Impaired diaphragmatic motility in treatment-naive adult patients with spinal muscular atrophy improved during nusinersen treatment.

INTRODUCTION/AIMS: The leading clinical feature of 5q-associated spinal muscular atrophy (SMA) is symmetric, proximal muscle weakness. Muscles involved in ventilation exhibit a specific pattern of denervation: intercostal muscles are severely atrophic, whereas the diaphragm muscle is less affected. The aim of this study was to investigate the involvement of diaphragmatic function by ultrasound imaging in adult patients with SMA and to quantify dynamics of diaphragmatic function during nusinersen treatment. METHODS: Diaphragmatic thickness, thickening, and excursion during quiet breathing were assessed in 24 adult patients with SMA type 2 and 3 by diaphragm ultrasound imaging before and during nusinersen treatment and were correlated with spirometric parameters. RESULTS: Diaphragm thickness was not reduced, but increased in a remarkable proportion of patients, whereas diaphragm thickening and excursion were reduced in about 20% to 30% of nusinersen-naive, adult patients with SMA types 2 and 3. During 26 months of nusinersen treatment, diaphragm thickening fraction and excursion improved. DISCUSSION: Diaphragm ultrasound imaging can provide disease- and treatment-relevant information that is not identified during routine clinical assessments and may therefore be a valuable complementary outcome measure.

Affection of Respiratory Muscles in ALS and SMA.

Respiratory dysfunction is a common cause of morbidity and mortality in motor neuron disease (MND). However, classical volitional measures of respiratory function in these patients are impeded by, e.g., bulbar paralysis or progressive disability. Diaphragm ultrasound imaging might be a valuable tool for assessing respiratory impairment, albeit different ultrasound measures have not been systematically investigated in adult MND patients and, in particular, have not yet been comparatively applied in adult patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). We hypothesized that in contrast to ALS patients, adult SMA patients show a relative sparing of diaphragm function. We retrospectively analyzed diaphragm ultrasound imaging data of 40 patients with ALS and 23 patients with SMA in comparison to a multitude of established parameters of respiratory function. Indeed, ALS patients showed more severe diaphragm dysfunction than adult SMA patients, however, diaphragm dysfunction was also common in adult SMA patients. Notably, dynamic measures of diaphragm function rather than thickness measures were impaired in ALS compared to SMA. Thus, diaphragm ultrasound imaging might be a useful tool to evaluate respiratory dysfunction in adult MND patients. Future larger and prospective studies are needed to validate our initial findings.

Asymmetry of Periodic Leg Movements in Sleep (PLMS) in Parkinson's Disease.

BACKGROUND: Periodic limb movements in sleep (PLMS) are repetitive movements usually of the legs strongly associated with Restless-legs syndrome (RLS), which appear more frequently in males, older age and other sleep disturbances, such as sleep-disordered breathing (SDB). Patients with Parkinson's disease (PD) suffer from various sleep disturbances including REM sleep behavior disorder, RLS and PLMS. Although a dopaminergic pathophysiology of PLMS is discussed, no systematic data on PLMS side-to-side distribution in PD and its correlation with asymmetry of motor symptoms are available. OBJECTIVE: This study aimed at elucidating PLMS asymmetry in correlation to that of motor symptoms in PD compared to SDB and RLS. METHODS: Cross-sectional, retrospective analysis of two polysomnography (PSG) recordings per patient scoring PLMS separately for both legs. RESULTS: Of 105 patients (44 PD, 44 age- and sex-matched SDB and 17 RLS patients) PLMS measures (number of PLM, PLM-Index, PLM-arousal index) showed significant side-to-side differences in all disease entities in both PSGs (P < 0.001; Wilcoxon rank test). PLM-Index asymmetry (PLM-I difference of >5/h between both sides) was observed less frequently in PD (34% of patients) compared to RLS (77% , P < 0.05) and SDB (59% , P < 0.05; χ2 test). In asymmetric PD patients, predominant side of PLMS was more stable than in SDB and RLS comparing the two PSGs, but we did not detect an agreement between PLMS predominant side with that of motor symptoms in PD patients. CONCLUSIONS: Only the minority of PD patients shows asymmetric PLMS distribution with relatively high night-to-night stability but no correlation with motor symptom asymmetry.