Miguel Valdes-Sueiras

Neurologic Presentations of AIDS

The human immunodeficiency virus (HIV), the cause of AIDS, has infected an estimated 33 million individuals worldwide. HIV is associated with immunodeficiency, neoplasia, and neurologic disease. The continuing evolution of the HIV epidemic has spurred an intense interest in a hitherto neglected area of medicine, neuroinfectious diseases and their consequences. This work has broad applications for the study of central nervous system (CNS) tumors, dementias, neuropathies, and CNS disease in other immunosuppressed individuals. HIV is neuroinvasive (can enter the CNS), neurotrophic (can live in neural tissues), and neurovirulent (causes disease of the nervous system). This article reviews the HIV-associated neurologic syndromes, which can be classified as primary HIV neurologic disease (in which HIV is both necessary and sufficient to cause the illness), secondary or opportunistic neurologic disease (in which HIV interacts with other pathogens, resulting in opportunistic infections and tumors), and treatment-related neurologic disease (such as immune reconstitution inflammatory syndrome).

HIV stroke risk: evidence and implications

An estimated 34 million men, women, and children are infected with human immunodeficiency virus type 1 (HIV-1), the virus that causes acquired immunodeficiency syndrome (AIDS). Current technology cannot eradicate HIV-1, and most patients with HIV-1-infection (HIV+) will require lifelong treatment with combined antiretroviral therapy (cART). Stroke was recognized as a complication of HIV-1 infection since the early days of the epidemic. Potential causes of stroke in HIV-1 include opportunistic infections, tumors, atherosclerosis, diabetes, hypertension, autoimmunity, coagulopathies, cardiovascular disease, and direct HIV-1 infection of the arterial wall. Ischemic stroke has emerged as a particularly significant neurological complication of HIV-1 and its treatment due to the aging of the HIV+ population, chronic HIV-1 infection, inflammation, and prolonged exposure to cART. New prevention and treatment strategies tailored to the needs of the HIV+ population are needed to address this issue.

Education correction using years in school or reading grade-level equivalent? Comparing the accuracy of two methods in diagnosing HIV-associated neurocognitive impairment.

Neuropsychological tests generally require adjustments for years of education when determining the presence of neurocognitive impairment. However, evidence indicates that educational quality, as assessed with reading tests, may be a better reflection of educational attainment among African Americans. Thus, African Americans with poor educational quality may be incorrectly classified with neurocognitive impairment based on neuropsychological tests. We compared the accuracy of neuropsychological test scores standardized using reading grade-equivalent versus years of education in predicting neurocognitive impairment among a sample of Whites and African-American adults who were HIV+. Participants were examined by a neurologist and classified with or without HIV-associated neurocognitive disorders according to accepted criteria. Participants were also classified as impaired versus not impaired based on their neuropsychological test scores standardized by 1) self-reported education or 2) WRAT-3 reading grade-level. Cross tabulation tables were used to determine agreement of the two methods in detecting impairment. Among African-Americans, standardized scores derived from reading scores had greater specificity than those derived from years of education (84.1% vs. 77.3). Among the Whites, correction based on years of education had both greater specificity and sensitivity. The results suggest that reading tests may be a useful alternative for determining NCI among African Americans.

An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults

Central nervous system opportunistic infections (CNS-OI) are a significant cause of morbidity and mortality in AIDS. While current interventions are increasingly successful in treating CNS-OI, little information exists regarding long-term behavioral outcomes among survivors. In this exploratory study we examined neurocognitive data among three groups of adults with different AIDS-related CNS-OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61 individuals with AIDS, but without CNS-OI, was used as a comparison group. A battery of standardized neuropsychological tests assessing a variety of cognitive domains was administered upon entry. Results indicate that individuals with a history of CNS-OI were most impaired on measures of cognitive and psychomotor speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals with history of TE had the most severe and varied deficits. The results are discussed in relation to what is known about the neuropathological consequences of the various CNS-OIs. While this is the first systematic group study of residual CNS-OI effects on neurocognitive function, future studies employing more participants, perhaps focusing on specific CNS-OIs, will further characterize the long-term outcomes in AIDS-related CNS-OI.

Field Validation of the Los Angeles Motor Scale as a Tool for Paramedic Assessment of Stroke Severity

Background and Purpose— The Los Angeles Motor Scale (LAMS) is a 3-item, 0- to 10-point motor stroke-deficit scale developed for prehospital use. We assessed the convergent, divergent, and predictive validity of the LAMS when performed by paramedics in the field at multiple sites in a large and diverse geographic region. Methods— We analyzed early assessment and outcome data prospectively gathered in the FAST-MAG trial (Field Administration of Stroke Therapy–Magnesium phase 3) among patients with acute cerebrovascular disease (cerebral ischemia and intracranial hemorrhage) within 2 hours of onset, transported by 315 ambulances to 60 receiving hospitals. Results— Among 1632 acute cerebrovascular disease patients (age 70±13 years, male 57.5%), time from onset to prehospital LAMS was median 30 minutes (interquartile range 20–50), onset to early postarrival (EPA) LAMS was 145 minutes (interquartile range 119–180), and onset to EPA National Institutes of Health Stroke Scale was 150 minutes (interquartile range 120–180). Between the prehospital and EPA assessments, LAMS scores were stable in 40.5%, improved in 37.6%, and worsened in 21.9%. In tests of convergent validity, against the EPA National Institutes of Health Stroke Scale, correlations were r=0.49 for the prehospital LAMS and r=0.89 for the EPA LAMS. Prehospital LAMS scores did diverge from the prehospital Glasgow Coma Scale, r=−0.22. Predictive accuracy (adjusted C statistics) for nondisabled 3-month outcome was as follows: prehospital LAMS, 0.76 (95% confidence interval 0.74–0.78); EPA LAMS, 0.85 (95% confidence interval 0.83–0.87); and EPA National Institutes of Health Stroke Scale, 0.87 (95% confidence interval 0.85–0.88). Conclusions— In this multicenter, prospective, prehospital study, the LAMS showed good to excellent convergent, divergent, and predictive validity, further establishing it as a validated instrument to characterize stroke severity in the field.

Enrollment Yield and Reasons for Screen Failure in a Large Prehospital Stroke Trial

Background and Purpose— The enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated. Methods— The Field Administration of Stroke Therapy–Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process—paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded. Results— From 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%). Conclusions— In this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

A comparison of screening batteries in the detection of neurocognitive impairment in HIV-infected Spanish speakers

BACKGROUND A substantial number of Spanish-speaking individuals from Mexico and Central America are now living in the United States. These individuals are at heightened risk for HIV infection and, due to late diagnosis and limited resources, for HIV-associated neurocognitive disorders (HAND). Early detection is key, yet adequate methods for detecting HAND in Spanish speakers, especially in resource-poor areas, remains problematic. Therefore, it is necessary to identify accurate yet efficient neurocognitive screening tools that are appropriate for use in resource-limited AIDS clinics serving Spanish-speaking patients. METHODS Twenty-one Spanish-speaking, HIV-positive adults who migrated from Mexico or Central America underwent neuromedical and neurocognitive evaluation in Spanish. The concordance of three neurocognitive screening measures (the HIV Dementia Scale [HDS], the Mini-Mental State Examination [MMSE], and the NEUROPSI) with a comprehensive neuropsychological battery was examined. In addition, accuracy in detecting neurocognitive impairment using standard and alternative cutoff scores was examined. RESULTS The HDS and the NEUROPSI showed high correlation with the comprehensive neuropsychological battery. The HDS and the NEUROPSI also had the highest sensitivity (67% and 75%, respectively) and specificity (50% and 38%, respectively). Both measures also showed greater sensitivity than the MMSE to very mild forms of HAND. CONCLUSION In this small sample of HIV-positive Spanish speakers from Mexico and Central America living in the United States, the HDS and the NEUROPSI demonstrated reasonable accuracy in detecting neurocognitive impairment, while the MMSE demonstrated very poor accuracy. The HDS and the NEUROPSI were equally sensitive in detecting mild HAND. Continued test development is required to capture this disorder, especially in resource-limited settings.

Los Angeles Motor Scale to Identify Large Vessel Occlusion: Prehospital Validation and Comparison With Other Screens

Background and Purpose— Prehospital scales have been developed to identify patients with acute cerebral ischemia (ACI) because of large vessel occlusion (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have been validated in the prehospital setting, and their impact on routing of patients with intracranial hemorrhage has not been delineated. The purpose of this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC-appropriate (LVO ACI and intracranial hemorrhage patients) recognition and compare the LAMS to other scales. Methods— The performance of the LAMS, administered prehospital by paramedics to consecutive ambulance trial patients, was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC-appropriate patients among all suspected strokes. Additionally, the LAMS administered postarrival was compared concurrently with 6 other scales proposed for paramedic use and the full National Institutes of Health Stroke Scale. Results— Among 94 patients, age was 70 (±13) and 49% female. Final diagnoses were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by paramedics in the field performed moderately well in identifying LVO among patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When concurrently performed in the emergency department postarrival, the LAMS showed comparable or better accuracy versus the 7 comparator scales, for LVO among ACI (accuracies LAMS, 0.70; other scales, 0.62–0.68) and CSC-appropriate (accuracies LAMS, 0.73; other scales, 0.56–0.73). Conclusions— The LAMS performed in the field by paramedics identifies LVO and CSC-appropriate patients with good accuracy. The LAMS performs comparably or better than more extended prehospital scales and the full National Institutes of Health Stroke Scale.

Paramedic Initiation of Neuroprotective Agent Infusions: Successful Achievement of Target Blood Levels and Attained Level Effect on Clinical Outcomes in the FAST-MAG Pivotal Trial (Field Administration of Stroke Therapy – Magnesium)

Background and Purpose— Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective therapy for acute stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome. Methods— The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy – Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation. Results— Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death. Conclusions— Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute stroke.