Background and aims
Most patients with multiple sclerosis presenting with a relapsing–remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1–2 decades ...after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients. Therefore, early diagnosis of SPMS is necessary for prompt treatment decisions. The aim of this review was to assess neurophysiological and fluid biomarkers that have the potential to monitor disease progression and support early SPMS diagnosis.
Methods
We performed a systematic review of studies that analyzed the role of neurophysiological techniques and fluid biomarkers in supporting SPMS diagnosis using the preferred reporting items for systematic reviews and meta-analyses statement.
Results
From our initial search, we selected 24 relevant articles on neurophysiological biomarkers and 55 articles on fluid biomarkers.
Conclusion
To date, no neurophysiological or fluid biomarker is sufficiently validated to support the early diagnosis of SPMS. Neurophysiological measurements, including short interval intracortical inhibition and somatosensory temporal discrimination threshold, and the neurofilament light chain fluid biomarker seem to be the most promising. Cross-sectional studies on an adequate number of patients followed by longitudinal studies are needed to confirm the diagnostic and prognostic value of these biomarkers. A combination of neurophysiological and fluid biomarkers may be more sensitive in detecting SPMS conversion.
Motor fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. Previous studies suggested that increased motor fatigue in MS may arise at the central nervous system level. ...However, the mechanisms underlying central motor fatigue in MS are still unclear.
This paper investigated whether central motor fatigue in MS reflects impaired corticospinal transmission or suboptimal primary motor cortex (M1) output (supraspinal fatigue). Furthermore, we sought to identify whether central motor fatigue is associated with abnormal M1 excitability and connectivity within the sensorimotor network.
Twenty-two patients affected by relapsing-remitting MS and 15 healthy controls (HCs) performed repeated blocks of contraction at different percentages of maximal voluntary contraction with the right first dorsal interosseus muscle until exhaustion. Peripheral, central, and supraspinal components of motor fatigue were quantified by a neuromuscular assessment based on the superimposed twitch evoked by peripheral nerve and transcranial magnetic stimulation (TMS). Corticospinal transmission, excitability and inhibition during the task were tested by measurement of motor evoked potential (MEP) latency, amplitude, and cortical silent period (CSP). M1 excitability and connectivity was measured by TMS-evoked electroencephalography (EEG) potentials (TEPs) elicited by M1 stimulation before and after the task.
Patients completed fewer blocks of contraction and showed higher values of central and supraspinal fatigue than HCs. We found no MEP or CSP differences between MS patients and HCs. Patients showed a post-fatigue increase in TEPs propagation from M1 to the rest of the cortex and in source-reconstructed activity within the sensorimotor network, in contrast to the reduction observed in HCs. Post-fatigue increase in source-reconstructed TEPs correlated with supraspinal fatigue values.
To conclude, MS-related motor fatigue is caused by central mechanisms related explicitly to suboptimal M1 output rather than impaired corticospinal transmission. Furthermore, by adopting a TMS-EEG approach, we proved that suboptimal M1 output in MS patients is associated with abnormal task-related modulation of M1 connectivity within the sensorimotor network. Our findings shed new light on the central mechanisms of motor fatigue in MS by highlighting a possible role of abnormal sensorimotor network dynamics. These novel results may point to new therapeutical targets for fatigue in MS.
Display omitted
•Motor fatigue in multiple sclerosis (MS) is not due to corticospinal mechanisms.•Motor fatigue in MS is due to a suboptimal M1 output.•Suboptimal M1 output in MS is associated with abnormal modulation of M1 connectivity.•Motor fatigue in MS reflects abnormal fatigue-related sensorimotor network changes.
Background:
Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical ...complexity of patients with multiple sclerosis (MS).
Objective:
To investigate the relationship between frailty and the clinical manifestations of MS.
Methods:
Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits.
Results:
Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype.
Conclusion:
Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.
Motor and non-motor subtypes of cervical dystonia Costanzo, Matteo; Belvisi, Daniele; Berardelli, Isabella ...
Parkinsonism & related disorders,
July 2021, 2021-07-00, 20210701, Letnik:
88
Journal Article
Recenzirano
Cervical dystonia (CD) is a heterogeneous condition. However, while motor subtypes of CD have recently been identified, it is still unknown whether and how non-motor symptoms contribute to CD ...heterogeneity. In the present cross-sectional study, we aimed to identify clinical CD subtypes on the basis of motor and non-motor symptoms by using a hypothesis-free data-driven approach.
Fifty-seven patients with CD participated in the study. Patients underwent a clinical evaluation that assessed motor and non-motor features of CD with standardized clinical scales. We investigated five clinical domains, including motor symptoms, psychiatric disturbances, sleep disorders, cognitive impairment and pain. These domains were used as variables in a k-means cluster analysis with two-, three-, and four-cluster solutions.
The two-cluster solution best fits our sample. Cluster I (n = 32) included patients who were younger and had less severe non-motor symptoms and a lower disability level than patients included in Cluster II (n = 25). The two clusters showed similar sex distribution and disease duration. Similarly, the type of motor pattern and the occurrence of tremor and sensory trick were equally distributed in the two subtypes.
We identified two clinical subtypes of CD. The two subtypes shared similar motor features but were characterized by different non-motor symptom severity. These findings suggest that motor network dysfunction is a common pathophysiological feature of CD, whereas the extent of non-motor network involvement may differ in CD, with age acting as a possible modulating factor.
•A motor-predominant and a non-motor predominant subtype exist in cervical dystonia.•Non-motor symptoms contribute to cervical dystonia clinical heterogeneity.•Age is a mediator of non-motor spread in cervical dystonia.
Introduction
Bowel dysfunction (BD) is reported as a common and disabling symptom in multiple sclerosis (MS) patients. To date, no studies have explored the prevalence of these symptoms in a large ...multicenter outpatient setting. The aims of the present study are to assess: (i) the prevalence of BD in a large multicenter Italian MS population, and (ii) the correlation between clinico-demographic variables and the severity of BD.
Methods
Each of the nine participating center screened MS patients prospectively: 1100 subjects were enrolled. All patients underwent the Expanded Disability Status Scale (EDSS) and completed the Neurogenic Bowel Dysfunction score (NBDs). Multivariable linear and logistic regression models were used to assess the association between NBDs and several clinico-demographic variables.
Results
Fourteen percent of MS patients showed a moderate/severe BD (NBDs > 10); this percentage increased in patients with high disability, ranging from 26 to 32%. Moderate/severe BD was more frequent in MS patients with: progressive phenotypes, higher disability, older age, and longer disease duration. NBDs severity was predicted by female sex, ambulation impairment and bladder symptoms.
Conclusion
This study confirms the relatively high prevalence of moderate/severe BD in a large, multicenter, unselected, outpatient MS population. BD appears to be mainly associated to female sex and MS-related disability.
The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to ...vaccination.
The aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled "responding T-cells", those cells that produced at least one of the three cytokines of interest, and "triple positive T-cells", those cells that produced simultaneously all the three cytokines.
The cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).
In pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.
Patients with cervical dystonia (CD) may display non-motor symptoms, including psychiatric disturbances, pain, and sleep disorders. Intramuscular injection of botulinum toxin type A (BoNT-A) is the ...most efficacious treatment for motor symptoms in CD, but little is known about its effects on non-motor manifestations. The aim of the present study was to longitudinally assess BoNT-A's effects on CD non-motor symptoms and to investigate the relationship between BoNT-A-induced motor and non-motor changes. Forty-five patients with CD participated in the study. Patients underwent a clinical assessment that included the administration of standardized clinical scales assessing dystonic symptoms, psychiatric disturbances, pain, sleep disturbances, and disability. Clinical assessment was performed before and one and three months after BoNT-A injection. BoNT-A induced a significant improvement in dystonic symptoms, as well as in psychiatric disturbances, pain, and disability. Conversely, sleep disorders were unaffected by BoNT-A treatment. Motor and non-motor BoNT-A-induced changes showed a similar time course, but motor improvement did not correlate with non-motor changes after BoNT-A. Non-motor symptom changes after BoNT-A treatment are a complex phenomenon and are at least partially independent from motor symptom improvement.
The Jebsen Taylor Hand Function Test (JTHFT) is a non-diagnostic assessment scale for hand and upper limb dexterity that is commonly used in various countries around the world for diseases, such as ...muscular dystrophy, stroke, spinal cord injury, Parkinson, carpal tunnel syndrome, and rheumatoid arthritis. This study aimed to evaluate the psychometric properties of the JTHFT in Italian adults with Multiple Sclerosis (MS).
The test's internal consistency was evaluated with Cronbach's alpha, whereas its concurrent validity was evaluated by comparing the JTHFT with the Health Assessment Questionnaire (HAQ) and by calculating Pearson's correlation coefficient.
The JTHFT was administered to 29 Italians with MS. The Cronbach's alpha showed that the nondominant hand has a value of 0.76 and 0.91 for the dominant hand. Pearson's correlation coefficient showed significant correlations between JTHFT and HAQ.
The JTHFT is a reliable tool to evaluate the functionality of the upper limb and hand in patients with MS. This tool is useful for testing the effectiveness of a treatment in various diseases. The results obtained in this study are coherent with previous studies that are conducted in populations with different diseases. In particular, the correlation between JTHFT and HAQ showed that a disability related to the upper limbs can often have repercussions, not only on activities of daily living, but also on walking. Based on this correlation, the motor deficits that emerged may be linked to a brain marrow disease rather than a spinal disease, even if an essential deepening can confirm this hypothesis.
The original version of this article unfortunately contained a mistake. The given and family names of authors were Interchanged except the following author Maria Chiara Buscarinu, Carolina Gabri ...Nicoletti, Alessandra Girolama Marfia and Antonio Gallo.
PDF
