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.

A review of methamphetamine use and stroke in the young.

Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to high levels of manufacturing in Mexico, the western United States has experienced greater consequences of meth use. The literature reviewed herein is comprised of case studies and series, and it suggests that hemorrhagic stroke (including hypertensive-like intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage), as opposed to ischemic stroke, is the more common type of neurovascular complication of meth use. Meth-related strokes are a particular concern for younger patients with stroke and may be a partial explanation for increasing stroke rates in this age group. We describe two cases (one intraparenchymal hemorrhage and one ischemic stroke) in young patients (<50 years old) with recent meth use to illustrate clinical characteristics and therapeutic considerations. There are several proposed pathophysiological explanations for meth-associated hemorrhagic stroke including an induced hypertensive surge, vasospasm, blood brain barrier breakdown, chronic hypertension, aneurysm development and rupture, and very rarely associated vasculitis. The increased risk of ischemic stroke related to meth use is less well supported in the literature, but this may, in part, be related to a lack of appropriately designed and powered research studies. Proposed mechanisms for ischemic stroke complications of meth use include those affecting blood vessels such as accelerated atherosclerosis, chronic hypertension, vasospasm, and vasculitis, plus mechanisms that affect the heart including cardiomyopathy, arrhythmias, and infective endocarditis (especially with injection drug use). Standard therapeutic interventions for acute stroke and approaches to secondary stroke prevention seem appropriate for meth-associated strokes, with the addition of abstinence from continued meth use. There is no evidence for any meth-specific stroke treatments. Finally, the prolonged duration of meth withdrawal is described. Larger, prospective studies of meth-related strokes are needed to allow for a better understanding and improved care for this often-devastating consequence of an increasingly prevalent cause of strokes in young patients.

Adding Fuel to the Fire: Infective Endocarditis and the Challenge of Cerebrovascular Complications.

PURPOSE OF REVIEW: Infective endocarditis is a deadly disease and made more deadly by neurologic complications. We review the cerebrovascular complications of infective endocarditis and focus our discussion on medical and surgical management. RECENT FINDINGS: While management of stroke in the setting of infective endocarditis differs from standard stroke treatment, mechanical thrombectomy has proven safe and successful. Optimal timing of cardiac surgery in the setting of stroke remains an area of debate, but additional observational studies continue to add more detail to the discussion. Cerebrovascular complications in the setting of infective endocarditis remain a high stakes clinical challenge. Timing of cardiac surgery in IE complicated by stroke exemplifies these dilemmas. While more studies have suggested that earlier cardiac surgery is likely safe for those with small ischemic infarcts, there remains a need for more data defining optimal timing of surgery in all forms of cerebrovascular involvement.

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.

Bias in Stroke Evaluation: Rethinking the Cookie Theft Picture.

Despite a current emphasis on equity in stroke care, one of the most common stroke assessment tools that is used both nationally and internationally, includes an anachronistic image that projects cultural, linguistic, and socioeconomic bias. This image, titled The Cookie Theft picture, is included in the National Institutes of Health Stroke Scale and was originally developed in 1972. Now, 50 years later, it does not reflect our current diverse, linguistically rich, and multicultural patient population.

Cognitive impairment in syphilis: Does treatment based on cerebrospinal fluid analysis improve outcome?

BACKGROUND: Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes. METHODS: Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP. RESULTS: Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07-0.88], p = 0.03). CONCLUSION: In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline.

How Well Do Neurologic Symptoms Identify Individuals With Neurosyphilis?

Background: Current guidelines recommend lumbar puncture (LP) in patients with syphilis who have neurologic symptoms. Methods: A total of 81 human immunodeficiency virus (HIV)-uninfected individuals and 385 HIV-infected individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent LP and a structured symptom history, including assessment of headache; stiff neck; photophobia; ocular inflammation; vision, hearing, or sensory loss; or gait incoordination. Neurosyphilis was defined as a reactive CSF-Venereal Disease Research Laboratory (VDRL) test. Association between categorical variables was assessed using χ2, Fisher exact test, or logistic regression. Association between continuous and categorical variables was assessed using Mann-Whitney U test. Results: CSF-VDRL was reactive in 20 (24.7%) HIV-uninfected and 68 (17.7%) HIV-infected (P = .14) individuals. No symptom was more common in HIV-uninfected individuals with neurosyphilis. Among the HIV-infected, the odds of a reactive CSF-VDRL were higher in those with mild or greater severity photophobia (2.0 [95% confidence interval [CI], 1.1-3.8]; P = .03), vision loss (2.3 [1.3-4.1]; P = .003), or gait incoordination (2.4 [1.3-4.4]; P = .006); or moderate or greater severity hearing loss (3.1 [1.3-7.5]; P = .01). Diagnostic specificity of these 4 symptoms for neurosyphilis was high when limited to moderate or greater severity (91.6%-100%); however, the diagnostic sensitivity was low (1.5%-38.1%). Conclusions: Among HIV-infected patients with syphilis, 4 specific neurologic symptoms are more common in those with a reactive CSF-VDRL. Lack of symptoms does not guarantee that the CSF-VDRL is nonreactive, regardless of HIV status.

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.

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.