[Epidemiology, diagnosis, and prevention of tick-borne encephalitis in Poland and selected European countries - a position statement of the Polish group of experts]. / Epidemiologia, diagnostyka i profilaktyka kleszczowego zapalenia mózgu w Polsce i wybranych krajach europejskich ­ stanowisko polskiej grupy ekspertów.

Tick-borne encephalitis (TBE) is one of the most common viral neuroinfections in Poland. Detection of specific IgM and IgG anti- TBE antibodies in the serum or cerebrospinal fluid with enzyme-linked immunosorbent assay (ELISA) is a method of choice in TBE diagnostics. No effective antiviral treatment is available for TBE. Increased intracranial pressure, epileptic seizures, and other neurological symptoms in the course of TBE are managed with standard procedures. A routine use of corticosteroids is not recommended. Adults with TBE-related neurological sequelae should undergo physical mobilization and periodic neurological assessments. All patients ought to control their psychological condition and visit a physician in case of worrisome symptoms. Additionally, children need to undergo regular psychological and otolaryngologic consultations. Notably, TBE cases are reported across Poland; therefore, the entire country must be considered as a TBE risk region. The degree of endemicity can be variable in particular parts of the country. Immunization against TBE containing a European subtype of the virus is the most effective prophylactic method. In areas where the disease is highly endemic (according to the WHO definition of ≥5 cases/100 000 population/year), immunization needs to be offered to all ages. Vaccination is recommended in the communities living in areas of moderate TBE endemicity (1-5 cases/100 000/ year), in particular for individuals at high risk of a TBE infection as well as children and the elderly. Vaccination should also be offered to subjects living in areas where TBE occurrence is rare (<1 case/100 000/year) but who are at high risk of infection. A TBE vaccine is recommended to the following populations at high risk of TBE: a) individuals undertaking outdoor leisure activities, b) all professionals working outdoors, particularly in green areas, and c) individuals traveling to endemic areas, if activities during their visit may pose a risk of a tick bite. Post-exposure immunization is not recommended. Med Pr. 2021;72(2):193-210.

Sleep architecture, obstructive sleep apnea and functional outcomes in adults with a history of Tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a widespread viral infection of the central nervous system with increasing incidence in Europe and northern Asia. Post-infectious sequelae are frequent, and patients with TBE commonly experience long-term fatigue and subjective sleep disturbances. Obstructive sleep apnea (OSA) may be a contributing factor, and objective sleep studies with polysomnography (PSG) are lacking. Forty-two adults, 22 TBE patients (cases), diagnosed in Region Västra Götaland, Sweden, between 2012 and 2015, and 20 controls without a known TBE history, underwent an overnight PSG, respectively. All participants responded to questionnaires. The cases and controls were similar regarding age, sex, obesity, concomitant diseases, smoking, and alcohol habits. Despite similar PSG characteristics such as total sleep time and OSA severity indices, the TBE cases reported statistically more sleep-related functional impairment on the Functional Outcome of Sleep Questionnaire (FOSQ) compared with the controls (median scores 18.1 vs. 19.9; p<0.05). In a multivariate analysis, TBE correlated significantly with the lower FOSQ scores (unstandardized ß -1.80 [%95 confidence interval -3.02 - -0.58]; p = 0.005) independent of age, sex, total sleep time and apnea-hypopnea-index. TBE cases with OSA reported the lowest scores on the FOSQ compared with the other subgroups with TBE or OSA alone, and the ones with neither TBE nor OSA. TBE is associated with impaired functional outcomes, in which concomitant OSA may worsen the subjective symptoms. Further studies are warranted to determine the effect of treatment of concomitant OSA on functional outcomes with regard to optimal rehabilitation of TBE.

The lymphocyte populations and their migration into the central nervous system in tick-borne encephalitis.

In tick-borne encephalitis (TBE) the cerebrospinal fluid (CSF) cytosis is dominated by T CD3+CD4+ and T CD3+CD8+ lymphocytes, but their pathogenetic roles and mechanisms of migration into central nervous system (CNS) are unclear. Currently, we have studied CSF lymphocyte subsets and chemotactic axes in TBE patients stratified according to the clinical presentation. Blood and CSF were obtained from 51 patients with TBE (presenting as meningitis in 30, meningoencephalitis in 18 and meningoencephalomyelitis in 3), 20 with non-TBE meningitis and 11 healthy controls. We have studied: (1) abundances of the main lymphocyte subsets and (2) CXCR3 and CCR5 expression on CD3+CD4+ and CD3+CD8+ lymphocytes cytometrically with fluorochrome-stained monoclonal antibodies; (3) concentrations of chemotactic cytokines: CCL5 (CCR5 ligand), CXCL10 (CXCR3 ligand), IL-16, CCL2, CCL20 and CXCL5 with ELISA. Cytokine concentrations were additionally studied in 8 pediatric TBE patients. Data were analyzed with non-parametric tests, p < 0.05 considered significant. The higher CSF lymphocyte counts were associated with symptoms of CNS involvement, especially with altered consciousness (B, Th and Tc cells) and focal neurologic deficits (B cells). The minor fraction of double-positive T CD4+CD8+ cells was unique in associating negatively with encephalitis and altered consciousness. CSF CD3+CD4+ and CD3+CD8+ lymphocyte population was enriched in CCR5-positive cells and CCL5 concentration in CSF was increased and associated with a milder presentation. Although CXCL10 was vividly up-regulated intrathecally and correlated with CSF T lymphocyte counts, the CXCR3 expression in CSF T lymphocytes was low. Serum and CSF concentrations of CCL2, CXCL5 and IL-16 were increased in adult TBE patients, CCL2 created a chemotactic gradient towards CSF and both CCL2 and IL-16 concentrations correlated positively with CSF lymphocyte counts. The particular lymphoid cell populations in CSF associate differently with the clinical presentation of TBE, suggesting their distinct roles in pathogenesis. CCR5/CCL5 axis probably contributes to T lymphocyte migration into CNS. CXCL10 mediates the intrathecal immune response, but is probably not directly responsible for T cell migration. Additional chemotactic factors must be involved, probably including CCL2 and IL-16.

Structural disorder in the proteome and interactome of Alkhurma virus (ALKV).

Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorder-dependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome.

Effect of a single dose of mannitol on hydration status and electrolyte concentrations in patients with tick-borne encephalitis.

OBJECTIVE: This study was performed to assess the effect of a single dose of 15% mannitol on the hydration status and electrolyte balance in patients with tick-borne encephalitis (TBE). METHODS: Forty-one patients with TBE were treated with 0.25 g/kg of 15% mannitol. The electrolyte concentrations (Na, K, and Cl), creatinine concentration, and hydration status were measured before and after mannitol infusion. RESULTS: After mannitol administration, 7 patients had hyponatremia, 3 had hypokalemia, 1 had hyperkalemia, and 17 had hypochloremia. The total body water volume (TBW) changed by 0.44% ± 0.55%, the external body water volume (EBW) changed by 0.12% ± 0.15%, and the internal body water volume (IBW) changed by 0.19% ± 0.40%. The mean ECW/ICW ratio was 0.7694 ± 0.07 before treatment and 0.7699 ± 0.07 after treatment. Age was correlated with the TBW change in men (R = 0.42, p < 0.05) and with the potassium change in women (R = 0.66, p < 0.05). CONCLUSIONS: Patients with TBE should receive mannitol two to four times daily depending on the clinical manifestation. Administration of a single dose of mannitol (0.25 g/kg) requires at least 300 mL of fluid supplementation. Bioimpedance might be useful for individual evaluation of dehydration. Additionally, patients require monitoring for potential hyponatremia. Older men may be more prone to dehydration after receiving mannitol.

Meningoencephaloradiculitis following infection with tick borne encephalitis virus: case report and review of the literature.

Tick borne encephalitis (TBE) is an infectious zoonotic disease caused by an RNA virus that is endemic to Central and Eastern Europe, Russia, and large parts of Asia. The tick borne encephalitis virus (TBEV) is transmitted through the saliva of infected ticks and infected goat milk. In the vast majority of cases, an infection with TBEV has a subclinical course. However, in some cases, it leads to neurological symptoms due to meningitis, meningoencephalitis, meningoencephalomyelitis, or meningoencephaloradiculitis. Here, we present the first case of meningoencephaloradiculitis in Belgium.

Epidemiological patterns of tick-borne encephalitis in Lithuania and clinical features in adults in the light of the high incidence in recent years: a retrospective study.

BACKGROUND AND PURPOSE: Lithuania is one of the countries with the highest incidence of tick-borne encephalitis (TBE) in Europe. The aim of this study was to describe the epidemiological patterns of TBE in Lithuania, and characterize clinical features in adults in the light of the high incidence in recent years. METHODS: Surveillance data available on the website of the Centre for Communicable Diseases and AIDS of Lithuania were used to describe the epidemiological patterns of TBE. The retrospective study included 712 patients hospitalized in the Centre for Infectious Diseases and the Centre for Neurology of Vilnius University in the years 2005-2014. RESULTS: Tick-borne encephalitis incidence rates have been increasing by 8.5% per year for the 45-year period from 1970 to 2014. The joinpoint model finds two joinpoints at 1991 and 1994, with a significant decrease of 8.4% per year (P < 0.05) prior to the joinpoint at 1991, and a rise of 195.2% afterwards. TBE presented with meningoencephalitis in 556 cases (81.3%). A total of 129 patients (18%) had a severe case of the disease. The most common neurological signs were ataxia (579, 81.3%), meningeal signs (474, 66.5%) and tremor (338, 47.5%). Limb paresis was observed in 6.3% of patients. Five patients (0.7%) died, and 544 patients (76.7%) were discharged with sequelae. CONCLUSIONS: Intensified efforts in promoting TBE vaccination will be needed in the light of the high incidence and expanded spatial distribution. Significant prognostic factors for severe cases of the disease were age above 61 and delayed immune response of specific immunoglobulin G.

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.

Saliva of Ixodes ricinus enhances TBE virus replication in dendritic cells by modulation of pro-survival Akt pathway.

It has been suggested that tick saliva facilitates transmission of tick-borne encephalitis virus (TBEV) to vertebrates. The mechanism of this facilitation has not been elucidated yet. Since dendritic cells (DCs) are among first cells attacked by the virus, we examined the amount of virus and changes induced by saliva in TBEV-infected DCs. We found that virus replication was significantly increased by saliva of Ixodes ricinus tick. Next, saliva-induced enhancement of Akt pathway activation was observed in TBEV-infected DCs. Akt mediated pathway is known for its anti-apoptotic and pro-survival effects. Accordingly, apoptosis of TBEV-infected DCs was declined and cellular viability increased in the presence of tick saliva. Saliva-induced enhancement of STAT1 and NF-κB was also observed in TBEV-infected DCs. In conclusion, we suggest that tick saliva provides pro-survival and anti-apoptotic signals to infected DCs via upregulation of Akt, which may have positive consequences for TBEV replication and transmission.

[Assessment of invalidity as a result of infectious diseases]. / Posuzování invalidity u infekcních onemocnení.

AIM: The article features the new medical assessment paradigm for invalidity as a result of infectious disease which is applied as of 1 January 2010. MATERIAL AND METHODS: The invalidity assessment criteria are regulated specifically by Regulation No. 359/2009. Chapter I of the Annexe to the invalidity assessment regulation addresses the area of infectious diseases with respect to functional impairment and its impact on the quality of life. Since 2010, the invalidity has also been newly categorized into three groups. The new assessment approach makes it possible to evaluate a persons functional capacity, type of disability, and eligibility for compensation for reduced capacity for work. RESULTS: In 2010, a total of 170 375 invalidity cases were assessed, and in 2014, 147 121 invalidity assessments were made. Invalidity as a result of infectious disease was assessed in 177 persons in 2010, and 128 invalidity assessments were made in 2014. The most common causes of invalidity as a result of infectious disease are chronic viral hepatitis, other spirochetal infections, tuberculosis of the respiratory tract, tick-borne viral encephalitis, and HIV/AIDS. CONCLUSION: The number of assessments of invalidity as a result of infectious disease showed a declining trend between 2010 and 2014, similarly to the total of invalidity assessments. In spite of this fact, the cases of invalidity as a result of infectious disease account for approximately half percent of all invalidity assessments made in the above-mentioned period of time.

Innate and adaptive immune responses to tick-borne flavivirus infection in sheep.

The flaviviruses tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are closely-related genetically and antigenically, have broadly similar host ranges that include rodents and other mammals (including sheep), and are both transmitted by the same tick species, Ixodes ricinus. Although human infection with TBEV results in a febrile illness followed in some cases by encephalitis, humans appear to be much less susceptible to infection with LIV. However, these viruses demonstrate different susceptibilities in sheep; LIV infection causes encephalitic disease, whereas TBEV infection generally does not. To investigate the role of the immune response in this mixed outcome, groups of sheep were inoculated with either virus, or with a primary inoculation with one virus and secondary inoculation with the other. Markers of both adaptive and innate immune responses were measured. In each group studied, infection resulted in seroconversion, demonstrated by the detection of virus specific neutralising antibodies. This appeared to control infection with TBEV but not LIV, which progressed to a febrile infection, with transient viraemia and elevated levels of serum interferon. This was followed by neuroinvasion, leading to up-regulation of innate immune transcripts in discrete areas of the brain, including interferon inducible genes and chemokines. Prior inoculation with TBEV did not prevent infection with LIV, but did appear to reduce disease severity and viraemia. We postulate that LIV has adapted to replicate efficiently in sheep cells, and disseminate rapidly following infection. By contrast, TBEV fails to disseminate in sheep and is controlled by the immune response.

The expression of the chemokine receptor CCR5 in tick-borne encephalitis.

BACKGROUND: Chemokine receptor 5 (CCR5) is hypothesized to drive the lymphocyte migration to central nervous system in flavivirus encephalitis, and the non-functional CCR5Δ32 genetic variant was identified as a risk factor of a West Nile virus infection and of tick-borne encephalitis (TBE). We have attempted to investigate how CCR5 expression corresponds to the clinical course and severity of TBE. METHODS: We have repeatedly studied CCR5 expression in 76 patients during encephalitic and convalescent TBE phase, analyzing its association with clinical features, cerebrospinal fluid (csf) pleocytosis, and concentrations of CCR5 ligands (chemokines CCL3, CCL4, and CCL5) and CCR5 genotype. Fifteen patients with neuroborreliosis, 7 with aseptic meningitis, 17 in whom meningitis/encephalitis had been excluded, and 18 healthy blood donors were studied as controls. Expression of CCR5 was measured cytometrically in blood and csf-activated Th lymphocytes (CD3+CD4+CD45RO+). Concentrations of chemokines in serum and csf were measured immunoenzymatically, and CCR5Δ32 was detected with sequence-specific primers. Data were analyzed with non-parametric tests, and p < 0.05 was considered significant. RESULTS: The blood expression of CCR5 did neither differ between the groups nor change in the course of TBE. The CCR5 expression in the inflammatory csf was several-fold increased in comparison with blood but lower in TBE than in neuroborreliosis. The csf concentration of CCL5 was increased in TBE, the highest in the most severe presentation (meningoencephalomyelitis) and correlated with pleocytosis. The CCR5Δ32/wt genotype present in 7 TBE patients was associated with a decreased CCR5 expression, but enrichment of csf Th population in CCR5-positive cells and the intrathecal inflammatory response were preserved, without a compensatory increase of CCL5 expression. CONCLUSIONS: We infer CCR5 and CCL5 participate in the response to TBE virus, as well as to other neurotropic pathogens. The intrathecal response to TBE is not hampered in the bearers of a single copy of CCR5Δ32 allele, suggesting that the association of CCR5Δ32 with TBE may be mediated in the periphery at the earlier stage of the infection. Otherwise, a variability of the CCR5 expression in the peripheral blood lymphocytes seems not to be associated with a variable susceptibility to TBE.

MRI and planimetric CT follow-up study of patients with severe tick-borne encephalitis.

BACKGROUND: The aim of the study was to evaluate the magnetic resonance imaging (MRI) and planimetric computed tomography (CT) of brain lesions in patients with a history of tick-borne encephalitis (TBE); to assess the influence of steroid treatment on the brain and whether lesions were age-dependent. METHODS: A total of 19 patients with abnormal initial imaging in the acute stage of the disease had a follow-up MRI after 1 year; 34 patients hospitalized for TBE encephalitis/encephalomyelitis had planimetric CT after 10 years. RESULTS: On MRI cortico-subcortical atrophy with widening of anterior horns of the lateral ventricles and vascular changes was more marked on follow-up examination. Virchow-Robin spaces dilatation, widening of the lateral ventricles, periventricular lesions, and cortico-subcortical atrophy correlated with age. Results of planimetric CT study showed increased percentage of tracings, widened anterior horns, lateral ventricles, and III ventricle, which suggest new non-age-related atrophic lesions. CONCLUSIONS: Radiological lesions in the acute phase of TBE and after recovery are non-specific. Cortico-subcortical atrophy with widening of the anterior horns of the lateral ventricles and vascular changes are most common. Long-term follow-up confirms the formation of new non-age-related cerebral atrophic lesions due to TBE. The logit model may serve as a background for the hypothesis concerning an accelerated local atrophy of the brain tissues in patients with a history of severe TBE.

Tick-borne encephalitis--lipid peroxidation and its consequences.

BACKGROUND: The purpose of this study was to assess the processes of lipid peroxidation with prostaglandin derivatives and reactive aldehydes being its major indicators in cerebrospinal fluid (CSF), plasma and urine of patients with tick-borne encephalitis (TBE). MATERIALS AND METHODS: This study included 60 patients with TBE and 56 healthy subjects. Lipid peroxidation was estimated by the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE), malondialdehyde (MDA), acrolein, crotonaldehyde, and 4-oxononenal (4-ONE), determined by GC-MS, F2-isoprostanes and neuroprostanes (NPs) level determined by LC-MS. The level of 4-HNE-protein adducts was determined by ELISA. Phospholipase A2 (PLA2), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activities and vitamin E level were determined spectrophotometrically and by HPLC, respectively. In parallel, the plasma levels of phospholipid acids such as arachidonic acid (AA), linoleic acid (LA) and docosahexaenoic acid (DHA) were monitored. RESULTS: A significant decrease in AA, LA, DHA level and GSH-Px activity (by about 20, 69, 11 and 18%, respectively) was observed. The consequence of enhanced phospholipid peroxidation was almost 7 times higher plasma level of F2-isoprostanes and 3-fold increase in NPs level in CSF of TBE patients. Additionally a 3.5-fold increase in the CSF level of MDA, 5-fold increase in the plasma level of 4-HNE and urine level of 4-HHE in TBE patients was observed. Decreased plasma activity of PLA2 with an increase in the PAF-AH activity was observed. CONCLUSION: Lipid peroxidation occurring during TBE development indicates its relevance in pathophysiology of this disease. Moreover lipid peroxidation products might be useful for the diagnosis of TBE.

Infection and injury of human astrocytes by tick-borne encephalitis virus.

Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents the most important flaviviral neural infection in Europe and north-eastern Asia. In the central nervous system (CNS), neurons are the primary target for TBEV infection; however, infection of non-neuronal CNS cells, such as astrocytes, is not well understood. In this study, we investigated the interaction between TBEV and primary human astrocytes. We report for the first time, to the best of our knowledge, that primary human astrocytes are sensitive to TBEV infection, although the infection did not affect their viability. The infection induced a marked increase in the expression of glial fibrillary acidic protein, a marker of astrocyte activation. In addition, expression of matrix metalloproteinase 9 and several key pro-inflammatory cytokines/chemokines (e.g. tumour necrosis factor α, interferon α, interleukin (IL)-1ß, IL-6, IL-8, interferon γ-induced protein 10, macrophage inflammatory protein, but not monocyte chemotactic protein 1) was upregulated. Moreover, we present a detailed description of morphological changes in TBEV-infected cells, as investigated using three-dimensional electron tomography. Several novel ultrastructural changes were observed, including the formation of unique tubule-like structures of 17.9 ±0.15 nm diameter with associated viral particles and/or virus-induced vesicles and located in the rough endoplasmic reticulum of the TBEV-infected cells. This is the first demonstration that TBEV infection activates primary human astrocytes. The infected astrocytes might be a potential source of pro-inflammatory cytokines in the TBEV-infected brain, and might contribute to the TBEV-induced neurotoxicity and blood-brain barrier breakdown that occurs during TBE. The neuropathological significance of our observations is also discussed.

Powassan virus infection: case series and literature review from a single institution.

BACKGROUND: Powassan virus is a flavivirus related to eastern hemisphere's tick-borne encephalitis viruses. It can cause a rare but potentially life-threatening disease including encephalitis. CASE PRESENTATION: We report four cases of POWV infection in Minnesota and North Dakota with known exposure to tick bites in 2011. Our first case was an 18-year-old male who dramatically presented with seizure and headache with positive serum analysis for Powassan virus immunoglobulin M. The second case was a 60 year old gentleman with intraparenchymal hemorrhage and was diagnosed via cerebrospinal fluid analysis. Thirdly, a 61 year old male developed altered mental status and encephalitis. Our fourth patient was a 69 year old male who had headache and non-focal weakness who was diagnosed with serum analysis. CONCLUSION: Symptoms of Powassan virus infection ranged from headaches to seizures and severe neurological symptoms. This study serves to highlight the increased detection of Powassan virus infection in the central north United States. This report focuses on the increasing incidence that can lead to increasing efforts for raising awareness regarding this infection. There is a need for clinician vigilance and public attention due to its increasing detection, westward progression and varied clinical presentations.

Epilepsia partialis continua in tick-borne Russian spring-summer encephalitis.

OBJECTIVES: Epilepsia partialis continua (EPC) is characterized by localized continuous jerks, from time to time with spreading Jacksonian seizures and, more rarely, secondarily generalized tonic-clonic seizures. EPC has numerous possible etiologies. In this paper we describe EPC in the tick-borne Russian spring-summer encephalitis (TBRSSE) and compare it with Rasmussen syndrome. METHODS AND METHODS: We included patients with EPC in TBRSSE (between 2003 and 2010). The diagnosis was verified by immunology (antibodies against TBRSSE virus). The patients were followed 1-7 (mean 3.4) years. RESULTS: We studied 10 patients (eight males, age 10-21 years) with MRI and video-EEG. Nine developed EPC after acute TBRSSE (meningoencephalitic form), and one had a tick bite without clinical symptoms of encephalitis, but with subsequent EPC. All patients came from Ural and Siberia. The onset was at age 4-14 (mean 8.6 years). The interval from onset of TBRSSE or the tick bite to seizure onset was 1 day-4 years. We identified three phases of clinical course EPC in TBRSSE: (i) acute (meningoencephalitic/encephalitic); (ii) development of EPC; and (iii) chronic EPC. The effect of antiepileptic drugs differed according to seizure types. CONCLUSION: EPC caused by TBRSSE is relatively frequent in the Eastern parts of the Russian Federation but not west of the Ural. Unlike Rasmussen encephalitis, EPC with TBRSSE does not progress even in the long term. It appears as disabling but not fatal condition with a time course where three phases can be distinguished.

Depletion of plasma gelsolin in patients with tick-borne encephalitis and Lyme neuroborreliosis.

BACKGROUND/AIMS: Cell damage during the course of inflammation results in cytoplasmic actin release, which if not eliminated by the extracellular actin scavenger system, composed of gelsolin and vitamin D binding protein, can cause dysfunction of hemostasis and toxicity towards surrounding cells. In this study, we test the hypothesis that an inflammatory reaction induced by central nervous system infections such as tick-borne encephalitis (TBE) or Lyme neuroborreliosis (LNB) will result in plasma gelsolin concentration changes in the blood and cerebrospinal fluid (CSF). METHODS: Quantitative Western blot was used to determine gelsolin levels in 58 samples, which include: 29 patients without infection (diagnosed with conditions such as idiopathic cephalalgia, idiopathic Bell's facial nerve palsy and ischialgia due to discopathy in which standard CSF diagnostic tests show no abnormalities), 12 patients diagnosed with TBE, and 17 patients diagnosed with LNB sub forma meningitis. RESULTS AND CONCLUSION: The gelsolin concentration in the blood of patients with TBE (163.2 ± 80.8 µg/ml) and LNB (113.6 ± 56.8 µg/ml) was significantly lower (p < 0.05 and p < 0.001, respectively) compared to the control group (226.3 ± 100.7 µg/ml). Furthermore, there was no statistically significant difference between the CSF gelsolin concentration in patients with TBE (3.9 ± 3.3 µg/ml), LNB (2.9 ± 1.2 µg/ml) and the control group (3.7 ± 3.3 µg/ml). An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response. Therefore, evaluation of blood gelsolin concentration and administration of recombinant plasma gelsolin might provide a new tool to develop diagnostic and therapeutic strategies for TBE and LNB.

What tick-borne encephalitis may look like: clinical signs and symptoms.

Tick-borne encephalitis is a zoonosis, endemic in a vast area of Europe and Asia. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life and sometimes also forces the individual to a change in lifestyle, develops in 35-58% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus causing infection. Severity of the disease increases with the age of patients. The risk of incomplete recovery is higher for patients who have more severe clinical illness during acute stage of tick-borne encephalitis.