Faculty Bibliography

OBJECTIVE:To establish cytometry profiles associated with disease stages and immunotherapy in MS. METHODS:Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center. Differences in immune cell subsets were assessed between groups of untreated patients with relapsing-remitting or progressive MS (RRMS or PMS) and HCs and between groups of patients with RRMS taking 6 commonly used disease-modifying drugs. RESULTS:T-regulatory and B-regulatory cells. CONCLUSIONS:Our highly standardized, multisite cytomics data provide further understanding of treatment impact on MS immunophenotype and could pave the way toward monitoring immune cells to help clinical management of MS individuals.

BACKGROUND AND PURPOSE/OBJECTIVE:Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). METHODS:From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. RESULTS:We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values. CONCLUSION/CONCLUSIONS:TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.

OBJECTIVE:To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine. METHODS:The databases of MEDLINE and EMBASE were searched for studies on dizziness and/or vertigo during the prodromal phase or headache phase of migraine. Pooled relative frequencies were estimated using a random-effects meta-analysis. RESULTS: = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies. CONCLUSION/CONCLUSIONS:We found that there is a scarcity of literature on dizziness and vertigo as prodromal- and headache-associated symptoms in individuals with migraine. Methodological variations confound comparisons of epidemiological patterns, although it appears that dizziness and vertigo are more frequent during the headache phase of migraine, compared with the prodromal phase. Future studies should ensure use of standardized definitions and rigorous methodology to enable accurate measurements of dizziness and vertigo in migraine.

OBJECTIVE:A meta-analysis of published studies was performed to determine whether the efficacy of antiseizure drugs in adults with primary generalized tonic-clonic seizures (PGTCS) is comparable with that in the pediatric population (2-12 years of age). METHODS:Electronic searches were conducted in EMBASE, Medline, and the Cochrane Central Register of Controlled Trials for clinical trials of PGTCS in adults and children 2-12 years of age. Neurologists used standardized search and study evaluations to select eligible trials. Median percent reduction in seizure frequency from baseline and ≥50% responder rates were used to compare drug efficacy in adults and children. RESULTS:Among 7 adjunctive-therapy PGTCS trials in adults and children (2-12 years of age) that met evaluation criteria, effect sizes were consistent between adults and children for lamotrigine and topiramate. The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults. The ≥50% responder rate was similar between children and adults in a topiramate study (50% in children compared with 58% in adults). CONCLUSIONS:This meta-analysis supports the use of drug response from antiseizure drug clinical trials for PGTCS in adults to predict comparable treatment response in children 2-12 years of age with PGTCS.

Functional imaging studies have implicated an area in the left lateral fusiform gyrus, known as the visual word form area (VWFA), in pre-lexical orthographic processing. There are very few studies that have examined the functional specificity of this area in patients with discrete lesions limited to this region. Here we describe a rare opportunity to examine the functional specificity of the VWFA in a patient with stereo EEG (sEEG) electrodes implanted for localization of seizures prior to epilepsy surgery. sEEG offers the opportunity to create a transient and highly localized electrophysiological lesion to examine brain behavior correlates during functional mapping. In this case, word reading and writing as well as a variety of non-orthographic language functions (e.g., picture and face naming, auditory naming, and non-word repetition), were tested during electrical stimulation at a series of different electrode contact sites in the ventral temporal region. Pure alexia resulted from stimulation of the lateral fusiform gyrus at coordinates nearly identical to those published for the VWFA in the functional imaging literature.

OBJECTIVE:To assess relative rates and clinical features of patients with genetic generalized epilepsy (GGE), focal epilepsy (FE), and developmental encephalopathic epilepsy (DEE) in the North American SUDEP Registry (NASR). METHODS:We identified all adjudicated definite, definite plus, and probable sudden unexpected death in epilepsy (SUDEP) cases (n = 262) and determined epilepsy type (GGE, FE, or DEE) from medical record review including history, imaging and EEG results, genetics, and next-of-kin interviews. RESULTS:Of the 262 SUDEP cases, 41 occurred in GGE, 95 in FE, 24 in DEE, and 102 were unclassifiable. GGE cases comprised 26% of NASR cases with an epilepsy syndrome diagnosis. The relative frequency of FE:GGE was slightly lower (2.3:1) than in population cohorts (2.1-6:1). Compared to patients with FE, patients with GGE had similar (1) ages at death and epilepsy onset and rates of (2) terminal and historical antiseizure medication adherence; (3) abnormal cardiac pathology; (4) illicit drug/alcohol use histories; and (5) sleep state when SUDEP occurred. CONCLUSIONS:GGE cases were relatively overrepresented in NASR. Because GGEs are less often treatment-resistant than FE or DEE, seizure type rather than frequency may be critical. Many people with GGE predominantly have generalized tonic-clonic seizures (GTCS) when they have uncontrolled or breakthrough seizures, whereas patients with FE more commonly experience milder seizures. Future mechanistic SUDEP studies should assess primary and focal-to-bilateral GTCS to identify potential differences in postictal autonomic and arousal disorders and to determine the differential role that lifestyle factors have on breakthrough seizures and seizure types in GGE vs FE to effectively target SUDEP mechanisms and prevention.

Individuals respond faster to presentations of bisensory stimuli (e.g. audio-visual targets) than to presentations of either unisensory constituent in isolation (i.e. to the auditory-alone or visual-alone components of an audio-visual stimulus). This well-established multisensory speeding effect, termed the redundant signals effect (RSE), is not predicted by simple linear summation of the unisensory response time probability distributions. Rather, the speeding is typically faster than this prediction, leading researchers to ascribe the RSE to a so-called co-activation account. According to this account, multisensory neural processing occurs whereby the unisensory inputs are integrated to produce more effective sensory-motor activation. However, the typical paradigm used to test for RSE involves random sequencing of unisensory and bisensory inputs in a mixed design, raising the possibility of an alternate attention-switching account. This intermixed design requires participants to switch between sensory modalities on many task trials (e.g. from responding to a visual stimulus to an auditory stimulus). Here we show that much, if not all, of the RSE under this paradigm can be attributed to slowing of reaction times to unisensory stimuli resulting from modality switching, and is not in fact due to speeding of responses to AV stimuli. As such, the present data do not support a co-activation account, but rather suggest that switching and mixing costs akin to those observed during classic task-switching paradigms account for the observed RSE.