Encephalopathy ciclosporin

Neurological symptoms were observed in 12-25% of liver-transplant patients and in 29% of bone marrow transplant patients, but severe neurotoxicity occurred only in about 1% (18,19/21). They usually appeared within the first month of treatment, but were sometimes delayed (19). Particular attention should be paid to prompt recognition of severe neurotoxicity, because abnormalities of the white matter can occur. Patients usually improved rapidly after temporary ciclosporin withdrawal or dosage reduction, and tacrolimus has sometimes been used successfully instead (SEDA-21, 383) (18). However, recurrence of seizures and persistent electroencephalographic abnormahties were found in 46 and 70% of pediatric transplant patients respectively who had had ciclosporin acute encephalopathy and seizure syndrome and who were followed-up for 49 months (22). 

Ciclosporin-induced vasculopathy, with endothelial injury and derangement of the blood-brain barrier, is the postulated mechanism of neurological damage. Transient cerebral perfusion abnormalities, demonstrable in SPECT scans of the brain, have been suggested as a reliable indicator of ciclosporin neurotoxicity (SEDA-20, 344). Clinical symptoms as well as CT and/or MRI scans were very similar to those observed in hypertensive encephalopathy, with predominant and reversible white-matter occipital lesions (23). There was complete neurological recovery in most patients after blood pressure was normalized, and deaths due to intracranial hemorrhage are reported only exceptionally. 

Based on postmortem findings in a 32-year-old woman who died with an acute encephalopathy (30) and another report of two patients investigated with tran-scranial Doppler ultrasound and MRI for symptoms of ciclosporin nenrotoxicity (31), vascular changes with vasospasm and dissection of the vascular intima strongly snggest that vascnlopathy is a possible mechanism of ciclosporin-indnced encephalopathy. 

Ciclosporin-induced encephalopathy was precipitated by diltiazem in a 76-year-old white woman with corticosteroid-resistant aplastic anemia and thrombocjdope-nia, type 2 diabetes, and coronary artery disease, who was taking diltiazem for hypertension (28). She became comatose after 13 days of therapy with ciclosporin, and clinical examination and electroencephalography showed diffuse encephalopathy of moderate severity. Ciclosporin was withdrawn and she regained consciousness after 36 hours. 

When neurological symptoms occur in patients taking tacrolimus they are very similar to those seen in patients taking ciclosporin, with more frequent insomnia, tremor, and headaches, but a similar rate of severe neurological adverse effects, such as acute psychosis, peripheral neuropathy, seizures, encephalopathy, coma, and paralysis. Persistent speech disorders (dysarthria, apraxia, expressive aphasia, akinetic mutism), and visual blurring can also occur (SEDA-21, 391) (SEDA-22, 420) (24). 

Nervous system A posterior reversible encephalopathy syndrome in a child with Langerhans cell histocytosis resolved completely when ciclosporin was withdrawn Similar cases have been reported in a 27-year-old man with collapsing focal glomerulosclerosis [2 ] and in a 68-year-old woman and a 19-year-old man after heart transplantation [3 ]. 

Neurologic In a prospective study, out of eight patients treated with ciclosporin for acquired haemophilia, one patient developed hypertensive posterior progressive encephalopathy after 1 month of use and the patient improved after ciclosporin was discontinued... 

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