Tick-borne encephalitis infections without CNS involvement: An observational study in Latvia, 2007-2022.

BACKGROUND: Tick-borne encephalitis (TBE) is a human viral infectious disease involving the central nervous system (CNS). It is caused by the tick-borne encephalitis virus (TBEV). At present, there is very limited information regarding the clinical importance and health burden of TBE infections without signs of CNS inflammation. Moreover, such cases are omitted from official TBE surveillances and there are no reports of population-based studies. METHODS AND FINDINGS: A nationwide population-based study was conducted in Latvia by intensively searching for symptomatic TBEV infections recorded in outpatient and hospital settings between 2007 and 2022. In total, 4,124 symptomatic TBEV infections were identified, of which 823 (20.0%) had no CNS involvement. Despite the lack of neurological symptoms, non-CNS TBE patients still experienced severe health conditions that required management in a hospital setting for a median duration of 7 days. Furthermore, lumbar puncture information was available for 708 of these patients, with 100 (14.1%) undergoing the procedure, suggesting a high suspicion of CNS involvement. CONCLUSIONS: Clearly, non-CNS TBE has the potential to negatively impact the health of patients. The actual burden of non-CNS TBEV cases may be higher than we think as these cases are omitted from official TBE surveillances and are challenging to recognize.

Brodmann Areas, V1 Atlas and Cognitive Impairment: Assessing Cortical Thickness for Cognitive Impairment Diagnostics.

Background and Objectives: Magnetic resonance imaging is vital for diagnosing cognitive decline. Brodmann areas (BA), distinct regions of the cerebral cortex categorized by cytoarchitectural variances, provide insights into cognitive function. This study aims to compare cortical thickness measurements across brain areas identified by BA mapping. We assessed these measurements among patients with and without cognitive impairment, and across groups categorized by cognitive performance levels using the Montreal Cognitive Assessment (MoCA) test. Materials and Methods: In this cross-sectional study, we included 64 patients who were divided in two ways: in two groups with (CI) or without (NCI) impaired cognitive function and in three groups with normal (NC), moderate (MPG) and low (LPG) cognitive performance according to MoCA scores. Scans with a 3T MRI scanner were carried out, and cortical thickness data was acquired using Freesurfer 7.2.0 software. Results: By analyzing differences between the NCI and CI groups cortical thickness of BA3a in left hemisphere (U = 241.000, p = 0.016), BA4a in right hemisphere (U = 269.000, p = 0.048) and BA28 in left hemisphere (U = 584.000, p = 0.005) showed significant differences. In the LPG, MPG and NC cortical thickness in BA3a in left hemisphere (H (2) = 6.268, p = 0.044), in V2 in right hemisphere (H (2) = 6.339, p = 0.042), in BA28 in left hemisphere (H (2) = 23.195, p < 0.001) and in BA28 in right hemisphere (H (2) = 10.015, p = 0.007) showed significant differences. Conclusions: Our study found that cortical thickness in specific Brodmann Areas-BA3a and BA28 in the left hemisphere, and BA4a in the right-differ significantly between NCI and CI groups. Significant differences were also observed in BA3a (left), V2 (right), and BA28 (both hemispheres) across LPG, MPG, NC groups. Despite a small sample size, these findings suggest cortical thickness measurements can serve as effective biomarkers for cognitive impairment diagnosis, warranting further validation with a larger cohort.

Chronic Kidney Disease and Cerebrovascular Pathology: Incidence and Functional Outcomes in Riga East University Hospital.

Background and Objectives: The aim of this study was to investigate the incidence of cerebrovascular pathology in patients with chronic kidney disease and its effect on functional outcomes. Materials and Methods: In a retrospective cross-sectional study (2018-2021), the medical records of patients with acute hemorrhagic and ischemic stroke with concomitant chronic kidney disease who received treatment in Riga East University Hospital Stroke Unit were analyzed. Data were analyzed using IBM SPSS 26.0. The Kruskal-Wallis, Mann-Whitney U test, and Spearman's rank correlation coefficient methods were used. Results: The final sample consisted of 305 acute cerebrovascular pathology patients (56.4% females). Overall, 57.3% of stroke patients had second-stage chronic kidney disease with average serum creatinine levels of 104.3 mmol/L (±32.8). The functional outcome of the stroke depended on the stage of chronic kidney disease. There was a statistically significant non-linear correlation between glomerular filtration rate and NIHSS (National Institute of Health Stroke Scale) score on admission (Rho -0.194, p = 0.016), glomerular filtration rate and NIHSS score on discharge (Rho -0.186, p = 0.020), and glomerular filtration rate and modified Rankin score on admission (Rho -0.237, p = 0.003) and discharge (Rho -0.224, p = 0.05). The mean NIHSS score of ischemic stroke patients was 8.3 ± 5.9 on admission and 6.5 ± 5.8 on discharge. In the hemorrhagic stroke patient group, the mean NIHSS score was 9.5 ± 7.3 on admission and 7.1 ± 6.9 on discharge. On average, 34.0% of ischemic stroke patients had an mRS score of 5 on admission, while in the hemorrhagic stroke patient group, this figure was 41%. There was no statistical difference in the glomerular filtration rate between the thrombolyzed versus non-thrombolyzed patient groups (Mann-Whitney U test = 1457, p = 0.794). Conclusions: Chronic kidney disease is an important predictor of the severity and functional outcome of a stroke; furthermore, the early management and prevention of complications should be a top priority in the prophylaxis of this cerebrovascular pathology.

Whole Brain and Corpus Callosum Fractional Anisotropy Differences in Patients with Cognitive Impairment.

Diffusion tensor imaging (DTI) is an MRI analysis method that could help assess cognitive impairment (CI) in the ageing population more accurately. In this research, we evaluated fractional anisotropy (FA) of whole brain (WB) and corpus callosum (CC) in patients with normal cognition (NC), mild cognitive impairment (MCI), and moderate/severe cognitive impairment (SCI). In total, 41 participants were included in a cross-sectional study and divided into groups based on Montreal Cognitive Assessment (MoCA) scores (NC group, nine participants, MCI group, sixteen participants, and SCI group, sixteen participants). All participants underwent an MRI examination that included a DTI sequence. FA values between the groups were assessed by analysing FA value and age normative percentile. We did not find statistically significant differences between the groups when analysing CC FA values. Both approaches showed statistically significant differences in WB FA values between the MCI-SCI and MCI-NC groups, where the MCI group participants showed the highest mean FA and highest mean FA normative percentile results in WB.

Effectiveness of tick-borne encephalitis vaccination in Latvia, 2018-2020: an observational study.

OBJECTIVES: Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) that results in symptoms of central nervous system inflammation. TBE is endemic in Latvia and other European countries. TBE vaccines are commonly used in Latvia, but vaccine effectiveness estimates are limited. METHODS: Study staff at Riga Stradins University conducted nationwide active surveillance for TBEV infections. Serum and cerebrospinal fluid were ELISA-tested for TBEV-specific IgG and IgM antibodies. Vaccination history was collected by interview and medical record review. Utilizing data from surveillance and population surveys, vaccine effectiveness (with 95% CIs) and cases averted were estimated using the screening method. RESULTS: There were 587 laboratory-identified TBE cases from 2018 to 2020; 98.1% (576/587) were unvaccinated, 1.5% (9/587) were unknown or partially vaccinated, and 0.3% (2/587) were fully vaccinated (three-dose primary series and appropriately timed boosters). TBE resulted in the death of 1.7% (10/587) of TBE cases. TBE vaccine history was ascertained from 92.0% (13 247/14 399) people from the general population: 38.6% (5113/13 247) were unvaccinated, 26.3% (3484/13 247) were fully vaccinated, and 35.1% (4650/13 247) were partially vaccinated. TBE vaccine effectiveness was 99.5% (98.0-99.9) against TBE, 99.5% (97.9-99.9) against TBE hospitalization, 99.3% (94.8-99.9) against moderate/severe TBE, and 99.2% (94.4-99.9) against TBE hospitalization >12 days. From 2018 to 2020, vaccination averted 906 TBE cases, including 20 deaths. DISCUSSION: TBE vaccine was highly effective in preventing TBE, moderate and severe disease, and prolonged hospitalization. To prevent life-threatening TBE, TBE vaccine uptake and compliance should be increased in Latvia and other European regions where TBE is endemic.

Effectiveness of Tick-borne Encephalitis Vaccines in Children, Latvia, 2018-2020.

BACKGROUND: Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1-15 years-of-age. METHODS: Riga Stradins University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1-15 years-of-age was estimated using the screening method: VE = 1 - [PCV/(1 - PCV)/PPV/(1 - PPV)]. RESULTS: From 2018 to 2020, surveillance identified 36 TBE cases in children 1-15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1-15 years-of-age was 94.9% (95% confidence interval 63.1-99.3). In 2018-2020, vaccination in children 1-15 years-of-age averted 39 hospitalized TBE cases. CONCLUSION: Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.

Clinical Symptoms Influencing Parkinson's Patients' Quality of Life in Latvia: A Single-Center Cohort Study.

Background and Objectives: Parkinson's disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence the quality of life throughout the course of the disease. This study aimed to evaluate PD patients' motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Materials and Methods: We evaluated 43 patients with Parkinson's disease. Fourteen patients had tremor dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients' mean age was 65.21 years, and the disease's mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, lightheadedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale's gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusions: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients' health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients' well-being.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Thrombolytic Therapy.

Background and Objectives: Thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) is used to treat acute ischemic stroke. Dabigatran is a reversible thrombin inhibitor approved for stroke prevention in patients with nonvalvular atrial fibrillation. In such cases, thrombolytic therapy can be administered to certain patients after idarucizumab treatment. We evaluated the effectiveness of idarucizumab in dabigatran-treated patients receiving rt-PA. Materials and Methods: We included the data of nine idarucizumab-treated patients from the Riga East University Hospital Stroke Registry from 2018 to 2022 in our retrospective medical records analysis. We used the National Institutes of Health Stroke Scale (LV-NIHSS) score and modified Rankin scale (mRS) on admission and discharge to evaluate neurological deficit and functional outcomes. Results: We analyzed the data of nine patients (seven males and two females) with a mean age of 75.67 ± 8.59 years. The median door-to-needle time for all patients, including those who received idarucizumab before rt-PA, was 51 min (IQR = 43-133); the median LV-NIHSS score was 9 (IQR = 6.0-16.0) on admission and 4 (IQR = 2.5-4.0) at discharge; and the intrahospital mortality rate was 11.1% due to intracranial hemorrhage as a complication of rt-PA. Conclusions: Our study shows that idarucizumab as an antidote of dabigatran appears to be effective and safe in patients with acute ischemic stroke. Furthermore, the administration of idarucizumab slightly prolongs the door-to-needle time; however, the majority of cases showed clinical improvement after receiving therapy. Further randomized controlled trials should be performed to evaluate the safety and effectiveness of idarucizumab for acute ischemic stroke treatment.

Combined Score of Perivascular Space Dilatation and White Matter Hyperintensities in Patients with Normal Cognition, Mild Cognitive Impairment, and Dementia.

Background and Objectives: Cerebral perivascular spaces (PVS) are part of the cerebral microvascular structure and play a role in lymphatic drainage and the removal of waste products from the brain. White matter hyperintensities (WMH) are hyperintense lesions on magnetic resonance imaging that are associated with cognitive impairment, dementia, and cerebral vascular disease. WMH and PVS are direct and indirect imaging biomarkers of cerebral microvascular integrity and health. In our research, we evaluated WMH and PVS enlargement in patients with normal cognition (NC), mild cognitive impairment (MCI), and dementia (D). Materials and Methods: In total, 57 participants were included in the study and divided into groups based on neurological evaluation and Montreal Cognitive Assessment results (NC group 16 participants, MCI group 29 participants, D group 12 participants). All participants underwent 3T magnetic resonance imaging. PVS were evaluated in the basal ganglia, centrum semiovale, and midbrain. WMHs were evaluated based on the Fazekas scale and the division between deep white matter (DWM) and periventricular white matter (PVWM). The combined score based on PVS and WMH was evaluated and correlated with the results of the MoCA. Results: We found statistically significant differences between groups on several measures. Centrum semiovale PVS dilatation was more severe in MCI and dementia group and statistically significant differences were found between D-MCI and D-NC pairs. PVWM was more severe in patients with MCI and dementia group, and statistically significant differences were found between D-MCI and D-NC pairs. Furthermore, we found statistically significant differences between the groups by analyzing the combined score of PVS dilatation and WMH. We did not find statistically significant differences between the groups in PVS dilation of the basal ganglia and midbrain and DWM hyperintensities. Conclusions: PVS assessment could become one of neuroimaging biomarkers for patients with cognitive decline. Furthermore, the combined score of WMH and PVS dilatation could facilitate diagnostics of cognitive impairment, but more research is needed with a larger cohort to determine the use of PVS dilatation and the combined score.

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

A fatal case of COVID-19-associated acute necrotizing encephalopathy.

INTRODUCTION: An increasing number of published reports on SARS-CoV-2 neurological manifestations have revealed a wide spectrum of symptoms, diagnostic features, and outcomes. We report a fatal case of a COVID-19-associated acute necrotizing encephalopathy (ANE). CASE REPORT: We report a 70-year-old man brought to the hospital after a generalized tonic-clonic seizure. He was confused and disoriented. Nasopharyngeal swab testing for SARS-CoV-2 was positive. A head computed tomography (CT) scan and cerebrospinal fluid (CSF) analysis showed no signs of acute pathology. After recurrent seizures, he was sedated and intubated. Throughout the days that followed he remained in a therapeutic coma. After discontinuation of sedatives, he remained unconscious. A repeated head CT scan showed signs of pontine edema, and brain magnetic resonance imaging (MRI) revealed inhomogeneous hyperintensities with microhemorrhages and small autonecrotic cavities in both thalami, brain stem, and cerebellar peduncles. With a high suspicion of a COVID-19-associated ANE, the patient was started on high-dose glucocorticoids; however, he died the next day. The CSF tested negative for SARS-CoV-2. DISCUSSION: A variety of COVID-19 neurological manifestations have been reported to date, including various forms of encephalitis and encephalopathy. In our patient, encephalopathy with seizures was the presenting symptom of SARS-CoV-2 infection. The radiological findings on days 8 and 9 were consistent with an ANE. The precise pathogenesis of ANE remains unclear; however, an immune-mediated mechanism is suspected. Early diagnostics with prompt administration of immunomodulators may be lifesaving. Suspicion of a COVID-19-related encephalopathy/encephalitis should be raised in all patients with altered mental status, seizures, and/or coma.

Cerebellar Cortex and Cerebellar White Matter Volume in Normal Cognition, Mild Cognitive Impairment, and Dementia.

The cerebellum is commonly viewed as a structure that is primarily responsible for the coordination of voluntary movement, gait, posture, and speech. Recent research has shown evidence that the cerebellum is also responsible for cognition. We analyzed 28 participants divided into three groups (9 with normal cognition, 9 with mild cognitive impairment, and 10 with moderate/severe cognitive impairment) based on the Montreal Cognitive Assessment. We analyzed the cerebellar cortex and white matter volume and assessed differences between groups. Participants with normal cognition had higher average values in total cerebellar volume, cerebellar white matter volume, and cerebellar cortex volume in both hemispheres, but by performing the Kruskal-Wallis test, we did not find these values to be statistically significant.

Brain Structural Connectivity Differences in Patients with Normal Cognition and Cognitive Impairment.

Advances in magnetic resonance imaging, particularly diffusion imaging, have allowed researchers to analyze brain connectivity. Identification of structural connectivity differences between patients with normal cognition, cognitive impairment, and dementia could lead to new biomarker discoveries that could improve dementia diagnostics. In our study, we analyzed 22 patients (11 control group patients, 11 dementia group patients) that underwent 3T MRI diffusion tensor imaging (DTI) scans and the Montreal Cognitive Assessment (MoCA) test. We reconstructed DTI images and used the Desikan-Killiany-Tourville cortical parcellation atlas. The connectivity matrix was calculated, and graph theoretical analysis was conducted using DSI Studio. We found statistically significant differences between groups in the graph density, network characteristic path length, small-worldness, global efficiency, and rich club organization. We did not find statistically significant differences between groups in the average clustering coefficient and the assortativity coefficient. These statistically significant graph theory measures could potentially be used as quantitative biomarkers in cognitive impairment and dementia diagnostics.

Clinical Characteristics of Patients with Tick-Borne Encephalitis (TBE): A European Multicentre Study from 2010 to 2017.

Tick-borne encephalitis (TBE) virus is a major cause of central nervous system infections in endemic countries. Here, we present clinical and laboratory characteristics of a large international cohort of patients with confirmed TBE using a uniform clinical protocol. Patients were recruited in eight centers from six European countries between 2010 and 2017. A detailed description of clinical signs and symptoms was recorded. The obtained information enabled a reliable classification in 553 of 555 patients: 207 (37.3%) had meningitis, 273 (49.2%) meningoencephalitis, 15 (2.7%) meningomyelitis, and 58 (10.5%) meningoencephalomyelitis; 41 (7.4%) patients had a peripheral paresis of extremities, 13 (2.3%) a central paresis of extremities, and 25 (4.5%) had single or multiple cranial nerve palsies. Five (0.9%) patients died during acute illness. Outcome at discharge was recorded in 298 patients. Of 176 (59.1%) patients with incomplete recovery, 80 (27%) displayed persisting symptoms or signs without recovery expectation. This study provides further evidence that TBE is a severe disease with a large proportion of patients with incomplete recovery. We suggest monitoring TBE in endemic European countries using a uniform protocol to record the full clinical spectrum of the disease.

The Riga East University Hospital Stroke Registry-An Analysis of 4915 Consecutive Patients with Acute Stroke.

Background and Objectives: A hospital-based stroke registry is a useful tool for systematic analyses of the epidemiology, clinical characteristics, and natural course of stroke. Analyses of stroke registry data can provide information that can be used by health services to improve the quality of care for patients with this disease. Materials and Methods: Data were collected from the Riga East University Hospital (REUH) Stroke Registry in order to evaluate the etiology, risk factors, clinical manifestations, treatment, functional outcomes, and other relevant data for acute stroke during the period 2016-2020. Results: During a five-year period, 4915 patients (3039 females and 1876 males) with acute stroke were registered in the REUH Stroke Registry. The causative factors of stroke were cardioembolism (45.7%), atherosclerosis (29.9%), lacunar stroke (5.3%), stroke of undetermined etiology (1.2%), and stroke of other determined causes (1.2%). The most frequent localizations of intracerebral hemorrhage were subcortical (40.0%), lobar (18.9%), and brainstem (9.3%). The most prevalent risk factors for stroke were hypertension (88.8%), congestive heart failure (71.2%), dyslipidemia (46.7%), and atrial fibrillation (44.2%). In addition, 1018 (20.7%) patients were receiving antiplatelet drugs, 574 (11.7%) were taking statins, and 382 (7.7%) were taking anticoagulants. At discharge, 35.5% of the patients were completely independent (mRS (modified Rankin Scale) score: 0-2), while 49.5% required some form of assistance (mRS score: 3-5). The intrahospital mortality rate was 13.7%, although it was higher in the hemorrhage group (30.9%). Conclusions: Our stroke registry data are comparable to those of other major registries. Analysis of stroke registry data is important for improving stroke care and obtaining additional information for stroke studies.

Electrocardiographic Abnormalities and Mortality in Epilepsy Patients.

Background and Objectives: People with epilepsy (PWE) have a 2-3 times higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) comprises a significant proportion of premature deaths, whereas sudden cardiac death (SCD) is among the leading causes of sudden death in the general population. Cardiac pathologies are significantly more prevalent in PWE. Whether electrocardiographic (ECG) parameters are associated with remote death in PWE has yet to be elucidated. The study objective was to assess whether interictal ECG parameters are associated with mortality in the long-term. Materials and Methods: The study involved 471 epilepsy patients who were hospitalized after a bilateral tonic-clonic seizure(s). ECG parameters were obtained on the day of hospitalization (heart rate, PQ interval, QRS complex, QT interval, heart rate corrected QT interval (QTc), ST segment and T wave changes), as well as reported ECG abnormalities. Mortality data were obtained from the Latvian National Cause-of-Death database 3-11, mean 7.0 years after hospitalization. The association between the ECG parameters and the long-term clinical outcome were examined. Results: At the time of assessment, 75.4% of patients were alive and 24.6% were deceased. Short QTc interval (odds ratio (OR) 4.780; 95% confidence interval (CI) 1.668-13.698; p = 0.004) was associated with a remote death. After the exclusion of known comorbidities with high mortality rates, short QTc (OR 4.631) and ECG signs of left ventricular hypertrophy (OR 5.009) were associated with a remote death. Conclusions: The association between routine 12-lead rest ECG parameters-short QTc interval and a pattern of left ventricular hypertrophy-and remote death in epilepsy patients was found. To the best of our knowledge, this is the first study to associate rest ECG parameters with remote death in an epileptic population.

Subspecialty training of neurology residents and junior neurologists in the Baltic States.

BACKGROUND: Neurology is a field of increasing subspecialization. There is no published data regarding the proportion of neurology subspecialists in the Baltic States. The aim of this cross-sectional study was to identify factors associated with neurology subspecialty choice, to examine possible differences between neurology residents' and junior neurologists' view of subspecialty, and to assess perceived subspecialty acquisition opportunities and subspecialty attractiveness. METHODS: The research was conducted as an anonymous online survey between December 28, 2020, and January 24, 2021 of neurology residents and neurologists who completed their residency during the last 5 years in the Baltic States. RESULTS: In total, 72 residents and 65 neurologists participated. "Cerebrovascular diseases" and "multiple sclerosis and autoimmune diseases of the nervous system" were rated as the two most attractive subspecialties by residents, whereas "headache" and "clinical neurophysiology" were the most attractive among junior neurologists. "Vertigo and dizziness" and "dementia" were ranked the least attractive among both groups. "Cerebrovascular diseases" were perceived as having the most acquisition opportunities. The two most common determinants of subspecialty choice were "medical content of the subspecialty" and "influence of mentor during undergraduate studies or residency". CONCLUSIONS: Two-thirds of junior neurologists subspecialize in at least one subspecialty, and one-third of residents are already determined to pursue subspecialty training. Junior neurologists rated most outpatient-related subspecialties as more attractive than neurology residents. Between the Baltic States' universities, there was a significant difference in the number of residents who were determined to pursue subspecialty training.

Structural Analysis of Brain Hub Region Volume and Cortical Thickness in Patients with Mild Cognitive Impairment and Dementia.

Background and Objectives: A complex network of axonal pathways interlinks the human brain cortex. Brain networks are not distributed evenly, and brain regions making more connections with other parts are defined as brain hubs. Our objective was to analyze brain hub region volume and cortical thickness and determine the association with cognitive assessment scores in patients with mild cognitive impairment (MCI) and dementia. Materials and Methods: In this cross-sectional study, we included 11 patients (5 mild cognitive impairment; 6 dementia). All patients underwent neurological examination, and Montreal Cognitive Assessment (MoCA) test scores were recorded. Scans with a 3T MRI scanner were done, and cortical thickness and volumetric data were acquired using Freesurfer 7.1.0 software. Results: By analyzing differences between the MCI and dementia groups, MCI patients had higher hippocampal volumes (p < 0.05) and left entorhinal cortex thickness (p < 0.05). There was a significant positive correlation between MoCA test scores and left hippocampus volume (r = 0.767, p < 0.01), right hippocampus volume (r = 0.785, p < 0.01), right precuneus cortical thickness (r = 0.648, p < 0.05), left entorhinal cortex thickness (r = 0.767, p < 0.01), and right entorhinal cortex thickness (r = 0.612, p < 0.05). Conclusions: In our study, hippocampal volume and entorhinal cortex showed significant differences in the MCI and dementia patient groups. Additionally, we found a statistically significant positive correlation between MoCA scores, hippocampal volume, entorhinal cortex thickness, and right precuneus. Although other brain hub regions did not show statistically significant differences, there should be additional research to evaluate the brain hub region association with MCI and dementia.

Persistent Roseoloviruses Infection in Adult Patients with Epilepsy.

BACKGROUND: Human herpesviruses (HHV)-6A, HHV-6B and HHV-7 are considered to be involved in the pathogenesis of epilepsy, a common neurological disorder. The objective of this study was to determine the association of roseoloviruses infection with epilepsy. METHODS: 53 epilepsy patients and 104 ordinary blood donors were analyzed to determine presence of virus-specific antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), genomic sequences, viral load and gene expression by polymerase chain reactions (PCRs) and restriction analysis, HHV-6 protein expression by IFA and level of cytokines by ELISA. RESULTS: Roseoloviruses genomic sequences in DNA samples from whole blood were found in 86.8% of patients versus 54.8% of controls and active infection was revealed only in patients with epilepsy (19.6% of roseolovirus-positive patients). Significantly higher viral load and more frequent gene expression was detected in patients compared to the controls. HHV-6-encoded protein expression was demonstrated in 53.3% of patients with previously detected HHV-6 DNA. Changes in level of cytokines were determined in patients with elevated viral load compared to the patients without elevated viral loads and to the controls. CONCLUSIONS: Results on frequent active HHV-6 and HHV-7 infection in epilepsy patient' peripheral blood indicate on possible involvement of these viruses in the disease development.