Movement disorders secondary to long-term treatment with cyclosporine A

Abstract

-Objective: To analyze the prevalence, severity and functional interf e rence of movement diso rders (MD) secondary to chronic use of cyclosporine A (CsA). Method: We conducted a cro s s -s e c t i o n a l study of 60 patients (58.3% male) with mean age 23.1 (3-75) years, followed at the Bone Marro w Transplantation Service of the Hospital de Clínicas of the Federal University of Paraná, Brazil, taking CsA for at least six months. Our protocol included clinical data, assessment of functional interf e rence of symptoms and neurological examination including observation and grading of MD. Results: Eight (13.3%) subjects re p o rted the presence of tremor at the moment of interview and 29 (48.3%) recalled this symptom at some point during treatment. Neurological examination identified 14 (23.3%) subjects with MD: upper limb symmetric action tremor in 13 (21.6%) and parkinsonism (rigidity and bradykinesia) in 1 (1.7%). No other MD was detected. The mean scores indicated mild clinical signs in all cases. Symptoms were conside red subjectively mild with no functional interf e re n c e . Conclusion: Almost one quarter of patients using CsA chronically presented MD, almost always mild and transitory action tre m o r, with minimal interf e re n c e on daily living activities, not requiring any form of intervention in the majority of cases.KEY WORDS: cyclosporine A, tremor, movement disorders, bone marrow transplant.Transtornos do movimento secundários ao tratamento prolongado com ciclosporina A RESUMO -Objetivo: Analisar a prevalência, gravidade e interferência funcional de transtornos do movimento (TM) secundários ao uso crônico de ciclosporina A (CsA). Método: Realizamos um estudo transversal em 60 pacientes (58.3% do sexo masculino) com idade média de 23.1 (3-75) anos, acompanhados pelo Serviço de Transplante de Medula Óssea do Hospital de Clínicas da Universidade Federal do Paraná, usando CsA por pelo menos seis meses. A avaliação incluiu dados clínicos, interferência funcional de possíveis sintomas e exame neurológico incluindo observação e graduação de TM. Resultados: Oito (13.3%) e n t revistados relataram tremor no momento da entrevista e 29 (48.3%) em alguma fase do tratamento. O exame neurológico identificou 14 (23.3%) pacientes com TM: 13 (21.6%) tremor de ação simétrico de membros superiores e em 1 (1.7%) parkinsonismo (rigidez e bradicinesia). Nenhum outro TM foi detectado. Os escores médios indicaram quadros leves em todos os casos. Os sintomas foram também considerados subjetivamente leves e sem interferência funcional. Conclusão: Quase um quarto dos pacientes usando CsA cronicamente apresenta TM, quase sempre tremor de ação leve e transitório, interferindo pouco funcionalmente, não requerendo intervenção na maioria dos casos. PALAVRAS-CHAVE: ciclosporina A, tremor, transtornos do movimento, transplante de medula óssea.Cyclosporine A (CsA) is an immunosuppressive agent used broadly in the prevention of re j e c t i o n of solid organ transplantation due to its effect as a reversible inhibitor of T...

Insights into Pathophysiology from Medication-induced Tremor

“…61 Cyclosporine has effects on dopaminergic neurotransmission and it may influence receptor physiology, phosphorylation pathways, and transcription as well. [62][63][64][65] A recent study in pigs demonstrated gross normal brain pathology after chronic treatment with low-dose cyclosporine; however, on histological examination, there were signs of neuronal, perivascular, and meningeal granulocytic and mononuclear infiltrates in one of the five pigs. 66 Tacrolimus.…”

“…Up to 40% of patients taking cyclosporine will have neurological side effects including tremors, headache, paresthesias, seizures, encephalopathy, visual disorders, or other symptoms. [62][63][64] With this diffuse set of neurological symptoms and signs, there has been significant effort in trying to delineate the mechanism for these neurological problems. Tremor is the most common neurological adverse event and can occur in 20-40% of patients depending upon the clinical setting.…”

“…Tremor is the most common neurological adverse event and can occur in 20-40% of patients depending upon the clinical setting. [62][63][64] It appears that patients treated chronically with cyclosporine tend to have a mild postural tremor that typically does not significantly interfere with daily activities. [62][63][64] Many patients historically will relate a history of mild tremor during the earlier course of treatment, but after some time the tremor has abated or improved, similar to many MITs.…”

“…Toxic states and higher blood levels are associated with more patient complaints and perhaps larger tremor amplitude. [61][62][63][64] Interestingly, in a single case report, a 37-year-old female who was labeled with ET exacerbated by cyclosporine therapy following renal transplantation safely and successfully underwent thalamic deep brain stimulation surgery without infections and with good response. 65 There are numerous possible mechanisms for cyclosporine-induced tremor, but the tremor appears typical of EPT in its characteristics given a shift in the dominant EMG frequency to a lower frequency with weighting.…”

Cyclosporine-induced parkinsonism

“…Munhoz et al described an additional bone marrow transplant patient with rest tremor, bradykinesia and rigidity while on CyA therapy, but the authors could not establish a causal effect [4]. Parkinsonism is uncommon in the post-transplant period.…”