Impact of DM1 on the Brain

DM1 is characterized by involvement of multiple organ systems, raising challenges for understanding disease mechanisms, development of effective disease management strategies, and designing effective and testing therapeutics. The disease burden and unmet need represented by the CNS sequella of DM1 have received insufficient attention to date. Recent efforts by MDF, including the Consensus-based Care Recommendations for Adults with DM1 and the recent session at the 2017 MDF Annual Conference, “Bringing the Patient Voice to CNS-Targeting Drug Development in Myotonic Dystrophy” are important efforts to address this challenge. Given the impact on the brain, a key part of the challenge is understanding how aware are patients of their own disease and to what extent can they assist researchers in improving management and therapy of DM1?

A New Study of Disease Awareness in DM1

Dr. Sigrid Baldanzi and colleagues at the University of Pisa have published results from a cross-sectional study of 65 adult-onset DM1 patients, assessing cognitive function and quality of life. Specifically, the research team was interested in determining how cognitive dysfunction and neuropsychological manifestations of DM1 impacted the patient’s awareness of their own disease—a phenomenon known as anosgnosia or lack of insight.

Anosgnosia, and the consequent reduced patient participation with caregivers, can impact DM1 in multiple ways-- diagnosis can be delayed, lack of awareness and misattribution of the causes of their symptoms can occur, and patient compliance with treatment impacted. To better understand patient awareness in DM1, the research team used a battery of endpoints to assess clinical and neuropsychological status, quality of life, and disease unawareness. The team defined disease unawareness as “an altered ability to recognize the presence or appreciate the severity of deficits in sensory, perceptual, motor, affective, or cognitive functioning.”

The cognitive profile of study subjects was heterogeneous, but executive functions, cognitive flexibility, conceptualization, and visuo-spatial memory tasks ranked below matched control subjects. Assessment of quality of life using INQoL revealed only a mild impact of the patient’s disability. In assessing patient awareness of the impact of their disease, those with mild motor involvement frequently understated their degree of motor impairment in comparison to physician-rated (MIRS) motor abilities. For approximately half of the cohort, discrepancies were noted between patient INQoL ratings and caregivers reports of disease impact. Patients underreported psycho-social difficulties, including their independence and social relationships, when compared to caregiver reports. Patients did not exhibit deficits in awareness of emotional aspects as detected by INQoL.

The research team concluded that DM1 patients did not experience generalized disease unawareness, but rather that unawareness of particular psychosocial and behavioral deficits were present in over half of their cohort. They hypothesize a linkage between anosognosia and brain dysfunction in DM1 and suggest that the terminology “social cognition dysfunction” captures the disease unawareness seen here. Indeed, understanding of the specific features of anosognosia in DM1 may help elucidate its underlying neuroanatomical correlates.  

Finally, the research team noted that analytic tools for anosognisia must be tailored for specific diseases and suggest that patient/caregiver discrepancies in INQoL scores form the basis for such a tool for DM1.

Reference:

Disease awareness in myotonic dystrophy type 1: an observational cross-sectional study.
Baldanzi S, Bevilacqua F, Lorio R, Volpi L, Simoncini C, Petrucci A, Cosottini M, Massimetti G, Tognoni G, Ricci G,Angelini C, Siciliano G.
Orphanet J Rare Dis. 2016 Apr 4;11:34. doi: 10.1186/s13023-016-0417-z.