Myotonic Dystrophy 1, Myotonic Dystrophy 2
Conditions
Keywords
neuromuscular disorders, MRI, white matter, brain, myotonic dystrophy
Brief summary
The natural history of brain affection in myotonic dystrophy types 1 and 2 is still unknown. The investigators designed a 5-year longitudinal neuropsychological and neuroimaging follow-up study to address this issue. Myotonic dystrophy type 1, myotonic dystrophy type 2 patients, and healthy controls were enrolled. All participants undergo clinical-neurological examinations, neuropsychological analyses according to a 13-item neuropsychological test battery, and 3T-brain MRI including voxel-based morphometry and diffusion tensor imaging at baseline and at follow-up using identical examination protocols.
Detailed description
It is unknown whether brain affection in myotonic dystrophy types 1 and 2 is due to neurodevelopmental defects, neurodegeneration, or both. An exact definition of the nature and dynamic of brain affection is of urgent need for the identification of clinical trial outcome parameters and the design of therapy compounds. The investigators planned a 5-year longitudinal study to examine the natural history of functional and structural brain affection. Myotonic dystrophy type 1, myotonic dystrophy type 2 patients, and healthy controls were enrolled. All participants undergo clinical-neurological examinations, neuropsychological analyses according to a 13-item neuropsychological test battery, and 3T-brain MRI at baseline and at follow-up using identical examination protocols. The intended time span between baseline and follow-up examinations is 5 years minimum. To investigate gray and white matter affection, voxel-based morphometry and diffusion tensor imaging are performed, and data are statistically analyzed including (i) group comparisons between patients and controls at baseline and follow-up, and (ii) group comparisons using difference maps to focus on isolated disease-related effects over time.
Interventions
OTHERmedical history
The complete medical history (including cardiovascular risk factors and medication) will be assessed at baseline and follow-up.
Neurological examination will be performed at baseline and follow-up.
OTHERneuropsychological testing
Neuropsychological testing using a 13 item test battery will be performed at baseline and follow-up.
OTHERbrain MRI
Brain MRI ( 3.0 T) will be performed using the same hard- and software at baseline and follow-up.
Sponsors
Forschungszentrum Juelich
Life and Brain Center Bonn
The Marigold Foundation
University Hospital, Bonn
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
for healthy controls: * written informed consent * normal neurological examination without any acute or former neurological or severe psychiatric disease, no medical history of traumatic brain injury Inclusion criteria for patients: * written informed consent * diagnosis confirmed by genetic testing * no other neurological or severe psychiatric disease, no medical history of traumatic brain injury
Exclusion criteria
for healthy controls and patients: * use of psychoactive substances including alcohol (except nicotine), formerly or currently; treatment with modafinil * severe psychiatric disorders, serious physical illnesses, particularly cardiovascular diseases, formerly or currently * non-removable ferromagnetic metallic implants, sensors, stimulators, prostheses, pacemaker, large tattoos * claustrophobia * age under 18 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in diffusivity indices as assessed by brain MRI with diffusion tensor imaging (DTI) sequences | First analysis at baseline and after 5 years at follow-up |
| Gray matter changes assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM) | First analysis at baseline and after 5 years at follow-up |
| Quantification of white matter lesions using age-related white matter changes (ARWMC) rating scale | First analysis at baseline and after 5 years at follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Boston Naming Test | First analysis at baseline and after 5 years at follow-up | A test to evaluate semantic memory. |
| Verbal memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). | First analysis at baseline and after 5 years at follow-up | Word list learning: 3 repetitions of word list presentation, 12 words. Yes/No recognition test (items:distractors 1 : 2) (reaction intervall: 2 seconds). Data measurement: reaction time, number of correct hits |
| Figural memory recognition task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). | First analysis at baseline and after 5 years at follow-up | Figural pattern learning: 12 different checkerboard patterns are presented, 3 repetitions of checkboard pattern presentation. Checkerboard consists of 3x3 fields, each pattern consists of 4 highlighted fields. Yes/No recognition test (items:distractors 1 : 2) (reaction interval: 2 seconds). Data measurement: reaction time, number of correct hits |
| Focussed Attention. Focussed attention concerning processing speed is assessed with a symbol-counting task (subtest 1 of the Cerebraler Insuffizienztest, c.I.T.S. (Lehrl, 1997)). | First analysis at baseline and after 5 years at follow-up | Data measurement: time |
| Psychomotoric Speed. Psychomotoric speed is assessed using the Trail-Making Test, TMT A (Reitan, 1958). | First analysis at baseline and after 5 years at follow-up | The TMT-A test consists of 25 numbered circles randomly distributed over a sheet of paper. The study participant needs to draw lines to connect the numbers in ascending order. Data measurement: time |
| Reaction time, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). | First analysis at baseline and after 5 years at follow-up | Data measurement: time |
| Selective attention (Choice reaction time), a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). | First analysis at baseline and after 5 years at follow-up | Data measurement: time |
| Interference. Interference is analysed using two tasks. | First analysis at baseline and after 5 years at follow-up | 1. Response inhibition subtest of the Cerebraler Insuffizienztest (c.I.T.I; Lehrl and Fischer, 1997). 2. Inverted choice reaction with reversed conditions of a choice reaction task, a subtest of a computerised neuropsychological screening test battery, named NeuroCogFX (Fliessbach et al., 2006). Data measurement: reaction time |
| MIRS (Muscular impairment rating scale) | First analysis at baseline and after 5 years at follow-up | Rating scale to assess disease severity in myotonic dystrophy type 1 patients |
| Visual-spatial / visual-constructive abilities. Visual-spatial / visual-constructive abilities are investigated using the Block design Test (part of Hamburg-Wechsler Intelligenztest für Erwachsene-Revision (HAWIE-R); Tewes, 1991). | First analysis at baseline and after 5 years at follow-up | The block design test consists of 9 blocks and 9 pictures. The study participant needs to look at the picture and reconstruct each picture by arranging all 9 blocks. Data measurement: time |
| Phonematic fluency. Phonemic verbal word fluency is assessed using the oral word-fluency test, subtest 6 of the Leistungsprüfsystem; Horn, 1983. | First analysis at baseline and after 5 years at follow-up | In a given time (one minute) the study participant needs to list as many words that begin with a certain letter. Data measurement: number of correct words |
| Semantic fluency. Semantic word fluency is assessed using a test by Strauss et al.,2006. | First analysis at baseline and after 5 years at follow-up | A certain category is provided and in a given time (one minute) the study participant needs to list as many items belonging to that category. Data measurement: number of correct items |
| Daytime Sleepiness Scale (DSS) | First analysis at baseline and after 5 years at follow-up | — |
| Krupp's Fatigue Severity Scale (KFSS) | First analysis at baseline and after 5 years at follow-up | — |
| Epworth Sleepiness Scale (ESS) | First analysis at baseline and after 5 years at follow-up | — |
| Pittsburgh Sleep Quality Index (PSQI) | First analysis at baseline and after 5 years at follow-up | — |
| Ullanlinna-Narcolepsy Scale (UNS) | First analysis at baseline and after 5 years at follow-up | — |
| Attention shift. Attentional shift is analysed using the the Trail-Making Test, TMT B (Reitan, 1958). | First analysis at baseline and after 5 years at follow-up | The TMT B test consists of 25 circles randomly distributed over a sheet of paper. These circles include both numbers and letters. The study participant needs to draw lines to connect the numbers and letters in an ascending order, but alternating between numbers and letters. Data measurement: time |
| Motor performance (Purdue Pegboard, bimanual) | First analysis at baseline and after 5 years at follow-up | A bimanual task to assess fine motor function in patients and controls. Results are used as a covariate for neuropsychological tests |
| Beck Depression Inventory (BDI) | First analysis at baseline and after 5 years at follow-up | To assess depressive symptoms |
Outcome results
None listed