia antibodies and direct demonstration of Ehrlichia nucleic acid using the polymerase chain reaction (PCR) in patients in the Czech Republic]. / Detekce antiehrlichiových protilátek a prímý prukaz ehrlichiové nukleové kyseliny polymerázovou retezovou reakcí (PCR) u pacientu v Ceské republice.

PURPOSE OF THE STUDY: In patients presenting symptoms with a suspicion of ehrlichiosis we determined antiehrlichia antibodies and investigated the presence of Ehrlichia nucleic acid in the plasma. MATERIAL AND METHODS: In our group were 46 patients with tick sucks in their case history, who presented symptoms compatible with ehrlichiosis. Anti-Ehrlichia antibodies were determined by an indirect immunofluorescent test with a commercial kit from MRL Diagnostics. Ehrlichia DNA was detected using a nested PCR - the target sequence was a part of the antigen Anaplasma phagocytophilum. RESULTS: Antibodies against HGE agents were demonstrated in 28 % of the patients; 10.5 % of the patients had in their serum antibodies reacting to the Ehrlichia chaffeensis antigen. The nucleic acid of A. phagocytophilum was detected in 11 % of the patients. CONCLUSIONS: The Czech population is relatively often exposed to Ehrlichia infections. Although most cases are asymptomatic, we should bear in mind this diagnosis, especially in immunodeficient patients, where early treatment may prevent a complicated course of the disease.