The frequency of relapse in multiple sclerosis

Summary The authors analyze the course of 245 cased of multiple sclerosis. The mean annual frequency of attacks is 0.66 for all the patients (remittent forms and progressive forms). Although it is usually suggested that this frequency decreases with the years, this has not been found in our study. Our results also indicate that we would have to follow 590 patients over 1 year or 190 over 2 years before being able to attest the effectiveness of a treatment decreasing the frequency of attacks by 25%.Ingénieur I.N.S.E.R.M.     

Callosal function in multiple sclerosis: bimanual motor coordination

Evidence of callosal dysfunction in patients with multiple sclerosis (MS) was examined using a test of bimanual coordination. MS patients were slower than non-patients on the Bimanual Coordination Test (BCT) on both unimanual trials (simple motor speed) and bimanual trials (intermanual coordination). Further, when compared to normals, MS patients exhibited a substantially greater difference between bimanual and unimanual response time, suggesting a deficit in interhemispheric motor interactions. A subgroup of MS subjects who showed markedly inefficient callosal transmission had previously been identified on the basis of abnormal evoked potentials (low amplitude cross-callosal evoked potentials). In comparisons of MS subgroups, the deficit in bimanual motor coordination was found only in MS patients with EP evidence of inefficient callosal transmission. These data support the conclusion that deficits in bimanual motor coordination occur in MS and that these deficits are related to callosal dysfunction.     

Long-term effect of ACTH treatment of relapse in multiple sclerosis

A controlled, randomized study of the long-term effects of ACTH-treatment (100 units intramuscular, tapered over 12 weeks) of acute relapse in 29 MS patients was performed. Follow-up lasted one year. In some Kurtzke Functional System, the Ambulation Index and the Kurtzke Incapacity Scale a transient greater improvement in the ACTH-treated patients was observed. These superior results in the ACTH group were no longer present at 6 months. Significantly more side-effects were reported in the ACTH-group. After treatment with ACTH a higher, though not statistically significant, relapse rate in the following months was noticed.     

Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural–vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO₂), and flow–metabolism coupling (ΔCBF/ΔCMRO₂), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO₂ increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow–metabolism coupling (ΔCBF/ΔCMRO₂) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO₂ in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO₂ responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural–vascular coupling.     

The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence

Brain plasticity is the basis for systems‐level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25‐minutes of task practice, were performed. Within‐session between‐run change in task‐related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium‐enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between‐run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice‐induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short‐term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery‐oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431–2445, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Lower motor neuron dysfunction in patients with multiple sclerosis.

A patient in whom multiple sclerosis (MS) was ultimately diagnosed presented with a lower motor neuron syndrome involving 1 hand, with EMG evidence of denervation. Twelve other patients were subsequently identified with definite MS and asymmetric hand atrophy. These patients were studied clinically and electrophysiologically. Evidence of chronic and ongoing denervation was noted in the hands of 12 of the 13 patients; in only 3 patients could the EMG abnormalities be accounted for by peripheral nerve lesions. Thus, lesions resulting in lower motor neuron damage may occur in the central nervous system in MS patients. We suggest that demyelination in the region of the ventral root exit zone may account for these findings.     

Management of acute exacerbations in multiple sclerosis

A key component of multiple sclerosis is the occurrence of episodes of clinical worsening with either new symptoms or an increase in older symptoms over a few days or weeks. These are known as exacerbations of multiple sclerosis. In this review, we summarize the pathophysiology and treatment of exacerbations and describe how they are related to the overall management of this disease.     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society     

Frequency-dependent conduction delay of motor-evoked potentials in multiple sclerosis

Paired transcranial magnetic stimulation was applied in 33 multiple sclerosis (MS) patients and in 21 healthy controls. A major abnormality was found in latency of the second motor-evoked potential in MS patients. At interstimulus intervals of 75, 100, and 150 ms the central motor conduction time (CMCT) was significantly prolonged in MS patients to 139%, 150%, and 125% of the CMCT of a single magnetic stimulation (P = 0.02, P = 0.004, P = 0.03), respectively. Voluntary contraction of the target muscle abolished the difference in latency independent of the degree of contraction. Stimulation intensity influenced the length of the interstimulus interval during which the maximal conduction delay was obtained. In MS patients there was no correlation between prolonged CMCT to a single magnetic stimulus and the frequency-dependent conduction delay to paired magnetic stimuli. It is hypothesized that the conduction delay of the conditioned response of paired magnetic stimuli in MS is of cortical origin and induced by abnormalities of the ascending volley to the neocortex. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1264–1274, 1997     

The relapse rate of multiple sclerosis changes during pregnancy: a cohort study

Objective – To evaluate the influence of pregnancy and puerperium on the relapse rate of multiple sclerosis (MS).
Methods – We determined retrospectively the yearly mean relapse rate (MRR) during pregnancies occurring in the course of relapsing–remitting MS. We compared the MRR of pregnancy-time with that of non-pregnancy time by paired t -test. Relative risk (RR) of relapses during the pregnancy-time was also compared with that of non-pregnancy time by χ ² analysis and 95% confidence intervals.
Results – From a population of 351 women affected by clinically definite MS, only 70 reported pregnancies during their relapsing–remitting phase of MS for a total of 98 pregnancies. Both MRR ( P  = 0.006) and RR (RR = 0.63, 95% CI = 0.40–0.94) decreased during the three trimesters of pregnancy. RR increased in the first 3 months of puerperium, although this was not statistically significant (RR = 1.36, 95% CI = 0.79–2.20).
Conclusion – Our study confirms that in MS the relapse rate decreases throughout pregnancy and increases during puerperium. This suggests a complex interplay between hormonal and immune factors.