Background
The wide variability of dystonic postures manifested in the clinical course of Parkinson’s disease (PD) represents a complicated on-going issue. Several recently published reports of Pisa ...syndrome (PS) in parkinsonian patients on dopaminergic therapy have described a variable means of onset and clinical course of this truncal dystonia.
Objective
To describe PD patients with PS, with the aim of stressing the frequent iatrogenic origin and potential reversibility of this syndrome during the initial stages of its appearance.
Subjects and methods
Eight consecutive PD patients who developed a PS after modifications of antiparkinson therapy were studied. All patients underwent detailed clinical assessment,
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IFP-CIT-SPECT being performed in three cases. Four patients were videotaped.
Results
All patients developed PS within a variable time-span ranging from 15 days to 3 months after adjustment of treatment. Seven cases of PS were manifested following an increase and one a decrease of dopaminergic treatment. A marked reversal of dystonia was produced in the first seven patients by the withdrawal or dose decrease of dopaminergic PS priming drug, and in the eighth patient an increase of dopaminergic therapy was necessary.
Conclusions
In our opinion, the recognition of reversibility of PS during the initial stages of its appearance may be of considerable clinical importance. Indeed, it may facilitate the rapid withdrawal or reintroduction of dopaminergic treatment, thus avoiding an initial veering towards the subchronic variant and, subsequently into a chronic irreversible variant.
Sardinia acts as an ideal setting for multiple sclerosis (MS) studies because its prevalence of MS is one of the highest worldwide. Several pathogens have been investigated amongst 119 Sardinian MS ...patients and 117 healthy controls to determine whether they might have a role in triggering MS in genetically predisposed individuals. Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein Barr virus DNA were detected in 27.5% and 17.3%, respectively, of the MS patients. Moreover an extremely high humoral immune response against MAP recombinant protein MAP FprB (homologous to human myelin P0) was observed, whereas no significant results were found against Mycobacterium tuberculosis FprA and Helicobacter pylori HP986 protein.
Abstract Bacillus Calmette-Guérin (BCG) and Mycobacterium avium subspecies paratuberculosis (MAP) have been associated with multiple sclerosis (MS). Clinical data indicates that BCG vaccination ...exerts anti-inflammatory effects in MS; conversely, MAP is thought to be one of the possible infectious factors responsible of MS through a molecular mimicry mechanism. A peptide-based indirect ELISA was used to detect antibodies against the encephalitogenic myelin oligodendrocyte glycoprotein (MOG)35–55 epitope, and two mycobacterial peptides sharing sequence homology with the latter: MAP_2619c352–361 /BCG_1224355–364 and BCG_3329c64–74 . Among 40 MS patients and 39 healthy volunteers included in the study, only MOG35–55 was capable of inducing a significantly higher humoral response in MS subjects compared to controls. Indeed, 11 out of 40 MS subjects (27.5%) and only 2 out of 39 controls (5%) were antibody-positive for MOG35–55 ( p = 0.01, AUC = 0.65). These findings strengthen the importance of MOG35–55 in MS pathogenesis. The MAP and BCG MOG-homologues epitopes investigated were not recognized in MS patients. Overall, the results allow us concluding that sharing homology of linear epitopes is necessary but not sufficient to induce antibody-mediated cross-reactivity.
Abstract Background Mycobacterium avium subspecies paratuberculosis (MAP) is associated with MS in Sardinia. Because anti-MAP antibodies (Abs) were more frequent in interferon-beta treated patients, ...we hypothesize that interferon-beta could interact with the immune system. Methods Anti-MAP Abs were searched in the blood of 89 patients before commencing interferon-beta and after at least six months. Results Anti-MAP Abs were detected before and during treatment in 18.7% and 34.7% of patients, respectively. Twenty-three (20.5%) patients became positive during therapy, and 5 (4.4%) patients became negative (p = 0.001). Conclusions The study supports the hypothesis that interferon-beta could interact with the immune system, enhancing the immunological response against MAP.
In people with Multiple Sclerosis (pwMS), balance assessment is essential in estimating the risk of falls, monitoring disease progression and verifying the effectiveness of rehabilitative treatment. ...Clinical tools and instrumental techniques are available for testing static and dynamic balance, but the relationship between such abilities is still not clear. Having information about this link would be important in properly planning the type and number of tests to administer.
One hundred and six pwMS (Expanded Disability Status Scale, EDSS 0-6.5) stratified in three sub-groups (Class 1 EDSS 0-1.5, Class 2 EDSS 2-4 and Class 3 EDSS 4.5-6.5) and 42 healthy controls (HC) participated in the study. All underwent static posturography and instrumented Timed-Up-and-Go (TUG) performed using a wearable inertial sensor. Raw data were processed to extract postural sway features, overall duration of TUG and its main sub-phases (i.e. sit-to-stand, 180° turns and stand-to-sit).
All sway parameters of pwMS of Classes 2 and 3, as well as total TUG duration and time necessary to perform 180° turns, were found significantly higher than HC and Class 1 participants. However, poor correlations were found between sway and TUG parameters. When pwMS are grouped, small/moderate correlations (in the range 0.20-0.41) were found between all sway parameters and total TUG duration.
Static and dynamic balance in pwMS appear scarcely correlated, although both worsen as disability increases. This implies that they should be separately assessed using specific tests to have a complete view of postural control performance in MS.
Age-related disability in multiple sclerosis Trojano, Maria; Liguori, Maria; Bosco Zimatore, Giovanni ...
Annals of neurology,
April 2002, Letnik:
51, Številka:
4
Journal Article
Recenzirano
There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital‐based ...cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person‐years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan–Meier method with age as a categorical time‐varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age‐adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.
Abstract Background Parkinson's disease (PD) occurs more frequently in men than in women and a higher risk for PD development in males compared with females has been hypothesized, suggesting gender ...may be a significant factor in the development and progression of parkinsonism. To date, gender differences in non-motor symptoms are under-reported. Objective To assess gender differences in motor and non-motor symptoms among Sardinian PD patients. Methods One hundred fifty-six (91 male and 65 female) consecutive Sardinian PD outpatients were included in this analysis. Modified Hoehn and Yahr scale and UPDRS were used to assess motor symptoms, while non-motor disturbances were evaluated with the non-motor symptoms scale (NMSS). Presence of depression, anxiety and other iatrogenic behavioral disorders was also investigated. In order to determine how gender differences could be specific to PD, 132 age-matched normal controls were assessed with the NMSS. Results Women were more likely than men to present with tremor as initial symptom (p < .025) and worse UPDRS instability score (p < .02). NMSS score in females was significantly higher than that in males (p < .018). A significantly higher severity in cardiovascular (p < 0.002), sleep/fatigue (p < .018) and mood/apathy (p < .001) domains was observed in female PD patients, while the sexual dysfunction domain was reported with a significantly higher score in male patients (p < .017). Fatigue (p < .03), lack of motivation (p < .015) and sadness (p < .009) were observed significantly more frequent in females, while altered interest in sex was noted as more common in males (p < .001). Frequency of depression (p < .011) and anxiety (p < .001) was significantly higher in females, while male patients had increased frequency of compulsive sexual behaviors (p < .05). There was a significantly higher frequency of non-motor symptoms in eight domains in both male and female PD patients compared with controls (p < .001, for all comparisons, with the exception of urinary disturbances in females: p < .004). Only sexual dysfunctions were not significantly higher in male and female PD patients compared with controls. Discussion The present study highlights the role of gender differences associated with the occurrence of motor and non-motor disorders and our findings indicate that spectrum and severity of non-motor symptoms may present with different gender distribution in PD patients, suggesting a possible sex-related effect.
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•A characterization of metabolomic profile plasma from patients with MS is presented.•GC–MS-based metabolomic analysis is able to discriminate the profile of MS from HC.•Asparagine ...and citrulline biosynthesis are the canonical pathways affected in MS.
Multiple sclerosis (MS) is a chronic, demyelinating disease that affects the central nervous system and is characterized by a complex pathogenesis and difficult management. The identification of new biomarkers would be clinically useful for more accurate diagnoses and disease monitoring. Metabolomics, the identification of small endogenous molecules, offers an instantaneous molecular snapshot of the MS phenotype. Here the metabolomic profiles (utilizing plasma from patients with MS) were characterized with a Gas cromatography-mass spectrometry-based platform followed by a multivariate statistical analysis and comparison with a healthy control (HC) population. The obtained partial least square discriminant analysis (PLS-DA) model identified and validated significant metabolic differences between individuals with MS and HC (R2X=0.223, R2Y=0.82, Q2=0.562; p<0.001). Among discriminant metabolites phosphate, fructose, myo-inositol, pyroglutamate, threonate, l-leucine, l-asparagine, l-ornithine, l-glutamine, and l-glutamate were correctly identified, and some resulted as unknown. A receiver operating characteristic (ROC) curve with AUC 0.84 (p=0.01; CI: 0.75–1) generated with the concentrations of the discriminant metabolites, supported the strength of the model. Pathway analysis indicated asparagine and citrulline biosynthesis as the main canonical pathways involved in MS. Changes in the citrulline biosynthesis pathway suggests the involvement of oxidative stress during neuronal damage. The results confirmed metabolomics as a useful approach to better understand the pathogenesis of MS and to provide new biomarkers for the disease to be used together with clinical data.
Mitoxantrone is an immunosuppressive drug approved for aggressive relapsing and progressive multiple sclerosis. In recent years, its use has decreased due to the risk of severe adverse events and the ...introduction of novel therapies, such as natalizumab or fingolimod. Mitoxantrone is effective in reducing inflammatory activity by decreasing the number of relapses and MRI lesions and simultaneously decreasing the worsening of disability. Apart from its role as a second/third-line therapy, some studies suggest its use as an induction therapy. However, mitoxantrone use is limited because of its potential risk of severe adverse events, such as cardiotoxicity and the induction of therapy-related acute leukemia. Genetic markers are on evaluation to predict side effects and therapeutic efficacy, which is consistent with the direction of personalized treatment. Considering its efficacy and the potential risks, mitoxantrone use is limited to active patients after a careful, individualized evaluation of the risk/benefit balance.
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