Neuromuscular Weakness in Intensive Care.

Diseases of the peripheral nervous system create an additional diagnostic conundrum within the intensive care setting. Causes are vast, presentations are myriad, and symptoms are often ill-defined or misidentified. Care benefits from a multidisciplinary approach including a neuromuscular specialist, rehabilitation services, and a specialty pharmacist in addition to the neurocritical care team. In general, survivors achieve a good functional recovery relative to their preintensive care unit baseline.

Ride the Wave: Continuous Electroencephalography is Indicated in the Management of Traumatic Brain Injury.

Introduction: Patients with traumatic brain injury (TBI) are at risk for seizures and other abnormalities that can have permanent adverse effects on the brain. We aimed to report the incidence of seizures and continuous EEG (cEEG) abnormalities after TBI and identify any risk factors associated with the development of these abnormalities. Materials and Methods: This retrospective study identified 245 adult patients with mild to severe TBI who had a cEEG performed within one week of admission to a Midwest Level 1 Trauma Center between July 2014 and July 2019. Trauma registry and electronic medical record (EPIC) data were extracted. Results: Twelve percent of patients with TBI developed seizures and an additional 23% demonstrated electrographic patterns that are correlated with risk for seizures (such as lateralized periodic patterns and sporadic epileptiform discharges). Fifty three percent of seizures would have been missed unless a cEEG was performed. Age, history of epilepsy or prior TBI, hypertension, bleeding disorder, and dementia were associated with an increased risk of developing seizures or higher risk patterns. Conclusions: Thirty-five percent of patients who presented with TBI were noted to have seizures or electrographic patterns associated with a higher risk of seizures. The incidence of cEEG abnormalities in this study is higher than previously reported and these patients are at risk for permanent neurological injury. We recommend the routine use of cEEG for all critically ill patients with TBI as over half of the seizures would have been missed if cEEG was not employed.

The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration.

Neurons and sensory cells are particularly vulnerable to oxidative stress due to their high oxygen demand during stimulus perception and transmission. The mechanisms that protect them from stress-induced death and degeneration remain elusive. Here we show that embryonic deletion of the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons or hair cells leads to sensorineural hearing loss due to postnatal degeneration of both cell types. Mechanistically, we demonstrate that CHD7 controls the expression of major stress pathway components. In its absence, hair cells are hypersensitive, dying rapidly after brief exposure to stress inducers, suggesting that sound at the onset of hearing triggers their degeneration. In humans, CHD7 haploinsufficiency causes CHARGE syndrome, a disorder affecting multiple organs including the ear. Our findings suggest that CHD7 mutations cause developmentally silent phenotypes that predispose cells to postnatal degeneration due to a failure of protective mechanisms.

Neurocritical Care of the Pregnant Patient.

PURPOSE OF REVIEW: To summarize recent changes in management and emerging therapies for pregnant neurocritical care patients. RECENT FINDINGS: Diagnostic and treatment options for managing neurologic emergencies in pregnant patients have expanded with both greater understanding of the effects of imaging modalities and medications on pregnancy and application of standard treatments for non-pregnant patients to pregnant populations. Specifically, this includes cerebrovascular diseases (pregnancy-associated ischemic stroke, pregnancy-associated intracerebral hemorrhage, cerebral venous sinus thrombosis), post-maternal cardiac arrest care, seizures and status epilepticus, myasthenia gravis, and fetal somatic support in maternal death by neurologic criteria. SUMMARY: With the exception of direct abdominal computed tomography (CT), most imaging studies are reasonably safe in pregnancy. When emergent imaging is needed to prevent maternal morbidity or mortality, any CT sequence with or without contrast is appropriate to pursue. Though new safety data on antiplatelets, antihypertensives, thrombolytics, and antiepileptic drugs have increased options for disease management in pregnancy, unfractionated and low-molecular weight heparin remain the safest options for anticoagulation. Early studies on hypothermia, ketamine, and immunomodulating therapies in pregnancy are promising. In myasthenia gravis, new data on adjunct devices may allow more patients to undergo safe vaginal delivery, avoiding cesarean section and the associated risk of crisis. When difficult decisions regarding preterm delivery arise, recent outcome studies can help inform discussion. Lastly, when the feared complication of maternal death by neurologic criteria occurs, fetal somatic support may help to save at least one life.

Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19.

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10-12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes.

BACKGROUND AND PURPOSE: Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP). METHODS: We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome. RESULTS: A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome. CONCLUSIONS: Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.

Functional analysis of candidate genes from genome-wide association studies of hearing.

The underlying causes of age-related hearing loss (ARHL) are not well understood, but it is clear from heritability estimates that genetics plays a role in addition to environmental factors. Genome-wide association studies (GWAS) in human populations can point to candidate genes that may be involved in ARHL, but follow-up analysis is needed to assess the role of these genes in the disease process. Some genetic variants may contribute a small amount to a disease, while other variants may have a large effect size, but the genetic architecture of ARHL is not yet well-defined. In this study, we asked if a set of 17 candidate genes highlighted by early GWAS reports of ARHL have detectable effects on hearing by knocking down expression levels of each gene in the mouse and analysing auditory function. We found two of the genes have an impact on hearing. Mutation of Dclk1 led to late-onset progressive increase in ABR thresholds and the A430005L14Rik (C1orf174) mutants showed worse recovery from noise-induced damage than controls. We did not detect any abnormal responses in the remaining 15 mutant lines either in thresholds or from our battery of suprathreshold ABR tests, and we discuss the possible reasons for this.

Cohort analysis of desmopressin effect on hematoma expansion in patients with spontaneous intracerebral hemorrhage and documented pre-ictus antiplatelet use.

Antiplatelet therapy at the time of spontaneous intracerebral hemorrhage (sICH) may increase risk for hemorrhage expansion and mortality. Current guidelines recommend considering a single dose of desmopressin in sICH associated with cyclooxygenase-1 inhibitors or adenosine diphosphate receptor inhibitors. Adult subjects with sICH and concomitant antiplatelet therapy admitted to a large, tertiary care center were included. We sought to compare the risk of hematoma expansion in patients that received desmopressin for antiplatelet reversal in the setting of sICH to similar patients that did not receive desmopressin. The primary outcomes were the incidence of relative and absolute hematoma expansion. In total, 71 patients (29 received desmopressin, 42 did not receive desmopressin) were analyzed. All patients in the desmopressin group received a 0.3 mcg/kg intravenous dose prior to hematoma expansion assessment. Relative hematoma expansion occurred in 5/29 (17%) with desmopressin compared to 11/42 (26%) without desmopressin (OR 0.59 [95% CI 0.18-1.92]). Absolute hematoma expansion occurred in 9/29 (30%) with desmopressin compared to 12/42 (28%) without desmopressin (OR 1.13 [95% CI 0.40-3.16]). Multiple logistic regression controlling for significant covariates did not reveal a significant effect of desmopressin on relative or absolute hematoma expansion (OR 0.65 [95% CI 0.18-2.43] and OR 1.55 [0.48-4.99], respectively). We failed to find evidence that desmopressin administration for antiplatelet reversal in sICH reduces the incidence of hematoma expansion. Larger studies, focusing on the early phase of sICH, are needed to characterize the clinical efficacy and safety of desmopressin for antiplatelet reversal before widespread implementation.

Clevidipine for acute hypertension in patients with subarachnoid hemorrhage: a pilot study.

PURPOSE: Clevidipine is a novel, ultra-short acting dihydropyridine. We hypothesized that clevidipine would rapidly control elevated blood pressure (BP) in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This prospective open-label pilot study evaluated the efficacy and safety of clevidipine in reducing blood pressure (BP) to a pre-specified range and within 30 min before or after clipping or coiling of the aneurysm. RESULTS: We enrolled five patients who received eight clevidipine infusions, including 1587 systolic or diastolic BP data points. The mean SBP upper and lower goals were set at 154 and 122 mmHg. The primary end point of achieving SBP control within <30 min was reached in all patients within 14.2 ± 6.4 min at an infusion rate of 10.8 ± 9.1 mg/h. The mean pre-infusion, during infusion and post-infusion SBP measurements were 165.5 ± 2.55, 146.4 ± 2.48 and 159.3 ± 11.5 mmHg ( p < 0.05 for pre- vs infusion comparison), respectively. After reaching the primary end point and during the clevidipine infusion, 17.5% and 11.8% of SBP readings were above the upper and below the lower goals, respectively. No patients re-bled. In one patient, the infusion had to be stopped temporarily three times due to SBP decrease below the lower goal. CONCLUSION: Clevidipine controlled SBP in all patients with aneurysmal SAH in <22 min and kept it within the elective range 70% of the time without major complications.

Acute Statin Treatment Improves Recovery after Experimental Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We have previously demonstrated that 2-week treatment of experimental intracerebral hemorrhage (ICH) with a daily dose of 2 mg/kg statin starting 24 hours post-injury exerts a neuroprotective effect. The present study extends our previous investigation and tests the effect of acute high-dose (within 24 hours) statin therapy on experimental ICH. MATERIAL AND METHODS: Fifty-six male Wistar rats were subjected to ICH by stereotactic injection of 100 µl of autologous blood into the striatum. Rats were divided randomly into seven groups: saline control group (n = 8); 10, 20 and 40 mg/kg simvastatin-treated groups (n = 8); and 10, 20 and 40 mg/kg atorvastatin-treated groups (n = 8). Simvastatin or atorvastatin were administered orally at 3 and 24 hours after ICH. Neurological functional outcome was evaluated using behavioral tests (mNSS and corner turn test) at multiple time points after ICH. Animals were sacrificed at 28 days after treatment, and histological studies were completed. RESULTS: Acute treatment with simvastatin or atorvastatin at doses of 10 and 20 mg/kg, but not at 40 mg/kg, significantly enhanced recovery of neurological function starting from 2 weeks post-ICH and persisting for up to 4 weeks post ICH. In addition, at doses of 10 mg/kg and 20 mg/kg, histological evaluations revealed that simvastatin or atorvastatin reduced tissue loss, increased cell proliferation in the subventricular zone and enhanced vascular density and synaptogenesis in the hematoma boundary zone when compared to saline-treated rats. CONCLUSIONS: Treatment with simvastatin or atorvastatin at doses of 10 and 20 mg/kg significantly improves neurological recovery after administration during the first 24 hours after ICH. Decreased tissue loss, increased cell proliferation and vascularity likely contribute to improved functional recovery in rats treated with statins after ICH.

Involvement of peripheral adenosine A2 receptors in adenosine A1 receptor-mediated recovery of respiratory motor function after upper cervical spinal cord hemisection.

BACKGROUND/OBJECTIVE: In an animal model of spinal cord injury, a latent respiratory motor pathway can be pharmacologically activated through central adenosine A1 receptor antagonism to restore respiratory function after cervical (C2) spinal cord hemisection that paralyzes the hemidiaphragm ipsilateral to injury. Although respiration is modulated by central and peripheral mechanisms, putative involvement of peripheral adenosine A2 receptors in functional recovery in our model is untested. The objective of this study was to assess the effects of peripherally located adenosine A2 receptors on recovery of respiratory function after cervical (C2) spinal cord hemisection. METHODS: Respiratory activity was electrophysiologically assessed (under standardized recording conditions) in C2-hemisected adult rats with the carotid bodies intact (H-CBI; n=12) or excised (H-CBE; n=12). Animals were administered the adenosine A2 receptor agonist, CGS-21680, followed by the A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), or administered DPCPX alone. Recovered respiratory activity, characterized as drug-induced activity in the previously quiescent left phrenic nerve of C2-hemisected animals in H-CBI and H-CBE rats, was compared. Recovered respiratory activity was calculated by dividing drug-induced activity in the left phrenic nerve by activity in the right phrenic nerve. RESULTS: Administration of CGS-21680 before DPCPX (n=6) in H-CBI rats induced a significantly greater recovery (58.5 +/- 3.6%) than when DPCPX (42.6 +/- 4.6%) was administered (n=6) alone. In H-CBE rats, prior administration of CGS-21680 (n=6) did not enhance recovery over that induced by DPCPX (n=6) alone. Recovery in H-CBE rats amounted to 39.7 +/- 3.7% and 38.4 + 4.2%, respectively. CONCLUSIONS: Our results suggest that adenosine A2 receptors located in the carotid bodies can enhance the magnitude of adenosine A1 receptor-mediated recovery of respiratory function after C2 hemisection. We conclude that a novel approach of targeting peripheral and central adenosine receptors can be therapeutically beneficial in alleviating compromised respiratory function after cervical spinal cord injury.