Filling the gap in CNS drug development: evaluation of the role of drug repurposing.

Background and objective: Background and objective: Drug repurposing has been considered a cost-effective and reduced-risk strategy for developing new drugs. Little is known and documented regarding the efficiency of repurposing strategies in drug development. The objective of this article is to assess the extent and meaning of this process in the CNS area. Methods: In order to identify repurposed drugs that target the CNS, an extensive search was performed. For each identified case, its initial and target indication, development status and the type of repurposing strategy (repositioning, reformulation or both) was recorded. Results: One hundred and eighteen source products were identified. They were repurposed (mainly repositioned) 203 times with 81 products repurposed once and 38 products repurposed twice or more. The highest number of source drugs originated from the CNS area. Alzheimer's disease was targeted most often. Half of the new indications were approved. Regarding repurposing within the CNS area, epilepsy, schizophrenia and depression were the richest sources of repurposed drugs. Conclusions: Repurposing drugs into CNS is an efficient and very active drug development method, exemplified by the considerable number of new indications that have been found via this strategy, with approximately half of the target indications currently under development.

The prevalence of cervical spondylolisthesis.

This study assessed the prevalence of cervical spondylolisthesis in patients undergoing radiographic studies for reasons unrelated to their cervical spine. Scout lateral cervical spine radiographs of 174 patients who had barium swallows were reviewed for the degree and level of cervical spondylolisthesis. Nine patients were found to have >2 mm of anterior subluxation of the cervical spine for a prevalence of 5.2%. Two patients had involvement at the C2-C3 level, one patient at C3-C4, four patients at C4-C5, one patient at C5-C6, and one patient at C7-T1. Subluxation ranged from 2 to 4 mm. Posterior subluxation (retrolisthesis) was not found in any patient. None of the nine patients with spondylolisthesis had complaints of neck pain or upper extremity symptoms, and none had a history of rheumatoid arthritis or cervical trauma.

Effect of timing of stabilization on length of stay and medical complications following spinal cord injury.

This retrospective study examines length of acute hospital stay (LOS) and the development of medical complications in 64 patients with cervical, thoracolumbar or cauda equina injuries divided into two groups according to whether they underwent spinal stabilization < 24 hours after injury or > 24 hours after injury. The mean length of stay for the early stabilization group was 37.5 days (SD +/- 34.2) and for the late stabilization group 54.7 days (SD +/- 40.1). This difference was statistically significant by Mann Whitney U test (Z = 2.53, P = 0.01). There was no statistically significant difference between the early and the late groups with respect to the occurrence of common medical complications. There was a statistically significant difference in age in the early group (mean of 32.4 years) versus the late group (mean of 41.9 years) (t = 2.36, P = 0.02); however we do not feel that this age difference is clinically significant. There was not a statistically significant difference between the early group (17.9, SD = +/-7.2) and the late group (21.3, SD = +/- 8.3) (t = 1.71, p = 0.10) in mean injury Severity Scores (ISS). Also the correlation between length of stay and ISS scores was not significant (r = 0.18, P = 0.2). Timing of spinal stabilization appears to be an important factor in the management of spinal cord injury survivors. Our limited retrospective study suggests that when spinal stabilization is indicated, performance < 24 hours after injury is associated with a significantly shorter length of stay in the hospital. We suspect this is due to earlier mobilization of the patient. Medical complication rates were not significantly affected.

Occipitocervical arthrodesis in children. A new technique and analysis of results.

A new wiring technique for occipitocervical arthrodesis was used in sixteen consecutive children between 1985 and 1992. The twelve boys and four girls had an average age of nine years and six months (range, two years and five months to nineteen years and three months) at the operation. The arthrodesis was performed between the occiput and the second cervical vertebra in ten patients and between the occiput and the third cervical vertebra in six. The instability was related to congenital anomalies (six patients), decompression for cervical stenosis (four patients), Down syndrome (three patients), trauma (one patient), resection of a tumor (one patient), and neurofibromatosis (one patient). Six patients needed a laminectomy for decompression because of cervical stenosis or for removal of a tumor. All of the patients were managed with an autogenous bone graft from the iliac crest and postoperative immobilization with a halo device. Fusion was achieved in fifteen of the sixteen patients. Complications developed in seven patients. The use of wire fixation, combined with the inherent stability of the bone-graft construct, allowed for removal of the halo device relatively early (range, six to twelve weeks), before the fusion was fully mature. No graft was displaced. All of the patients were followed at least until there was radiographic evidence of fusion (fifteen patients) or until a reoperation was performed (one patient). The average duration of follow-up was thirty-seven months (range, twelve to 108 months).