High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations

We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement.     

Comparison of combination pergolide and levodopa to levodopa alone after 63 months of treatment

We retrospectively compared the clinical state of 14 patients with Parkinson's disease who took pergolide continuously for 63 +/- 17 months (Group I) to that of 12 similar patients who started pergolide and then stopped it after 60 +/- 5 days (Group II). Disability measured during the "on" state did not worsen during the observations period in Group I patients, whereas disability in Group II showed significant deterioration. There were no significant differences in the progression of motor fluctuations between the two groups. Combination treatment with pergolide and levodopa is effective long-term symptomatic therapy for advanced Parkinson's disease and deserves more rigorous study to determine whether or not it also retards progression of Parkinson's disease.     

T-cell subsets in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients treated with high-dose intravenous methylprednisolne

To determine the effects of high-dose intravenous methylprednisolone (MP) on lymphocytes and lymphocyte subpopulations in the cerebrospinal fluid (CSF) and peripheral blood (PB) in multiple sclerosis (MS) patients, we studied 67 patients with definite MS treated with MP. They were classified according to the disease course: 32 chronic progressive (CP) patients, 25 relapsing-remitting (RR) patients, and 10 patients with a chronic progressive disease course accompanied by relapses and remissions (CP + RR). MS patients were treated with 1000 mgr intravenous MP daily for 10 consecutive days. Before and after MP treatment we simultaneously studied CSF and PB CD3 +, CD4 +, CD8 +, CD20 +, and Ial + cells subsets. Kurtzke's Expanded Disability Status Scale (EDSS) was used for clinical evaluation. Progression rate was defined as the ratio of EDSS to disease duration. Thirteen patients with lumbar disk herniation were investigated as controls. Before MP, we found in MS patients, especially in the CP group, significantly lower CD4 + T-cell percentages in the PB with respect to controls (P<0.05). The percentage of CD4 + T-cells in the CSF of MS patients was significantly higher compared with PB (p = 0.0001), and tended to be higher than in controls (p = 0.072). The CSF mononuclear cell counts were significantly correlated with higher percentages of CSF CD3 + (r = 0.40) and CD4 + (r = 0.47) T-cells and lower CSF CD8 + (r = -0.33) T-cell percentages. B-cell percentages in the CSF were significantly elevated compared with controls for all MS groups. No relation could be obtained between T- or B-cell subsets and EDSS or progression rate. After MP, a significant decrease in PB CD8 + T-cell percentage and simultaneously an increase of the percentage CD8 + T-cells in CSF was noted in the entire MS group and in the CP and RR MS patients. Except for the CP + RR MS patients, CD4 + T-cell percentages in the PB or CSF showed insignificant changes. Our findings support the view that in MS MP might affect the inflammatory process of demyelination by a selective and dissociative effect on T-suppressor/cytotoxic cells in the PB and CSF.     

Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions.In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score.In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.     

A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS.

OBJECTIVE: To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study. BACKGROUND: It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS. METHODS: Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints. RESULTS: The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol-planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group. CONCLUSIONS: Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity.     

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study.

Patients with a clinical diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were randomised in a double-blind, placebo-controlled multicentre trial to investigate whether high-dose intravenous immunoglobulin treatment (IVIg) for 5 consecutive days has a beneficial effect. Fifteen patients were randomised to IVIg and 13 to placebo. In the IVIg treatment group 4 patients improved and 3 patients in the placebo group. The degree of improvement of the patients in the IVIg treatment group was no different from the patients in the placebo group. Electrophysiological studies did not show significant differences between the groups. Since a previously performed cross-over trial showed that a selected group of CIDP patients responded better to IVIg than to placebo, it is concluded that we need better criteria to select CIDP patients for treatment with IVIg.     

恩他卡朋添加治疗症状波动的帕金森病的随机、双盲、安慰剂对照临床研究

目的:探讨添加恩他卡朋治疗PD患者剂末现象的疗效和安全性。方法:40例伴有剂末现象的PD患者进行随机、双盲、安慰剂、平行分组临床对照试验。根据患者日记记录的"开"、"关"期时间、UPDRS各部分评分、研究者总体评估变化量表和左旋多巴每日剂量来评定疗效。结果:恩他卡朋治疗12周时能显著延长"开"期时间、缩短"关"期时间,降低UPDRS评分,减少每日左旋多巴用量,研究者主观感觉65%的患者病情好转,与安慰剂组相比差异有显著意义。不良事件的发生率与安慰剂组相比差异无显著意义。结论:添加恩他卡朋治疗伴有剂末现象的PD患者安全、有效。     

Controlled study of iprazochrome effectiveness (Divascan) in prophylactic treatment of migraine]

The study was designed as double blind, placebo controlled. The patients were treated with 15 mg of iprazochrome daily in three equal doses for eight weeks, or--with equal amount of placebo tablets. The effectiveness was calculated with the use of Migraine Score (MS) by Couch et. al. 44 patients completed the study. In 21 the therapy was positive: 16 out of them were treated with iprazochrome, 5--with placebo. In 23 patients the treatment was negative: 19 out of them took placebo, 4--iprazochrome. Statistical analysis showed significant influence (chi 2 test: p < 0.001; Youle coeff. = 0.88). In iprazochrome group mean decrease of MS was significant after treatment (p < 0.01), but not significantly changed in the placebo group. According to our results iprazochrome was found effective in the prophylaxis of migraine.     

Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized,double-blind,placebo-controlled phase 3 trial

The growing need for symptomatic treatment of post-traumatic neuropathic pain (PTNP) continues to be unmet. Studies evaluating the efficacy of pregabalin for reducing neuropathic pain following trauma and surgery yielded positive results over ≤?8-week treatment. To assess the efficacy and tolerability of pregabalin over 3 months in patients with PTNP, a randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients with PTNP at 101 centers in 11 countries—the longest, largest such trial. Adults diagnosed with PTNP were randomly assigned (1:1) to 15 weeks of pregabalin (flexibly dosed 150–600 mg/day) or matching placebo. Primary efficacy analysis was by mixed-model repeated measures comparing change from baseline to week 15 in weekly mean pain scores between active and placebo groups. Evaluable patients included 274 in the pregabalin group and 265 in the placebo group. Trauma was surgical in 49.6% of patients, non-surgical in the remainder. The primary efficacy analysis showed no statistically significant difference between pregabalin and placebo groups in the change from baseline to week 15 [mean difference, ??0.22 points (95% confidence interval, 0.54–0.10); p?=?0.1823]. However, comparisons for key secondary outcome measures yielded p values?<?0.05 favoring pregabalin. Consistent with the known safety profile of pregabalin, the most common adverse events were dizziness and somnolence (14.6 and 9.9% of patients, respectively) with pregabalin (vs 4.2 and 3.4% with placebo). These findings demonstrate the feasibility of conducting a large, phase 3 registration trial in the heterogeneous PTNP study population.ClinicalTrials.gov NCT01701362.     

Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study

Background

Methylphenidate (MP) is a dopamine- and noradrenaline-enhancing agent beneficial for post-stroke depression (PSD) and stroke recovery due to its therapeutic effects on cognition, motivation, and mood; however, the neural mechanisms underlying its clinical effects remain unknown. This study used functional magnetic resonance imaging (f MRI) to investigate the effect of MP on brain activity in response to cognitive tasks in patients with PSD.

Methods

Nine stroke outpatients with DSM IV defined major depression underwent fMRI during two cognitive tasks (2-back and serial subtraction) on four occasions, on the first and third day of a three-day treatment of MP and placebo. Nine healthy control (HC) subjects matched for age and sex scanned during a single session served as normative data for comparison. The main outcome measure was cognitive task-dependent brain activity.

Results

For the 2-back task, left prefrontal, right parietal, posterior cingulate, and temporal and bilateral cerebellar regions exhibited significantly greater activity during the MP condition relative to placebo. Less activity was detected in rostral prefrontal and left parietal regions. For serial subtraction, greater activity was detected in medial prefrontal, biparietal, bitemporal, posterior cingulate, and bilateral cerebellar regions, as well as thalamus, putamen, and insula. Further, underactivation observed during the placebo condition relative to HC improved or reversed during MP treatment. No significant differences in behavioral measures were found between MP and placebo conditions or between patients and HC.

Conclusions

Short-term MP treatment may improve and normalize activity in cognitive neuronal networks in patients with PSD.     

Acyclovir treatment of relapsing-remitting multiple sclerosis

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on intent-to-treat data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0–2), medium (3–5) and high (6–8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.     

Brainstem lesions may be important in the development of epilepsy in multiple sclerosis patients: An evoked potential study

Objective

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with epileptic seizures sometimes observed in the same patients. In this study, we used evoked responses to study the pathogenesis of epilepsy in MS.

Methods

Patients with a diagnosis of definite MS and who had EPs performed (visual (VEP), brainstem auditory (BAEP) and short latency somatosensory (upper (USSEP) and lower (LSSEP))) were retrospectively included in this study. They were divided into three groups; Group I: Patients with no epilepsy and who were not taking anti-epileptic drugs (AED); Group II: Patients with epilepsy and taking AEDs; and Group III: Patients with no epilepsy who were taking AEDs for symptoms related to neuropathic pain.

Results

Three hundred and fifty-five patients were included in this study; Group I: 229 patients (64.5%), Group II: 20 patients (5.6%) and Group III: 106 patients (29.9%). The proportion of patients with abnormal BAEP and USSEP was higher in Group II.

Conclusions

A positive association exists between the presence of epilepsy in MS patients and BAEP and USSEP abnormalities. Analysis of Group III ruled out AED use as a factor.

Significance

Brainstem lesions may be the cause of epileptogenicity in MS.     

Double-blind crossover study with dolasetron mesilate,a 5-HT<Subscript>3</Subscript> receptor antagonist in cerebellar syndrome secondary to multiple sclerosis

Abstract. Cerebellar syndrome is one of the most disabling developments in multiple sclerosis (MS). In neurodegenerative disorders, cerebellar syndrome is thought to be related to a neurochemical deficit of 5-hydroxytryptamine (5-HT). Previous studies found that a levorotatory form of 5-hydroxytryptophan, a 5-HT precursor, and ondansetron, a 5-HT₃ receptor antagonist, decreased cerebellar symptoms in Friedreichs ataxia and MS. We studied the effect of another 5-HT₃ receptor antagonist, dolasetron mesilate, on cerebellar syndrome in MS patients.Thirty-four MS patients were included in a placebo-controlled double-blind crossover study. They received a single dose of intravenous dolasetron mesilate or placebo. A quantitative evaluation of cerebellar syndrome using the nine-hole peg test and an ataxia score comprising static and kinetic parameters were performed before and after each treatment. No statistical difference was observed in the dolasetron mesilate group, compared with the placebo group. There was, however, inter-individual variability in the treatment response.This double-blind study on cerebellar syndrome in MS patients did not confirm the positive effect of dolasetron mesilate suggested by previous studies.     

Intensive immunosuppression in progressive multiple sclerosis. An open study comparing 3 groups: cyclophosphamide, cyclophosphamide-plasmapheresis and control subjects. Results after 3 years

Three groups of 10 patients each with multiple sclerosis (MS) in a progressive phase were openly matched on the basis of age and invalidity (DSS Kurtzke). Variance analysis showed no significant difference between them for the main MS features. Group 1 received cyclophosphamide for 3 weeks (mean total dose: 152 mg/kg) with methylprednisolone (mean total dose: 2.77 g). Group 2 had a mean number of 9 plasma exchanges prior to a cyclophosphamide-methylprednisolone regimen similar to Group 1 (mean total dose of cyclophosphamide: 160 mg/kg and of methylprednisolone: 3.16 g). Group 3 was made up of controls. At three years, the proportion of stabilized and improved cases was 6/10 in group 1, 9/10 in Group 2 (statistically significant when compared with Group 1), and 0/10 in Group 3. The study of the variations of invalidity (DSS gains) showed a clear significant benefit in the treated groups when compared to controls, but no difference between the treated groups. Longitudinal studies showed that the mean therapeutic benefit was about 2.5 years. The role of cyclophosphamide and of plasma exchanges in these results is discussed.     

Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS

Standard clinical endpoints in multiple sclerosis (MS) studies, such as disability progression defined by the expanded disability status scale (EDSS) and annualized relapse rate, may not fully reflect all aspects of therapeutic benefit experienced by patients. Pivotal studies showed that natalizumab is effective both as monotherapy (AFFIRM study) and in combination with interferon beta-1a (IFNβ-1a) (SENTINEL study) in patients with relapsing MS. We present AFFIRM and SENTINEL data demonstrating the efficacy of natalizumab on prespecified tertiary endpoints, including extent of confirmed change in EDSS score from baseline, time to sustained progression to EDSS milestone scores, hospitalizations, corticosteroid use, and time to confirmed progression of cognitive deficits. Natalizumab significantly reduced changes in EDSS scores (P < 0.001) and proportion of patients progressing to an EDSS score ≥4.0 (P < 0.001) and ≥6.0 (P = 0.002) compared with placebo. Natalizumab + IFNβ-1a significantly reduced changes in EDSS scores compared with placebo + IFNβ-1a (P = 0.011). Based on 0.5 standard deviation change in paced auditory serial addition test-3 score, natalizumab treatment reduced the risk of confirmed progression of cognitive deficits by 43% compared with placebo (HR 0.57 [95% CI 0.37, 0.89], P = 0.013); however, no significant difference between groups was seen in SENTINEL. Natalizumab, both as monotherapy and in combination with IFNβ-1a, significantly reduced the annualized rate of MS-related hospitalizations (by 64 and 61%, respectively) and the annualized rate of relapses severe enough to require steroid treatment (by 69 and 61%, respectively) compared with placebo and placebo + IFNβ-1a (P < 0.001). These analyses underline beneficial effects of natalizumab therapy in relapsing MS patients.     

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study

OBJECTIVE: Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. METHODS: During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test. RESULTS: In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase. CONCLUSION: A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.     

A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy. METHODS: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. RESULTS: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated. CONCLUSION: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.     

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.     

Aggressive multiple sclerosis-is there a role for stem cell transplantation?

Conventional drugs, including disease-modifying drugs, various cytostatic regimens and steroids, are unable to control disease activity in a small group of patients with "malignant" multiple sclerosis (MS). This group of patients could be offered aggressive therapies, such as high-dose immunosuppression followed by haematopoietic stem cell transplant (HSCT). Bone marrow or peripheral blood HSCT has been proposed for the treatment of autoimmune diseases because of its immunosuppressive and immunomodulatory effects, and recapitulation of lymphocyte ontogeny may stabilise or improve the course of MS in some patients. There have been a few small studies conducted using high-dose immunoablation and HSCT. A recent clinical trial of 85 patients treated by HSCT revealed that more than 60% of patients may benefit from this procedure. Due to the perceived risks associated with HSCT, only patients with malignant MS who no longer benefit from more conventional therapies were enrolled. HSCT is thus a justified and feasible treatment in certain patient groups, although transplant-related mortality must be reduced.     

Evaluation of clinical parameters during and after treatment of attack in patients with clinically isolated syndrome: Comparison of the results with that of multiple sclerosis patients

Objectives

The aim of the present study was to examine the changes in the measurement of functions during and after pulse methylprednisolone (MP) treatment during a clinically isolated syndrome (CIS) attack, using the multiple sclerosis functional composite (MSFC) and Expanded Disability Status Scale (EDSS), and to compare the results with that of MS patients.

Patients and method

The present study included 44 patients with CIS and 26 patients with clinically definite multiple sclerosis (MS), as the control group. All patients were having an acute attack and were treated with 1000-mg intravenous methylprednisolone. The scales were administered before-and after-treatment, and at 30 days after treatment.

Results

A 5-days treatment was adequate in 36.9% of CIS patients and 62.5% of MS patients (p = 0.003). A moderate correlation was found between Auditory Consonant Trigram Test (ACT) and paced auditory serial addition test in CIS patients before-treatment. A poor correlation was found between EDSS scores and ACT in CIS patients at all measurement periods. The level of correlation between EDSS and ACT scores was similar in MS patients.

Conclusion

Although MS and CIS patients show similar response to corticosteroid treatment and had similar fatigue characteristics, overall cognitive functioning was better in CIS patients.