Status Myoclonus with Post-cardiac-arrest Syndrome: Implications for Prognostication.

BACKGROUND: Status myoclonus (SM) after cardiac arrest (CA) may signify devastating brain injury. We hypothesized that SM correlates with severe neurologic and systemic post-cardiac-arrest syndrome (PCAS). METHODS: Charts of patients admitted with CA to Mayo Clinic Saint Marys Hospital between 2005 and 2019 were retrospectively reviewed. Data included the neurologic examination, ancillary neurologic tests, and systemic markers of PCAS. Nonsustained myoclonus was clinically differentiated from SM. The cerebral performance category score at discharge was assessed; poor outcome was a cerebral performance category score > 2 prior to withdrawal of life-sustaining therapies or death. RESULTS: Of 296 patients included, 276 (93.2%) had out-of-hospital arrest and 202 (68.5%) had a shockable rhythm; the mean time to return of spontaneous circulation was 32 ± 19 min. One hundred seventy-six (59.5%) patients had a poor outcome. One hundred one (34.1%) patients had myoclonus, and 74 (73.2%) had SM. Neurologic predictors of poor outcome were extensor or absent motor response to noxious stimulus (p = 0.02, odds ratio [OR] 3.8, confidence interval [CI] 1.2-12.4), SM (p = 0.01, OR 10.3, CI 1.5-205.4), and burst suppression on EEG (p = 0.01, OR 4.6, CI 1.4-17.4). Of 74 patients with SM, 73 (98.6%) had a poor outcome. A nonshockable rhythm (p < 0.001, OR 4.5, CI 2.6-7.9), respiratory arrest (p < 0.001, OR 3.5, CI 1.7-7.2), chronic kidney disease (p < 0.001, OR 3.1, CI 1.6-6.0), and a pressor requirement (p < 0.001, OR 4.4, CI 1.8-10.6) were associated with SM. No patients with SM, anoxic-ischemic magnetic resonance imaging findings, and absent electroencephalographic reactivity had a good outcome. CONCLUSIONS: Sustained status myoclonus after CPR is observed in patients with other reliable indicators of severe acute brain injury and systemic PCAS. These clinical determinants should be incorporated as part of a comprehensive approach to prognostication after CA.

Neurologic complications of infective endocarditis.

Infective endocarditis (IE) is an infection primarily affecting the endocardium of heart valves that can embolize systemically and to the brain. Neurologic manifestations include strokes, intracerebral hemorrhages, mycotic aneurysms, meningitis, cerebral abscesses, and infections of the spine. Neurologic involvement is associated with worse mortality, though it does not always portend a poor functional prognosis. Neuroimaging is indicated in patients who have neurologic symptoms, including cerebral vessel imaging in patients who have subarachnoid hemorrhage. In the case of acute ischemic stroke (IS), IV thrombolysis is contraindicated but endovascular thrombectomy may be a consideration. Neurologic findings understandably raise concern about valve surgery when indicated due to the risk of hemorrhage with perioperative anticoagulation. However, most neurologic complications do not preclude valve surgery and valve surgery may in fact be indispensable in some cases to prevent further neurologic problems. Management decisions in patients with IE and neurologic complications should therefore be multidisciplinary with a major contribution from the neurologist.

CT-Negative Subarachnoid Hemorrhage in the First Six Hours.

BACKGROUND: There are no reported cases of negative CT head in the first six hours after a thunderclap headache in a patient found to have an aneurysmal subarachnoid hemorrhage (SAH). METHODS: We present a case of an anemic patient who experienced aneurysmal SAH with a negative head CT within the first 6 h following thunderclap headache. RESULTS: A 47-year-old woman presented with a thunderclap headache and examination showed somnolence and marked meningismus. After a negative CT head was obtained within the first 6 hours of symptom onset, a non-traumatic lumbar puncture (LP) showed consistently bloody collection tubes, prompting repeat imaging that demonstrated a tiny amount of intraventricular hemorrhage. CT angiography revealed an intradural carotid artery aneurysm, and pipeline embolization was successfully performed. CONCLUSION: Non-contrast head CT may be falsely negative within the first 6 hours of aneurysmal SAH in the setting of anemia. In our case, the cause may not have been determined if an LP had not been performed. LP still has a role in diagnosing SAH, particularly in the setting of significant anemia, despite the high sensitivity of non-contrast head CT.

Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes.

BACKGROUND: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes. METHODS: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded. RESULTS: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02). CONCLUSIONS: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.

Weaning from antiseizure drugs after new onset status epilepticus.

OBJECTIVE: In patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE). METHODS: Retrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected. RESULTS: One hundred seventy-seven patients with mean age 63 ± 18 years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow-up was 3.8 ± 3.2 years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow-up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P = 0.009) and those with RSE (P = 0.048, odds ratio = 2.12, 95% confidence interval = 1.00-4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence. SIGNIFICANCE: We found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

The Clinical Spectrum of New-Onset Status Epilepticus.

OBJECTIVES: There is a paucity of data on patients with new-onset status epilepticus in patients without a prior history of epilepsy; we aimed to describe clinical characteristics and assess variables predictive of outcomes. DESIGN: Retrospective cohort. SETTING: Quaternary academic medical center. PATIENTS: Adult patients with new-onset status epilepticus. METHODS: Retrospective review of adults with new-onset status epilepticus admitted to Mayo Clinic, Rochester MN between January 1, 1990, and December 31, 2015, was performed. Patient demographics, status epilepticus etiology, Status Epilepticus Severity Score, and status epilepticus classification per the Status Epilepticus Severity Score were recorded. Six-month mortality and functional outcomes defined as modified Rankin scale (≥3 at last follow-up was considered poor) were primary outcomes. Refractory status epilepticus was a secondary outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred seventy-seven patients were included. Status epilepticus was convulsive in 124 (70.1%) and nonconvulsive in 53 (29.9%); 96 cases (54.2%) were refractory status epilepticus. Mean age at onset was 63 ± 18 years; 52.5% were greater than or equal to 65 years. Etiologies were acute in 50.8%, progressive in 18.1%, remote in 19.2%, and unknown in 11.9% patients. Six-month mortality was 32.2%, and 70.1% had poor modified Rankin scale at mean follow-up 3.1 ± 3.5 years. Age greater than or equal to 65 was a significant predictor of poor functional outcome and 6-month mortality. Loss of consciousness, status epilepticus classification, or age greater than or equal to 65 did not predict progression to refractory status epilepticus. Progression to refractory status epilepticus did not impact functional outcome or mortality at last follow-up. CONCLUSIONS: Poor outcomes in new-onset status epilepticus were associated with older age as well as predominantly progressive or remote symptomatic disease. Further prospective investigations assessing the course and outcomes of these patients would be useful in management and prognostication.

Variable Significance of Brain MRI Findings in Infective Endocarditis and Its Effect on Surgical Decisions.

OBJECTIVE: To determine how brain magnetic resonance imaging (MRI) findings impact clinical outcomes in patients with infective endocarditis (IE) and to propose a management algorithm for patients with neurologic symptoms who are candidates for valve surgery (VS). PATIENTS AND METHODS: Data from our center were retrospectively reviewed for patients hospitalized with IE between January 1, 2007, and December 31, 2014. Outcomes were postoperative intracerebral hemorrhage (ICH), 6-month mortality, and functional outcome at last follow-up as described by the modified Rankin Scale (mRS) score. Good outcome was defined as an mRS score of 2 or less. RESULTS: A total of 361 patients with IE were identified, including 127 patients (35%) who had MRI. One hundred twenty-six of 361 patients (35%) had neurologic symptoms, which prompted MRI in 79 of 127 patients (62%); 74 of 79 (94%) had acute or subacute MRI abnormalities. One patient with subarachnoid and multifocal ICH on MRI developed postoperative ICH. Patients with VS despite MRI abnormalities had lower 6-month mortality (odds ratio [OR], 0.17; 95% CI, 0.06-0.48; P<.001) and better functional outcome (OR, 4.43; 95% CI, 1.51-13.00; P=.005). Irrespective of VS, lobar or posterior fossa ICH on MRI was associated with 6-month mortality (OR, 3.58; 95% CI, 1.22-10.50; P=.02) and territorial ischemic stroke was inversely associated with good mRS (OR, 0.29; 95% CI, 0.13-0.66; P=.002). In neurologically asymptomatic patients who had VS, MRI findings did not impact 6-month mortality or functional outcomes. CONCLUSION: Magnetic resonance imaging detects a large number of abnormalities in patients with IE. Preoperative lobar hematoma and large territorial stroke determine outcome irrespective of VS. When indicated, VS increases the odds of a good outcome despite MRI abnormalities.

Vertebrobasilar dolichoectasia presenting simultaneously with ischemic and hemorrhagic strokes.

BACKGROUND: Vertebrobasilar dolichoectasia (VBDE) can present with brainstem- compressive symptoms, cerebral ischemia, or hemorrhage. Herein we describe a unique patient with VBDE who presented with hemorrhage and cerebral ischemia simultaneously. CASE: Patient is a 76-year-old man presenting with an acute, symptomatic left pontine ischemic stroke heralded by ataxic dysarthria and right ataxic-hemiparesis. MRI scan of the brain demonstrated acute cerebral ischemia in the left pons, a small right thalamic hemorrhage, and evidence of VBDE. CONCLUSION: The perforating vessels branching off of the pathologic VBDE may result in both ischemia and hemorrhage. This is the first known case, to our knowledge, in which hemorrhage and cerebral ischemia occurred simultaneously.

Utility of Brain Magnetic Resonance Imaging in the Surgical Management of Infective Endocarditis.

BACKGROUND: Brain magnetic resonance imaging (MRI) is frequently obtained in patients with infective endocarditis, yet its utility in predicting outcomes for valve replacement surgery in patients is unknown. The objective of this study was to determine how brain MRI findings impact clinical management and outcomes. METHODS: Demographic and clinical data from electronic medical records at Mayo Clinic were retrospectively reviewed for patients hospitalized with definite or possible infective endocarditis according to the modified Duke criteria between January 1, 2007 and December 31, 2014. There were 364 patients included in the study. RESULTS: Cardiac valve replacement surgery was performed in 195 of 364 (53.6%) patients, and 95 (48.7%) of the surgical patients underwent preoperative MRI, which was associated with preoperative neurologic symptoms in 56 of 95 (58.9%) patients (odds ratio = 12.92; 95% confidence interval, 5.98-27.93; P <.001). Postoperative neurologic complications occurred in 24 of 195 (12.3%) patients, including new ischemic stroke in 4 of 195 (2.1%) and new intracerebral hemorrhage in 3 of 195 (1.5%). No patients with microhemorrhages developed postoperative hemorrhage. No significant differences existed in rates of postoperative complications between patients with and those without preoperative MRI. There were no substantial associations between preoperative MRI findings and postoperative neurologic complications, functional outcomes as described by the modified Rankin Scale score, or 6-month mortality. CONCLUSIONS: In patients undergoing valve replacement surgery, preoperative MRI findings were not associated with differences in postoperative outcomes, irrespective of finding or timing of valve replacement surgery.

Endovascular management of cerebral septic embolism: three recent cases and review of the literature.

Endovascular management of acute ischemic stroke secondary to septic emboli from bacterial endocarditis is case-specific and outside established guidelines. We report three new cases of an acute ischemic stroke secondary to septic embolus from two different centers. All cases reported here were large vessel occlusions of the middle cerebral artery in anticoagulated patients. In one case the embolus was noted to be firm and aspiration thrombectomy was attempted in lieu of stent retrieval. Thrombolysis in Cerebral Ischemia (TICI) 3 recanalization was achieved and the patient experienced a good outcome with resolution of deficits. In this case, pathologic analysis of the embolus was available. These additional three cases from two centers add to the small but growing literature for interventional management of acute ischemic stroke in bacterial endocarditis.

Reduced apoptosis by combining normobaric oxygenation with ethanol in transient ischemic stroke.

BACKGROUND AND PURPOSE: The effect of normobaric oxygen (NBO) on apoptosis remains controversial. The present study evaluated the effect of NBO on ischemia-induced apoptosis and assessed the potential for improved outcomes by combining NBO administration with another neuroprotective agent, ethanol, in a rat stroke model. METHODS: Rats were subjected to right middle cerebral artery occlusion (MCAO) for 2h. At the onset of reperfusion, ischemic animals received either NBO (2h duration), an intraperitoneal injection of ethanol (1.0g/kg), or both NBO and ethanol. Extent of brain injury was determined by infarct volume, neurological deficit, and apoptotic cell death. Expression of pro- and anti-apoptotic proteins was evaluated through Western immunoblotting. RESULTS: Given alone, NBO and ethanol each slightly (p<0.05) reduced infarct volume to 38% and 37%, respectively, as compared to the impressive reduction of 51% (p<0.01) seen with combined NBO-ethanol administration. Neurologic deficits were also significantly reduced by 48% with combined NBO-ethanol therapy, as compared to lesser reductions of 24% and 23% with NBO or ethanol, respectively. Combined NBO-ethanol therapy decreased apoptotic cell death by 49%, as compared to 31% with NBO and 30% with ethanol. Similarly, combination therapy significantly increased expression of anti-apoptotic factors (Bcl-2 and Bcl-xL) and significantly reduced expression of pro-apoptotic proteins (BAX, Caspase-3, and AIF), as compared to the minimal or nil protein expression changes elicited by NBO or ethanol alone. CONCLUSIONS: In rats subjected to ischemic stroke, NBO administration salvages ischemic brain tissue through evidenced decrease in apoptotic cell death. Combined NBO therapy with ethanol administration greatly improves both degree of neuroprotection and associated apoptosis.

At low doses ethanol maintains blood-brain barrier (BBB) integrity after hypoxia and reoxygenation: a brain slice study.

Post-ischemia ethanol (EtOH) treatments have been shown to exhibit neuroprotective effects in stroke. However, the mechanisms underlying these effects and those on blood-brain barrier (BBB) integrity have yet to be elucidated. In the present study, we determined whether administering differing concentrations of EtOH alter the expressions of BBB integral proteins, including aquaporins-4 and -9 (AQP-4, AQP-9), matrix metallopeptidases-2 and -9 (MMP-2, MMP-9), zonula occludens-1 (ZO-1), and basal lamina (laminin). We employed an organotypic brain slice culture model that utilizes oxygen-glucose deprivation followed by reoxygenation (OGD/R). Brain slices were obtained from 10-day-old Sprague-Dawley rats and divided into the following five groups (n = 8 subjects per group): (1) control, (2) hypoxia (OGD/R), no EtOH, (3) OGD/R and 10 mM EtOH, (4) OGD/R and 30 mM EtOH, and (5) OGD/R and 90 mM EtOH. To assess BBB integrity, levels of AQPs, MMPs, ZO-1, and laminin were determined by Western blot. Compared to control, OGD/R without EtOH significantly increased AQP-4, AQP-9, MMP-2, and MMP-9 levels, while decreasing ZO-1 and laminin levels. All EtOH concentration treatments (groups 3 through 5) significantly reduced the expressions of AQP-4, AQP-9, MMP-2, and MMP-9, compared to the OGD/R, non-alcohol treated slices. Furthermore, compared to the OGD/R without EtOH group, the 30 mM EtOH treatment significantly increased ZO-1 and laminin levels. In contrast, the 90 mM EtOH level neither enhanced the reduction in AQP and MMP levels nor increased ZO-1 or basal lamina expressions observed in the 30 mM treatment. In conclusion, at an optimal dose of 30 mM, EtOH improves the expressions of MMP-2, MMP-9, AQP-4, AQP-9, ZO-1, and basal laminin, previously altered by OGD/R. These effects may indicate a beneficial effect of EtOH on BBB integrity after stroke.

Hyperglycemia in stroke and possible treatments.

Hyperglycemia affects approximately one-third of acute ischemic stroke patients and is associated with poor clinical outcomes. In experimental and clinical stroke studies, hyperglycemia has been shown to be detrimental to the penumbral tissue for several reasons. First, hyperglycemia exacerbates both calcium imbalance and the accumulation of reactive oxygen species (ROS) in neurons, leading to increased apoptosis. Second, hyperglycemia fuels anaerobic energy production, causing lactic acidosis, which further stresses neurons in the penumbral regions. Third, hyperglycemia decreases blood perfusion after ischemic stroke by lowering the availability of nitric oxide (NO), which is a crucial mediator of vasodilation. Lastly, hyperglycemia intensifies the inflammatory response after stroke, causing edema, and hemorrhage through disruption of the blood brain barrier and degradation of white matter, which leads to a worsening of functional outcomes. Many neuroprotective treatments addressing hyperglycemia in stroke have been implemented in the past decade. Early clinical use of insulin provided mixed results due to insufficiently controlled glucose levels and heterogeneity of patient population. Recently, however, the latest Stroke Hyperglycemia Insulin Network Effort trial has addressed the shortcomings of insulin therapy. While glucagon-like protein-1 administration, hyperbaric oxygen preconditioning, and ethanol therapy appear promising, these treatments remain in their infancy and more research is needed to better understand the mechanisms underlying hyperglycemia-induced injuries. Elucidation of these mechanistic pathways could lead to the development of rational treatments that reduce hyperglycemia-associated injuries and improve functional outcomes for ischemic stroke patients.