Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection

Background Urinary tract infection (UTI) is frequently implicated as a precipitant of delirium, which refers to an acute confusional state that is associated with high mortality, increased length of stay, and long-term cognitive decline. The pathogenesis of delirium is thought to involve cytokine-mediated neuronal dysfunction of the frontal cortex and hippocampus. We hypothesized that systemic IL-6 inhibition would mitigate delirium-like phenotypes in a mouse model of UTI. Methods C57/BL6 mice were randomized to either: (1) non-UTI control, (2) UTI, and (3) UTI + anti-IL-6 antibody. UTI was induced by transurethral inoculation of 1 × 108Escherichia coli. Frontal cortex and hippocampus-mediated behaviors were evaluated using functional testing and corresponding structural changes were evaluated via quantification of neuronal cleaved caspase-3 (CC3) by immunohistochemistry and western blot. IL-6 in the brain and plasma were evaluated using immunohistochemistry, ELISA, and RT-PCR. Results Compared to non-UTI control mice, mice with UTI demonstrated significantly greater impairments in frontal and hippocampus-mediated behaviors, specifically increased thigmotaxis in Open Field (p < 0.05) and reduced spontaneous alternations in Y-maze (p < 0.01), while treatment of UTI mice with systemic anti-IL-6 fully reversed these functional impairments. These behavioral impairments correlated with frontal and hippocampal neuronal CC3 changes, with significantly increased frontal and hippocampal CC3 in UTI mice compared to non-UTI controls (p < 0.0001), and full reversal of UTI-induced CC3 neuronal changes following treatment with systemic anti-IL-6 antibody (p < 0.0001). Plasma IL-6 was significantly elevated in UTI mice compared to non-UTI controls (p < 0.01) and there were positive and significant correlations between plasma IL-6 and frontal CC3 (r2 = 0.5087/p = 0.0028) and frontal IL-6 and CC3 (r2 = 0.2653, p < 0.0001). Conclusions These data provide evidence for a role for IL-6 in mediating delirium-like phenotypes in a mouse model of UTI. These findings provide pre-clinical justification for clinical investigations of IL-6 inhibitors to treat UTI-induced delirium.

Electroencephalographic Findings in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Neuropsychiatric Manifestations

Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P &lt; 0.01). ACL IgM positivity was higher in NPSLE group (P &lt; 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

Incidence Of Post-Operative Delirium In Geriatric Patients Undergoing Hip Replacement Surgery Using Pre-Operative Haloperidol

Background Delirium is acute onset & fluctuating disturbance in mental state that causes patient appear confused, disoriented or with difficulty to focus and with decline in cognitive function (memory, orientation, speech), circadian disturbance and behavior of patient either agitated or sleepy,in other words sudden confusion. Delirium, also known as acute confusional state, is an organically-caused decline from a previously baseline level of mental function that develops over a short period of time (hours to days). Delirium is not a disease itself, but a syndrome encompassing disturbances in attention, consciousness, and cognition. It may also involve other neurological deficits, like psychomotor disturbances (e.g. hyperactive, hypoactive, or mixed), impaired sleepwake cycle, emotional disturbances, and perceptual disturbances (e.g. hallucinations and delusions). Objective To determine incidence of post-operative delirium in geriatric patients undergoing hip replacement surgery using pre-operative haloperidol. Patients and Methods This study is conducted through geriatric patients undergoing orthopedic surgery and the incidence of pre.& post-operative delirium. This randomized, double-blind, placebo-controlled trial was conducted post-operative surgical ICU in Demerdash hospital which was closed unit and had the same well-established pain, sedation and delirium assessment practices. A delirium was monitored through CAM score in their stay in ICU (max. for &7 days from admission post-operative). Results Several trials stated that the usage of Haloperidol pre-operative decrease the duration and the severity of Delirium rather than the incidence of delirium. In our trial we will detect the incidence of delirium with using prophylactic haloperidol in geriatric patients undergoing Hip replacement surgery. In our study revealed that using prophylactic pre-operative haloperidol decrease the incidence of delirium among geriatric patient as well as decreasing both the duration and the severity of delirium among the study group. Conclusion Our study and results revealed that Haloperidol as antipsychotic drug have beneficial effect on reduction of incidence of delirium in post-operative geriatric patients, also it showed effect on duration of delirium and severity of the disease as well as ICU stay.

Evaluation and Management of Delirium

Delirium, sometimes referred to as encephalopathy, is an acute confusional state that is both common in hospitalized patients and associated with poor outcomes. For patients, families, and caregivers, delirium can be a traumatic experience. While delirium is one of the most common diagnoses encountered by the consulting neurologist, the majority of the time it will have been previously unrecognized as such by the care team. Neurologic syndromes such as dementia or aphasia can either be misdiagnosed as delirium or may coexist with it, necessitating careful neurologic assessment. Once the diagnosis of delirium has been established, a careful evaluation for predisposing and precipitating factors can help uncover modifiable contributors, which should be addressed as part of a multicomponent, primarily nonpharmacologic intervention. Importantly, delirium management, which begins with comprehensive prevention, should emphasize the humanity of the delirious patient and the challenges of caring for this vulnerable population. When considered, delirium represents an important opportunity for the neurologist to substantially enhance patient care.

Acute Confusional State Revealing Moyamoya Disease in the Emergency Department: A Rare Entity

A 54-year-old woman was admitted to the emergency department for an acute, fluctuating altered mental status and reduced perceptual awareness of her surroundings as well as disorganized thinking. Blood tests, including for drugs, were normal. A CT scan of the brain was normal. Magnetic resonance imaging and CT angiography of the supra-aortic vessels were both were consistent with moyamoya disease. The patient was hospitalized for further investigations.

Acute confusional state as a prognostic sign of COVID-19 large-vessel occlusion (LVO)

COVID-19 is well known for its respiratory symptoms, but severe presentations can alter haemostasis, causing acute end-organ damage with poor outcomes. Among its various neurological presentations, cerebrovascular events often present as small-vessel strokes. Although uncommon, in predisposed individuals, large-vessel occlusions (LVOs) can occur as a possible consequence of direct viral action (viral burden or antigenic structure) or virus-induced cytokine storm. Subtle presentations and complicated stroke care pathways continue to exist, delaying timely care. We present a unique case of COVID-19 LVO manifesting as an acute confusional state in an elderly man in April 2020. CT angiography revealed 'de novo' occlusions of the left internal carotid artery and proximal right vertebral artery, effectively blocking anterior and posterior circulations. Delirium can lead to inaccurate stroke scale assessments and prolong initiation of COVID-19 stroke care pathways. Future studies are needed to look into the temporal relationship between confusion and neurological manifestations.

Etiological Evaluation of Acute Confusional State in Elderly (≥60 Years) Patients

Background: Acute confusional state or delirium is a frequent cause of hospital admission in the elderly. It is characterized by an acute fluctuating impairment of cognitive functions and inattention. Recognition and prompt treatment is crucial to decrease the morbidity and mortality of hospitalized elderly patients. Aim of this study was to evaluate the distribution of common medical conditions related to acute confusional state among elderly hospitalized Patients. Methods: This was a cross sectional study. We enrolled 380 patients from different medicine wards in Dhaka Medical College Hospital. We included patients with acute confusional state/delirium of less than 7 days duration. The enrolled patients fulfilled the diagnostic criteria of an acute confusional state. A predesigned checklist was used for data collection. Head injury was excluded by history and CT scan of brain. Patients with preexisting illnesses, such as dementia, psychiatric illnesses and recurrent seizures, and any case of poisoning was excluded. All findings were noted and recorded. A written informed consent was taken from the attendant and relatives. Result: Among 380 patients, most of confusional state developed after the age of 65 years and the mean age was 69 +/-7.6 years. Associated medical conditions were uncontrolled hypertension (63.2%), fever & infection (41.6%), uncontrolled DM (36.6%), CVD (28.4%), CKD & electrolytes abnormalities (10.5%), joint diseases & pain (13.7%). Most of the patients used plyphormacy (76.6%) out of which antihypertensive (60%) were common. The mean duration of presentation was 6.1+/-0.6 days, and among all patients about 63.7% were improved, 29.50% was in persistant symptom of confusion and 6.8% of them died. Conclusion: Acute confusional state was common after 65 years. Uncontrolled hypertension, fever & infection, uncontrolled diabetes, CVD, CKD & electrolytes abnormalities and polypharmacy were found commonly in patients with acute confusional state. J MEDICINE JAN 2021; 22 (1) : 41-45