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.

Lipid mediators of cerebrospinal fluid in response to TBE and bacterial co-infections.

Tick-borne diseases are caused by monoinfection or co-infection with different pathogens, including viruses, bacteria and protozoa. Tick-borne diseases are usually accompanied by oxidative stress which promotes the modifications of the host's lipid metabolism. The aim of the study was to compare total antioxidant status and the level of lipid mediators in the cerebrospinal fluid in response to tick-borne encephalitis (TBE) and bacterial co-infections that cause diseases such as that is Lyme borreliosis (LB) and human granulocytic anaplasmosis (HGA). In our study cerebrospinal fluid samples were obtained from 15 patients with TBE and 6 patients with TBE co-infection with LB and/or HGA at admission and after treatment. Control group consisted of 14 patients in whom meningitis was excluded. Total antioxidant status, levels of lipid peroxidation products, endocannabinoids and eicosanoids (determined by liquid and gas chromatography-mass spectrometry) were compared between the groups. It was found that in TBE patients, total antioxidant status was decreased and accompanied by increased levels of lipid peroxidation products (4-HNE, MDA, isoprostanes and neuroprostanes), major endocannabinoids (AEA and 2AG), and eicosanoids (both anti-inflammatory and pro-inflammatory), which generally declined after treatment. On the other hand, in co-infections, significant changes in the levels of some lipid mediators were observed even after the treatment. TBE alone or along with bacterial co-infections promote redox balance disturbances in the cerebrospinal fluid leading to oxidative stress and increased metabolism of phospholipids in the brain tissue reflected in the level of lipid peroxidation products and lipid mediators. Changes in the level of lipid mediators in patients with co-infections after treatment suggest further intensification of metabolic disturbances rather than their resolution.

Tick-borne encephalitis: Acute clinical manifestations and severity in 581 cases from Germany, 2018-2020.

OBJECTIVES: Tick-borne encephalitis (TBE) is a growing public health problem with an average of 361 cases notified annually to Germany's passive surveillance system since 2001. We aimed to assess clinical manifestations and identify covariates associated with severity. METHODS: We included cases notified 2018-2020 in a prospective cohort study and collected data with telephone interviews, questionnaires to general practitioners, and hospital discharge summaries. Covariates' causal associations with severity were evaluated with multivariable logistic regression, adjusted for variables identified via directed acyclic graphs. RESULTS: Of 1220 eligible cases, 581 (48%) participated. Of these, 97.1% were not (fully) vaccinated. TBE was severe in 20.3% of cases (children: 9.1%, ≥70-year-olds: 48.6%). Routine surveillance data underreported the proportion of cases with central nervous system involvement (56% vs. 84%). Ninety percent required hospitalization, 13.8% intensive care, and 33.4% rehabilitation. Severity was most notably associated with age (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.05), hypertension (OR: 2.27, 95%CI: 1.37-3.75), and monophasic disease course (OR: 1.67, 95%CI: 1.08-2.58). CONCLUSIONS: We observed substantial TBE burden and health service utilization, suggesting that awareness of TBE severity and vaccine preventability should be increased. Knowledge of severity-associated factors may help inform patients' decision to get vaccinated.

Severe tick-borne encephalitis in a patient recovered from COVID 19.

North-eastern Poland is an endemic region for tick-borne encephalitis (TBE). The COVID-19 pandemic overlapped with the activity period of ticks that are the main vectors for TBE. As we know from short observation worldwide, SARS-CoV-2 virus affects significantly the immune system and can lead to serious complications of other infections even in previously healthy patients. A 24-year-old female patient, who lived close to the forest, was admitted to the Department of Neurology at Medical University of Bialystok with fever, dizziness, and progressive left-sided hemiparesis for three days. She had no medical history of chronic disease and was not vaccinated against TBE. The patient had SARS-CoV-2 infection three weeks prior to admission to the hospital (positive IgG against SARS-CoV-2). During COVID-19 infection she had fever, myalgia, a mild dyspnoea without indications for oxygen therapy and recovered after one week. During hospitalisation in the Department of Neurology the patient presented neck stiffness, progressing tetraparesis, dysarthria and weakness of the neck muscles. The magnetic resonance of the head revealed numerous lesions, mainly in both thalamus, longitudinal lesion was found in the cervical spinal cord. The cerebrospinal fluid analysis indicated lymphocytic inflammation. A high level of TBE antibodies in both serum and CSF was found. After immunoglobulin and symptomatic treatment her condition gradually improved. The recovery after SARS-CoV-2 infection overlapping with TBE might have influenced the course of tick-borne disease in a bad manner. The correct diagnosis can be a challenge as COVID-19 can lead to further complications, also neurological. The co-incidence we observed is very rare, however during the pandemic it is pivotal to remember about possible occurrence of other infections and their atypical course.

Clinical course and neurological sequels after tick-borne encephalitis in children - case report.

INTRODUCTION: Tick-borne encephalitis (TBE) is a neurotropic, tick-transmitted infection. Clinical presentation ranges from mild aseptic meningitis to severe encephalitis, and may result in long-term neurological sequels. OBJECTIVE: The aim of the study is to present the clinical features of TBE in children, and the laboratory findings, in order to identify neurological sequels and the risk of cognitive deficits in long-term TBE infections. MATERIAL AND METHODS: The study included eight children with serologically-confirmed TBE, hospitalized in the Paediatric Centre in Kielce, Poland. RESULTS: Despite the more benign clinical course of TBE infections in children compared to adults, the potential for long-term cognitive sequels can be serious. It is hypothesized that a developing CNS is more susceptible to long-term infection effects. CONCLUSIONS: Paediatric TBE should be considered in children with unexplained acute CNS-related symptoms. The long-term consequences may occur with permanent impairment of the quality of life due to neurological consequences.

The manifestation of myositis in tick-borne encephalitis as a prophet of severe disease course: a rare case report.

Tick-borne encephalitis (TBE) is one of the most serious neurological tick-transmitted diseases. The initial phase usually occurs with non-specific symptoms such as fever, headache, and muscular pain. The clinical spectrum of the second phase of the disease typically ranges from mild meningitis to severe meningoencephalitis. Our case demonstrates a rare clinical case of acute myositis as manifestation of TBE virus infection. A 33-year-old female was admitted to the Rheumatology centre with a fever followed by proximal muscle pain and weakness. Despite the tick bite history and marginally positive anti-TBE virus IgM titre, the patient did not present any neurological symptoms. Laboratory test results showed elevated creatine kinase (CK) and myoglobin. Other infections, idiopathic inflammatory myopathies, were excluded. TBE virus infection was confirmed by rapid seroconversion of specific IgG class antibodies in serum. The second phase of the disease was followed by neurological symptoms and a repeated increase of CK and myoglobin. We suggest that in the case of acute myositis of unknown cause and the history of thick bite, TBE virus infection should be considered and creatine kinase might be considered as a laboratory marker of disease activity that correlates with the severity of the disease.

Tick-borne encephalitis related uveitis: a case report.

BACKGROUND: Tick-borne encephalitis (TBE) is an infectious disease of the central nervous system caused by the TBE virus (TBEV), which is usually transmitted by a tick-bite, with increasing incidence in northeastern Europe and eastern Asia during the past decade. Ocular involvement has not been described in the literature to date. CASE PRESENTATION: A 58-year-old patient presented to the emergency department with occipital headaches and poor balance for 5 days. He reported a tick-bite 6 weeks before without erythema migrans followed by a flu-like syndrome. Serological testing was negative for Borreliosis and TBEV. At presentation, he was febrile with neck stiffness and signs of ataxia. Three days later, he presented unilateral visual loss in his right eye. Examination revealed non granulomatous anterior uveitis, vitreous inflammation, and retinal haemorrhages at the posterior pole without macular oedema or papillitis. Polymerase chain reaction (PCR) of the cerebrospinal fluid returned negative for all Herpes family viruses. No clinical evidence of other infection nor malignancy was identified. A seroconversion of the TBEV- immunoglobulin titres was observed 2 weeks later while the serum antibodies for Borrelia were still not detected. Magnetic resonance imaging was unremarkable. We concluded to the diagnosis of TBE-related uveitis. Under supportive treatment, there was complete resolution of the neurological symptoms and the intraocular inflammation without sequelae within the following weeks. CONCLUSIONS: We describe a new association of TBEV with uveitis. In view of the growing number of TBE cases and the potential severity of the disease we aim at heightening awareness to achieve prompt recognition, prevention, and treatment.

[A case of tick-borne encephalitis without any sequelae].

A 43-year-old woman with a history of tick bite in the mountains in Hokkaido presented with a fever of 39°C, headache, and nausea. Cerebrospinal fluid findings indicated meningitis. On day 3 after admission, she presented with restlessness, disturbance of consciousness, and ataxic breathing, indicative of encephalitis. We administered steroid pulse therapy, tracheal intubation, and a respirator. Her symptoms improved gradually and she was able to breathe without the respirator on day 10 after admission. She was discharged on day 24 after admission with no sequelae. This is the fifth reported case of tick-borne encephalitis in Japan. In the previous four cases, the patients died or suffered severe sequelae. This is the first case without any sequelae in Japan.

Epilepsy after brain infection in adults: A register-based population-wide study.

OBJECTIVE: To describe risk and risk factors of epilepsy after hospitalization for brain infection in adults in Sweden. METHODS: This was a matched retrospective cohort study based on the comprehensive National Patient and Cause of Death Registers. All individuals age >18 without prior epilepsy who received inpatient care in 2000-2010 for a brain infection were included, with 3 age- and sex-matched unexposed controls per exposed individual (n = 12,101 exposed and 36,228 controls). Kaplan-Meier risks of epilepsy after different brain infections were calculated and risk factors identified by Cox regression. Patients were followed until the end of 2017. RESULTS: The 10-year risk of epilepsy was 5.9% (95% confidence interval [CI] 5.5-6.3) in cases and 1.2% (95% CI 1.0-1.4) in controls: 1.7% (95% CI 0.7-2.7) after tick-borne encephalitis, 4.1% (95% CI 3.3-4.9) after bacterial meningitis, 26.0% (95% CI 21.5-30.5) after herpes simplex virus encephalitis, and 30.2% (95% CI 27.1-33.3) after brain abscess. In Cox regression, seizure during the index admission and mechanical ventilation were epilepsy risk factors. CONCLUSIONS: Epilepsy is common after several types of brain infections in adults. The type of infection, its severity, and propensity to cause seizures in the acute phase influence the risk of subsequent epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in adults, brain infection is associated with an increased risk of subsequent epilepsy.

Analysis of CCL-4, CCL-17, CCL-20 and IL-8 concentrations in the serum of patients with tick-borne encephalitis and anaplasmosis.

PURPOSE: Tick-borne co-infections are a serious epidemiological and clinical problem. Only a few studies aimed to investigate the effect of tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) co-infection in the course of the inflammatory process and the participation of chemokines in the pathomechanism of these diseases. The aim of the study was to evaluate CCL-4, CCL-17, CCL-20, and IL-8 serum concentrations in patients with HGA, TBE and HGA + TBE co-infection. METHODS: Eighty-seven patients with HGA (n = 20), TBE (n = 49) and HGA + TBE (n = 18) were included to the study. The control group (CG) consisted of 20 healthy people. Concentrations of cytokines were measured in serum using commercial ELISA assays. In patients with TBE and HGA + TBE inflammatory markers were assessed during the acute and convalescent period. The results were analyzed using non-parametric tests with p < 0.05 considered as significant. RESULTS: Before treatment, significantly higher concentrations of IL-8, CCL-4 and CCL-20 were observed in HGA patients. CCL-4 and CCL-20 concentrations were significantly higher in TBE patients compared to CG. Concentrations of IL-8, CCL-4, and CCL-20 were significantly higher in HGA + TBE than in CG. After treatment, a significant reduction of IL-8, CCL-4, and CCL-20 concentrations in TBE patients and IL-8 in HGA + TBE co-infection was observed. CCL-4 concentration was higher in HGA + TBE co-infection in comparison to patients with TBE after treatment. CONCLUSIONS: Our study confirms that concentrations of IL-8, CCL-4, and CCL-20 are increased in the course of HGA and TBE. Their concentrations in serum may be used to monitor the course of TBE and HGA, as well as possibly detect co-infections with the diseases.

Experimental infection of lambs with tick-borne encephalitis virus and co-infection with Anaplasma phagocytophilum.

Tick-borne encephalitis virus (TBEV) is a zoonotic pathogen which may cause tick-borne encephalitis (TBE) in humans and animals. More than 10,000 cases of TBE are reported annually in Europe and Asia. However, the knowledge on TBE in animals is limited. Co-infection with Anaplasma phagocytophilum and louping ill virus (LIV), a close relative to TBEV, in sheep has been found to cause more severe disease than single LIV or A. phagocytophilum infection. The aim of this study was to investigate TBEV infection and co-infection of TBEV and A. phagocytophilum in lambs. A total of 30 lambs, aged five to six months, were used. The experiment was divided into two. In part one, pre- and post-infection of TBEV and A. phagocytophilum was investigated (group 1 to 4), while in part two, co-infection of TBEV and A. phagocytophilum was investigated (group 5 and 6). Blood samples were drawn, and rectal temperature was measured daily. Lambs inoculated with TBEV displayed no clinical symptoms, but had a short or non-detectable viremia by reverse transcription real-time PCR. All lambs inoculated with TBEV developed neutralizing TBEV antibodies. Our study is in accordance with previous studies, and indicates that TBEV rarely causes symptomatic disease in ruminants. All lambs inoculated with A. phagocytophilum developed fever and clinical symptoms of tick-borne fever, and A. phagocytophilum was present in the blood samples of all infected lambs, shown by qPCR. Significantly higher mean TBEV titer was detected in the group co-infected with TBEV and A. phagocytophilum, compared to the groups pre- or post-infected with A. phagocytophilum. These results indicate that co-infection with TBEV and A. phagocytophilum in sheep stimulates an increased TBEV antibody response.

Powassan virus encephalitis, severe babesiosis and lyme carditis in a single patient.

Ixodes scapularis is responsible for transmission of Borrelia burgdorferi, B. miyamotoi, Babesia microti, Anaplasma phagocytophilum and Powassan virus to humans. We present a case of an 87-year-old man who presented with fever and altered mental status. Initial workup revealed haemolytic anaemia, thrombocytopenia, mild hepatitis and acute kidney injury. Patient tested positive for B. burgdorferi and Babesia microti, and was started on doxycycline, atovaquone and azithromycin. He also underwent exchange transfusion twice. After some initial improvement, patient had acute deterioration of mental status and appearance of neurological findings like myoclonus and tremors. Therefore, testing for arboviruses was done and results were positive for Powassan virus. During a protracted course of hospitalisation, patient required intubation for respiratory failure and temporary pacemaker for unstable arrythmias from Lyme carditis. Patient developed permanent neurological deficits even after recovery from the acute illness.

Tick-borne Encephalitis: Stroke-like Presentation.

Tick-borne encephalitis, caused by the tick-borne virus (TBEV), is endemic in central, eastern, and northern Europe eastwards through Russian Siberia and China. For the year 2009, the highest incidence in Scandinavian countries was in Sweden. The clinical symptoms have a wide spectrum. We report a unique case of clinical symptoms and radiological findings compatible with a stroke-like inflammatory lesion in the thalamus, suggesting microangiopathy from TBEV. Our case shows that TBEV could be a possible cause of stroke-like lesions.

Anti-NMDAR encephalitis preceded by non-herpetic central nervous system infection: Systematic literature review and first case of tick-borne encephalitis triggering anti-NMDAR encephalitis.

After the recent description of biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE), anti-NMDARE preceded by non-HSV central nervous system (CNS) infection has been more rarely reported. We report the first case of TBE followed by anti-NMDARE and carry out a systematic literature review on anti-NMDARE preceded by non-HSV CNS infection.

Assessment of the tau protein concentration in patients with tick-borne encephalitis.

There have been suggestions that tick-borne encephalitis (TBE) may cause neurodenenerative changes in the brain. The aim of this study was the assessment of the tau protein concentration in cerebrospinal fluid (CSF) of patients with different clinical forms of TBE. The concentration of tau protein in CSF was determined using Fujirebio tests (Ghent, Belgium) in 35 patients with TBE: group I-patients with meningitis (n = 16); group II-patients with meningoencephalitis (n = 19). None of the patients reported any neurodegenerative disorder that could affect the results of the study. The control group (CG) consisted of 10 patients in whom inflammatory process in central nervous system was excluded. Tau protein concentration in CSF before treatment did not differ significantly between the examined groups, while its concentration was significantly higher in encephalitis group than in CG after 14 days of treatment. Significant increase in tau protein concentration after treatment was observed in both examined groups. The comparison between the group of patients who fully recovered and patients who presented with persistent symptoms on discharge showed significant differences in tau protein concentration before and after treatment. ROC curve analysis indicates that CSF tau protein concentration before treatment may predict complicated course of the disease with 90.9% specificity and 80% sensitivity, while after treatment, specificity became 72.7% and 71.4% for sensitivity. Correlation analysis showed that in TBE patients (both meningoencephalitis and meningitis groups), CSF pleocytosis before treatment correlated negatively with tau protein concentration in CSF. (1) Neurodegeneration process is present in TBE encephalitis. (2) Tau protein concentration may be used as a predictor of complicated course of TBE.

Reviewing estimates of the burden in disability-adjusted life years (DALYs) of tick-borne encephalitis in Slovenia.

INTRODUCTION: Tick-borne encephalitis (TBE) reflects an increasing burden and can affect public health policy. Vaccination could be the most effective option to reduce the disease burden, this review can support national recommendations for TBE vaccination in Slovenia. AREAS COVERED: This burden is relatively high in Slovenia and can be estimated by using an incidence-based disability-adjusted life years (DALYs) methodology. Notably, DALYs have been estimated for Slovenia in various studies. The present study summarizes the main differences and conclusions between two studies that dealt with the calculation of DALYs for TBE in Slovenia. The databases of PubMed and Embase were used to get information about publications that dealt with the TBE burden, using an incidence-based DALYs methodology, in Slovenia. EXPERT OPINION: Permanent sequelae contribute the most to the total burden in DALYs. Increasing vaccination in all ages and age groups can be the most effective and efficient strategy to reduce the burden of TBE and protect the whole population health.

Epilepsia partialis continua following a Western variant tick-borne encephalitis.

Epilepsia partialis continua (EPC) is a rare entity, first described in 1894 by Kozevnikov, as a variant of simple focal motor status epilepticus. EPC is most frequently characterized by motor symptoms, but as recently described, non-motor manifestations may occur, such as somatosensory symptoms or aura continua. EPC in adults has been attributed to various etiologies: infectious, vascular, neoplastic, and metabolic. According to the recent definition, we reported a case of EPC with behavioral symptoms, following a tick-borne encephalitis (TBE) contracted in an endemic area (North Eastern Italy). Patient's symptom was a poorly localized "whole body sensation", which is reported as a condition occurring only in frontal lobe epilepsy. Patient's EEG showed a left frontal predominance of epileptiform discharges. Literature highlighted the importance of the Far-eastern TBE variant as a cause of EPC, since no Western variant TBE cases are reported. In contrast to what was claimed so far, our case demonstrates that not only the Far-eastern TBE variant, but also Western variant TBE is a cause of EPC. Prognosis of EPC depends largely on the underlying etiology, and it is frequently drug-resistant. Our patient was treated with intravenous levetiracetam, with a subsequent clinical recovery and a disappearance of epileptiform discharges. The rapid clinic and electroencephalographic response to levetiracetam confirm that it can be a promising therapeutic option for treatment of EPC.

Sequelae of tick-borne encephalitis in retrospective analysis of 1072 patients.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe. The aim of the study was to evaluate sequelae and to analyse the potential risk factors predisposing to sequelae development. We performed a retrospective analysis of medical records of 1072 patients who received a 1-month follow-up appointment after hospital discharge. Medical data, such as patients' age, gender, place of living, subjective complaints, neurological and psychiatric sequelae were evaluated twice: at the moment of discharge and at follow-up visits 1 month after discharge. We observed that sequelae may affect 20.6% of TBE patients. Subjective sequelae were more frequent than subjective complaints during the hospitalisation (P < 0.001), while objective neurological symptoms during the hospitalisation were more pronounced than neurological sequelae (P < 0.001). Patients with meningoencephalomyelitis were predisposed to neurological complications, while subjective symptoms were more common in meningoencephalitis. Independent risk factors for sequelae development were: age and cerebrospinal fluid (CSF) protein concentration. The risk of late neurological complications persisting was increased in patients with higher CSF protein concentration. Based on the results of our study we concluded that, there is a need for a better vaccination program, which would prevent the development of sequelae.