tacrolimus and Paralysis

Differential diagnosis of the underlying cause of new-onset total body paralysis can be challenging and unsatisfying. In akinetic mutism, a rare side effect of tacrolimus, patients become apathetic, mute, and lose voluntary muscle movement. Epidural subarachnoid migration can present with similar symptoms. Delayed emergence/paralysis after anesthesia can include the common culprits of residual operative medications, stroke, as well as tacrolimus-induced akinetic mutism and thoracic epidural migration. We present a case of new-onset total body paralysis, presenting on postoperative day 1 following a double-lung transplant in a patient started on tacrolimus with a thoracic epidural catheter in place.

Topics: Akinetic Mutism; Anesthesia, Epidural; Catheters; Humans; Paralysis; Tacrolimus

We comparatively evaluated the protective effect of the immunophilin ligands cyclosporine A (INN: ciclosporin), FK506, and rapamycin on the spinal cord in a rabbit model of transient ischemia. Both cyclosporine A and FK506 inhibit calcineurin, whereas rapamycin does not.. Thirty-six male New Zealand White rabbits were divided into the following 6 groups: group C, 15 minutes of spinal cord ischemia; group FK, FK506 (1 mg/kg) administered 30 minutes before ischemia; group CsA, cyclosporine A (30 mg/kg) administered 30 minutes before ischemia; group CsA-C, chronic administration of cyclosporine A (20 mg/kg) for 9 days before ischemia; group R, rapamycin (1 mg/kg) administered 30 minutes before ischemia; and group R+FK, rapamycin (1 mg/kg) administered 20 minutes before FK506 pretreatment (1 mg/kg). Group CsA-C was added because the drug does not readily cross the blood-brain barrier. Neurologic function was evaluated by Johnson's 5-point scale at 8, 24, and 48 hours after ischemia, and histopathology was assessed 48 hours after ischemia.. At 24 and 48 hours after ischemia, the Johnson score was better in groups FK (4.0 +/- 1.1), R+FK (3 +/- 1.1), and CsA-C (2.7 +/- 1.2) than in group C (0.8 +/- 1.2). Numbers of morphologically intact anterior horn cells were higher in groups FK (31.3 +/- 9.9), R+FK (23.2 +/- 4.5), and CsA-C (18.3 +/- 6.8) than in group C (6.3 +/- 4.3).. FK506 and chronic administration of cyclosporine A, but not rapamycin, protect the spinal cord from transient ischemia. Although these results are compatible with inhibition of calcineurin in the mechanism of neuroprotective action of these drugs, other effects through different pathways cannot be excluded before further study.

Topics: Animals; Ataxia; Biopsy, Needle; Cyclosporine; Disease Models, Animal; Drug Interactions; Immunohistochemistry; Male; Neurologic Examination; Neuroprotective Agents; Paralysis; Paraparesis; Probability; Rabbits; Random Allocation; Risk Factors; Sensitivity and Specificity; Sirolimus; Spinal Cord Ischemia; Statistics, Nonparametric; Tacrolimus

In this study we examine whether the systemic administration of FK506 or Cyclosporin A (CsA) expedited functional recovery following an axonotmetic nerve injury, and compared their effects in a rat model. Seventy-five adult Buffalo rats received a crush injury to the right posterior tibial nerve and subsequently underwent either no treatment (group I), daily injections of FK506 (group II), or daily injections of CsA (group III). Walking track analysis demonstrated return of hindlimb function by 20 days postoperatively in group I, 14 days in group II, and 18 days in group III. The blood-nerve barrier (BNB) was reconstituted by postoperative day (POD) 7 in both FK506- and CsA-treated animals and by POD 13 in control animals. These results suggest that recovery of function is more rapid with daily administration of FK506 than with CsA or no treatment, perhaps because of earlier restoration of the blood-nerve barrier. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy seen with prolonged denervation, thereby limiting permanent functional loss.

Topics: Analysis of Variance; Animals; Cyclosporine; Male; Motor Activity; Nerve Crush; Paralysis; Rats; Rats, Inbred BUF; Sciatic Nerve; Tacrolimus; Tibial Nerve; Time Factors

Topics: Animals; Brain; Encephalomyelitis, Autoimmune, Experimental; Evoked Potentials, Somatosensory; Female; Paralysis; Rats; Rats, Inbred Lew; Reference Values; Spinal Cord; Tacrolimus