Developing a Standardized Approach to Grading the Level of Brain Dysfunction on EEG.

PURPOSE: To assess variability in interpretation of electroencephalogram (EEG) background activity and qualitative grading of cerebral dysfunction based on EEG findings, including which EEG features are deemed most important in this determination. METHODS: A web-based survey (Qualtrics) was disseminated to electroencephalographers practicing in institutions participating in the Critical Care EEG Monitoring Research Consortium between May 2017 and August 2018. Respondents answered 12 questions pertaining to their training and EEG interpretation practices and graded 40 EEG segments (15-second epochs depicting patients' most stimulated state) using a 6-grade scale. Fleiss' Kappa statistic evaluated interrater agreement. RESULTS: Of 110 respondents, 78.2% were attending electroencephalographers with a mean of 8.3 years of experience beyond training. Despite 83% supporting the need for a standardized approach to interpreting the degree of dysfunction on EEG, only 13.6% used a previously published or an institutional grading scale. The overall interrater agreement was fair ( k = 0.35). Having Critical Care EEG Monitoring Research Consortium nomenclature certification (40.9%) or EEG board certification (70%) did not improve interrater agreement ( k = 0.26). Predominant awake frequencies and posterior dominant rhythm were ranked as the most important variables in grading background dysfunction, followed by continuity and reactivity. CONCLUSIONS: Despite the preference for a standardized grading scale for background EEG interpretation, the lack of interrater agreement on levels of dysfunction even among experienced academic electroencephalographers unveils a barrier to the widespread use of EEG as a clinical and research neuromonitoring tool. There was reasonable agreement on the features that are most important in this determination. A standardized approach to grading cerebral dysfunction, currently used by the authors, and based on this work, is proposed.

Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

The "head snap": a subtle clinical feature during the finger-nose-finger maneuver in essential tremor.

BACKGROUND: Essential tremor is characterized by several hyperkinetic movements, including arm and head tremors. We report another movement of the head in patients with essential tremor, which we term the "head snap." This was observed as a jerking motion of the head in some patients while they performed the finger-nose-finger maneuver. METHODS: We compared the prevalence of the head snap in essential tremor patients vs. Parkinson's disease patients. We also assessed the clinical correlates of the head snap. RESULTS: Ten (20%) of 50 essential tremor patients exhibited a head snap of any severity (rating ≥0.5) vs. 0 of 50 Parkinson's disease patients (p = 0.001). Patients with head snap had more severe arm tremor on Archimedes spiral drawings (p = 0.019) and were more likely to have head tremor (p = 0.03) than those without it. CONCLUSIONS: This sign could be a useful aid in the clinical diagnosis of tremor.

Postural and Intention Tremors: A Detailed Clinical Study of Essential Tremor vs. Parkinson's Disease.

BACKGROUND: An estimated 30-50% of essential tremor (ET) diagnoses are incorrect, and the true diagnosis in those patients is often Parkinson's disease (PD) or other tremor disorders. There are general statements about the tremor in these ET and PD, but published data on the more subtle characteristics of tremor are surprisingly limited. Postural tremor may occur in both disorders, adding to the difficulty. There are several anecdotal impressions regarding specific features of postural tremor in ET vs. PD, including joint distribution (e.g., phalanges, metacarpal-phalangeal joints, wrist), tremor directionality (e.g., flexion-extension vs. pronation-supination), and presence of intention tremor. However, there is little data to support these impressions. METHODS: In this cross-sectional study, 100 patients (ET, 50 PD) underwent detailed videotaped neurological examinations. Arm tremor was rated by a movement disorder neurologist who assessed severity and directionality across multiple joints. RESULTS: During sustained arm extension, ET patients exhibited more wrist than metacarpal-phalangeal and phalangeal joint tremor than did PD patients (p < 0.001), and more wrist flexion-extension tremor than wrist pronation-supination tremor (p < 0.001). During the finger-nose-finger maneuver, intention tremor was present in approximately one in four (28%) ET patients vs. virtually none (4%) of the Parkinson's patients (p < 0.001). CONCLUSIONS: We evaluated the location, severity, and directionality of postural tremor in ET and PD, and the presence of intention tremor, observing several clinical differences. We hope that detailed phenomenological data on tremor in ET and PD will help practicing physicians delineate the two diseases.

Habit and nonhabit systems for unconscious and conscious behavior: implications for multitasking.

The study of human consciousness has demonstrated that there are both conscious and unconscious systems. Other work, particularly in animals, has shown that there are habit and nonhabit systems and that these involve different brain regions and memory processes. Here we argue that habits can be equated with unconscious behavior and nonhabits with conscious behavior. This equation makes the extensive physiological literature on habit/nonhabit relevant to the less tractable issue of consciousness. On the basis of this line of reasoning, it appears that different parts of the BG and different memory structures mediate conscious and unconscious processes. It is further argued here that the unconscious system is highly capable; it can both process sensory information and produce behavior. The benefit of such a dual system is multitasking: The unconscious system can execute background tasks, leaving the conscious system to perform more difficult tasks.

The Confusion Assessment Method: a systematic review of current usage.

OBJECTIVES: To examine the psychometric properties, adaptations, translations, and applications of the Confusion Assessment Method (CAM), a widely used instrument and diagnostic algorithm for identification of delirium. DESIGN: Systematic literature review. SETTING: Not applicable. MEASUREMENTS: Electronic searches of PubMED, EMBASE, PsychINFO, CINAHL, Ageline, and Google Scholar, augmented by reviews of reference listings, were conducted to identify original English-language articles using the CAM from January 1, 1991, to December 31, 2006. Two reviewers independently abstracted key information from each article. PARTICIPANTS: Not applicable. RESULTS: Of 239 original articles, 10 (4%) were categorized as validation studies, 16 (7%) as adaptations, 12 (5%) as translations, and 222 (93%) as applications. Validation studies evaluated performance of the CAM against a reference standard. Results were combined across seven high-quality studies (N=1,071), demonstrating an overall sensitivity of 94% (95% confidence interval (CI)=91-97%) and specificity of 89% (95% CI=85-94%). The CAM has been adapted for use in the intensive care unit, emergency, and institutional settings and for scoring severity and subsyndromal delirium. The CAM has been translated into 10 languages where published articles are available. In application studies, CAM-rated delirium is most commonly used as a risk factor or outcome but also as an intervention or reference standard. CONCLUSION: The CAM has helped to improve identification of delirium in clinical and research settings. To optimize performance, the CAM should be scored based on observations made during formal cognitive testing, and training is recommended. Future action is needed to optimize use of the CAM and to improve the recognition and management of delirium.