Development of a disability scale for myotonic dystrophy type 1.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease-specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability. MATERIALS AND METHODS: Thirty-three patients were tested in basal condition, 18 were re-evaluated after therapeutic intervention with mexiletine, and 13 at one year follow-up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter- and intra-observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach's alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow-up. RESULTS: Our analysis provided good results for inter-observer agreement (ICC = 0.72-0.97), intra-observer reliability, and internal consistency for all areas (Cronbach's α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients. DISCUSSION: Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.

Impact of sleep deprivation and obstructive sleep apnea syndrome on daytime vigilance and driving performance: a laboratory perspective.

INTRODUCTION: To study the impact of sleepiness, a well-established cause of car accidents, on driving ability, we designed a 30-min monotonous simulated driving task. MATERIALS AND METHODS: Our simulated driving task encompasses both primary vehicle control (standard deviation of lane position, crash occurrence) and secondary tasks (type and reaction times to divided attention tasks). Driving simulator data were correlated to subjective (state/trait) and objective (MSLT/MWT) sleepiness measures in healthy subjects undergoing sleep deprivation (SD) and in obstructive sleep apnea (OSAS) patients. RESULTS: SD induced severe sleepiness during nighttime, when state sleepiness increased while primary vehicle control ability worsened. After SD, driving ability decreased and was inversely correlated to subjective and objective sleepiness at MSLT. OSAS patients driving ability was well correlated to objective sleepiness, with inverse correlation to sleep propensity at the MSLT and even more strict relation with the ability to maintain wakefulness at the MWT. CONCLUSIONS: Sleepiness worsens driving ability in healthy subjects after SD and in OSAS patients. Driving ability correlates with subjective and objective sleepiness measures, in particular to the ability to maintain wakefulness.

Refinement of the SPG9 locus on chromosome 10q23.3-24.2 and exclusion of candidate genes.

BACKGROUND AND PURPOSE: The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders, characterized by a progressive spasticity of the lower limbs. So far, 33 different loci (SPGs) have been mapped and the 15 genes responsible have been identified. We mapped a locus responsible for a form of spastic paraplegia, complicated by bilateral cataracts, gastroesophageal reflux with persisting vomiting and amyotrophy to chromosome 10q23.3-q24.2, in an Italian family. The critical region was in a 12 cm chromosomal interval between markers D10S564 and D10S603 (SPG9, MIM601162). In the same region, two other forms of HSP have been recently mapped: SPG27 and SPG33. In the latter case, the gene responsible has been identified. MATERIALS AND METHODS: To better characterize this region, we genotyped individuals from SPG9-linked families using additional markers and reduced the candidate region to a 4.8 Mb, excluding several genes by positional cloning. RESULTS: The refined SPG9 locus is positioned completely within SPG27 and does not include the SPG33 gene. DISCUSSION: Fifty-two transcripts are present in the refined critical region and 25 strong candidates have been excluded as disease causing genes by direct sequencing. Six of them were also excluded as responsible for SPG27.