Clinical Outcome Evaluations and CBT Response Prediction in Myotonic Dystrophy.

Background: The European OPTIMISTIC clinical trial has demonstrated a significant, yet heterogenous effect of Cognitive Behavioural Therapy (CBT) for Myotonic Dystrophy type 1 (DM1) patients. One of its remaining aims was the assessment of efficacy and adequacy of clinical outcome measures, including the relatively novel primary trial outcome, the DM1-Activ-c questionnaire.

Objectives: Assessment of the relationship between the Rasch-built DM1-Activ-c questionnaire and 26 commonly used clinical outcome measurements.

Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1.

Objective: To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.

Methods: Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months.

Human brain pathology in myotonic dystrophy type 1: A systematic review.

Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative of widespread grey and white matter involvement. The aim of the present study was to systematically review the literature on brain pathology in DM1. We conducted a structured search in EMBASE (index period 1974-2017) and MEDLINE (index period 1887-2017) on December 11, 2017, using free text and index search terms related to myotonic dystrophy type 1 and brain structures or regions.

Quantitative Muscle MRI Depicts Increased Muscle Mass after a Behavioral Change in Myotonic Dystrophy Type 1.

Background Patients with myotonic dystrophy type 1 (DM1) increased their physical activity and exercise capacity following a behavioral intervention. However, it is unknown what is altered in muscles of patients with DM1 as a result of this intervention. The increased exercise capacity suggests that decelerated fat infiltration or increased muscle cross-sectional area (CSA) could be involved.

Characterization of EEG-based functional brain networks in myotonic dystrophy type 1.

Objective: In the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits.

Methods: In this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment.

Inclusion body myositis in patients with spinocerebellar ataxia types 3 and 6.

Objectives: To describe the combination of spinocerebellar ataxia (SCA) types 3 and 6 and sporadic inclusion body myositis (IBM).

Methods: A description of five patients with SCA type 3 and 6 who were diagnosed with IBM. We explore possible mechanisms explaining the coexistence of both diseases.

Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease characterized by multi-system involvement. Affected organ system includes skeletal muscle, heart, gastro-intestinal system and the brain. In this review, we evaluate the evidence for alterations in insulin signaling and their relation to clinical DM1 features.

Genetic determinants of disease severity in the myotonic dystrophy type 1 OPTIMISTIC cohort.

Objective: To evaluate the role of genetic variation at the locus on symptomatic diversity in 250 adult, ambulant patients with myotonic dystrophy type 1 (DM1) recruited to the Observational Prolonged Trial in Myotonic Dystrophy Type 1 to Improve Quality of Life-Standards, a Target Identification Collaboration (OPTIMISTIC) clinical trial.

Methods: We used small pool PCR to correct age at sampling biases and estimate the progenitor allele CTG repeat length and somatic mutational dynamics, and AciI digests and repeat primed PCR to test for the presence of variant repeats.

Results: We confirmed disease severity is driven by progenitor allele length, is further modified by age, and, in some cases, sex, and that patients in whom the CTG repeat expands more rapidly in the soma develop symptoms earlier than predicted.

Affective symptoms and apathy in myotonic dystrophy type 1 a systematic review and meta-analysis.

Background: To gain insight into the prevalence of apathy, depression and anxiety symptoms in myotonic dystrophy type 1 (DM1) patients on the basis of a systematic review with a meta-analysis.

Methods: One author systematically searched and selected studies from Embase, Medline, PsychInfo and Web of Science (index periods up to August 2018). Data extraction and bias assessment were performed independently by two authors.

Structural white matter networks in myotonic dystrophy type 1.

The myriad of neuropsychiatric manifestations reported in myotonic dystrophy type 1 may have its origin in alterations of complex brain network interactions at the structural level. In this study, we tested the hypothesis that altered white matter microstructural integrity and network organisation were present in a cohort of individuals with DM1 compared to unaffected controls, which was expected to be associated with CNS related disease manifestations of DM1. We performed a cross-sectional neuropsychological assessment and brain MRI in 25 myotonic dystrophy type 1 (DM1) patients and 26 age, sex and educational level matched unaffected controls.

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse.

In a Dutch consanguineous family with recessively inherited nonsyndromic hearing impairment (HI), homozygosity mapping combined with whole-exome sequencing revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs22).

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1.

Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK).

Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data.

Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients.

The cognitive profile of myotonic dystrophy type 1: A systematic review and meta-analysis.

Objective: To examine the cognitive profile of patients with myotonic dystrophy type 1 (DM1) on the basis of a systematic review and meta-analysis of the literature.

Methods: Embase, Medline and PsycInfo were searched for studies reporting ≥1 neuropsychological test in both DM1 patients and healthy controls. Search, data extraction and risk of bias analysis were independently performed by two authors to minimize error.

Brain imaging in myotonic dystrophy type 1: A systematic review.

Objective: To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1).

Methods: We searched Embase (index period 1974-2016) and MEDLINE (index period 1946-2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias.