Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report

Abstract

-We report the case of a 41-year-old man with iatrogenic Creutzfeldt-Jakob disease (CJD) acquired after the use of growth hormone (GH) obtained from a number of pituitary glands sourced from autopsy material. The incubation period of the disease (from the midpoint of treatment to the onset of clinical symptoms) was rather long (28 years). Besides the remarkable cerebellar and mental signs, the patient exhibited sleep disturbance (excessive somnolence) from the onset of the symptoms, with striking alteration of the sleep architecture documented by polysomnography. 14-3-3 protein was detected in the CSF, and MRI revealed increased signal intensity bilaterally in the striatum, being most evident in diffusion-weighted (DW-MRI) sequences. This is the second case of iatrogenic CJD associated with the use of GH reported in Brazil.KEY WORDS: Creutzfeldt-Jakob disease, iatrogenic form, growth hormone, diffusion MRI, CSF 14-3-3 protein.Doença de Creutzfeldt-Jakob iatrogênica após uso de hormônio de crescimento humano: relato de caso Doença de Creutzfeldt-Jakob iatrogênica após uso de hormônio de crescimento humano: relato de caso Doença de Creutzfeldt-Jakob iatrogênica após uso de hormônio de crescimento humano: relato de caso Doença de Creutzfeldt-Jakob iatrogênica após uso de hormônio de crescimento humano: relato de caso Doença de Creutzfeldt-Jakob iatrogênica após uso de hormônio de crescimento humano: relato de caso RESUMO -Relatamos o caso de um homem de 41 anos com doença de Creutzfeldt-Jakob (DCJ) iatrogênica, adquirida após uso de hormônio de crescimento (GH) obtido a partir de extrato de hipófises de cadáveres humanos. O período de incubação da doença (calculado a partir do meio do tratamento com GH até o aparecimento dos sintomas) foi longo (28 anos). Além dos sinais cerebelares marcantes e dos sintomas cognitivos, desde o início da doença o paciente apresentava distúrbio do sono (sonolência excessiva), com alteração da arquitetura do sono documentada por polissonografia. Detectou-se a presença da proteína 14-3-3 no líquido cefalorraquidiano do paciente, e o exame de ressonância magnética do encéfalo mostrou hipersinal no striatum bilateralmente, mais evidente na sequência pesada em difusão. Este é o segundo caso registrado no Brasil de DCJ iatrogênica associada ao uso de GH. PALAVRAS-CHAVE: doença de Creutzfeldt-Jakob, forma iatrogênica, hormônio de crescimento, ressonância magnética com difusão, proteína 14-3-3 no LCR.

The imaging appearance of Creutzfeldt–Jakob disease caused by the E200K mutation

“…In less than 1% of cases, CJD results from direct, usually iatrogenic, contamination with an abnormal prion protein. Contaminated human growth hormone, corneal transplantation and cadaveric dura mater are documented causes of CJD [28][29][30]. There are several variants of CJD, including variant CJD (vCJD) that was described recently in Great Britain and France [2,31].…”

Neuroimaging findings in human prion disease

“…Imaging appearances in symptomatic patients fall broadly into four categories: no change, 34 35 cortical atrophy, 40 Caboclo, 41 Oppenheim, 42 Wakisaka, 43 Kretzschmar, 44 Preusser, 45 Martinez-Lage, 46 Garcia Santos, 47 Rabinstein, 48 Llewelyn, 49 Peden, 50 cerebellar atrophy (fig 1D-E) or decreased T2 signal in the basal ganglia. [35][36][37] Atrophic changes can be progressive.…”

Diffusion-weighted MR Imaging of Early-Stage Creutzfeldt-Jakob Disease: Typical and Atypical Manifestations

“…Hereditary disease accounts for another 10% of cases of human prion disease, and most of the remaining cases are represented by Gerstmann-Straü ssler-Sheinker disease (16). The possible causes of iatrogenic Creutzfeldt-Jakob disease include corneal transplantation (17); ingestion of prion-contaminated human growth hormone (18); and transplantation of cadaveric dura mater, which was common in Japan during the 1980s. The latter caused iatrogenic Creutzfeldt-Jakob disease in 97 patients before 2003 (19).…”