Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19.

BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.

Evaluation of Clinical and Paraclinical Findings for the Differential Diagnosis of Autoimmune and Infectious Encephalitis.

Background: The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. Methods: We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis. The discharge diagnoses served as the reference standard for testing the clinical algorithm for two conditions: use of all the clinical information available on a patient during the first week of hospital admission assuming undefined autoantibody status and microbiological test results (C1) vs. consideration of all the information available on a patient, including the results of serological and microbiological testing (C2). Results: Eighty-four patients (33 autoimmune, 51 infectious encephalitis) were included in the study. Fifty-one (17 autoimmune, 34 infectious) had a definite clinical diagnosis. The two groups differed significantly for the presence of headache, fever, epileptic seizures, and CSF cell-count at presentation. Application of the clinical algorithm resulted in a low sensitivity (58%) and very low specificity (8%) for the diagnosis of possible autoimmune encephalitis. The latter increased considerably in the subgroups of probable and definite autoimmune encephalitis. Whereas the sensitivity of the individual diagnostic categories was clearly time-dependent, the specificity rested foremost on the knowledge of the results of microbiological testing. Anti-CASPR2- and -LGI1-associated autoimmune encephalitis and tick-borne virus encephalitis presented particular diagnostic pitfalls. Conclusions: We define clinical symptoms and paraclinical test results which prove valuable for the differentiation between infectious and autoimmune encephalitis. Sensitivity and specificity of the clinical algorithm clearly depended on the amount of time passed after hospital admission and knowledge of microbiological test results. Accepting this limitation for the acute setting, the algorithm remains a valuable diagnostic aid for antibody-negative autoimmune encephalitis or in resource-poor settings. The initiation of immune therapy however should not be delayed if an autoimmune etiology is considered likely, even if the diagnostic criteria of the algorithm are not (yet) fulfilled.

Interferon-alpha controls IL-17 expression in vitro and in vivo.

The type I interferons interferon alpha (IFNalpha) and IFNbeta are the first line of defense potently induced upon viral infection, and at the same time are immunomodulatory cytokines bridging innate and adaptive immunity. T cells secreting interleukin-17 (IL-17) have recently been identified to regulate neutrophil-mediated inflammation, and have been implicated in the pathogenesis of experimental colitis and human inflammatory bowel disease, and are considered to regulate the inflammatory response in these models. We therefore hypothesized that type I IFNs as sentinels of viral infection might counteract the development of Th17 cells. We studied the effects of IFNalpha on IL-17 mRNA and protein expression in human peripheral blood mononuclear cells (PBMC) and during differentiation of human and murine naïve T cells into Th17 cells. In patients with ulcerative colitis (UC) treated systemically with IFNalpha, we studied colonic expression of IL-17 before and 4 weeks after therapy. IFNalpha potently suppressed IL-17 production in PBMC both at the mRNA and protein level. Th17 differentiation of human and murine naïve T cells was markedly suppressed in the presence of IFNalpha. UC patients exhibited increased IL-17 expression in colonic tissue biopsies compared to healthy controls, which was down-regulated during IFNalpha therapy. IL-17 expression in colonic tissue correlated with clinical remission in these patients. Our data suggest that IFNalpha down-regulates IL-17 expression and Th17 differentiation in vitro and in vivo. As a corollary, these effects might play a role in the mode of action of type I IFNs in the treatment of various diseases.

Die Steuerung von Jahresrhythmik und Diapause bei Larval-und Imagoüberwinterern der Gattung Pterostichus (Col., Carab.).

1. Among the species of the Carabid genus Pterostichus different types of annual periodicity can be found. P. cupreus and P. coerulescens were investigated as representatives of spring breeders with summer larvae (hibernating as adults) and P. vulgaris as a representative of autumn breeders with winter larvae. 2. The female spring breeders enter dormancy, irrespective of the photoperiod. This can be overcome by successive treatment with short-day followed by longday in continuous warmth (photoperiodic parapause). In the field the increasing length of day in spring terminates the parapause. In both species the percentage of mature females depends on the duration of short-day treatment. After eight weeks of short-day the percentage of females with ripe eggs reaches maximal values of up to 100%. By a repeated treatment with first short-day and then long-day old females can be stimulated to a second development of ripe eggs. A temporary drastic lowering of temperature for four months terminates the parapause of the females even under constant photoperiods (continuous short-day or long-day), but under these conditions less than 40% of the females of P. coerulescens and less than 20% of those of P. cupreus mature. The parapause in females can also be terminated by raising the light intensity under constant short-day. In this case, however, only 33% of the females of P. coerulescens became ripe. 3. Not more than 25% of the males of both species of spring breeders mature under continuous warmth after a change from short-to long-day. They do mature, however, when short-day treatment is combined with cold. If the influence of cold and short-day is prolonged from 2 to 4 months and if the temperature is lowered from +5\2-7\dg to +2\2-3\dg the percentage of mature males rises steeply (up to more than 80%). Females from laboratory cultures paired with males treated with cold and short-day are much more prolific than those paired with males which have been treated with warmth and short-day. The dormancy of a high percentage of the males of P. cupreus in warmth can also be terminated in continuous long or continuous short-day by temporary lowering of temperature (thermic parapause). Males of P. coerulescens mature due to changing temperatures only in continuous short-day, but not in long-day. 4. In warmth, development and metamorphosis of both the spring breeders under investigation takes place under short-as well as under long-day. Mortality is equal in both cases. The duration of development is prolonged in both species under long-day. 5. The adults of both sexes of the autumn breeder P. vulgaris mature irrespective of the photoperiod. They show no dormancy. 6. The larval development ofP. vulgaris is indepent of the photoperiod. In warmth, the 2nd or 3rd instar falls into a form of dormancy which will be called a thermic parapause of the larvae, because it can be terminated by a temporary treatment of the 3rd instar with cold.