Thursday, 3 September 2015

ResearchSpeak: brain plasticity in early MS

Is MS shredding your reserve capacity? #ResearchSpeak #MSBlog

"What protects MSers from noticing cognitive and physical impairments early in the course of their disease are compensatory mechanisms that adjust for the damage that has already accumulated from MS. The ability to compensate is dependent on so called brain, or neuronal, reserve. With increasing damage the reserve capacity gets exhausted and MSers then notice their disabilities and enter the clinically-apparent progressive phase of the disease. Using reserve systems to compensate for damage does come with a downside, characteristically cognitive fatigue."

"The neurophysiological study below shows that MSers are using reserve systems to complete a cognitive task called the auditory oddball task. The oddball task is an experimental design used within event-related potential research (neurophysiology), where presentations of sequences of repetitive auditory stimuli are infrequently interrupted by a deviant stimulus (odd-stimulus). The MSer is asked to react either by counting or by button pressing incidents of target stimuli that are hidden as rare occurrences amongst a series of more common stimuli, that don't require a response. It has been found that an event related electrical activity across the central areas of the brain usually occur around 300 ms and are referred to as the P300 wave (p = positive wave); this positive wave  is larger after the deviant or target stimulus. In the study below the waveform across the brain in MSers differed from normal control subject implying MSers were using different/additional neuronal systems to complete the task; i.e. identify the deviant stimulus."

"Does this research  have relevance to you? Yes, it does. Simply because you 'feel normal' and appear to be 'functioning normally' does not mean to say you have not acquired any damage and long-lasting problems as a result of your MS. In the initial stages of MS the damage accumulates slowly and silently. MS may be gradually chewing-up, or shredding, your reserve capacity. Please note this does not necessarily happen in all MSers; the only way to find out if your MS is active is to be monitored with regular MRI scans. Clinical monitoring is simply not good enough. We know that benign MS does occur, but in untreated populations benign MS is relatively uncommon. What we are trying to do with early effective treatments is to increase the proportion of MSers who turn out to have benign disease. To get this message across and to get people to adopt early effective treatment, with active monitoring, we are launching a policy document at ECTRIMS called 'Brain Health: time matters in MS'. As soon as the document is available I will be sharing it with you."





López-Góngora et al. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis. PLoS One. 2015; 10(8):e0136786.

Background: Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. 


Methods: Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. 

Results: No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. 

Conclusions: Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.

To shrink or not to shrink what will I remember


Rocca MA, Morelli ME, Amato MP, Moiola L, Ghezzi A, Veggiotti P, Capra R, Pagani E, Portaccio E, Fiorino A, Pippolo L, Pera MC, Comi G, Falini A, Filippi MRegional hippocampal involvement and cognitive impairment in paediatric multiple sclerosis.Mult Scler. 2015 Aug. pii: 1352458515598569. [Epub ahead of print]

OBJECTIVES:We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics.
METHODS: From 53 paediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired.
RESULTS: Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired (n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus.
CONCLUSIONS: Hippocampal subregions have different vulnerability to damage in paediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests.




In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis. Rocca MA, Longoni G, Pagani E, Boffa G, Colombo B, Rodegher M, Martino G, Falini A, Comi G, Filippi M.Hum Brain Mapp. 2015 Aug. doi: 10.1002/hbm.22946. [Epub ahead of print]

Using MR-based radial mapping, we assessed morphological alterations of the hippocampal dentate gyrus (DG) in patients with relapse-onsetmultiple sclerosis (MS). We analyzed different stages of the disease and the association of DG alterations with hippocampal-related cognitive functions. Using high-resolution morphological imaging, hippocampal radial mapping analysis was performed in 28 relapsing-remitting (RR), 34 secondary progressive, and 26 benign MS patients and 28 healthy controls (HC). Between-groups differences of DG radial distance (from surface points to the central core of the hippocampus) and correlations with clinical, neuropsychological, and radiological measures were evaluated using surface-based mesh modeling. Compared with HC, all MS clinical phenotypes revealed a larger radial distance of the DG, which was more marked on the left side. Radial distance enlargement was more pronounced in RRMS patients compared with the other disease clinical phenotypes and was inversely correlated to disease duration. Radial distance enlargement was correlated with higher T2 lesion volume and a better cognitive performance in RRMS and with a poor cognitive performance in secondary progressive and benign MS patients. Surface expansion of the DG might represent an inflammation-induced neurogenic (reactive) process of the subgranular zone of the hippocampus primarily aimed at rescuing the functional competence of hippocampal circuitry.

To shrink or not to shrink that is the question? 

The hippocampus is where your short term memory is formed, which facts will you put there, left or right, big or small?

Calabrese M, Reynolds R, Magliozzi R, Castellaro M, Morra A, Scalfari A, Farina G, Romualdi C, Gajofatto A, Pitteri M, Benedetti MD, Monaco S.Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients. PLoS One. 2015 Aug;10(8):e0135428.

BACKGROUND:Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients.
METHODS:We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration ≥ 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up.
RESULTS:The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r2 = 50.0, p<0.001) and in early RRMS (r2 = 52.3, p<0.001), compared to late RRMS (r2 = 25.5, p<0.001) and SPMS (r2 = 6.3, p = 0.133).
CONCLUSIONS: We conclude that GM atrophy and lesions appear to be different signatures of cortical disease in MS having in common overlapping spatio-temporal distribution patterns. However, the correlation between focal and diffuse damage is only moderate and more evident in the early phase of the disease.

3D Regional map of the frequency of the appearance of new grey matter lesions during the 5-year follow up in the whole group and in the different MS subsets.

"The development of regional cortical thinning was not homogeneous across different MS groups. The reduction of CTh and volume of the hippocampus and the parahippocampal gyrus, the insula, and the cingulate cortex were particularly severe in CIS and early RRMS patients whereas in late RRMS and SPMS cortical thinning and volume loss were significantly greater in the precentral gyrus, the postcentral gyrus, and the cerebellum"


To shrink or is it the left gets bigger or is it the right shrinks so the left is bigger.