Disability progression in relapse-free multiple sclerosis patients on fingolimod versus interferon-beta/glatiramer acetate.

BACKGROUND: Disability progression independent of relapses (PIRA) has been described as a frequent phenomenon in relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To compare the occurrence of disability progression in relapse-free RRMS patients on interferon-beta/glatiramer acetate (IFN/GA) versus fingolimod. METHODS: This study is based on data from the Swiss association for joint tasks of health insurers. Time to relapse and 12-month confirmed disability progression were compared between treatment groups using multivariable Cox regression analysis with confounder adjustment. Inverse-probability weighting was applied to correct for the bias that patients on fingolimod have a higher chance to remain relapse-free than patients on IFN/GA. RESULTS: We included 1640 patients (64% IFN/GA, 36% fingolimod, median total follow-up time = 4-5 years). Disease-modifying treatment (DMT) groups were well balanced with regard to potential confounders. Disability progression was observed in 155 patients (8.8%) on IFN/GA and 51 (7.6%) on fingolimod, of which 44 and 23 were relapse-free during the initial DMT, respectively. Adjusted standard regression analysis on all patients indicated that those on fingolimod experience less frequently disability progression compared with IFN/GA (hazard ratio = 0.53 (95% confidence interval = 0.37-0.76)). After bias correction, this was also true for patients without relapses (hazard ratio=0.56 (95% confidence interval = 0.32-0.98). CONCLUSION: Our analysis indicates that fingolimod is superior to IFN/GA in preventing disability progression in both relapsing and relapse-free, young, newly diagnosed RRMS patients.

Comparative analysis of natalizumab versus fingolimod as second-line treatment in relapsing-remitting multiple sclerosis.

BACKGROUND: No randomized controlled trials have compared the efficacy of fingolimod or natalizumab as second-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To compare clinical outcomes after escalation to fingolimod versus natalizumab in patients with clinically active RRMS. METHODS: Using the registry of the Swiss Federation for Common Tasks of Health Insurances, we identified patients with RRMS and ≥1 relapse in the year before switching from interferon beta or glatiramer acetate to fingolimod or natalizumab. Propensity score matching was used to select patients with comparable baseline characteristics. Relapse and Expanded Disability Status Scale (EDSS) outcomes were compared in paired, pairwise-censored analyses. RESULTS: Of the 547 included patients, 358 were matched (fingolimod, n = 179; natalizumab, n = 179). Median follow-up time was 1.8 years (interquartile range 0.9-2.9). Patients switching to natalizumab had a lower risk of relapses (incidence rate ratio 0.5, 95% confidence interval (CI) 0.3-0.8, p = 0.001) and were more likely to experience EDSS improvement (hazard ratio (HR) 1.8, 95% CI 1.1-2.7, p = 0.01) compared to fingolimod. We found no differences in the proportion of patients free from EDSS progression (HR 0.9, 95% CI 0.5-1.5, p = 0.62). CONCLUSION: Natalizumab seems to be more effective in reducing relapse rate and improving disability compared with fingolimod.

Trunk sway in mildly disabled multiple sclerosis patients with and without balance impairment.

Multiple sclerosis (MS) causes a broad range of neurological symptoms. Most common is poor balance control. However, knowledge of deficient balance control in mildly affected MS patients who are complaining of balance impairment but have normal clinical balance tests (CBT) is limited. This knowledge might provide insights into the normal and pathophysiological mechanisms underlying stance and gait. We analysed differences in trunk sway between mildly disabled MS patients with and without subjective balance impairment (SBI), all with normal CBT. The sway was measured for a battery of stance and gait balance tests (static and dynamic posturography) and compared to that of age- and sex-matched healthy subjects. Eight of 21 patients (38%) with an Expanded Disability Status Scale of 1.0-3.0 complained of SBI during daily activities. For standing on both legs with eyes closed on a normal and on a foam surface, patients in the no SBI group showed significant differences in the range of trunk roll (lateral) sway angle and velocity, compared to normal persons. Patients in the SBI group had significantly greater lateral sway than the no SBI group, and sway was also greater than normal in the pitch (anterior-posterior) direction. Sway for one-legged stance on foam was also greater in the SBI group compared to the no SBI and normal groups. We found a specific laterally directed impairment of balance in all patients, consistent with a deficit in proprioceptive processing, which was greater in the SBI group than in the no SBI group. This finding most likely explains the subjective symptoms of imbalance in patients with MS with normal CBT.

Comparative analysis of dimethyl fumarate and fingolimod in relapsing-remitting multiple sclerosis.

BACKGROUND: Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To compare the effectiveness of dimethyl fumarate and fingolimod in a real-world setting, where both agents are licensed as a first-line DMT for the treatment of RRMS. METHODS: We identified patients with RRMS commencing dimethyl fumarate or fingolimod in the Swiss Federation for Common Tasks of Health Insurances (SVK) Registry between August 2014 and July 2019. Propensity score-matching was applied to select subpopulations with comparable baseline characteristics. Relapses and disability outcomes were compared in paired, pairwise-censored analyses. RESULTS: Of the 2113 included patients, 1922 were matched (dimethyl fumarate, n = 961; fingolimod, n = 961). Relapse rates did not differ between the groups (incident rate ratio 1.0, 95%CI 0.8-1.2, p = 0.86). Moreover, no difference in the hazard of 1-year confirmed disability worsening (hazard ratio [HR] 0.9; 95%CI 0.6-1.6; p = 0.80) or disability improvement (HR 0.9; 95%CI 0.6-1.2; p = 0.40) was detected. These findings were consistent both for treatment-naïve patients and patients switching from another DMT. CONCLUSION: Dimethyl fumarate and fingolimod have comparable effectiveness regarding reduction of relapses and disability worsening in RRMS.

[Cerebral vasculitis]. / Zerebrale Vaskulitis.

Cerebral vasculitis is a rare disease with a potentially harmful or even fatal outcome that often affects young adults. Primary autoimmune mediated disease can be distinguished from secondary vasculitis associated to infectious disorders, connective tissue diseases, malignancies or toxic drug effects. Pathomechanisms lead to destruction of the vessel wall and consecutive hemorrhagic or ischemic brain lesions. Beyond these mechanisms direct autoimmune mediated neurotoxicity is postulated. Clinical presentation is highly variable with potentially fluctuating signs and symptoms. Besides multifocal deficits from disseminated CNS involvement, diffuse encephalopathy or psychosis may result from diffuse CNS affection. For systemic vasculitis with CNS involvement, affection of joints, skin and organs may facilitate the diagnostic evaluation. CNS affection in systemic diseases is highly variable and may even precede systemic manifestation. The diagnostic work-up includes clinical evaluation, analysis of autoantibodies, MRI, digital subtraction angiography and biopsy of the affected tissue in doubtful cases. Standard therapy are corticosteroids often combined with immunosuppressants such as azathioprine, methotrexate or mycophenolate mofetil in chronic disease or cyclophosphamid in acute disorder. When therapy can be initiated timely, prognosis of cerebral vasculitis is usually favourable.

Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease.

BACKGROUND: In Switzerland, the first course of intravenous steroids for treatment of episodes of demyelinating CNS disease is usually administered in an inpatient setting. We prospectively evaluated short term tolerance of treatment with special emphasis on sleep quality. METHODS: Patients with a first event of presumed demyelinating disease (CIS), multiple sclerosis relapses (MS) or sub-acute disease progression were treated with a 5-day regimen of intravenous methylprednisolone (IVMP) in our inpatient clinic. Patients' experience was documented by self-report questionnaires including a standardised depression scale (ADSL). Laboratory tests were performed on a routine basis. Fasting glucose, blood pressure and pulse were measured before every infusion. Activity and sleep patterns were analysed by wrist actigraphs during the 5 day infusion period and at follow-up after 1-2 months. RESULTS: A total of 66 patients participated in the study. Of these, 55 were steroid treatment naïve, and 11 patients, who had received intravenous steroid relapse treatment before, were admitted because of disabling symptoms. Mood disturbances were reported before steroid treatment, however significantly less often at the end of the steroid pulse and during follow-up. Sleep efficiency as measured by wrist actimetry was high before, during and after steroid treatment. CONCLUSION: Therapy was well tolerated without severe side effects in CIS and MS patients. Sleep efficiency was not disturbed. In conclusion there are no obstacles to change from an inpatient to an outpatient setting for the steroid treatment of relapses in MS and CIS, but rare psychotic reactions to steroid treatment are not predictable.

Infantile spasms: does season influence onset and long-term outcome?

To study whether onset of infantile spasms manifests seasonal variation, as previously reported, and whether any such seasonality is associated with treatment response and long-term outcome, data for 57 patients were retrospectively reviewed. The data were collected from hospital files and through a mail survey of children with infantile spasms born from 1980 to 2002 and monitored at the University Children's Hospital of Berne, Switzerland. The mean age at time of onset of infantile spasms was 7 months (range, 0.75-40), at diagnosis 8 months (range, 1-42) and at follow-up 11.3 years (range, 1-23 years). In 77% of participants, the etiology of infantile spasms was known (symptomatic); in the remaining 23% it was not known (nonsymptomatic). In contrast to previous findings, onset of infantile spasms was not associated with calendar month, photoperiod, or global solar radiation. Long-term prognosis was poor: 4 of the 57 (7%) children died; 49 (86%) had cognitive impairment and 40 (70%) had physical impairment; 31 (54%) had cerebral palsy, 37 had (65%) persistent seizures, and 9 (16%) had Lennox-Gastaut syndrome. Symptomatic infantile spasms were associated with worse cognitive outcome (P < 0.001), but treatment modality and overall duration of infantile spasms were not. There was no association of calendar month or photoperiod at onset with cognitive outcome or treatment response.

An unusual cause of stridor in childhood due to focal epileptic seizures.

Respiratory disorders with stridor are a frequent cause of admission for children in an emergency department. Laryngospasm, as an isolated symptom of epilepsy, is a rare phenomenon [1, 3, 5]. Other respiratory symptoms of epilepsy, rarely seen in childhood, might be apnoeic spells [2, 4]. We report on a child with laryngospasm due to focal epileptic seizures.

Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis.

In order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 +/- 0.4 pg/ml, range 1.1-2.8 vs. 1.5 +/- 0.2 pg/ml, range 0.9-2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.