Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). A subject is considered CCSVI positive if ≥ 2 venous hemodynamic (VH) criteria are ...fulfilled.
To determine prevalence of CCSVI in a large cohort of patients with MS, clinically isolated syndrome (CIS), other neurologic diseases (OND), and healthy controls (HC), using specific proposed echo-color Doppler (ECD) criteria.
Transcranial and extracranial ECD were carried out in 499 enrolled subjects (289 MS, 163 HC, 26 OND, 21 CIS). Prevalence rates for CCSVI were calculated in 3 ways: first, using only the subjects for whom diagnosis was certain (i.e., borderline subjects were excluded); secondly, including the borderline subjects in the "no CCSVI" group; and finally, taking into account subjects who presented any of the VH criteria.
CCSVI prevalence with borderline cases included in the "no CCSVI" group was 56.1% in MS, 42.3% in OND, 38.1% in CIS, and 22.7% in HC (p < 0.001). The CCSVI prevalence figures were 62.5% for MS, 45.8% for OND, 42.1% for CIS, and 25.5% for HC when borderline cases were excluded (p < 0.001). The prevalence of one or more positive VH criteria was the highest in MS (81.3%), followed by CIS (76.2%), OND (65.4%), and HC (55.2%) (p < 0.001). CCSVI prevalence was higher in patients with progressive than in nonprogressive MS (p = 0.004).
Our findings are consistent with an increased prevalence of CCSVI in MS but with modest sensitivity/specificity. Our findings point against CCSVI having a primary causative role in the development of MS.
Disease-modifying agents (DMAs), including interferon beta (IFNbeta) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent anti-inflammatory ...agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFNbeta administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFNbeta demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the resolution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remyelination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs induce accelerated, non-tissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent anti-inflammatory treatments may prevent, stabilize, or induce BV loss.
Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the ...extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes.
Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex.
Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P < .0001), total SDGM (P = .0001), and globus pallidus (P = .01). Patients with CIS with a median T2 lesion volume >4.49 mL showed lower total SDGM, caudate, thalamus (P < .001), globus pallidus (P = .007), hippocampus (P = .004), and putamen (P = .01) volumes and higher lateral ventricle volume (P = .001) than those with a median T2 lesion volume <4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P < .0001) in patients with CIS.
Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.
Purpose Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric ...urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. Materials and Methods Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. Results A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). Conclusions Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.
We have surveyed the spectral and compositional properties of suprathermal heavy ions during quiet times from 1995 January 1 to 2007 December 31 using Wind/Energetic Particles: Anisotropy, ...Composition, and Transport/SupraThermal-through-Energetic Particle Telescope and Advanced Composition Explorer/Ultra-low Energy Isotope Spectrometer at energies between 0.04 and 2.56 MeV nucleon-1. We find the following. (1) Quiet-time Fe/O and C/O abundances are correlated with solar cycle activity, reflecting corresponding values measured in solar energetic particle and interplanetary (IP) shock events during solar maximum, and those measured in the solar wind and corotating interaction regions (CIRs) during solar minimum conditions. (2) The 3He/4He ratio lies in the 3%-8% range during the quiet times of 1998-2004 with finite 3He detected on ~27.4% of the days. This ratio drops to 0.3%-1.2% during 2005-2007 and finite 3He is detected on ~5% of the days. (3) All heavy-ion species exhibit suprathermal tails between 0.04 and 0.32 MeV nucleon-1 with spectral indices ranging from ~1.27 to 2.29. These tails sometimes extend above ~2 MeV nucleon-1 with Fe spectra rolling over at lower energies than those of CNO. (4) The suprathermal tail spectral indices of heavier species (i.e., Fe) are harder than those of the lighter ones (i.e., CNO). These indices do not exhibit a clear solar cycle dependence and for ~50% of the time, they deviate significantly from the 1.5 value. These compositional observations provide evidence that even during the quietest times in IP space, the suprathermal population (3He and C-through-Fe) consists of ions from different sources whose relative contributions vary with solar activity. The heavy-ion energy spectra exhibit suprathermal tails with variable spectral indices that do not exhibit the spectral index of 1.5 predicted by some recent models.
The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in ...patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction.
The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models.
Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness.
Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for Parkinson disease-mild cognitive impairment.
Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast ...subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement.
We enrolled 258 consecutive patients with MS (212 with relapsing-remitting MS, 32 with secondary-progressive MS, and 14 with clinically isolated syndrome) who underwent both pre- and 10-minute postcontrast 3D-FLAIR sequences after a single dose of gadolinium injection on 3T MR imaging. The analysis included leptomeningeal contrast-enhancement evaluation on 3D-FLAIR postcontrast images in native space (method A), on pre- and postcontrast 3D-FLAIR images in native space (method B), and on pre-/postcontrast 3D-FLAIR coregistered and subtracted images (method C, used as the criterion standard).
In total, 51 (19.7%) patients with MS showed the presence of leptomeningeal contrast enhancement using method A; 39 (15.1%), using method B; and 39 (15.1%), using method C (
= .002). Compared with method C as the criterion standard, method A showed 89.8% sensitivity and 92.7% specificity, while method B showed 84.6% sensitivity and 97.3% specificity (
< .001) at the patient level. Reproducibility was the highest using method C (κ agreement,
= 088,
< .001). The mean time to analyze the 3D-FLAIR images was significantly lower with method C compared with methods A and B (
< .001).
3D-FLAIR postcontrast imaging offers a sensitive method for detecting leptomeningeal contrast enhancement in patients with MS. However, the use of subtraction imaging helped avoid false-positive cases, decreased reading time, and increased the accuracy of leptomeningeal contrast-enhancement foci detection in a clinical routine.
Increasing evidence suggests that iron deposition is present in the later stages of MS. In this study we examined abnormal phase values, indicative of increased iron content on SWI-filtered phase ...images of the SDGM in CIS patients and HC. We also examined the association of abnormal phase with conventional MR imaging outcomes at first clinical onset.
Forty-two patients with CIS (31 female, 11 male) and 65 age and sex-matched HC (41 female, 24 male) were scanned on a 3T scanner. Mean age was 40.1 (SD = 10.4) years in patients with CIS, and 42.8 (SD = 14) years in HC, while mean disease duration was 1.2 years (SD = 1.3) in patients with CIS. MP-APT, NPTV, and normalized volume measurements were derived for all SDGM structures. Parametric and nonparametric group-wise comparisons were performed, and associations were determined with other MR imaging metrics.
Patients with CIS had significantly increased MP-APT (P = .029) and MP-APT volume (P = .045) in the pulvinar nucleus of the thalamus compared with HC. Furthermore, the putamen (P = .004), caudate (P = .035), and total SDGM (P = .048) displayed significant increases in MP-APT volume, while MP-APT was also significantly increased in the putamen (P = .029). No global or regional volumetric MR imaging differences were found between the study groups. Significant correlations were observed between increased MP-APT volumes of total SDGM, caudate, thalamus, hippocampus, and substantia nigra with white matter atrophy and increased T2 lesion volume (P < .05).
Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement, in the various SDGM structures, suggesting that iron deposition may precede structure-specific atrophy.
Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year ...confirmed disability progression.
We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (
= 76) and confirmed disability progression (
= 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression.
The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54,
= .004) and remained significant across all time points (
≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (
= 0.27,
change 0.11,
= .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23,
= .04) and 0-12 months (hazard ratio = 2.41,
= .022) was the only significant MR imaging predictor of time to confirmed disability progression.
Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.
Using instruments on the ACE spacecraft, we surveyed the heavy-ion spectra and composition over the range He-Fe for 41 corotating interaction regions (CIRs) during 1998-2007. Below image1 MeV nucleon ...super(-1) the spectra are power laws in kinetic energy nucleon super(-1) with an average spectral index of image, rolling over above image1 MeV nucleon super(-1) to power-law spectra with an average index of image. The spectral shapes for different species are similar, leading to relative abundances that are constant over our energy range, even though the intensities cover up to 8 orders of magnitude. Relative to oxygen, the measured abundances at 385 keV nucleon super(- 1) for super(4)He, C, N, Ne, Mg, Si, S, Ca, and Fe are image, and image, respectively. Except for an overabundance of super(4)He and Ne, the abundances are quite close to that of the fast solar wind. We have found super(3)He/ super(4)He ratios to be enhanced over solar wind values in image40% of the CIRs. The Fe/O ratio in individual CIRs is observed to vary over a factor of image10 and is strongly correlated with the solar wind Fe/O ratio measured 2-4 days preceding each CIR. Taken together with previous studies showing the presence of pickup He super(+) in CIRs, the observational data provide evidence that CIR energetic particles are accelerated out of a suprathermal ion pool that includes heated solar wind ions, pickup ions, and remnant suprathermals from impulsive solar energetic particle events.
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