B. Weinstock-Guttman

Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis

Introduction: The Beck Depression Inventory-Fast Screen (BDI-FS) is a brief self-report inventory designed to evaluate depression in patients with medical illness. A s depressive disorder is especially prominent in multiple sclerosis (MS), a cost-effective procedure for identifying depressive disorder in MS is sorely needed. The BDI-FS may be useful in this regard although, to date, its validity in MS patients has not been assessed. Methods: Fifty-four consecutive MS patients were studied. A ll underwent psychological assessment, which included the BDI-FS and other self-report measures of depression. Forty-eight caregiver/informants were interviewed using the Neuorpsychiatric Inventory (NPI). Retrospective chart reviews were conducted by a single trained research assistant, blind to the results of psychological testing and interviews, to determine if antidepressant medications had been prescribed. Results: The BDI-FS was significantly correlated with other self-report measures of depression (P B-0.001) and with informant reported dysphoria (P B-0.01), In addition, BDI-FS scores discriminated MS patients undergoing treatment for depressive disorder from untreated MS patients (P =0.01). Conclusion: These data support the concurrent and discriminative validity of the BDI-FS in MS. A s the test is brief and not confounded with neurological symptoms, it is recommended for depression screening in this population.

Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS

Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: 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.

Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18–59 years, clinically definite multiple sclerosis (MS), and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participants impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinicians impression of memory change. Results: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinicians impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. Conclusions: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. Classification of evidence: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average.

Subjective fatigue is not associated with cognitive impairment in multiple sclerosis: cross-sectional and longitudinal analysis

Background Studies in multiple sclerosis (MS) report conflicting conclusions regarding fatigue and cognition, which may partly be due to the use of small sample sizes and frequent reliance on a cross-sectional approach. Objective The ability to distinguish between these two disabling symptoms is necessary in order to properly assess and treat MS patients. Methods In a retrospective analysis, we assessed the correlation between fatigue and neuropsychological (NP) testing using a cross-sectional (n = 465) and longitudinal approach (n = 69). Cognition was measured using a comprehensive battery called the Minimal Assessment of Cognitive Function in MS (MACFIMS), and fatigue was measured with the Fatigue Severity Scale (FSS). FSS scores were categorized as normal (≤4.0), borderline fatigue (4 < FSS < 5.0), and fatigued (≥5.0). Repeat assessments (n = 69) were categorized as improved or worsened by a change in FSS of either 0.5 or 1.0. Results MS patients had significantly higher FSS scores than normal controls (P < 0.001). No correlation was found between FSS and NP scores in either cross-sectional or longitudinal analyses. Fatigue was moderately correlated with depression, assessed using the Beck Depression Inventory Fast Screen (BDIFS) (r = 0.44, P < 0.001). Longitudinally, there was a medium correlation between change in FSS and BDIFS (r = 0.34, P = 0.001), but no significant differences on NP scores using either definition of change. Conclusion We conclude that self-reported fatigue, while correlated with self-reported depression, is not significantly related to cognitive capacity in MS.

Intra- and extraluminal structural and functional venous anomalies in multiple sclerosis, as evidenced by 2 noninvasive imaging techniques.

Here is another article that should add to the controversy over the relationship between MS and venous anomalies. The authors assessed the utility of sonography and MRV (2 different techniques) for detecting intra- and extraluminal venous abnormalities in 150 patients with MS and 63 matched controls. Results were as follows: patients with MS had significantly more intraluminal and structural abnormalities than controls and patients with progressive MS had more extraluminal and flow abnormalities than those with nonprogressive disease. BACKGROUND AND PURPOSE: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the main extracranial cerebrospinal venous routes that interfere with normal venous outflow. Research into CCSVI will determine its sensitivity and specificity for a diagnosis of MS, its prevalence in MS patients, and its clinical, MRI, and genetic correlates. Our aim was to investigate the prevalence and number of intra- and extraluminal structural and functional extracranial venous abnormalities by using DS and MRV, in patients with MS and HCs. MATERIALS AND METHODS: One hundred fifty patients with MS, 104 (69.3%) with RR and 46 (30.7%) with a progressive MS course, and 63 age- and sex-matched HCs were scanned with 3T MR imaging by using TOF and TRICKS sequences (only patients with MS). All subjects underwent DS examination for intra- and extraluminal structural and functional abnormalities of the IJVs. Absent/pinpoint IJV flow morphology on MRV was considered an abnormal finding. Prominence of collateral extracranial veins was assessed with MRV. RESULTS: Patients with MS had a significantly higher number of functional (P < .0001), total (P = .001), and intraluminal (P = .005) structural IJV DS abnormalities than HCs. There was a trend for more patients with MS with extraluminal IJV DS abnormalities (P = .023). No significant differences were found on the MRV IJV flow morphology scale between patients with MS and HCs. Patients with progressive MS showed more extraluminal IJV DS abnormalities (P = .01) and more MRV flow abnormalities on TOF (P = .006) and TRICKS (P = .01) than patients with nonprogressive MS. There was a trend for a higher number of collateral veins in patients with MS than in HCs (P = .016). CONCLUSIONS: DS is more sensitive than MRV in detecting intraluminal structural and functional venous abnormalities in patients with MS compared with HCs, whereas MRV is more sensitive in showing collaterals.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset

Purpose To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases. Methods This is a cross-sectional study of patients seen between 2006–2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed. All children received OCT testing and assessment of visual acuity (VA) using Snellen and low contrast letter acuity (LCLA) charts. Results Thirty-eight children diagnosed with acquired demyelinating disease, 15 healthy controls, and five children with other neurological disorders (OND) were included. Average RNFLT in healthy controls was 107 ± 12 μm(n = 30) versus 108 ± 5 μm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT ± SD was 99 ± 14 μm in unaffected (n = 24) versus 83 ± 12 μmin eyes affected by optic neuritis (“affected eyes”) (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 ± 15 μm in unaffected (n = 18) versus 67 ± 17 μm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT ± SD was 97 ± 13 μm in unaffected (n = 5) versus 89 ± 12 μm in affected eyes (n = 9). Differences between children with demyelinating disease and controls and between ON and nonON eyes were statistically significant (P < 0.001). Bivariate correlations of RNFLT with LCLA (P = 0.002) and VA (P < 0.001) were significant. Conclusions OCT may be a valuable tool for the assessment and monitoring of anterior optic pathway dysfunction in children with demyelinating diseases.

Voxel-wise magnetization transfer imaging study of effects of natalizumab and IFNβ-1a in multiple sclerosis:

Objective: To determine the effects of intravenous natalizumab and intramuscular interferon beta-1a (IFNβ-1a) on the volume of white-matter (WM) lesions and normal appearing brain tissue (NABT) undergoing voxel-wise (VW) increases in magnetization transfer ratio (MTR) suggestive of remyelination in patients with relapsing multiple sclerosis. Methods: This prospective, open-label, single-blinded study enrolled patients with relapsing–remitting multiple sclerosis (RRMS) and relapsing secondary progressive multiple sclerosis (RSPMS) as well as a group of age/sex-matched healthy controls (n=22). Patients with multiple sclerosis were assigned to receive natalizumab monotherapy (n=77; RRMS/RSPMS) or intramuscular IFNβ-1a (n=26) as either monotherapy (RRMS) or combined with pulsed i.v. methylprednisolone, as needed (RSPMS). The primary endpoint was the two-year change in volume of NABT VWMTR, by quantifying the number of voxels that increased (suggesting remyelination) or decreased (suggesting demyelination) in their MTR value. Results: The volume of tissue undergoing increases in VWMTR was significantly larger in natalizumab compared with IFNβ-1a-treated patients (year 1: p=0.001 in NABT and p<0.006 in WM lesions; year 2: p=0.008 in NABT) and compared with healthy control subjects (year 1: p=0.05 and year 2: p=0.007 in NABT). The larger volume within NABT undergoing decreases in VWMTR was detected in multiple sclerosis patients compared with healthy controls (p<0.001), and in the IFNβ-1a group compared with the natalizumab group (year 1: p=0.05; year 2: p=0.002). One patient on natalizumab died from progressive multifocal leukoencephalopathy eight months after completing the study. Conclusion: Natalizumab may promote remyelination and stabilize demyelination in lesions and NABT in relapsing multiple sclerosis, compared with intramuscular IFNβ-1a.

Prevalence of Radiologically Isolated Syndrome and White Matter Signal Abnormalities in Healthy Relatives of Patients with Multiple Sclerosis

Healthy individuals who either had no relatives with multiple sclerosis or had a family history of it were studied and evaluated according the Okuda and Swanton criteria for radiologically isolated syndrome. These investigators found that the frequency of white matter signal abnormalities and radiologically isolated syndrome were higher in the healthy relatives of patients with multiple sclerosis compared with nonfamilial healthy control subjects. In healthy relatives of patients with MS, smoking and obesity also contributed to the presence of white matter lesions. BACKGROUND AND PURPOSE: The exact prevalence of WM signal abnormalities in healthy relatives of MS patients and their impact on disease development has not been fully elucidated. The purpose of this study was to compare WM signal abnormality characteristics and the prevalence of radiologically isolated syndrome in healthy control subjects selected randomly from the population with the healthy relatives of patients with MS. MATERIALS AND METHODS: Healthy control subjects (n = 150) underwent physical and 3T MR imaging examinations. Healthy control subjects were classified as non-familial healthy control subjects (n = 82) if they had no family history of MS or as healthy relatives of patients with MS (n = 68) if they had ≥1 relative affected with MS. The presence of radiologically isolated syndrome was evaluated according to the Okuda criteria; dissemination in space on MR imaging and fulfillment of radiologically isolated syndrome criteria were also evaluated according to Swanton criteria. RESULTS: There was a significantly higher total volume of WM signal abnormality in the healthy relatives of patients with MS compared with the non-familial healthy control subjects (P = .024 for signal abnormality ≥3 mm in size and P = .025 for all sizes). Periventricular localization and the number of lesions in all groups (P = .034 and P = .043) were significantly higher in the healthy relatives of patients with MS; 8.8% of the healthy relatives of patients with MS and 4.9% of non-familial healthy control subjects showed ≥9 WM signal abnormalities; 2.9% of subjects in the healthy relatives of patients with MS group and 2.4% of non-familial healthy control subjects fulfilled radiologically isolated syndrome according to the Okuda criteria, whereas 10.3% and 3.7% of subjects fulfilled radiologically isolated syndrome according to the Swanton criteria. In the healthy relatives of patients with MS, smoking was associated with the presence of WM signal abnormalities, whereas obesity was related to the presence of ≥9 WM signal abnormalities and to fulfillment of radiologically isolated syndrome according to the Swanton criteria. CONCLUSIONS: The frequency of WM signal abnormalities and radiologically isolated syndrome is higher in the healthy relatives of patients with multiple sclerosis patients compared with non-familial healthy control subjects.

Gray matter SWI-filtered phase and atrophy are linked to disability in MS

The association between clinical outcomes and abnormal susceptibility-weighted imaging (SWI)-filtered phase, indicative of increased iron content, as well as atrophy, was investigated in the subcortical deep-gray matter (SDGM) of multiple sclerosis (MS) patients. 149 relapsing-remitting (RR) and 61 secondary-progressive (SP) MS patients underwent SWI on a 3T scanner. Mean phase of the abnormal phase tissue (MP-APT) and normalized volumes were determined for the total and region-specific SDGM structures. In an age- and gender-adjusted regression model, total SDGM volume was the strongest predictor of Expanded Disability Status Scale (EDSS) (beta = -.224, p<.001), followed by total SDGM MP-APT (beta = -.168, p <.019). This model accounted for 30.4% of the variance in EDSS. Only SDGM MP-APT added additional variance in predicting EDSS, compared to conventional MRI metrics. Caudate and red nucleus MP-APT and amygdala volume were associated with EDSS. Our findings suggest that disability in MS patients is associated better with SDGM pathology, as indicated by increased iron content and atrophy, than with lesion burden or white matter and cortical volumes.

Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis

BackgroundChronic 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.MethodsThe 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).ResultsDisability 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).ConclusionsThe presence and severity of CCVSI in multiple sclerosis correlate with disease status but has no or very limited association with clinical disability.