Troponin T is elevated in a relevant proportion of patients with 5q-associated spinal muscular atrophy.

Troponin T concentration (TNT) is commonly considered a marker of myocardial damage. However, elevated concentrations have been demonstrated in numerous neuromuscular disorders, pointing to the skeletal muscle as a possible extracardiac origin. The aim of this study was to determine disease-related changes of TNT in 5q-associated spinal muscular atrophy (SMA) and to screen for its biomarker potential in SMA. We therefore included 48 pediatric and 45 adult SMA patients in this retrospective cross-sequential observational study. Fluid muscle integrity and cardiac markers were analyzed in the serum of treatment-naïve patients and subsequently under disease-modifying therapies. We found a TNT elevation in 61% of SMA patients but no elevation of the cardiospecific isoform Troponin I (TNI). TNT elevation was more pronounced in children and particularly infants with aggressive phenotypes. In adults, TNT correlated to muscle destruction and decreased under therapy only in the subgroup with elevated TNT at baseline. In conclusion, TNT was elevated in a relevant proportion of patients with SMA with emphasis in infants and more aggressive phenotypes. Normal TNI levels support a likely extracardiac origin. Although its stand-alone biomarker potential seems to be limited, exploring TNT in SMA underlines the investigation of skeletal muscle integrity markers.

Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases.

5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are two distinct neurological disorders leading to degeneration of lower motor neurons. The antisense oligonucleotides (ASOs) nusinersen and tofersen are novel disease-modifying agents for these diseases, respectively. In the context of ASO treatment, the cytological characteristics and composition of cerebrospinal fluid (CSF) have recently garnered particular interest. This report presents a case series of CSF cytology findings in two patients with SMA and ALS revealing comparable unspecified macrophage inclusions following treatment initiation with nusinersen and tofersen. Yet, the presence of these "asophages" in the treatment course of two different ASOs is of unclear significance. While both treatments have been well tolerated, this phenomenon warrants attention, given the long-term nature of these treatments.

Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study.

Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.

C-tactile touch perception in patients with chronic pain disorders.

INTRODUCTION: Slow brushing over the skin activates C-tactile nerve fibers that transmit pleasant tactile experiences in healthy subjects, leading to an inverted U-shaped velocity dependence of ratings: C-tactile optimal stroking stimulations are rated as more pleasant than slower or faster stimulations. Chronic pain diseases such as postherpetic neuralgia (PHN) and complex regional pain syndrome show altered C-fiber innervation density, sensory loss, and pain sensitization. OBJECTIVES: We aimed to investigate whether C-tactile function is affected in painful conditions. METHODS: We assessed psychophysically C-tactile function and sensory perception thresholds in 16 patients with PHN, 19 patients with complex regional pain syndrome, and 22 healthy controls. RESULTS: Assessment of C-tactile function showed a significantly altered perceived pleasantness of CT stimulation between healthy controls and patients with chronic pain. In specific, tactile stimulation was perceived less pleasant on the affected and contralateral side when compared with controls. In patients with PHN, velocity-dependent pleasantness ratings could not be obtained, suggesting highly impaired C-tactile function with functional loss of pleasant touch perception. CONCLUSIONS: In conclusion, this is the first report of impaired C-tactile function in patients with PHN. Reduced pleasantness resulting from gentle touch can reflect defective C-fiber function or result from central nervous system effects in a chronic pain state.

Insights from the German Version of the Social Touch Questionnaire: How Attitude towards Social Touch relates to Symptoms of Social Anxiety.

Social interpersonal touch is an important part of nonverbal communication and mediates human bonding. However, one's attitude towards touch is highly individual, and touch is not always perceived as pleasant. For instance, socially anxious people show less touch comfort and higher touch avoidance than socially extroverted people. To investigate which aspects of touch attitude relate to symptoms of social anxiety, we adapted the "Social Touch Questionnaire" (STQ) to the German-speaking population and related it to the "Brief Fear of Negative Evaluation Scale" which assesses symptoms related to social anxiety. In a sample of 479 students, validation of the STQ disclosed good reliability and internal consistency. Exploratory factor analysis conducted in half of the sample revealed a three-factor model and suggested shortening the STQ for higher quality. Confirmatory factor analysis in the other half supported these findings. Subscale analyses revealed a correlation between symptoms of social anxiety and dislike of social touch but not between the former and liking of social touch. Overall, touch is an important channel of social communication which individuals with symptoms of social anxiety seem hindered to benefit from. Screening for this issue via the shortened STQ might provide supporting information for therapists. To investigate the transferability of the STQ as a screening tool for daily clinical practice, we suggest further research in clinical samples.

C-tactile touch perception in migraineurs - a case-control study.

BACKGROUND: Migraine is characterized by sensory hypersensitivity and habituation deficits. Slow brushing over the skin activates C-tactile nerve fibers, which mediate pleasant touch and analgesic effects in healthy subjects. As this function is altered in painful conditions, we aimed to examine whether the C-tactile processing is disrupted in migraines. METHODS: To psychophysically assess C-tactile function, we applied optimal and suboptimal C-tactile stroking stimuli on the dorsal forearm (body reference area) and the trigeminally innervated skin of 52 interictal migraineurs and 52 matched healthy controls. For habituation testing, 60 repeated C-tactile optimal stimuli were presented in both test areas. The participants rated each stimulus on a visual analogue scale by intensity, pleasantness, and painfulness. RESULTS: Regarding C-tactile function, migraineurs showed unphysiological rating patterns but no significantly different pleasantness ratings than controls. During repeated stimulation, controls showed stable pleasantness ratings while migraineurs' ratings decreased, especially in those experiencing tactile allodynia during headaches. Migraineurs taking triptans responded like controls. CONCLUSION: The C-tactile function of migraineurs is subclinically altered. Repeated C-tactile stimulation leads to altered habituation but differs from previous work by the direction of the changes. Although the pathophysiology remains unknown, causative mechanisms could include central and peripheral neuronal sensitization, tactile allodynia and hedonic stimulus attributions.