The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

The COVID-19 pandemic and neurology: A survey on previous and continued restrictions for clinical practice, curricular training, and health economics.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. METHODS: An online 18-item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID-19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. RESULTS: We collected 430 responses from 79 countries. Most health care professionals were aged 35-44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID-19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in- and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. CONCLUSIONS: Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID-19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale.

Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2.

BACKGROUND AND PURPOSE: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective. METHODS: We summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA). RESULTS: Nirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4. CONCLUSIONS: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

Prevalence of stroke, associated risk factors and stroke related physical, mental, and economic burden in the Republic of Georgia.

Introduction: We investigated the prevalence, risk factors and physical, mental, and economic consequences of ischemic Janelidze and hemorrhagic stroke in the population of the Republic of Georgia. Materials and Methods: A population-based, cross-sectional study was conducted among 3036 adults residing in the Imereti Region of Georgia, selected using a multistage, probability proportionate-to-size, cluster sampling technique. Data were collected by medical students, using an interviewer-administered questionnaire. Diagnosis of stroke was confirmed by neurologists based on clinical examination and corroborated by documental evidence. Results: Of the targeted 3036 subjects, 2811 (92.6%) participated, of whom 1223 (43.5%) were women. Mean age of the sample was 49.7 (SD 15.2) years. The overall prevalence of stroke was 8.9%, the prevalence of ischemic stroke - 7.8% (95% CI 6.9-8.9) and of hemorrhagic stroke - 0.7% (95% CI 0.4-1.0). Ischemic stroke was more prevalent in males, while hemorrhagic stroke was more prevalent in females. Age, smoking, hypertension, and diabetes were associated with stroke. Stroke victims were young, many of them in the fifth decade of life. Sixty-five percent of them had a modified Rankin scale of three or greater, 25% were depressed, and 85% suffered cognitive impairment. Discussion: Stroke affected people and their families, experiencing a significant economic burden due to loss of the income and increase in out-of-pocket payment for post-stroke medical care. Conclusion: The stroke prevalence in the Republic of Georgia is higher than in Europe and is associated with a significant physical, mental, and economic burden.

Establishing Stroke Services in the Republic of Georgia.

INTRODUCTION: This article summarizes the medical experience in establishing stroke units and systemic thrombolysis in Georgia, which, like many other post-Soviet countries, still faces problems in organizing stroke care even after 30 years of independence. PATIENTS AND METHODS: We created an example of treating acute stroke with systemic thrombolysis and introduced stroke units in several hospitals in the country, including standardization of the diagnostic and treatment process, consistent evaluation, and monthly feedback to the stroke unit staff. RESULTS: Systemic thrombolysis has become a clinical routine in some large hospitals and is meanwhile reimbursed by the state insurance. The data of consecutive 1,707 stroke patients in 4 major cities demonstrated significant time lost at the prehospital level, due to failure in identifying stroke symptoms, delay in notification, or transportation. The consequent quality reports resulted in a dramatic increase in adherence to the European and national guidelines. A mandatory dysphagia screening and subsequent treatment led to a decrease in pneumonia rates. DISCUSSION: We discuss our experience and suggestions on how to overcome clinical, financial, and ethical problems in establishing a stroke services in a developing country. CONCLUSION: The Georgian example might be useful for doctors in other post-Soviet countries or other parts of the world.

Multivariate relationships between epidemiologic risk factors and zoonotic infections among military personnel in the country of Georgia: A non-linear canonical correlation analysis.

Zoonotic diseases are endemic in the country of Georgia. Using the non-linear canonical correlation (NCC) method, the aim of this study was to examine the relationship between thirteen epidemiological risk factors and seropositivity to five zoonotic infections (anthrax, Q fever, tularemia, leptospirosis, and Crimean-Congo hemorrhagic fever [CCHF]) among Georgian military recruits during 2014-2016. According to this multivariate statistical technique, which is suitable for the analysis of two or more sets of qualitative variables simultaneously, two canonical variables were identified. These variables accounted for 68% of the variation between the two sets of categorical variables ("risk factors" and "zoonotic infections"). For the first canonical variable, there was a relationship among CCHF (canonical loading, which is interpreted in the same way as the Pearson's correlation coefficient, [cl] = 0.715), tick bites (cl = 0.418) and slaughter of animals (cl = 0.351). As for the second canonical variable, Q fever (cl = -0.604) and leptospirosis (cl = -0.486) were related to rodents inside and outside home (cl = -0.346) and sweeping in or around home (cl = -0.317). The NCC method allows researchers to obtain additional insights into the complex relationship between epidemiological risk factors and multiple zoonotic infections.

Arthropod Borne and Zoonotic Infections Among Military Personnel in Georgia.

Military personnel are at an increased risk for exposure to arthropod- borne and zoonotic pathogens. The prevalence of these pathogens has not been adequately described in the country of Georgia. As the Georgian military moves toward an increased level of capability and the adoption of European Union and North Atlantic Treaty Organization standards, international field exercises will become more frequent and will likely involve an increasing number of international partners. This study was undertaken with the goal of defining the arthropod-borne and zoonotic pathogen threat in Georgia so force health protection planning can proceed in a rational and data-driven manner. To estimate disease burden, blood was taken from 1,000 Georgian military recruits between October 2014 and February 2016 and screened for previous exposure to a set of bacterial and viral pathogens using a antibody-based, serologic procedure. The highest rate of exposure was to Salmonella enterica serovar Typhi, and the lowest rate of exposure was to Coxiella burnettii (the causative agent of Q fever). These data provide insight into the prevalence of arthropod-borne infections in Georgia, fill a critical knowledge gap, will help guide future surveillance efforts, and will inform force health protection planning.

Epidemiological and Clinical Features of Brucellosis in the Country of Georgia.

BACKGROUND: Brucellosis is an endemic disease in the country of Georgia. According to the National Center for Disease Control and Public Health of Georgia (NCDC), the average annual number of brucellosis cases was 161 during 2008-2012. However, the true number of cases is thought to be higher due to underreporting. The aim of this study was to provide current epidemiological and clinical information and evaluate diagnostic methods used for brucellosis in Georgia. METHODOLOGY: Adult patients were eligible for participation if they met the suspected or probable case definition for brucellosis. After consent participants were interviewed using a standardized questionnaire to collect information on socio-demographic characteristics, epidemiology, history of present illness, and clinical manifestation. For the diagnosis of brucellosis, culture and serological tests were used. RESULTS: A total of 81 participants were enrolled, of which 70 (86%) were from rural areas. Seventy-four percent of participants reported consuming unpasteurized milk products and 62% consuming undercooked meat products before symptom onset. Forty-one participants were positive by the Wright test and 33 (41%) were positive by blood culture. There was perfect agreement between the Huddelston and Wright tests (k = 1.0). Compared with blood culture (the diagnostic gold standard), ELISA IgG and total ELISA (IgG + IgM), the Wright test had fair (k = 0.12), fair (k = 0.24), and moderate (k = 0.52) agreement, respectively. CONCLUSIONS: Consumption of unpasteurized milk products and undercooked meat were among the most common risk factors in brucellosis cases. We found poor agreement between ELISA tests and culture results. This report also serves as an initial indication that the suspected case definition for brucellosis surveillance purposes needs revision. Further research is needed to characterize the epidemiology and evaluate the performance of the diagnostic methods for brucellosis in Georgia.

Expansion of brucellosis detection in the country of Georgia by screening household members of cases and neighboring community members.

BACKGROUND: Brucellosis is considered as endemic zoonotic disease in the country of Georgia. However, the burden of the disease on a household level is not known. Therefore, this study sought to determine the benefits of active surveillance coupled to serological screening for the early detection of brucellosis among close contacts of brucellosis cases. METHODS: We used an active surveillance approach to estimate the rate of seropositivity among household family members and neighboring community members of brucellosis index cases. All participants were screened using the serum tube agglutination test (SAT). Blood cultures were performed, obtained isolates were identified by a bacteriological algorithm, and confirmed as Brucella spp. using real-time PCR. Further confirmation of Brucella species was done using the AMOS PCR assay. RESULTS: A total of 141 participants enrolled. Of these, 27 were brucellosis index cases, 86 were household family members, and 28 were neighboring community members. The serological evidence of brucellosis in the household member group was 7% and the rate at the household level was 21%. No screened community members were Brucella seropositive. Majority of brucellosis cases were caused by B. melitensis; only one index case was linked to B. abortus. CONCLUSION: We found evidence of brucellosis infection among household family members of brucellosis index cases. B. melitensis was the most common species obtained. Findings of this active surveillance study highlight the importance of screening household family members of brucellosis cases and of the use of culture methods to identify Brucella species in the country of Georgia.

Etiologic agents of central nervous system infections among febrile hospitalized patients in the country of Georgia.

OBJECTIVES: There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. METHODS: Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis. RESULTS: Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2. CONCLUSIONS: Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia.

The changing pattern of human brucellosis: clinical manifestations, epidemiology, and treatment outcomes over three decades in Georgia.

BACKGROUND: Brucellosis is an endemic infection in Georgia. We conducted a review of patient records with a suspected or confirmed diagnosis of brucellosis over three decades at the central referral hospital for brucellosis cases, the Institute of Parasitology and Tropical Medicine (IPTM) in Tbilisi. The purpose was to describe the demographic profile and clinical characteristics as well as diagnostic and treatment strategies in patients with brucellosis. METHODS: Data were abstracted from randomly selected patient records at the IPTM. In total, 300 records were reviewed from three time periods: 1970-73, 1988-89, and 2004-2008. RESULTS: The age distribution of patients shifted from a median age of 40 years in the first time period to 20 years in the third time period. Azeri ethnicity was an increasing proportion of the total number of cases. The frequency of relapsed infection was 14.7% (44 cases). A total of 50 patients received vaccine therapy, and although the vaccine produced immune responses, demonstrated by an increase in agglutination titers, it was not associated with improved outcome. CONCLUSION: The demographics of brucellosis in Georgia fit a profile of persons that tend sheep. Osteoarticular complications were commonly detected, especially in children. The changing pattern of brucellosis in Georgia suggests clinicians should be updated about different trends in brucellosis in their country.

Adaptive metabolic changes in CADASIL white matter.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using (1)H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. (1)H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T (E) = 288 ms) and non-accelerated medium-resolution MRSI (T (E) = 35 ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre/Cho, Glx/Cho and Glx/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx/Cre and mI/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx/Cre and mI/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia.