Faculty Bibliography

Background: Sound lateralization is dependent upon precise timing of neuronal discharges in the auditory brainstem. Slowed processing speed in auditory brainstem pathways interferes with MS patients' ability to lateralize sound. A test of sound lateralization may be useful for detecting subtle brainstem deficits even among minimally impaired MS subjects. Objective: To determine whether a test of sound lateralization may be more sensitive to differences between controls and minimally impaired MS subjects than standard cognitive tasks. Design/Methods: 16 healthy controls and 45 MS subjects were recruited. Patients were divided into three disability strata: No Disability (Expanded Disability Status Scale (EDSS) =0; N=15), Mild Disability (EDSS=1 to 3.5; N=17), and Moderate Disability (EDSS=4 to 6.5; N=13). Using an interleaved staircase method, the interaural time difference (ITD) to a dichotically presented 910 Hz tone burst was varied to determine ITD thresholds for the tone localized just to the right or just to the left of center. Two standard tests used to assess processing speed, the Paced Auditory Serial Addition Test (PASAT3 and PASAT2) and the Symbol Digit Modalities Test (SDMT), were also administered. Results: Right and left threshold ITDs were averaged to provide a deviation score for each subject. The mean threshold ITD score was lowest for controls (M=196.9 mus, SD=76.4), increased for the No and Mild Disability groups (M=280.7 mus, SD=77.5 and M=268.8 mus, SD=105.3, respectively), and was greatest for the Moderate Disability group ( M=342.3 mus, SD=62.2). A MANOVA showed highly significant effects for IDT (p<.001, eta2=.28) and for the three other dependent variables (PASAT3, p<0.02; eta2=.23; PASAT2, p<.01, eta2=.18; SDMT, p<.001, eta2=.30). However, post hoc analysis showed that only the IDT test was sensitive to differences between controls and each MS group including, most importantly, the No Disability group(p<0.02). Conclusions: In our study, sound localization was the only te!

Objective: To test the utility of a backward masking task for assessing speed of processing in Multiple Sclerosis (MS) on a millisecond scale. Background: Slowed speed of processing is a central component of cognitive impairment in patients with MS. Standard methods of assessing speed of processing, such as the Processing Speed Index, Symbol Digit Modalities Test, or the Paced Auditory Serial Addition Test provide a global measure of processing speed, but do not capture more subtle changes that might occur in the millisecond range. In the present study, we used a backward masking paradigm, in which the stimulus to be reported is followed by a masking pattern. A longer interstimulus interval (ISI) needed to correctly identify the primary stimulus is indicative of slower processing speed and the ISIs producing backward masking would be expected to occur in the range of less than 100 milliseconds. Method/Design: 11 healthy controls and 42 MS patients with scores on the Expanded Disability Status Scale (EDSS) ranging from 0 to 6.5 were recruited for the study. Stimuli consisted of 4 to 6 lower-case- letter words presented on a computer screen. The stimulus word was followed by a mask of upper-case letters forming a nonsense word. The letters of the mask overlay the stimulus word. The ISI between the stimulus word and mask was increased in increments of 5 milliseconds (msec) until the subject was unable to report the word correctly. At that point, 5 iterations of the staircase method were presented to zero in on the threshold ISI. Results: A regression analysis with EDSS as the independent variable and Backward Masking ISI threshold as the dependent measure showed that EDSS was a significant predictor of ISI threshold (unstandardized coefficient B=7.51, t(51)=4.58, p<.001). EDSS also accounted for a significant amount of the variance in ISI scores (R2=.28, F(1,51)=20.96, p<.001). ISI thresholds ranged from an average of 45 msec for controls to an average of 115 msec for EDSS of 6.5. The slope (B) in!

Purpose: Normal neuronal activity is tightly linked to and depends on the increase of blood flow for instantaneous supply of oxygen and glucose. This study is to evaluate whether there are cerebral blood flow (CBF) regulation abnormalities in MS with measurement of cerebrovascular reactivity (CVR) using hypercapnia perfusion MRI. Materials and Methods: Sixteen patients with MS (14 relapsing remitting and 2 secondary progressive) (mean age: 45.1+14.2 years, mean EDSS: 2.9+1.6) and age-matched 13 healthy controls (mean age: 44.5+12.2 years) were recruited for this study. CO2 is a potent vasodilator, and an increase of CO2 tension in blood (referred to as hypercapnia) is known to cause CBF increase. Such CBF changes were measured with a standard pseudo-continuous arterial spin labeling (pCASL) MRI at 3T, with quantitative CBF (ml/min/100g) maps generated during both room air and hypercapnia (mixed 5%CO2, 21%O2, and 74%N2) exposure. The imaging parameters of pCASL include TR/TE=3950/17ms, 52 repetitions, FOV=22cm, in-plane matrix=64x64, slice thickness=5mm, labeling duration=1500ms, postlabeling delay=1230ms, and label location = 84mm below AC-PC line. End-tidal CO2 (EtCO2) was recorded continuously during the scan with a capnograph device and was used as an input function in the analysis. The CVR was calculated as (% change in CBF comparing CO2 inhalation to room-air breathing) divided by (EtCO2 during CO2 inhalation - EtCO2 during room-air breathing). Segmented whole brain grey matter (GM), white matter (WM), and brain parenchymal CVR were calculated for the group analysis. Results: The averaged CVR (%CBF/mmHg EtCO2) showed significant difference for whole brain parenchymal (P=0.009), GM (P=0.008), and WM (P=0.03) between patients (4.74+0.88%, 4.89+1.08%, and 4.73+1.02%) and healthy controls (3.46+1.51%, 3.51+1.47%, and 3.53+1.83%, respectively). There was a significant correlation between brain parenchymal CVR and EDSS (r=-0.69, P=0.007). Whole brain CVR changes correlate with fractional brain p!

OBJECTIVE: To analyze time-trends in age at disability milestones among MS patients who were enrolled into the MSBase International Registry during 1996-2010 period. METHODS: We used linear regression to describe the relationship between mean age at major EDSS benchmarks and calendar time. We then assessed time-trend in age at initial EDSS rating with a three level linear growth model specifying that patients were nested within each of 20 participating countries. The model estimated the average of time-trends in mean age at initial clinical assessment within each country while controlling for patients' EDSS and sex in each country. Analyses were repeated in subsamples of patients diagnosed according to Poser or McDonald criteria. RESULTS: The MSBase Registry contained data on 11,108 MS patients enrolled between 1996 and 2010 who fulfilled our inclusion criteria. During the 1996-2010 period, enrollment age for patients with EDSS 4/4.5 increased by 7.9years, from 43 to 51years (p<0.001), and for EDSS 6/6.5 - by 4.9years, from 48 to 53year (p<0.001). These trends were consistent across 20 investigator countries and were observed in Poser-diagnosed as well as McDonald-diagnosed patient subsets. CONCLUSIONS: The more recent MSBase enrollees in each of the mild-to-moderate disability strata were significantly older than earlier enrollees. Possible explanations for this phenomenon are discussed.

AQP4 water channels are thought to be the target of autoimmune attack in neuromyelitis optica-spectrum disorders (NMOsd). AQP4 are highly expressed on ventricular ependyma. The objective of this study was to describe a novel pattern of linear, 'pencil-thin' enhancement of ventricular ependyma in NMOsd. We report two NMOsd patients with pencil-thin ependymal enhancement along the frontal and occipital horns of lateral ventricles. Differential diagnosis of ependymal enhancement should include NMOsd alongside with infectious and neoplastic etiologies. Pencil-thin ependymal enhancement may be a helpful radiological marker of NMOsd that can be used to differentiate this condition from multiple sclerosis.

Background and purpose: Numerous case series have demonstrated that lesions on brain MRI are common in neuromyelitis optica (NMO), but there has not been an attempt to survey and synthesize the literature on neuro-radiology of brain findings in NMO. Objectives: To review the studies on conventional brain MRI in NMO and to propose to incorporate characteristic brain MRI lesions into the diagnostic criteria of NMO. Methods: We searched for articles with descriptions of brain MRI findings in NMO in EBSCO, EMBASE, PubMed/Medline, Science Citation Index, and SCOPUS. Results: Brain abnormalities are seen in majority of NMO patients as disease duration increases. A minority of NMO patients meet Barkhof criteria for space dissemination in multiple sclerosis (MS), and these criteria should not be used to exclude NMO diagnosis. Distinctive brain lesions of NMO are cataloged and described. Conclusions: Brain lesions in NMO are a consistent feature of the disease. International consensus MRI criteria are needed for NMO analogous to the existing criteria for MS.