No abstract

We used the magnetic search coil technique to record horizontal (yaw) and vertical (pitch) head rotations of 20 normal subjects during (1) walking in place, (2) running in place, (3) vigorous, voluntary, horizontal head rotation and (4) vigorous, voluntary, vertical head rotation. During walking or running, the predominant frequency of pitch rotations was at least twice that of yaw rotations. During running, the median, predominant pitch frequency from all subjects was 3.2 Hz, but significant harmonics were present up to 15-20 Hz in several subjects. Group median maximal head velocity during walking or running did not exceed 90 degrees/second. During vigorous, voluntary head rotations median frequency for yaw and pitch was similar and did not exceed 2.6 Hz. However, group median maximal head velocity during vigorous voluntary yaw rotation was 780 degrees/second. Thus, (1) during locomotion, the head is stabilized in space incompletely but adequately so that the vestibulo-ocular reflex (VOR) is not saturated, (2) during vigorous, voluntary head rotations, the maximum head velocity exceeds the range where the VOR can stabilize gaze, (3) the frequencies of head rotations that occur during locomotion greatly exceed frequencies conventionally used in the laboratory for testing the VOR.

Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twentyeight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.