Brain Involvement in Myotonic Dystrophy Type I: From Functional Neuroimaging to the Impact on Quality of Life
Condition: Myotonic Dystrophy Type 1 (DM1)
MeSH terms: Myotonic Dystrophy
Study type: Observational

Summary: 
      This project aims to characterize DM1 patients, by collecting clinical, neuropsychological,
      neuroimaging, and molecular rehabilitative data, in order to elucidate the etiology of
      cognitive troubles, with special attention to the impact of those dysfunctions on quality of
      life.
    

Detailed description: 
      Myotonic Dystrophy Type 1 (DM1), the most common form of muscular dystrophy in adulthood, is
      characterized by a multisystemic involvement in skeletal muscle (atrophy and progressive
      hyposthenia, predominantly in the distal districts, and myotonic phenomenon), and of the
      cardiac, ocular, endocrine, gastrointestinal and central nervous system (CNS) systems. The
      disease, of a genetic nature, is transmitted as an autosomal dominant trait and is due to an
      abnormal expansion of the CTG nucleotide triplet of the gene that encodes a kinase protein
      (DMPK), located on chromosome 19q13.3. Based on the expansion number of nucleotide triplets,
      4 classes of expansion were identified: E1, E2, E3, E4, which are directly related to the
      severity of the phenotype. The pathogenetic basis of the disease is not yet clear to date;
      however, it is hypothesized that the mutation results in the expression of abnormal RNA
      transcripts that induce an alteration of the splicing mechanisms of different gene products.
      The disease frequently presents a typical profile of CNS disorders, characterized by a
      chronic and progressive pattern. The clinically identifiable symptomatology consists of
      cognitive disorders (visual-spatial, attention, executive functions), from alterations in the
      emotional sphere (depressed mood, anxiety and apathetic temperament) and from obsessive /
      avoiding / passive-aggressive personality traits. A difficulty in recognizing facial
      emotional states has also been reported. The overall intellectual performance tends to be at
      the lower limits of the norm when compared to the population of equal age and education. From
      the neuroradiological point of view, the presence of cortical atrophy, usually more evident
      in the frontal and temporal, and of white matter lesions spread on both hemispheres, often
      asymmetric, was detected. Despite the high number of studies on the subject, the frequency
      and localization of these abnormalities, as well as their relationship to cognitive
      involvement, the age of onset, duration of disease and genetic profile have not yet been
      clarified. In clinical practice, patients frequently present a partial impairment of insight,
      or the psychological ability to have a clear and complete awareness of their condition of
      illness, the incidence of which, however, has never been investigated. This disorder, also
      defined by the name of anosognosia, generates in the patient a partial admission of
      difficulties, which interferes with its adaptability to treatments and in the relationship
      with the caregiving figures. Lack of awareness about one's state of illness is a
      psychological condition found in various neurological diseases of an organic or
      neurodegenerative nature. The neuroanatomical and neuropsychological bases are complex and to
      date not fully known. The frontal lobes have been identified as possible neuroanatomical
      localizations of the disorder; however, data in the literature about the relationship between
      executive function deficits and anosognosia are extremely conflicting. In this patients, the
      rehabilitative intervention is useful for optimizing muscle tropism and prevents further
      atrophy of disused muscle fibers. MicroRNAs (miRNAs/miRs) miR-1, miR-206, miR-133a, and
      miR-133b are called "myomiRs" and are involved in myogenesis, muscle maintenance, and
      recovery and can be used as possible biomarkers to follow the effectiveness of rehabilitation
      treatment. There are currently no similar studies on patients with DM1.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        DM1 subjects of both sexes: de novo or with previous diagnosis that show significant
        worsening detectable during the follow-up foreseen by the normal cure procedure with
        clinical presentation indicating a CNS compromise. DM1 is frequently characterized by a
        significant involvement of the CNS, causing cognitive disorders, mood and behavior, varying
        from case to case.
      
Keywords: DM1; Brain; MRI