Frozen conflict in the midst of a global pandemic: potential impact on mental health in Armenian border communities.

Armenia has been in a conflict with its neighbor, Azerbaijan, since 1988. Civilians in Tavush Province are regularly affected by ceasefire violations along the armed border with recent escalations further threatening the population's safety. In the midst of the COVID-19 pandemic, concerns regarding the mental health of border village residents in Armenia are prevalent. We present context-related factors of psychiatric illness, the prevalence of mental health disorders, and the state of mental health services in Armenia. We recommend directing greater attention towards the mental health status of civilians residing in conflict zones during the ongoing COVID-19 pandemic.

Community Violence, PTSD, Hopelessness, Substance Use, and Perpetuation of Violence in an Urban Environment.

We investigated the relationships among chronic violence exposure, post-traumatic stress disorder (PTSD) symptom severity, hopelessness, substance use, and perpetuation of violence to facilitate the development of trauma-related interventions for residents of Newark, NJ. A convenience sample of Newark residents (N = 153) was recruited from community centers during various events in 2016-2017. Anonymous, self-report survey measures included a PTSD screen (PCL-C), Beck's Hopelessness Scale, the CAGE questionnaire, and a CDC Health Behavior Scale. Descriptive statistics, Pearson's correlations, Chi square analyses, logistic, and linear regressions were used for analysis. Thirty percent (95% CI [22.7, 37.4]) of our sample screened positive for PTSD. Drug and alcohol use, fighting, and hopelessness were related to severity of PTSD symptoms (p < 0.05). Female gender, CAGE scores, and hopelessness predicted the severity of PTSD symptoms (R2 = 0.354, p < 0.05). Our data has informed the development of a resilience support group currently in the pilot stage for community members.

Mood disorders of childhood and adolescence in a low-income, urban community: A retrospective chart review.

BACKGROUND: Our goal was to determine the risk factors that most correlated with mood disorder diagnoses in children in a low-income, urban community. METHODS: We conducted a retrospective chart review of 174 patients age 6 to 18 who were seen between November 2016 and July 2017 at the University Hospital Psychiatric Pediatric Emergency Services in Newark, New Jersey, United States. RESULTS: Bivariate and multivariate analyses revealed that increasing age, female sex, exposure to trauma, and family history of psychiatric illness were significantly associated with mood disorders in our sample. CONCLUSIONS: The correlation of mood disorders with trauma and family psychiatric history is of particular significance in our sample. In low-income cities with high crime rates and a lack of positive influences, children often have difficulty obtaining the skills to cope with trauma in a healthy manner. Also, the paucity of resources in these communities prevents family members from getting the mental health treatment that they need, further inhibiting children in these families from developing healthy habits. Mental health treatment must be targeted towards entire families and not just in children with mood disorders in order to most effectively improve the mental health outcomes of those who grow up in these communities.

Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

BACKGROUND: Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). OBJECTIVES: To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. METHODS: In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. RESULTS: Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. CONCLUSIONS: Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy.

Medical Student Education in State Psychiatric Hospitals: A Survey of US State Hospitals.

OBJECTIVE: State hospitals may be underutilized in medical education. US state psychiatric hospitals were surveyed on current and potential psychiatry medical student education. METHODS: A 10-item questionnaire, with multiple response formats, was sent to identified hospitals in late 2012. RESULTS: Ninety-seven of 221 hospitals contacted responded. Fifty-three (55%) reported current medical student education programs, including 27 clinical clerkship rotations. Education and training in other disciplines was prevalent in hospitals both with and without medical students. The large majority of responders expressed enthusiasm about medical education. The most frequent reported barrier to new programs was geographic distance from the school. Limited resources were limiting factors for hospitals with and without current programs. CONCLUSIONS: Only a minority of US state hospitals may be involved in medical student education. While barriers such as geographic distance may be difficult to overcome, responses suggest opportunities for expanding medical education in the state psychiatric hospitals.

Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.

BACKGROUND: Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS). METHODS: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon ß-1a 44 µg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue-specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed. RESULTS: Interferon ß-1a 44 µg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume. CONCLUSIONS: These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon ß-1a 44 µg SC tiw, rather than disease-related tissue loss. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01085318.

Policies for Individuals With Autism: Gaps, Research, and Recommendations.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social, behavioral, and learning challenges. Individuals with autism and their families often struggle to get an appropriate diagnosis and continuation of specialty services, including general healthcare, mental health and transition services, special education, employment, and social and emotional support. This paper presents information about the current policies and support mechanisms that exist to help these individuals and their families. This paper identifies the gaps and recommends areas of improvement based on evidence-based research and current data. ASD is a lifelong disability without a cure, but by constructing robust policies and providing enhanced support, the quality of lives of those with ASD and their families can be improved.

Dynamic disability measures decrease the clinico-radiological gap in people with severely affected multiple sclerosis.

BACKGROUND: Expanded Disability Status Scale (EDSS) is limited when utilized in highly disabled people with multiple sclerosis (pwMS). OBJETIVE: To explore the relationship between disability measures and MRI outcomes in severely-affected pwMS. METHODS: PwMS recruited from The Boston Home (TBH), a specialized residential facility for severly-affected pwMS and University at Buffalo (UB) MS Center were assessed using EDSS, MS Severity Scale, age-related MSS, Scripps Neurological Rating Scale (SNRS) and Combinatorial Weight-Adjusted Disability Score (CombiWISE). In all scores except SNRS, higher score indicates greater disability. MRI measures of T1, T2-lesion volume (LV), whole brain, gray matter, medulla oblongata and thalamic volumes (WBV, GMV, MOV, TV) and thalamic dysconnectivity were obtained. RESULTS: Greatest disability differences between the TBH and UB pwMS were in SNRS (24.4 vs 71.9, p < 0.001, Cohen's d = 4.05) and CombiWISE (82.3 vs. 38.9, p < 0.001, Cohen's d = 4.02). In combined analysis of all pwMS, worse SNRS scores were correlated with worse MRI pathology in 8 out of 9 outcomes. EDSS only with 3 measures (GMV, MOV and TV). In severely-affected pwMS, SNRS was associated with T1-LV, T2-LV and WBV (not surviving false discovery rate (FDR) correction for multiple comparisons) whereas EDSS did not. CONCLUSION: Granular and dynamic disability measures may bridge the clinico-radiologcal gap present in severely affected pwMS.

Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.

BACKGROUND: A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0-6.5) community dwelling (CD) progressive pwMS, matched on age-, sex- and disease-duration (DDM). OBJECTIVES: To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS. METHODS: This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons. RESULTS: 42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS. CONCLUSIONS: The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.

Chronic cerebrospinal venous insufficiency is not associated with cognitive impairment in multiple sclerosis.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been reported in multiple sclerosis (MS) yet its significance in relation to cognitive function is undetermined.This study measured the association between the presence and severity of CCSVI and cognitive impairment in patients with MS. METHODS: CCSVI was assessed using extra-cranial and trans-cranial Doppler sonography in 109 MS patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with primary-progressive disease subtype). A subject was considered CCSVI-positive if ≥2 venous hemodynamic criteria were fulfilled. The Minimal Assessment of Cognitive Function in MS (MACFIMS) battery was administered assessing the full spectrum of cognitive domains known to be affected by MS. Depression was quantified using the Beck Depression Inventory Fast Screen (BDIFS). Partial correlations, analysis of variance (or covariance) and linear regression were used to examine the hypothesis that CCSVI status is related to cognition or depression after controlling for education and gender. RESULTS: There were 64 (58.7%) patients who were considered CCSVI-positive. The regression models predicting venous hemodynamic insufficiency severity score were not statistically significant for any of the MACFIMS predictor variables. The analysis of variance tests showed a significant effect of CCSVI-positive diagnosis on cognitive ability in only one of the 10 MACFIMS outcomes, and that one was in the opposite direction of the tested hypothesis. There was no correspondence between CCSVI diagnosis and depression, as measured by the BDIFS. CONCLUSIONS: We find no evidence of an association between the presence and severity of CCSVI with cognitive impairment and depression in patients with MS.

Changes of cine cerebrospinal fluid dynamics in patients with multiple sclerosis treated with percutaneous transluminal angioplasty: a case-control study.

PURPOSE: To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis. RESULTS: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group. CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

Comparison of intravascular ultrasound with conventional venography for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency.

PURPOSE: To investigate prevalence of extracranial abnormalities in azygos and internal jugular (IJ) veins using conventional venography and intravascular ultrasound (IVUS) in patients with multiple sclerosis (MS) being evaluated for chronic cerebrospinal venous insufficiency, a condition of vascular hemodynamic dysfunction. MATERIALS AND METHODS: PREMiSe (Prospective Randomized Endovascular therapy in Multiple Sclerosis) is a venous angioplasty study that enrolled 30 patients with relapsing MS. The patients fulfilled two or more venous hemodynamic extracranial Doppler sonography screening criteria. Phase I of the study included 10 patients and was planned to assess safety and standardize venography, IVUS, and angioplasty and blinding procedures; phase II enrolled 20 patients and further validated diagnostic assessments using the two invasive techniques. Venography was considered abnormal when ≥ 50% lumen-diameter restriction was detected. IVUS was considered abnormal when ≥ 50% lumen-diameter restriction, intraluminal defects, or reduced pulsatility was detected. RESULTS: No venography-related or IVUS-related complications, including vessel rupture, thrombosis, or side effects of contrast media were recorded among the 30 study patients. IVUS-detected venous abnormalities, including chronic, organized, thrombus-like inclusions were observed in 85% of azygos, 50% of right IJ, and 83.3% of left IJ veins, whereas venography demonstrated stenosis of ≥ 50% in 50% of azygos, 55% of right IJ, and 72% of left IJ veins. Sensitivity of venography for detecting IVUS abnormalities was 52.9%, 73.3%, and 80% for the azygos, left IJ, and right IJ veins, respectively. CONCLUSIONS: IVUS assessment of azygos and IJ veins showed a higher rate of venous abnormalities than venography. IVUS provides a diagnostic advantage over conventional venography in detecting extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency.

Multimodal noninvasive and invasive imaging of extracranial venous abnormalities indicative of CCSVI: results of the PREMiSe pilot study.

BACKGROUND: There is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a 'gold standard' or "benchmark" for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated the sensitivity and specificity of 2 invasive vs. 2 noninvasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS). METHODS: The data for this multimodal imaging comparison pilot study was collected in phase 2 of the "Prospective Randomized Endovascular therapy in Multiple Sclerosis" (PREMiSe) study using standardized imaging techniques. Thirty MS subjects were screened initially with Doppler sonography (DS), out of which 10 did not fulfill noninvasive screening procedure requirements on DS that consisted of ≥2 venous hemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS were enrolled into the multimodal diagnostic imaging study. For magnetic resonance venography (MRV), IJVs abnormal findings were considered absent or pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities of the VVs were determined only using non-invasive testing. Catheter venography (CV) was considered abnormal when ≥50% lumen restriction was detected, while intravascular ultrasound (IVUS) was considered abnormal when ≥50% restriction of the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive and invasive imaging modality comparisons between left, right and total IJVs and between the VVs and azygos vein were performed. Because there is no reliable way of non-invasively assessing the azygos vein, the VVs abnormalities detected by the non-invasive testing were compared to the azygos abnormalities detected by the invasive testing. All image modalities were analyzed in a blinded manner by more than one viewer, upon which consensus was reached. The sensitivity and specificity were calculated using contingency tables denoting the presence or absence of vein-specific abnormality findings between all imaging modalities used individually as the benchmark. RESULTS: The sensitivity of CV + IVUS was 68.4% for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs, compared to venous anomalies detected on DS. Compared to the venous anomalies detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9% and 11.8%, respectively. The sensitivity between the two invasive imaging techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for the azygos vein but the IVUS showed a higher rate of venous anomalies than the CV. There was excellent correspondence between identifying collateral veins on MRV and CV. CONCLUSIONS: Noninvasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for further multimodal invasive imaging testing of the IJVs. However, the noninvasive screening methods were inadequate to depict the total amount of azygos vein/VVs anomalies identified with invasive testing. This pilot study, with limited sample size, shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. However, lack of invasive testing on the study subjects whose results were negative on the DS screening and of healthy controls, limits further generalizibility of our findings. In addition, the findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients.

Abnormal subcortical deep-gray matter susceptibility-weighted imaging filtered phase measurements in patients with multiple sclerosis: a case-control study.

OBJECTIVE: To investigate abnormal phase on susceptibility-weighted imaging (SWI)-filtered phase images indicative of iron content, in subcortical deep-gray matter (SDGM) of multiple sclerosis (MS) patients and healthy controls (HC), and to explore its relationship with MRI outcomes. METHODS: 169 relapsing-remitting (RR) and 64 secondary-progressive (SP) MS patients, and 126 age- and sex-matched HC were imaged on a 3T scanner. Mean phase of the abnormal phase tissue (MP-APT), normal phase tissue volume (NPTV) and normalized volume were determined for total SDGM, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus of thalamus (PVN), hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. 63 HC were used for establishment of normal reference phase values, while additional 63 HC were used for blinded comparisons with MS patients. RESULTS: Increased MP-APT, decreased normalized volume and decreased NPTV were detected in total SDGM, caudate, putamen, globus pallidus, thalamus and PVN in MS patients compared to HC (p<.0004). MS patients also showed decreased volume in hippocampus (<.0001) and decreased NPTV in the hippocampus, amygdala and accumbens (<.0004). SPMS patients had increased MP-APT, decreased volume and decreased NPTV in total SDGM, caudate and amygdala compared to RRMS (p<.005), while individual measure differences were also detected in putamen, thalamus, hippocampus and accumbens (p<.006). RRMS patients showed a significant relationship between increased MP-APT and increased lesion burden and more advanced brain atrophy (p<.004). CONCLUSIONS: Abnormal phase, indicative of higher iron content was significantly increased in MS patients compared to HC, and was related to more severe lesion burden and brain atrophy.

Iron deposition in multiple sclerosis lesions measured by susceptibility-weighted imaging filtered phase: a case control study.

PURPOSE: To investigate phase lesions identified on susceptibility-weighted imaging (SWI)-filtered phase images in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS) and healthy controls (HC). To relate phase lesion characteristics to other clinical and MRI outcomes. MATERIALS AND METHODS: 95 relapsing-remitting (RR), 40 secondary-progressive (SP) MS patients, as well as 19 CIS patients and 49 age- and sex-matched HC, were scanned on a 3T scanner. Phase-, T1-, and T2-lesion characteristics were determined. Overlap of T1- and T2-weighted imaging (WI) lesions with phase lesions (T1P and T2P), as well as brain atrophy outcomes, was assessed. RESULTS: MS patients showed significantly greater numbers and larger volume of phase lesions, compared with HC (P < 0.001). 23.6% of T2 lesions overlapped with phase lesions, whereas the same figure for T1 lesions was 37.3%. Conversely, 33.4% and 69.7% of phase lesions were not visible on T2- or T1-WI, respectively. Phase, T1P and T2P lesions were not related to clinical outcomes, but phase lesions were related to ventricular enlargement. CONCLUSION: Phase lesions were present in both MS and CIS patients, and showed partial overlap with lesions observed using conventional MRI. The role of phase lesions in clinical progression remains unclear and should be further explored.

Cine cerebrospinal fluid imaging in multiple sclerosis.

PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. MATERIALS AND METHODS: In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age- and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes. RESULTS: Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 µL/beat, P = 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P = 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05). CONCLUSION: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the primary veins outside the skull that has been reported to be associated with MS. In the blinded Combined Transcranial (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) study, we found that prevalence of CCSVI was significantly higher in multiple sclerosis (MS) vs. healthy controls (HC) (56.1% vs. 22.7%, p < 0.001).The objective was to evaluate the clinical correlates of venous anomalies indicative of CCSVI in patients with MS. METHODS: The original study enrolled 499 subjects; 163 HC, 289 MS, 21 CIS and 26 subjects with other neurological disorders who underwent a clinical examination and a combined Doppler and TCD scan of the head and neck. This analysis was restricted to adult subjects with MS (RR-MS: n = 181, SP-MS: n = 80 and PP-MS: n = 12). Disability status was evaluated by using the Kurtzke Expanded Disability Status Scale (EDSS) and MS severity scale (MSSS). RESULTS: Disability was not associated with the presence (≥2 venous hemodynamic criteria) or the severity of CCSVI, as measured with venous hemodynamic insufficiency severity score (VHISS). However, the severity of CCSVI was associated with the increased brainstem functional EDSS sub-score (p = 0.002). In logistic regression analysis, progressive MS (SP-MS or PP-MS) vs. non-progressive status (including RR-MS) was associated with CCSVI diagnosis (p = 0.004, OR = 2.34, CI = 1.3-4.2). CONCLUSIONS: The presence and severity of CCVSI in multiple sclerosis correlate with disease status but has no or very limited association with clinical disability.

Comparison of standard 1.5 T vs. 3 T optimized protocols in patients treated with glatiramer acetate. A serial MRI pilot study.

This study explored the effect of glatiramer acetate (GA, 20 mg) on lesion activity using the 1.5 T standard MRI protocol (single dose gadolinium [Gd] and 5-min delay) or optimized 3 T protocol (triple dose of Gd, 20-min delay and application of an off-resonance saturated magnetization transfer pulse). A 15-month, phase IV, open-label, single-blinded, prospective, observational study included 12 patients with relapsing-remitting multiple sclerosis who underwent serial MRI scans (Days -45, -20, 0; the minus ign indicates the number of days before GA treatment; and on Days 30, 60, 90, 120, 150, 180, 270 and 360 during GA treatment) on 1.5 T and 3 T protocols. Cumulative number and volume of Gd enhancing (Gd-E) and T2 lesions were calculated. At Days -45 and 0, there were higher number (p < 0.01) and volume (p < 0.05) of Gd-E lesions on 3 T optimized compared to 1.5 T standard protocol. However, at 180 and 360 days of the study, no significant differences in total and cumulative number of new Gd-E and T 2 lesions were found between the two protocols. Compared to pre-treatment period, at Days 180 and 360 a significantly greater decrease in the cumulative number of Gd-E lesions (p = 0.03 and 0.021, respectively) was found using the 3 T vs. the 1.5 T protocol (p = NS for both time points). This MRI mechanistic study suggests that GA may exert a greater effect on decreasing lesion activity as measured on 3 T optimized compared to 1.5 T standard protocol.

Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects.

PURPOSE: To investigate the differences in the extracranial venous system in patients with multiple sclerosis (MS) and healthy control (HC) subjects by using magnetic resonance (MR) venography. MATERIALS AND METHODS: This HIPAA-compliant, prospective study was approved by the local institutional review board, and all participants gave informed consent. Fifty-seven patients, 41 (72%) with relapsing-remitting MS and 16 (28%) with secondary-progressive MS, and 21 HC subjects were imaged with a 3-T MR unit by using two-dimensional (2D) time-of-flight (TOF) and three-dimensional (3D) time-resolved imaging of contrast kinetics (TRICKS) sequences. In addition, six MS patients and six HC subjects underwent two sequential MR venographic examinations during 1 week to test image-reimage reproducibility. The morphologic features of internal jugular vein flow were classified as absent, pinpoint, flattened, crescentic, or ellipsoidal flow. Only absent and pinpoint flow were considered abnormal. The flow of the vertebral veins was classified as absent or present. The prominence of collateral neck veins and venous asymmetries between the left and right sides were assessed. Differences among groups were tested with a two-tailed Mann-Whitney two-sample rank-sum test. RESULTS: No significant differences in morphologic features of flow in the internal jugular veins and vertebral veins were found between MS patients and HC subjects in any of the examined MR venographic parameters. No differences in asymmetry or prominence were found between MS patients and HC subjects. There was modest agreement (κ = 0.67) between 2D TOF and 3D TRICKS sequences. Image-reimage reproducibility showed modest agreement (κ = 0.66) for 2D TOF and low agreement for 3D TRICKS (κ = 0.33). CONCLUSION: No significant differences in the extracranial venous systems between MS patients and HC subjects were detected by using MR venography. Standardized guidelines are needed to define parameters for the presence of venous anomalies.

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report.

BACKGROUND: Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI). METHODS: We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities. RESULTS: There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction. CONCLUSIONS: This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.