Rapid, Sensitive, and Versatile: A 5-Year Perspective on Applications of Ambient Ionization Mass Spectrometry in Bioanalytical Science.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder, characterized not only by myotonia and progressive muscle weakness, but also by a broad range of clinical features, including cardiac conduction defects and central nervous system (CNS) alterations. DM1 is highly variable in terms of age at onset, symptom severity, and clinical presentation. Anticipation, manifested by increasing severity and earlier onset in successive generations, is particularly pronounced in DM1, which can affect adults, children, and newborns (congenital DM1, or CDM). Although initially considered primarily a muscle and cardiac disorder, accumulating clinical, neuropsychological, imaging, and histopathological evidence has demonstrated that DM1 is also a true brain disorder. Central nervous system (CNS) involvement in DM1 has been well documented in early-onset forms, especially congenital and pediatric-onset DM1. Although the congenital form (CDM) is associated with severe systemic symptoms at birth, children who survive the neonatal period frequently present with significant neurological and cognitive impairments. These include moderate to severe intellectual disability, reduced IQ, delays in speech and language development, deficits in visuospatial and visuo-constructive abilities, and attention deficit, with or without hyperactivity (ADHD). Several studies have also reported autism spectrum disorder, communication difficulties, and social anxiety. A parental survey further emphasized that communication difficulties and fatigue had the greatest impact on children's daily lives. In the pediatric form of DM1, classical neuromuscular symptoms may be absent. In such cases, cognitive impairments, such as visuo-spatial deficits, executive dysfunction, and learning difficulties, as well as psychiatric manifestations, including difficulties in forming relationships with peers, may represent the only clinical signs of the disease. Executive dysfunction, in particular, results in reduced initiative, impaired planning and decision-making abilities, and frequently leads to apathy and inactivity, which significantly impact quality of life in this patient population. In adult DM1 patients, cognitive impairment with lower IQ scores is a common but variable feature, even in the least severe forms. Deficits in executive functions, episodic memory, and visuo-constructive abilities are frequently reported and are suggestive of a frontal dysexecutive syndrome. Patients are often described as apathetic, avoidant, and lacking initiative, with significant difficulties in social interactions and daily activities. Apathy has been linked to frontal lobe dysfunction and cognitive decline, independently of fatigue, sleepiness, age, or motor disability. Many DM1 patients also show impairments in social cognition, including difficulties recognizing facial expressions and understanding others’ mental states, as demonstrated by deficits in theory of mind tasks. In addition to cognitive and behavioral symptoms, DM1 patients frequently suffer from excessive daytime sleepiness (EDS), sleep apnea, periodic limb movements, REM sleep dysregulation, and prolonged nocturnal sleep. EDS appears to result primarily from central dysfunction of sleep regulation, while both respiratory muscle involvement and impaired central ventilatory control contribute to sleep-related breathing disorders. Fatigue, a major complaint in DM1, likely arises from both central and peripheral mechanisms, with CNS dysfunction playing a primary role in the subjective sense of tiredness.