Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients

OBJECTIVES: To compare cerebrospinal fluid (CSF) and serum transferrin (Tf) concentrations, transferrin quotient and index in various subgroups of MS patients. MATERIAL AND METHODS: CSF and serum transferrin concentrations, transferrin quotient QTf (i.e. CSF transferrin/serum transferrin x 10(3)) and index (QTf/Qalbumin) were determined in a group of 51 patients with clinically definite or probable multiple sclerosis (MS). Patients were subdivided according to the disease form (relapsing-remitting = RR, secondary progressive = SP, primary progressive = PP; patients with RR form were further subdivided into those in the attack and those in remission), disease severity (EDSS 0-5.5, EDSS 6.0-10.0), its treatment (non-treated - including patients treated with vitamins and/ or vasodilators only, treated - i.e. glucocorticoids and/or immunosuppressants and/or (exceptionally) beta-interferon), disease duration (0-2 years, >2-10 years, > 10 years) and sex. Correlation of transferrin values with age was also performed. RESULTS: Serum transferrin was somewhat lower and significantly more frequently subnormal in PP patients in comparison with the SP form and the RR form in remission. Transferrin index was significantly higher in the PP form than in the RR as well as the SP form. Transferrin quotient was significantly more frequently subnormal in patients in remission compared to those in the attack of the RR disease. CSF transferrin as well as transferrin quotient were more frequently subnormal in patients with short disease duration (0-2 years) than in patients with longer disease duration; these parameters, however, correlated also significantly with age. CSF transferrin and transferrin quotient were higher in male than in female patients. CONCLUSION: The authors conclude that evaluation of transferrin in MS patients - along with albumin - may help to differentiate among various MS subgroups, since there are significant differences among RR, SP and PP forms. For this purpose, however, other CSF protein fractions should be evaluated in parallel in order to obtain more complex information and to establish a panel of examinations enabling multiple statistical analyses. Transferrin evaluation in MS may also be of significant theoretical interest, since transferrin is known to be involved in the regulation of iron metabolism and it may have a protective role against the oxidative stress. Moreover, transferrin is a growth factor important for proliferation of activated T lymphocytes. By means of the use of transferrin quotient and especially transferrin index, it may be possible to estimate the proportion of intra-CNS-synthesized transferrin and/or rate of specific transferrin transport across the blood-CSF barrier. Further studies are, however, needed for such an evaluation.     

Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis

Abstract The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta-1a used in the treatment of relapsing-remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n=339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p=0.007), and were due predominantly to differences in injection-site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p<0.001),with no difference seen for severe events. Flu-like symptoms were more common with 30 mcg qw (p=0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high-dose, high-frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the risk-benefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.for the EVIDENCE Study GroupSee Acknowledgements for a full listing of the study participants.     

Magnetic resonance imaging findings in 22 cases of myelitis: comparison between patients with and without multiple sclerosis

We reviewed the magnetic resonance imaging (MRI) database of the Dent Neurologic Institute to study the abnormal findings in myelitis. We identified 22 patients, and compared non-MS-related acute transverse myelitis (ATM, n = 9), to myelitis associated with multiple sclerosis (MS-myelitis, n = 13). The ATM patients were significantly older than MS patients at the time of the myelitis diagnosis (mean age 46 vs 35, p < 0.05). ATM appeared as a "longitudinal myelitis", with fusiform cord expansion on T ₁-weighted images and intramedullary increased signal on T ₂-weighted images, each involving multiple spinal levels (mean = 7–8). However, MS-myelitis lesions appeared focal, involving significantly fewer spinal levels (mean = 1–2, p < 0.001), although the lesions were equally likely to expand the cord. Four (42%) of the ATM lesions showed abnormal, variable enhancement, whereas none of the MS myelitis lesions enhanced. Cranial MRI was more likely to be normal in ATM (78%) than in MS-myelitis patients (15%, p < 0.001). Although readily distinguishable from lesions due to MS, the various etiologies for ATM, including post-infectious ( n = 2), post-vaccination ( n = 3), and idiopathic ( n = 4) were indistinguishable on MRI. The MRI findings of an extensively lesioned, swollen cord, suspicious for an intramedullary tumor and providing a temptation for a biopsy, may reflect a non-neoplastic inflammatory disorder.     

Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis

OBJECTIVES: The current review evaluates the safety and efficacy of desmopressin in patients with multiple sclerosis (MS) who suffer from both daytime and nocturnal voiding frequency and from incontinence. MATERIALS AND METHODS: A literature search was carried out looking for studies published between 1990 and 2003 which evaluated desmopressin in MS patients with bladder dysfunction. RESULTS: The grand total mean effect sizes show the following estimates of clinical relevant differences: desmopressin has a moderate effect on the number of voids during the day or during the night over a period of 6 h after taking the drug. A large effect associated with the use of desmopressin was detected by the mean difference in urine volume (ml) in 6 h. A small effect was detected in the mean 24-h urine volume. Serum sodium levels were combined with plasma osmolality in some studies and were found to be not significantly affected by desmopressin treatment.     

Stress and depression symptoms in patients with multiple sclerosis: the mediating role of the loss of social functioning

Kirchner T, Lara S. Stress and depression symptoms in patients with multiple sclerosis: the mediating role of the loss of social functioning.
Acta Neurol Scand: 2011: 123: 407–413.
© 2010 John Wiley & Sons A/S. Objective – Depression symptoms are very frequent in patients with multiple sclerosis (MS) and have been associated with several quality of life indicators, especially physical and social functioning. The objectives were as follows: (i) to analyse the extent to which the loss of physical and social functioning may explain the depression symptoms observed in 65 Spanish patients diagnosed with MS; and (ii) to analyse the degree to which loss of social functioning may act as a mediator between depression symptoms and the stress associated with the disease. Materials and Methods – Participants were 65 Spanish patients diagnosed with MS and recruited from several MS centres and foundations. Results – The loss of social functioning had greater explanatory power as regards depression symptoms than did the loss of physical functions. Social functioning was also found to have an important mediating effect between MS stress and depression symptoms: specifically, more than half (52%) of the relationship between MS stress and depression symptoms was mediated by the perceived loss of social functions in Spanish patients with MS. Conclusion – The importance of social functioning for Spanish patients with MS may have noteworthy implications when designing prevention and treatment programmes aimed at improving their quality of life.     

诊断多发性硬化的Poser标准与McDonald新标准的比较

目的 比较诊断多发件硬化(multiple sclerosis,MS)的Poser标准和McDonald新标准.方法 将Poser标准和McDonald新标准回顾性应用于临床表现提示为MS的67例患者,采用Fisher精确枪验对两种诊断标准进行比较分析.结果 符合Poser临床和实验室确诊者分别为34例和24例,可能MS者9例,符合McDonald标准的MS确诊者36例,可能MS者31例,两种标准的诊断阳性率差异有统计学意义(OR=5.549,95%CI 2.37～13.00,P<0.01).结论 两种标准住诊断MS,尤其在确诊MS时有明显差异,这可能主要与Poser标准更多地依赖各种亚临床证据,而McDonald标准采用了更为严格的MRI规定有关,脑脊液分析可能在一定程度上有助于提高MS的确诊率和MRI异常的病理特异性.     

Intrathecal polyspecific immune response to neurotropic viruses in multiple sclerosis: a comparative report from Cuban patients

OBJECTIVE: Intrathecal measles(M)- rubella(R)- and varicella zoster(Z)-antibody synthesis in German and Cuban multiple sclerosis (MS) patients are compared considering the different rubella epidemiology in the tropics. PATIENTS AND METHODS: Twenty-three Cuban MS patients with a representative age distribution and gender ratio like the group of 177 German MS patients were analysed for albumin, IgG, IgA IgM, oligoclonal IgG and MRZ- antibodies in cerebrospinal fluid (CSF) and serum. RESULTS: Cuban MS patients show similar CSF data patterns like German patients and high frequencies of intrathecal measles- (78/78%) and varicella zoster- (59/55%) antibody synthesis correspondingly. A lower frequency of intrathecal rubella antibody synthesis (rubella-AI >or= 1.5) in Cuban patients (30%, gender ratio of increased rubella - AI m:f = 1:6) compared with German patients (60%, m:f = 1:1.8) is explained by low incidence of rubella infections in Cuba. Only about 10% of the male population (not immunized before 1986, in contrast to females) had rubella antibodies compared to at least 60% in a European male population, representing the relation of increased rubella-AI in male MS patients. CONCLUSION: In MS the frequency of intrathecal antibody synthesis is limited by the fraction of seropositives in the population. Natural infection or vaccination are a necessary and equivalent precondition contributing to the arguments against microorganisms as a cause of MS.     

Eyes are mirror of the brain: comparison of multiple sclerosis patients and healthy controls using OCT

Abstract

Objective: To evaluate the thickness of choroid and retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis using enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods: In this cross-sectional study, both eyes of 52?MS patients [n?=?104 eyes; 62 eyes of MS patients without optic neuritis (MS-NON) and 42 eyes of MS patients with optic neuritis (MS-ON)] and only one eye of 36 healthy control subjects (n?=?36 eyes) were evaluated. Complete ophthalmologic examination and EDI-OCT scanning were completed for all participants. Choroidal thickness measurements were executed at three different points.

Results: Choroidal thickness measurements were similar between MS patients and healthy control subjects. However, the mean subfoveal choroidal thickness was increased significantly in MS-ON group (399.13?±?82.91?μm) compared to MS-NON group (342.71?±?82.46?μm; p?=?0.004). Mean RNFL thickness was significantly reduced in MS patients (90.42?±?13.31?μm) compared to healthy controls (101.18?±?10.75?μm; p?<?0.001). Moreover, temporal RNFL thickness was significantly thinner in MS-ON group (54?±?14.50?μm) than MS-NON group (62.15?±?15.88?μm; p?=?0.01). In MS patients, temporal RNFL thickness was correlated with both Expanded Disability Status Score (r?=?0.383; p?<?0.001) and longer disease duration (r=–0.202; p?=?0.04).

Conclusion: The results of the present study suggest that RNFL thickness can be used as an important parameter while following up with MS patients. However, more studies using EDI-OCT are required with larger MS patient groups and automated method.     

Mental fatigue alters the pattern and increases the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue

Fatigue is one of the most disabling symptoms in multiple sclerosis (MS) and there is increasing evidence it has a central origin. Our aim was to assess the impact of mental fatigue on motor task-related cerebral activation. Ten relapsing-remitting MS patients with fatigue were recruited and compared with seven controls. Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed a finger-thumb apposition task. The Paced-Auditory-Serial Addition Task (PASAT) was administered to induce fatigue and the fMRI motor paradigm was then repeated. Our results revealed that the PASAT altered the MS patients' activation patterns on the motor task. After the mentally fatiguing PASAT task, repeating the motor task was associated with patients recruiting significantly more of their brain including bilateral cingulate gyri and left primary sensory cortex, while activating less of the left premotor and supplementary motor area. The control subjects decreased their level of activation after the PASAT. Our current results reveal that a challenging mental task can alter the pattern and increase the volume of cerebral activation on an unrelated motor task in fatigued MS patients. These data support the hypothesis that a substrate for MS fatigue could be a generally elevated demand placed on functioning neural circuits.     

Health-related quality of life and depressive symptoms in significant others of people with multiple sclerosis: a community study

Background and purpose: Uncertain prognosis and modest treatment efficacy make multiple sclerosis (MS) a particularly difficult disease to adjust to for both patients and their significant others (SOs). Few studies have assessed health‐related quality of life (HRQOL) and depressive symptoms in SOs of people with MS in the community. We assessed, and identified predictors of, HRQOL and depression in SOs of adults with MS. Methods: POSMOS (postal survey of self‐assessed health in MS adults and SOs) is a longitudinal survey on a random sample of 251 people with MS in the Milan area. In 2010, SOs and contemporaneous controls completed the SF‐36 and Chicago Multiscale Depression Inventory (CMDI). Results: Overall, 142 SOs (mean age 53.1 years; 50% women, 65% partners) and 120 controls (similar to SOs for sex and education, but older) participated. By multivariable modeling of the SO plus control population, SF‐36 vitality was lower in SOs (proportional odds ratio 0.45; 95% confidence interval 0.28–0.70), women (0.41; 0.27–0.64), and older subjects (0.98; 0.97–0.99). SF‐36 mental health was also lower in SOs (0.62; 0.40–0.96) and women (0.43; 0.28–0.67). Regarding MS characteristics associated with HRQOL and depression in SOs, severe disability [Expanded Disability Status Scale (EDSS > 6.5)] had no effect, whilst depressive symptoms (pathologic CMDI) negatively influenced most SF‐36 and all CMDI scores in SOs. Conclusions: SOs had significantly lower vitality and psychological well‐being than controls, identifying a burden in being the companion of a person with MS. This burden was unrelated to physical compromise but associated with depressive symptoms in MS.     

Benefits from an autobiographical memory facilitation programme in relapsing-remitting multiple sclerosis patients: a clinical and neuroimaging study

While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n?=?10), who underwent the MVI programme, and control (n?=?10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design. Only the experimental group showed a significant AM improvement in post-facilitation, accompanied by changes in brain activation (medial and lateral frontal regions), functional connectivity (posterior brain regions), and grey matter volume (parahippocampal gyrus). Minor activations and functional connectivity changes were observed in the control group. The MVI programme improved AM in MS patients leading to functional and structural changes reflecting (1) an increase reliance on brain regions sustaining a self-referential process; (2) a decrease of those reflecting an effortful research process; and (3) better use of neural resources in brain regions sustaining MVI. Functional changes reported in the control group likely reflected ineffective attempts to use the sham strategy in AM.     

Seroreactivity to human T cell leukemia/lymphoma virus type 1 and related retroviruses in multiple sclerosis patients from Denmark and the Faroes

A total of 40 multiple sclerosis (MS) patients from Denmark and 10 from the Faroes were examined for antibodies with affinity to human T cell leukemia/lymphoma virus type 1 (HTLV-I) and human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2). Using ELISA, MS patients and a group of healthy controls did not differ significantly in their reactivities to HTLV-I. However, elevated reactivities were recorded with 5 MS sera, whereas only 2 of the sera from the controls produced highly values. Ten patients with other neurological diseases all seemed to exhibit low reactivity in HTLV-I ELISA. The reactivities of 2 MS sera decreased considerably by absorption with an HTLV-I lysate. In immunofluorescence assay, two other MS sera reacted with HTLV-I transformed cell lines as well as with non-infected cells. Examined by Western blotting (WB), a single MS serum produced a distinct HTLV-I p19 band. With ELISA for detection of HIV-1 and HIV-2 antibodies, 2 MS sera exhibited borderline reactions. Further examination of these two sera by WB revealed weak reactivities against p24 and p53 of HIV-1. One the whole, the present observations do not suggest that a putative MS retrovirus would be closely related with HTLV-I, HIV-1 or HIV-2.     

Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co‐twin study

Background and purpose: The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. Methods: Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)‐6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. Results: A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co‐twins. Conclusion: As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS.     

Causes of death in patients with multiple sclerosis and matched referent subjects: a population‐based cohort study

Background and purpose: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death. Methods: We conducted a population‐based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs). Results: Patients with MS had a 3.5‐fold increased mortality rate for all‐cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63–4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16–10.87) (but not in ex‐smokers) and subjects with a body mass index of <20 kg/m² (HR 6.67, 95% CI 3.50–12.73). The HR was highest for infectious/respiratory‐related deaths (HR 7.69, 95% CI 4.92–12.02) and was significantly increased for deaths related to cardiovascular diseases (2.4‐fold) and cancer (1.9‐fold), but not for accidents and suicide related deaths. Conclusion: British patients with MS have a 3.5‐fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.