Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury.

KEY POINTS: Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists the passive lengthening of muscles. Previously, we established that application of anodal trans-spinal direct current stimulation (a-tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long-term effects of repeated a-tsDCS and its mechanism of action remained unknown. In the present study, a-tsDCS was performed for 7 days and this was found to cause long-term reduction in spasticity, increased rate-dependent depression in spinal reflexes, and improved ground and skill locomotion. Pharmacological, molecular and cellular evidence further suggest that a novel mechanism involving Na-K-Cl cotransporter isoform 1 mediates the observed long-term effects of repeated a-tsDCS. ABSTRACT: Spasticity can cause pain, fatigue and sleep disturbances; restrict daily activities such as walking, sitting and bathing; and complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans-spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long-term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity-dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, with electrophysiological, molecular and cellular studies being conducted to reveal a potential underlying mechanism of action. A 4 week reduction in spasticity was associated with an increase in rate-dependent depression of spinal reflexes, and ground and skill locomotion were improved following 7 days of anodal-tsDCS (a-tsDCS). Secondary molecular, cellular and pharmacological experiments further demonstrated that the expression of K-Cl co-transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na-K-Cl cotransporter isoform 1 (NKCC1) was significantly up-regulated in mice that exhibited spasticity. When mice were treated with a-tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non-injured control mice. Thus, long lasting reduction of spasticity by a-tsDCS via downregulation of NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.

Multifactorial jaundice and pigmented choledocholithiasis secondary to warm autoimmune hemolytic anemia and alcoholic cirrhosis.

A 67-year-old man with a history of alcoholic cirrhosis presented with acute abdominal pain. His total bilirubin was 43.8 mg/dL and fractionated to a direct bilirubin of 32.7 mg/dL. A warm agglutinin IgG1 antibody was positive, and abdominal magnetic resonance imaging detected an obstructing stone at the level of the sphincter of Oddi. Two pigmented gallstones were removed by endoscopic retrograde cholangiopancreatography. His total bilirubin decreased to 24.6 mg/dL the following day, and he was initiated on 20 mg of prednisone for his autoantibody.

An operative and anatomic study to help in nerve sparing during laparoscopic and robotic radical prostatectomy.

OBJECTIVE: To provide a detailed description of the steps involved in a laparoscopic radical prostatectomy in relation to the complex neurovascular anatomy of the male pelvis. AIM AND HYPOTHESIS: We aimed at delineating the neurovascular anatomy to assist in nerve preservation during laparoscopic and robotic radical prostatectomies. METHODS: A team of urologists and an anatomist performed anatomic dissections of 12 male cadavers using a combination of laparoscopic equipment, magnification, and open surgical dissection. Each step involved in laparoscopic prostatectomy was reviewed in relation to the possible impact the step could have on the neurovascular bundles. RESULTS: Dissections were performed systematically to mimic various steps of laparoscopic and robotic prostatectomy. The neurovascular bundles were identified and correlated with video images of actual surgery. This enabled us to construct computer simulations and show the actual nerves on the operative pictures. We specially unraveled the relationship between neurovascular bundles and lateral pelvic and Denonvillier's fascias, both of which enclose and hide these important structures. The course of the bundles was traced from its origin at pelvic plexus to its distal course along the urethra. We also showed the important relationship between pelvic plexus ganglions and seminal vesicles to illustrate the vulnerability of these nerves to thermal, electrical and/or crush injury during seminal vesicle and prostatic pedicle dissections. The importance of additional fine neural plexus along the posterior and antero-lateral surface of the prostate was shown by both gross anatomical and microscopic images. The distal precarious location of the bundles was illustrated by dissections showing anteriorly lifted prostate.These anatomico-operative correlations have not been published for laparoscopic and robotic prostatectomies, which differ significantly in its visual angles, magnifications and sometimes three-dimensional (3D) visualization from its open counter part. CONCLUSION: Laparoscopic and robotic radical prostatectomy provides exposure and visualization of male pelvis not previously appreciated. It is only through a careful reexamination of the anatomy of the male pelvis, in the context of this new procedure, that the improvements in visualization and exposure benefit the surgeon. Our work provides a detailed map relating to operative steps to aid the surgeon in the performance of a nerve sparing robotic and laparoscopic radical prostatectomy.