Cerebrospinal Creatine Kinase BB Isoenzyme: A Biomarker for Predicting Outcome After Cardiac Arrest.

BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

Sleep Health as a Determinant of Disparities in Stroke Risk and Health Outcome.

Sleep is essential to human survival and overall vascular health. Sleep health encompasses the objective and subjective qualities associated with one's daily pattern of sleep and wakefulness and has become a growing clinical and public health concern. Impaired sleep duration and quality can increase stroke risk and mediate the relationship between the physical aspects of an individual's environment and disparities in stroke incidence. Here, we review observational studies evaluating the association between sleep health and cerebrovascular disease. We assess the influence on sleep of the physical environment, including the ambient environment with noise levels and the built environment. We also describe the influences on sleep health and stroke risk of social determinants of health, including the chronic stressor of racial discrimination. Finally, we discuss how changes in historical neighborhood characteristics or societal policies can influence the social factors affecting sleep health and stroke risk among socioeconomically disadvantaged groups or ethnic and racial minorities. Given the regional and racial or ethnic differences in stroke risk across the United States, an understanding of novel vascular risk factors, such as the multifaceted role of sleep health, will be critical to develop effective public policies to improve population health.

Pheochromocytoma-induced Subarachnoid and Intracerebral Hemorrhage.

Pheochromocytomas are rare adrenal tumors that are often diagnosed in workup for endocrine causes of refractory hypertension, as an incidental imaging finding, or in patients with classic symptoms of headache, palpitations, and/or diaphoresis. We describe a case of pheochromocytoma presenting in a 63-year-old woman with spontaneous and multifocal subarachnoid and intracerebral hemorrhage without underlying vasculopathy. The patient previously had no documented episodes of hypertension and took no regular medications. She experienced sudden-onset severe headache and presented with hypertensive crisis. Cranial imaging showed bifrontal and right temporal convexal subarachnoid and intracerebral hemorrhage of unknown etiology. Cranial arterial catheterization showed no vascular malformation underlying the site of hemorrhage. Given concern for potential malignant etiology, cross-sectional body imaging was performed that revealed a 7-cm right adrenal heterogeneous mass. Biochemical workup demonstrated markedly elevated plasma metanephrine and normetanephrine levels, diagnostic of pheochromocytoma. She underwent α- and ß-blockade, and evaluation with a multidisciplinary team including repeat intracranial imaging to ensure resolution of the intracranial bleeding before definitive surgical management. She then underwent successful laparoscopic adrenalectomy. This case demonstrates that the workup of cryptogenic intracranial hemorrhage and hypertensive crisis should include evaluation for catecholamine-secreting tumors.

Cerebral fat embolism syndrome at a single trauma center.

OBJECTIVES: Based on a 16-year case series, we sought lessons about diagnosis and treatment of cerebral fat embolism syndrome. MATERIALS AND METHODS: Using discharge codes at a Level 1 Trauma Center, we performed a retrospective chart review of clinical characteristics, diagnostic studies, treatments, and outcome in cerebral fat embolism syndrome. RESULTS: Thirty-nine (40%) of 97 patients with fat embolism syndrome were diagnosed with cerebral fat embolism syndrome, with 29 (74%) presenting with coma. All had abnormal brain magnetic resonance imaging, with scattered cytotoxic edema (starfield pattern) in 29 (74%). All but two of the 21 patients with dilated fundoscopy showed retinal embolism. Among 29 patients with transcranial Doppler, the presence of microembolic signals in 15 (52%) was associated with fever (p = 0.039), right-to-left intracardiac shunting (p = 0.046) and a trend towards initial coma. In 11 patients with serial transcranial Dopplers and treatment with high-intensity statin therapy, the frequency of microembolic signals tended to decrease after therapy was initiated. Of the 28 (72%) of the 39 patients discharged, 16 (57%) had mild to moderate disability at last follow up. CONCLUSIONS: The recognition of cerebral fat embolism syndrome may be improved with routine inclusion of brain magnetic resonance imaging, dilated fundoscopy, and transcranial Doppler. We share our empiric management algorithm for cerebral fat embolism syndrome using these studies and with consideration of experimental therapies in select patients to prevent ongoing cerebral injury.

Stroke and breathing.

Stroke remains a leading cause of neurologic disability with wide ranging effects, including a variety of respiratory abnormalities. Stroke may influence the central control of the respiratory drive and breathing pattern, airway protection and maintenance, and the respiratory mechanics of inspiration and expiration. In the acute phase of stroke, the central control of breathing is affected by changes in consciousness, cerebral edema, and direct damage to brainstem respiratory centers, resulting in abnormalities in respiratory pattern and loss of airway protection. Common acute complications related to respiratory dysfunction include dysphagia, aspiration, and pneumonia. Respiratory control centers are located in the brainstem, and brainstem stroke causes specific patterns of respiratory dysfunction. Depending on the exact location and extent of stroke, respiratory failure may occur. While major respiratory abnormalities often improve over time, sleep-disordered breathing remains common in the subacute and chronic phases and worsens outcomes. Respiratory mechanics are impaired in hemiplegic or hemiparetic stroke, contributing to worse cardiopulmonary health in stroke survivors. Interventions to address the respiratory complications are under researched, and further investigation in this area is critical to improving outcomes among stroke survivors.

Novel and modifiable factors associated with adherence to continuous positive airway pressure therapy initiated during stroke rehabilitation: An exploratory analysis of a prospective cohort study.

OBJECTIVE/BACKGROUND: Continuous positive airway pressure (CPAP) for the treatment of sleep apnea may improve stroke recovery but is limited by poor adherence. We evaluated baseline features and psychosocial factors associated with CPAP adherence among stroke patients enrolled in a pilot study of an intensive CPAP adherence protocol initiated during inpatient rehabilitation. PATIENTS/METHODS: In a retrospective analysis of a prospective cohort study, we compared participants adherent to CPAP (≥4 h for ≥70% of nights over 3 months) to non-adherent participants. Using mixed methods, we quantitatively compared baseline demographic and stroke-related factors associated with adherence and qualitatively compared facilitators and barriers to adherence. RESULTS: There were 32 adherent and 20 non-adherent participants. Quantitative analysis revealed more severe stroke, aphasia and white race were associated with adherence. Adherent compared to non-adherent participants also had fewer early CPAP complaints, especially claustrophobia. In a thematic qualitative analysis, facilitators of adherence included improvement in sleep and stroke symptoms, confidence in CPAP use, and positive treatment expectations. Conversely, barriers to adherence included both potentially modifiable factors (lack of confidence in CPAP use, discomfort with a new health technology, and common CPAP-related complaints), and less modifiable factors (social stressors, sleep disturbance, and lack of home social support). DISCUSSION: Adherence programs for CPAP use after stroke should address modifiable barriers, with early desensitization to improve CPAP-related complaints and claustrophobia, and training to address perceived self-efficacy with CPAP. Future studies should explore individual goals and barriers associated with CPAP use among stroke survivors to improve long-term CPAP adherence. CLINICAL TRIAL REGISTRATION NUMBER: NCT02809430.

Effect of Continuous Positive Airway Pressure on Stroke Rehabilitation: A Pilot Randomized Sham-Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) predicts poor functional outcome after stroke and increases the risk for recurrent stroke. Less is known about continuous positive airway pressure (CPAP) treatment on stroke recovery. METHODS: In a pilot randomized, double-blind, sham-controlled trial, adult stroke rehabilitation patients were assigned to auto-titrating or sham CPAP without diagnostic testing for OSA. Change in Functional Independence Measure (FIM), a measure of disability, was assessed between rehabilitation admission and discharge. RESULTS: Over 18 months, 40 patients were enrolled and 10 withdrew from the study: 7 from active and 3 from sham CPAP (p > 0.10). For the remaining 30 patients, median duration of CPAP use was 14 days. Average CPAP use was 3.7 h/night, with at least 4 h nightly use among 15 patients. Adherence was not influenced by treatment assignment or stroke severity. In intention-to-treat analyses (n = 40), the median change in FIM favored active CPAP over sham but did not reach statistical significance (34 versus 26, p = 0.25), except for the cognitive component (6 versus 2.5, p = 0.04). The on-treatment analyses (n = 30) yielded similar results (total FIM: 32 versus 26, p = 0.11; cognitive FIM: 6 versus 2, p = 0.06). CONCLUSIONS: A sham-controlled CPAP trial among stroke rehabilitation patients was feasible in terms of recruitment, treatment without diagnostic testing and adequate blinding-though was limited by study retention and CPAP adherence. Despite these limitations, a trend towards a benefit of CPAP on recovery was evident. Tolerance and adherence must be improved before the full benefits of CPAP on recovery can be assessed in larger trials.

Emerging treatments for motor rehabilitation after stroke.

Although numerous treatments are available to improve cerebral perfusion after acute stroke and prevent recurrent stroke, few rehabilitation treatments have been conclusively shown to improve neurologic recovery. The majority of stroke survivors with motor impairment do not recover to their functional baseline, and there remains a need for novel neurorehabilitation treatments to minimize long-term disability, maximize quality of life, and optimize psychosocial outcomes. In recent years, several novel therapies have emerged to restore motor function after stroke, and additional investigational treatments have also shown promise. Here, we familiarize the neurohospitalist with emerging treatments for poststroke motor rehabilitation. The rehabilitation treatments covered in this review will include selective serotonin reuptake inhibitor medications, constraint-induced movement therapy, noninvasive brain stimulation, mirror therapy, and motor imagery or mental practice.

High-dose rosuvastatin treatment for multifocal stroke in trauma-induced cerebral fat embolism syndrome: a case report.

BACKGROUND: Fat embolism syndrome is a life-threatening condition with treatment centering on the provision of excellent supportive care and early fracture fixation. No pharmacologic intervention has yet shown any clear benefit. We used high-dose rosuvastatin specifically for its anti-inflammatory effects to treat a patient with severe fat embolism syndrome. We also suggest that magnetic resonance imaging and transcranial Doppler studies are helpful in establishing the diagnosis and for monitoring the patient's course. PATIENT: A 17-year-old boy developed severe cerebral fat embolism syndrome with multifocal strokes after sustaining bilateral femur fractures. RESULTS: In spite of profound and prolonged neurological impairment, our patient experienced dramatic recovery by the time he was discharged from inpatient rehabilitation several weeks after his initial injury. Magnetic resonance imaging revealed the classic "starfield" pattern of infarcts on diffusion-weighted sequences early in the illness. Additionally, serial transcranial Doppler studies demonstrated dramatically elevated microembolic events that resolved completely during the course of treatment. CONCLUSION: We feel that the acute administration of high-dose rosuvastatin early in the development of our patient's illness may have contributed to his ultimate recovery. Therapeutic guidelines cannot be extrapolated from a single patient, but our experience suggests that statin therapy could be potentially beneficial for individuals with severe fat embolism syndrome, and this approach deserves further clinical evaluation. Additionally, the diagnosis and monitoring of cerebral involvement in fat embolism syndrome is facilitated by both magnetic resonance imaging and transcranial Doppler studies.

Early diagnosis and treatment of obstructive sleep apnea after stroke: Are we neglecting a modifiable stroke risk factor?

Sleep-disordered breathing is an increasingly recognized disorder that is particularly prevalent among stroke patients. Obstructive sleep apnea, a form of sleep-disordered breathing, is associated with multiple major stroke risk factors but is also an independent risk factor for stroke. In addition, untreated sleep apnea is associated with poor functional outcome after stroke. Sleep apnea is amenable to treatment and should be considered a modifiable stroke risk factor, though long-term compliance remains a major barrier. A better understanding of the relationship between sleep apnea and stroke may prompt providers to pursue the early diagnosis and treatment of underlying sleep-disordered breathing to both improve the chance of recovery from stroke in the short term and to reduce the risk of recurrent stroke in the long term.

Do-not-attempt-resuscitation orders and prognostic models for intraparenchymal hemorrhage.

OBJECTIVES: Statistical models predicting outcome after intraparenchymal hemorrhage include patients irrespective of do-not-attempt-resuscitation orders. We built a model to explore how the inclusion of patients with do-not-attempt-resuscitation orders affects intraparenchymal hemorrhage prognostic models. DESIGN: Retrospective, observational cohort study from May 2001 until September 2003. SETTING: University-affiliated tertiary referral hospital in Seattle, WA. PATIENTS: Four hundred twenty-four consecutive patients with spontaneous intraparenchymal hemorrhage. MEASUREMENTS AND MAIN RESULTS: We retrospectively abstracted information from medical records of intraparenchymal hemorrhage patients admitted to a single hospital. Using multivariate logistic regression of presenting clinical characteristics, but not do-not-attempt-resuscitation status, we generated a prognostic score for favorable outcome (defined as moderate disability or better at discharge). We compared observed probability of favorable outcome with that predicted, stratified by do-not-attempt-resuscitation status. We then generated a modified prognostic score using only non-do-not-attempt-resuscitation patients. Records of 424 patients were reviewed: 44% had favorable outcome, 43% had a do-not-attempt-resuscitation order, and 38% died in hospital. The observed and predicted probability of favorable outcome agreed well with all patients taken together. The observed probability of favorable outcome was significantly higher than predicted in non-do-not-attempt-resuscitation patients and significantly lower in do-not-attempt-resuscitation patients. Results were similar when applying a previously published and validated prognostic score. Our modified prognostic score was no longer pessimistic in non-do-not-attempt-resuscitation patients but remained overly optimistic in do-not-attempt-resuscitation patients. CONCLUSIONS: Although our prognostic model was well-calibrated when assessing all intraparenchymal hemorrhage patients, predictions were significantly pessimistic in patients without and optimistic in those with do-not-attempt-resuscitation orders. Such pessimism may drive decisions not to attempt resuscitation in patients in whom a favorable outcome may have been possible, thereby creating a self-fulfilling prophecy. To be most useful in clinical decision making, intraparenchymal hemorrhage prognostic models should be calibrated to large intraparenchymal hemorrhage cohorts in whom do-not-attempt-resuscitation orders were not used.

Lethal giant cell arteritis with multiple ischemic strokes despite aggressive immunosuppressive therapy.

Two patients with giant cell arteritis (GCA) had a malignant course despite aggressive immunosuppressive therapy. A 63-year-old woman presented with symptoms of headache, jaw claudication, scalp paresthesia, and visual disturbances. A temporal artery biopsy showed GCA. While on prednisone, she suffered ischemic strokes, and serial cerebral angiograms demonstrated bilateral, severe and progressive narrowing of distal vertebral and internal carotid arteries. Despite escalating immunosuppressive therapies, she suffered more infarcts and eventually died. Postmortem examination of arteries showed no active inflammation. A 65-year-old man presented with extrapyramidal symptoms though no symptoms typical of GCA. Imaging showed multiple ischemic strokes. Because serial angiograms demonstrated findings similar to the first patient, he underwent temporal artery biopsy that showed GCA. He died 7 months after his presentation with complications of aggressive immunosuppressive therapy. These two patients confirm that GCA can follow a lethal course despite escalating immunosuppressive therapies. Our two patients were unique in that eventually both anterior and posterior circulations were involved bilaterally in a characteristic location where the arteries penetrate the dura. This pattern should always raise the possibility of GCA and, if confirmed, should prompt aggressive immunosuppressive therapy. The dismal outcomes despite this approach may suggest a non-inflammatory arteriopathy, as seen on necropsy in one of our patients. Such an arteriopathy may require novel therapies to be considered for this severe variant of GCA.

Airhead: intraparenchymal pneumocephalus after commercial air travel.

BACKGROUND: Commercial air travel either in the postoperative setting or after open skull fracture has the potential to place patients at unnecessary risk. Although the timing is not clearly known, it should be established that there is no persistent fistulous tract that could introduce additional intraparenchymal air. CASE DESCRIPTION: We present a case of a gentleman with dramatic pneumocephalus after commercial air travel. CONCLUSION: Because of the potential for serious and permanent injury that can result from a dramatic and sustained increase in intracranial pressure, air travel should be delayed until there is no evidence of a fistulous tract. We discuss some basic in-flight options and precautions should change in timing of travel not be possible.