Objectives Occurrence of EEG spindles has been recently associated with favorable outcome in ICU patients. Available data mostly rely on relatively small patients' samples, particular etiologies, and limited variables ascertainment. We aimed to expand previous findings on a larger dataset, to identify clinical and EEG patterns correlated with spindle occurrence, and explore its prognostic implications. Methods Retrospective observational study of prospectively collected data from a randomized trial (CERTA, NCT03129438) assessing the relationship of continuous (cEEG) versus repeated routine EEG (rEEG) with outcome in adults with acute consciousness impairment. Spindles were prospectively assessed visually as 12‐16Hz activity on fronto‐central midline regions, at any time during EEG interventions. Uni‐ and multivariable analyses explored correlations between spindles occurrence, clinical and EEG variables, and outcome (modified Rankin Scale, mRS; mortality) at 6 months. Results Among the analyzed 364 patients, spindles were independently associated with EEG background reactivity (OR 13.2, 95% CI: 3.11–56.26), and cEEG recording (OR 4.35, 95% CI: 2.5 – 7.69). In the cEEG subgroup (n=182), 33.5% had spindles. They had better FOUR scores (p=0.004), fewer seizures or status epilepticus (p=0.02), and lower mRS (p=0.02). Mortality was reduced (p=0.002), and independently inversely associated with spindle occurrence (OR 0.50, CI 95% 0.25–0.99) and increased EEG background continuity (OR 0.16, 95% CI: 0.07 – 0.41). Conclusions Besides confirming that spindle activity occurs in up to one third of acutely ill patients and is associated with better outcome, this study shows that cEEG has a higher yield than rEEG in identifying them. Furthermore, it unravels associations with several clinical and EEG features in this clinical setting.

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Progressive multifocal leukoencephalopathy (PML) is a severe infection of the central nervous system occurring in immunocompromised individuals in which large demyelinating lesions are induced by polyomavirus JC (JCV). In the absence of effective antiviral treatment, control of the infection relies on restoring anti-JCV immunity. Thus, particularly in longstanding immunocompromising conditions such as organ transplantation, lymphoproliferative disorders, or idiopathic lymphopenia, new strategies to boost anti-JCV immune responses are needed. Here, we report the case of a patient developing PML in the context of kidney transplantation who received rh-IL-7 to foster immune responses against JCV. We give an overview of the immunological mechanisms underlying the development of PML and immune restoration within the central nervous system following JCV infection. Immunotherapeutic strategies developed based on current understanding of the disease hold promise in managing patients with PML.

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