Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tacrolimus (FK506), an immunosuppressant, has been associated with mutism in adults after liver transplant. Speech arrest, agitation, tremor, ataxia, and downward gaze deviation in a 5-year-old female 13 days after orthotopic liver transplant are reported. FK506, which began to be administered 12 days earlier, rose to a level of 44 ng/mL (normal range, 10-20 ng/mL) 1 day before neurologic abnormalities began. FK506 dose level was maintained and then reduced. Three days later the patient could say a few single words and extra-ocular movement returned to normal. Four months later, she continued to exhibit decreased fluency and dysarthria with ataxia. One year later, decreased fluency and mild ataxia persists. Rapid identification of speech loss linked to FK506 may be important because reduction or cessation of the drug may be associated with reverse of speech loss.
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PMID:Tacrolimus (FK506)-induced mutism after liver transplant. 1269 71

Acrylamide (AC) is a known industrial neurotoxic chemical that has been recently found in carbohydrate-rich foods cooked at high temperatures. Repeated AC administration produces a pronounced neuropathy characterized by flaccid paralysis and ataxia and represents a well-established animal model of progressive axonal loss. AC also elicits prominent morphologic alterations (e.g., eccentrically placed nuclei, infolding of the nuclear membrane, accumulations of dense bodies, and clusters of smooth endoplasmic reticulum (SER) associated with numerous microtubules) in cerebellar Purkinje cells that may contribute to the pronounced ataxia in these animals. Here, we examined the neuroprotective action of FK506 (tacrolimus) in male and female rats given daily intraperitoneal injections of AC (30 mg/kg) for 4 weeks. Daily subcutaneous injections of FK506 (2 mg/kg/day) dramatically reduced the behavioral signs of neuropathy (i.e., paralysis and ataxia), markedly protected against axonal loss (by 82% and 73% in the tibial nerves of male and female rats, respectively), and reduced the pathologic changes in Purkinje cells. In a separate study, subcutaneous injections of FK506 (2 or 10 mg/kg) for 2 weeks markedly increased heat shock protein-70 (Hsp-70) immunostaining in sensory neurons, motor neurons, Purkinje cells, and other regions of the brain (in particular, the amygdala) from nonintoxicated and AC-intoxicated rats compared to controls. In contrast, AC-intoxicated animals not given FK506 demonstrated reduced Hsp-70 staining. Thus, the ability of FK506 to increase Hsp-70 expression may underlie its neuroprotective action. We suggest that compounds capable of eliciting a heat shock response may be useful for the treatment of human neuropathies.
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PMID:The immunosuppressant FK506 elicits a neuronal heat shock response and protects against acrylamide neuropathy. 1508 97

A 68-year-old female with severe aplastic anemia (SAA) refractory to initial immunosuppressive therapy, including anti-thymocyte globulin (ATG) and cyclosporine, received a reduced-intensity cord blood transplant (CBT) in June 2015. Tacrolimus (TAC) and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis, and she received prolonged TAC and prednisolone to treat chronic GVHD. The patient presented with progressive ataxia 14 months after CBT. A brain magnetic resonance image (MRI, FLAIR) detected a high-intensity lesion in the left cerebellar hemisphere, which suggested infarction. Her consciousness level gradually continued to deteriorate and another brain MRI (T2) revealed that the size of the cerebellar lesion had increased and had involved the pons. A cerebrospinal fluid (CSF) examination showed normal cell count and protein levels; however, polymerase chain reaction (PCR) analysis of CSF was positive for JC virus (JCV). Therefore, she was eventually diagnosed with progressive multifocal leukoencephalopathy (PML) and treated with mefloquine. The symptoms were reduced after 3 months, and JCV in CSF disappeared without new lesions after 6 months. This is an unusual case of PML initially involving the cerebellum, and we report here PML after an immunosuppressive therapy and CBT in the patient with SAA.
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PMID:[Progressive multifocal leukoencephalopathy developing subsequent to cord blood transplantation in a patient with severe aplastic anemia]. 3084 86