Autoimmune and inflammatory neurological disorders in the intensive care unit.

PURPOSE OF REVIEW: The present review summarizes the diagnostic approach to autoimmune encephalitis (AE) in the intensive care unit (ICU) and provides practical guidance on therapeutic management. RECENT FINDINGS: Autoimmune encephalitis represents a group of immune-mediated brain diseases associated with antibodies that are pathogenic against central nervous system proteins. Recent findings suggests that the diagnosis of AE requires a multidisciplinary approach including appropriate recognition of common clinical syndromes, brain imaging and electroencephalography to confirm focal pathology, and cerebrospinal fluid and serum tests to rule out common brain infections, and to detect autoantibodies. ICU admission may be necessary at AE onset because of altered mental status, refractory seizures, and/or dysautonomia. Early management in ICU includes prompt initiation of immunotherapy, detection and treatment of seizures, and supportive care with neuromonitoring. In parallel, screening for neoplasm should be systematically performed. Despite severe presentation, epidemiological studies suggest that functional recovery is likely under appropriate therapy, even after prolonged ICU stays. CONCLUSION: AE and related disorders are increasingly recognized in the ICU population. Critical care physicians should be aware of these conditions and consider them early in the differential diagnosis of patients presenting with unexplained encephalopathy. A multidisciplinary approach is mandatory for diagnosis, ICU management, specific therapy, and prognostication.

Prospective Comparative Study of External Ventricular Drain Catheter Colonization: Antibiotic-Impregnated versus Conventional Drains.

OBJECTIVE: Our aim was to compare the prevalence of biofilm formation on antibiotic-impregnated (AIC) versus standard (SC) external ventricular drain (EVD) catheters. METHODS: From March 2018 to November 2020, all consecutive EVD catheters inserted in adult patients were included. After removal, EVD catheters were analyzed under scanning electronic microscopy, on both extraluminal and intraluminal faces. Standard culture of catheter tips was also performed. RESULTS: Overall, 114 catheters were included in 101 patients. There were 48 AICs and 66 SCs. Standard culture showed that ventriculostomy-related colonization was more frequent in SC than in AIC (26 vs. 10%; P = 0.06). Gram-negative rods accounted for 25% of ventriculostomy-related colonization in AICs, and none was documented in SCs. Scanning electronic microscopy observation showed mature biofilm on more than 80% of catheters, without significant difference between catheter type. Also, there was no difference between extraluminal and intraluminal colonization rate. There were 2 ventriculostomy-related infections in each group (5% and 3% among AICs and SCs respectively; P = 1). CONCLUSIONS: Mature biofilm presence on the intraluminal and the extraluminal faces is similar on AICs and SCs. Accordingly, AICs do not seem to efficiently prevent biofilm formation on EVD catheters. The impact of AICs on the microbiological epidemiology of colonizing biofilm should be further evaluated.

Discrepancies in the late auditory potentials of post-anoxic patients: Watch out for focal brain lesions, a pilot retrospective study.

AIMS: Late auditory evoked potentials, and notably mismatch negativity (MMN) and P3 responses, can be used as part of the multimodal prognostic evaluation in post-anoxic disorders of consciousness (DOC). MMN response preferentially stems from the temporal cortex and the arcuate fasciculus. Situations with discrepant evaluations, for example MMN absent but P3 present, are frequent and difficult to interpret. We hypothesize that discrepant MMN-/P3+ results could reflect a higher prevalence of lesions in MMN generating regions. This study presents correlations between neurophysiological and neuroradiological results. METHODS: This retrospective study was conducted on 38 post-anoxic DOC patients. Brain lesions were analyzed on 3T MRI both anatomically and through computation of the local arcuate fasciculus fractional anisotropy values on Diffusion Tensor Imaging sequences. Neurophysiological data and outcome were also analyzed. RESULTS: Our cohort included 8 MMN-/P3+, 7 MMN+/P3+, 21 MMN-/P3- and 2 MMN-/P3+ patients, assessed at a median delay of 20.5 days since cardiac arrest. Our results show that MMN-/P3+ patients tended to have fewer temporal and basal ganglia lesions than MMN-/P3- patients, and more than MMN+/P3+ patients (p-values for trend: p = 0.02 for temporal and p = 0.02 for basal ganglia lesions). There was a statistical difference across groups for mean fractional anisotropy values in the arcuate fasciculus (p = 0.008). The percentage of patients regaining consciousness at three months in MMN-/P3+ patients was higher than in MMN-/P3- patients and lower than in MMN+/P3+ patients. CONCLUSION: This study suggests that discrepancies in late auditory evoked potentials may be linked to focal post-anoxic brain lesions, visible on brain MRI.

Quantitative analysis of early-stage EEG reactivity predicts awakening and recovery of consciousness in patients with severe brain injury.

BACKGROUND: Decisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery. METHODS: In this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Of 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81-0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted ß=-0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99-1.18, P=0.10). CONCLUSIONS: An early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.

Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation.

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU. DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020). SETTING: Two academic hospital ICUs, Paris, France. PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge. INTERVENTIONS: Follow-up by face-to-face neurologic consultation. MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome. CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

Association of Standard Electroencephalography Findings With Mortality and Command Following in Mechanically Ventilated Patients Remaining Unresponsive After Sedation Interruption.

CONTEXT: Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation. OBJECTIVES: We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting. DESIGN, SETTING, AND PATIENTS: In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients' outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography. MEASUREMENTS AND MAIN RESULTS: Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1-4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16-0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings. CONCLUSIONS: In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following.

Ureaplasma parvum causes hyperammonemia presenting as refractory status epilepticus after kidney transplant.

PURPOSE: Alert intensivists about the diagnostic pitfalls arising from hyperammonemia due to Ureaplasma infections in post-transplant patients. MATERIALS AND METHODS: Clinical observation of one patient. CASE REPORT: A 65-year-old female with a medical history of semi-recent kidney transplant was admitted to the Intensive Care Unit for refractory status epilepticus. There were no lesions on brain imaging. Bacterial cultures and viral PCR of cerebrospinal fluid were negative. The first blood ammonia level measured on day 2 was 13 times the normal level, but biological liver tests were normal. The persistence of elevated ammonia levels led to the initiation of symptomatic ammonia lowering-treatments and continuous renal replacement therapy, which led to its decrease without normalization. An Ureaplasma spp infection was then diagnosed. Levofloxacin and doxycyline were administered resulting in normalization of ammonia levels within 48 h. However repeat MRI showed diffuse cortical cytotoxic edema and the patient remained in a minimally conscious state. She eventually died 4 months later from a recurrent infection. CONCLUSION: Ureaplasma infection must be suspected in cases of neurological symptoms associated with hyperammonemia without liver failure, following an organ transplant. Only urgent treatment could improve the prognosis and prevent severe neurological damage or death.