High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study.

OBJECTIVES: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. METHOD: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. RESULTS: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). CONCLUSION: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

BACKGROUND: This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE). METHODS: Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients' characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores. RESULTS: Most COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52). DISCUSSION: These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

[Cerebral amyloid angiopathy-related cognitive decline: small vessels, big problems]. / Déclin cognitif vasculaire et angiopathie amyloïde cérébrale : petits vaisseaux, gros problèmes.

Cerebral amyloid angiopathy (CAA) is a common and well-defined small vessel disease characterized by the deposition of amyloid ß in the vascular wall. CAA causes devastating outcomes related to intracerebral hemorrhage and cognitive decline in older adults. The shared pathogenic pathway between CAA and Alzheimer's disease, co-occuring frequently in the same subject, has important implications for cognitive outcomes and novel anti-amyloid-ß immunotherapies. In this review, we present the epidemiology, pathophysiology, current diagnostic criteria of CAA, and future developments in the field.

L'angiopathie amyloïde cérébrale (AAC) est une maladie fréquente des petits vaisseaux, caractérisée par un dépôt de ß-amyloïde dans la paroi vasculaire entraînant des hémorragies cérébrales et un déclin cognitif. L'AAC et la maladie d'Alzheimer présentent des caractéristiques physiopathologiques communes et peuvent se retrouver chez un même individu. Cela influence le tableau cognitif et sera à prendre en compte lors de l'utilisation prochaine des nouvelles immunothérapies anti-amyloïde. Dans cet article, nous passons en revue l'épidémiologie, la pathophysiologie, les présentations cliniques ainsi que les critères diagnostiques de l'AAC et discutons des futurs développements dans le domaine.

[Dementia with Lewy bodies: state of the art and perspectives for the clinician]. / Démence à corps de Lewy : état de l'art et perspectives pour le clinicien.

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia, after Alzheimer's disease (AD) and vascular dementia. Its diagnosis remains a challenge for the clinician because of the variety of clinical presentations and comorbidities. The diagnosis is based on clinical criteria such as cognitive fluctuations, visual hallucinations, progressive cognitive impairment, Parkinsonian signs and REM sleep behavioral disorder. Although not specific, biomarkers are helpful for increasing the likelihood of LBD diagnosis and for differentiating LBD from other differential diagnoses such as Parkinson's disease with dementia and Alzheimer's disease. Clinicians should be aware of LBD clinical features and actively look for them in patients with cognitive symptoms, take into consideration the often-associated co-pathologies and to optimize patient's management.

La démence à corps de Lewy (DCL) est l'une des démences les plus fréquentes, après la maladie d'Alzheimer (MA) et la démence vasculaire. Son diagnostic est un défi pour le clinicien du fait de la variété des présentations cliniques et des comorbidités. Le diagnostic repose sur des critères cliniques comme des fluctuations cognitives, des hallucinations visuelles, des troubles cognitifs progressifs, des signes parkinsoniens et un trouble comportemental du sommeil paradoxal. L'utilisation des biomarqueurs, bien que non spécifiques, permet d'augmenter la probabilité de diagnostic de la DCL et de la différencier de la maladie de Parkinson avec démence et de la MA. De ce fait, devant tout sujet âgé avec trouble cognitif, une recherche des symptômes de la DCL est à réaliser en considérant aussi les traitements iatrogènes et les copathologies.

Acute symptomatic seizures and hippocampal sclerosis: the major contributor for post-stroke epilepsy?

OBJECTIVE: Hippocampal sclerosis (HS) is a prominent biomarker of epilepsy. If acquired later in life, it usually occurs in the context of degenerative or acute inflammatory-infectious disease. Conversely, acute symptomatic seizures (ASS) are considered a risk factor for developing post-stroke epilepsy, but other factors remain unrecognized. Here, we hypothesize that silent hippocampal injury contributes to the development of post-stroke epilepsy. METHODS: We performed a retrospective observational study of patients hospitalized between 1/2007 and 12/2018 with an acute stroke in the Stroke Center of the Geneva University Hospital. Patients were included if they had a documented normal hippocampal complex at onset and a control MRI at ≥ 2 year interval without new lesion in the meantime. RESULTS: 162 patients fulfilled our inclusion criteria. ASS during the first week (p < 0.0001) and epileptiform abnormalities in electroencephalography (EEG; p = 0.02) were more frequently associated with the development of epilepsy. Hemorrhagic stroke was strongly associated to both ASS and future focal epilepsy (p = 0.00097). Three patients (1.8%) developed hippocampal sclerosis ipsilateral to the cerebrovascular event between 2 and 5 years, all with ASS and hemorrhagic stroke. INTERPRETATION: ASS and epileptiform EEG abnormalities are strong predictors of post-stroke epilepsy. HS develops in a minority of patients after hemorrhagic lesions, leading to focal epilepsy. Prospective studies are required, including follow-up with EEG and if characterized by epileptiform discharges, with MRI, to determine the true frequency of HS and to better understand predictors of post-stroke epilepsy (AAS, stroke type, and HS), and their impact on stroke recovery.

Decrease in pain perception during acute SARS-CoV-2 infection: a case series.

ABSTRACT: Many reports have described pain appearance or an increase of chronic pain concomitant to severe acute respiratory syndrome coronavirus 2 infection. Here, we describe the cases of 3 patients with chronic cancer pain, in which COVID-19 was associated with a dramatic reduction or disappearance of pain. Pain reappeared after recovery from COVID-19. Neurological imaging and pathological findings, when available, were inconclusive. To the best of our knowledge, this is the first case series reporting an acute reduction in pain perception in COVID-19. We believe further investigation is mandatory because it could shed new light on the mechanisms of pain perception and modulation.

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy.

Encephalopathy is a neurological complication of COVID-19. The objective of this exploratory study is to investigate the link between systemic inflammation and brain microstructural changes (measured by diffusion-weighted imaging) in patients with COVID-19 encephalopathy. 20 patients with COVID-19 encephalopathy (age: 67.3 [Formula: see text] 10.0 years; 90% men) hospitalized in the Geneva University Hospitals for a SARS-CoV-2 infection between March and May 2020 were included in this retrospective cohort study. COVID-19 encephalopathy was diagnosed following a comprehensive neurobiological evaluation, excluding common causes of delirium, such as hypoxemic or metabolic encephalopathy. We investigated the correlation between systemic inflammation (measured by systemic C-reactive protein (CRP)) and brain microstructural changes in radiologically normal white matter (measured by apparent diffusion coefficient (ADC)) in nine spatially widespread regions of the white matter previously associated with delirium. Systemic inflammation (CRP = 60.8 ± 50.0 mg/L) was positively correlated with ADC values in the anterior corona radiata (p = 0.0089), genu of the corpus callosum (p = 0.0064) and external capsule (p = 0.0086) after adjusting for patients' age. No statistically significant association between CRP and ADC was found in the other six white matter regions. Our findings indicate high risk of white matter abnormalities in COVID-19 encephalopathy patients with high peripheral inflammatory markers, suggesting aggressive imaging monitoring may be warranted in these patients. Future studies should clarify a possible specificity of the spatial patterns of CRP-white matter microstructure association in COVID-19 encephalopathy patients and disentangle the role of individual cytokines on brain inflammatory mechanisms.

[COVID-19-related acute encephalopathy: physiopathological hypothesis]. / Encéphalopathie aiguë et Covid-19: hypothèses physiopathologiques.

Acute encephalopathy is one of the most frequent neurological complication in patients hospitalized for COVID-19. Electrolyte imbalance, drugs, and hypoxemia can all affect brain homeostasis, leading to acute cognitive dysfunction and direct implications of the SARS-CoV-2 are not completely understood. Neurological complications of SARS-CoV-2 infection are poorly understood: an inflammatory insult to the endothelium affecting the blood-brain barrier may explain the clinical presentation, but other hypotheses including direct viral damage or an immune-mediated reaction are also suggested. Among these various potential mechanisms, often combined, the controversy remains.

L'encéphalopathie aiguë est l'une des principales complications neurologiques des patients hospitalisés pour un Covid-19. Si les complications électrolytiques, les différents traitements et l'hypoxémie ont un effet sur l'homéostasie cérébrale entraînant une perturbation de la cognition, les conséquences cérébrales directes ou indirectes du SARS-CoV-2 ne sont pas complètement élucidées. L'implication du virus entraînant une atteinte endothéliale des vaisseaux cérébraux pourrait participer à cette encéphalopathie, via une fragilisation de la barrière hémato-encéphalique et un passage facilité des cytokines pro-inflammatoires. L'atteinte virale directe ou la réaction autoimmune secondaire ont également été invoquées. Face aux multiples mécanismes physiopathologiques possibles pouvant expliquer cette encéphalopathie, le débat est ouvert.