Adherence to practice parameters in Medicare beneficiaries with amyotrophic lateral sclerosis.

OBJECTIVE: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence. METHODS: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.20) in 2009 and no prior years (N = 8,575). Variables of interest included race/ethnicity, sex, age, urban residence, Area Deprivation Index (ADI), and provider specialty (neurologist vs. non-neurologist). Outcomes were use of practice parameters, which included feeding tubes, non-invasive ventilation (NIV), riluzole, and receiving care from a neurologist. RESULTS: Overall, 42.9% of patients with ALS received neurologist care. Black beneficiaries (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.47-0.67), older beneficiaries (OR 0.964, 95% CI 0.961-0.968 per year), and those living in disadvantaged areas (OR 0.70, 95% CI 0.61-0.80) received less care from neurologists. Overall, only 26.7% of beneficiaries received a feeding tube, 19.2% NIV, and 15.3% riluzole. Neurologist-treated patients were more likely to receive interventions than other ALS patients: feeding tube (OR 2.80, 95% CI 2.52-3.11); NIV (OR 10.8, 95% CI 9.28-12.6); and riluzole (OR 7.67, 95% CI 6.13-9.58), after adjusting for sociodemographics. These associations remained marked and significant when we excluded ALS patients who subsequently received a code for other diseases that mimic ALS. CONCLUSIONS: ALS patients treated by neurologists received care consistent with practice parameters more often than those not treated by a neurologist. Black, older, and disadvantaged beneficiaries received less care consistent with the practice parameters.

Association of Data-Driven White Matter Hyperintensity Spatial Signatures With Distinct Cerebral Small Vessel Disease Etiologies.

OBJECTIVES: Topographical distribution of white matter hyperintensities (WMH) are hypothesized to vary by cerebrovascular risk factors. We used an unbiased pattern discovery approach to identify distinct WMH spatial patterns and investigate their association with different WMH etiologies. METHODS: We performed a cross-sectional study on participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify spatially distinct WMH distribution patterns using voxel-based spectral clustering analysis of aligned WMH probability maps. We included all participants from the ADNI Grand Opportunity/ADNI 2 study with available baseline 2D-FLAIR MRI scans, without prior history of stroke or presence of infarction on imaging. We evaluated the associations of these WMH spatial patterns with vascular risk factors, amyloid-ß PET, and imaging biomarkers of cerebral amyloid angiopathy (CAA), characterizing different forms of cerebral small vessel disease (CSVD) using multivariable regression. We also used linear regression models to investigate whether WMH spatial distribution influenced cognitive impairment. RESULTS: We analyzed MRI scans of 1,046 ADNI participants with mixed vascular and amyloid-related risk factors (mean age 72.9, 47.7% female, 31.4% hypertensive, 48.3% with abnormal amyloid PET). We observed unbiased partitioning of WMH into five unique spatial patterns: deep frontal, periventricular, juxtacortical, parietal, and posterior. Juxtacortical WMH were independently associated with probable CAA, deep frontal WMH were associated with risk factors for arteriolosclerosis (hypertension and diabetes), and parietal WMH were associated with brain amyloid accumulation, consistent with an Alzheimer's disease (AD) phenotype. Juxtacortical, deep frontal, and parietal WMH spatial patterns were associated with cognitive impairment. Periventricular and posterior WMH spatial patterns were unrelated to any disease phenotype or cognitive decline. DISCUSSION: Data-driven WMH spatial patterns reflect discrete underlying etiologies including arteriolosclerosis, CAA, AD, and normal aging. Global measures of WMH volume may miss important spatial distinctions. WMH spatial signatures may serve as etiology-specific imaging markers, helping to resolve WMH heterogeneity, identify the dominant underlying pathological process, and improve prediction of clinical-relevant trajectories that influence cognitive decline.

Patient characteristics and outcome associations in AMPA receptor encephalitis.

Antibody-mediated encephalitis defines a class of diseases wherein antibodies directed at cell-surface receptors are associated with behavioral and cognitive disturbances. One such recently described encephalitis is due to antibodies directed at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). This entity is exceptionally rare and its clinical phenotype incompletely described. We present findings from two cases of AMPAR encephalitis that exemplify variability in the disease spectrum, and summarize findings in published cases derived from a systematic literature review. When all patients are considered together, the presence of psychiatric symptoms at presentation portended a poor outcome and was associated with the presence of a tumor. Furthermore, we provide evidence to suggest that the topography of magnetic resonance imaging abnormalities in reported cases mirrors the distribution of AMPARs in the human brain. The potential for neurological improvement following immunomodulatory therapy together with the favorable outcome reported in most cases emphasizes the importance of testing for autoantibodies against neuronal cell-surface proteins, including AMPAR, in patients with clinical and neuroimaging findings suggestive of autoimmune encephalitis. Close attention to the clinical phenotype may inform the presence of malignancy and long-term prognosis.

Intrinsic network reactivity differentiates levels of consciousness in comatose patients.

OBJECTIVE: We devise a data-driven framework to assess the level of consciousness in etiologically heterogeneous comatose patients using intrinsic dynamical changes of resting-state Electroencephalogram (EEG) signals. METHODS: EEG signals were collected from 54 comatose patients (GCS ⩽ 8) and 20 control patients (GCS > 8). We analyzed the EEG signals using a new technique, termed Intrinsic Network Reactivity Index (INRI), that aims to assess the overall lability of brain dynamics without the use of extrinsic stimulation. The proposed technique uses three sigma EEG events as a trigger for ensuing changes to the directional derivative of signals across the EEG montage. RESULTS: The INRI had a positive relationship with GCS and was significantly different between various levels of consciousness. In comparison, classical band-limited power analysis did not show any specific patterns correlated to GCS. CONCLUSIONS: These findings suggest that reaching low variance EEG activation patterns becomes progressively harder as the level of consciousness of patients deteriorate, and provide a quantitative index based on passive measurements that characterize this change. SIGNIFICANCE: Our results emphasize the role of intrinsic brain dynamics in assessing the level of consciousness in coma patients and the possibility of employing simple electrophysiological measures to recognize the severity of disorders of consciousness (DOC).

EEG dynamical correlates of focal and diffuse causes of coma.

BACKGROUND: Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. METHODS: We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. RESULTS: Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. CONCLUSIONS: Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) Score: A Risk Prediction Tool.

BACKGROUND AND PURPOSE: Rapid recognition of those at high risk for malignant edema after stroke would facilitate triage for monitoring and potential surgery. Admission data may be insufficient for accurate triage decisions. We developed a risk prediction score using clinical and radiographic variables within 24 hours of ictus to better predict potentially lethal malignant edema. METHODS: Patients admitted with diagnosis codes of cerebral edema and ischemic stroke, NIHSS score (National Institute of Health Stroke Score) of ≥8 and head computed tomographies within 24 hours of stroke onset were included. Primary outcome of potentially lethal malignant edema was defined as death with midline shift ≥5 mm or decompressive hemicraniectomy. We performed multivariate analyses on data available within 24 hours of ictus. Bootstrapping was used to internally validate the model, and a risk score was constructed from the results. RESULTS: Thirty-three percent of 222 patients developed potentially lethal malignant edema. The final model C statistic was 0.76 (confidence interval, 0.68-0.82) in the derivation cohort and 0.75 (confidence interval, 0.72-0.77) in the bootstrapping validation sample. The EDEMA score (Enhanced Detection of Edema in Malignant Anterior Circulation Stroke) was developed using the following independent predictors: basal cistern effacement (=3); glucose ≥150 (=2); no tPA (tissue-type plasminogen activator) or thrombectomy (=1), midline shift >0 to 3 (=1), 3 to 6 (=2), and 6 to 9 (=4); >9 (=7); and no previous stroke (=1). A score over 7 was associated with 93% positive predictive value. CONCLUSIONS: The EDEMA score identifies patients at high risk for potentially lethal malignant edema. Although it requires external validation, this scale could help expedite triage decisions in this patient population.

Surgical Treatment of Neuromas Improves Patient-Reported Pain, Depression, and Quality of Life.

BACKGROUND: Surgical management of neuromas is difficult, with no consensus on the most effective surgical procedure to improve pain and quality of life. This study evaluated the surgical treatment of neuromas by neurectomy, crush, and proximal transposition on improvement in pain, depression, and quality of life. METHODS: Patients who underwent neuroma excision and proximal transposition were evaluated. Preoperative and postoperative visual analogue scale scores for pain (worst and average), depression, and quality of life were assessed using linear regression, and means were compared using paired t tests. The Disabilities of the Arm, Shoulder, and Hand questionnaire score was calculated preoperatively and postoperatively for upper extremity neuroma patients. Patients with long-term follow-up were analyzed using repeated measures analysis of variance comparing preoperative, postoperative, and long-term visual analogue scale scores. RESULTS: Seventy patients (37 with upper extremity neuromas and 33 with lower extremity neuromas) met inclusion criteria. Statistically significant improvements in visual analogue scale scores were demonstrated for all four patient-rated qualities (p < 0.01) independent of duration of initial clinical follow-up. The change in preoperative to postoperative visual analogue scale scores was related inversely to the severity of preoperative scores for pain and depression. Neuroma excision and proximal transposition were equally effective in treating lower and upper extremity neuromas. Upper extremity neuroma patients had a statistically significant improvement in Disabilities of the Arm, Shoulder, and Hand questionnaire scores after surgical treatment (p < 0.02). CONCLUSIONS: Surgical neurectomy, crush, and proximal nerve transposition significantly improved self-reported pain, depression, and quality-of-life scores. Surgical intervention is a viable treatment of neuroma pain and should be considered in patients with symptomatic neuromas refractory to nonoperative management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Peripheral nerve injury after local anesthetic injection.

BACKGROUND: A well-known complication of peripheral nerve block is peripheral nerve injury, whether from the needle or toxicity of the medication used. In this study, we sought to determine the extent of damage that results from intrafascicular injection of various commonly used local anesthetics (LAs). METHODS: Sixteen Lewis rats received an intrafascicular injection of saline (control) or 1 of 3 LAs (bupivacaine, lidocaine, or ropivacaine) into the sciatic nerve (n = 4). At a 2-week end point, the sciatic nerves were harvested for histomorphometric and electron microscopic analysis. RESULTS: Animals that received intrafascicular LA injections showed increased severity of injury as compared with control. In particular, there was a significant loss of large-diameter fibers as indicated by decreased counts (P < 0.01 for all LAs) and area (P < 0.01 for all LAs) of remaining fibers in severely injured versus noninjured areas of the nerve. There was a layering of severity of injury with most severely injured areas closest to and noninjured areas furthest from the injection site. Bupivacaine caused more damage to large fibers than the other 2 LAs. In all groups, fascicular transection injury from the needle was observed. Electron microscopy confirmed nerve injury. CONCLUSIONS: Frequently used LAs at traditional concentrations are toxic to and can injure the peripheral nerve. Any combination of motor and/or sensory sequelae may result due to the varying fascicular topography of a nerve.