Jelena Dackovic

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.

Relationship between Damage to the Cerebellar Peduncles and Clinical Disability in Multiple Sclerosis

PURPOSE To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). MATERIALS AND METHODS This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. RESULTS Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P = .05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P = .03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P = .04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). CONCLUSION The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS.

Clinically Isolated Syndrome Suggestive of Multiple Sclerosis: Dynamic Patterns of Gray and White Matter Changes-A 2-year MR Imaging Study.

PURPOSE To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset. MATERIALS AND METHODS Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P < .001, uncorrected) and tract-based spatial statistics (P < .05, corrected). RESULTS At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months. CONCLUSION After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis.

Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5‐year study

In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five‐year follow‐up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual‐echo and 3D T1‐weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse‐onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor‐based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left‐lateralized pattern of GM and WM atrophy, involving deep GM, fronto‐temporo‐parieto‐occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017.

Gait pattern in patients with different multiple sclerosis phenotypes

BACKGROUND Gait pattern is frequently impaired in multiple sclerosis (MS), however gait characteristics in patients with different MS phenotypes have not been fully elucidated. METHODS We analyzed spatio-temporal gait pattern characteristics in patients with relapsing-remitting (RR, n=52) and primary-progressive (PP, n=18) MS in comparison with age-matched healthy controls (HC, n=40). All subjects performed a standardized simple walking task, a dual motor- motor task, a dual motor-mental task, and a triple combined motor-mental task at a GAITRite electronic walkway of 5.5m active area. We measured: cycle time (CT), stride length (SL), swing time (ST), double support time (DST), gait velocity (GV) and calculated symmetry index (SI) for CT, SL and ST. RESULTS With each task performed, CT and DST in the total MS group were significantly longer while SL was significantly shorter and GV significantly lower than in HC. ST was similar in the total MS patient group and HC. In both MS patients and HC, CT and DST increased and SL and GV decreased over repeated assessments. Dual and triple tasks while walking influenced walking performance in both MS patients and HC. Although patients with PPMS differed significantly from those with RRMS in the majority of gait parameters, the subgroup analysis in patients matched for age and disability (Expanded Disability Status Scale Score -EDSS, 3.0-5.0) showed similar gait performance in RRMS and PPMS patients having the same level of disability, except for CT and ST- symmetry parameters that were more impaired in the PPMS group. The EDSS score correlated significantly with CT, DST, SL and GV, but no significant correlation was found with ST except at the triple combined motor-mental task. CONCLUSION A disturbed gait pattern in MS patients with different MS phenotypes depends on disability and reflects a cognitive-motor interference.

Validation of the Serbian Version of Multiple Sclerosis Spasticity Scale 88 (MSSS-88)

Objective Multiple Sclerosis Spasticity Scale (MSSS)-88 has been developed for self-assessment of spasticity symptoms in patients with multiple sclerosis (MS). The objective of this study was to validate MSSS-88 and evaluate the psychometric properties in patients with MS in Serbia. Methods The study comprised 65 MS patients with spasticity. MSSS-88 consists of 88 items grouped in eight sections. Internal consistency of the MSSS-88SR subscales was determined using Cronbach’s alpha coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each MSSS-88SR subscale was performed. Clinical validity of MSSS-88SR was determined by correlations with the Numeric Rating Scale (NRS) and the Modified Ashworth Scale (MAS). Results The range of Cronbach’s alpha for all scales and ICC was 0.91–0.96 and 0.84–0.91, respectively. All ICCs were statistically significant (p<0.05). All evaluated subscales of MSSS-88 were significantly correlated with the NRS scale. The highest correlation coefficients were registered between the WL subscale and the EDSS and MAS, while the strongest relationship was observed between the MSS subscale and the NRS. Conclusion The Serbian translated version of this instrument may be useful as a clinical measure for spasticity and functionality in patients with MS.

Teaching NeuroImages: Reversible widespread brain MRI lesions in Marchiafava-Bignami disease

A 54-year-old woman with a history of alcoholism presented with stupor. Brain MRI disclosed extensive callosal and widespread extracallosal white matter and cortical lesions (figure) suggestive of Marchiafava-Bignami disease (MBD).1 After 4 weeks of treatment with thiamine and corticosteroids, a complete resolution of brain MRI lesions along with a good clinical recovery was observed.

Multidisciplinary rehabilitation and steroids in the management of multiple sclerosis relapses: a randomized controlled trial

Introduction Periodic relapses are one of the main characteristics of multiple sclerosis (MS), from which recovery is often incomplete despite high-dose methylprednisolone (HDMP) treatment. The aim of our study was to evaluate the potential benefits of short-term HDMP combined with multidisciplinary rehabilitation (MDR) in persons with MS in relapse in order to assess whether combination of steroid therapy with MDR is more beneficial than steroid therapy alone. Material and methods This investigation was conducted as a randomized controlled trial. The MS patients were eligible if they had an established diagnosis and relapse requiring application of HDMP. Forty-nine patients were included in the study and randomized to control and treatment groups, and 37 completed the study. High-dose methylprednisolone was administered to all patients. The treatment group additionally underwent an MDR program over a 3-week period. All outcome measures were completed at baseline and 1 and 3 months later. Results The Expanded Disability Status Scale (EDSS) and Functional Independence Measure (FIM) motor scores improved statistically significantly 1 month after HDMP, in both treatment and control groups. During the study period, in the treatment group, a sustained large effect size (ES) was found for both physical and mental composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54), while in the controls, a sustained moderate ES was demonstrated only for physical composite score. Conclusions Our findings suggest that MDR improves MS relapse outcome.

Validity and reliability of the Serbian version of Patient-Reported Impact of Spasticity Measure in multiple sclerosis.

The Patient-Reported Impact of Spasticity Measure (PRISM) has been developed recently to assess the impact of spasticity on quality of life after spinal cord injury. Although PRISM may also be useful in patients with multiple sclerosis (MS), its psychometric properties in MS have not been established and PRISM is currently available only in English. The aims of this cross-sectional study were to translate PRISM into the Serbian language (PRISMSR) and examine its validity (construct, convergent, divergent) and reliability (internal consistency, test–retest reliability) in 48 patients with spasticity because of MS diagnosed at least 1 year earlier and in remission at least 3 months. PRISMSR was administered twice 3 days apart. The validity of seven PRISMSR subscales was examined against the Modified Ashworth Scale (MAS), the Numerical Rating Scale (NRS) for spasticity, sex, and education. Internal consistency was assessed with Cronbach &agr; and test–retest reliability with intraclass correlation coefficient for agreement (ICC2,1). During the forward–backward translation, only one PRISM item required minor cultural adaption. Almost all PRISMSR scores correlated significantly with MAS and NRS scores (r=0.29–0.51, 0.001⩽P⩽0.043). They were all significantly higher for MAS≥2 group versus the MAS<2 group (0.003⩽P⩽0.035) and for the NRS≥7 group versus the NRS<7 group (0.001⩽P⩽0.042), except for the Social Embarrassment subscale (P=0.083). The PRISMSR scores were not significantly different between sexes (P≥0.104) or those with high school versus college degree (P≥0.139). Both Cronbach &agr; (0.78–0.93) and test–retest ICC2,1 (0.82–0.90) were high. The original PRISM may be translated successfully into other languages. PRISMSR shows adequate validity and reliability for assessing the impact of spasticity on quality of life in patients with MS.

Dynamic volumetric changes of hippocampal subfields in clinically isolated syndrome patients: A 2-year MRI study

Background: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. Objective: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. Methods: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. Results: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. Conclusion: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions.