Faculty Bibliography

OBJECTIVE:To systematically identify risk factors for the development of post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) as defined in the International Classification of Headache Disorders (ICHD). BACKGROUND:PTH is a common sequela of TBI and a leading cause of injury-related disability worldwide. However, little is known about risk factors for the development of PTH attributed to TBI. METHODS:We searched PubMed and Embase for literature on risk factors for the development of acute and/or persistent PTH attributed to TBI in accordance with any version of the ICHD. Original studies published in English and of prospective, cross-sectional or retrospective design were considered for the review. Data extraction was performed independently by 2 investigators. RESULTS:Of 1993 potentially relevant articles identified, 3 articles met the inclusion criteria. The following risk factors were assessed for the development of acute PTH: age, sex, type of injury, loss of consciousness, previous TBIs, history of primary headache disorders, history of chronic pain condition other than headache, current treatment for depression/anxiety, attention or learning disorders, body mass index, and other diseases (not further specified). None of the included studies assessed risk factors for the development of persistent PTH. CONCLUSIONS:We found that there is little evidence for any risk factors involved in the development of acute PTH, whereas no study had assessed risk factors for the development of persistent PTH. Further studies are warranted and should be powered to examine possible risk factors for the development of PTH. Rigorous methodology and standardized monitoring should be prioritized to support high-quality research and validate potential findings.

Persons who have disorders of consciousness (DoC) require care from multidisciplinary teams with specialized training and expertise in management of the complex needs of this clinical population. The recent promulgation of practice guidelines for patients with prolonged DoC by the American Academy of Neurology (AAN), American Congress of Rehabilitation Medicine (ACRM), and National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) represents a major advance in the development of care standards in this area of brain injury rehabilitation. Implementation of these practice guidelines requires explication of the minimum competencies of clinical programs providing services to persons who have DoC. The Brain Injury Interdisciplinary Special Interest Group of the ACRM, in collaboration with the Disorders of Consciousness Special Interest Group of the NIDILRR-Traumatic Brain Injury Model Systems (TBIMS) convened a multidisciplinary panel of experts to address this need through the present position statement. Content area-specific workgroups reviewed relevant peer-reviewed literature and drafted recommendations which were then evaluated by the expert panel using a modified Delphi voting process. The process yielded 21 recommendations on the structure and process of essential services required for effective DoC-focused rehabilitation, organized into four categories: Diagnostic and Prognostic Assessment (four recommendations), Treatment (eleven recommendations), Transitioning Care/Long Term Care Needs (five recommendations), and Management of Ethical Issues (one recommendation). With few exceptions, these recommendations focus on infrastructure requirements and operating procedures for the provision of DoC-focused neurorehabilitation services across subacute and post-acute settings.

In rodents, pyramidal cell firing patterns from waking may be replayed in nonrapid eye movement sleep (NREM) sleep during hippocampal sharp wave ripples (HC-SWR). In humans, HC-SWR have only been recorded with electrodes implanted to localize epileptogenicity. Here, we characterize human HC-SWR with rigorous rejection of epileptiform activity, requiring multiple oscillations and coordinated sharp waves. We demonstrated typical SWR in those rare HC recordings which lack interictal epileptiform spikes (IIS) and with no or minimal seizure involvement. These HC-SWR have a similar rate (~12 min^-1 on average, variable across NREM stages and anterior/posterior HC) and apparent intra-HC topography (ripple maximum in putative stratum pyramidale, slow wave in radiatum) as rodents, though with lower frequency (~85 Hz compared to ~140 Hz in rodents). Similar SWR are found in HC with IIS, but no significant seizure involvement. These SWR were modulated by behavior, being largely absent (<2 min^-1 ) except during NREM sleep in both Stage 2 (~9 min^-1 ) and Stage 3 (~15 min^-1 ), distinguishing them from IIS. This study quantifies the basic characteristics of a strictly selected sample of SWR recorded in relatively healthy human hippocampi.

Background: Headache diaries are a mainstay of headache treatment. Various headache smartphone applications (apps) are commercially available. While a Modified Delphi Study aimed to determine specialists' expectations of what a headache app should entail, consumer expectations of these apps have not been evaluated extensively. The aim of this study was to evaluate publicly available reviews of headache apps in the Google Play Store and Apple store to understand app features that motivate consumers to use apps.
Method(s): Using pre-specified criteria, the Google and Apple Play Stores were systematically searched for headache/migraine diary apps with at least 10 consumer reviews. A maximum of 300 'Most Helpful' reviews for each app were extracted into Google Sheets. Four coders qualitatively reviewed and coded reviews until discrepancies were resolved. Codes were counted, and 4 themes with sub-themes were created based on codes used 5+ times.
Result(s): 15 apps met study criteria (9 Android, 6 IOS). The four main themes with sub-themes were: (1) Apps allows user to track headache characteristics, potential triggers, and treatments: track triggers; track treatments; track headache information; users suggest features to log relevant information. (2) App usability: apps allow viewing/editing of existing records; design features for migraine patients are appreciated; technical difficulties limit app usage; developer services satisfy customers. (3) Personalization and features to assess trends in data are key motivators for app use: apps point out trends in data; customization by collection of user's personal information; app provides relief. (4) Ease with exportation and viewing data is critical: app generates data reports; app assists doctors in better treating user's headaches.
Conclusion(s): A user-centered design with the ability to customize key features including headache characteristics, potential triggers and treatments, assess trends in data and view and export the data would best optimize headache smartphone applications based on consumer preference

Bioelectronic devices must be fast and sensitive to interact with the rapid, low-amplitude signals generated by neural tissue. They should also be biocompatible and soft, and should exhibit long-term stability in physiologic environments. Here, we develop an enhancement-mode, internal ion-gated organic electrochemical transistor (e-IGT) based on a reversible redox reaction and hydrated ion reservoirs within the conducting polymer channel, which enable long-term stable operation and shortened ion transit time. E-IGT transient responses depend on hole rather than ion mobility, and combine with high transconductance to result in a gain-bandwidth product that is several orders of magnitude above that of other ion-based transistors. We used these transistors to acquire a wide range of electrophysiological signals, including in vivo recording of neural action potentials, and to create soft, biocompatible, long-term implantable neural processing units for the real-time detection of epileptic discharges. E-IGTs offer a safe, reliable and high-performance building block for chronically implanted bioelectronics, with a spatiotemporal resolution at the scale of individual neurons.

BACKGROUND:The primary objective was to determine the association of patient-reported vision-specific quality of life to disease status and visual function in patients with Friedreich's ataxia (FRDA). METHODS:Patients with FRDA were assessed with the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) along with measures of disease status (ataxia stage) and visual function (low- and high-contrast letter acuity scores). The relations of NEI-VFQ-25 scores to those for disease status and visual function were examined. RESULTS:Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function. CONCLUSIONS:The NEI-VFQ-25 captures the subjective component of visual function in patients with FRDA.

OBJECTIVE:To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches. METHOD/METHODS:Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment. RESULTS:Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis. SIGNIFICANCE/CONCLUSIONS:We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE.

BACKGROUND:Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. METHODS:We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. RESULTS:Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) CONCLUSIONS: Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.