Elevated levels of serum muscle enzymes in the initial phase of tick-borne encephalitis.

PURPOSE: Since some patients with tick-borne encephalitis (TBE) have pronounced myalgias, and since myositis is reported in Flavivirus diseases such as dengue, we performed systematic search for abnormalities of muscle enzymes in a group of patients in whom the presence of tick-borne encephalitis virus (TBEV) RNA in the first phase of the disease was demonstrated and who developed second phase of TBE. METHODS: Total leukocyte and platelet blood counts were determined routinely at the initial examination during the first and the second phase of TBE. Activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), myoglobin and troponin was determined from the available stored serum specimens; the first and second phase disease specimens were tested simultaneously. RESULTS: Of 24 patients with biphasic course of TBE, 83% had leukopenia, 65% thrombocytopenia, 83% elevated AST and 4% elevated ALT level. Furthermore, 33% had elevated serum CK, 26% myoglobin and 22% troponin activity; at least one of the muscle enzymes was elevated in 42% of patients. Leukopenia, thrombocytopenia, elevated liver enzymes and elevations of CK and myoglobin were present in the initial phase but resolve later, while troponin abnormalities were also found in the second phase of TBE. CONCLUSIONS: The present study exposes that in addition to previously known leukopenia, thrombocytopenia and increased liver enzymes activity, the initial phase of TBE is relatively often associated also with elevated muscle enzymes. Clinical relevance of these findings remains to be determined.

Why Is the Duration of Erythema Migrans at Diagnosis Longer in Patients with Lyme Neuroborreliosis Than in Those without Neurologic Involvement?

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth's syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB.

Comparison of laboratory and immune characteristics of the initial and second phase of tick-borne encephalitis.

Tick-borne encephalitis (TBE) usually has a biphasic course which begins with unspecific febrile illness, followed by central nervous system involvement. Because TBE is not yet suspected during the initial phase, knowledge of early TBE pathogenesis is incomplete. Herein we evaluated laboratory and immune findings in the initial and second (meningoencephalitic) phase of TBE in 88 well-defined adult patients. Comparison of nine laboratory blood parameters in both phases of TBE revealed that laboratory abnormalities, consisting of low leukocyte and platelet counts and increased liver enzymes levels, were predominately associated with the initial phase of TBE and resolved thereafter. Assessment of 29 immune mediators in serum during the initial phase, and in serum and cerebrospinal fluid (CSF) during the second phase of TBE revealed highly distinct clustering patterns among the three groups. In the initial phase of TBE, the primary finding in serum was a rather heterogeneous immune response involving innate (CXCL11), B cell (CXCL13, BAFF), and T cell mediators (IL-27 and IL-4). During the second phase of TBE, growth factors associated with angiogenesis (GRO-α and VEGF-A) were the predominant characteristic in serum, whereas innate and Th1 mediators were the defining feature of immune responses in CSF. These findings imply that distinct immune processes play a role in the pathophysiology of different phases of TBE and in different compartments.

Clinical and Laboratory Characteristics and Outcome of Illness Caused by Tick-Borne Encephalitis Virus without Central Nervous System Involvement.

Information on febrile illness caused by tick-borne encephalitis virus (TBEV) without central nervous system involvement is limited. We characterized 98 patients who had TBEV RNA in their blood but no central nervous system involvement at the time of evaluation. Median duration of illness was 7 days; 37 (38%) patients were hospitalized. The most frequent findings were malaise or fatigue (98%), fever (97%), headache (86%), and myalgias (54%); common laboratory findings were leukopenia (88%), thrombocytopenia (59%), and abnormal liver test results (63%). During the illness, blood leukocyte counts tended to improve, whereas thrombocytopenia and liver enzymes tended to deteriorate. At the time of positive PCR findings, 0/98 patients had serum IgG TBEV and 7 serum IgM TBEV; all patients later seroconverted. Viral RNA load was higher in patients with more severe illness but did not differ substantially in relation to several other factors. Illness progressed to tick-borne encephalitis in 84% of patients within 18 days after defervescence.

Colocalization of Radicular Pain and Erythema Migrans in Patients With Bannwarth Syndrome Suggests a Direct Spread of Borrelia Into the Central Nervous System.

BACKGROUND: There is a general assumption that after deposition into skin, Lyme borreliae disseminate hematogenously to other organs, resulting in extracutaneous manifestations of Lyme borreliosis, including Lyme neuroborreliosis. However, our experience over the past 40 years, along with several published case reports that observed colocalization of radicular pain and erythema migrans (EM) in patients with borrelial meningoradiculoneuritis (Bannwarth syndrome), argues against hematogenous dissemination in Lyme neuroborreliosis. METHODS: We compared the location of EM in 112 patients with Bannwarth syndrome to 12315 EM patients without neurological involvement. Moreover, we assessed the colocalization of EM and radicular pain in patients with Bannwarth syndrome. RESULTS: Compared to >12000 EM patients without neurological involvement, patients with Bannwarth syndrome had a significantly higher frequency of EM on head/neck (6% vs 1%; P=.0005) and trunk (47% vs 24%; P<.0001), similar frequency on arms (16% vs 16%; P=.91), but lower frequency on legs (30% vs 59%; P<.0001). Moreover, in 79% (89/112) of patients the site of EM matched the dermatomes of radicular pain. The odds for a congruent location of EM and radicular pain were highly significant with the highest odds ratios (OR) observed for head (OR=221), followed by neck (OR=159), legs (OR=69), arms (OR=48), and trunk (OR=33). CONCLUSIONS: The greater frequency of EM on head/neck and trunk and the colocalization of EM with radicular pain in patients with Bannwarth syndrome suggest that central nervous system involvement in Lyme neuroborreliosis is due to a retrograde spread of borrelia from skin to the spinal cord via peripheral nerves.

Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis.

Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-ß and higher systemic levels of neutrophil chemoattractants IL-8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients.

Comparison of Clinical, Laboratory and Immune Characteristics of the Monophasic and Biphasic Course of Tick-Borne Encephalitis.

The biphasic course of tick-borne encephalitis (TBE) is well described, but information on the monophasic course is limited. We assessed and compared the clinical presentation, laboratory findings, and immune responses in 705 adult TBE patients: 283 with monophasic and 422 with biphasic course. Patients with the monophasic course were significantly (p ≤ 0.002) older (57 vs. 50 years), more often vaccinated against TBE (7.4% vs. 0.9%), more often had comorbidities (52% vs. 37%), and were more often treated in the intensive care unit (12.4% vs. 5.2%). Multivariate logistic regression found strong association between the monophasic TBE course and previous TBE vaccination (OR = 18.45), presence of underlying illness (OR = 1.85), duration of neurologic involvement before cerebrospinal fluid (CSF) examination (OR = 1.39), and patients' age (OR = 1.02). Furthermore, patients with monophasic TBE had higher CSF levels of immune mediators associated with innate and adaptive (Th1 and B-cell) immune responses, and they had more pronounced disruption of the blood-brain barrier. However, the long-term outcome 2-7 years after TBE was comparable. In summary, the monophasic course is a frequent and distinct presentation of TBE that is associated with more difficult disease course and higher levels of inflammatory mediators in CSF than the biphasic course; however, the long-term outcome is similar.

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis.

Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with detailed clinical and laboratory parameters during acute illness and with the presence of post-encephalitic syndrome (PES) 2-7 years after TBE. Specific IgG antibody levels ranged from below cut-off value (in 32/691 patients, 4.6%), to 896 U/mL (median = 37.3 U/mL). Patients with meningoencephalomyelitis were more often seronegative (24.3%; 9/37) than those with meningoencephalitis (4.7%; 20/428) or meningitis (1.3%; 3/226). Moreover, patients with antibody levels below cut-off had longer hospitalization (13 versus 8 days); more often required intensive care unit treatment (22% versus 8%) and artificial ventilation (71% versus 21%); and had a higher fatality rate (3/32; 9.4% versus 1/659; 0.2%) than seropositive patients. These results were confirmed when antibody levels, rather than cut-off values, were correlated with clinical parameters including the likelihood to develop PES. Low serum IgG antibody responses against TBEV at the onset of neurologic involvement are associated with a more difficult clinical course and unfavorable long-term outcome of TBE, providing a diagnostic and clinical challenge for physicians.

Effect of Statin Use on the Clinical Manifestations, Laboratory Test Results and Outcome of Lyme Neuroborreliosis.

Statins have anti-inflammatory and potentially antimicrobial activity, but whether they have a beneficial effect on the course of infectious diseases is controversial. In this study, we assessed the impact of pre-existing statin use on the course and outcome of Lyme neuroborreliosis manifested as meningoradiculitis (Bannwarth's syndrome). One hundred and twenty three consecutive patients with Bannwarth's syndrome, of whom 18 (14.6%) were being treated with statins, were included in the study. To assess the influence of statin use on the course and outcome of the disease, univariate and multivariable analyses were performed. No statistically significant association was found between statin pre-treatment and the clinical manifestations, laboratory test results, and outcome of Bannwarth's syndrome. In conclusion, pre-existing use of statins did not significantly impact either the clinical presentation or the outcome of Bannwarth's syndrome.

Inflammatory Immune Responses in Patients with Tick-Borne Encephalitis: Dynamics and Association with the Outcome of the Disease.

Information on the association of inflammatory immune responses and disease outcome after tick-borne encephalitis (TBE) is limited. In the present study, we assessed the levels of 24 cytokines/chemokines associated with innate and adaptive immune responses in matched serum and cerebrospinal fluid (CSF) samples of 81 patients at first visit, and in serum at follow-up time points. Serum levels of several cytokines/chemokines obtained during the meningoencephalitic phase of TBE differed compared to the levels at a follow-up visit 2 months later; several significant differences were also found in cytokine/chemokine levels in serum at 2 months compared to the last time point, 2-7 years after acute illness. Cytokines/chemokines levels in CSF or serum obtained at the time of acute illness or serum levels obtained 2 months after the onset of TBE did not have predictive value for an unfavorable outcome 2-7 years later. In contrast, serum levels of mediators associated with Th17 responses were lower in patients with unfavorable outcome whereas those associated with other adaptive or innate immune responses were higher at the last visit in those with an unfavorable outcome. These findings provide new insights into the immunopathogenesis of TBE and implicate inflammatory immune responses with post-encephalitic syndrome years after the initial infection.

Inflammatory Immune Responses in the Pathogenesis of Tick-Borne Encephalitis.

Clinical manifestations of tick-borne encephalitis (TBE) are thought to result from the host immune responses to infection, but knowledge of such responses is incomplete. We performed a detailed clinical evaluation and characterization of innate and adaptive inflammatory immune responses in matched serum and cerebrospinal fluid (CSF) samples from 81 adult patients with TBE. Immune responses were then correlated with laboratory and clinical findings. The inflammatory immune responses were generally site-specific. Cytokines and chemokines associated with innate and Th1 adaptive immune responses were significantly higher in CSF, while mediators associated with Th17 and B-cell responses were generally higher in serum. Furthermore, mediators associated with innate and Th1 adaptive immune responses were positively associated with disease severity, whereas Th17 and B cell immune responses were not. During the meningoencephalitic phase of TBE, innate and Th1 adaptive inflammatory mediators were highly concentrated in CSF, the site of the disease. The consequence of this robust immune response was more severe acute illness. In contrast, inflammatory mediators associated with B cell and particularly Th17 responses were concentrated in serum. These findings provide new insights into the immunopathogenesis of TBE and implicate innate and Th1 adaptive responses in severity and clinical presentation of acute illness.

Borrelia burgdorferi sensu lato infection in patients with peripheral facial palsy.

The aims of the study were to determine the frequency of borrelial infection in patients with peripheral facial palsy (PFP) and to compare clinical and laboratory characteristics of patients with borrelial PFP and patients with PFP of unknown etiology. Adult patients with PFP who presented at our department between January 2006 and December 2013 qualified for the study if they had undergone lumbar puncture and also been tested for the presence of borrelial IgM and IgG antibodies in serum and cerebrospinal fluid (CSF) in indirect chemiluminescence immunoassay. Patients with PFP who had obvious signs/symptoms indicating a disease other than Lyme borreliosis (LB) were excluded. Patients who qualified for the study were classified into three groups according to the clinical and microbiological criteria: those having confirmed LB, those with possible LB, and those with PFP of unknown etiology. Of 589 patients diagnosed with PFP during the eight-year period, 436 patients (240 males, 196 females) with median age 42.5 years (15-87 years) qualified for the study. Among these patients, 64 (14.7%) fulfilled criteria for confirmed LB, 120 (27.5%) had a diagnosis of possible LB, and in 252 (57.8%) the cause of their PFP remained unknown. When compared with patients with unknown cause of PFP, the patients with confirmed LB were older, more often presented in summer, more often reported tick bites, more frequently had LB in the past, more often complained of constitutional symptoms and radicular pain, and more often had bilateral palsy and CSF pleocytosis. Among the patients with possible LB and patients with unknown cause of PFP there were no differences in frequency of constitutional symptoms, radicular pain, bilateral palsy or CSF pleocytosis. Presentation in summer, tick bites, constitutional symptoms and radicular pain, bilateral palsy, and CSF pleocytosis strongly suggest borrelial etiology of PFP.

Factors associated with severity of tick-borne encephalitis: A prospective observational study.

BACKGROUND: Information on parameters associated with the severity of tick-borne encephalitis (TBE) is limited. METHODS: The association between 15 pre-defined parameters and the severity of TBE was evaluated in 717 consecutive adult patients diagnosed in Slovenia 2007-2012. RESULTS: Multivariable logistic regression showed that patient age (odds ratio, OR 1.26, 95% CI 1.11-1.44; P = 0.001), previous vaccination against TBE (OR 14.23, 95% CI 1.72-117.87; P = 0.014), blood leukocyte count (OR 1.45, 95% CI 1.13-1.85; P = 0.004), and level of specific TBE virus serum IgG antibodies (OR 0.85, 95% CI 0.75-0.96; P = 0.009) were associated with severe acute illness based on the clinical diagnosis. When severity of TBE was based on the severity score and linear regression was used, corresponding association was found for age (estimated coefficient, EC 1.70, 95% CI 1.06-2.33; P<0.001), previous vaccination against TBE (EC 11.16, 95% CI 5.05-17.27; P < 0.001), serum C-reactive protein level (EC 1.20, 95% CI 0.48-1.91; P = 0.001), and level of specific TBE virus serum IgG antibodies (EC -0.74, 95% CI -1.27-0.20; P = 0.007). CONCLUSIONS: Previous vaccination against TBE, low levels of TBE virus serum IgG antibodies, older age, higher blood leukocyte count, and higher serum C-reactive protein levels are associated with more severe TBE.

Virus RNA Load in Patients with Tick-Borne Encephalitis, Slovenia.

We determined levels of tick-borne encephalitis (TBE) virus (TBEV) RNA in serum samples obtained from 80 patients during the initial phase of TBE in Slovenia. For most samples, levels were within the range of 3-6 log10 copies RNA/mL. Levels were higher in female patients than in male patients, but we found no association between virus load and several laboratory and clinical parameters, including severity of TBE. However, a weak humoral immune response was associated with a more severe disease course, suggesting that inefficient clearance of virus results in a more serious illness. To determine whether a certain genetic lineage of TBEV had a higher virulence potential, we obtained 56 partial envelope protein gene sequences by directly sequencing reverse transcription PCR products from clinical samples of patients. This method provided a large set of patient-derived TBEV sequences. We observed no association between phylogenetic clades and virus load or disease severity.

The long-term outcome of tick-borne encephalitis in Central Europe.

BACKGROUND: Information on the long-term outcome of tick-borne encephalitis (TBE) is limited. OBJECTIVES: To assess the frequency and severity of post-encephalitic syndrome (PES) at different time points after TBE, and to determine the parameters associated with unfavourable outcome. METHODS: Adult patients diagnosed with TBE in Slovenia in the period 2007-2012 were followed-up for 12 months and also examined 2-7 years after TBE. Each patient was asked to refer a person of similar age without a history of TBE to serve as control. RESULTS: A total of 420 patients and 295 control persons participated in the study. The proportion of patients with PES (defined as the presence of ≥ 2 subjective symptoms that newly developed or worsened since the onset of TBE and which had no other known medical explanation, and/or ≥ 1 objective neurological sign) was higher (P < 0.001) at the follow-up visit 6 months after the acute illness (127/304, 42%, 95% CI: 36-47%) than at 12 months (68/207, 33%, 95% CI: 26-40%); the proportion at 12 months was the same as at 2-7 years after TBE (137/420, 33%, 95% CI: 28-37%). However, the proportion of severe PES at the last two time points differed (9.7% vs 4.3%, P = 0.008). Multivariate logistic regression showed that unfavourable outcome at 6 months was associated with CSF leukocyte count (OR = 1.003, 95% CI: 1.001-1.005%, P = 0.017), at 12 months with the disease outcome at 6 months (OR = 115.473, 95% CI: 26.009-512.667%, P < 0.001), and at the final visit with disease outcome at 6 months (OR = 3.808, 95% CI: 1.151-12.593%, P = 0.028) and 12 months (OR = 26.740, 95% CI: 8.648-82.680%, P < 0.001). Unspecific symptoms that occurred within the four weeks before the final examination were more frequent and more constant in patients than in the control group. CONCLUSIONS: The frequency of PES diminished over time and stabilized 12 months after the acute illness, whereas the severity of PES continued to decline. Unfavourable outcomes at 12 months and at the final visit were strongly associated with the presence of PES at previous time points.

Cross-neutralisation of viruses of the tick-borne encephalitis complex following tick-borne encephalitis vaccination and/or infection.

The tick-borne encephalitis complex contains a number of flaviviruses that share close genetic homology, and are responsible for significant human morbidity and mortality with widespread geographical range. Although many members of this complex have been recognised for decades, licenced human vaccines with broad availability are only available for tick-borne encephalitis virus. While tick-borne encephalitis virus vaccines have been demonstrated to induce significant protective immunity, as determined by virus-neutralisation titres, vaccine breakthrough (clinical infection following complete vaccination), has been described. The aim of this study was to confirm the cross-neutralisation of tick-borne flaviviruses using mouse immune ascitic fluids, and to determine the magnitude of cross-neutralising antibody titres in sera from donors following tick-borne encephalitis vaccination, infection, and vaccine breakthrough. The results demonstrate that there is significant cross-neutralisation of representative members of the tick-borne encephalitis complex following vaccination and/or infection, and that the magnitude of immune responses varies based upon the exposure type. Donor sera successfully neutralised most of the viruses tested, with 85% of vaccinees neutralising Kyasanur forest disease virus and 73% of vaccinees neutralising Alkhumra virus. By contrast, only 63% of vaccinees neutralised Powassan virus, with none of these neutralisation titres exceeding 1:60. Taken together, the data suggest that tick-borne encephalitis virus vaccination may protect against most of the members of the tick-borne encephalitis complex including Kyasanur forest disease virus and Alkhumra virus, but that the neutralisation of Powassan virus following tick-borne encephalitis vaccination is minimal.

Pathogenetic implications of the age at time of diagnosis and skin location for acrodermatitis chronica atrophicans.

BACKGROUND: The pathogenesis of acrodermatitis chronica atrophicans (ACA) is not well understood. OBJECTIVE: The purpose of this study was to gain a better understanding of ACA by utilizing a large data set of adult Slovenian patients with Lyme borreliosis. METHODS: The age of 590 ACA patients was compared with that of patients with other manifestations of Lyme borreliosis. The location of the ACA lesion on the body was compared with that of erythema migrans (EM). RESULTS: Patients diagnosed with ACA were on average 14.3 years older than patients with EM (p<0.001). ACA patients were also significantly older than patients with Lyme neuroborreliosis or Lyme arthritis (p<0.001). The average delay in diagnosis of ACA was 1.6 years (range 0.1-20 years). For 572 (96.9%) of the ACA patients, the site of the skin lesion(s) was confined to an extremity vs. 79.6% for patients with EM, p<0.001. For the 20 ACA patients who reported a preceding untreated EM lesion at the same body site, the mean time between the development of the EM and the onset of ACA was 3.0±4.4 (median 1.3, range 0.1-15.0) years. CONCLUSIONS: ACA is more likely to be diagnosed in older individuals than any other manifestation of Lyme borreliosis. ACA is more likely than EM to be localized anatomically to the extremities. Available data favor the hypothesis that ACA occurs most often on the extremities of older individuals because of predisposing age-related anatomic or physiologic changes, but more data are needed to define the latency period and other aspects of the pathogenesis of this skin condition.

Cluster of ulceroglandular tularemia cases in Slovenia.

In Slovenia, a small Central European country, where tularemia cases are very rare and mostly sporadic, six cases of ulceroglandular tularemia were recognised in 2012-2013 in patients residing in or visiting a small geographical area of <6km2. Epidemiological data indicated transmission by a tick bite in at least 3/6 patients.

Course and Outcome of Early European Lyme Neuroborreliosis (Bannwarth Syndrome): Clinical and Laboratory Findings.

BACKGROUND: Information on the course and outcome of early European Lyme neuroborreliosis is limited. METHODS: The study comprised 77 patients (38 males, 39 females; median age, 58 years) diagnosed with painful meningoradiculitis (Bannwarth syndrome) who were followed up for 1 year at a single center. RESULTS: Duration of neurological symptoms before diagnosis was 30 (interquartile range, 14-50) days. The most frequent symptoms/signs were radicular pain (100%), sleep disturbances (75.3%), erythema migrans (59.7%), headache (46.8%), fatigue (44.2%), malaise (39%), paresthesias (32.5%), peripheral facial palsy (PFP) (36.4%), meningeal signs (19.5%), and pareses (7.8%). Cerebrospinal fluid (CSF) analysis revealed lymphocytic/monocytic pleocytosis, elevated protein concentration, and intrathecal synthesis of borrelial immunoglobulin M and immunoglobulin G antibody in 100%, 81.1%, 63%, and 88.7% of patients, respectively. Borreliae (predominantly Borrelia garinii) were isolated from CSF, skin, and blood in 15.6%, 40.6%, and 2.7% of patients, respectively. The outcome after 14-day treatment with ceftriaxone was favorable in 87.8% of patients. Control CSF examination at 3 months showed decreased leukocyte counts in all patients; however, 23.3% still had pleocytosis (>10 × 10(6) cells/L). A model based on pretreatment data and the findings at the end of 14-day antibiotic treatment accurately predicted which patients would have an unfavorable outcome 6 or 12 months after treatment. CONCLUSIONS: Our patients had fewer pretreatment neurological complications (PFP, pareses) than reported for Bannwarth syndrome decades ago, probably as the result of earlier recognition and prompt antibiotic treatment. Unfavorable outcome was rare and was predicted by the continued presence of symptoms 14 days after commencement of treatment.