Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome

Chronotherapy Advances in the Management of Chronic Neurological and Cardiovascular Diseases: Complex Interactions of Circadian Rhythm Environmental Inputs, Nutrition and Drug Administration and Their Impact on Human Health

New scientific evidence raises awareness concerning the human-specific interplay among primary environmental conditions, such as the light–dark cycle, activity–rest alternation, nutritional patterns, and their reflection on the physiological and pathological characteristics that are displayed uniquely by every individual. One of the critical aspects in the clinic is to understand the role of circadian rhythms as remarkable modulators of the biological effects of drugs and to aim for an optimal overlapping of the time of administration of medicines with the physiologic release of certain hormones, the time-dependent expression of genes, or the key-regulatory protein synthesis, which are all circadian-driven processes. The pharmacokinetics and pharmacodynamics profiles, as well as the possible drug interactions of neurotropic and cardiovascular agents, are intensely subjected to endogenous circadian rhythms, being essential to identify as much as possible the patients’ multiple risk factors, from age and gender to lifestyle elements imprinted by dietary features, sleep patterns, psychological stress, all the way to various other associated pathological conditions and their own genetic and epigenetic background. This review chapter will highlight the involvement of biological rhythms in physiologic processes and their impact on various pathological mechanisms, and will focus on the nutritional impact on the circadian homeostasis of the organism and neurologic and cardiovascular chronotherapy