Auditory neuropathy is asymptomatic in one of two forms of autosomal dominant axonal Charcot-Marie-Tooth disease linked to 8P21 chromosome

Short Communications SC318 Auditory neuropathy is asymptomatic in one of two forms of autosomal dominant axonal Charcot-Marie- Tooth disease linked to 8P21 chromosome D. Butinar, 1 A. Starr, 2 J. Zidar, 1 D.-M. Georgiou 3 and J. Vatovec 4 Department of Neurology, Institute of Clinical Neurophysiol- ogy, University Medical Center, Ljubljana, Slovenia, Department of Neurology, University of California Irvine, USA, 3 The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 4 Department for Othorhinolaryngology and Head and Neck Surgery, University Medical Center, Ljubljana, Slovenia Hearing loss and deafness is recognized as an uncommon phenotypic variant in CMT. It can be found in both heredit- ary and sporadic forms of peripheral neuropathies due to associated auditory neuropathy. It is characterised by hearing impairment, abnormal auditory brainstem responses (ABRs) in the presence of normal cochlear receptor functions. We have searched for AN in 17 members of two families with the axonal dominant Charcot-Marie-Tooth (CMT) disease that showed linkage to the same chromosomal region at chromo- some 8p21 and have no hearing complaint. DNA sequencing revealed a novel missense mutation in the neurofilament-light (NF-L) gene in family 1, while no mutation in the coding region of this gene has been identified in the family 2. In addition to the typical clinical and electrophysiological signs of the axonal CMT disease, three members of the second family exhibited also clinical and electrophysiological signs of the pyramidal and lateral lemniscus tracts involvement. Auditory measurements included ABRs, distortion product otoacoustic emission (DPOAE), tonal audiogram and speech audiogram. In eight members of the family 2, ABR’s were not elicitable or abnormal, while DPOAEs and speech audiograms and gap detection were normal. The members of the family 1 had completely normal test results. We conclude that, in addition to the pyramidal tract involvement, a subclinical AN is an additional attribute that differentiates the two families. It can be speculated that the diseases in these two families, despite being linked to the same chromosomal locus, may be dissimilar, i.e. caused by mutations in different genes. Sleep disorders SC319 Effect of tiagabine on sleep consolidation in patients with primary insomnia T. Roth 1 and J. K. Walsh 2,3 Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, 2 Sleep Medicine and Research Center, affiliated with St. John’s Mercy Medical Center and St. Luke’s Hospital, Department of Psychology, St. Louis University, St. Louis, MO, USA Introduction: The selective GABA reuptake inhibitor (SGRI) tiagabine has been shown to have sleep-consolidating effects in healthy elderly. This study aimed to assess sleep-consolidating effects of tiagabine in primary insomnia patients. Method: This cross-over (Latin-Square), double-blind, pla- cebo-controlled study evaluated tiagabine 4, 8, 12, and 16 mg O 2004 EFNS European Journal of Neurology 11 (Suppl. 2), 9–35 in adult patients. Tiagabine was administered for two con- secutive nights with 5- to 12-day washout between treatment periods. Assessments included polysomnography and psy- chomotor performance (Digit Symbol Substitution Test). 58 patients were randomized. A qualitative treatment-by-period interaction was apparent; thus, efficacy data are presented from period 1 only (n = 11–12 per treatment group). Results: Significant reduction in wake after sleep onset was observed (see table). Dose-related increase in slow-wave sleep, and decreases in stage 1 and number of awakenings were observed. Residual impairment in morning performance was observed only for the two highest doses. Most commonly reported adverse events across treatment arms (placebo and tiagabine 4, 8, 12, 16 mg) were dizziness (0%, 2%, 0%, 11%, 21%, respectively), nausea (0%, 0%, 0%, 7%, 16%, respect- ively), and somnolence (2%, 2%, 0%, 6%, 9%, respectively). Tiagabine Placebo Wake after sleep onset, min Slow-wave sleep, % Stage 1 sleep, % Awadenings, n 4 mg 8 mg 12 mg 16 mg P < 0.05. Conclusion: Tiagabine significantly consolidated sleep at = 8 mg dose and enhanced ‘deeper’ NREM stages of sleep. Tiagabine = 8 mg was well tolerated without residual seda- tion. Further investigation is warranted. SC320 Modafinil for excessive sleepiness associated with shift work sleep disorder C. A. Czeisler, 1,2 J. K. Walsh, 3,4 T. Roth, 5 J. R. L. Schwartz, 6 K. P. Wright 7 and D. F. Dinges 8 Division of Sleep Medicine, Harvard Medical School, Brigham & Women’s Hospital, Boston, MA, 3 St. John’s Mercy/St. Luke’s Hospitals, 4 Saint Louis University, St. Louis, MO, 5 Henry Ford Sleep Disorders Center, Detroit, MI, Integris Sleep Disorders Center of Oklahoma, Integris Southwest and Baptist Medical Centers, Oklahoma City, OK, Department of Integrative Physiology, University of Colorado at Boulder, CO, 8 Division of Sleep and Chronobiology, University of Pennsylvania, Philadelphia, PA, USA Objective: We present the first double-blind, placebo-con- trolled trial of modafinil in patients with excessive sleepiness associated with shift work sleep disorder (SWSD). Methods: This 12-week, randomized trial enrolled 209 SWSD patients who worked = 5 night shifts/month. Inclusion cri- teria included mean sleep latency = 6 minutes on nighttime Multiple Sleep Latency Test (MSLT), baseline sleep effi- ciency = 87.5% on daytime polysomnography, and reported excessive sleepiness for = 3 months. Patients received placebo or modafinil (200 mg) 60–30 minutes before each night shift. At 4-week intervals, patients attended the clinic for laboratory night shift. Efficacy measures included MSLT, Karolinska Sleepiness Scale (KSS), Clinical Global Impression of Change (CGI-C), and Psychomotor Vigilance Task (PVT). Results: 153 patients completed the study. Modafinil signifi- cantly improved wakefulness; mean change from baseline in