Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

The computer-based Symbol Digit Modalities Test: establishing age-expected performance in healthy controls and evaluation of pediatric MS patients.

Decreased information processing speed (IPS) is frequently reported in pediatric multiple sclerosis (MS) patients. The computerized version of the Symbol Digit Modalities Test (c-SDMT) measures IPS over eight consecutive trials per session and additionally captures changes in performance within the session. Here, we establish normative c-SDMT performance and test-retest reliability in healthy children (HC) and explore differences in the overall c-SDMT-performance between HC and MS patients. This cross-sectional study included 478 HC (237 female, 49.5%) divided into five age groups (2 years each), and 27 MS patients (22 female, 81.5%) aged 8-18 years. The average time to complete the c-SDMT increased with age (|r| 0.70, 95% CI -0.74, -0.64). Test-retest reliability was high (ICC = 0.91) in HC. The total time to complete the c-SDMT did not differ between children with MS and sex- and age- matched HC (p = 0.23). However, MS patients were less likely to show faster performance across all the successive eight trials compared to HC (p = 0.0001). Healthy children demonstrate faster IPS with increasing age, as well as during successive trials of the c-SDMT. The inability of pediatric MS patients to maintain the increase in processing speed over successive trials suggests a reduced capacity for procedural learning, possibly resulting from cognitive fatigue.

Suicidal Ideation After Mild Traumatic Brain Injury: A Consecutive Canadian Sample.

This study aims to elucidate psychosocial and injury features contributing to SI following concussion or mild traumatic brain injury (mTBI) and the time course for its development. Between 1998 and 2012, a sample of 871 patients referred to a follow-up clinic after concussion treatment in an urban tertiary care ED were consecutively offered enrollment at 3 months post injury. Data from psychiatric and social-demographic assessments were consecutively collected at 2 visits (3 and 6 months after injury) respectively. Chi-square and t-tests were performed to identify associations between variables related with SI. Logistic regression analysis was performed to identify factors independently associated. During the enrolment period, 2,296 patients with mTBI presented to the ED. 871 adults completed psychiatric and social demographic clinic assessments at 3 months, and 500 returned at 6 months. Suicidal ideation was expressed by 6.3% at 3 months and 8.2% at 6 months. Regression models showed SI independently associated with: speaking English as a second language (ESL) and injury mechanism (MVC passenger) at 3 and 6 months; and history of depression and marital status at 3 months only. SI is common 3 months after mTBI, and appears more at 6 month follow up. These findings suggest earlier screening for predisposing factors and closer monitoring of those at risk for suicidality.

Comparison of Quantitative Cerebral Blood Flow Measurements Performed by Bookend Dynamic Susceptibility Contrast and Arterial Spin-Labeling MRI in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative CBF usage as a biomarker for cognitive impairment and disease progression in MS is potentially a powerful tool for longitudinal patient monitoring. Dynamic susceptibility contrast perfusion with bookend T1-calibration (bookend technique) and pseudocontinuous arterial spin-labeling have recently been used for CBF quantification in relapsing-remitting MS. The noninvasive nature of pseudocontinuous arterial spin-labeling is advantageous over gadolinium-based techniques, but correlation between the techniques is not well-established in the context of MS. MATERIALS AND METHODS: We compared pseudocontinuous arterial spin-labeling CBF with the bookend technique in a prospective cohort of 19 healthy controls, 19 subjects with relapsing-remitting MS without cognitive impairment, and 20 subjects with relapsing-remitting MS with cognitive impairment on a voxelwise and Brodmann region basis. The linear Pearson correlation, SNR, and coefficient of variation were quantified. RESULTS: Voxelwise paired t tests revealed no significant CBF differences between techniques after normalization of global mean intensities. The highest Pearson correlations were observed in deep GM structures (average r = 0.71 for the basal ganglia and r = 0.65 for the thalamus) but remained robust for cortical GM, WM, and white matter lesions (average r = 0.51, 0.53, 0.54, respectively). Lower Pearson correlations were observed for cortical lesions (average r = 0.23). Brodmann region correlations were significant for all groups. All correlations were maintained in healthy controls and in patients with relapsing-remitting multiple sclerosis. The highest SNR was present in bookend perfusion, while the highest coefficient of variation was present in white matter lesions. CONCLUSIONS: Agreement between pseudocontinuous arterial spin-labeling and bookend technique CBF measurements is demonstrated in healthy controls and patients with relapsing-remitting MS.

Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline.

BACKGROUND AND PURPOSE: Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in patients with MS, contributing to cognitive impairment. We sought to localize perfusion distribution differences in patients with relapsing-remitting MS with and without cognitive impairment and healthy controls. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS (20 cognitively impaired, 19 nonimpaired) and 19 age- and sex-matched healthy controls underwent a neurocognitive battery and MR imaging. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. RESULTS: After we adjusted for localized volumetric differences in the right frontal, temporal, and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for patients with cognitive impairment compared with patients without impairment and controls. Compared with healthy controls, reduced CBF was present in the limbic regions of patients with cognitive impairment, and reduced CBV was present in the right middle frontal gyrus in patients with cognitive impairment and in the temporal gyrus of relapsing-remitting MS patients without cognitive impairment. CONCLUSIONS: Consistent regional frontal cortical perfusion deficits are present in patients with relapsing-remitting MS, with more widespread hypoperfusion in those with cognitive impairment, independent of structural differences, indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS.

Cortical Perfusion Alteration in Normal-Appearing Gray Matter Is Most Sensitive to Disease Progression in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: The role of gray matter in multiple sclerosis is increasingly evident; however, conventional images demonstrate limitations in cortical lesion identification. Perfusion imaging appears sensitive to changes in tissue type and disease severity in MS. We sought to use bookend perfusion to quantify parameters in healthy controls and normal-appearing and lesional tissue at different relapsing-remitting MS stages. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS and 19 age-matched healthy controls were prospectively recruited. The Minimal Assessment of Cognitive Function in MS battery was used to assess cognitive performance. Perfusion parameters, including cerebral blood flow and volume and mean transit time, were compared for healthy controls and normal-appearing and lesional tissue for all study groups. Dispersion of perfusion measures for white matter lesions and cortical lesions was assessed. RESULTS: Twenty of the 39 patients with relapsing-remitting MS were cognitively impaired. Significant differences were displayed between all relapsing-remitting MS subgroups and healthy controls in all comparisons except for normal-appearing gray matter CBV between healthy controls and unimpaired patients with relapsing-remitting MS and for all normal-appearing white matter perfusion parameters between healthy controls and unimpaired patients with relapsing-remitting MS. White matter lesion but not cortical lesion perfusion was significantly reduced in cognitively impaired patients with relapsing-remitting MS versus unimpaired patients with relapsing-remitting MS. Perfusion reduction with disease progression was greater in normal-appearing gray matter and normal-appearing white matter compared with cortical lesions and white matter lesions. Smaller dispersion was observed for cortical lesions compared with white matter lesions for each perfusion parameter. CONCLUSIONS: Quantitative GM and WM analysis demonstrated significant but disproportionate white matter lesion, cortical lesion, normal-appearing white matter, and normal-appearing gray matter changes present between healthy controls and patients with relapsing-remitting MS with and without cognitive impairment, necessitating absolute rather than relative lesion perfusion measurement.

Extensive white matter dysfunction in cognitively impaired patients with secondary-progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. MATERIALS AND METHODS: Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. RESULTS: Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (p(corr) < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (p(corr) > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. CONCLUSIONS: Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.

Detecting cognitive dysfunction in a busy multiple sclerosis clinical setting: a computer generated approach.

BACKGROUND AND PURPOSE: This study aims to explore the effectiveness of a brief, computerized battery of tests in detecting cognitive differences between clinically isolated syndromes (CIS), relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) patients. METHODS: Four groups of patients between the ages of 18 and 63 were enrolled from two hospital-based multiple sclerosis clinics: CIS (n = 42), RRMS (n = 44), PPMS (n = 15) and SPMS (n = 37). All subjects were administered a validated battery of five computerized cognitive tests: the STROOP Color-Word Test, the Computerized Symbol Digit Modalities Test, the Paced Visual Serial Addition Test (PVSAT) 4 s and 2 s trials, and a speed of cognition index obtained by subtracting simple reaction time from choice reaction time. Results were recorded by the test administrator. RESULTS: Significant between-group differences in cognition were evident on all tests (P < 0.01) with the exception of the PVSAT 2 s trial. CIS patients were the least impaired, SPMS the most. RRMS and PPMS patients generally had a similar cognitive profile, more impaired than the CIS patients but less so than the SPMS patients. These differences persisted after controlling for the effects of age and education. CONCLUSIONS: The ability of this computerized cognitive battery to distinguish the progression of cognitive deficits across the entire multiple sclerosis disease spectrum from CIS through to SPMS enhances its construct validity. This finding, coupled with the battery's brevity (20 min) and ease of administration, highlights its potential utility in a busy clinic setting.

Normal-appearing white matter permeability distinguishes poor cognitive performance in processing speed and working memory.

BACKGROUND AND PURPOSE: Secondary-progressive MS is characterized by reduced acute inflammation and contrast enhancement but with increased axonal degeneration and cognitive/clinical disability that worsens with advanced disease. Relative recirculation, extracted from DSC is a surrogate measure of BBB integrity. We hypothesized that normal-appearing white matter relative recirculation is reduced in cognitively impaired compared with nonimpaired secondary-progressive MS, reflecting more advanced disease. MATERIALS AND METHODS: Cognitive performance was classified as impaired or nonimpaired by use of Minimal Assessment of Cognitive Function In MS test components. Demographic data, brain parenchymal fraction, WM lesion fraction, and weighted mean normal-appearing white matter relative recirculation were compared in cognitively dichotomized groups. Univariate and multivariate logistic regressions were used to study the association between cognitive test results and normal-appearing white matter relative recirculation. RESULTS: The mean (SD) age of 36 patients with secondary-progressive MS studied was 55.9 ± 9.3 years; 13 of 36 (36%) patients were male. A highly significant difference between normal-appearing white matter relative recirculation and WM lesion relative recirculation was present for all patients (P < .001). Normal-appearing white matter relative recirculation in impaired patients was significantly lower than in nonimpaired subjects for the Symbol Digit Modalities Test (P = .007), Controlled Word Association Test (P = .008), and Paced Auditory Serial Addition Test (P = .024). The Expanded Disability Status Scale demonstrated an inverse correlation with normal-appearing white matter relative recirculation (r = -0.319, P = .075). After adjustment for confounders, significant normal-appearing white matter relative recirculation reduction persisted for the Symbol Digit Modalities Test (P = .023) and the Paced Auditory Serial Addition Test (P = .047) but not for the Controlled Word Association Test (P = .13) in impaired patients. CONCLUSIONS: Significant normal-appearing white matter relative recirculation reduction exists in cognitively impaired patients with secondary-progressive MS, localizing to the domains of processing speed and working memory.

Cognitive and neuropsychiatric disease manifestations in MS.

Multiple sclerosis is associated with a wide array of behavioral problems. This brief overview begins with a summary of the pathophysiology and treatment of MS. Thereafter, sections are devoted to psychiatric syndromes and cognitive decline linked to MS. The immune basis and brain imaging data associated with these changes are subsequently reviewed. The frequency and severity of these changes in mentation highlight the point that MS patients should, as part of their routine care, have access to psychiatrists, neuropsychologists and allied mental health specialists.

Robust perfusion deficits in cognitively impaired patients with secondary-progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the impact of cerebral perfusion and brain and lesion volumetry on cognitive performance in 45 patients with SPMS by using MR imaging. MATERIALS AND METHODS: Cognition was assessed by using a standard battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. qCBF and qCBV maps were analyzed by using SPM and PLS. SPM was also used to conduct the GM, WM, and WML volumetric analyses. RESULTS: Both SPM and PLS demonstrated significantly reduced qCBV in the superior medial frontal cortex of impaired patients. PLS also revealed significantly lower qCBV in the bilateral thalami and caudate nuclei of impaired patients and identified a pattern of significantly attenuated qCBF similar to that of qCBV. Performance on the Symbol Digit Modalities Test, which assesses information-processing speed, correlated most strongly overall with cerebral perfusion. Focal (ie, voxelwise) analyses of GM, WM, and WML volume revealed no significant differences between patients with and without cognitive impairment, though global GM volume was significantly decreased and global WML volume was significantly increased in impaired patients. CONCLUSIONS: These results suggest that cognitively impaired patients with SPMS exhibit robust perfusion deficits in cortical and subcortical GM and impaired processing speed.

Decreased frontal lobe gray matter perfusion in cognitively impaired patients with secondary-progressive multiple sclerosis detected by the bookend technique.

BACKGROUND AND PURPOSE: There is increasing evidence implicating microvascular impairment in MS pathogenesis. Perfusion imaging offers a unique opportunity to investigate the functional impact of GM pathology. We sought to quantify differences in MR imaging-based bookend-derived cerebral perfusion between cognitively impaired and nonimpaired patients with SPMS. MATERIALS AND METHODS: Patients were prospectively recruited and assessed using MR imaging and the standard cognitive battery called the Minimal Assessment of Cognitive Function in MS. Patients exhibiting impairment on ≥ 2 individual tests were classified as cognitively impaired. Healthy controls were prospectively recruited and assessed using MR imaging to validate bookend assumptions. Structural and perfusion scans were coregistered and partitioned into anatomic brain regions and tissue compartments. Clinical and radiologic characteristics were compared between patients with and without impairment to identify potential confounders. A Bonferroni adjusted P value threshold (P < .005) was used for lobar and sublobar level analyses to correct for multiple comparisons. RESULTS: Thirty-seven patients with SPMS (age 56 ± 9 years; 23 women, 14 men) and 10 age- and sex-matched healthy controls were recruited. Bookend assumptions were found to be valid in MS. GM and WM qCBV were all globally reduced in impaired patients. After adjusting for potential confounders while examining sublobar level perfusion, only GM qCBV was significantly different between cognitive groups, and this hypoperfusion localized to the bilateral medial superior frontal regions and left inferior, middle, and superior frontal regions (P < .005) of impaired patients compared with nonimpaired patients. GM qCBV accounted for 22.5% of the model variance compared with a model including only confounders (P = .0007). CONCLUSIONS: Bookend-derived GM qCBV was significantly reduced in cognitively impaired patients with SPMS in functionally relevant brain regions.

Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

APOE epsilon4 and the cognitive genetics of multiple sclerosis.

BACKGROUND: Evidence linking APOE to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggests that it may be relevant in multiple sclerosis (MS). The purpose of this study was to determine whether the epsilon4 allele of APOE is associated with cognitive deficits in patients with MS. METHOD: Using a case-control design, 50 patients with MS with the epsilon4 allele (epsilon4+) and 50 epsilon4-negative (epsilon4-) patients with MS were tested using a comprehensive battery of tests evaluating the cognitive domains most often affected in MS. RESULTS: The epsilon4+ and epsilon4- patients with MS were well-matched with respect to demographic variables (age, gender, ethnicity, education, employment status, premorbid IQ) and disease variables (disease course, disease duration, Expanded Disability Status Scale, 25-foot timed walk, 9-hole pegboard test). In addition, the groups were similar in depressive symptoms, in the proportion of patients receiving disease-modifying therapy, and in carriage of the APOE epsilon2 allele. Results showed that none of the 11 cognitive outcome variables differed between epsilon4+ and epsilon4- patients with MS. Cognitive measures were also unrelated to epsilon4 interactions with age and gender. The incidence of overall cognitive dysfunction did not differ between epsilon4+ and epsilon4- groups, nor did failure on any test, and epsilon4 carriage was not a significant predictor of any adverse cognitive outcome. These negative results endured with the exclusion of epsilon2+ subjects from the analyses. CONCLUSION: This study does not support a role for the epsilon4 allele in cognitive dysfunction in multiple sclerosis.

Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients.

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory > or = 19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.

An open-label study of citalopram for major depression following traumatic brain injury.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti-depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of < or =7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.

Anxiety disorders and their clinical correlates in multiple sclerosis patients.

OBJECTIVE: To assess prevalence rates and clinical correlates of anxiety disorders in patients with multiple sclerosis (MS). METHODS: Demographic and neurological data were collected on 140 consecutive clinic attendees, and their lifetime and point prevalences of anxiety disorders were determined with the Structured Clinical Interview for DSM-IV disorders (SCID-IV). All subjects completed the self-report Hospital Anxiety and Depression Scale (HADS). Suicidal intent was rated with the Beck Suicide Scale (BSS), psychosocial stressors and supports were quantified with Social Stress and Support Interview (SSSI), and cognition assessed with Neuropsychological Screening Battery for MS. RESULTS: The lifetime prevalence of any anxiety disorder was 35.7%, with panic disorder (10%), obsessive compulsive disorder (8.6%), and generalized anxiety disorder (18.6%), the most common diagnoses obtained. Subjects with an anxiety disorder were more likely to be female, have a history of depression, drink to excess, report higher social stress and have contemplated suicide. The diagnosis of an anxiety disorder had been missed in the majority of subjects, therefore, they had not received treatment. A discriminant function analysis identified a series of variables that correctly classified 75% of patients with an anxiety disorder. CONCLUSION: Anxiety disorders are common in patients with MS, but are frequently overlooked and under-treated. Risk factors include being female, a co-morbid diagnosis of depression, and limited social support. Clinicians should evaluate all MS subjects for anxiety disorders, as they represent a treatable cause of disability in MS.

Semiautomatic brain region extraction: a method of parcellating brain regions from structural magnetic resonance images.

Structural MR imaging has become essential to the evaluation of regional brain changes in both healthy aging and disease-related processes. Several methods have been developed to measure structure size and regional brain volumes, but many of these methods involve substantial manual tracing and/or landmark identification. We present a new technique, semiautomatic brain region extraction (SABRE), for the rapid and reliable parcellation of cortical and subcortical brain regions. We combine the SABRE parcellation with tissue compartment segmentation [NeuroImage 17 (2002) 1087] to produce measures of gray matter (GM), white matter (WM), ventricular CSF, and sulcal CSF for 26 brain regions. Because SABRE restricts user input to a few easily identified landmarks, inter-rater reliability is high for all volumes, with all coefficients between 0.91 and 0.99. To assess construct validity, we contrasted SABRE-derived volumetric data from healthy young and older adults. Results from the SABRE parcellation and tissue segmentation showed significant differences in multiple brain regions in keeping with regional atrophy described in the literature by researchers using lengthy manual tracing methods. Our findings show that SABRE is a reliable semiautomatic method for assessing regional tissue volumes that provides significant timesavings over purely manual methods, yet maintains information about individual cortical landmarks.