Minimal clinically important differences in functional motor scores in adults with spinal muscular atrophy.

BACKGROUND AND PURPOSE: In patients with spinal muscular atrophy (SMA), functional disease scores are frequently used to evaluate the course of the disease and the efficacy of treatment. The aim of the present study was to propose minimal clinically important difference (MCID) values for motor scores in order to estimate the degree of change within a functional score that can be considered clinically meaningful. METHODS: To estimate the MCID, distribution-based approaches were used. For each assessment [Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE) and 6-min walk test (6MWT)] and subgroup (SMA type 2, SMA type 3, ambulatory and non-ambulatory), the following MCID values based on a cohort of 51 adults with SMA were calculated: standard error of measurement (SEm), one-half of standard deviation (1/2 SD) and one-third of standard deviation (1/3 SD) of patients' baseline scores. RESULTS: For the overall cohort, the SEm, 1/2 SD and 1/3 SD MCID values were 2.9, 6.4 and 4.3 for the RULM and 4.3, 10.6 and 7.0 for the HFMSE, respectively. Subgroup analysis led to generally lower standard deviations and consecutively lower MCID values due to the significantly different motor functions of the groups. The respective MCID values for the 6MWT were 55.5 m, 71.1 m and 47.8 m. CONCLUSIONS: Our data provide MCID values for functional motor scores commonly used in adults with SMA in order to distinguish statistical effects from 'real' changes. A complementary systematic consensus process could help to further adjust the MCID values we propose.

Fatigue in adults with spinal muscular atrophy under treatment with nusinersen.

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Treatment with the antisense oligonucleotide nusinersen has been shown to improve motor function. Fatigue can be measured within the Fatigue Severity Scale (FSS). FSS is a self-reported questionnaire consisting of nine items to quantify fatigue severity within the last week. Higher values indicating a higher severity. Using the FSS, fatigue was measured in 28 adult patients, subdivided into ambulatory and non-ambulatory, suffering from a genetically confirmed 5q-SMA under treatment with nusinersen in accordance with the label. Correlations were performed among FSS and motor scales, 6-minute walk test (6MWT) and Hammersmiths Functional Motor Scale Expanded (HFMSE). Evaluation was performed prior to treatment initiation and after 6 and 10 months. The mean FSS score for all 28 patients at baseline was 4.61 ± 1.44. After 6 months mean FSS score significantly reduced to 3.92 ± 1.35. After 10 months mean FSS score had not differed from baseline, 3.84 ± 1.25. A moderate negative correlation of the difference of FSS and 6MWT after 6 months compared to baseline conditions was measured. Nusinersen reduces fatigue as measured by the FSS in adult patients with 5q-SMA transiently after initiation of treatment. There was no reduction of FSS 10 months after the beginning of treatment when compared to baseline.

Early platelet and leukocyte decline in patients with neuroinflammatory disorders after intravenous immunoglobulins.

BACKGROUND AND PURPOSE: Intravenous immunoglobulins (IVIGs) are a common therapy in patients with neuroinflammatory disorders, especially chronic inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndrome. Hematological toxicities upon IVIG infusion are a known side effect and still an important subject of investigation. METHODS: Laboratory results and data for clinical efficacy and tolerability of 62 patients with neuroinflammatory disorders treated with IVIG (0.4 g/kg bodyweight per day over 5 days) at the Department of Neurology, University of Duisburg-Essen, Germany, were retrospectively analyzed. Blood samples were taken before and 1 day after IVIG administration. RESULTS: In pre-treated and first-time treated patients, there was a significant decrease in white blood cell count (WBC) (8.10 ± 2.85/nl to 5.61 ± 2.50/nl, P < 0.001, n = 57) and platelets (255 ± 72/nl to 215 ± 66/nl, P < 0.001, n = 57). Mild hemolysis of red blood cells was found in patients who received IVIG for the first time (red blood cell count 4.61 ± 0.67/pl to 4.28 ± 0.52/pl, hemoglobin 13.7 ± 1.7 g/l to 13.0 ± 1.7 g/l, P < 0.001, n = 40). Hemolysis was associated with less tolerability of IVIG treatment and clinical efficacy was accompanied with a higher decline of WBC (not significant). CONCLUSIONS: Next to mild hemolysis, a significant decrease in WBC and platelets can be detected early after high dose IVIGs in patients with neuroinflammatory disorders. Changes in blood counts may be possible markers for clinical efficacy and tolerability. Patients with low blood counts in advance should be particularly closely monitored whilst on IVIG treatment.

[The role of opioids in the treatment of primary headache disorders]. / Stellenwert von Opioiden in der Therapie von primären Kopfschmerzerkrankungen.

There is no sufficient evidence for opioids in the acute treatment of primary headache disorders. Controlled clinical trials using triptans as comparator are missing. Data show high frequent headache recurrence, typical side effects of opioids, increased risk of chronification, and development of addiction in primary headache patients treated with opioids. Chronic headache patients with opioid therapy often experience lengthy withdrawal treatment. On the basis of the current scientific data, opioids should be avoided in acute and prophylactic treatment of primary headache disorders.