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BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
Subject(s)
COVID-19 , Cerebral Hemorrhage , Ischemic Stroke , Nervous System Diseases , Aged , COVID-19/complications , COVID-19/epidemiology , Cerebral Hemorrhage/virology , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Ischemic Stroke/virology , Male , Middle Aged , Nervous System Diseases/virology , Pandemics , Prospective Studies , Registries , SARS-CoV-2ABSTRACT
INTRODUCTION: Successful thrombectomy improves morbidity and mortality after stroke. The present prospective, observational cohort study investigated a potential correlation between the successful restoration of tissue perfusion by mechanical thrombectomy and intact cerebrovascular autoregulation (CA). OBJECTIVE: Status of CA in patients with large vessel occlusive stroke after thrombectomy. METHODS: After thrombectomy CA was measured using transcranial Doppler ultrasound. For this purpose a moving correlation index (Mxa) based on spontaneous arterial blood pressure fluctuations and corresponding cerebral blood flow velocity changes was calculated. CA impairment was defined by Mxa values more than .3. RESULTS: Twenty patients with an acute occlusion of the middle cerebral artery or distal internal carotid artery were included. A successful recanalization of the occluded vessel via interventional thrombectomy was achieved in 10 of these patients (successful recanalization group), while in 10 patients mechanical recanalization failed or could not be applied (no recanalization group). Mean Mxa at stroke side was .58 ± .21 Table 2a in patients with successful intervention. At the unaffected hemisphere Mxa was .50 ± .20 Table 2a in successful recanalization group and .45 ± .24 Table 2b in no recanalization group without statistically significant differences. Based on the previously defined Mxa cut off more than .3, CA impairment was observable in all successful recanalized patients and in 8 of 10 patients with unsuccessful interventional treatment. CONCLUSIONS: These results suggest that brain perfusion may be affected due to impaired CA even after successful mechanical thrombectomy. Therefore, a tight blood pressure management is of great importance in post-thrombectomy stroke treatment to avoid cerebral hypo- and hyperperfusion.
Subject(s)
Brain Ischemia/therapy , Cerebrovascular Circulation , Intracranial Thrombosis/therapy , Stroke/therapy , Thrombectomy , Aged , Aged, 80 and over , Arterial Pressure , Blood Flow Velocity , Brain Ischemia/diagnostic imaging , Brain Ischemia/physiopathology , Female , Homeostasis , Humans , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/physiopathology , Male , Prospective Studies , Recovery of Function , Stroke/diagnostic imaging , Stroke/physiopathology , Thrombectomy/adverse effects , Time Factors , Treatment Outcome , Ultrasonography, Doppler, TranscranialABSTRACT
BACKGROUND: Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically. METHODS: Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up. RESULTS: 114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1). CONCLUSION: The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.
Subject(s)
Anticoagulants/therapeutic use , Disease Progression , Intracranial Thrombosis/diagnosis , Intracranial Thrombosis/drug therapy , Outcome Assessment, Health Care , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Cerebral Angiography , Cerebral Veins/diagnostic imaging , Cerebral Veins/pathology , Female , Follow-Up Studies , Humans , Intracranial Thrombosis/diagnostic imaging , Male , Middle Aged , Phlebography , Prognosis , Retrospective Studies , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/drug therapy , Sinus Thrombosis, Intracranial/pathology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Venous Thrombosis/pathology , Young AdultABSTRACT
BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. METHODS: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. RESULTS: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. CONCLUSIONS: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.
Subject(s)
Cerebellar Ataxia , Limbic Encephalitis , Stiff-Person Syndrome , Humans , Cerebellar Ataxia/drug therapy , Glutamate Decarboxylase , Autoantibodies , Oligoclonal Bands , Limbic Encephalitis/therapy , Stiff-Person Syndrome/therapyABSTRACT
PURPOSE: During an ICU stay, changes in muscles and nerves occur that is accessible via neuromuscular sonography. METHODS: 17 patients recruited from the neurological and neurosurgical ICU (six women; 66 ± 3 years) and 7 healthy controls (three women, 75 ± 3 years) were included. Muscle sonography (rectus abdominis, biceps, rectus femoris and tibialis anterior muscles) using gray-scale values (GSVs), and nerve ultrasound (peroneal, tibial and sural nerves) analyzing the cross-sectional area (CSA) were performed on days 1 (t1), 3 (t2), 5 (t3), 8 (t4), and 16 (t5) after admission. RESULTS: Time course analysis revealed that GSVs were significantly higher within the patient group for all of the investigated muscles (rectus abdominis: F = 7.536; p = 0.011; biceps: F = 14.761; p = 0.001; rectus femoris: F = 9.455; p = 0.005; tibialis anterior: F = 7.282; p = 0.012). The higher GSVs were already visible at t1 or, at the latest, at t2 (tibialis anterior muscles). CSA was enlarged in all of the investigated nerves in the patient group (peroneal nerve: F = 7.129; p = 0.014; tibial nerve: F = 28.976, p < 0.001; sural nerve: F = 13.051; p = 0.001). The changes were visible very early (tibial nerve: t1; peroneal nerve: t2). The CSA of the motor nerves showed an association with the ventilation time and days within the ICU (t1 through t4; p < 0.05). DISCUSSION: We detected very early changes in the muscles and nerves of ICU-patients. Nerve CSA might be a useful parameter to identify patients who are at risk for difficult weaning. Therefore our observations might be severity signs of neuromuscular suffering for the most severe patients.
Subject(s)
Muscle, Skeletal , Tibial Nerve , Female , Humans , Intensive Care Units , Muscle, Skeletal/diagnostic imaging , Sural Nerve , UltrasonographyABSTRACT
INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.
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BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.
Subject(s)
COVID-19 , Encephalitis , Mastoiditis , Meningitis, Pneumococcal , Meningitis, Viral , COVID-19/epidemiology , Hospitals , Humans , Meningitis, Pneumococcal/epidemiology , Meningitis, Pneumococcal/microbiology , Meningitis, Viral/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND AND OBJECTIVES: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD). METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. RESULTS: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.
Subject(s)
Encephalitis , Status Epilepticus , Humans , Glutamate Decarboxylase , Receptors, N-Methyl-D-Aspartate , Prospective Studies , Leucine , Intracellular Signaling Peptides and Proteins , Seizures/etiology , AutoantibodiesABSTRACT
PURPOSE: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation. METHOD: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy. RESULT: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients (p = 0.009). Patients without oral diet had higher need for intubation (p = 0.007), tracheotomy (p = 0.032) and higher mortality (p < 0.001) in comparison to patients with at least small amounts of oral intake. CONCLUSION: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.
Subject(s)
Deglutition Disorders , Stroke , Critical Care , Deglutition , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Diet , HumansABSTRACT
Objective: To assess intensive care unit (ICU) complications, their management, and prognostic factors associated with outcomes in a cohort of patients with autoimmune encephalitis (AE). Methods: This study was an observational multicenter registry of consecutively included patients diagnosed with AE requiring Neuro-ICU treatment between 2004 and 2016 from 18 tertiary hospitals. Logistic regression models explored the influence of complications, their management, and diagnostic findings on the dichotomized (0-3 vs 4-6) modified Rankin Scale score at hospital discharge. Results: Of 120 patients with AE (median age 43 years [interquartile range 24-62]; 70 females), 101 developed disorders of consciousness, 54 autonomic disturbances, 42 status epilepticus, and 39 severe sepsis. Sixty-eight patients were mechanically ventilated, 85 patients had detectable neuronal autoantibodies, and 35 patients were seronegative. Worse neurologic outcome at hospital discharge was associated with necessity of mechanical ventilation (sex- and age-adjusted OR 6.28; 95% CI, 2.71-15.61) tracheostomy (adjusted OR 6.26; 95% CI, 2.68-15.73), tumor (adjusted OR 3.73; 95% CI, 1.35-11.57), sepsis (adjusted OR 4.54; 95% CI, 1.99-10.43), or autonomic dysfunction (adjusted OR 2.91; 95% CI, 1.24-7.3). No significant association was observed with autoantibody type, inflammatory changes in CSF, or pathologic MRI. Conclusion: In patients with AE, mechanical ventilation, sepsis, and autonomic dysregulation appear to indicate longer or incomplete convalescence. Classic ICU complications better serve as prognostic markers than the individual subtype of AE. Increased awareness and effective management of these AE-related complications are warranted, and further prospective studies are needed to confirm our findings and to develop specific strategies for outcome improvement.