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Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

There is an accumulating volume of research into neurological manifestations of coronavirus disease 2019 (COVID‐19). However, inconsistent study designs, inadequate controls, poorly validated tests, and differing settings, interventions, and cultural norms weaken study quality and comparability, hence the understanding of the spectrum, burden, and pathophysiology of these complications. Therefore, a global COVID‐19 Neuro Research Coalition, together with the World Health Organization, has reviewed reports of COVID‐19 neurological complications and harmonized clinical measures for future research. This will facilitate well‐designed studies using precise, consistent case definitions of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and neurological complications, with standardized forms for pooled data analyses that nonspecialists can use, including those in low‐income settings. ANN NEUROL 2021;89:1059–1067

Additional file 1: Appendix Information 1. Methodology of the included studies. Appendix information 2. Ethical clearance obtained. Appendix Table 1. Epilepsy screening questionnaire Malawi. Appendix Table 2. Epilepsy screening questionnaire Uganda. Appendix Table 3. Type and dosage of ASM among patients treated with monotherapy¥.

Additional file 1. Reporting checklist for protocol of a clinical trial based on the SPIRIT guidelines.

Additional file 1: Figure S1. The results of the questionnaire regarding hearing and understanding in absolute numbers (n = 31). Figure S2. The wave reproducibility rates of each ear (left and right) are compared according to the setting in which the measurement was taken: at the research facility (CERMEL, Centre des Rechèrches Médicales Lambaréné, n = 15) or at home (n = 16). Statistical significance is assessed using independent samples t-test. Table S1. Of the 31 patients that could be included in the follow-up study, 15 were assessed in the research facility and 16 at home.

In diesem Kapitel werden zunächst die für die Neurointensivmedizin wesentlichen bakteriellen Infektionen (Meningitis, spinale und Hirnabszesse, Spondylodiszitis, septisch-embolische Herdenzephalitis) abgehandelt, die trotz gezielt eingesetzter Antibiotika und neurochirurgischer Therapieoptionen noch mit einer erheblichen Morbidität und Mortalität behaftet sind. Besonderheiten wie neurovaskuläre Komplikationen, die Tuberkulose des Nervensystems, Neuroborreliose, Neurosyphilis und opportunistische Infektionen bei Immunsuppressionszuständen finden hierbei besondere Berücksichtigung. Der zweite Teil dieses Kapitels behandelt akute und chronische Virusinfektionen des ZNS sowie in einem gesonderten Abschnitt die HIVInfektion und HIV-assoziierte Krankheitsbilder sowie Parasitosen und Pilzinfektionen, die in Industrieländern seit Einführung der HAART bei HIV zwar eher seltener, aber mit zunehmender Globalisierung auch in unseren Breiten immer noch anzutreffen sind.

Background: Taenia solium and Taenia saginata are zoonotic parasites of public health importance. Data on their occurrence in humans and animals in western Europe are incomplete and fragmented. In this study, we aimed to update the current knowledge on the epidemiology of these parasites in this region. Methods: We conducted a systematic review of scientific and grey literature published from 1990 to 2015 on the epidemiology of T. saginata and T. solium in humans and animals. Additionally, data about disease occurrence were actively sought by contacting local experts in the different countries. Results: Taeniosis cases were found in twelve out of eighteen countries in western Europe. No cases were identified in Iceland, Ireland, Luxembourg, Norway, Sweden and Switzerland. For Denmark, Netherlands, Portugal, Slovenia, Spain and the UK, annual taeniosis cases were reported and the number of detected cases per year ranged between 1 and 114. Detected prevalences ranged from 0.05 to 0.27%, whereas estimated prevalences ranged from 0.02 to 0.67%. Most taeniosis cases were reported as Taenia spp. or T. saginata, although T. solium was reported in Denmark, France, Italy, Spain, Slovenia, Portugal and the UK. Human cysticercosis cases were reported in all western European countries except for Iceland, with the highest number originating from Portugal and Spain. Most human cysticercosis cases were suspected to have acquired the infection outside western Europe. Cases of T. solium in pigs were found in Austria and Portugal, but only the two cases from Portugal were confirmed with molecular methods. Germany, Spain and Slovenia reported porcine cysticercosis, but made no Taenia species distinction. Bovine cysticercosis was detected in all countries except for Iceland, with a prevalence based on meat inspection of 0.0002-7.82%. Conclusions: Detection and reporting of taeniosis in western Europe should be improved. The existence of T. solium tapeworm carriers, of suspected autochthonous cases of human cysticercosis and the lack of confirmation of porcine cysticercosis cases deserve further attention. Suspected cases of T. solium in pigs should be confirmed by molecular methods. Both taeniosis and human cysticercosis should be notifiable and surveillance in animals should be improved.

Country sheets template. (DOCX 47 kb)

Identified taeniosis cases in case reports in western Europe (1990–2015). Table S5. Aggregated taeniosis cases reported in authorities’ reports, epidemiological bulletins, and national registries in western Europe (1990–2015). Table S6. Aggregated taeniosis cases reported at hospital/laboratory level in western Europe (1990–2015). Table S7. Taeniosis prevalence data reported in epidemiological studies (1990–2015). Table S8. Taeniosis estimates published in western Europe (1990–2015). Table S9. Identified human cysticercosis cases in case reports in western Europe (1990–2015). Table S10. Aggregated human cysticercosis cases identified in registries and reports in western Europe (1990–2015). Table S11. Aggregated human cysticercosis cases reported at hospital/laboratory level in western Europe (1990–2015). Table S12. Porcine cysticercosis cases and prevalence reported in western Europe (1990–2015) based on meat inspection. Table S13. Bovine cysticercosis cases reported (when prevalence not available) in western Europe (1990–2015) based on meat inspection. Table S14. Bovine cysticercosis prevalence detected in western Europe (1990–2015) by more sensitive methods than routine meat inspection. Table S15. Bovine cysticercosis prevalence data per age reported in western Europe (1990–2015) based on routine meat inspection. (DOCX 99 kb)

PRISMA 2009 Checklist. (DOC 64 kb)

Identified taeniosis cases in case reports in western Europe (1990–2015). Table S5. Aggregated taeniosis cases reported in authorities’ reports, epidemiological bulletins, and national registries in western Europe (1990–2015). Table S6. Aggregated taeniosis cases reported at hospital/laboratory level in western Europe (1990–2015). Table S7. Taeniosis prevalence data reported in epidemiological studies (1990–2015). Table S8. Taeniosis estimates published in western Europe (1990–2015). Table S9. Identified human cysticercosis cases in case reports in western Europe (1990–2015). Table S10. Aggregated human cysticercosis cases identified in registries and reports in western Europe (1990–2015). Table S11. Aggregated human cysticercosis cases reported at hospital/laboratory level in western Europe (1990–2015). Table S12. Porcine cysticercosis cases and prevalence reported in western Europe (1990–2015) based on meat inspection. Table S13. Bovine cysticercosis cases reported (when prevalence not available) in western Europe (1990–2015) based on meat inspection. Table S14. Bovine cysticercosis prevalence detected in western Europe (1990–2015) by more sensitive methods than routine meat inspection. Table S15. Bovine cysticercosis prevalence data per age reported in western Europe (1990–2015) based on routine meat inspection. (DOCX 99 kb)

Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above.This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate.In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %).The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies.

Supplementary material. (DOC 123 kb)

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.

Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933